SRF

Summary

SRF (serum response factor, HGNC:11291) is a protein-coding gene on chromosome 6p21.1, encoding Serum response factor (P11831). SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5’ of the site of transcription initiation of some genes (such as FOS). It is a selective cancer dependency (DepMap: 60.3% of cell lines).

This gene encodes a ubiquitous nuclear protein that stimulates both cell proliferation and differentiation. It is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors. This protein binds to the serum response element (SRE) in the promoter region of target genes. This protein regulates the activity of many immediate-early genes, for example c-fos, and thereby participates in cell cycle regulation, apoptosis, cell growth, and cell differentiation. This gene is the downstream target of many pathways; for example, the mitogen-activated protein kinase pathway (MAPK) that acts through the ternary complex factors (TCFs). Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6722 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen)
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 60.3% of screened cell lines
• Transcription factor: yes — 121 downstream targets (CollecTRI)
• MANE Select transcript: NM_003131

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11291
Approved symbol	SRF
Name	serum response factor
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	MCM1
Ensembl gene	ENSG00000112658
Ensembl biotype	protein_coding
OMIM	600589
Entrez	6722

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000265354, ENST00000922430, ENST00000922431

RefSeq mRNA: 2 — MANE Select: NM_003131 NM_001292001, NM_003131

CCDS: CCDS4889

Canonical transcript exons

ENST00000265354 — 7 exons

Exon	Start	End
ENSE00000619140	43178294	43178485
ENSE00000751938	43175706	43175967
ENSE00000751955	43176548	43176667
ENSE00000751956	43178806	43178882
ENSE00000850067	43179095	43181506
ENSE00001848318	43171269	43172169
ENSE00003589895	43173847	43174113

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 96.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6975 / max 163.6229, expressed in 1817 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67876	9.7426	1774
67872	5.6249	1638
67873	5.4477	1674
67877	0.6563	413
67878	0.6428	378
67875	0.4895	282
67879	0.4280	228
67874	0.3890	192
203999	0.2767	122

Top tissues by expression

297 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus muscularis layer	UBERON:0035833	96.18	gold quality
lower esophagus	UBERON:0013473	96.15	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.66	gold quality
left uterine tube	UBERON:0001303	95.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.58	gold quality
popliteal artery	UBERON:0002250	95.49	gold quality
tibial artery	UBERON:0007610	95.48	gold quality
right coronary artery	UBERON:0001625	95.45	gold quality
saphenous vein	UBERON:0007318	95.03	gold quality
aorta	UBERON:0000947	94.82	gold quality
body of uterus	UBERON:0009853	94.58	gold quality
right atrium auricular region	UBERON:0006631	94.38	gold quality
mucosa of stomach	UBERON:0001199	94.23	gold quality
thoracic aorta	UBERON:0001515	94.02	gold quality
ascending aorta	UBERON:0001496	93.99	gold quality
cardiac atrium	UBERON:0002081	93.82	gold quality
apex of heart	UBERON:0002098	93.76	gold quality
heart left ventricle	UBERON:0002084	93.67	gold quality
cardiac ventricle	UBERON:0002082	93.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.16	gold quality
left coronary artery	UBERON:0001626	93.13	gold quality
tendon of biceps brachii	UBERON:0008188	93.01	gold quality
coronary artery	UBERON:0001621	92.91	gold quality
heart	UBERON:0000948	92.89	gold quality
descending thoracic aorta	UBERON:0002345	92.73	gold quality
myometrium	UBERON:0001296	92.50	gold quality
gastrocnemius	UBERON:0001388	92.16	gold quality
smooth muscle tissue	UBERON:0001135	91.82	gold quality
muscle of leg	UBERON:0001383	91.57	gold quality
esophagus	UBERON:0001043	91.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

121 targets.

Target	Regulation
ACTA1	Unknown
ACTA2	Activation
ACTB	Unknown
ACTC1	Activation
ACTG1	Unknown
ACTG2	Activation
ADAM2
AKAP12	Unknown
ANK1	Unknown
AR
ARC	Unknown
BARX2	Activation
BCL2	Unknown
BIRC5	Activation
BMP10
BOK	Activation
CALCA	Activation
CALD1	Unknown
CCN2	Activation
CCND1	Activation
CD74
CDH1	Unknown
CDH5	Unknown
CDKN1A	Unknown
CDKN2B	Activation
CEL
CFTR	Unknown
CKM	Unknown
CNN1	Activation
COL1A2

JASPAR motifs

Motif	Name	Family
MA0083.1	SRF	Responders to external signals (SRF/RLM1)
MA0083.2	SRF	Responders to external signals (SRF/RLM1)
MA0083.3	SRF	Responders to external signals (SRF/RLM1)

JASPAR matrix evidence (PMIDs): PMID:2243767

Upstream regulators (CollecTRI, top): ATF6, E2F1, EGR1, ELK1, ETS1, KAT5, MECP2, MEF2C, MRTFA, NFKB, NKX3-1, NR3C1, PPM1F, SIRT1, SMAD3, SP1, SRF, TBX2, TBX5, TEAD1

miRNA regulators (miRDB)

167 targeting SRF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AT-5P	99.96	70.83	2666

