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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

SRC Gene

protein-coding GIFtS: 76
GCID: GC20P035973

v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog...

(Previous name: v-src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene...)
(Previous symbol: SRC1)

Explore 152 diseases affiliated with
SRC via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 4

Aliases
V-Src Sarcoma (Schmidt-Ruppin A-2) Viral Oncogene Homolog (Avian)¹ ²		C-SRC¹
SRC1¹ ² ³ ⁵		Proto-Oncogene Tyrosine-Protein Kinase Src²
ASV¹ ² ⁵		Protooncogene SRC, Rous Sarcoma²
Proto-Oncogene C-Src² ³		Tyrosine Kinase Pp60c-Src²
P60-Src¹		Tyrosine-Protein Kinase SRC-1²
EC 2.7.10.2³ ⁸		Pp60c-Src¹
C-Src¹		EC 2.7.10⁸
V-Src Avian Sarcoma (Schmidt-Ruppin A-2) Viral Oncogene Homolog¹

External Ids:	HGNC: 11283¹	Entrez Gene: 6714²	Ensembl: ENSG00000197122⁷	OMIM: 190090⁵	UniProtKB: P12931³

ORGUL members:	fRNAdb¹⁰:FR349626
	H-InvDB:HIT000326568
	NCBI:Z18364
	NONCODE:n336581 n339669
	RNAdb:HIV2756

Export aliases for SRC gene to outside databases

Previous GC identifers: GC20P035740 GC20P036650 GC20P036696 GC20P036658 GC20P035406 GC20P032708

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SRC:

This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the

regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase

whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the

malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this

gene. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: SRC_HUMAN, P12931

Function: Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of

cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein

tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that

control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell

cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC

kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the

primary kinases activated following engagement of receptors and plays a role in the activation of other protein

tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor

complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important

role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1.

Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal

reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal

adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine

phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to

phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and

phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type

of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is

implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a

role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of

these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in

EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR)

internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in

beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of ADRBK1, leading to

beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3

mitogen-activated protein kinase cascade by epidermal growth factor. Might be involved not only in mediating the

transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the

cell cycle via interaction with regulatory proteins in the nucleus. Plays an important role in osteoclastic bone

resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are

necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in

turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling

pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating

mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent

autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'.

Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'.

Phosphorylates BCAR1 at 'Tyr-128'

summary for SRC:

Src kinases consist of eight non-receptor tyrosine kinases (Src, Fyn, Yes, Lck, Lyn, Hck, Fgr and Blk) that

interact with the intracellular domains of growth factor/cytokine receptors, GPCRs and integrins. Members of

the Src kinase family have a very similar domain structure with a high degree of homology in the SH1

(catalytic), linker, SH2 (p-Tyr binding), SH3 (protein-protein interaction) and SH4 (membrane association)

domains. c-Src, Fyn and Yes are ubiquitously expressed, although high levels of c-Src are found in

platelets, neural tissue and osteoclasts. For c-Src, autophosphorylation of Tyr418 and dephosphorylation of

Tyr530 is required to switch the kinase from the inactive closed formation to the active open formation.

c-Src can be inactivated by two kinases, c-Src kinase (CSK) and CSK homologous kinase (CHK), both of which

phosphorylate Tyr530 of c-Src. The activity of the Src kinase family can also be regulated by phosphatases

(e.g. SHP1), binding to adaptor proteins (e.g. Cbp) and proteasomal degradation. Src kinases are key

upstream mediators of both the PI 3-K and MAPK signaling pathways, and have been shown to have important

roles in cell proliferation, migration and survival.

Gene Wiki entry for SRC (Src)

fRNAdb sequence ontology for SRC:
ncRNA - An RNA transcript that does not encode for a protein rather the RNA molecule is the gene product.

View fRNAdb secondary structures for SRC

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000020.10 NC_018931.1 NT_011362.10

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the SRC gene promoter:
CREB STAT3
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): SRC promoter sequence

Search SABiosciences Chromatin IP Primers for SRC

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SRC

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q12-q13 Ensembl cytogenetic band: 20q11.23 HGNC cytogenetic band: 20q12-q13

SRC Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SRC gene location

GeneLoc information about chromosome 20 GeneLoc Exon Structure

GeneLoc location for GC20P035973: view genomic region (about GC identifiers)

Start:	35,973,088 bp from pter	End:	36,034,453 bp from pter
Size:	61,366 bases	Orientation:	plus strand

ORGUL member locations:
Legend (see complete legend)

n339669
FR0349626
n336581

lncRNA
Full Legend

35973087 35992142 36011196 chr20

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: SRC_HUMAN, P12931 (See protein sequence)

Recommended Name: Proto-oncogene tyrosine-protein kinase Src

Size: 536 amino acids; 59835 Da

Subunit: Interacts with DDEF1/ASAP1; via the SH3 domain. Interacts with CCPG1. Identified in a complex containing

FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with ERBB2, STAT1 and PNN. Interacts with DDR1,

DDR2 and DAB2. Interacts with CDCP1, PELP1, TGFB1I1 and TOM1L2. Interacts with the cytoplasmic domain of MUC1,

phosphorylates it and increases binding of MUC1 with beta-catenin. Interacts with RALGPS1; via the SH3 domain.

Interacts with HEV ORF3 protein; via the SH3 domain. Interacts with CAV2 (tyrosine phosphorylated form). Interacts

(via the SH3 domain and the protein kinase domain) with ARRB1; the interaction is independent of the phosphorylation

state of SRC C-terminus. Interacts with ARRB1 and ARRB2. Interacts with SRCIN1. Interacts with NDFIP2 and more weakly

with NDFIP1. Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1 and ESR1 (dimethylated on arginine). Interacts with

FASLG. Interacts (via SH2 domain) with the 'Tyr-402' phosphorylated form of PTK2B/PYK2. Interacts (via SH2 domain)

with FLT3 (tyrosine phosphorylated). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with CSF1R. Interacts

(via SH2 and SH3 domain) with TNK2. Interacts (via protein kinase domain) with the tyrosine phosphorylated form of

RUNX3 (via runt domain). Interacts with TRAF3 (via RING-type zinc finger domain). Interacts with DDX58, MAVS and TBK1.

Interacts (via SH2 domain) with GNB2L1/RACK1; the interaction is enhanced by tyrosine phosphorylation of GNB2L1 and

inhibits SRC activity. Interacts with EPHB1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with

FCAMR. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with AMOTL2; this

interaction regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites

Subcellular location: Cell membrane. Mitochondrion inner membrane. Nucleus. Cytoplasm, cytoskeleton. Note=Localizes to

focal adhesion sites following integrin engagement. Localization to focal adhesion sites requires myristoylation and

the SH3 domain

6/52 PDB 3D structures from and Proteopedia for SRC (see all 52):

1A07 (3D)

1A08 (3D)

1A09 (3D)

1A1A (3D)

1A1B (3D)

1A1C (3D)

Secondary accessions: E1P5V4 Q76P87 Q86VB9 Q9H5A8

Alternative splicing: 2 isoforms: P12931-1 P12931-2

Explore the universe of human proteins at neXtProt for SRC: NX_P12931

Post-translational modifications:

Myristoylated at Gly-2, and this is essential for targeting to membranes¹

Dephosphorylated at Tyr-530 by PTPRJ (By similarity). Phosphorylated on Tyr-530 by c-Src kinase (CSK). The

phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-419. Normally maintained in an inactive

conformation with the SH2 domain engaged with Tyr-530, the SH3 domain engaged with the SH2-kinase linker, and Tyr-419

dephosphorylated. Dephosphorylation of Tyr-530 as a result of protein tyrosine phosphatase (PTP) action disrupts the

intramolecular interaction between the SH2 domain and Tyr-530, Tyr-419 can then become autophosphorylated, resulting

in SRC activation. Phosphorylation of Tyr-530 by CSK allows this interaction to reform, resulting in SRC inactivation.

CDK5-mediated phosphorylation at Ser-75 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal

reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this

enhances kinase activity¹

S-nitrosylation is important for activation of its kinase activity (By similarity)¹

Ubiquitinated in response to CDK5-mediated phosphorylation¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P12931

4/41 DME Specific Peptides for SRC (P12931) (see all 41)

DLSFKKG

KWTAPEA

FLEDYFT

LPQLVDM

SRC Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_005408.1 NP_938033.1

ENSEMBL proteins:

ENSP00000362680 ENSP00000362668 ENSP00000362659 ENSP00000408503 ENSP00000353950

ENSP00000350941

Reactome Protein details: P12931
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant SRC Protein
	R&D Systems Recombinant & Natural Proteins for SRC
	Enzo Life Sciences proteins for SRC
	OriGene Purified Proteins (see all 4): SRC OriGene Protein Over-expression Lysate (see all 2): SRC OriGene Custom Protein Services for SRC
	GenScript Custom Purified and Recombinant Proteins Services for SRC
	Novus Biologicals SRC Proteins Novus Biologicals SRC Lysates
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for SRC
	Uscn Proteins for SRC

Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IEA	--
GO:0005743	mitochondrial inner membrane	IDA	12615910
GO:0005764	lysosome	IDA	--
GO:0005770	late endosome	IDA	--
GO:0005829	cytosol	TAS	--

SRC for ontologies About GeneDecksing

SRC Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of SRC
	R&D Systems Antibodies for SRC
	Cell Signaling Technology (CST) Antibodies for SRC
	OriGene Antibodies (see all 3): SRC OriGene Custom Antibody Services for SRC
	GenScript Superior Antibodies for SRC
	Novus Biologicals SRC Antibodies
	Abcam antibodies for SRC
	Uscn Antibodies for SRC
	ThermoFisher Antibody for SRC

Assay Products for SRC:

	EMD Millipore Kits and Assays for the Analysis of SRC
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for SRC (see all)
	GenScript SRC-Activity-based Kinase Assay for Compound Screening
	Cell Signaling Technology (CST) Sandwich ELISA Kits for SRC
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for SRC

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

SRC for domains About GeneDecksing

5/8 InterPro domains/families (see all 8):

IPR017441 Protein_kinase_ATP_BS

IPR001245 Ser-Thr/Tyr_kinase_cat_dom

IPR011009 Kinase-like_dom

IPR000980 SH2

IPR001452 SH3_domain

Graphical View of Domain Structure for InterPro Entry P12931

ProtoNet protein and cluster: P12931

3 Blocks protein families:

IPB000980 SH2 domain signature

IPB001452 SH3 domain signature

IPB008266 Tyrosine protein kinase

UniProtKB/Swiss-Prot: SRC_HUMAN, P12931

Domain: The SH2 and SH3 domains are important for the intramolecular and intermolecular interactions that regulate

catalytic activity, localization, and substrate recruitment

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily

Similarity: Contains 1 protein kinase domain

Similarity: Contains 1 SH2 domain

Similarity: Contains 1 SH3 domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: