SRC

Summary

SRC (SRC proto-oncogene, non-receptor tyrosine kinase, HGNC:11283) is a protein-coding gene on chromosome 20q11.23, encoding Proto-oncogene tyrosine-protein kinase Src (P12931). Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cyt….

This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 6714 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombocytopenia 6 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 148 total — 1 pathogenic
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈6% of expected missense variation)
• GTEx eGene: eQTL in 14 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 17
• Drug target: yes — 8 curated mechanism-of-action drugs, 5 via a complex or family; 103 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 3 — Bosutinib, Tirbanibulin, Vandetanib
• Approved drugs acting on a complex or family including it: 1 — Dasatinib Anhydrous (SRC)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.38 (moderately constrained)
• MANE Select transcript: NM_198291
• Interaction hub: 7,832 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11283
Approved symbol	SRC
Name	SRC proto-oncogene, non-receptor tyrosine kinase
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	ASV, c-src
Ensembl gene	ENSG00000197122
Ensembl biotype	protein_coding
OMIM	190090
Entrez	6714

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 24 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000373578

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 2, TSL 3: 2, TSL 4: 1, TSL 5: 3

ENST00000373578, ENST00000358208, ENST00000373558, ENST00000373567, ENST00000467556, ENST00000472968, ENST00000477066, ENST00000477475, ENST00000489153, ENST00000493775, ENST00000497734, ENST00000692112, ENST00000692423, ENST00000693012, ENST00000876226, ENST00000876227, ENST00000876228, ENST00000876229, ENST00000876230, ENST00000876231, ENST00000876232, ENST00000876233, ENST00000876234, ENST00000876235, ENST00000876236, ENST00000876237, ENST00000921683, ENST00000921684, ENST00000950593, ENST00001018779, ENST00001058973, ENST00001058974, ENST00001133018

RefSeq mRNA: 2 — MANE Select: NM_198291 NM_005417, NM_198291

CCDS: CCDS13294

Canonical transcript exons

ENST00000373578 — 14 exons

Exon	Start	End
ENSE00000661877	37384150	37384403
ENSE00000661879	37393895	37393993
ENSE00001460945	37346140	37346255
ENSE00001460955	37403171	37406050
ENSE00001460974	37365204	37365277
ENSE00001798147	37382619	37382786
ENSE00003516229	37397699	37397854
ENSE00003523341	37394174	37394277
ENSE00003543788	37402435	37402588
ENSE00003544319	37386075	37386174
ENSE00003564760	37400115	37400294
ENSE00003638193	37402749	37402880
ENSE00003669255	37401602	37401678
ENSE00003678936	37396162	37396311

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 95.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5002 / max 491.3724, expressed in 1721 samples.

Highest expression (Bgee): body of stomach, gall bladder, rectum, body of pancreas, lower esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SRC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	1.1e-06	-0.39	20:37222593:G:A
Pancreas	eqtl	1.4e-06	-0.26	20:37347695:G:A
Stomach	sqtl	8.3e-06	-0.46	20:37352001:G:C
Brain Cerebellum	eqtl	1.4e-05	-0.37	20:37231800:G:T
Liver	eqtl	4.4e-04	-0.40	20:37352925:C:T
Adipose Subcutaneous	eqtl	3.5e-03	-0.12	20:37352001:G:C
Cells Cultured fibroblasts	eqtl	6.9e-03	+0.26	20:37680320:C:A
Testis	eqtl	8.1e-03	+0.17	20:37319689:A:G
Lung	eqtl	9.0e-03	+0.27	20:37336738:T:C
Cells EBV-transformed lymphocytes	sqtl	9.1e-03	-0.59	20:37372201:A:G
Cells Cultured fibroblasts	sqtl	1.4e-02	+0.92	20:37382626:C:T
Spleen	sqtl	2.1e-02	-2.07	20:38006641:C:T
Brain Putamen basal ganglia	eqtl	2.1e-02	+0.16	20:37331411:T:C
Brain Spinal cord cervical c-1	eqtl	2.2e-02	+0.72	20:38335285:C:T
Skin Not Sun Exposed Suprapubic	eqtl	2.5e-02	-0.12	20:37600773:A:AC
Skin Sun Exposed Lower leg	eqtl	2.7e-02	-0.39	20:38199362:G:T
Colon Sigmoid	eqtl	4.2e-02	+0.14	20:36855068:C:G
Whole Blood	eqtl	4.6e-02	+0.23	20:37370737:A:C
Adipose Subcutaneous	sqtl	4.7e-02	-0.31	20:37442313:G:A

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
184494	13.7854	1581
184493	9.4955	1658
184492	1.7431	1020
184490	1.1960	241
184491	1.0197	673
184497	0.8238	199
184496	0.2611	72
184499	0.0598	33
209101	0.0502	30
184498	0.0480	26

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of stomach	UBERON:0001161	95.98	gold quality
gall bladder	UBERON:0002110	95.89	gold quality
rectum	UBERON:0001052	95.58	gold quality
body of pancreas	UBERON:0001150	95.45	gold quality
lower esophagus mucosa	UBERON:0035834	95.36	gold quality
transverse colon	UBERON:0001157	95.11	gold quality
ganglionic eminence	UBERON:0004023	94.92	gold quality
cortical plate	UBERON:0005343	94.65	gold quality
stomach	UBERON:0000945	94.25	gold quality
ectocervix	UBERON:0012249	94.18	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.16	gold quality
body of uterus	UBERON:0009853	93.98	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.83	gold quality
mucosa of transverse colon	UBERON:0004991	93.62	gold quality
mucosa of stomach	UBERON:0001199	93.52	gold quality
ascending aorta	UBERON:0001496	93.25	gold quality
small intestine	UBERON:0002108	93.15	gold quality
thoracic aorta	UBERON:0001515	93.12	gold quality
right testis	UBERON:0004534	92.96	gold quality
endocervix	UBERON:0000458	92.93	gold quality
esophagus mucosa	UBERON:0002469	92.91	gold quality
ventricular zone	UBERON:0003053	92.88	gold quality
metanephros cortex	UBERON:0010533	92.86	gold quality
left testis	UBERON:0004533	92.75	gold quality
right adrenal gland cortex	UBERON:0035827	92.73	gold quality
right adrenal gland	UBERON:0001233	92.60	gold quality
right ovary	UBERON:0002118	92.56	gold quality
left adrenal gland	UBERON:0001234	92.48	gold quality
left uterine tube	UBERON:0001303	92.48	gold quality
left adrenal gland cortex	UBERON:0035825	92.40	gold quality
left ovary	UBERON:0002119	92.20	gold quality
monocyte	CL:0000576	91.86	gold quality
pancreas	UBERON:0001264	91.84	gold quality
esophagus	UBERON:0001043	91.76	gold quality
fundus of stomach	UBERON:0001160	91.68	gold quality
adrenal cortex	UBERON:0001235	91.67	gold quality
descending thoracic aorta	UBERON:0002345	91.65	gold quality
colon	UBERON:0001155	91.63	gold quality
stromal cell of endometrium	CL:0002255	91.60	gold quality
intestine	UBERON:0000160	91.48	gold quality
adenohypophysis	UBERON:0002196	91.45	gold quality
mononuclear cell	CL:0000842	91.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.19	gold quality
large intestine	UBERON:0000059	91.07	gold quality
sigmoid colon	UBERON:0001159	90.97	gold quality
adrenal gland	UBERON:0002369	90.97	gold quality
leukocyte	CL:0000738	90.84	gold quality
vagina	UBERON:0000996	90.67	gold quality
lower esophagus	UBERON:0013473	90.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.58	gold quality
aorta	UBERON:0000947	90.57	gold quality
upper lobe of left lung	UBERON:0008952	90.37	gold quality
smooth muscle tissue	UBERON:0001135	90.28	gold quality
testis	UBERON:0000473	90.23	gold quality
colonic epithelium	UBERON:0000397	89.34	gold quality
pituitary gland	UBERON:0000007	89.29	gold quality
right coronary artery	UBERON:0001625	89.20	gold quality
upper lobe of lung	UBERON:0008948	89.10	gold quality
right lung	UBERON:0002167	89.00	gold quality
islet of Langerhans	UBERON:0000006	88.94	gold quality
popliteal artery	UBERON:0002250	88.75	gold quality
prostate gland	UBERON:0002367	88.75	gold quality
tibial artery	UBERON:0007610	88.74	gold quality
duodenum	UBERON:0002114	88.66	gold quality
urinary bladder	UBERON:0001255	88.47	gold quality
skin of abdomen	UBERON:0001416	88.03	gold quality
skin of leg	UBERON:0001511	87.92	gold quality
granulocyte	CL:0000094	87.88	gold quality
left coronary artery	UBERON:0001626	87.68	gold quality
spleen	UBERON:0002106	87.60	gold quality
minor salivary gland	UBERON:0001830	87.18	gold quality
coronary artery	UBERON:0001621	87.13	gold quality
tibial nerve	UBERON:0001323	86.95	gold quality
uterine cervix	UBERON:0000002	86.62	gold quality
right frontal lobe	UBERON:0002810	86.14	gold quality
right uterine tube	UBERON:0001302	86.11	gold quality
ovary	UBERON:0000992	86.06	gold quality
mouth mucosa	UBERON:0003729	86.02	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.93	gold quality
right lobe of thyroid gland	UBERON:0001119	85.90	gold quality
myometrium	UBERON:0001296	85.85	gold quality
ileal mucosa	UBERON:0000331	85.73	silver quality
left lobe of thyroid gland	UBERON:0001120	85.61	gold quality
jejunal mucosa	UBERON:0000399	85.42	gold quality
embryo	UBERON:0000922	85.23	gold quality
type B pancreatic cell	CL:0000169	85.09	gold quality
right atrium auricular region	UBERON:0006631	85.03	gold quality
adult mammalian kidney	UBERON:0000082	84.90	gold quality
olfactory bulb	UBERON:0002264	84.82	gold quality
zone of skin	UBERON:0000014	84.67	gold quality
nucleus accumbens	UBERON:0001882	84.27	gold quality
cingulate cortex	UBERON:0003027	84.15	gold quality
thyroid gland	UBERON:0002046	84.13	gold quality
prefrontal cortex	UBERON:0000451	84.10	gold quality
saliva-secreting gland	UBERON:0001044	84.06	gold quality
cardiac atrium	UBERON:0002081	84.02	gold quality
female reproductive system	UBERON:0000474	83.95	gold quality
anterior cingulate cortex	UBERON:0009835	83.86	gold quality
vermiform appendix	UBERON:0001154	83.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.16

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	53.6
Caudate putamen	tissue	36.5
Hippocampal formation	tissue	29.8
Hippocampus	tissue	28.4	low
Postcentral gyrus	tissue	27.0
Thalamus	tissue	25.5
Olfactory bulb	tissue	25.3
Cerebral cortex	tissue	24.8	low
Somatosensory cortex	tissue	24.8
Superior colliculi	tissue	23.4
Temporal cortex	tissue	23.3
Midbrain	tissue	23.2
Entorhinal cortex	tissue	23.1
Occipital cortex	tissue	22.8
Basal ganglia	tissue	22.5	not detected
Amygdala	tissue	22.2
Motor cortex	tissue	22.1
Prefrontal cortex	tissue	22.0
Insular cortex	tissue	21.5
Pons	tissue	21.4
Septum	tissue	21.3
Hypothalamus	tissue	21.0
Nucleus accumbens	tissue	20.8
Cerebellum	tissue	20.3	not detected
Retrosplenial and cingulate cortex	tissue	20.2
Stomach 1	tissue	20.0	medium
Retrosplenial cortex	tissue	19.7
Ventral forebrain	tissue	19.3
Duodenum	tissue	19.1	medium
Putamen	tissue	18.7
Locus coeruleus	tissue	17.7
Small intestine	tissue	17.6	low
Substantia nigra	tissue	17.0
Medulla oblongata	tissue	16.2
Spinal cord	tissue	15.9
Periaqueductal gray	tissue	15.7
Choroid plexus	tissue	15.1
Seminal vesicle	tissue	14.3	high
Gallbladder	tissue	13.2	medium
Testis	tissue	10.7	medium
Corpus callosum	tissue	10.4
Pancreas	tissue	10.1	not detected
Urinary bladder	tissue	10.0	medium
Vagina	tissue	9.7	high
Colon	tissue	9.4	not detected
Prostate	tissue	9.3	high
Rectum	tissue	7.4	medium
Endometrium 1	tissue	7.3	not detected
Smooth muscle	tissue	7.1	low
Spleen	tissue	7.1	low
Adrenal gland	tissue	7.0	high
Esophagus	tissue	6.7	medium
Lung	tissue	6.3	not detected
Ovary	tissue	6.2	not detected
Pituitary gland	tissue	5.8
Appendix	tissue	5.7	low
Cervix	tissue	5.4	high
Fallopian tube	tissue	5.2	not detected
Bone marrow	tissue	4.7	not detected
Skin 1	tissue	4.4	high

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Hippocampus, CA3 (32.8), Precentral gyrus (30.3), Corticomedial amygdala (30.2), Dorsal hippocampus (29.8), Temporo-occipital transitional zone (28.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ARNT, EGR1, ESR1, ESR2, FOXO3, GTF2I, HHEX, HIF1A, HNF1A, HNF4A, IER2, JDP2, JUN, JUNB, KAT7, MAFB, NCOA1, NCOA2, NCOA3, NFATC1, NFIC, NFKB, RBPJ, RELA, RELB, SP1, SP3, STAT5A, TAF1, THRA

miRNA regulators (miRDB)

Targeting SRC by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 85 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-488-3P	99.61	68.79	1731

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.383, missense Z 2.86 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000373578 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈6% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
20:37,384,154–37,386,084	132 / 135.4	0.98	no
20:37,386,085–37,393,917	16 / 45.7	0.35	yes (p 1.1e-05)
20:37,393,918–37,397,810	141 / 198.4	0.71	no
20:37,397,811–37,403,376	168 / 357.8	0.47	no

Literature-anchored findings (GeneRIF, showing 40)

• Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton. (PMID:11940607)
• v-Src’s hold over actin and cell adhesions. (PMID:11994743)
• PLD1 is threonine-phosphorylated in human-airway epithelial cells by a PKCdelta and src dependent mechanism (PMID:12014986)
• The Src-cortactin pathway is required for clustering of E-selectin and ICAM-1 in endothelial cells (PMID:12060669)
• Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells. (PMID:12063167)
• REVIEW: Arsenic carcinogenicity: relevance of c-Src activation (PMID:12162444)
• Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells (PMID:12216109)
• The p85 subunit of PI 3-kinase activates Src independently of the enzymatic activity of PI 3- kinase. Ligand binding of GPIb, without receptor clustering, is sufficient to activate Src. (PMID:12393736)
• pp60c-src may be involved in stabilization of dynamic HT-29 cell adhesion to ECM components, and this kinase appears to be part of a mechanosensory protein complex during integrin-mediated cell adhesion (PMID:12416028)
• Src activation may contribute to colon tumor progression and metastasis in part by activating Akt-mediated survival pathways that decrease sensitivity of detached cells to anoikis. (PMID:12420216)
• mediation of synergism with epidermal growth factor receptor by STAT5b (PMID:12429742)
• Data report a novel positioning of Src, mediating signals from insulin to phosphatidylinositol 3-kinase and to beta(2)-adrenergic receptor trafficking. (PMID:12429837)
• Mutual interaction of c-Src with EGFR is required for many EGFR-mediated cellular functions including proliferation, migration, survival and EGFR endocytosis, as discussed in this review. (PMID:12456372)
• c-Src activation is associated with early stages of breast carcinomas with low aggressiveness. (PMID:12462387)
• src has a role in promoting destruction of c-Cbl and enabling EGFR to evade desensitization as part of an oncogenesis pathway (PMID:12604776)
• c-Src, lacking cysteine at position 520, is resistant to 1 microM N-(9-acridinyl) maleimide (NAM) but sensitive to 5 microM. Changing Phe520 to cysteine made it sensitive to 1 microM. Double mutation in clustered cysteines restored resistance to 5 microM. (PMID:12618767)
• Results demonstrate that c-Src and TRAF6 are key mediators of interleukin-1-induced AP-1 activation and provide evidence of cross talk between c-Src and TRAF6 molecules through PI3 kinase-Akt-JNK pathways. (PMID:12631284)
• c-Src regulates NAD(P)H oxidase-derived *O2- generation acutely by stimulating p47phox phosphorylation and translocation and chronically by increasing protein content of gp91phox, p22phox, and p47phox in Ang II-stimulated cells. (PMID:12663375)
• stimulated by HBX protein acting on the mitochondrial transition pore and effecting hepatitis B virus replication. (PMID:12829810)
• involvement of G(i), Src tyrosine kinase and PI3 Kinase, respectively, in TNFalpha production (PMID:12842760)
• v-SRC regulates the nucleo-cytoplasmic delocalization of the major isoform of TEL-ETV6 (PMID:12893822)
• role of c-Src on PRL-stimulated proliferation of T47D and MCF7 breast cancer cells (PMID:12907754)
• FAK and Src are both important survival factors, playing a role in protecting colon cancer cell lines from Adenovirus-containing FAK-CD (Ad-FAK-CD)-induced apoptosis (PMID:12939401)
• Inhibition of Src signaling results in a marked reduction of pancreatic cancer cellular invasiveness. Src may represent a novel therapeutic target for this deadly cancer. (PMID:12947321)
• Src has an appreciable role in the organization of the Golgi apparatus, which may be linked to its involvement in protein transport from the Golgi apparatus to the endoplasmic reticulum (PMID:12975382)
• SRC tyrosine kinases are activated and have a role in tyrosine phosphorylation of ezrin and activation of p38 (PMID:14504278)
• c-src activation of PLCgamma is mediated by GIT1 (PMID:14523024)
• The data indicate an increase in the expression and total activity of endogenous p60(c-Src) in several GM-CSF-independent 1 cultured leukemia cell mutants. (PMID:14562045)
• focal adhesion kinase and src are stimulated by G alpha q and platelet activating factor receptor in vascular endothelium (PMID:14617636)
• role of IGF-1R and c-Src in human pancreatic carcinogenesis. Coexpression of both these molecules may play important role in transformation of pancreatic ductal cells. (PMID:14627343)
• data suggest that agonist-induced binding of Src kinase to the Src homology 3 binding sites in the P2Y(2) purinergic receptor facilitates Src activation and allows Src to efficiently phosphorylate the epidermal growth factor receptor (PMID:14670955)
• A novel regulatory network RAFTK/Pyk2, Src and p38 appears to be critical for VEGF-induced endothelial cell migration. (PMID:14676843)
• v-Src and receptor tyrosine kinase ErbB2 activate beta-catenin-TCF-mediated transcription. (PMID:14706618)
• Ret tyrosine 981 constitutes the major binding site of the Src homology 2 domain of Src and therefore the primary residue responsible for Src activation upon Ret engagement (PMID:14766744)
• EGFR and c-Src-mediated Stat-3 activation is facilitated by Pyk2 (PMID:14963038)
• src and protein kinase C have roles in inducing phosphorylation of p38 mitogen-activated protein kinase in epithelial cells after mechanical pressure (PMID:15033452)
• mechanisms of c-Src activation in human cancer (review) (PMID:15060621)
• both the androgen receptor interacting domains of the coactivator SRC1 and of the corepressor SMRT compete for interaction with the androgen receptor N-terminus (PMID:15062576)
• SH2 and SH3 domains of Src mediate peripheral accumulation of phospho-myosin, leading to integrin adhesion complex assembly, whereas loss of SH2 or SH3 function restores normal regulation of E-cadherin and inhibits vimentin expression (PMID:15075377)
• hTAF(II)68-mediated transactivation is linked to the cytoplasmic Src signal transduction pathway. The hTAF(II)68 protein can associate with the SH3 domains of several cell signaling proteins, including v-Src. (PMID:15094065)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	src	ENSDARG00000008107
mus_musculus	Src	ENSMUSG00000027646
rattus_norvegicus	Src	ENSRNOG00000009495

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), LYN (ENSG00000254087)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98397) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 53 distinct phenotype terms.

Mouse phenotype (MP)	Records
absent incisors	2
decreased body weight	2
decreased body size	2
abnormal bone marrow cavity morphology	1
osteopetrosis	1
abnormal tooth eruption	1
failure of tooth eruption	1
decreased compact bone thickness	1
diluted coat color	1
shortened head	1
abnormal femur morphology	1
delayed eyelid opening	1
abnormal social investigation	1
impaired coordination	1
increased startle reflex	1
abnormal vocalization	1
increased inflammatory response	1
female infertility	1
abnormal learning/memory/conditioning	1
abnormal motor capabilities/coordination/movement	1
premature death	1
abnormal tooth morphology	1
abnormal limb morphology	1
abnormal craniofacial bone morphology	1
abnormal bone marrow morphology	1

+28 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P00523	100.0%	Diamond
Coturnix japonica	P34908	100.0%	Diamond
Drosophila melanogaster	Q08012	100.0%	Diamond
Bos taurus	A0JNB0	99.6%	Diamond
Sus scrofa	A1Y2K1	99.4%	Diamond
Pan troglodytes	P0C0K6	99.3%	Diamond
Felis catus	P14238	98.7%	Diamond
Xenopus laevis	P87379	98.7%	Diamond
Calliphora vicina	P11681	98.6%	Diamond
Macaca fascicularis	Q1KL86	98.0%	Diamond
Avian retrovirus IC10	P10533	100.0%	Diamond
Avian sarcoma virus PR2257	P15054	100.0%	Diamond
Rous-associated virus type 1	P27966	100.0%	Diamond
Avian sarcoma virus S2	P14085	99.8%	Diamond
Avian sarcoma virus S1	P14084	99.6%	Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 2)	P10447	99.3%	Diamond
Gardner-Arnstein feline sarcoma virus	P00542	99.1%	Diamond
Snyder-Theilen feline sarcoma virus	P00543	99.1%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin A)	P00524	99.0%	Diamond
Avian sarcoma virus RASV1441	P00525	99.0%	Diamond
Rous sarcoma virus - Prague C	P00526	99.0%	Diamond
Rous sarcoma virus (strain H-19)	P25020	99.0%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin E)	P63185	99.0%	Diamond
Y73 sarcoma virus	P00527	98.9%	Diamond
Avian carcinoma Mill Hill virus 2	P00531	98.9%	Diamond
Murine sarcoma virus 3611	P00532	98.8%	Diamond
Abelson murine leukemia virus	P00521	98.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GHRH	protein-coding	2691
MANBAL	protein-coding	63905
LINC01746	ncRNA	105372608
NNAT	protein-coding	4826
MROH8	protein-coding	140699
RPN2	protein-coding	6185
BLCAP	protein-coding	10904