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 60.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex (PMID:11846562)
• mechanisms by which Vav1 can regulate c-fos serum response element transcriptional activity. (PMID:11859076)
• activation by muscarinic receptors via RhoA (PMID:12200418)
• Interaction of serum response factor (SRF) with the Elk-1 B box inhibits RhoA-actin signaling to SRF and potentiates transcriptional activation by Elk-1 (PMID:12242287)
• Results show that alpha-catulin co-expression leads to increased Lbc-induced serum response factor activation and may modulate Rho pathway signaling in vivo by providing a scaffold for the Lbc Rho guanine nucleotide exchange factor. (PMID:12270917)
• Tissue inhibitor of metalloproteinase-3 is downregulated in lymphangioleiomyomatosis as a consequence of abnormal SRF expression. (PMID:12654640)
• role in signal cascade in immediate-early gene induction by anisomycin and arsenite (PMID:12660819)
• SRF is modified by SUMO-1 chiefly at lysine(147) within the DNA-binding domain. (PMID:12788062)
• serum response factor plays a role in facilitating a program of smooth muscle cell-restricted gene expression [review] (PMID:12788374)
• SRF was reduced and processed into 55- and 32-kDa subfragments in failing hearts; SRF-N the N-terminal fragment inhibited transcription of alpha-actin gene promoters in myogenic cells suggesting function as a dominant-negative transcription factor (PMID:12874181)
• SRF is a downstream mediator of VEGF signaling in endothelial cells and a critical requirement for VEGF-induced angiogenesis. (PMID:15180964)
• Results identify protein kinase C delta as the kinase responsible for inactivation of serum response factor both in vitro and endogenously in senescent cells. (PMID:15282327)
• Galphaz signals may attenuate Rho-induced stimulation of serum response factor-mediated transcription. (PMID:15326221)
• TCF-SRF-regulated gene activity has a role in regulating proliferation and in protecting cells from apoptotic cell death (PMID:15542842)
• H. pylori induction of villin in the stomach correlates with activation and cooperative binding of Elk-1 and the SRF to the proximal promoter of villin (PMID:15576363)
• NFAT and SRF may interact to cooperatively regulate smooth muscle cell-specific gene expression and NFAT may have a role in the phenotypic maintenance of smooth muscle (PMID:15857835)
• HERP1 may play a role in promoting the phenotypic modulation of vascular smooth muscle cells during vascular injury and atherosclerotic process by interfering with SRF binding to CArG-box through physical association between HERP1 and SRF (PMID:16151017)
• preventing the age-associated increase in serum response factor is associated with better preserved intracellular calcium handling and functional response to stress (PMID:17122890)
• identified 216 putative SRF binding sites in the genome (PMID:17200232)
• SRF-myocardin overexpression in small cerebral arteries appears to initiate independently of amyloid beta-peptide a pathogenic pathway mediating arterial hypercontractility (PMID:17215356)
• In the presence of Tax, SRF selects more divergent consensus (CArG) box sequences than in the absence of Tax, revealing a novel mechanism for regulating SRF-responsive gene expression. (PMID:17376895)
• Our data indicate that the SRF isoforms were differentially expressed in the human versus mouse cardiac muscle. (PMID:17629633)
• These results suggest a novel indirect mechanism of androgen action on FHL2 expression and provide evidence that SRF is an important determinant of AR action in prostate cancer cells. (PMID:17975004)
• These results suggest induction of SRF-mediated transcription by alpha(E)-catenin either downstream of RhoA or via a parallel pathway. (PMID:18078809)
• identified novel protein-protein interacting domains within Nkx3.1 and SRF (PMID:18296735)
• Mosaic inactivation of the SRF gene in the myocardium induces focal lesions and heart failure. (PMID:18501668)
• Serum induction initially stimulates MKL1 nuclear localization due to a decrease in G-actin levels, but MKL1 is then downregulated by nuclear export due to ERK1/2 phosphorylation. (PMID:18694962)
• growth factors and serum induce expression of Egr-1 and SRF, respectively, which in turn induces E2-EPF UCP expression that positively regulates cancer cell growth (PMID:18780286)
• An important age associated decrease in SRF expression in mice and human muscles, is reported. (PMID:19079548)
• We suggest that SRF and MYOCD function as a transcriptional switch, controlling Abeta cerebrovascular clearance and progression of AD. (PMID:19098903)
• Data show that TGF-beta-induced pulmonary myofibroblast differentiation is mediated by SRF, and that inhibition of myofibroblast differentiation by PKA occurs through down-regulation of SRF expression levels and activity, independent of Smad signaling. (PMID:19151320)
• transcriptional SRF-pathway fingerprint in fumarate hydratase-deficient and sporadic leiomyomas emphasizes the potential importance of this pathway in primary events leading to leiomyomatosis (PMID:19151755)
• RNA interference was used to investigate the contribution of the MRTF-SRF pathway to cytoskeletal dynamics in MDA-MB-231 breast carcinoma and B16F2 melanoma cells, in which basal MRTF-SRF activity is Rho-dependent. (PMID:19198601)
• Promoter analysis showed that PRIP acted through serum-responsive factor to regulate FOS gene expression. (PMID:19329434)
• Results indicate that the altered expression of SRF in papillary carcinoma cells may play an important role in carcinogenesis and progression. (PMID:19513551)
• Data show that a significant overlaps between the ELK1- and SRF-binding regions, and between ELK1- and GABPA-binding regions. (PMID:19687146)
• MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9. (PMID:19724058)
• Results reveal the first ion channel subunit as a direct target of SRF-MYOCD transactivation, providing further insight into the role of MYOCD as a master regulator of the SMC contractile phenotype. (PMID:19801679)
• features in the flanking sequences of functional CArG boxes probably contributing to SRF selectively recognizing and binding to the functional CArG from millions of functionless CArG boxes in mammalian genomes. (PMID:19953255)
• Data show that serum response factor is an essential regulator of primary human vascular smooth muscle cell proliferation and senescence. (PMID:20096952)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	srfb	ENSDARG00000102867
mus_musculus	Srf	ENSMUSG00000015605
rattus_norvegicus	Srf	ENSRNOG00000018232
caenorhabditis_elegans	unc-120	WBGENE00006844

Paralogs (4): MEF2A (ENSG00000068305), MEF2C (ENSG00000081189), MEF2D (ENSG00000116604), MEF2B (ENSG00000213999)

Protein

Protein identifiers

Serum response factor — P11831 (reviewed: P11831)

All UniProt accessions (1): P11831

UniProt curated annotations — full annotation on UniProt →

Function. SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5’ of the site of transcription initiation of some genes (such as FOS). Together with MRTFA transcription coactivator, controls expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration. The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. Required for cardiac differentiation and maturation.

