Proto-oncogene tyrosine-protein kinase Src

Mammalian protein found in humans

SRC

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
1A07, 1A08, 1A09, 1A1A, 1A1B, 1A1C, 1A1E, 1FMK, 1HCS, 1HCT, 1KSW, 1O41, 1O42, 1O43, 1O44, 1O45, 1O46, 1O47, 1O48, 1O49, 1O4A, 1O4B, 1O4C, 1O4D, 1O4E, 1O4F, 1O4G, 1O4H, 1O4I, 1O4J, 1O4K, 1O4L, 1O4M, 1O4N, 1O4O, 1O4P, 1O4Q, 1O4R, 1SHD, 1Y57, 1YI6, 1YOJ, 1YOL, 1YOM, 2BDF, 2H8H, 3VRO, 3ZMP, 3ZMQ, 4F59, 4F5A, 4F5B, 4HXJ, 4K11, 4MXO, 4MXX, 4MXY, 4MXZ

Identifiers

Aliases

SRC, ASV, SRC1, c-p60-Src, SRC proto-oncogene, non-receptor tyrosine kinase, THC6

External IDs

OMIM: 190090 MGI: 98397 HomoloGene: 21120 GeneCards: SRC

EC number

2.7.10.2

Gene location (Human)

Chr.	Chromosome 20 (human)^[1]

Band	20q11.23	Start	37,344,685 bp^[1]
Band	20q11.23	End	37,406,050 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 2 (mouse)^[2]

Band	2 H1\|2 78.35 cM	Start	157,418,444 bp^[2]
Band	2 H1\|2 78.35 cM	End	157,471,862 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

body of stomach

gallbladder

rectum

body of pancreas

transverse colon

ganglionic eminence

gastric mucosa

ascending aorta

canal of the cervix

left adrenal gland

Top expressed in

external carotid artery

superior frontal gyrus

internal carotid artery

molar

aortic valve

ascending aorta

jejunum

medial geniculate nucleus

ganglionic eminence

yolk sac

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	transmembrane transporter binding protein domain specific binding protein-containing complex binding SH2 domain binding kinase activity signaling receptor binding estrogen receptor binding ATP binding protein kinase activity insulin receptor binding non-membrane spanning protein tyrosine kinase activity kinase binding heme binding enzyme binding transferase activity ephrin receptor binding scaffold protein binding integrin binding protein binding protein kinase binding cell adhesion molecule binding protein kinase C binding hormone receptor binding nucleotide binding growth factor receptor binding phosphoprotein binding protein tyrosine kinase activity protein C-terminus binding ubiquitin protein ligase binding cadherin binding connexin binding phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Cellular component	cytoplasm cytosol membrane extrinsic component of cytoplasmic side of plasma membrane ruffle membrane mitochondrion perinuclear region of cytoplasm caveola neuron projection cytoskeleton nucleus lysosome extracellular exosome late endosome plasma membrane actin filament postsynaptic density mitochondrial inner membrane podosome nucleoplasm glutamatergic synapse postsynaptic specialization, intracellular component
Biological process	response to mineralocorticoid negative regulation of telomere maintenance via telomerase response to interleukin-1 positive regulation of MAP kinase activity positive regulation of canonical Wnt signaling pathway negative regulation of telomerase activity cellular response to progesterone stimulus regulation of intracellular estrogen receptor signaling pathway stress fiber assembly positive regulation of protein serine/threonine kinase activity platelet activation positive regulation of smooth muscle cell migration protein phosphorylation regulation of vascular permeability vascular endothelial growth factor receptor signaling pathway positive regulation of ERK1 and ERK2 cascade regulation of podosome assembly cell cycle substrate adhesion-dependent cell spreading osteoclast development cell population proliferation transforming growth factor beta receptor signaling pathway cellular response to hypoxia cellular response to transforming growth factor beta stimulus negative regulation of protein homooligomerization positive regulation of protein kinase B signaling positive regulation of lamellipodium morphogenesis epidermal growth factor receptor signaling pathway branching involved in mammary gland duct morphogenesis Fc-gamma receptor signaling pathway involved in phagocytosis negative regulation of intrinsic apoptotic signaling pathway negative regulation of extrinsic apoptotic signaling pathway response to mechanical stimulus response to virus positive regulation of epithelial cell migration signal complex assembly stimulatory C-type lectin receptor signaling pathway positive regulation of platelet-derived growth factor receptor signaling pathway oogenesis positive regulation of transcription, DNA-templated regulation of epithelial cell migration response to nutrient levels positive regulation of DNA biosynthetic process cellular response to insulin stimulus protein autophosphorylation viral process negative regulation of focal adhesion assembly response to acidic pH response to fatty acid regulation of cell projection assembly phosphorylation immune system process negative regulation of mitochondrial depolarization positive regulation of integrin activation negative regulation of apoptotic process cellular response to platelet-derived growth factor stimulus positive regulation of podosome assembly positive regulation of glucose metabolic process transcytosis cellular response to fluid shear stress response to electrical stimulus positive regulation of protein transport uterus development protein destabilization regulation of cell-cell adhesion peptidyl-tyrosine autophosphorylation integrin-mediated signaling pathway positive regulation of insulin receptor signaling pathway progesterone receptor signaling pathway negative regulation of transcription, DNA-templated adherens junction organization negative regulation of anoikis response to hydrogen peroxide leukocyte migration activation of protein kinase B activity negative regulation of cysteine-type endopeptidase activity involved in apoptotic process intracellular signal transduction regulation of early endosome to late endosome transport ephrin receptor signaling pathway T cell costimulation positive regulation of intracellular signal transduction regulation of caveolin-mediated endocytosis regulation of cell cycle positive regulation of phosphatidylinositol 3-kinase activity cellular response to reactive oxygen species cellular response to peptide hormone stimulus positive regulation of gene expression cellular response to fatty acid regulation of cell population proliferation angiotensin-activated signaling pathway involved in heart process peptidyl-serine phosphorylation positive regulation of protein autophosphorylation positive regulation of cyclin-dependent protein serine/threonine kinase activity positive regulation of apoptotic process forebrain development regulation of protein binding cellular response to lipopolysaccharide regulation of bone resorption cell migration signal transduction positive regulation of cell adhesion cell adhesion positive regulation of protein processing innate immune response positive regulation of peptidyl-tyrosine phosphorylation neurotrophin TRK receptor signaling pathway positive regulation of small GTPase mediated signal transduction bone resorption central nervous system development positive regulation of protein localization to nucleus platelet-derived growth factor receptor signaling pathway ERBB2 signaling pathway intracellular estrogen receptor signaling pathway axon guidance macroautophagy peptidyl-tyrosine phosphorylation entry of bacterium into host cell cell-cell adhesion primary ovarian follicle growth positive regulation of ovarian follicle development transmembrane receptor protein tyrosine kinase signaling pathway positive regulation of phosphatidylinositol 3-kinase signaling cell differentiation phosphatidylinositol phosphate biosynthetic process regulation of postsynaptic neurotransmitter receptor activity positive regulation of non-membrane spanning protein tyrosine kinase activity G protein-coupled receptor signaling pathway cellular response to hydrogen peroxide positive regulation of platelet-derived growth factor receptor-beta signaling pathway odontogenesis
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


6714


20779

Ensembl


ENSG00000197122


ENSMUSG00000027646

UniProt


P12931


P05480

RefSeq (mRNA)


NM_005417 NM_198291


NM_001025395 NM_009271

RefSeq (protein)


NP_005408 NP_938033


NP_001020566 NP_033297

Location (UCSC)

Chr 20: 37.34 – 37.41 Mb

Chr 2: 157.42 – 157.47 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc", as it is short for sarcoma), is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. It belongs to a family of Src family kinases and is similar to the v-Src (viral Src) gene of Rous sarcoma virus. It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. Two transcript variants encoding the same protein have been found for this gene.^[5]

c-Src phosphorylates specific tyrosine residues in other tyrosine kinases. It plays a role in the regulation of embryonic development and cell growth. An elevated level of activity of c-Src is suggested to be linked to cancer progression by promoting other signals.^[6] Mutations in c-Src could be involved in the malignant progression of colon cancer. c-Src should not be confused with CSK (C-terminal Src kinase), an enzyme that phosphorylates c-Src at its C-terminus and provides negative regulation of Src's enzymatic activity.

c-Src was originally discovered by American scientists J. Michael Bishop and Harold E. Varmus, for which they were awarded the 1989 Nobel Prize in Physiology or Medicine.^[7]

Discovery

In 1979, J. Michael Bishop and Harold E. Varmus discovered that normal chickens possess a gene that is structurally closely related to v-Src.^[8] The normal cellular gene was called c-src (cellular-src).^[9] This discovery changed the current thinking about cancer from a model wherein cancer is caused by a foreign substance (a viral gene) to one where a gene that is normally present in the cell can cause cancer. It is believed that at one point an ancestral virus mistakenly incorporated the c-Src gene of its cellular host. Eventually this normal gene mutated into an abnormally functioning oncogene within the Rous sarcoma virus. Once the oncogene is transfected back into a chicken, it can lead to cancer.

Structure

There are 9 members of the Src family kinases: c-Src, Yes, Fyn, Fgr, Yrk, Lyn, Blk, Hck, and Lck.^[10] The expression of these Src family members are not the same throughout all tissues and cell types. Src, Fyn and Yes are expressed ubiquitously in all cell types while the others are generally found in hematopoietic cells.^[11]^[12]^[13]^[14]

c-Src is made up of 6 functional regions: Src homology 4 domain (SH4 domain), unique region, SH3 domain, SH2 domain, catalytic domain and short regulatory tail.^[15] When Src is inactive, the phosphorylated tyrosine group at the 527 position interacts with the SH2 domain which helps the SH3 domain interact with the flexible linker domain and thereby keeps the inactive unit tightly bound. The activation of c-Src causes the dephosphorylation of the tyrosine 527. This induces long-range allostery via protein domain dynamics, causing the structure to be destabilized, resulting in the opening up of the SH3, SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416.^[16]^[17]^[18]

The autophosphorylation of Y416 as well as phosphorylation of selected Src substrates is enhanced through dimerization of c-Src.^[19] The dimerization of c-Src is mediated by the interaction of the myristoylated N-terminal region of one partner and the kinase domain of another partner.^[19] Both the N-terminally attached myristic acid and the peptide sequences of the unique region are involved in the interaction.^[19] Given the versatility inherent in this intrinsically disordered region, its multisite phosphorylations, and its divergence within the family, the unique domain likely functions as a central signaling hub overseeing much of the enzymatic activities and unique functions of Src family kinases.^[19]

c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein coupled receptors and cytokine receptors. Most studies have looked at the receptor tyrosine kinases and examples of these are platelet derived growth factor receptor (PDGFR) pathway and epidermal growth factor receptor (EGFR).

Src contains at least three flexible protein domains, which, in conjunction with myristoylation, can mediate attachment to membranes and determine subcellular localization.^[20]

Function

This proto-oncogene may play a role in the regulation of embryonic development and cell growth.

When src is activated, it promotes survival, angiogenesis, proliferation and invasion pathways. It also regulates angiogenic factors and vascular permeability after focal cerebral ischemia-reperfusion,^[21]^[22] and regulates matrix metalloproteinase-9 activity after intracerebral hemorrhage.^[23]

Role in cancer

The activation of the c-Src pathway has been observed in about 50% of tumors from colon, liver, lung, breast and the pancreas.^[24] Since the activation of c-Src leads to the promotion of survival, angiogenesis, proliferation and invasion pathways, the aberrant growth of tumors in cancers is observed. A common mechanism is that there are genetic mutations that result in the increased activity or the overexpression of the c-Src leading to the constant activation of the c-Src.

Colon cancer

The activity of c-Src has been best characterized in colon cancer. Researchers have shown that Src expression is 5 to 8 fold higher in premalignant polyps than normal mucosa.^[25]^[26]^[27] The elevated c-Src levels have also been shown to have a correlation with advanced stages of the tumor, size of tumor, and metastatic potential of tumors.^[28]^[29]

Breast cancer

EGFR activates c-Src while EGF also increases the activity of c-Src. In addition, overexpression of c-Src increases the response of EGFR-mediated processes. So both EGFR and c-Src enhance the effects of one another. Elevated expression levels of c-Src were found in human breast cancer tissues compared to normal tissues.^[30]^[31]^[32]

Overexpression of Human Epidermal Growth Factor Receptor 2 (HER2), also known as erbB2, is correlated with a worse prognosis for breast cancer.^[33]^[34] Thus, c-Src plays a key role in the tumor progression of breast cancers.

Prostate cancer

Members of the Src family kinases Src, Lyn and Fgr are highly expressed in malignant prostate cells compared to normal prostate cells.^[35] When the primary prostate cells are treated with KRX-123, which is an inhibitor of Lyn, the cells in vitro were reduced in proliferation, migration and invasive potential.^[36] So the use of a tyrosine kinase inhibitor is a possible way of reducing the progression of prostate cancers.

As a drug target

A number of tyrosine kinase inhibitors that target c-Src tyrosine kinase (as well as related tyrosine kinases) have been developed for therapeutic use.^[37] One notable example is dasatinib which has been approved for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (PH+) acute lymphocytic leukemia (ALL).^[38] Dasatinib is also in clinical trials for the use in non-Hodgkin’s lymphoma, metastatic breast cancer and prostate cancer. Other tyrosine kinase inhibitor drugs that are in clinical trials include bosutinib,^[39] bafetinib, Saracatinib(AZD-0530), XLl-999, KX01 and XL228.^[6] HSP90 inhibitor NVP-BEP800 has been described to affect stability of Src tyrosine kinase and growth of T-cell and B-cell acute lymphoblastic leukemias. ^[40]

Interactions

Src (gene) has been shown to interact with the following signaling pathways:

Survival

Angiogenesis

Proliferation

Motility

Additional images

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Tyrosine kinase

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Top row: Beta-strand region

Hydrogen bonded turn Helical region

site	2	2	lipid-binding
site	17	17	Phosphoserine
site	35	35	Phosphoserine
site	69	69	Phosphoserine
site	74	74	Phosphothreonine
site	75	75	Phosphoserine; by CDK5
region	87	93	Beta-strand region
region	88	143	SH3
site	88	88	swapped dimer interface [polypeptide binding]
site	93	93	peptide ligand binding site [polypeptide binding]
region	99	102	Beta-strand region
region	110	114	Beta-strand region
region	117	117	Splicing variant
region	118	126	Beta-strand region
region	127	129	Hydrogen bonded turn
region	132	136	Beta-strand region
region	137	139	Helical region
region	140	142	Beta-strand region
region	146	148	Helical region
region	147	247	SH2
region	152	154	Beta-strand region
site	158	158	autoinhibitory site [polypeptide binding]
site	158	158	phosphotyrosine binding pocket [polypeptide binding]
region	158	165	Helical region
region	167	170	Beta-strand region
region	174	179	Beta-strand region
region	176	176	Variant
region	181	183	Beta-strand region
region	187	195	Beta-strand region
site	187	187	Phosphotyrosine (By similarity)
region	196	198	Hydrogen bonded turn
region	199	209	Beta-strand region
site	205	205	hydrophobic binding pocket [polypeptide binding]
region	211	213	Beta-strand region
region	215	218	Beta-strand region
region	221	225	Beta-strand region
region	226	233	Helical region
region	237	237	Variant
region	240	242	Beta-strand region
region	256	259	Beta-strand region
region	267	269	Helical region
region	270	519	Tyrosine kinase
region	270	278	Beta-strand region
site	276	276	Active site (ATP binding)
region	283	289	Beta-strand region
site	290	290	SH3/SH2 domain interface [polypeptide binding]
region	290	292	Hydrogen bonded turn
region	293	299	Beta-strand region
site	298	298	ATP
region	302	304	Hydrogen bonded turn
region	307	319	Helical region
region	328	332	Beta-strand region
region	334	336	Beta-strand region
region	338	341	Beta-strand region
region	349	353	Helical region
region	355	358	Helical region
region	363	382	Helical region
site	389	389	Proton acceptor
region	392	394	Helical region
region	395	397	Beta-strand region
region	399	401	Helical region
region	403	405	Beta-strand region
site	406	406	activation loop (A-loop)
region	410	413	Helical region
region	417	420	Helical region
site	419	419	Phosphotyrosine; by autocatalysis; alternate
site	419	419	Phosphotyrosine; by FAK2; alternate (By similarity)
region	423	426	Hydrogen bonded turn
region	429	431	Helical region
region	434	439	Helical region
site	439	439	Phosphotyrosine
region	444	459	Helical region
region	460	462	Hydrogen bonded turn
region	471	479	Helical region
region	492	501	Helical region
site	501	501	S-nitrosocysteine (By similarity)
region	506	508	Helical region
site	511	511	Phosphothreonine
region	512	520	Helical region
region	521	523	Hydrogen bonded turn
site	522	522	Phosphotyrosine
site	530	530	Phosphotyrosine; by CSK

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000197122 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027646 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: SRC v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian)".
^ ^a ^b Wheeler DL, Iida M, Dunn EF (July 2009). "The role of Src in solid tumors". Oncologist. 14 (7): 667–78. doi:10.1634/theoncologist.2009-0009. PMC 3303596. PMID 19581523.
^ "The Nobel Prize in Physiology or Medicine 1989: J. Michael Bishop, Harold E. Varmus". Nobelprize.org. 1989-10-09. for their discovery of 'the cellular origin of retroviral oncogenes'
^ Stehelin D, Fujita DJ, Padgett T, Varmus HE, Bishop JM (1977). "Detection and enumeration of transformation-defective strains of avian sarcoma virus with molecular hybridization". Virology. 76 (2): 675–84. doi:10.1016/0042-6822(77)90250-1. PMID 190771.
^ Oppermann H, Levinson AD, Varmus HE, Levintow L, Bishop JM (April 1979). "Uninfected vertebrate cells contain a protein that is closely related to the product of the avian sarcoma virus transforming gene (src)". Proc. Natl. Acad. Sci. U.S.A. 76 (4): 1804–8. Bibcode:1979PNAS...76.1804O. doi:10.1073/pnas.76.4.1804. PMC 383480. PMID 221907.
^ Thomas SM, Brugge JS (1997). "Cellular functions regulated by Src family kinases". Annu. Rev. Cell Dev. Biol. 13: 513–609. doi:10.1146/annurev.cellbio.13.1.513. PMID 9442882.
^ Cance WG, Craven RJ, Bergman M, Xu L, Alitalo K, Liu ET (December 1994). "Rak, a novel nuclear tyrosine kinase expressed in epithelial cells". Cell Growth Differ. 5 (12): 1347–55. PMID 7696183.
^ Lee J, Wang Z, Luoh SM, Wood WI, Scadden DT (January 1994). "Cloning of FRK, a novel human intracellular SRC-like tyrosine kinase-encoding gene". Gene. 138 (1–2): 247–51. doi:10.1016/0378-1119(94)90817-6. PMID 7510261.
^ Oberg-Welsh C, Welsh M (January 1995). "Cloning of BSK, a murine FRK homologue with a specific pattern of tissue distribution". Gene. 152 (2): 239–42. doi:10.1016/0378-1119(94)00718-8. PMID 7835707.
^ Thuveson M, Albrecht D, Zürcher G, Andres AC, Ziemiecki A (April 1995). "iyk, a novel intracellular protein tyrosine kinase differentially expressed in the mouse mammary gland and intestine". Biochem. Biophys. Res. Commun. 209 (2): 582–9. doi:10.1006/bbrc.1995.1540. PMID 7733928.
^ Arbesú M, Maffei M, Cordeiro TN, Teixeira JM, Pérez Y, Bernadó P, Roche S, Pons M (March 2017). "The Unique Domain Forms a Fuzzy Intramolecular Complex in Src Family Kinases". Structure. 25 (4): 630–640.e4. doi:10.1016/j.str.2017.02.011. PMID 28319009.
^ Cooper JA, Gould KL, Cartwright CA, Hunter T (March 1986). "Tyr527 is phosphorylated in pp60c-src: implications for regulation". Science. 231 (4744): 1431–4. Bibcode:1986Sci...231.1431C. doi:10.1126/science.2420005. PMID 2420005.
^ Okada M, Nakagawa H (December 1989). "A protein tyrosine kinase involved in regulation of pp60c-src function". J. Biol. Chem. 264 (35): 20886–93. doi:10.1016/S0021-9258(19)30019-5. PMID 2480346.
^ Nada S, Okada M, MacAuley A, Cooper JA, Nakagawa H (May 1991). "Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src". Nature. 351 (6321): 69–72. Bibcode:1991Natur.351...69N. doi:10.1038/351069a0. PMID 1709258. S2CID 4363527.
^ ^a ^b ^c ^d Spassov DS, Ruiz-Saenz A, Piple A, Moasser MM (Oct 2018). "A Dimerization Function in the Intrinsically Disordered N-Terminal Region of Src". Cell Rep. 25 (2): 6449–463. doi:10.1016/j.celrep.2018.09.035. PMC 6226010. PMID 30304684.
^ Kaplan JM, Varmus HE, Bishop JM (March 1990). "The src protein contains multiple domains for specific attachment to membranes". Molecular and Cellular Biology. 10 (3): 1000–9. doi:10.1128/mcb.10.3.1000. PMC 360952. PMID 1689455.
^ Zan L, Wu H, Jiang J, Zhao S, Song Y, Teng G, Li H, Jia Y, Zhou M, Zhang X, Qi J, Wang J (2011). "Temporal profile of Src, SSeCKS, and angiogenic factors after focal cerebral ischemia: correlations with angiogenesis and cerebral edema". Neurochem. Int. 58 (8): 872–9. doi:10.1016/j.neuint.2011.02.014. PMC 3100427. PMID 21334414.
^ Zan L, Zhang X, Xi Y, Wu H, Song Y, Teng G, Li H, Qi J, Wang J (2013). "Src regulates angiogenic factors and vascular permeability after focal cerebral ischemia-reperfusion". Neuroscience. 262 (3): 118–128. doi:10.1016/j.neuroscience.2013.12.060. PMC 3943922. PMID 24412374.
^ Zhao X, Wu T, Chang CF, et al. (2015). "Toxic role of prostaglandin E2 receptor EP1 after intracerebral hemorrhage in mice". Brain Behav. Immun. 46: 293–310. doi:10.1016/j.bbi.2015.02.011. PMC 4422065. PMID 25697396.
^ Dehm SM, Bonham K (April 2004). "SRC gene expression in human cancer: the role of transcriptional activation". Biochem. Cell Biol. 82 (2): 263–74. doi:10.1139/o03-077. PMID 15060621.
^ Bolen JB, Rosen N, Israel MA (November 1985). "Increased pp60c-src tyrosyl kinase activity in human neuroblastomas is associated with amino-terminal tyrosine phosphorylation of the src gene product". Proc. Natl. Acad. Sci. U.S.A. 82 (21): 7275–9. Bibcode:1985PNAS...82.7275B. doi:10.1073/pnas.82.21.7275. PMC 390832. PMID 2414774.
^ Cartwright CA, Kamps MP, Meisler AI, Pipas JM, Eckhart W (June 1989). "pp60c-src activation in human colon carcinoma". J. Clin. Invest. 83 (6): 2025–33. doi:10.1172/JCI114113. PMC 303927. PMID 2498394.
^ Talamonti MS, Roh MS, Curley SA, Gallick GE (January 1993). "Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer". J. Clin. Invest. 91 (1): 53–60. doi:10.1172/JCI116200. PMC 329994. PMID 7678609.
^ Aligayer H, Boyd DD, Heiss MM, Abdalla EK, Curley SA, Gallick GE (January 2002). "Activation of Src kinase in primary colorectal carcinoma: an indicator of poor clinical prognosis". Cancer. 94 (2): 344–51. doi:10.1002/cncr.10221. PMID 11900220. S2CID 2103781.
^ Cartwright CA, Meisler AI, Eckhart W (January 1990). "Activation of the pp60c-src protein kinase is an early event in colonic carcinogenesis". Proc. Natl. Acad. Sci. U.S.A. 87 (2): 558–62. Bibcode:1990PNAS...87..558C. doi:10.1073/pnas.87.2.558. PMC 53304. PMID 2105487.
^ Ottenhoff-Kalff AE, Rijksen G, van Beurden EA, Hennipman A, Michels AA, Staal GE (September 1992). "Characterization of protein tyrosine kinases from human breast cancer: involvement of the c-src oncogene product". Cancer Res. 52 (17): 4773–8. PMID 1380891.
^ Biscardi JS, Belsches AP, Parsons SJ (April 1998). "Characterization of human epidermal growth factor receptor and c-Src interactions in human breast tumor cells". Mol. Carcinog. 21 (4): 261–72. doi:10.1002/(SICI)1098-2744(199804)21:4<261::AID-MC5>3.0.CO;2-N. PMID 9585256. S2CID 24236532.
^ Verbeek BS, Vroom TM, Adriaansen-Slot SS, Ottenhoff-Kalff AE, Geertzema JG, Hennipman A, Rijksen G (December 1996). "c-Src protein expression is increased in human breast cancer. An immunohistochemical and biochemical analysis". J. Pathol. 180 (4): 383–8. doi:10.1002/(SICI)1096-9896(199612)180:4<383::AID-PATH686>3.0.CO;2-N. PMID 9014858. S2CID 26892937.
^ Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (January 1987). "Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene". Science. 235 (4785): 177–82. Bibcode:1987Sci...235..177S. doi:10.1126/science.3798106. PMID 3798106.
^ Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A (May 1989). "Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer". Science. 244 (4905): 707–12. Bibcode:1989Sci...244..707S. doi:10.1126/science.2470152. PMID 2470152.
^ Nam S, Kim D, Cheng JQ, Zhang S, Lee JH, Buettner R, Mirosevich J, Lee FY, Jove R (October 2005). "Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells". Cancer Res. 65 (20): 9185–9. doi:10.1158/0008-5472.CAN-05-1731. PMID 16230377.
^ Chang YM, Bai L, Yang I (2002). "Survey of Src activity and Src-related growth and migration in prostate cancer lines". Proc Am Assoc Cancer Res. 62: 2505a.
^ Musumeci F, Schenone S, Brullo C, Botta M (April 2012). "An update on dual Src/Abl inhibitors". Future Med Chem. 4 (6): 799–822. doi:10.4155/fmc.12.29. PMID 22530642.
^ Breccia M, Salaroli A, Molica M, Alimena G (2013). "Systematic review of dasatinib in chronic myeloid leukemia". OncoTargets Ther. 6: 257–65. doi:10.2147/OTT.S35360. PMC 3615898. PMID 23569389.
^ Amsberg GK, Koschmieder S (2013). "Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia". OncoTargets Ther. 6: 99–106. doi:10.2147/OTT.S19901. PMC 3594007. PMID 23493838.
^ Mshaik R, Simonet J, Georgievski A, Jamal L, Bechoua S, Ballerini P, Bellaye PS, Mlamla Z, Pais de Barros JP, Geissler A, Francin PJ, Girodon F, Garrido C, Quéré R (March 2021). "HSP90 inhibitor NVP-BEP800 affects stability of SRC kinases and growth of T-cell and B-cell acute lymphoblastic leukemias". Blood Cancer J. 3 (11): 61. doi:10.1038/s41408-021-00450-2. PMC 7973815. PMID 33737511.

External links

src+Gene at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
src-Family+Kinases at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Proteopedia SRC - interactive 3D model of the structure of SRC
Vega geneview
Src Info with links in the Cell Migration Gateway Archived 2014-12-11 at the Wayback Machine
Overview of all the structural information available in the PDB for UniProt: P12931 (Proto-oncogene tyrosine-protein kinase Src) at the PDBe-KB.

PDB gallery

1a07: C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-MALONYL TYR-GLU-(N,N-DIPENTYL AMINE)
1a08: C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-DIFLUORO PHOSPHOTYR-GLU-(N,N-DIPENTYL AMINE)
1a09: C-src (SH2 domain) complexed with ace-formyl phosphotyr-glu-(n,n-dipentyl amine)
1a1a: C-SRC (SH2 DOMAIN WITH C188A MUTATION) COMPLEXED WITH ACE-FORMYL PHOSPHOTYR-GLU-(N,N-DIPENTYL AMINE)
1a1b: C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(N,N-DIPENTYL AMINE)
1a1c: C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(N-ME(-(CH2)3-CYCLOPENTYL))
1a1e: C-SRC (SH2 DOMAIN) COMPLEXED WITH ACE-PHOSPHOTYR-GLU-(3-BUTYLPIPERIDINE)
1bkl: SELF-ASSOCIATED APO SRC SH2 DOMAIN
1bkm: COCRYSTAL STRUCTURE OF D-AMINO ACID SUBSTITUTED PHOSPHOPEPTIDE COMPLEX
1f1w: SRC SH2 THREF1TRP MUTANT COMPLEXED WITH THE PHOSPHOPEPTIDE S(PTR)VNVQN
1f2f: SRC SH2 THREF1TRP MUTANT
1fmk: CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC
1hcs: NMR STRUCTURE OF THE HUMAN SRC SH2 DOMAIN COMPLEX
1hct: NMR STRUCTURE OF THE HUMAN SRC SH2 DOMAIN COMPLEX
1is0: Crystal Structure of a Complex of the Src SH2 Domain with Conformationally Constrained Peptide Inhibitor
1kc2: structure of the triple (Lys(beta)D3Ala, Asp(beta)C8Ala, AspCD2Ala) mutant of the Src SH2 domain bound to the PQpYEEIPI peptide
1ksw: Structure of Human c-Src Tyrosine Kinase (Thr338Gly Mutant) in Complex with N6-benzyl ADP
1nlo: STRUCTURE OF SIGNAL TRANSDUCTION PROTEIN, NMR, MINIMIZED AVERAGE STRUCTURE
1nlp: STRUCTURE OF SIGNAL TRANSDUCTION PROTEIN, NMR, MINIMIZED AVERAGE STRUCTURE
1nzl: Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYEpYIPI
1nzv: Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYIpYVPA
1o41: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78300.
1o42: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU81843.
1o43: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU82129.
1o44: Crystal structure of sh2 in complex with ru85052
1o45: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU84687.
1o46: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU90395.
1o47: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU82209.
1o48: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU85053.
1o49: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU85493.
1o4a: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU82197.
1o4b: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU83876.
1o4c: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PHOSPHATE.
1o4d: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78262.
1o4e: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78299.
1o4f: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU79073.
1o4g: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH DPI59.
1o4h: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU79072.
1o4i: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PAS219.
1o4j: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH ISO24.
1o4k: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PASBN.
1o4l: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH FRAGMENT2.
1o4m: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH MALONICACID.
1o4n: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH OXALIC ACID.
1o4o: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH PHENYLPHOSPHATE.
1o4p: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78791.
1o4q: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU79256.
1o4r: CRYSTAL STRUCTURE OF SH2 IN COMPLEX WITH RU78783.
1p13: Crystal Structure of the Src SH2 Domain Complexed with Peptide (SDpYANFK)
1prl: TWO BINDING ORIENTATIONS FOR PEPTIDES TO SRC SH3 DOMAIN: DEVELOPMENT OF A GENERAL MODEL FOR SH3-LIGAND INTERACTIONS
1prm: TWO BINDING ORIENTATIONS FOR PEPTIDES TO SRC SH3 DOMAIN: DEVELOPMENT OF A GENERAL MODEL FOR SH3-LIGAND INTERACTIONS
1qwe: C-SRC SH3 DOMAIN COMPLEXED WITH LIGAND APP12
1qwf: C-SRC SH3 DOMAIN COMPLEXED WITH LIGAND VSL12
1rlp: TWO BINDING ORIENTATIONS FOR PEPTIDES TO SRC SH3 DOMAIN: DEVELOPMENT OF A GENERAL MODEL FOR SH3-LIGAND INTERACTIONS
1rlq: TWO BINDING ORIENTATIONS FOR PEPTIDES TO SRC SH3 DOMAIN: DEVELOPMENT OF A GENERAL MODEL FOR SH3-LIGAND INTERACTIONS
1sha: CRYSTAL STRUCTURE OF THE PHOSPHOTYROSINE RECOGNITION DOMAIN SH2 OF V-SRC COMPLEXED WITH TYROSINE-PHOSPHORYLATED PEPTIDES
1shb: CRYSTAL STRUCTURE OF THE PHOSPHOTYROSINE RECOGNITION DOMAIN SH2 OF V-SRC COMPLEXED WITH TYROSINE-PHOSPHORYLATED PEPTIDES
1shd: PEPTIDE INHIBITORS OF SRC SH3-SH2-PHOSPHOPROTEIN INTERACTIONS
1skj: COCRYSTAL STRUCTURE OF UREA-SUBSTITUTED PHOSPHOPEPTIDE COMPLEX
1spr: BINDING OF A HIGH AFFINITY PHOSPHOTYROSYL PEPTIDE TO THE SRC SH2 DOMAIN: CRYSTAL STRUCTURES OF THE COMPLEXED AND PEPTIDE-FREE FORMS
1sps: BINDING OF A HIGH AFFINITY PHOSPHOTYROSYL PEPTIDE TO THE SRC SH2 DOMAIN: CRYSTAL STRUCTURES OF THE COMPLEXED AND PEPTIDE-FREE FORMS
1srl: 1H AND 15N ASSIGNMENTS AND SECONDARY STRUCTURE OF THE SRC SH3 DOMAIN
1srm: 1H AND 15N ASSIGNMENTS AND SECONDARY STRUCTURE OF THE SRC SH3 DOMAIN
1y57: Structure of unphosphorylated c-Src in complex with an inhibitor
1yi6: C-term tail segment of human tyrosine kinase (258-533)
1yoj: Crystal structure of Src kinase domain
1yol: Crystal structure of Src kinase domain in complex with CGP77675
1yom: Crystal structure of Src kinase domain in complex with Purvalanol A
2bdf: Src kinase in complex with inhibitor AP23451
2bdj: Src kinase in complex with inhibitor AP23464
2h8h: Src kinase in complex with a quinazoline inhibitor
2hwo: Crystal structure of Src kinase domain in complex with covalent inhibitor
2hwp: Crystal structure of Src kinase domain in complex with covalent inhibitor PD168393
2oiq: Crystal Structure of chicken c-Src kinase domain in complex with the cancer drug imatinib.
2ptk: CHICKEN SRC TYROSINE KINASE
2src: CRYSTAL STRUCTURE OF HUMAN TYROSINE-PROTEIN KINASE C-SRC, IN COMPLEX WITH AMP-PNP

Tumor suppressor genes and Oncogenes

Ligand

Growth factors

ONCO	c-Sis/PDGF HGF

Receptor

Wnt signaling pathway

TSP	CDH1

Hedgehog signaling pathway

TSP	PTCH1

TGF beta signaling pathway

TSP	TGF beta receptor 2

Receptor tyrosine kinase

ONCO	ErbB/c-ErbB HER2/neu Her 3 c-Met c-Ret

JAK-STAT signaling pathway

ONCO	c-Kit Flt3

Intracellular signaling P+Ps

Wnt signaling pathway

ONCO	Beta-catenin
TSP	APC

TGF beta signaling pathway

TSP	SMAD2 SMAD4

Akt/PKB signaling pathway

ONCO	c-Akt
TSP	PTEN

Hippo signaling pathway

TSP	Neurofibromin 2/Merlin

MAPK/ERK pathway

ONCO	c-Ras HRAS c-Raf
TSP	Neurofibromin 1

Other/unknown

ONCO	c-Src
TSP	Maspin

Nucleus

Cell cycle

ONCO	CDK4 Cyclin D Cyclin E
TSP	p53 pRb WT1 p16/p14arf

DNA repair/Fanconi

TSP	BRCA1 BRCA2

Ubiquitin ligase

ONCO	CBL MDM2
TSP	VHL

Transcription factor

ONCO	AP-1 c-Fos c-Jun c-Myc
TSP	KLF6

Mitochondrion

Apoptosis inhibitor	SDHB SDHD

Other/ungrouped

Protein kinases: tyrosine kinases (EC 2.7.10)

Receptor tyrosine kinases (EC 2.7.10.1)

Growth factor receptors

EGF receptor family	EGFR ERBB2 ERBB3 ERBB4
Insulin receptor family	IGF1R INSR INSRR
PDGF receptor family	CSF1R FLT3 KIT PDGFR (PDGFRA PDGFRB)
FGF receptor family	FGFR1 FGFR2 FGFR3 FGFR4
VEGF receptors family	VEGFR1 VEGFR2 VEGFR3
HGF receptor family	MET RON
Trk receptor family	NTRK1 NTRK2 NTRK3

EPH receptor family

LTK receptor family

TIE receptor family

ROR receptor family

ROR1
ROR2

DDR receptor family

DDR1
DDR2

PTK7 receptor family

PTK7

RYK receptor family

MuSK receptor family

MUSK

ROS receptor family

ROS1

AATYK receptor family

AATYK
AATYK2

AXL receptor family

RET receptor family

uncategorised

STYK1

Non-receptor tyrosine kinases (EC 2.7.10.2)

ABL family	ABL1 ARG
ACK family	ACK1 TNK1
CSK family	CSK MATK
FAK family	FAK PYK2
FES family	FES FER
FRK family	FRK BRK SRMS
JAK family	JAK1 JAK2 JAK3 TYK2
SRC-A family	SRC FGR FYN YES1
SRC-B family	BLK HCK LCK LYN
TEC family	TEC BMX BTK ITK TXK
SYK family	SYK ZAP70

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)