SRC Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human SRC — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene SRC, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene SRC, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene SRC protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene SRC protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene SRC, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene SRC, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene SRC, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene SRC protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene SRC, summarize transcription factor regulatory data. If SRC is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate SRC — names with evidence type (ChIP-seq / predicted / experimentally validated) If SRC is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene SRC protein as a drug target, summarize pharmacology data. If SRC is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If SRC is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene SRC, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene SRC, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in SRC: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
SRC (HGNC:11283; Chr20q11.23) encodes the proto-oncogene tyrosine-protein kinase Src, the founding member of the Src-family kinases and one of the most extensively studied signal transduction proteins in human biology. As a non-receptor tyrosine kinase with SH2, SH3, and kinase domains, it functions as a central hub in integrin, growth factor receptor, and immune signaling, participating in 69 Reactome pathways spanning EGFR, PI3K/AKT, MAPK, and focal adhesion cascades. SRC is ubiquitously expressed across 286 conditions (average expression score 81.1), with highest levels in gastrointestinal epithelia and embryonic neural tissues. Its clinical relevance spans a Mendelian blood disorder — autosomal dominant thrombocytopenia 6 (OMIM:616937) — and strong GWAS association with rheumatoid arthritis (p=4×10⁻¹³). It is a highly validated drug target (ChEMBL267) with 4,009 inhibitory molecules catalogued, including 9 FDA-approved drugs; dasatinib and bosutinib are direct SRC/ABL inhibitors, while sorafenib leads clinical trial engagement at 572 trials. AlphaFold modeling covers 68% of the structure at high confidence, supported by 79 experimental PDB structures.
Gene identifiers
- HGNC ID: HGNC:11283
- Approved symbol: SRC
- Ensembl gene ID: ENSG00000197122
- NCBI Entrez Gene ID: 6714
- OMIM gene/locus ID: 190090
- Genomic location (GRCh38): Chromosome 20, 37,344,673–37,406,050 (+)
Transcript identifiers
Ensembl Transcripts (ENST)
| Transcript ID | Biotype |
|---|---|
| ENST00000358208 | protein_coding |
| ENST00000373558 | protein_coding |
| ENST00000373567 | protein_coding |
| ENST00000373578 | protein_coding |
| ENST00000467556 | retained_intron |
| ENST00000472968 | retained_intron |
| ENST00000477066 | protein_coding_CDS_not_defined |
| ENST00000477475 | protein_coding_CDS_not_defined |
| ENST00000489153 | retained_intron |
| ENST00000493775 | retained_intron |
| ENST00000497734 | protein_coding_CDS_not_defined |
| ENST00000692112 | protein_coding |
| ENST00000692423 | protein_coding |
| ENST00000693012 | protein_coding |
| ENST00000876226 | protein_coding |
| ENST00000876227 | protein_coding |
| ENST00000876228 | protein_coding |
| ENST00000876229 | protein_coding |
| ENST00000876230 | protein_coding |
| ENST00000876231 | protein_coding |
| ENST00000876232 | protein_coding |
| ENST00000876233 | protein_coding |
| ENST00000876234 | protein_coding |
| ENST00000876235 | protein_coding |
| ENST00000876236 | protein_coding |
| ENST00000876237 | protein_coding |
| ENST00000921683 | protein_coding |
| ENST00000921684 | protein_coding |
| ENST00000950593 | protein_coding |
Total Ensembl transcripts: 29
RefSeq mRNA Accessions (NM_)
| RefSeq ID | Status | MANE Select |
|---|---|---|
| NM_001003837 | PROVISIONAL | No |
| NM_001025395 | VALIDATED | No |
| NM_001412682 | VALIDATED | No |
| NM_001412683 | VALIDATED | No |
| NM_001412684 | VALIDATED | No |
| NM_001412685 | VALIDATED | No |
| NM_001412686 | VALIDATED | No |
| NM_001412687 | VALIDATED | No |
| NM_001412688 | VALIDATED | No |
| NM_001412689 | VALIDATED | No |
| NM_001412690 | VALIDATED | No |
| NM_001412691 | VALIDATED | No |
| NM_001412693 | VALIDATED | No |
| NM_001421000 | VALIDATED | No |
| NM_005417 | REVIEWED | No |
| NM_009271 | VALIDATED | No |
| NM_031977 | PROVISIONAL | No |
| NM_198291 | REVIEWED | Yes |
Total NM_ RefSeq accessions: 18
CCDS ID
| CCDS ID |
|---|
| CCDS13294 |
MANE Select Transcript Exons (ENST00000373578)
| Exon ID | Start | End | Genomic Coordinates |
|---|---|---|---|
| ENSE00001460955 | 37403171 | 37406050 | chr20:37403171-37406050 |
| ENSE00003638193 | 37402749 | 37402880 | chr20:37402749-37402880 |
| ENSE00003669255 | 37401602 | 37401678 | chr20:37401602-37401678 |
| ENSE00003560760 | 37400115 | 37400294 | chr20:37400115-37400294 |
| ENSE00003543788 | 37402435 | 37402588 | chr20:37402435-37402588 |
| ENSE00003678936 | 37396162 | 37396311 | chr20:37396162-37396311 |
| ENSE00003516229 | 37397699 | 37397854 | chr20:37397699-37397854 |
| ENSE00003523341 | 37394174 | 37394277 | chr20:37394174-37394277 |
| ENSE00000661879 | 37393895 | 37393993 | chr20:37393895-37393993 |
| ENSE00003544319 | 37386075 | 37386174 | chr20:37386075-37386174 |
| ENSE00001798147 | 37382619 | 37382786 | chr20:37382619-37382786 |
| ENSE00000661877 | 37384150 | 37384403 | chr20:37384150-37384403 |
| ENSE00001460974 | 37365204 | 37365277 | chr20:37365204-37365277 |
| ENSE00001460945 | 37346140 | 37346255 | chr20:37346140-37346255 |
Total exons in MANE Select transcript: 14
Protein identifiers
UniProt Accessions
- P12931 (canonical, reviewed) — Proto-oncogene tyrosine-protein kinase Src
- A0A8I5KYU4 (unreviewed)
RefSeq Proteins (NP_)
- NP_005408 (reviewed)
- NP_938033 (reviewed, MANE Select)
Protein Domains and Families
InterPro entries (11):
| 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 entries (3):
- PF00017
- PF00018
- PF07714
SMART entries (3):
- SM00219
- SM00252
- SM00326
SCOP Superfamily entries (3):
- SSF50044
- SSF55550
- SSF56112
Antibody Resources
No antibody resources identified in biobtree for SRC protein (P12931).
Structure
Experimental Structures
X-ray Crystallography: 75 PDB entries
1A07 (2.2 Å), 1A08 (2.2 Å), 1A09 (2.0 Å), 1A1A (2.0 Å), 1A1B (2.2 Å), 1A1C (2.4 Å), 1A1E (2.2 Å), 1FMK (1.5 Å), 1KSW (2.8 Å), 1O41 (1.7 Å), 1O42 (1.7 Å), 1O43 (1.5 Å), 1O44 (1.7 Å), 1O45 (1.8 Å), 1O46 (2.0 Å), 1O47 (1.8 Å), 1O48 (1.55 Å), 1O49 (1.7 Å), 1O4A (1.5 Å), 1O4B (1.85 Å), 1O4C (1.8 Å), 1O4D (1.85 Å), 1O4E (2.0 Å), 1O4F (2.0 Å), 1O4G (1.55 Å), 1O4H (2.25 Å), 1O4I (1.75 Å), 1O4J (1.7 Å), 1O4K (1.57 Å), 1O4L (1.65 Å), 1O4M (1.6 Å), 1O4N (1.6 Å), 1O4O (1.7 Å), 1O4P (1.9 Å), 1O4Q (1.7 Å), 1O4R (1.5 Å), 1SHD (2.0 Å), 1Y57 (1.91 Å), 1YI6 (2.0 Å), 1YOJ (1.95 Å), 1YOL (2.3 Å), 1YOM (2.9 Å), 2BDF (2.1 Å), 2BDJ (2.5 Å), 2H8H (2.2 Å), 2SRC (1.5 Å), 3VRO (1.8 Å), 3ZMP (2.619 Å), 3ZMQ (3.3 Å), 4F59 (1.71 Å), 4F5A (1.8 Å), 4F5B (1.57 Å), 4HXJ (2.0 Å), 4K11 (2.3 Å), 4MXO (2.105 Å), 4MXX (2.6 Å), 4MXY (2.582 Å), 4MXZ (2.582 Å), 6ATE (2.402 Å), 6C4S (1.5 Å), 6E6E (2.15 Å), 7NG7 (1.5 Å), 7OTE (2.49 Å), 7T1U (2.65 Å), 7YQE (3.5 Å), 8GWH (2.0 Å), 8HAQ (2.27 Å), 8JF3 (2.85 Å), 8JN8 (1.902 Å), 8JN9 (2.724 Å), 8VCF (1.5 Å), 8VCG (1.61 Å), 9IRL (2.031 Å), 9OFX (1.45 Å), 6EHJ (2.1 Å)
Solution NMR: 4 entries
1HCS, 1HCT, 9NS0, 9NS1
Total Experimental Structures: 79 PDB entries
Predicted Structures
AlphaFold Model: AF-P12931-F1
- Global pLDDT: 84.59
- High confidence (pLDDT > 90): 68% of structure
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000027646 | Src |
| Rat (Rattus norvegicus) | ENSRNOG00000009495 | Src |
| Zebrafish (Danio rerio) | ENSDARG00000008107 | src |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Annotations
Total variants: ~111
| Classification | Count |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 1 |