Subunit / interactions. Binds DNA as a multimer, probably a dimer. Interacts with MRTFA, forming the SRF-MRTFA nuclear complex which binds the 5’-CArG-3’ consensus motif (CArG box) on DNA via SRF. Forms a nuclear ternary complex with MRTFA and SCAI. Interacts with MRTFB. Interacts with MLLT7/FOXO4, NKX3A and SSRP1. Interacts with ARID2. Interacts with SRFBP1. Interacts with FOXK1. Interacts with LPXN. Interacts with OLFM2; the interaction promotes dissociation of SRF from the transcriptional repressor HEY2, facilitates binding of SRF to target genes and promotes smooth muscle differentiation. Interacts with NKX3-1. Interacts with KAT5. Interacts with PURB.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated by PRKDC.

RefSeq proteins (2): NP_001278930, NP_003122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002100	TF_MADSbox	Domain
IPR033897	SRF-like_MADS-box	Domain
IPR036879	TF_MADSbox_sf	Homologous_superfamily
IPR050142	MADS-box/MEF2_TF	Family

Pfam: PF00319

UniProt features (31 total): modified residue 9, glycosylation site 5, compositionally biased region 4, region of interest 4, helix 3, strand 3, chain 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1HBX	X-RAY DIFFRACTION	3.15
1K6O	X-RAY DIFFRACTION	3.19
1SRS	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11831-F1	53.17	0.18

Functional residue map

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

Post-translational modifications (9): 77, 79, 83, 85, 103, 224, 253, 435, 446

Glycosylation sites (5): 277, 307, 309, 316, 383

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling
R-HSA-9733709	Cardiogenesis
R-HSA-9768777	Regulation of NPAS4 gene transcription
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9009391	Extra-nuclear estrogen signaling
R-HSA-9634815	Transcriptional Regulation by NPAS4
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-9768759	Regulation of NPAS4 gene expression

MSigDB gene sets: 595 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_MEMORY, RNGTGGGC_UNKNOWN, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COGNITION, GOBP_AXIS_SPECIFICATION, GOBP_BEHAVIOR

GO Biological Process (81): branching involved in blood vessel morphogenesis (GO:0001569), response to hypoxia (GO:0001666), mesoderm formation (GO:0001707), neuron migration (GO:0001764), trophectodermal cell differentiation (GO:0001829), heart looping (GO:0001947), morphogenesis of an epithelial sheet (GO:0002011), cell migration involved in sprouting angiogenesis (GO:0002042), transcription by RNA polymerase II (GO:0006366), cell-matrix adhesion (GO:0007160), heart development (GO:0007507), long-term memory (GO:0007616), negative regulation of cell population proliferation (GO:0008285), associative learning (GO:0008306), response to toxic substance (GO:0009636), response to hormone (GO:0009725), epithelial structure maintenance (GO:0010669), hippocampus development (GO:0021766), tangential migration from the subventricular zone to the olfactory bulb (GO:0022028), actin cytoskeleton organization (GO:0030036), regulation of cell adhesion (GO:0030155), platelet activation (GO:0030168), platelet formation (GO:0030220), negative regulation of cell migration (GO:0030336), thyroid gland development (GO:0030878), response to cytokine (GO:0034097), megakaryocyte development (GO:0035855), dorsal aorta morphogenesis (GO:0035912), stress fiber assembly (GO:0043149), skin morphogenesis (GO:0043589), positive thymic T cell selection (GO:0045059), sarcomere organization (GO:0045214), positive regulation of cell differentiation (GO:0045597), positive regulation of axon extension (GO:0045773), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of smooth muscle contraction (GO:0045987), positive regulation of transcription by glucose (GO:0046016), muscle cell cellular homeostasis (GO:0046716), filopodium assembly (GO:0046847), thymus development (GO:0048538)