Protein

Protein identifiers

Proto-oncogene tyrosine-protein kinase Src — P12931 (reviewed: P12931)

Alternative names: Proto-oncogene c-Src, pp60c-src

All UniProt accessions (2): A0A8I5KYU4, P12931

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Phosphorylates PKP3 at ‘Tyr-195’ in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at ‘Tyr-1477’. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Upon activation of the G(q)-dependent KISS1/KISS1R signaling pathway, active SRC is recruited, together with the phosphatase DUSP18, to the KISS1R C-terminus. This leads to DUSP18-mediated SRC dephosphorylation and inactivation, down-regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on ‘Tyr-284’ and CBL on ‘Tyr-731’. Enhances RIGI-elicited antiviral signaling. Phosphorylates PDPK1 at ‘Tyr-9’, ‘Tyr-373’ and ‘Tyr-376’. Phosphorylates BCAR1 at ‘Tyr-128’. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at ‘Tyr-341’ activates CBLC E3 activity. Phosphorylates synaptic vesicle protein synaptophysin (SYP). Involved in anchorage-independent cell growth. Required for podosome formation. Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration. Phosphorylates OTUB1, promoting deubiquitination of RPTOR. Phosphorylates caspase CASP8 at ‘Tyr-380’ which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function. Mediates laminin-induced activation of RAC1 signaling through phosphorylation of syntrophin. Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity. Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation. The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity. Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs. Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth. Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation. The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity. Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs. Plays a role in neurite elongation.

Subunit / interactions. Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2 domain) and SRC; the formation of the complex is dependent on integrin mediated-tyrosine phosphorylation of PTPRA. Interacts with DDEF1/ASAP1; via the SH3 domain. Interacts with CCPG1. Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with ERBB2, STAT1 and PNN. Interacts with DDR1, DDR2 and DAB2. Interacts with CDCP1, TGFB1I1 and TOM1L2. Interacts with the cytoplasmic domain of MUC1, phosphorylates it and increases binding of MUC1 with beta-catenin. Interacts with RALGPS1; via the SH3 domain. Interacts with CAV2 (tyrosine phosphorylated form). Interacts (via the SH3 domain and the protein kinase domain) with ARRB1; the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with ARRB1 and ARRB2. Interacts with SRCIN1. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1 and ESR1 (dimethylated on arginine). Interacts with FASLG. Interacts (via SH2 domain) with the ‘Tyr-402’ phosphorylated form of PTK2B/PYK2. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with CSF1R. Interacts (via SH2 and SH3 domain) with TNK2. Interacts (via protein kinase domain) with the tyrosine phosphorylated form of RUNX3 (via runt domain). Interacts with TRAF3 (via RING-type zinc finger domain). Interacts with RIGI, MAVS and TBK1. Interacts (via SH2 domain) with RACK1; the interaction is enhanced by tyrosine phosphorylation of RACK1 and inhibits SRC activity. Interacts with EPHB1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with FCAMR. Interacts (via SH2 domain) with the ‘Tyr-9’ phosphorylated form of PDPK1. Interacts with AMOTL2; this interaction regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Interacts with TRAP1. Interacts with CBLC; the interaction is enhanced when SRC is phosphorylated at Tyr-419. Interacts with ARHGEF5. Interacts (via cytoplasmic domain) with CEACAM1 (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion. Interacts with MPP2. Interacts with PRR7. Interacts (via kinase domain and to a lesser extent the SH2 domain) directly with PDLIM4; this interaction results in PTPN13-mediated dephosphorylation of this protein leading to its inactivation. Interacts with P85 (PIK3R1 or PIK3R2). Interacts with HNRNPA2B1. Interacts with IL6ST/gp130. Interacts (via SH3 domain) with PELP1 in the presence of 17-beta-estradiol. Interacts with AMBRA1. Interacts with KISS1R and DUSP18; the interaction depends on activation of KISS1/KISS1R signaling pathway. Interaction with KISS1R and DUSP18 is required for SRC dephosphorylation and inactivation, and down-regulation of osteoclast activity and bone resorption. (Microbial infection) Interacts with HEV ORF3 protein; via the SH3 domain. (Microbial infection) Interacts (via SH2 domain) with HCV non-structural protein 5A (via N-terminus).

Subcellular location. Cell membrane. Mitochondrion inner membrane. Nucleus. Cytoplasm. Cytoskeleton. Perinuclear region. Cell junction. Focal adhesion.

Tissue specificity. Expressed ubiquitously. Expressed in the skin (at protein level). Platelets, neurons and osteoclasts express 5-fold to 200-fold higher levels than most other tissues. Expressed in spleen and liver. Expressed in brain. Expressed in brain.

Post-translational modifications. Myristoylated at Gly-2, and this is essential for targeting to membranes. Dephosphorylated at Tyr-530 by PTPRJ. Phosphorylated on Tyr-530 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-419. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-530, the SH3 domain engaged with the SH2-kinase linker, and Tyr-419 dephosphorylated. Dephosphorylation of Tyr-530 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-530, Tyr-419 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-530 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-75 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase activity. Upon activation of IL6ST by IL6, Tyr-419 is phosphorylated and Tyr-530 dephosphorylated. Displays reduced levels of autophosphorylation at Tyr-419 compared to isoforms 2 and 3. Displays enhanced levels of autophosphorylation at Tyr-419 compared to isoform 1. Displays enhanced levels of autophosphorylation at Tyr-419 compared to isoform 1. Shows reduced phosphorylation at Tyr-527 compared to isoforms 1 and 2. S-nitrosylation is important for activation of its kinase activity. Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-419 and may lead to lysosomal degradation.

Disease relevance. SRC kinase activity has been shown to be increased in several tumor tissues and tumor cell lines such as colon carcinoma cells. Thrombocytopenia 6 (THC6) [MIM:616937] A form of thrombocytopenia, a hematologic disorder defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC6 is an autosomal dominant form. Affected individuals may also have bone abnormalities and an increased risk for myelofibrosis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphorylation by CSK at Tyr-530 inhibits kinase activity. Inhibitory phosphorylation at Tyr-530 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors. Phosphorylation at Tyr-419 increases kinase activity.

Domain organisation. The SH2 and SH3 domains are important for the intramolecular and intermolecular interactions that regulate catalytic activity, localization, and substrate recruitment.

Miscellaneous. May be involved in blister formation in Pemphigus vulgaris, phosphorylated-SRC is abundant at blister sites but not in normally adherent tissue, which corresponds with loss and disruption of CDH1 in cells adjacent to blisters. Phosphorylated SRC is increasingly abundant at pre-lesional sites of blister formation and occurs prior to changes in abundance of CDH1 and DSG3.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P12931-1	1, c-src	yes
P12931-2	2, c-srcN1, N1-Src
P12931-3	3, c-srcN2, N2-Src

RefSeq proteins (2): NP_005408, NP_938033* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, PF07714

Enzyme classification (BRENDA)

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea)

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (83 total): strand 27, helix 23, turn 7, modified residue 6, mutagenesis site 4, sequence variant 3, domain 3, splice variant 2, binding site 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

showing 30 of 79 structures by resolution:

PDB	Title	Method	Resolution (Å)
9OFX	Crystal structure of c-Src SH3 domain in H32 space group mediated by nickel	X-RAY DIFFRACTION	1.45
1FMK	CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC	X-RAY DIFFRACTION	1.5
1O43	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU82129.	X-RAY DIFFRACTION	1.5
1O4A	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU82197.	X-RAY DIFFRACTION	1.5
1O4R	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78783.	X-RAY DIFFRACTION	1.5
2SRC	CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP	X-RAY DIFFRACTION	1.5
6C4S	Human cSrc SH3 Domain in complex with Choline Kinase fragment 60-69	X-RAY DIFFRACTION	1.5
7NG7	Src kinase bound to eCF506 trapped in inactive conformation	X-RAY DIFFRACTION	1.5
8VCF	Crystal structure of Superbinder Src SH2 domain with Cysteine to Serine mutations	X-RAY DIFFRACTION	1.5
1O48	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU85053.	X-RAY DIFFRACTION	1.55
1O4G	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH DPI59.	X-RAY DIFFRACTION	1.55
1O4K	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PASBN.	X-RAY DIFFRACTION	1.57
4F5B	Triple mutant Src SH2 domain bound to phosphotyrosine	X-RAY DIFFRACTION	1.57
1O4M	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH MALONICACID.	X-RAY DIFFRACTION	1.6
1O4N	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH OXALIC ACID.	X-RAY DIFFRACTION	1.6
8VCG	Mutant Src SH2 domain in complex with phosphotyrosine	X-RAY DIFFRACTION	1.61
1O4L	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH FRAGMENT2.	X-RAY DIFFRACTION	1.65
1O41	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78300.	X-RAY DIFFRACTION	1.7
1O42	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU81843.	X-RAY DIFFRACTION	1.7
1O44	Crystal structure of sh2 in complex with ru85052	X-RAY DIFFRACTION	1.7
1O49	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU85493.	X-RAY DIFFRACTION	1.7
1O4J	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH ISO24.	X-RAY DIFFRACTION	1.7
1O4O	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PHENYLPHOSPHATE.	X-RAY DIFFRACTION	1.7
1O4Q	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU79256.	X-RAY DIFFRACTION	1.7
4F59	Triple mutant Src SH2 domain	X-RAY DIFFRACTION	1.71
1O4I	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PAS219.	X-RAY DIFFRACTION	1.75
1O45	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU84687.	X-RAY DIFFRACTION	1.8
1O47	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU82209.	X-RAY DIFFRACTION	1.8
1O4C	CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PHOSPHATE.	X-RAY DIFFRACTION	1.8
3VRO	Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with …	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12931-F1	84.59	0.68

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cell junctions; plasma membrane; vesicles

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
389	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
276–284	ATP
298	ATP

Post-translational modifications (7)

Type	Positions
Phosphoserine	17, 75
Phosphotyrosine	187, 419, 419, 530
N-myristoyl glycine	2

Mutagenesis-validated functional residues (4)

Position	Phenotype
298	kinase inactive. abolishes ubiquitination promoted by cblc.
302	kinase active. interacts with pdlim4; when associated with e-307 and f-419.
307	kinase active. interacts with pdlim4; when associated with e-302 and f-419.
419	loss of kinase activity. loss of interaction with pdlim4.

Function

Pathways and Gene Ontology

Reactome pathways

48 curated (TAS) of 129; 19 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 129 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9664323	FCGR3A-mediated IL10 synthesis ⚕	curated
R-HSA-9664422	FCGR3A-mediated phagocytosis ⚕	curated
R-HSA-8876493	InlA-mediated entry of Listeria monocytogenes into host cells ⚕	curated
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF ⚕	curated
R-HSA-6802952	Signaling by BRAF and RAF1 fusions ⚕	curated
R-HSA-9656223	Signaling by RAF1 mutants ⚕	curated
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants ⚕	curated
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants ⚕	curated
R-HSA-9670439	Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants ⚕	curated
R-HSA-9649948	Signaling downstream of RAS mutants ⚕	curated
R-HSA-418592	ADP signalling through P2Y purinoceptor 1	curated
R-HSA-5607764	CLEC7A (Dectin-1) signaling	curated
R-HSA-389513	Co-inhibition by CTLA4	curated
R-HSA-389356	Co-stimulation by CD28	curated
R-HSA-69231	Cyclin D associated events in G1	curated
R-HSA-9766229	Degradation of CDH1	curated
R-HSA-1253288	Downregulation of ERBB4 signaling	curated
R-HSA-186763	Downstream signal transduction	curated
R-HSA-3928665	EPH-ephrin mediated repulsion of cells	curated
R-HSA-9009391	Extra-nuclear estrogen signaling	curated
R-HSA-2029481	FCGR activation	curated
R-HSA-418555	G alpha (s) signalling events	curated
R-HSA-180292	GAB1 signalosome	curated
R-HSA-430116	GP1b-IX-V activation signalling	curated
R-HSA-9634597	GPER1 signaling	curated
R-HSA-354194	GRB2:SOS provides linkage to MAPK signaling for Integrins	curated
R-HSA-354192	Integrin signaling	curated
R-HSA-5674135	MAP2K and MAPK activation	curated
R-HSA-8874081	MET activates PTK2 signaling	curated
R-HSA-1251985	Nuclear signaling by ERBB4	curated
R-HSA-210990	PECAM1 interactions	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-5673000	RAF activation	curated
R-HSA-8853659	RET signaling	curated
R-HSA-5663220	RHO GTPases Activate Formins	curated
R-HSA-8934903	Receptor Mediated Mitophagy	curated
R-HSA-437239	Recycling pathway of L1	curated
R-HSA-1433559	Regulation of KIT signaling	curated
R-HSA-8941858	Regulation of RUNX3 expression and activity	curated
R-HSA-191650	Regulation of gap junction activity	curated
R-HSA-177929	Signaling by EGFR	curated
R-HSA-1227986	Signaling by ERBB2	curated
R-HSA-1295596	Spry regulation of FGF signaling	curated
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)	curated
R-HSA-5218921	VEGFR2 mediated cell proliferation	curated
R-HSA-372708	p130Cas linkage to MAPK signaling for integrins	curated
R-HSA-9824439	Bacterial Infection Pathways ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-8876384	Listeria monocytogenes entry into host cells ⚕	—
R-HSA-6802957	Oncogenic MAPK signaling ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-6802949	Signaling by RAS mutants ⚕	—
R-HSA-9032500	Activated NTRK2 signals through FYN	electronic
R-HSA-9603381	Activated NTRK3 signals through PI3K	electronic
R-HSA-442755	Activation of NMDA receptors and postsynaptic events	—
R-HSA-418990	Adherens junctions interactions	—

MSigDB gene sets: 945 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_CHROMOSOME_ORGANIZATION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_GLAND_MORPHOGENESIS

GO Biological Process (67): negative regulation of transcription by RNA polymerase II (GO:0000122), stimulatory C-type lectin receptor signaling pathway (GO:0002223), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), cell adhesion (GO:0007155), signal transduction (GO:0007165), signal complex assembly (GO:0007172), epidermal growth factor receptor signaling pathway (GO:0007173), transforming growth factor beta receptor signaling pathway (GO:0007179), integrin-mediated signaling pathway (GO:0007229), lactation (GO:0007595), regulation of epithelial cell migration (GO:0010632), positive regulation of epithelial cell migration (GO:0010634), macroautophagy (GO:0016236), peptidyl-tyrosine phosphorylation (GO:0018108), regulation of cell-cell adhesion (GO:0022407), cell differentiation (GO:0030154), platelet activation (GO:0030168), osteoclast differentiation (GO:0030316), T cell costimulation (GO:0031295), negative regulation of protein-containing complex assembly (GO:0031333), protein destabilization (GO:0031648), negative regulation of telomere maintenance (GO:0032205), positive regulation of integrin activation (GO:0033625), regulation of toll-like receptor 3 signaling pathway (GO:0034139), cellular response to reactive oxygen species (GO:0034614), positive regulation of Rac protein signal transduction (GO:0035022), positive regulation of dephosphorylation (GO:0035306), negative regulation of hippo signaling (GO:0035331), intracellular signal transduction (GO:0035556), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), ERBB2 signaling pathway (GO:0038128), angiotensin-activated signaling pathway (GO:0038166), vasodilation (GO:0042311), negative regulation of apoptotic process (GO:0043066), regulation of vascular permeability (GO:0043114), stress fiber assembly (GO:0043149), regulation of bone resorption (GO:0045124), bone resorption (GO:0045453), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of glycolytic process (GO:0045821), symbiont entry into host cell (GO:0046718), vascular endothelial growth factor receptor signaling pathway (GO:0048010), ephrin receptor signaling pathway (GO:0048013), focal adhesion assembly (GO:0048041), progesterone receptor signaling pathway (GO:0050847), leukocyte migration (GO:0050900), positive regulation of small GTPase mediated signal transduction (GO:0051057), negative regulation of focal adhesion assembly (GO:0051895), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), negative regulation of mitochondrial depolarization (GO:0051902), intestinal epithelial cell development (GO:0060576), interleukin-6-mediated signaling pathway (GO:0070102), positive regulation of ERK1 and ERK2 cascade (GO:0070374), response to interleukin-1 (GO:0070555), cellular response to peptide hormone stimulus (GO:0071375), cellular response to progesterone stimulus (GO:0071393), regulation of heart rate by cardiac conduction (GO:0086091), negative regulation of neutrophil activation (GO:1902564), positive regulation of TORC1 signaling (GO:1904263), positive regulation of lamellipodium morphogenesis (GO:2000394)

+7 more (showing top 60).

GO Molecular Function (27): protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), integrin binding (GO:0005178), ATP binding (GO:0005524), phospholipase activator activity (GO:0016004), enzyme binding (GO:0019899), heme binding (GO:0020037), protein tyrosine kinase activator activity (GO:0030296), signaling receptor activator activity (GO:0030546), ionotropic glutamate receptor binding (GO:0035255), SH2 domain binding (GO:0042169), phospholipase binding (GO:0043274), transmembrane transporter binding (GO:0044325), cadherin binding (GO:0045296), ephrin receptor binding (GO:0046875), ATPase binding (GO:0051117), phosphoprotein binding (GO:0051219), BMP receptor binding (GO:0070700), connexin binding (GO:0071253), scaffold protein binding (GO:0097110), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), protein domain specific binding (GO:0019904)

GO Cellular Component (21): podosome (GO:0002102), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), lysosome (GO:0005764), late endosome (GO:0005770), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), caveola (GO:0005901), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), cell junction (GO:0030054), ruffle membrane (GO:0032587), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Oncogenic MAPK signaling	3
Signaling by ERBB4	2
Integrin signaling	2
GPCR downstream signalling	2
Netrin-1 signaling	2
RAF/MAP kinase cascade	2
Signaling by Receptor Tyrosine Kinases	1
Intracellular signaling by second messengers	1
Signaling by EGFR	1
Signaling by PDGF	1
PI3K/AKT Signaling in Cancer	1
Signal Transduction	1
Platelet Aggregation (Plug Formation)	1
Signaling by ROBO receptors	1

GO top-level categories

showing 60 of 86 GO namespaces:

Category	Terms
cellular anatomical structure	5
protein binding	4
cytoplasm	3
cellular process	2
protein-containing complex assembly	2
epithelial cell migration	2
protein tyrosine kinase activity	2
signaling receptor binding	2
cell adhesion molecule binding	2
enzyme binding	2
intracellular membrane-bounded organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of signal transduction	1
ERBB signaling pathway	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell surface receptor signaling pathway	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
regulation of cell migration	1
regulation of multicellular organismal process	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
autophagosome assembly	1
autophagy	1
protein phosphorylation	1
regulation of cell adhesion	1
cell-cell adhesion	1
cellular developmental process	1
cell activation	1
blood coagulation	1
myeloid leukocyte differentiation	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein kinase activity	1
protein-containing complex binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
glycerophospholipase activity	1
lipase activator activity	1
tetrapyrrole binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 61 of 115 annotations. The rest are phylogenetic / computational / electronic (IEA).

showing 60 of 61 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to reactive oxygen species	BP	mutant phenotype
focal adhesion assembly	BP	mutant phenotype
integrin-mediated signaling pathway	BP	mutant phenotype
interleukin-6-mediated signaling pathway	BP	direct assay
intestinal epithelial cell development	BP	direct assay
intracellular signal transduction	BP	direct assay
negative regulation of anoikis	BP	mutant phenotype
negative regulation of apoptotic process	BP	mutant phenotype
negative regulation of extrinsic apoptotic signaling pathway	BP	mutant phenotype
negative regulation of hippo signaling	BP	mutant phenotype
negative regulation of intrinsic apoptotic signaling pathway	BP	mutant phenotype
negative regulation of mitochondrial depolarization	BP	mutant phenotype
negative regulation of neutrophil activation	BP	direct assay
negative regulation of protein-containing complex assembly	BP	mutant phenotype
negative regulation of telomere maintenance	BP	mutant phenotype
negative regulation of transcription by RNA polymerase II	BP	mutant phenotype
peptidyl-tyrosine phosphorylation	BP	direct assay
positive regulation of Notch signaling pathway	BP	direct assay
positive regulation of TORC1 signaling	BP	direct assay
positive regulation of dephosphorylation	BP	direct assay
positive regulation of epithelial cell migration	BP	mutant phenotype
positive regulation of lamellipodium morphogenesis	BP	mutant phenotype
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	mutant phenotype
positive regulation of small GTPase mediated signal transduction	BP	mutant phenotype
regulation of caveolin-mediated endocytosis	BP	mutant phenotype
regulation of cell-cell adhesion	BP	mutant phenotype
regulation of early endosome to late endosome transport	BP	mutant phenotype
regulation of epithelial cell migration	BP	mutant phenotype
regulation of toll-like receptor 3 signaling pathway	BP	direct assay
response to interleukin-1	BP	mutant phenotype
stress fiber assembly	BP	mutant phenotype
transforming growth factor beta receptor signaling pathway	BP	mutant phenotype
vasodilation	BP	mutant phenotype
caveola	CC	direct assay
cell junction	CC	direct assay
cell-cell junction	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
late endosome	CC	direct assay
lysosome	CC	direct assay
mitochondrial inner membrane	CC	direct assay
mitochondrion	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
plasma membrane	CC	direct assay
BMP receptor binding	MF	physical interaction
SH2 domain binding	MF	physical interaction
cadherin binding	MF	high-throughput assay
enzyme binding	MF	physical interaction
ephrin receptor binding	MF	physical interaction
heme binding	MF	direct assay
integrin binding	MF	physical interaction
non-membrane spanning protein tyrosine kinase activity	MF	direct assay
phospholipase activator activity	MF	direct assay
phospholipase binding	MF	physical interaction
phosphoprotein binding	MF	physical interaction
protein kinase activity	MF	direct assay
protein tyrosine kinase activity	MF	direct assay
scaffold protein binding	MF	physical interaction
signaling receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 7,832 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRC	PIK3CA	P42336	920
SRC	PIK3CG	P48736	915
SRC	PIK3CB	P42338	909
SRC	PIK3CD	O00329	908
SRC	CRK	P46108	869
SRC	PLEK2	Q9NYT0	868
SRC	PLEK	P08567	868
SRC	BCAR1	P56945	863
SRC	EGF	P01133	861
SRC	PXN	P49023	854
SRC	RHOA	P06749	849
SRC	CTTN	Q14247	839
SRC	CDC42	P21181	837
SRC	FN1	P02751	832
SRC	CTNNB1	P35222	829

