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FLASH GENE
Symbol SRC contributors: mct/npt/pgu - updated : 19-06-2017
HGNC name v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)
HGNC id 11283
DNA
TYPE functioning gene
STRUCTURE 60.73 kb     14 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
text structure binding site for hepatic nuclear factor 1 (HNF1) alpha isoform
MAPPING cloned Y linked Y status confirmed
Physical map
EPB41L1 20q11.2-q12 erythrocyte membrane protein band 4.1-like 1 C20orf4 20pter-q12 chromosome 20 open reading frame 4 DAP4 20q11.23 disks large-associated protein 4 MYL9 20q11.22 myosin, light polypeptide 9, regulatory TGIF2 20q11.2-q12 TGFB-induced factor 2 (TALE family homeobox) C20orf24 20q11.23 chromosome 20 open reading frame 24 SLA2 20q11.22 Src-like-adaptor 2 NDRG3 20q11.21-q11.23 NDRG family member 3 C20orf172 20q11.23 chromosome 20 open reading frame 172 KIAA0889 20q11.23 KIAA0889 protein LOC343574 20q11.23 similar to dJ132F21.2 (Contains a novel protein similar to the L82E from Drosophila) SAMHD1 20q11.22 SAM domain and HD domain 1 RBL1 20q11.21 retinoblastoma-like 1 (p107) RPS3AP3 20q11.2 ribosomal protein S3A pseudogene 3 C20orf132 20q11.22 chromosome 20 open reading frame 132 RPN2 20q11.22-q11.23 ribophorin II GHRH 20q11.21 growth hormone releasing hormone MANBAL 20q11.23-q12 mannosidase, beta A, lysosomal-like SRC 20q11.21 v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) RPL7AL4 20q11.2 ribosomal protein L7A-like 4 BLCAP 20q11.2-q12 bladder cancer associated protein NNAT 20q11.2-q12 neuronatin PPIAP3 20q11.23 peptidylprolyl isomerase A (cyclophilin A) pseudogene 3 GLRXP 20q11.2 glutaredoxin (thioltransferase) pseudogene CTNNBL1 20q11.23-q12 catenin, beta like 1 C20orf102 20q11.23 chromosome 20 open reading frame 102 KIAA0406 20q11.21-q12 Homo sapiens KIAA0406 gene product (KIAA0406), mRNA. C20orf77 20q11.21-q12 chromosome 20 open reading frame 77 TGM2 20q11.2 transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase) KIAA1755 20q12 KIAA1755 protein BPI 20q11.23 bactericidal/permeability-increasing protein LBP 20q11.23-q12 lipopolysaccharide binding protein LOC388796 20 LOC388796 LOC128439 20q12 hypothetical gene LOC128439 KIAA1219 20q12 KIAA1219 protein
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 splicing 4145 59 536 - 2009 19258394
  • this variant represents the longer transcript
  • both isoforms 1 ant 2 encode the same protein
  • 14 splicing 4044 59 536 - 2009 19258394
  • this variant differs in the 5'UTR compared to variant 1
  • both isoforms 1 ant 2 encode the same protein
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  moderately
     intestinelarge intestinecolon moderately
     mouth   moderately
    Endocrinethyroid   moderately
    Nervousnerve   moderately
    Reproductivemale systemmale genital tractepididymis highly Mus musculus
    Respiratorylung   moderately
    Skin/Tegumentskin   moderately
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four highly conserved Src homology (SH) domains termed SH1 to SH4 followed by a bipartite kinase domain
  • tyrosine kinase catalytic domain
  • C-terminus as a ligand for a PDZ (postsynaptic density 95, PSD-95)
  • HOMOLOGY
    interspecies homolog to avian sarcoma (Schmidt-Ruppin A-2) viral (v-src) oncogene
    homolog to rattus Src (99,25 pc)
    homolog to murine Src (99,07 pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • SRC subfamily
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • membrane associated
  • localize to the cytoplasmic face of the plasma membrane through lipid modification
  • a truncated Src fragment of ~52 kDa, localized predominantly to the cytosol
  • basic FUNCTION
  • non receptor tyrosine kinase, direct effector of G proteins
  • playing a role in the regulation of embryonic development and cell growth
  • has an appreciable role in the organization of the Golgi apparatus, which may be linked to its involvement in protein transport from the Golgi apparatus to the endoplasmic reticulum
  • has an appreciable role in the organization of the Golgi apparatus, which may be linked to its involvement in protein transport from the Golgi apparatus to the endoplasmic reticulum
  • SRC and PTK2 cooperate to phosphorylate GIT2, stimulate its focal adhesion localization, and regulate cell spreading and protrusiveness
  • monopalmitoylated SFK required for VEGF mitogenic signaling with SRC and FYN, but maintaining distinct properties in the regulation of VEGF-mediated endothelial cell events
  • regulates Golgi structure and KDELR1-dependent retrograde transport to the endoplasmic reticulum
  • having a key role in the maintenance of epithelial integrity
  • major kinase implicated in PTK2 phosphorylation, and is directly translocated from focal adhesions to membrane ruffles, thereby promoting formation of new adhesion complexes
  • crucially involved in the ghrelin-mediated Akt activation
  • non palmitoylated SFK (Src-family tyrosine kinase), rapidly exchanged between the plasma membrane and late endosomes/lysosomes (suggest that SFK trafficking is specified by the palmitoylation state in the SH4 domain)
  • interacting with PDLIM4 and PTPN13 (PDLIM4 suppresses SRC activation through interacting with SRC and PTPN13, allowing PTPN13-dependent dephosphorylation of SRC at the activation loop)
  • SRC inhibits SGK1-mediated phosphorylation hereby restoring the WNK4-mediated inhibition of ROMK channels thus suppressing K secretion)
  • binds DVL2, a key phosphoprotein in Wnt signaling, at two positions: an SH3-binding domain and a C-terminal domain
  • its activity is required for IL13-induced STAT1 and STAT3 Ser-727 phosphorylation
  • important and novel role for the SRC-SH3PXD2A pathway in neural crest cell migration during embryonic development
  • regulatory role on MAPK14 phosphorylation in alternatively activated monocytes/macrophages
  • SRC-stimulated BAIAP2L1 phosphorylation is essential for its function in cell motility
  • SRC and FURIN play crucial roles in tumorigenesis
  • SRC and IL6 inhibit osteoblast differentiation and integrate IGFBP5 signalling
  • preservation of complex I function by mitochondrial SRC kinase could be important in the development of the overall phenotype of cancer
  • organizes the cell cytoskeleton in response to the cytokine, but it does not participate in TNFSF11-stimulated osteoclast formation
  • is involved in spindle orientation through centrosome-mediated aster formation
  • is essential for cauda epididymal development, suggesting an essential role of this kinase in epididymal sperm maturation involving SRC extracellular trafficking
  • maintains neuronal survival, and calpain cleavage is a molecular switch converting SRC from a promoter of cell survival to a mediator of neuronal death in excitotoxicity
  • SRC inhibits likely cytokinesis through the delocalization of KIF23 and AURKB from the spindle midzone, resulting in binucleation
  • is able to physically associate with, and phosphorylate ING1, which results in a nuclear to cytoplasmic relocalization of ING1 in cells and a decrease of ING1 stability
  • SRC, FERMT2 and FBLIM1 together constitute a positive feedback loop that controls SRC activity and regulates integrin-mediated cellular functions
  • NAA15, a subunit of the N-terminal acetyltransferase NatA, complexes with the SRC substrate CTTN and supports adult retinal homeostasis through regulation of vascular permeability
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with MLLT4 (through its PDZ domain)
  • interacted with both EPHA2 and ACP1, and the interactions increased in EPHA2-overexpressing cells
  • CA9 is a new down-stream target for SRC oncogene
  • ARHGEF5 is tyrosine-phosphorylated by SRC and bound to SRC to positively regulate its activity
  • SH3PXD2B is a scaffold protein that plays a key role in regulating the actin cytoskeleton via SRC and CTTN
  • association between FURIN and MMP14 is regulated by the tyrosine kinase SRC
  • SRC stimulates IL6 expression through the STAT3 factor, which, in response to IL6 induces insulin-like growth factor 5 (IGFBP5), a SRC activating factor that amplifies this loop only in immature osteoblasts
  • NOTCH1-FURIN interaction is regulated by the non-receptor tyrosine kinase, SRC
  • ATP1A1 might interact with and regulate SRC activity in a conformation-dependent manner
  • AURKB, which regulates KIF23 localization at the midzone, is delocalized from the spindle midzone and the midbody but not from the metaphase chromosomes upon SRC expression
  • SRC antagonizes the ability of ING1 to induce apoptosis, most likely through relocalization of ING1 and down regulation of ING1 levels
  • downregulated the expression of PAG1, a lipid raft-associated inhibitor of SRC, which was restored by wild-type NDUFA13
  • ITGB4 and SRC activation is important early signaling events to lead MTOR activation and cap-dependent translation of VEGFA
  • GNAT1, NPHP3, and PKD1 bind with high affinity to UNC119, whereas a peptide derived from a non-ciliary localizing protein (SRC) has low affinity
  • increase of ATP1A1 activity is dependent on activation of the SRC pathway
  • adaptor protein SRCIN1 is a novel SRC-binding protein that regulates SRC activation through C-terminal SRC kinase (Csk)
  • key role for SRC signaling in regulating the functions of TLK2
  • cell & other
    REGULATION
    activated by HNF1A
    G proteins alphaS and alphaI
    SP1, SP3
    CLEC1B, that activates platelets through SRC and SYK tyrosine kinases, leading to tyrosine phosphorylation of downstream adapter proteins and effector enzymes, including PLCG2
    Phosphorylated by CASP8, SRC-mediated CASP8 phosphorylation stimulates SRC phosphorylation at Tyr-416 via the linkage of SRC SH2 domain with phosph-Tyr-380 site of CASP8
    Other cleaved by calpains at a site in the N-terminal unique domain
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in a small proportion of endometrial carcinoma and colon cancer
    tumoral   deletion    
    in some leukemia
    tumoral     --over  
    in some cancers
    constitutional     --over  
    results in the tyrosine phosphorylation and cytoplasmic localization of RUNX3
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    RUNX3 can be relocalized in the nucleus by an SRC inhibitor, in gastric cancers, providing an additional rationale for developing SRC inhibitors as anti-cancer drugs
    cancerreproductivebreast
    RUNX3 can be relocalized in the nucleus by an SRC inhibitor, in breast cancers, providing an additional rationale for developing SRC inhibitors as anti-cancer drugs
    immunologyinflammatory 
    both SRC and NOS3 inhibition may be important therapeutic targets to prevent or limit vascular inflammation
    ANIMAL & CELL MODELS
  • despite normal phosphorylation, sperm from cSrc null mice display a severe reduction in forward motility, and are unable to fertilize