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Symbol SRF contributors: shn/npt - updated : 13-05-2015
HGNC name serum response factor (c-fos serum response element-binding transcription factor)
HGNC id 11291
Location 6p21.1      Physical location : 43.138.919 - 43.149.243
Synonym name
  • C-fos serum response element-binding factor
  • MADS-box protein
  • serum response factor
  • Synonym symbol(s) MCM1, ELK3, SAP2, MCM1
    TYPE functioning gene
    STRUCTURE 10.33 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D6S1552 - D6S1582 - SRF - D6S282 - D6S271 - cen
    Physical map
    RDS 6p21.2-p11.1 retinal degeneration, slow LOC391920 6 similar to Vacuolar ATP synthase 16 kDa proteolipid subunit TBCC 6p21.1 tubulin-specific chaperone c KIAA0240 6p21.1 KIAA0240 RPL7L1 6p21.1 ribosomal protein L7-like 1 PTCRA 6p21.2-p21.3 pre T-cell antigen receptor alpha TNRC5 6pter-p12.1 trinucleotide repeat containing 5 LOC389390 6 LOC389390 RPL24P4 6p21.1 ribosomal protein L24 pseudogene 4 GNMT 6p12 glycine N-methyltransferase PEX6 6p21.1 peroxisomal biogenesis factor 6 PPP2R5D 6p21.1 protein phosphatase 2, regulatory subunit B (B56), delta isoform MEA 6p21.3-p21.1 male-enhanced antigen KLHDC3 6p21.1 kelch domain containing 3 C6orf153 6p21.1 chromosome 6 open reading frame 153 KIAA0076 6p21.1 chromosome 6 open reading frame 153 MRPL2 6p21.3 mitochondrial ribosomal protein L2 KNSL8 6p21.1 kinesin-like 8 PTK7 6p21.1-p12.2 PTK7 protein tyrosine kinase 7 SRF 6p12.3 serum response factor (c-fos serum response element-binding transcription factor) PARC 6p21.1 p53-associated parkin-like cytoplasmic protein C6orf108 6p21.1 chromosome 6 open reading frame 108 TTBK1 6p21.1 tau tubulin kinase 1 SLC22A7 6p21.2-p21.1 solute carrier family 22 (organic anion transporter), member 7 LOC389391 6 similar to thymus LIM protein TLP-B ZNF318 6pter-p12.1 zinc finger protein 318 ABCC10 6p21.2-p21.1 ATP-binding cassette, sub-family C (CFTR/MRP), member 10 EGFL9 6p21.1 EGF-like-domain, multiple 9 TJP4 6p12.3 tight junction protein 4 (peripheral)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 4343 55 508 - -
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Lymphoid/Immunespleen   highly
     thymus   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text pancreas
  • DNA binding domain
  • dimerization domain
  • MADS domain
  • RPEL motifs that are monomeric globular actin (G-actin) binding elements that regulate MYOCD and MYOCD-related transcription factors (MRTFs) localization and activity
  • conjugated GlycoP , PhosphoP
    mono polymer homomer , dimer
    interspecies ortholog to Srf, Rattus norvegicus
    ortholog to srf, Danio rerio
    ortholog to SRF, Pan troglodytes
    ortholog to Srf, Mus musculus
  • MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • playing an essential role for transcriptional regulation of numerous growth-factor-inducible genes, such as C-FOS oncogene and muscle-specific actin genes
  • stimulating both cell proliferation and differentiation
  • participating in cell cycle regulation, apoptosis, cell growth, and cell differentiation
  • required for the FOXK1 to regulate and be recruited to the SM alpha-actin promoter
  • particularly important in T cell activation
  • activates basal transcription from the human T-cell leukemia virus-I (HTLV-I) long terminal repeat (LTR)
  • plays an important role in sprouting angiogenesis and small vessel integrity
  • major regulator of genes encoding contractile proteins, notably all muscle actin isoforms, but also of genes involved in energy transfer like muscle creatine kinase (MCK) or in calcium homeostasis
  • regulates neuronal migration and axon guidance and learning
  • SRF controls amyloid beta-peptide clearance from cerebral vascular smooth muscle cells in Alzheimer’s disease (AD), the degree of cerebral amyloid angiopathy (CAA) and focal amyloid beta-peptide brain accumulations in animal models of CAA and AD
  • maintains a balanced expression of CKM and sarcomeric Actin gene expression ensuring the adequacy between phosphocreatine flux and ATP demand by the actomyosin complex
  • major transcription factor that regulates activity-driven gene expression in neurons
  • SRF and the myocardin-related transcription factors (MKL1, MKL2) are key mediators of the contractile gene program in response to TGFB1 or RHOA signaling
  • SRF-cofilin-actin signaling axis modulates potentially neuronal mitochondrial function
  • is selectively required for endothelial filopodia formation and cell contractility during sprouting angiogenesis
  • has a unique function in regulating migratory tip cell behavior during sprouting angiogenesis
  • required for optimal responses of elicited peritoneal macrophages to type I interferons
  • FOXF1 and SRF synergistically activate the telokin promoter and FOXF1 promotes SRF-myocardin binding
  • binds to coactivators, such MKL1, and mediates gene transcription elicited by diverse signaling pathways
  • essential for megakaryocyte maturation and platelet formation and function
  • plays a critical role in regulating axon growth in the mammalian brain
  • CELLULAR PROCESS cell cycle, progression
    cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    signaling signal transduction
    being the downstream target of many pathways, for example, the mitogen-activated protein kinase pathway (MAPK) that acts through the ternary complex factors (TCFs)
    a component
  • binding 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
  • binding to the CArG box consensus sequence found in the control regions of numerous serum-inducible and muscle-specific genes
  • SRF binds the Fhl2 promoter in vivo and regulates Fhl2 expression in response to RhoA activation
  • ATF sites of the FRA-1 promoter
  • c-fos promoter of transcription factor TFIIF
  • RNA
    small molecule
  • SRE of FOS, in cooperation with ATF6 and transiently activating FOS transcription
  • myocardin (MYOCD)
  • TEAD1 through the MADS domain to coactivate the skeletal alpha-actinin promoter
  • interacting with ZIC3 (physically and functionally associate with ZIC3 suggesting that it may play a role as a mediator of its activities in mesoderm and committed cardiac lineages)
  • interaction with FOXK1 (important for the regulation of the SRF target genes SM alpha-actin and PPGB)
  • CCAAT/enhancer-binding protein-beta
  • CRP1, CRP2 and GATA
  • ELK1, SAP1a, FLI1, EWS-FLI1, ETS1, ETS2, PEA3 and PU.1 proteins can form ternary complexes with SRF on the Egr1 SREI and II
  • spindlin (SPIN), homeodomain-only protein (HOP)
  • TEA/ATTS DNA-binding domain of transcription enhancer factor-1
  • steroid receptor coactivator-1 (SRC-1) and p300
  • SSRP1 (structure-specific recognition protein)
  • NF-kappaB subunit p65, Nkx-2.5
  • homologue of the Drosophila NK-3 homeodomain gene bagpipe (Nkx3-1)
  • subunit of nuclear factor-Y (NF-YA)
  • myogenin-E12
  • megakaryoblastic leukemia-1 and 2 (MKL1, MKL2)
  • high mobility group at-hook 1 (HMGA1)
  • cysteine-rich LIM-only proteins, CRP1 and CRP2
  • activating transcription factor 6 (ATF6)
  • TEA/ATTS DNA-binding domain of transcription enhancer factor-1
  • PEA3-binding factor, p35C/EBPbeta and p20C/EBPbeta
  • barH-like homeobox 2b (BARX2b)
  • interaction with PDLIM3
  • human activating signal cointegrator 1 (hASC-1)
  • interacting with KLF3 (SRF may regulate many striated- and smooth-muscle genes that lack known SRF control elements)
  • essential co-regulator of the CKM and genes encoding sarcomeric proteins in the adult heart
  • LMOD1 is a Smooth muscle cell-restricted SRF/MYOCD target gene
  • overexpression of SRF induced RUNX2 transactivity in control cells and restored RUNX2 transactivity in the SRF-deficient cells)
  • MYOCD functions as a transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression
  • dysfunction of MKL2 and its transcriptional coactivation partner, SRF, was supported by a decrease in gene and protein expression of CDK16, a downstream target of MKL2:SRF heterodimer transcriptional activation
  • TEAD1 is a novel general repressor of smooth muscle-specific gene expression through interfering with MYOCD binding to SRF
  • ACTR5 bound to a DNA binding domain of SRF via its C-terminal sequence and prevented the association of the MYOCD-SRF complex with the promoter regions of smooth muscle genes
  • GSK3B binds to and directly phosphorylates SRF on a highly conserved serine residue
  • SRF utilizes MKL1/2 to fulfill steady state cellular functions, including cytoskeletal organization, and utilizes ELK4 to facilitate acute responses to external infection
  • SRF regulates craniofacial development through selective recruitment of MKL1 cofactors by PDGF signaling
  • MYOCD is a co-factor of serum response factor (SRF) and is considered to be the master regulator of VSMC differentiation
  • cell & other
    activated by human immunodeficiency virus (HIV)-1 transmembrane protein gp41 (gp41C)
    thyroid hormone receptors (SMRT)
    cytokines, growth factors, and G-coupled receptors, which are known to play a major role in cardiac remodeling
    GSK3B (phosphorylation and activation of SRF by GSK3B is critical for SRF-dependent axon growth in mammalian central neurons)
    inhibited by LAGY
    Other RhoA signaling regulates the activity of the transcription factor SRF during muscle differentiation
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in the failing heart
    Variant & Polymorphism
    Candidate gene
    Therapy target
    targeting the SRF pathway could provide an opportunity to selectively target tip cell filopodia-driven angiogenesis to restrict tumor growth
  • Srf-null mouse embryos fail to gastrulate and form mesoderm
  • Mice with skeletal muscle-specific Srf deletion died during the perinatal period from severe skeletal muscle hypoplasia