IntAct

Human interaction partners of SRC in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 320 partners by confidence:

Partner	Interaction type	MIscore	Records
PTPN1	physical association	0.940	12
PTK2	physical association	0.920	8
EGFR	physical association	0.910	9
ESR1	association	0.850	13
CBL	physical association	0.840	8
MET	association	0.790	6
CDCP1	physical association	0.790	3
PIK3R1	proximity	0.780	8
KDR	physical association	0.770	6
MUC1	physical association	0.750	5
ADAM15	direct interaction	0.750	4
PTPRA	association	0.730	4
ERBB2	association	0.710	9
CDC37	physical association	0.710	2
BCAR1	physical association	0.690	3
LNX1	direct interaction	0.680	9
ROR1	physical association	0.680	8
LYN	association	0.670	2
FYN	physical association	0.670	1
HSP90AA1	physical association	0.670	1
MED28	physical association	0.660	3
AFDN	direct interaction	0.650	7
PDCD6IP	physical association	0.650	7
PTK2B	association	0.640	3
ARRB1	physical association	0.620	4
LDB3	direct interaction	0.620	2
PIK3R3	physical association	0.620	2
ADRB2	direct interaction	0.610	3
ASAP1	physical association	0.610	3
SPRR2A	direct interaction	0.600	3

BioGRID (1,091 interactions; top human partners by supporting records in a sample of 600 records): EGFR (Two-hybrid; 19 records), PTK2 (Two-hybrid; 14 records), KHDRBS1 (Affinity Capture-Western; 11 records), BCAR1 (Biochemical Activity; 10 records), ESR1 (Reconstituted Complex; 10 records), ERBB2 (Negative Genetic; 7 records), FZR1 (Affinity Capture-Western; 6 records), PIK3R1 (Co-localization; 6 records), CASP8 (Affinity Capture-Western; 5 records), GNB2L1 (Affinity Capture-Western; 5 records), MDM2 (Protein-peptide; 5 records), AR (Affinity Capture-Western; 4 records), EPHB2 (Two-hybrid; 4 records), MAPT (Biochemical Activity; 4 records), PSMB9 (Reconstituted Complex; 4 records)

SIGNOR signaling

showing 45 of 200 signaling interactions:

A	Effect	B	Mechanism
SRC	“up-regulates activity”	BCAR1	phosphorylation
SRC	“up-regulates activity”	IKBKB	phosphorylation
DOK4	up-regulates	SRC	binding
SRC	“up-regulates activity”	LRP1	phosphorylation
SRC	down-regulates	DAG1	phosphorylation
SRC	down-regulates	TERT	phosphorylation
SRC	up-regulates	TIAM1	phosphorylation
PTPN1	up-regulates	SRC	dephosphorylation
SRC	down-regulates	PTEN	phosphorylation
SRC	“up-regulates activity”	PLSCR1	phosphorylation
SRC	“up-regulates activity”	KIT	phosphorylation
SRC	“up-regulates activity”	CTNNB1	phosphorylation
SRC	“down-regulates activity”	CTNNB1	phosphorylation
SRC	“up-regulates activity”	PDPK1	phosphorylation
SRC	up-regulates	STAT5A	phosphorylation
SRC	“down-regulates activity”	RRAS	phosphorylation
SRC	“up-regulates activity”	PTPRA	phosphorylation
SRC	up-regulates	PRKCI	phosphorylation
SRC	up-regulates	MPZL1	phosphorylation
herbimycin	down-regulates	SRC	“chemical inhibition”
PP2	down-regulates	SRC	“chemical inhibition”
SRC	up-regulates	MAPK7
PRKACA	up-regulates	SRC	phosphorylation
SRC	up-regulates	KCNA3	phosphorylation
SRC	up-regulates	GLRB	phosphorylation
SRC	“down-regulates activity”	CAV1	phosphorylation
SRC	up-regulates	CDC42	phosphorylation
SRC	up-regulates	PTPN6	phosphorylation
SRC	up-regulates	WWOX	phosphorylation
PTPN21	up-regulates	SRC	dephosphorylation
SRC	up-regulates	ANXA2	phosphorylation
SRC	up-regulates	RAPGEF1	phosphorylation
SRC	down-regulates	CAV2	phosphorylation
SRC	up-regulates	SPRY2	phosphorylation
SRC	up-regulates	EZR	phosphorylation
SRC	up-regulates	PTK2B	phosphorylation
SRC	up-regulates	PTK2	phosphorylation
SRC	up-regulates	PIP5K1C	phosphorylation
SRC	down-regulates	SH3GL1	phosphorylation
SRC	unknown	SH3GL1	phosphorylation
SRC	up-regulates	DDR2	phosphorylation
SRC	up-regulates	BDKRB2	phosphorylation
SRC	down-regulates	CHRNA7	phosphorylation
SRC	up-regulates	WASF1	phosphorylation
SRC	down-regulates	CDH2	phosphorylation

Protein complexes (CORUM) (26)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

26 complexes by size:

Complex	Subunits	Members
★ Polycystin-1 multiprotein complex	11	BCAR1, JUP, PTK2, TLN1, CDH1, CTNNB1, PKD1, PXN, SRC, VCL, ACTN1
★ MASH1 promoter-coactivator complex	9	CREBBP, NONO, POLR2A, SRC, H3C1, H4C1, HES1, KAT2B, PARP1
★ CAMK2-delta-MASH1 promoter-coactivator complex	8	SRC, CAMK2D, CREBBP, HES1, KAT2B, NONO, PARP1, POLR2A
★ ITGA2b-ITGB3-CD47-SRC complex	4	CD47, ITGA2B, ITGB3, SRC
★ BCAR1-ESR1-PIK3R1-SRC complex	4	BCAR1, ESR1, PIK3R1, SRC
★ ABCB1-ANXA2-RACK1-SRC complex	4	ABCB1, ANXA2, RACK1, SRC
★ KDR-PTPN6-SRC complex	3	KDR, PTPN6, SRC
★ KDR-MMP14-SRC complex	3	SRC, KDR, MMP14
★ FLT4-ITGB1-SRC complex	3	FLT4, ITGB1, SRC
★ PTK2B-ROS1-SRC complex	3	SRC, PTK2B, ROS1
★ SRC-TNFRSF11A-TRAF6 complex	3	SRC, TNFRSF11A, TRAF6
★ CDCP1-PRKCD-SRC complex	3	SRC, CDCP1, PRKCD
★ BCAR1-PTK2-SRC complex	3	SRC, BCAR1, PTK2
★ CBL-OSTF1-SRC complex	3	CBL, OSTF1, SRC
★ CNK1-SRC-RAF1 complex	3	CNKSR1, RAF1, SRC
★ CDCP1-EGFR-SRC complex	3	CDCP1, EGFR, SRC
★ ESR1-PELP1-SRC complex	3	ESR1, PELP1, SRC
★ AR-RACK1-SRC complex	3	AR, RACK1, SRC
★ AR-PIK3R1-SRC complex	3	AR, PIK3R1, SRC
★ PTK2-PXN-SRC complex	3	PTK2, PXN, SRC
★ FOLR1-PGR-SRC complex	3	SRC, FOLR1, PGR
★ SMIM30-SRC complex	2	SMIM30, SRC
★ KDR-SRC complex	2	KDR, SRC
★ EPHA2-SRC complex	2	EPHA2, SRC
★ RARG-SRC complex	2	RARG, SRC
★ ASAP1-SRC complex	2	ASAP1, SRC

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 320 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ERBB2 ECD mutants	10	26.8×	1e-10
Constitutive Signaling by EGFRvIII	9	25.6×	2e-09
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	10	22.8×	9e-10
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	9	18.6×	5e-08
Signaling by ERBB2 KD Mutants	11	18.5×	1e-09
Erythropoietin activates RAS	6	18.2×	1e-05
Regulation of signaling by CBL	9	17.8×	7e-08
GAB1 signalosome	7	17.7×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	18.8×	4e-08
Schwann cell development	5	17.0×	5e-04
receptor clustering	8	16.2×	5e-06
apical protein localization	5	16.0×	7e-04
epidermal growth factor receptor signaling pathway	19	15.2×	2e-14
protein localization to synapse	6	14.9×	2e-04
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	5	14.3×	1e-03
positive regulation of phosphorylation	5	13.6×	1e-03

Disease & clinical

Genetic variants

Variant evidence for SRC: 148 ClinVar records (1 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

148 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	47
Likely benign	49
Benign	19

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
12573	NM_198291.3(SRC):c.1591C>T (p.Gln531Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore SRC’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 1,908):

Position(s)	Effect	Δscore	Sites
20:37386175–37386176	donor_loss	1.0000	4
20:37394172–37394173	acceptor_loss	1.0000	4
20:37396312–37396313	donor_loss	1.0000	4
20:37397697–37397698	acceptor_loss	1.0000	5
20:37400113–37400114	acceptor_loss	1.0000	5
20:37400295	donor_gain	1.0000
20:37400295	donor_loss	1.0000
20:37402433–37402434	acceptor_loss	1.0000	5
20:37402589–37402590	donor_loss	1.0000	5
20:37402747–37402748	acceptor_loss	1.0000	4

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	3.05e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000214

Disease associations

OMIM: gene MIM:190090 | disease phenotypes: MIM:166710, MIM:254450, MIM:616937

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
thrombocytopenia 6	Strong	Autosomal dominant	3
colorectal cancer	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
thrombocytopenia 6	Moderate	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Bleeding and platelet disorders	green
Cytopenia - NOT Fanconi anaemia	green
Inherited bleeding disorders	green

Mondo (5): thrombocytopenia (MONDO:0002049), osteoporosis (MONDO:0005298), primary myelofibrosis (MONDO:0009692), thrombocytopenia 6 (MONDO:0014837), colorectal cancer (MONDO:0005575)

Orphanet (2): Hereditary thrombocytopenia with early-onset myelofibrosis (Orphanet:480851), Primary myelofibrosis (Orphanet:824)

HPO phenotypes

17 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000490	Deeply set eye
HP:0000601	Hypotelorism
HP:0000939	Osteoporosis
HP:0001442	Typified by somatic mosaicism
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0002003	Large forehead
HP:0002891	Uterine leiomyosarcoma
HP:0003003	Colon cancer
HP:0004406	Spontaneous, recurrent epistaxis
HP:0005584	Renal cell carcinoma
HP:0006716	Hereditary nonpolyposis colorectal carcinoma
HP:0006740	Transitional cell carcinoma of the bladder
HP:0006753	Neoplasm of the stomach
HP:0011974	Myelofibrosis
HP:0031020	Bone marrow hypercellularity

GWAS associations

4 associations:

Study	Trait	p-value
GCST007843_28	Rheumatoid arthritis	4e-13
GCST003422_3	Squamous cell carcinoma	1e-6
GCST012488_34	L1-L4 bone mineral density x serum urate levels interaction	3e-6
GCST001854_10	Retinopathy in non-diabetics	4e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D010024	Osteoporosis	C05.116.198.579; C18.452.104.579
D055728	Primary Myelofibrosis	C15.378.190.636.765
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2111336 (SELECTIVITY GROUP), CHEMBL2363074 (PROTEIN FAMILY), CHEMBL267 (SINGLE PROTEIN), CHEMBL3885535 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523733 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523978 (SELECTIVITY GROUP), CHEMBL4630728 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the SRC protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

8 curated-mechanism drugs:

Drug	Modality	Max phase
BOSUTINIB	Small molecule	4
TIRBANIBULIN	Small molecule	4
VANDETANIB	Small molecule	4
SARACATINIB	Small molecule	3
AZM-475271	Small molecule	2
AZD-0424	Small molecule	1
JNJ-26483327	Small molecule	1
PD-0166285 HYDROCHLORIDE	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes SRC — the drug acts on the assembly or class, not necessarily on this subunit alone.

5 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
DASATINIB ANHYDROUS	SRC	10	4
ENMD-981693	SRC	10	2
ILORASERTIB	SRC	10	2
TG100-801	SRC	10	2
XL-228	SRC	10	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 705,785 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 103 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL571546	TIRBANIBULIN	4	1,248
CHEMBL24828	VANDETANIB	4	43,290
CHEMBL752	ADENOSINE PHOSPHATE	4	166,120
CHEMBL1173655	AFATINIB	4	15,878
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL2110732	DACOMITINIB ANHYDROUS	4	6,949
CHEMBL5416410	DASATINIB	4	674
CHEMBL1421	DASATINIB ANHYDROUS	4	55,947
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL939	GEFITINIB	4	119,425
CHEMBL1873475	IBRUTINIB	4	8,363
CHEMBL941	IMATINIB	4	113,105
CHEMBL1852688	INFIGRATINIB	4	2,298
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	330
CHEMBL554	LAPATINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL180022	NERATINIB	4
CHEMBL1448	NICLOSAMIDE	4
CHEMBL255863	NILOTINIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL477772	PAZOPANIB	4
CHEMBL1171837	PONATINIB	4
CHEMBL4298138	REPOTRECTINIB	4
CHEMBL1336	SORAFENIB	4
CHEMBL535	SUNITINIB	4
CHEMBL1289494	TIVOZANIB	4
CHEMBL217092	SARACATINIB	3
CHEMBL483158	ALISERTIB	3
CHEMBL428690	ALVOCIDIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL545315	CANERTINIB DIHYDROCHLORIDE	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL599552	INDIGO	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL50	QUERCETIN	3
CHEMBL276711	SEMAXANIB	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL426161	AZM-475271	2
CHEMBL495727	AT-9283	2
CHEMBL3623290	AZD-3759	2
CHEMBL2165191	AZD-6482	2
CHEMBL3809489	BEMCENTINIB	2
CHEMBL5083772	BIIB-091	2
CHEMBL3545396	BMS-690514	2
CHEMBL575448	BMS-754807	2
CHEMBL3900554	BMS-986142	2
CHEMBL1967878	CENISERTIB	2
CHEMBL2010872	CEP-11981	2
CHEMBL3818247	DALMELITINIB	2
CHEMBL402548	DANUSERTIB	2

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Src family

Most potent curated ligand interactions (28 total), top 25:

Ligand	Action	Affinity	Parameter
elzovantinib	Inhibition	9.85	pIC50
eCF506	Inhibition	9.3	pIC50
dasatinib	Inhibition	9.1	pIC50
bosutinib	Inhibition	9.0	pIC50
compound 2 [PMID: 15546730]	Inhibition	9.0	pIC50
dorsomorphin	Inhibition	8.7	pIC50
saracatinib	Inhibition	8.57	pIC50
nefextinib	Inhibition	8.22	pIC50
WH-4-023	Inhibition	8.22	pIC50
PD166285	Inhibition	8.08	pKi
CCT241161	Inhibition	8.0	pIC50
PP121	Inhibition	7.85	pIC50
ibrutinib	Inhibition	7.72	pIC50
ENMD-2076	Inhibition	7.7	pIC50
CCT196969	Inhibition	7.52	pIC50
compound 8h [PMID: 22765894]	Inhibition	7.48	pIC50
SU6656	Inhibition	7.14	pIC50
GSK-3 inhibitor XIII	Inhibition	7.09	pKi
NG-25	Inhibition	6.95	pIC50
SI306	Inhibition	6.89	pKi
compound 19a [PMID: 30503936]	Inhibition	6.62	pIC50
balamapimod	Inhibition	6.55	pIC50
compound 36 [PMID: 21958547]	Inhibition	6.53	pIC50
TAK-020	Inhibition	6.2	pIC50
compound 25 [PMID: 31260299]	Inhibition	6.04	pIC50

Binding affinities (BindingDB)

3707 measured of 4842 human assays (5165 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3808884	EC50	0.04 nM
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-piperidin-1-yl )propoxy]-3-quinolinecarbonitrile	IC50	0.14 nM
(11S)-16-amino-2-ethyl-6-fluoro-11-methyl-14-oxo-10-oxa-2,13,17,18,21-pentazatetracyclo[13.5.2.04,9.018,22]docosa-1(21),4(9),5,7,15(22),16,19-heptaene-5-carbonitrile	IC50	0.14 nM	US-20240132517: MACROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION, AND USE THEREOF
4-[(4-chloro-5-methoxy-2-methylphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.15 nM
N-(2-Chloro-6-methylphenyl)-2-(6-(2-hydroxyethylamino)-2-methylpyrimidin-4-ylamino)-1,3-thiazole-5-carboxamide	IC50	0.2 nM
7-methoxy-8-[2-(morpholin-4-yl)ethoxy]-4-[(3,4,5-trimethoxyphenyl)amino]benzo[g]quinoline-3-carbonitrile	IC50	0.22 nM
4-[(2-chloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinoline-3-carbonitrile	IC50	0.23 nM
BDBM50375663	IC50	0.23 nM
Inhibitor 3	IC50	0.25 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-methoxy-8-[2-(4-methylpiperazin-1-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.29 nM
({4-[6-(2,6-Dichloro-phenyl)-8-(3-dimethylamino-propyl)-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-phenyl}-hydroxy-phosphinoylmethyl)-phosphonic acid	IC50	0.3 nM
CHEMBL5431206	IC50	0.3 nM
4-[(4-chloro-5-methoxy-2-methylphenyl)amino]-7-methoxy-8-[2-(4-methylpiperazin-1-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.31 nM
CHEMBL474998	IC50	0.316 nM
CHEMBL516062	IC50	0.316 nM
4-[(2-chloro-5-methoxy-4-methylphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.33 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinoline-3-carbonitrile	IC50	0.42 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.46 nM
4-[(2-chloro-4-fluoro-5-methoxyphenyl)amino]-7-methoxy-8-[2-(morpholin-4-yl)ethoxy]benzo[g]quinoline-3-carbonitrile	IC50	0.48 nM
4-[[7-(6-chloro-2-fluoro-3-hydroxyphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-methyl-N-(2-pyrrolidin-1-ylethyl)benzamide	IC50	0.542 nM	US-8481536: Benzotriazine inhibitors of kinases
4-[(2-chloro-5-methoxy-4-methylphenyl)amino]-8-[2-(4-hydroxypiperidin-1-yl)ethoxy]-7-methoxybenzo[g]quinoline-3-carbonitrile	IC50	0.55 nM
CHEMBL5419830	IC50	0.6 nM
4-[(E)-2-{3-cyano-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxyquinolin-7-yl}ethenyl]-1-oxidopyridin-1-ium	IC50	0.6 nM
trans-1,2-cyclohexanediol	IC50	0.6 nM
CHEMBL2408777	KI	0.62 nM
4-[(2-chloro-5-methoxyphenyl)amino]-6,7-dimethoxyquinoline-3-carbonitrile	IC50	0.64 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-[3-(4-hydroxypiperidin-1-yl)propoxy]-6-methoxy-3-quinolinecarbonitrile	IC50	0.64 nM
7-methoxy-8-[2-(4-methylpiperazin-1-yl)ethoxy]-4-[(3,4,5-trimethoxyphenyl)amino]benzo[g]quinoline-3-carbonitrile	IC50	0.69 nM
CHEMBL4436406	IC50	0.7 nM
CHEMBL5399309	IC50	0.7 nM
CHEMBL6149340	IC50	0.7 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-8-[2-(4-hydroxypiperidin-1-yl)ethoxy]-7-methoxybenzo[g]quinoline-3-carbonitrile	IC50	0.72 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-{5-[(dimethylamino)methyl]furan-3-yl}-6-methoxyquinoline-3-carbonitrile	IC50	0.75 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile	IC50	0.76 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propoxy}-3-quinolinecarbonitrile	IC50	0.76 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-7-[3-(4-ethyl-1-piperazinyl)propoxy]-6-methoxy-3-quinolinecarbonitrile	IC50	0.77 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-{5-[(4-methylpiperazin-1-yl)methyl]-3-furyl}-3-quinolinecarbonitrile	IC50	0.78 nM
1-[(2R)-2-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one	IC50	0.8 nM	US-20240317756: INHIBITORS OF BRUTON’S TYROSINE KINASE
CHEMBL2408779	KI	0.82 nM
9-(2,6-dimethylstyryl)-N-(4-(dimethylphosphoryl)phenyl)-2-isopropyl-9H-purin-6-amine	IC50	0.89 nM
CHEMBL4560385	IC50	0.9 nM
CHEMBL5439245	IC50	0.9 nM
(11S)-2-ethyl-6-fluoro-11-methyl-14-oxo-10,13-dioxa-2,17,18,21-tetrazatetracyclo[13.5.2.04,9.018,22]docosa-1(21),4(9),5,7,15(22),16,19-heptaene-5-carbonitrile	IC50	0.93 nM	US-20240132517: MACROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION, AND USE THEREOF
4-[(2-bromo-4-chloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinoline-3-carbonitrile	IC50	0.95 nM
4-[[7-(5-hydroxy-2-methylphenyl)-5-methyl-1,2,4-benzotriazin-3-yl]amino]-N-(2-pyrrolidin-1-ylethyl)benzenesulfonamide	IC50	0.955 nM	US-8481536: Benzotriazine inhibitors of kinases
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	IC50	1 nM	US-8530652: Pyrrolopyrazoles, potent kinase inhibitors
N-[3-[2-[4-(2-hydroxyethylcarbamoyl)anilino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]-4-methylphenyl]-3-(trifluoromethyl)benzamide	IC50	1 nM	US-8962637: Bicyclic compounds and their uses as dual c-SRC/JAK inhibitors

ChEMBL bioactivities

5079 potent at pChembl≥5 of 5572 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	Ki	0.016	nM	DASATINIB
10.52	IC50	0.03	nM	DASATINIB
9.92	IC50	0.12	nM	ELZOVANTINIB
9.92	IC50	0.12	nM	CHEMBL1241676
9.82	IC50	0.15	nM	CHEMBL196797
9.74	IC50	0.18	nM	CHEMBL3976548
9.70	IC50	0.2	nM	CHEMBL281957
9.70	IC50	0.2	nM	CHEMBL3216659
9.68	Kd	0.21	nM	DASATINIB
9.68	IC50	0.21	nM	DASATINIB
9.66	IC50	0.22	nM	CHEMBL425389
9.60	IC50	0.25	nM	CHEMBL78455
9.58	Ki	0.261	nM	CHEMBL4474070
9.54	IC50	0.29	nM	CHEMBL198650
9.53	Ki	0.295	nM	DASATINIB
9.52	IC50	0.3	nM	DASATINIB
9.52	IC50	0.3	nM	CHEMBL421024
9.51	IC50	0.31	nM	CHEMBL196889
9.50	IC50	0.3162	nM	CHEMBL516062
9.50	IC50	0.3162	nM	CHEMBL474998
9.48	IC50	0.33	nM	CHEMBL370633
9.40	IC50	0.4	nM	DASATINIB
9.37	IC50	0.43	nM	CHEMBL3984621
9.35	IC50	0.45	nM	CHEMBL1089405
9.35	Ki	0.449	nM	CHEMBL4538000
9.34	IC50	0.46	nM	CHEMBL195029
9.32	IC50	0.48	nM	CHEMBL198868
9.30	IC50	0.5	nM	DASATINIB
9.30	IC50	0.5	nM	CHEMBL364623
9.27	IC50	0.542	nM	CHEMBL3639501
9.26	IC50	0.55	nM	CHEMBL436486
9.26	IC50	0.55	nM	CHEMBL1242568
9.22	IC50	0.6	nM	CHEMBL178787
9.22	IC50	0.6	nM	CHEMBL3823104
9.22	IC50	0.6	nM	DASATINIB
9.22	IC50	0.6	nM	CHEMBL591325
9.21	IC50	0.61	nM	CHEMBL495306
9.19	IC50	0.64	nM	CHEMBL424262
9.16	IC50	0.69	nM	CHEMBL197713
9.15	IC50	0.7	nM	CHEMBL250821
9.15	IC50	0.7	nM	CHEMBL6149340
9.15	Kd	0.71	nM	CHEMBL386051
9.14	IC50	0.72	nM	CHEMBL197744
9.12	IC50	0.75	nM	CHEMBL219964
9.12	IC50	0.76	nM	CHEMBL338194
9.11	IC50	0.78	nM	CHEMBL219557
9.11	Ki	0.785	nM	CHEMBL4469856
9.11	IC50	0.77	nM	CHEMBL130529
9.10	IC50	0.8	nM	CHEMBL3695571
9.10	Ki	0.8	nM	CHEMBL3824089

PubChem BioAssay actives

2292 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	1893830: Binding affinity to Src (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
(11S)-16-amino-2-ethyl-6-fluoro-11-methyl-14-oxo-10-oxa-2,13,17,18,21-pentazatetracyclo[13.5.2.04,9.018,22]docosa-1(21),4(9),5,7,15(22),16,19-heptaene-5-carbonitrile	2003537: Inhibition of SRC (unknown origin)	ic50	0.0001	uM
5-(4-amino-1-cyclopentylpyrazolo[3,4-d]pyrimidin-3-yl)-2-chlorophenol	507081: Inhibition of recombinant c-Src by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0001	uM
[5-amino-1-(2-chloro-5-hydroxyphenyl)pyrazol-4-yl]-(1H-indol-2-yl)methanone	1322599: Inhibition of human SRC by time-resolved fluorescence or time-resolved fluorescence assay	ic50	0.0002	uM
6-bromo-3-[(3E)-3-(2-piperazin-1-ylethoxyimino)indol-2-yl]-1H-indol-2-ol;dihydrochloride	1993951: Inhibition of recombinant GST-tagged c-Src catalytic domain (unknown origin) using pEY (4:1) as substrate incubated for 120 mins in presence of 33P-labeled ATP	ic50	0.0002	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-morpholin-4-ylpurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0002	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-(4-methylpiperazin-1-yl)purin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0002	uM
[[4-[[6-(2,6-dichlorophenyl)-8-[3-(dimethylamino)propyl]-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]phenyl]-hydroxyphosphoryl]methylphosphonic acid	205332: Inhibition of Src protein tyrosine kinase	ic50	0.0003	uM
2-[[6-[4-[2-[2-(2-aminoethoxy)ethoxy]ethyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0003	uM
3-[4-amino-7-[4-[2-(2-hydroxyethylamino)ethoxy]phenyl]pyrrolo[2,3-d]pyrimidin-5-yl]phenol	352998: Inhibition of c-Src	ic50	0.0003	uM
3-[4-amino-7-[2-[2-(dimethylamino)ethyl]phenyl]pyrrolo[2,3-d]pyrimidin-5-yl]phenol	352998: Inhibition of c-Src	ic50	0.0003	uM
N-(2-chloro-6-methylphenyl)-2-[(2-methyl-6-piperazin-1-ylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0004	uM
[5-amino-1-(2-chloro-5-hydroxyphenyl)pyrazol-4-yl]-[5-(morpholin-4-ylmethyl)-1H-indol-2-yl]methanone	1322599: Inhibition of human SRC by time-resolved fluorescence or time-resolved fluorescence assay	ic50	0.0004	uM
N-(2-chloro-6-methylphenyl)-2-[(2,6-dimethylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	2206134: Inhibition of SRC (unknown origin)	ic50	0.0005	uM
tert-butyl N-[4-[4-amino-1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl]carbamate	1224919: eCF506, a potent and selection SRC inhibitor	ic50	0.0005	uM
tert-butyl N-[4-[4-amino-1-[2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl]carbamate	1310131: Inhibition of C-terminal His-tagged full length human SRC expressed in insect cells preincubated for 20 mins using poly[Glu,Tyr]4:1 as substrate measured after 5 to 120 mins in presence of [gamma-33P]ATP by Kinome assay	ic50	0.0005	uM
3-[2-[(E)-[2-(6-bromo-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxyethyl-methylamino]propane-1,2-diol	1459479: Inhibition of recombinant c-Src (unknown origin) after 120 mins in presence of [33P]ATP	ic50	0.0005	uM
N-(4-dimethylphosphorylphenyl)-9-[(E)-2-(5-methyl-1H-indazol-4-yl)ethenyl]purin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-imidazol-1-ylpurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-methoxypurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-propan-2-yloxypurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-(2-methoxyethoxy)purin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-(1-methylpiperidin-4-yl)purin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-pyridin-3-yloxypurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
3-[9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-6-(4-dimethylphosphorylanilino)purin-2-yl]propanenitrile	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0005	uM
1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-amine	1407821: Inhibition of Src (unknown origin) using Src-family kinase bisamide rhodamine 110 peptide substrate after 1 hr by fluorescence assay	ic50	0.0005	uM
tert-butyl N-[4-[4-amino-1-[2-(4-piperidin-1-ylpiperidin-1-yl)ethyl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl]carbamate	1310131: Inhibition of C-terminal His-tagged full length human SRC expressed in insect cells preincubated for 20 mins using poly[Glu,Tyr]4:1 as substrate measured after 5 to 120 mins in presence of [gamma-33P]ATP by Kinome assay	ic50	0.0006	uM
8-[2-(dimethylamino)ethoxy]-2-(4-phenoxyphenyl)-6,11-dihydro-5H-pyrazolo[5,1-b][1,3]benzodiazepine-1-carboxamide	452196: Inhibition of SRC	ic50	0.0006	uM
3-[2-[(E)-[2-(6-bromo-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxyethyl-methylamino]propane-1,2-diol;hydrochloride	1459479: Inhibition of recombinant c-Src (unknown origin) after 120 mins in presence of [33P]ATP	ic50	0.0006	uM
5-(4-amino-1-cyclopentylpyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenol	507081: Inhibition of recombinant c-Src by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0006	uM
N-(5-hydroxy-2-methylphenyl)-2-[[1-methyl-6-(2-morpholin-4-ylethylsulfanyl)pyrazolo[3,4-d]pyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	2223316: Inhibition of Src (unknown origin)	ic50	0.0007	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625016: Binding constant for SRC kinase domain	kd	0.0007	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[5-[(4-methylpiperazin-1-yl)methyl]furan-3-yl]quinoline-3-carbonitrile	1796979: Homogeneous Time-resolved Fluorescence (HTRF) Assay from Article 10.1021/jm061031t: “Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles.”	ic50	0.0008	uM
4-(2,4-dichloro-5-methoxyanilino)-7-[5-[(dimethylamino)methyl]furan-3-yl]-6-methoxyquinoline-3-carbonitrile	1796979: Homogeneous Time-resolved Fluorescence (HTRF) Assay from Article 10.1021/jm061031t: “Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles.”	ic50	0.0008	uM
6-bromo-3-[(3E)-3-[2-[4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]ethoxyimino]indol-2-yl]-1H-indol-2-ol	1459479: Inhibition of recombinant c-Src (unknown origin) after 120 mins in presence of [33P]ATP	ic50	0.0008	uM
tert-butyl N-[2-[2-[2-[4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethoxy]ethoxy]ethyl]carbamate	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0008	uM
Dasatinib	2193617: Inhibition of GST tagged Src (unknown origin) assessed as inhibition of phosphorylation using PTK biotinylated peptide substrate 2 as substrate preincubated for 5 mins followed by [gamma-32P]ATP addition	ic50	0.0008	uM
Vandetanib	1876282: Inhibition of SRC (unknown origin)	ic50	0.0008	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	627293: Inhibition of c-Src using biotinylated substrate preincubated for 15 mins before substrate addition measured after 30 mins by fluorescence microplate analysis	ic50	0.0008	uM
3-[2-(4-amino-1-ethylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1206214: Inhibition of human Src	ic50	0.0009	uM
2-[2-[2-[2-[4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethoxy]ethoxy]ethylamino]-2-oxoethanesulfonic acid	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0009	uM
4-[2-[2-[2-[4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]ethoxy]ethoxy]ethylcarbamoyl]cyclobutane-1,2,3-tricarboxylic acid	1515651: Binding affinity to wild-type human partial length SRC (L240 to L536 residues) expressed in bacterial expression system by TR-FRET assay	ki	0.0009	uM
9-[(E)-2-(2,6-dimethylphenyl)ethenyl]-N-(4-dimethylphosphorylphenyl)-2-propan-2-ylpurin-6-amine	363598: Inhibition of human Src kinase by TR-FRET assay	ic50	0.0009	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	360772: Inhibition of Src kinase	ic50	0.0010	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1425175: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0010	uM
methyl 2-[4-[4-amino-5-(3-hydroxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]piperidin-1-yl]acetate	224318: Inhibition of p60 c-Src tyrosine kinase enzyme activity in liquid-phase tyrosine phosphorylation assay at 830 ng/mL	ic50	0.0010	uM
(2,6-dimethylphenyl) N-[(2,5-dimethoxyphenyl)methyl]-N-[2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]carbamate	1797647: HTRF Kinase Inhibition Assay from Article 10.1021/jm060435i: “Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.”	ic50	0.0010	uM
(2,6-dimethylphenyl) N-[2-[3,5-dimethoxy-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]-N-(2,4-dimethoxyphenyl)carbamate	1797647: HTRF Kinase Inhibition Assay from Article 10.1021/jm060435i: “Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.”	ic50	0.0010	uM
(2,6-dimethylphenyl) N-[2-[3,5-dimethoxy-4-[3-(4-methylpiperazin-1-yl)propoxy]anilino]pyrimidin-4-yl]-N-(2,4-dimethoxyphenyl)carbamate	1797647: HTRF Kinase Inhibition Assay from Article 10.1021/jm060435i: “Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.”	ic50	0.0010	uM
(2,6-dimethylphenyl) N-[2-[3,5-dimethoxy-4-[2-(4-methylpiperazin-1-yl)ethoxy]anilino]pyrimidin-4-yl]-N-(2,4-dimethoxyphenyl)carbamate	1797647: HTRF Kinase Inhibition Assay from Article 10.1021/jm060435i: “Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.”	ic50	0.0010	uM

CTD chemical–gene interactions

247 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
AG 1879	increases reaction, decreases expression, decreases phosphorylation, affects cotreatment, increases response to substance (+9 more)	25
Dasatinib	decreases phosphorylation, affects binding, decreases reaction, increases phosphorylation, decreases activity (+2 more)	12
Estradiol	decreases reaction, increases reaction, increases activity, affects reaction, increases abundance (+4 more)	8
Resveratrol	decreases reaction, affects reaction, increases activity, affects binding, increases abundance (+6 more)	7
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation, increases phosphorylation, decreases reaction (+3 more)	7
bisphenol A	affects expression, decreases activity, decreases reaction, increases phosphorylation, affects binding (+3 more)	6
sodium arsenite	increases phosphorylation, affects reaction, affects expression, increases abundance, decreases reaction (+4 more)	6
Tetrachlorodibenzodioxin	increases phosphorylation, affects localization, increases reaction, increases expression, affects cotreatment (+3 more)	6
Hexachlorobenzene	affects activity, affects binding, increases phosphorylation, affects localization, affects phosphorylation (+4 more)	5
Zinc	decreases reaction, increases phosphorylation, increases expression, decreases activity	5
Arsenic Trioxide	decreases expression, increases response to substance, increases reaction, decreases reaction, increases phosphorylation (+1 more)	4
Arsenic	increases expression, increases phosphorylation, increases activity, increases reaction, increases abundance (+1 more)	4
Ozone	affects cotreatment, increases oxidation, increases expression, increases abundance, decreases expression (+1 more)	4
Valproic Acid	increases methylation, affects cotreatment, decreases expression	4
evodiamine	affects binding, decreases reaction, increases reaction, increases phosphorylation, decreases expression (+1 more)	3
4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine	decreases reaction, increases phosphorylation, affects binding, increases reaction, decreases phosphorylation	3
4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline	decreases reaction, increases phosphorylation, increases abundance	3
Acetylcysteine	decreases reaction, increases phosphorylation, decreases phosphorylation	3
Dihydrotestosterone	increases phosphorylation, decreases reaction, affects cotreatment, affects binding, increases reaction (+1 more)	3
Aflatoxin B1	increases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases phosphorylation, decreases activity, affects binding (+2 more)	3
methyleugenol	increases expression	2
perfluorooctanoic acid	increases expression, affects cotreatment, affects expression	2
ochratoxin A	decreases expression, increases phosphorylation	2
butylbenzyl phthalate	decreases expression, increases phosphorylation, decreases reaction	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases expression, increases abundance	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, affects binding, affects cotreatment, decreases expression	2
RTKI cpd	decreases reaction, increases phosphorylation	2
CGP 77675	increases phosphorylation, affects activity, affects binding, affects localization, decreases activity (+3 more)	2
monomethylarsonous acid	decreases activity, decreases reaction, increases expression, increases phosphorylation, affects reaction	2

ChEMBL screening assays

1917 unique, capped per target: 1858 binding, 43 functional, 16 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL807847	Binding	Selectivity for Vascular endothelial growth factor receptor 2 over c-Src kinase	Synthesis and initial SAR studies of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines: a new class of KDR kinase inhibitors. — *Bioorg Med Chem Lett*
CHEMBL845306	Functional	Selectivity for VEGF-receptor 2 (KDR) over c-Src	Design and synthesis of 1,5-diarylbenzimidazoles as inhibitors of the VEGF-receptor KDR. — *Bioorg Med Chem Lett*
CHEMBL4136609	ADMET	Inhibition of recombinant SRC (unknown origin) using polyE4Y as substrate by pyruvate kinase-lactate dehydrogenase coupled assay	Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design To Minimize Host Kinase Interactions. — *ACS Med Chem Lett*

Cellosaurus cell lines

11 cell lines: 9 cancer cell line, 1 telomerase immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8Q5	Abcam HCT 116 SRC KO	Cancer cell line	Male
CVCL_B9BV	Abcam MCF-7 SRC KO	Cancer cell line	Female
CVCL_B9SL	Abcam A-549 SRC KO	Cancer cell line	Male
CVCL_C3KI	N/Tert-1 SRC	Telomerase immortalized cell line	Male
CVCL_D8BE	Ubigene A-549 SRC KO	Cancer cell line	Male
CVCL_D8W8	Ubigene HCT 116 SRC KO	Cancer cell line	Male
CVCL_D9T0	Ubigene HEK293 SRC KO	Transformed cell line	Female
CVCL_E0PY	Ubigene HeLa SRC KO	Cancer cell line	Female
CVCL_TQ36	HAP1 SRC (-) 1	Cancer cell line	Male
CVCL_TQ37	HAP1 SRC (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 600 trials:

NCT	Phase	Status	Title
NCT00114829	Phase 4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	Phase 4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	Phase 4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	Phase 4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	Phase 4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	Phase 4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	Phase 4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	Phase 4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	Phase 4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	Phase 4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	Phase 4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	Phase 4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	Phase 4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	Phase 4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	Phase 4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	Phase 4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	Phase 4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	Phase 4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	Phase 4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	Phase 4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	Phase 4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	Phase 4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	Phase 4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	Phase 4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	Phase 4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	Phase 4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	Phase 4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	Phase 4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	Phase 4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	Phase 4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	Phase 4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	Phase 4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	Phase 4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	Phase 4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	Phase 4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	Phase 4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	Phase 4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	Phase 4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	Phase 4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	Phase 4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer
NCT02575378	Phase 4	UNKNOWN	Maintenance Treatment With Capecitabine Metronomic Chemotherapy and Chinese Traditional Medicine in Metastatic Colorectal Cancer
NCT02581423	Phase 4	COMPLETED	A Study of Capecitabine (Xeloda) in the Adjuvant Treatment of Participants With Resected Colon Cancer
NCT02582970	Phase 4	COMPLETED	A Study of Bevacizumab (Avastin) in Combination With Chemotherapy in Participants With Metastatic Cancer of the Colon or Rectum
NCT03084809	Phase 4	COMPLETED	Chemotherapy Combined With CIK Treating Colon Cancer
NCT03130634	Phase 4	COMPLETED	The Efficacy of Silymarin as Adjuvant Therapy on Colorectal Cancer Patients Undergoing FOLFIRI Treatment
NCT03298945	Phase 4	COMPLETED	Comparative Effectiveness of Split-Dose Colonoscopy Bowel Preparation Regimens
NCT03465202	Phase 4	UNKNOWN	Association of Capecitabine Pharmacokinetics and Toxicity With Aging
NCT03564938	Phase 4	COMPLETED	Regorafenib in Indian Patients With Metastatic Colorectal Cancer (mCRC).
NCT03700411	Phase 4	COMPLETED	Influence of Opioid Analgesia on Circulating Tumor Cells in Open Colorectal Cancer Surgery
NCT03700541	Phase 4	COMPLETED	Influence of Opioid Analgesia on Circulating Tumor Cells in Laparoscopic Colorectal Cancer Surgery
NCT03723447	Phase 4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT04074460	Phase 4	COMPLETED	Volatile Anaesthesia and Perioperative Outcomes Related to Cancer Feasibility Study
NCT04281667	Phase 4	ACTIVE_NOT_RECRUITING	Mechanical Bowel Preparation and Oral Antibiotics Versus Mechanical Bowel Preparation Only Prior Rectal Surgery
NCT04297423	Phase 4	COMPLETED	Two Low Volume Regimens for Colorectal Cancer Screening Colonoscopy
NCT04874207	Phase 4	COMPLETED	Evaluation of Treatment PERSOnalization Based on Its Therapeutic Monitoring in Patients With Metastatic Colorectal Cancer Treated With REgorafenib
NCT04874883	Phase 4	UNKNOWN	Effect of the Use of Symbiotics in Patients With Colon Cancer
NCT04973007	Phase 4	TERMINATED	Comparison of Contrast Agents in Liver Magnetic Resonance (MR) for the Detection of Hepatic Metastases
NCT05661357	Phase 4	UNKNOWN	Disitamab Vedotin Combined With Fruquintinib for mCRC With HER2 Expression
NCT05726136	Phase 4	RECRUITING	Fluid Challenge and Plasma Volume, During Surgery
NCT05897749	Phase 4	UNKNOWN	Clinical Study on the Effect of Brucea Javanica Oil Emulsion Injection on the Survival of Patients With Advanced Colorectal Cancer Who Failed to Receive Multi-line Treatment

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SRC across ~30M SureChEMBL compounds — explore on Sugi Predict.