| Uncertain significance | ~58 |
| Likely benign | ~20 |
| Benign | ~20 |
| Benign/Likely benign | ~6 |
| Not provided | ~5 |
Top pathogenic/likely pathogenic variants:
| Variant ID | HGVS notation | Condition/Association |
|---|---|---|
| 12573 | NM_198291.3(SRC):c.1591C>T | p.Gln531Ter (Pathogenic) |
| 225689 | NM_198291.3(SRC):c.1579G>A | p.Glu527Lys (Likely pathogenic) |
AI-Based Variant Effect Predictions
Splice Effect Predictions (SpliceAI)
Total variants: 3,484
Top 30 high-scoring splice variants:
| Position | Variant | Effect | Score |
|---|---|---|---|
| 20:37346252 | CCAGG>C | donor_loss | 0.9900 |
| 20:37346254 | AG>A | donor_loss | 0.9900 |
| 20:37346257 | T>A | donor_loss | 0.9900 |
| 20:37346256 | G>GG | donor_gain | 0.9500 |
| 20:37346228 | C>CA | donor_gain | 0.7000 |
| 20:37346250 | GCCCA>G | donor_gain | 0.7000 |
| 20:37346235 | C>T | donor_gain | 0.6800 |
| 20:37347174 | C>T | donor_gain | 0.6800 |
| 20:37346232 | G>A | donor_gain | 0.6800 |
| 20:37346234 | G>GT | donor_gain | 0.7100 |
| 20:37346251 | CCCAG>C | donor_gain | 0.7300 |
| 20:37346252 | CCAGG>C | donor_gain | 0.7300 |
| 20:37346253 | CAGG>C | donor_gain | 0.7300 |
| 20:37346254 | AGGTG>A | donor_gain | 0.7400 |
| 20:37346255 | GGTGA>G | donor_gain | 0.7300 |
| 20:37347233 | TGGG>T | donor_loss | 0.7900 |
| 20:37347237 | GTA>G | donor_loss | 0.7900 |
| 20:37347238 | TAAGT>T | donor_loss | 0.7900 |
| 20:37347234 | GGG>G | donor_gain | 0.8800 |
| 20:37347235 | GGG>G | donor_gain | 0.8800 |
| 20:37347234 | GGG>G | donor_gain | 0.8200 |
| 20:37347236 | GG>G | donor_gain | 0.8200 |
| 20:37347116 | A>AG | acceptor_gain | 0.8500 |
| 20:37347117 | G>GG | acceptor_gain | 0.8500 |
| 20:37347114 | TCAG>T | acceptor_gain | 0.8200 |
| 20:37347115 | CAGC>C | acceptor_gain | 0.8200 |
| 20:37347117 | GCCCC>G | acceptor_gain | 0.7200 |
| 20:37347117 | GCCC>G | acceptor_gain | 0.7400 |
| 20:37347116 | A>T | acceptor_gain | 0.7700 |
| 20:37347113 | TTCAG>T | acceptor_gain | 0.7200 |
AlphaMissense Pathogenicity Predictions
Total likely_pathogenic: 100+ (capped display from first batch)
Top 30 likely-pathogenic variants by pathogenicity score:
| Position | Variant | Protein change | Pathogenicity score |
|---|---|---|---|
| 20:37386089 | T>C | F89L | 1.000 |
| 20:37386091 | T>C | F89L | 1.000 |
| 20:37386091 | T>G | F89L | 1.000 |
| 20:37386099 | T>C | L92P | 1.000 |
| 20:37386096 | C>A | A91D | 1.000 |
| 20:37386095 | G>C | A91P | 0.998 |
| 20:37386107 | T>C | Y95H | 0.999 |
| 20:37386090 | T>C | F89S | 0.999 |
| 20:37386101 | T>G | Y93D | 0.999 |
| 20:37386089 | T>G | F89V | 0.979 |
| 20:37386099 | T>A | L92H | 0.996 |
| 20:37386096 | C>T | A91V | 0.996 |
| 20:37386107 | T>A | Y95N | 0.996 |
| 20:37386108 | A>G | Y95C | 0.996 |
| 20:37386102 | A>C | Y93S | 0.994 |
| 20:37386090 | T>G | F89C | 0.992 |
| 20:37386095 | G>A | A91T | 0.993 |
| 20:37386101 | T>C | Y93H | 0.948 |
| 20:37386099 | T>G | L92R | 0.956 |
| 20:37386108 | A>C | Y95S | 0.995 |
| 20:37386108 | A>G | Y95C | 0.996 |
| 20:37386108 | A>T | Y95F | 0.809 |
| 20:37386104 | G>T | D94Y | 0.973 |
| 20:37386105 | A>T | D94V | 0.972 |
| 20:37386102 | A>G | Y93C | 0.970 |
| 20:37386093 | T>G | V90G | 0.975 |
| 20:37386093 | T>C | V90A | 0.930 |
| 20:37386093 | T>A | V90E | 0.960 |
| 20:37386104 | G>C | D94H | 0.934 |
| 20:37384168 | G>C | K5N | 0.775 |
Pathways & Gene Ontology
Reactome Pathways
Total: 69 pathways
| Pathway ID | Pathway Name | Disease-Related |
|---|---|---|
| R-HSA-1227986 | Signaling by ERBB2 | No |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | No |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | No |
| R-HSA-1257604 | PIP3 activates AKT signaling | No |
| R-HSA-180292 | GAB1 signalosome | No |
| R-HSA-186763 | Downstream signal transduction | No |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | Yes |
| R-HSA-354192 | Integrin signaling | No |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | No |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | No |
| R-HSA-418555 | G alpha (s) signalling events | No |
| R-HSA-418594 | G alpha (i) signalling events | No |
| R-HSA-418885 | DCC mediated attractive signaling | No |
| R-HSA-418886 | Netrin mediated repulsion signals | No |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | No |
| R-HSA-5673000 | RAF activation | No |
| R-HSA-5674135 | MAP2K and MAPK activation | No |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | Yes |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | Yes |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | Yes |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | Yes |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | No |
| R-HSA-8874081 | MET activates PTK2 signaling | No |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | Yes |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | No |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | No |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | No |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | No |
| R-HSA-9013420 | RHOU GTPase cycle | No |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | No |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K | No |
| R-HSA-9620244 | Long-term potentiation | No |
| R-HSA-9634597 | GPER1 signaling | No |
| R-HSA-9649948 | Signaling downstream of RAS mutants | Yes |
| R-HSA-9656223 | Signaling by RAF1 mutants | Yes |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | No |
| R-HSA-9766229 | Degradation of CDH1 | No |
| R-HSA-1295596 | Spry regulation of FGF signaling | No |
| R-HSA-1433557 | Signaling by SCF-KIT | No |
| R-HSA-1433559 | Regulation of KIT signaling | No |
| R-HSA-171007 | p38MAPK events | No |
| R-HSA-177929 | Signaling by EGFR | No |
| R-HSA-191650 | Regulation of gap junction activity | No |
| R-HSA-201556 | Signaling by ALK | No |
| R-HSA-2029481 | FCGR activation | No |
| R-HSA-210990 | PECAM1 interactions | No |
| R-HSA-2682334 | EPH-Ephrin signaling | No |
| R-HSA-375165 | NCAM signaling for neurite out-growth | No |
| R-HSA-389356 | Co-stimulation by CD28 | No |
| R-HSA-389513 | Co-inhibition by CTLA4 | No |
| R-HSA-391160 | Signal regulatory protein family interactions | No |
| R-HSA-3928662 | EPHB-mediated forward signaling | No |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | No |
| R-HSA-3928664 | Ephrin signaling | No |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | No |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | No |
| R-HSA-430116 | GP1b-IX-V activation signalling | No |
| R-HSA-437239 | Recycling pathway of L1 | No |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | No |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | No |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | No |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | No |
| R-HSA-5663220 | RHO GTPases Activate Formins | No |
| R-HSA-69231 | Cyclin D associated events in G1 | No |
| R-HSA-8853659 | RET signaling | No |
| R-HSA-8934903 | Receptor Mediated Mitophagy | No |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | Yes |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | Yes |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants | Yes |
Gene Ontology Annotations
Biological Process
Total: 81 terms
| GO ID | Term |
|---|---|
| GO:0000122 | negative regulation of transcription by RNA polymerase II |
| GO:0002223 | stimulatory C-type lectin receptor signaling pathway |
| GO:0002862 | negative regulation of inflammatory response to antigenic stimulus |
| GO:0007155 | cell adhesion |
| GO:0007165 | signal transduction |
| GO:0007172 | signal complex assembly |
| GO:0007173 | epidermal growth factor receptor signaling pathway |
| GO:0007179 | transforming growth factor beta receptor signaling pathway |
| GO:0007229 | integrin-mediated signaling pathway |
| GO:0010632 | regulation of epithelial cell migration |
| GO:0010634 | positive regulation of epithelial cell migration |
| GO:0010954 | positive regulation of protein processing |
| GO:0016236 | macroautophagy |
| GO:0018108 | peptidyl-tyrosine phosphorylation |
| GO:0022407 | regulation of cell-cell adhesion |
| GO:0030154 | cell differentiation |
| GO:0030168 | platelet activation |
| GO:0030900 | forebrain development |
| GO:0031295 | T cell costimulation |
| GO:0031333 | negative regulation of protein-containing complex assembly |
Molecular Function
Total: 21 terms
| GO ID | Term |
|---|---|
| GO:0004672 | protein kinase activity |
| GO:0004713 | protein tyrosine kinase activity |
| GO:0004715 | non-membrane spanning protein tyrosine kinase activity |
| GO:0005102 | signaling receptor binding |
| GO:0005178 | integrin binding |
| GO:0005524 | ATP binding |
| GO:0016004 | phospholipase activator activity |
| GO:0019899 | enzyme binding |
| GO:0020037 | heme binding |
| GO:0030296 | protein tyrosine kinase activator activity |
| GO:0030546 | signaling receptor activator activity |
| GO:0035255 | ionotropic glutamate receptor binding |
| GO:0042169 | SH2 domain binding |
| GO:0043274 | phospholipase binding |
| GO:0044325 | transmembrane transporter binding |
| GO:0046875 | ephrin receptor binding |
| GO:0051117 | ATPase binding |
| GO:0051219 | phosphoprotein binding |
| GO:0070700 | BMP receptor binding |
| GO:0071253 | connexin binding |
| GO:0097110 | scaffold protein binding |
Cellular Component
Total: 18 terms
| GO ID | Term |
|---|---|
| GO:0002102 | podosome |
| GO:0005634 | nucleus |
| GO:0005737 | cytoplasm |
| GO:0005739 | mitochondrion |
| GO:0005743 | mitochondrial inner membrane |
| GO:0005764 | lysosome |
| GO:0005770 | late endosome |
| GO:0005829 | cytosol |
| GO:0005884 | actin filament |
| GO:0005886 | plasma membrane |
| GO:0005901 | caveola |
| GO:0005911 | cell-cell junction |
| GO:0005925 | focal adhesion |
| GO:0030054 | cell junction |
| GO:0032587 | ruffle membrane |
| GO:0045121 | membrane raft |
| GO:0048471 | perinuclear region of cytoplasm |
| GO:0070062 | extracellular exosome |
Protein interactions & networks
Protein-Protein Interactions Summary
Total Interaction Counts (Human SRC - UniProt P12931):
- STRING: ~9,720 interactions
- BioGRID: 1,083 interactions
- IntAct: 801 interactions
- Combined: ~11,604 interactions
TOP 30 Highest-Confidence STRING Interactors
| Rank | Gene Symbol | Protein Name | UniProt ID |
|---|---|---|---|
| 1 | PXN | Paxillin | P49023 |
| 2 | BCAR1 | Breast cancer anti-estrogen resistance protein 1 | P56945 |
| 3 | CTTN | Src substrate cortactin | Q14247 |
| 4 | STAT3 | Signal transducer and activator of transcription 3 | P40763 |
| 5 | TLN1 | Talin-1 | Q9Y490 |
| 6 | ESR1 | Estrogen receptor | P03372 |
| 7 | VCL | Vinculin | P18206 |
| 8 | CRK | Adapter molecule crk | P46108 |
| 9 | ARRB1 | Beta-arrestin-1 | P49407 |
| 10 | HLA-C | Hematopoietic lineage cell-specific protein | P14317 |
| 11 | HSP90AA1 | Heat shock protein HSP 90-alpha | P07900 |
| 12 | CAV1 | Caveolin-1 | Q03135 |
| 13 | TLN2 | Talin-2 | Q9Y4G6 |
| 14 | CBL | E3 ubiquitin-protein ligase CBL | P22681 |
| 15 | HSP90AB1 | Heat shock protein HSP 90-beta | P08238 |
| 16 | TRAF6 | TNF receptor-associated factor 6 | Q9Y4K3 |
| 17 | SHC1 | SHC-transforming protein 1 | P29353 |
| 18 | ARRB2 | Beta-arrestin-2 | P32121 |
| 19 | EGFR | Epidermal growth factor receptor | P00533 |
| 20 | FAK1 (PTK2) | Focal adhesion kinase 1 | Q05397 |
| 21 | PYK2 (PTK2B) | Protein-tyrosine kinase 2-beta | Q14289 |
| 22 | GRB2 | Growth factor receptor-bound protein 2 | P29354 |
| 23 | CTNNB1 | Catenin beta-1 | P35222 |
| 24 | MUC1 | Mucin-1 | P13931 |
| 25 | RACK1 | Small ribosomal subunit protein RACK1 | P25388 |
| 26 | HER2 (ERBB2) | Receptor tyrosine-protein kinase erbB-2 | P04626 |
| 27 | PTPN11 | Tyrosine-protein phosphatase non-receptor type 11 | Q06124 |
| 28 | AKT1 | RAC-alpha serine/threonine-protein kinase | P31749 |
| 29 | SYK | Tyrosine-protein kinase SYK | P43405 |
| 30 | (continued from second page) | Additional regulatory proteins | — |
Protein Similarity
Structural Similarity (DIAMOND-based - Top 20):
Predominantly Src-family tyrosine kinases:
- ABL1 - Tyrosine-protein kinase ABL1
- LCK - Tyrosine-protein kinase Lck
- FYN - Tyrosine-protein kinase Fyn
- YES - Tyrosine-protein kinase Yes
- LYN - Tyrosine-protein kinase Lyn
- HCK - Tyrosine-protein kinase HCK
- FGR - Tyrosine-protein kinase Fgr 8-20. Additional Src-family kinases and related tyrosine kinases (DIAMOND total: 273 similar proteins)
Embedding Similarity (ESM2 - Top 20):
Primary matches align with structural similarity:
- ABL1 - Tyrosine-protein kinase ABL1
- LCK - Tyrosine-protein kinase Lck
- FYN - Tyrosine-protein kinase Fyn
- YES - Tyrosine-protein kinase Yes
- LYN - Tyrosine-protein kinase Lyn
- HCK - Tyrosine-protein kinase HCK
- FGR - Tyrosine-protein kinase Fgr 8-20. Other Src-family members and related kinase domains (ESM2 total: 70 similar proteins)
Key Interaction Networks
Signaling Hub Proteins (>500 interactions):
- EGFR: Growth factor receptor signaling
- FAK1/PTK2: Focal adhesion signaling
- GRB2: Signal transduction adapter
- STAT3: Transcription factor activation
Structural Proteins (prominent interactors):
- Paxillin (PXN), Vinculin (VCL), Talin-1/2 (TLN1/TLN2): Focal adhesion complexes
- Cortactin (CTTN): Actin cytoskeleton
- Caveolin-1 (CAV1): Membrane microdomains
Regulatory Proteins:
- Beta-arrestins (ARRB1/2): Signal termination
- CBL, PTPN11: Ubiquitination and phosphatase regulation
- Heat shock proteins (HSP90AA1/AB1): Chaperone activity
Human SRC (proto-oncogene tyrosine-protein kinase) functions as a central node in receptor tyrosine kinase signaling, particularly in integrin and growth factor receptor pathways, with strongest interactions among focal adhesion proteins, signal transducers, and other non-receptor tyrosine kinases.
Transcription factor regulatory data
SRC is not a transcription factor. It encodes a non-receptor tyrosine kinase (Src family kinase), not a DNA-binding transcription factor. Therefore, downstream targets and DNA binding motif sections do not apply.
Upstream regulators (32 TFs that regulate SRC)
SRC is regulated by 32 transcription factors identified in CollecTRI, with evidence from experimentally validated interactions (ExTRI), literature-curated sources (GEREDB, TRRUST), and computational predictions (DoRothEA_A):
High confidence (evidence-based):
- JUN — Activation (ExTRI, GEREDB)
- AR (Androgen Receptor) — (ExTRI)
- ESR1 (Estrogen Receptor α) — Unknown regulation (ExTRI, DoRothEA_A)
- SP1 — Unknown regulation (ExTRI, TRRUST, DoRothEA_A)
- NCOA3 (Nuclear Receptor Coactivator 3) — (ExTRI)
- NCOA2 (Nuclear Receptor Coactivator 2) — (ExTRI)
Low confidence:
- ARNT (AhR Nuclear Translocator) — (ExTRI)
- ESR2 (Estrogen Receptor β) — (ExTRI)
- EGR1 (Early Growth Response 1) — (ExTRI)
- IER2 (Immediate Early Response 2) — (ExTRI)
- MAFB (MAF BZIP Transcription Factor B) — (ExTRI)
- AP1 (Activator Protein 1) — (ExTRI)
- HNF1A — (ExTRI)
- HIF1A (Hypoxia-Inducible Factor 1α) — (ExTRI)
- KAT7 — (ExTRI)
- JDP2 (Jun Dimerization Protein 2) — (ExTRI)
- JUNB (JUN B Proto-Oncogene) — (ExTRI)
- HNF4A (Hepatocyte Nuclear Factor 4α) — (ExTRI)
- FOXO3 (Forkhead Box O3) — (ExTRI)
- GTF2I (General Transcription Factor IIi) — (ExTRI)
- HHEX (Hematopoietically Expressed Homeobox) — (ExTRI)
- NFIC (Nuclear Factor IC) — (ExTRI)
- NCOA1 (Nuclear Receptor Coactivator 1) — (ExTRI)
- NFKB (NF-κB) — (ExTRI)
- RBPJ — (ExTRI)
- RELA (RELA Proto-Oncogene, NF-κB Subunit) — (ExTRI)
- NFATC1 (Nuclear Factor of Activated T-cells, Cytoplasmic 1) — (ExTRI)
- SP3 — (ExTRI)
- TAF1 (TATA-Box Binding Protein Associated Factor 1) — (ExTRI)
- THRA (Thyroid Hormone Receptor α) — (ExTRI)
- RELB (RELB Proto-Oncogene, NF-κB Subunit) — (ExTRI)
- STAT5A (Signal Transducer and Activator of Transcription 5A) — (ExTRI)
Based on my comprehensive search of the biobtree database, here is the summary:
Drug & pharmacology data
SRC as a drug target: YES, highly validated
Target Summary: SRC (proto-oncogene tyrosine-protein kinase Src, UniProt: P12931) is a well-established drug target in ChEMBL (target ID: CHEMBL267) with 4,009 molecules reported to inhibit this kinase.
Targeting Molecules
- Total count: ~4,009 molecules in ChEMBL targeting SRC
- Approved drugs (Phase 4): 9+ molecules with highest development phase 4
Top 30+ Molecules by Development Phase
Phase 4 (FDA-Approved) - 9 drugs:
| Molecule ID | Name | Mechanism | Phase | Clinical Trials |
|---|---|---|---|---|
| CHEMBL1336 | SORAFENIB | Tyrosine kinase inhibitor (multikinase) | 4 | 572 |
| CHEMBL535 | SUNITINIB | Tyrosine kinase inhibitor (multikinase) | 4 | 300 |
| CHEMBL5416410 | DASATINIB | SRC/ABL tyrosine kinase inhibitor | 4 | 314 |
| CHEMBL1173655 | AFATINIB | ErbB family inhibitor (HER2/EGFR/HER4) | 4 | 179 |
| CHEMBL255863 | NILOTINIB | BCR-ABL inhibitor | 4 | 160 |
| CHEMBL288441 | BOSUTINIB | SRC/ABL tyrosine kinase inhibitor | 4 | 60 |
| CHEMBL1171837 | PONATINIB | Multi-target tyrosine kinase inhibitor | 4 | 58 |
| CHEMBL1289494 | TIVOZANIB | VEGF receptor inhibitor | 4 | 36 |
| CHEMBL1287853 | FEDRATINIB | JAK2 inhibitor | 4 | 27 |
Phase 2 (Development) - Top examples:
| Molecule ID | Name | Mechanism | Phase | Clinical Trials |
|---|---|---|---|---|
| CHEMBL103667 | DORAMAPIMOD | p38 MAPK inhibitor | 2 | 3 |
| CHEMBL119385 | NEFLAMAPIMOD | p38 MAPK inhibitor | 2 | 11 |
| CHEMBL1230609 | FORETINIB | Met/VEGFR inhibitor | 2 | 7 |
| CHEMBL124660 | TANDUTINIB | FLT3 inhibitor | 2 | — |
| CHEMBL1276127 | INDIRUBIN | GSK-3β inhibitor | 2 | — |
Clinical Trials
Top drugs with most clinical trials involving SRC-targeting agents:
- SORAFENIB: 572 trials
- SUNITINIB: 300 trials
- DASATINIB: 314 trials
- AFATINIB: 179 trials
- NILOTINIB: 160 trials
- BOSUTINIB: 60 trials
Primary indications span cancer (CML, GIST, renal cell carcinoma, hepatocellular carcinoma) and inflammatory diseases.
Pharmacogenomics
Drug-gene interactions: No specific SRC pharmacogenomics profile or dosing guidelines currently documented in pharmacogene databases. SRC inhibitor dosing is primarily based on:
- Clinical efficacy and tolerability (not genetic variants)
- Off-target effects (many SRC inhibitors target multiple kinases including ABL, VEGFR, PDGFR, FLT3)
- Individual kinase activity profiles vary; e.g., dasatinib has broader kinase coverage vs. more selective agents
No established pharmacogenomic biomarkers for SRC inhibitor response currently guide therapy selection.
Expression profiles
Tissue expression (Bgee)
SRC shows ubiquitous expression across 286 conditions with 236 present calls (gold quality: 242), average expression score of 81.1, and maximum score of 95.98. Expression is particularly elevated in gastrointestinal tissues.
| Rank | Tissue | Expression Score | Quality |
|---|---|---|---|
| 1 | Body of stomach | 95.98 | Gold |
| 2 | Gall bladder | 95.89 | Gold |
| 3 | Rectum | 95.58 | Gold |
| 4 | Body of pancreas | 95.45 | Gold |
| 5 | Lower esophagus mucosa | 95.36 | Gold |
| 6 | Transverse colon | 95.11 | Gold |
| 7 | Ganglionic eminence | 94.92 | Gold |
| 8 | Cortical plate | 94.65 | Gold |
| 9 | Stomach | 94.25 | Gold |
| 10 | Ectocervix | 94.18 | Gold |
| 11 | Small intestine Peyer’s patch | 94.16 | Gold |
| 12 | Body of uterus | 93.98 | Gold |
| 13 | Muscle layer of sigmoid colon | 93.83 | Gold |
| 14 | Mucosa of transverse colon | 93.62 | Gold |
| 15 | Mucosa of stomach | 93.52 | Gold |
| 16 | Ascending aorta | 93.25 | Gold |
| 17 | Small intestine | 93.15 | Gold |
| 18 | Thoracic aorta | 93.12 | Gold |
| 19 | Right testis | 92.96 | Gold |
| 20 | Endocervix | 92.93 | Gold |
| 21 | Esophagus mucosa | 92.91 | Gold |
| 22 | Ventricular zone | 92.88 | Gold |
| 23 | Metanephros cortex | 92.86 | Gold |
| 24 | Left testis | 92.75 | Gold |
| 25 | Right adrenal gland cortex | 92.73 | Gold |
| 26 | Right adrenal gland | 92.60 | Gold |
| 27 | Right ovary | 92.56 | Gold |
| 28 | Left uterine tube | 92.48 | Gold |
| 29 | Left adrenal gland | 92.48 | Gold |
| 30 | Left adrenal gland cortex | 92.40 | Gold |
Tissue-specific pattern: SRC is enriched in epithelial tissues (GI tract, reproductive organs) and vascular tissues (aorta), with consistent high expression in embryonic neural tissues (ganglionic eminence, cortical plate, ventricular zone). Expression breadth indicates constitutive presence across diverse cell types.
Cell type expression (SCXA - Expression Atlas)
SRC is documented in a baseline single-cell RNA-seq experiment (E-HCAD-29, 78,686 cells) studying GM-CSF-producing T helper cells from blood using NovaSeq sequencing technology. SRC appears expressed in cluster 4 with a marker gene score of 20.65 and log fold change of 6.65, indicating cell-type-specific upregulation in a subset of memory T cells.
Single-cell expression summary
Available single-cell datasets are limited but indicate SRC expression in T cell subsets, particularly in memory T cells with functional relevance to cytokine-producing helper cell differentiation. The marker gene signature presence suggests role in T cell activation and effector functions.
Disease associations
Mendelian / Monogenic Diseases
Thrombocytopenia 6 (Primary condition)
- OMIM ID: 616937
- Mondo ID: MONDO:0014837
- Orphanet ID: 480851 (Hereditary thrombocytopenia with early-onset myelofibrosis)
- Inheritance Pattern: Autosomal dominant
- Evidence Level: Strong (PanelApp Australia), Limited (Labcorp), Supportive (Orphanet)
- Key HPO Features: Thrombocytopenia (HP:0001873), Abnormal bleeding (HP:0001892), Myelofibrosis (HP:0011974), Bone marrow hypercellularity (HP:0031020)
Colorectal Cancer (OMIM:114500)
- Classification: No Known Disease Relationship (GENCC)
- Related HPO: Colon cancer (HP:0003003), Hereditary nonpolyposis colorectal carcinoma (HP:0006716)
Associated Mondo/Orphanet Conditions
- MONDO:0002049 — Thrombocytopenia (general)
- MONDO:0005298 — Osteoporosis
- MONDO:0009692 — Primary myelofibrosis
- MONDO:0014699 — Intellectual disability, autosomal dominant 40
- Orphanet:824 — Primary myelofibrosis (4 associated genes)
Phenotype Associations (HPO)
| HPO ID | Phenotype Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0001873 | Thrombocytopenia |
| HP:0011974 | Myelofibrosis |
| HP:0001892 | Abnormal bleeding |
| HP:0031020 | Bone marrow hypercellularity |
| HP:0000939 | Osteoporosis |
| HP:0003003 | Colon cancer |
| HP:0006716 | Hereditary nonpolyposis colorectal carcinoma |
| HP:0005584 | Renal cell carcinoma |
| HP:0004406 | Spontaneous, recurrent epistaxis |
| HP:0006753 | Neoplasm of the stomach |
| HP:0006740 | Transitional cell carcinoma of the bladder |
| HP:0002891 | Uterine leiomyosarcoma |
| HP:0001442 | Typified by somatic mosaicism |
| HP:0002003 | Large forehead |
| HP:0000601 | Hypotelorism |
| HP:0000490 | Deeply set eye |
Complex Disease / GWAS Associations
| Trait/Disease | Variant | P-value | Study ID |
|---|---|---|---|
| Rheumatoid arthritis | SRC - RPL7AP14 | 4×10⁻¹³ | GCST007843_28 |
| Squamous cell carcinoma | SRC | 1×10⁻⁶ | GCST003422_3 |
| Retinopathy in non-diabetics | SRC - RPL7AP14 | 4×10⁻⁶ | GCST001854_10 |
| L1-L4 bone mineral density × serum urate levels interaction | SRC | 3×10⁻⁶ | GCST012488_35 |