GO Molecular Function (18): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), serum response element binding (GO:0010736), chromatin DNA binding (GO:0031490), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), primary miRNA binding (GO:0070878), DNA-binding transcription factor binding (GO:0140297), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), chromatin binding (GO:0003682), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), protein dimerization activity (GO:0046983)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Signal Transduction	2
RHO GTPase Effectors	1
Nuclear Events (kinase and transcription factor activation)	1
Extra-nuclear estrogen signaling	1
Developmental Biology	1
Regulation of NPAS4 gene expression	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by NTRKs	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signaling by NTRK1 (TRKA)	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Signaling by Nuclear Receptors	1
ESR-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
response to chemical	2
transcription cis-regulatory region binding	2
DNA binding	2
binding	2
angiogenesis	1
blood vessel morphogenesis	1
branching morphogenesis of an epithelial tube	1
response to stress	1
response to decreased oxygen levels	1
formation of primary germ layer	1
mesoderm morphogenesis	1
cell migration	1
generation of neurons	1
blastocyst formation	1
cell differentiation	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
morphogenesis of an epithelium	1
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
DNA-templated transcription	1
cell-substrate adhesion	1
animal organ development	1
circulatory system development	1
memory	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
learning	1
response to endogenous stimulus	1
tissue homeostasis	1
pallium development	1
limbic system development	1
anatomical structure development	1
olfactory bulb development	1
telencephalon cell migration	1
cytoskeleton organization	1
actin filament-based process	1

Protein interactions and networks

STRING

3032 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRF	MYOCD	Q8IZQ8	999
SRF	MRTFA	Q969V6	992
SRF	FOXG1	P55315	986
SRF	NKX2-5	P52952	979
SRF	MRTFB	Q9ULH7	955
SRF	GATA4	P43694	920
SRF	SRFBP1	Q8NEF9	889
SRF	MYOG	P15173	807
SRF	FOS	P01100	803
SRF	TAGLN	Q01995	803
SRF	MYOD1	P15172	801
SRF	FOXO1	Q12778	787
SRF	RHOA	P06749	775
SRF	CDC42	P21181	772
SRF	HDAC4	P56524	768

IntAct

24 interactions, top by confidence:

A	B	Type	Score
MRTFB	SRF	psi-mi:“MI:0915”(physical association)	0.660
SRF	MRTFB	psi-mi:“MI:0915”(physical association)	0.660
MRTFA	SRF	psi-mi:“MI:0915”(physical association)	0.590
SRF	MRTFA	psi-mi:“MI:0915”(physical association)	0.590
SRF	MYOD1	psi-mi:“MI:0407”(direct interaction)	0.530
MYOG	SRF	psi-mi:“MI:0407”(direct interaction)	0.530
SRF	MYOG	psi-mi:“MI:0915”(physical association)	0.530
MYOD1	SRF	psi-mi:“MI:0915”(physical association)	0.530
SRF	MYOCD	psi-mi:“MI:0915”(physical association)	0.520
MYOCD	SRF	psi-mi:“MI:0915”(physical association)	0.520
SRF	GTF2F1	psi-mi:“MI:0407”(direct interaction)	0.410
SRF	ELK4	psi-mi:“MI:0407”(direct interaction)	0.410
SRF	PCNA	psi-mi:“MI:0915”(physical association)	0.370
ALDH3A1	SRF	psi-mi:“MI:0915”(physical association)	0.370
CIRBP	SRF	psi-mi:“MI:0915”(physical association)	0.370
SRF	GPC4	psi-mi:“MI:0914”(association)	0.350
	BANF1	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
SRF	ZNF292	psi-mi:“MI:2364”(proximity)	0.270
	JUN	psi-mi:“MI:2364”(proximity)	0.270
	SRF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (172): SRF (Biochemical Activity), SRF (Reconstituted Complex), SRF (Reconstituted Complex), SRF (Reconstituted Complex), SRF (Affinity Capture-Western), FHL2 (Affinity Capture-Western), MKL1 (Reconstituted Complex), SRF (Two-hybrid), SRF (Affinity Capture-Western), MYOCD (Reconstituted Complex), TRIP4 (Reconstituted Complex), SRF (Reconstituted Complex), TRIP4 (Two-hybrid), NCOA1 (Two-hybrid), NCOA1 (Reconstituted Complex)

ESM2 similar proteins: A2ICN5, B3NAM7, B4NXA8, B7SBD2, E9Q7M2, F8VPJ6, M9PBE2, O54826, O75157, O89038, O94842, P11831, P45481, P46936, P55197, P62500, P62501, P83741, Q14814, Q15714, Q2KHR2, Q3LHL9, Q4R4H5, Q4VYR7, Q5F3U0, Q5M7C3, Q5R4H1, Q5R6A9, Q5REW7, Q5RFW2, Q63943, Q6DDH6, Q6JHU9, Q6R2V0, Q80W03, Q8BIH0, Q8BU11, Q8CHI8, Q8IVH2, Q8VIG0

Diamond homologs: A0A217EJJ0, A0A3Q7EKL1, A2RVQ5, A2XDY1, A2Y9P0, A2YNI2, A2Z9Q7, B4YPW6, F6I457, I1GN76, K4BND8, K4DEK0, O04067, O22456, O64645, O65874, O82743, O82794, P07249, P0C5B0, P0C5B2, P11746, P11831, P17839, P23790, P29381, P29382, P29383, P29384, P29385, P29386, P78926, Q003J2, Q01540, Q03378, Q03416, Q03488, Q03489, Q07472, Q07474

SIGNOR signaling

31 interactions.

A	Effect	B	Mechanism
SRF	“up-regulates quantity by expression”	ACTA2	“transcriptional regulation”
MAPKAPK2	up-regulates	SRF	phosphorylation
KLF4	down-regulates	SRF	binding
MRTFA	up-regulates	SRF	binding
MRTFB	up-regulates	SRF	binding
MYOCD	up-regulates	SRF	binding
SRF	“up-regulates quantity by expression”	CNN1	“transcriptional regulation”
SRF	“up-regulates quantity by expression”	TAGLN	“transcriptional regulation”
MRTFB	“up-regulates activity”	SRF	binding
SRF	“up-regulates quantity by expression”	PLG	“transcriptional regulation”
SRF	“up-regulates quantity by expression”	PLAU	“transcriptional regulation”
SRF	“down-regulates quantity by repression”	SERPINE1	“transcriptional regulation”
SRF	up-regulates	PTGS2
SRF	up-regulates	IL6
PRKCD	“down-regulates activity”	SRF	phosphorylation
PRRX1	up-regulates	SRF	binding
MAPKAPK2	unknown	SRF	phosphorylation
SRF	“form complex”	NKX3-1/SRF	binding
PRKACA	up-regulates	SRF	phosphorylation
PRKCA	up-regulates	SRF	phosphorylation
PRKG1	up-regulates	SRF	phosphorylation
PRKCA	down-regulates	SRF	phosphorylation
DMPK	up-regulates	SRF	phosphorylation
PRKDC	“up-regulates activity”	SRF	phosphorylation
CAMK2A	“up-regulates activity”	SRF	phosphorylation
CSNK2A1	“up-regulates activity”	SRF	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

887 predictions. Top by Δscore:

Variant	Effect	Δscore
6:43172148:G:GT	donor_gain	1.0000
6:43172166:GAAG:G	donor_gain	1.0000
6:43172169:GGTA:G	donor_loss	1.0000
6:43173844:CAG:C	acceptor_loss	1.0000
6:43173845:AGG:A	acceptor_loss	1.0000
6:43173846:G:GT	acceptor_loss	1.0000
6:43174111:AAG:A	donor_loss	1.0000
6:43174112:AGG:A	donor_loss	1.0000
6:43174113:GG:G	donor_loss	1.0000
6:43174114:G:T	donor_loss	1.0000
6:43174115:T:A	donor_loss	1.0000
6:43176664:ACAG:A	donor_loss	1.0000
6:43176665:CAG:C	donor_loss	1.0000
6:43176666:AGG:A	donor_loss	1.0000
6:43176667:GGTAT:G	donor_loss	1.0000
6:43176668:G:C	donor_loss	1.0000
6:43176669:T:A	donor_loss	1.0000
6:43178292:A:AG	acceptor_gain	1.0000
6:43178292:AGT:A	acceptor_gain	1.0000
6:43178293:G:GG	acceptor_gain	1.0000
6:43178293:GT:G	acceptor_gain	1.0000
6:43178293:GTG:G	acceptor_gain	1.0000
6:43178293:GTGAC:G	acceptor_gain	1.0000
6:43178481:GCCAG:G	donor_gain	1.0000
6:43178482:CCAGG:C	donor_loss	1.0000
6:43178483:CAGG:C	donor_loss	1.0000
6:43178484:AGGT:A	donor_loss	1.0000
6:43178485:GGTG:G	donor_loss	1.0000
6:43178486:G:C	donor_loss	1.0000
6:43178487:T:A	donor_loss	1.0000

