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FLASH GENE

Symbol

SRC

contributors: mct/npt/pgu - updated : 19-06-2019

HGNC name	v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)
HGNC id	11283

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	THC6 thrombocytopenia 6
Location	20q11.23      Physical location : 35.973.087 - 36.033.819
Synonym name	v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog
	proto-oncogene SRC, rous sarcoma
	tyrosine-protein kinase SRC-1
	Src family kinase
Synonym symbol(s)	SRC1, ASV, c-SRC, p60-Src, pp60c-src, v-sRC, SFK
EC.number	2.7.10.2

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

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005417 14 splicing 4145 NP_005408 59 536 - 2009 19258394 this variant represents the longer transcript both isoforms 1 ant 2 encode the same protein NM_198291 14 splicing 4044 NP_938033 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)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine     moderately   intestine large intestine colon   moderately   mouth       moderately Endocrine thyroid       moderately Nervous nerve       moderately Reproductive male system male genital tract epididymis   highly Mus musculus Respiratory lung       moderately Skin/Tegument skin       moderately Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     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
	reciprocal feedback circuit of FZR1 and SRC in the crosstalk between the cell cycle machinery and the SRC signaling pathway

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)

THC6

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer digestive stomach 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 cancer reproductive breast 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 immunology inflammatory   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