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FLASH GENE
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
    DNA
    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)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 4343 55 508 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Lymphoid/Immunespleen   highly
     thymus   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text pancreas
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
    HOMOLOGY
    interspecies ortholog to Srf, Rattus norvegicus
    ortholog to srf, Danio rerio
    ortholog to SRF, Pan troglodytes
    ortholog to Srf, Mus musculus
    Homologene
    FAMILY
  • MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    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
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    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
    INTERACTION
    DNA
  • 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
    protein
  • 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
    REGULATION
    activated by human immunodeficiency virus (HIV)-1 transmembrane protein gp41 (gp41C)
    p65/NF-kappaB
    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
    HOMEODOMAIN-ONLY PROTEIN (HOP)
    Other RhoA signaling regulates the activity of the transcription factor SRF during muscle differentiation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in the failing heart
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting the SRF pathway could provide an opportunity to selectively target tip cell filopodia-driven angiogenesis to restrict tumor growth
    ANIMAL & CELL MODELS
  • 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