AlphaMissense

3263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:43172080:G:C	G142R	1.000
6:43172080:G:T	G142C	1.000
6:43172081:G:A	G142D	1.000
6:43172081:G:T	G142V	1.000
6:43172083:C:A	R143S	1.000
6:43172083:C:G	R143G	1.000
6:43172083:C:T	R143C	1.000
6:43172084:G:A	R143H	1.000
6:43172089:A:G	K145E	1.000
6:43172091:G:C	K145N	1.000
6:43172091:G:T	K145N	1.000
6:43172093:T:A	I146N	1.000
6:43172093:T:C	I146T	1.000
6:43172093:T:G	I146S	1.000
6:43172099:T:A	M148K	1.000
6:43172099:T:C	M148T	1.000
6:43172099:T:G	M148R	1.000
6:43172104:T:A	F150I	1.000
6:43172104:T:C	F150L	1.000
6:43172104:T:G	F150V	1.000
6:43172105:T:C	F150S	1.000
6:43172105:T:G	F150C	1.000
6:43172106:C:A	F150L	1.000
6:43172106:C:G	F150L	1.000
6:43172108:T:A	I151N	1.000
6:43172108:T:G	I151S	1.000
6:43172116:A:G	K154E	1.000
6:43172117:A:T	K154M	1.000
6:43172118:G:C	K154N	1.000
6:43172118:G:T	K154N	1.000

dbSNP variants (sampled 300 via entrez): RS1000391147 (6:43171272 C>T), RS1000806155 (6:43169687 G>C), RS1001176403 (6:43169846 A>G), RS1001374789 (6:43176344 G>A), RS1001596910 (6:43171313 T>C), RS1001670409 (6:43177246 G>T), RS1002276812 (6:43170209 C>A), RS1002307726 (6:43169983 T>G), RS1002451924 (6:43177017 A>G), RS1002946135 (6:43173456 C>G), RS1003110652 (6:43170517 G>A), RS1003124230 (6:43179728 G>A), RS1003169912 (6:43178657 C>G), RS1003254142 (6:43179939 T>C), RS1003273382 (6:43171391 G>T)

Disease associations

OMIM: gene MIM:600589 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (1): congenital heart disease (MONDO:0005453)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523184 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases reaction, increases phosphorylation	2
tetrachlorodian	decreases reaction, increases expression, affects expression	2
SB 203580	decreases reaction, increases phosphorylation, increases expression	2
Arsenic Trioxide	decreases expression	2
Benzo(a)pyrene	affects activity, decreases methylation	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
8-bromocyclic GMP	affects cotreatment, increases activity	1
cobaltous chloride	affects cotreatment, affects expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
lead chloride	affects cotreatment, affects expression	1
latrunculin B	decreases activity, increases expression	1
cadmium sulfate	affects cotreatment, affects expression	1
beta-methylcholine	affects expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
8-((4-chlorophenyl)thio)cyclic-3’,5’-GMP	affects cotreatment, increases activity	1
jasplakinolide	increases activity	1
chromium hexavalent ion	increases abundance, decreases expression	1
3-nitrobenzanthrone	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline	decreases reaction, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Gefitinib	decreases reaction, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4423931	Binding	Inhibition of SRF (unknown origin) mediated VP16 transcription expressed in human HeLa cells assessed as basal transcriptional activity level up to 100 uM after 6 hrs by nanoluciferase reporter gene assay	Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6S4	SEES3-1V human SRF, clone1	Embryonic stem cell	Male
CVCL_A6S5	SEES3-1V human SRF, clone2	Embryonic stem cell	Male
CVCL_A6S6	SEES3-1V human SRF, clone3	Embryonic stem cell	Male
CVCL_B7ZK	Abcam Raji SRF KO	Cancer cell line	Male
CVCL_C0AD	Abcam THP-1 SRF KO	Cancer cell line	Male
CVCL_C7C1	Abcam PC-3 SRF KO	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE