CRK v-crk sarcoma virus CT10 oncogene homolog (avian) [ Homo sapiens ]

Gene ID: 1398, updated on 19-May-2012

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Summary

Official Symbol: CRKprovided by HGNC
Official Full Name: v-crk sarcoma virus CT10 oncogene homolog (avian)provided by HGNC
Primary source: HGNC:2362
See related: Ensembl:ENSG00000167193; HPRD:01267; MIM:164762; Vega:OTTHUMG00000090317
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: p38; CRKII; FLJ38130
Summary: This gene encodes a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. The product of this gene has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 17p13.3

Sequence :: Chromosome: 17; NC_000017.10 (1325440..1359544, complement)

See CRK in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

CrkI and p130(Cas) complex regulates the migration and invasion of prostate cancer cells.
Title: CrkI and p130(Cas) complex regulates the migration and invasion of prostate cancer cells.
positive regulatory role resulting from tyrosine phosphorylation of Crk, and identify a novel mechanism by which an adaptor protein activates a non-receptor tyrosine kinase by SH2 domain displacement
Title: Phosphorylation of Crk on tyrosine 251 in the RT loop of the SH3C domain promotes Abl kinase transactivation.
differential binding selectivity of Crk and CrkL to their downstream partners Dock 180 and C3G was demonstrated in ovarian cancer cell line SKOV3 through coimmunoprecipitation
Title: Crk and CrkL present with different expression and significance in epithelial ovarian carcinoma.
CRKII increases migration and invasive potential in oral squamous cell carcinoma
Title: Overexpression of CRKII increases migration and invasive potential in oral squamous cell carcinoma.
SOS1 is essential for CrkI-induced fibroblast transformation, and also reveal a surprising negative role for Abl kinases in Crk transformation.
Title: Proteins that bind the Src homology 3 domain of CrkI have distinct roles in Crk transformation.
These results imply that binding capacity of influenza A virus NS1 to CRK/CRKL has evolved in virus strains that over-induce the antiviral acting JNK-ATF2 signalling module and helps to suppress the detrimental apoptosis promoting action of this pathway.
Title: CRK adaptor protein expression is required for efficient replication of avian influenza A viruses and controls JNK-mediated apoptotic responses.
signal transfer of Crk/Dock180/Rac1 is implicated in actin cytoskeleton reorganization and thus in the cell proliferation, motility, invasion, and of human ovarian cancer cell line SKOV3.
Title: The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3.
Silencing of CRK-I/II increased endothelial cell migration.
Title: NDRG1 and CRK-I/II are regulators of endothelial cell migration under Intermittent Hypoxia.
Depletion of Crk by RNA interference markedly inhibited proliferation of the synovial sarcoma cell lines HS-SYII, SYO-1, and Fuji as well as prevented anchorage-independent growth.
Title: Adaptor protein Crk induces Src-dependent activation of p38 MAPK in regulation of synovial sarcoma cell proliferation.
is a signal transducing adaptor molecule that links tyrosine kinase and low-molecular weight G protein and plays role in various life phenomena.
Title: [Biological roles of signaling adaptor protein CRK].

Submit: New GeneRIF Correction See all (42)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_005197.3	NP_001070.2	ZAP70	BIND	PubMed	ZAP-70 interacts with Crk-I.
NP_005197.3			BIND	PubMed	Interaction between synthetic mouse Crk-Derived Phosphopeptide (PDB ID: 1JU5_B) and human CRK SH2 domain (PDB ID: 1JU5_A).
NP_058431.1	NP_009112.1	MAP4K1	BIND	PubMed	HPK1, a Ste-20 homologous serine/threonine kinase phosphorylates Crk, an adaptor protein.
NP_058431.2	NP_005148.1	ABL1	BIND	PubMed	Interaction between ABL (PDB ID: 1JU5_C) and CRK (PDB ID: 1JU5_A).
NP_058431.2	NP_009298.1	ABL2	BIND	PubMed	ABL2 (Arg) phosphorylates CRK.
NP_058431.2		ABL2	BIND	PubMed	Abl2 phosphorylates CRK. This interaction was modeled on a demonstrated interaction between ABL2 from an unspecified species and human CRK.
NP_058431.2	NP_002600.1	PDGFRB	BIND	PubMed	PDGFR interacts with Crk. This interaction was modelled on a demonstrated interaction between rat PDGFR and Crk from an unknown species.
NP_058431.2	NP_001070.2	ZAP70	BIND	PubMed	ZAP-70 interacts with Crk-II.
P46108	P00519	ABL1	HPRD	PubMed
P46108	P42684	ABL2	HPRD	PubMed
P46108	RICS	ARHGAP32	HPRD	PubMed
P46108	P54253	ATXN1	HPRD	PubMed
P46108	O75366	AVIL	HPRD	PubMed
P46108	P56945	BCAR1	HPRD	PubMed
P46108	P11274	BCR	HPRD	PubMed
P46108	O43683	BUB1	HPRD	PubMed
P46108	P22681	CBL	HPRD	PubMed
P46108	Q9ULV8	CBLC	HPRD	PubMed
P46108	P46109	CRKL	HPRD	PubMed
P46108	O75553	DAB1	HPRD	PubMed
P46108	Q14185	DOCK1	HPRD	PubMed
P46108	Q8IZD9	DOCK3	HPRD	PubMed
P46108	Q8TEW6	DOK4	HPRD	PubMed
P46108	Q7L190	DPPA4	HPRD	PubMed
P46108	P00533	EGFR	HPRD	PubMed
P46108	P29320	EPHA3	HPRD	PubMed
P46108	P54753	EPHB3	HPRD	PubMed
P46108	O15197	EPHB6	HPRD	PubMed
P46108	P42566	EPS15	HPRD	PubMed
P46108	Q15303	ERBB4	HPRD	PubMed
P46108	P11362	FGFR1	HPRD	PubMed
P46108	P17948	FLT1	HPRD	PubMed
P46108	Q8WU20	FRS2	HPRD	PubMed
P46108	P06241	FYN	HPRD	PubMed
P46108	Q13480	GAB1	HPRD	PubMed
P46108	P62993	GRB2	HPRD	PubMed
P46108	P08069	IGF1R	HPRD	PubMed
P46108	P06213	INSR	HPRD	PubMed
P46108	P35568	IRS1	HPRD	PubMed
P46108	Q9Y4H2	IRS2	HPRD	PubMed
P46108	Insulin receptor substrate 4	IRS4	HPRD	PubMed
P46108	P35968	KDR	HPRD	PubMed
P46108	P10721	KIT	HPRD	PubMed
P46108	Q92918	MAP4K1	HPRD	PubMed
P46108	Q9Y4K4	MAP4K5	HPRD	PubMed
P46108	P45983	MAPK8	HPRD	PubMed
P46108	P16333	NCK1	HPRD	PubMed
P46108	Q14511	NEDD9	HPRD	PubMed
P46108	P04629	NTRK1	HPRD	PubMed
P46108	P16234	PDGFRA	HPRD	PubMed
P46108	P09619	PDGFRB	HPRD	PubMed
P46108	P27986	PIK3R1	HPRD	PubMed
P46108	O15162	PLSCR1	HPRD	PubMed
P46108	P62333	PSMC6	HPRD	PubMed
P46108	Q05397	PTK2	HPRD	PubMed
P46108	Q14289	PTK2B	HPRD	PubMed
P46108	P49023	PXN	HPRD	PubMed
P46108	Q13905	RAPGEF1	HPRD	PubMed
P46108	Q96D71	REPS1	HPRD	PubMed
P46108	P07949	RET	HPRD	PubMed
P46108	Q9Y3L3	SH3BP1	HPRD	PubMed
P46108	Q15464	SHB	HPRD	PubMed
P46108	P29353	SHC1	HPRD	PubMed
P46108	Q07889	SOS1	HPRD	PubMed
P46108	P42229	STAT5A	HPRD	PubMed
P46108	P51692	STAT5B	HPRD	PubMed
P46108	P17600	SYN1	HPRD	PubMed
P46108	P15498	VAV1	HPRD	PubMed
P46108	Q92558	WASF1	HPRD	PubMed
P46108	P30291	WEE1	HPRD	PubMed
P46108	O14980	XPO1	HPRD	PubMed
P46108	P43403	ZAP70	HPRD	PubMed
	NP_005148.1	ABL1	BIND	PubMed	c-Abl interacts with Crk. This interaction was modeled on a demonstrated interaction between human c-Abl and Crk from an unspecified species.
BioGRID:107788	BioGRID:120424	ARHGAP17	BioGRID	PubMed	Reconstituted Complex
	NP_055530.2	ARHGAP32	BIND	PubMed	Crk interacts with GC-GAP. This interaction was modelled on a demonstrated interaction between Crk from an unspecified species and human GC-GAP.
BioGRID:107788	BioGRID:115091	ARHGAP32	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
	NP_060952.2	ASAP1	BIND	PubMed	DDEF1 (AMAP1) interacts with an unspecified isoform of CRK (Crk II).
BioGRID:107788	BioGRID:119126	ASAP1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:115918	AVIL	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:114934	BCAR1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:107164	BUB1	BioGRID	PubMed	Two-hybrid
BioGRID:107788	BioGRID:107315	CBL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:117156	CBLC	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:108128	DOCK1	BioGRID	PubMed	Affinity Capture-Western; Co-fractionation; Reconstituted Complex
	NP_060580.2	DOK4	BIND	PubMed	IRS5/DOK4 interacts with Crk. This interaction was modelled on a demonstrated interaction between human IRS5/DOK4 and hamster Crk.
BioGRID:107788	BioGRID:120507	DPPA4	BioGRID	PubMed	Two-hybrid
BioGRID:107788	BioGRID:108276	EGFR	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Biochemical Activity
BioGRID:107788	BioGRID:108356	EPHA3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:108362	EPHB2	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:108363	EPHB3	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:108374	EPS15	BioGRID	PubMed	Far Western; Reconstituted Complex
BioGRID:107788	BioGRID:108378	ERBB4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107788	BioGRID:116031	FRS2	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:109142	GRB2	BioGRID	PubMed	Affinity Capture-Western; Far Western; Reconstituted Complex
BioGRID:107788	BioGRID:114048	IRS4	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:119042	KCNIP3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:115900	KHDRBS1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:116354	MAP4K1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:116353	MAP4K5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:111585	MAPK8	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:122290	MICAL1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:110770	NCK1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:110816	NEDD9	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:111182	PDGFRA	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:111185	PDGFRB	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:111373	PLSCR1	BioGRID	PubMed	Two-hybrid
BioGRID:107788	BioGRID:111493	PPP1CA	BioGRID	PubMed	Two-hybrid
BioGRID:107788	BioGRID:111679	PSMC6	BioGRID	PubMed	Two-hybrid
BioGRID:107788	BioGRID:111719	PTK2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:111736	PTPN1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:111787	PXN	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:109146	RAPGEF1	BioGRID	PubMed	Affinity Capture-Western; Far Western
BioGRID:107788	BioGRID:111911	RET	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:117149	SH3BP1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:119029	SH3KBP1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:112358	SHB	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:114203	SOCS1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:112537	SOS1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107788	BioGRID:112592	SRC	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:123275	SRCIN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:112719	SYN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
	NP_003362.2	VAV2	BIND	PubMed	Crk interacts with Vav.
BioGRID:107788	BioGRID:113303	WEE1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107788	BioGRID:113348	XPO1	BioGRID	PubMed	Two-hybrid
BioGRID:107788	BioGRID:113367	ZAP70	BioGRID	PubMed	Reconstituted Complex
BioGRID:107788	BioGRID:100413	xpo1	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
SH2 domain binding	IPI Inferred from Physical Interaction more info	PubMed
SH3/SH2 adaptor activity	IEA Inferred from Electronic Annotation more info
ephrin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein phosphorylated amino acid binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
activation of MAPKK activity	TAS Traceable Author Statement more info
blood coagulation	TAS Traceable Author Statement more info
ephrin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
insulin receptor signaling pathway	TAS Traceable Author Statement more info
nerve growth factor receptor signaling pathway	TAS Traceable Author Statement more info
platelet activation	TAS Traceable Author Statement more info
regulation of Rac protein signal transduction	IEA Inferred from Electronic Annotation more info
regulation of Rho GTPase activity	IDA Inferred from Direct Assay more info	PubMed
regulation of actin cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
regulation of transcription from RNA polymerase II promoter	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IC Inferred by Curator more info	PubMed
cytosol	TAS Traceable Author Statement more info
endosome	TAS Traceable Author Statement more info
nucleus	TAS Traceable Author Statement more info	PubMed
plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: adapter molecule crk

Names: adapter molecule crk; proto-oncogene c-Crk

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029008.1 RefSeqGene

Range

4984..39898

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005206.4 → NP_005197.3 adapter molecule crk isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (I) represents the shorter transcript and encodes the shorter isoform (b). Isoform b increases transformation activity due to the loss of a SH3 domain.

Source sequence(s)

AC032044, AK291060, AU125411

Consensus CDS

CCDS45561.1

UniProtKB/Swiss-Prot

P46108

Related

ENSP00000381942, OTTHUMP00000198330, ENST00000398970, OTTHUMT00000319735

Conserved Domains (2) summary

cd00174
Location:136 – 189
Blast Score: 168

SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...

cd09926
Location:5 – 122
Blast Score: 453

SH2_CRK_like; Src homology 2 domain found in cancer-related signaling adaptor protein CRK
NM_016823.3 → NP_058431.2 adapter molecule crk isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (II) includes an alternate segment, compared to variant I, resulting in a longer protein (isoform a) that has a distinct C-terminus and an additional SH3 domain, compared to isoform b. Isoform a is a negative modulator of transformation activity.

Source sequence(s)

AC032044, AU125411, BC008506

Consensus CDS

CCDS11002.1

UniProtKB/Swiss-Prot

P46108

Related

ENSP00000300574, OTTHUMP00000115366, ENST00000300574, OTTHUMT00000206679

Conserved Domains (3) summary

cd00174
Location:136 – 189
Blast Score: 171

SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...

cd09926
Location:5 – 122
Blast Score: 463

SH2_CRK_like; Src homology 2 domain found in cancer-related signaling adaptor protein CRK

cl15350
Location:239 – 292
Blast Score: 157

SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000017.10 Reference GRCh37.p5 Primary Assembly

Range

1325440..1359544, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

1226186..1259667, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC032044.28	None
genomic	AC100748.2 (113723..120640)	None
genomic	CH471108.2	EAW90621.1
		EAW90622.1
		EAW90623.1
		EAW90624.1
		EAW90625.1
		EAW90626.1
genomic	EU332838.1	ABY87527.1
genomic	S65701.1	AAB28213.1
mRNA	AK095449.1	None
mRNA	AK291060.1	BAF83749.1
mRNA	AU125411.1	None
mRNA	BC001718.1	AAH01718.1
mRNA	BC008506.1	AAH08506.1
mRNA	BC009837.1	AAH09837.1
mRNA	BT007277.1	AAP35941.1
mRNA	D10656.1	BAA01505.1
other-genetic	DQ891147.2	ABM82073.1
other-genetic	DQ894327.2	ABM85253.1