CRK CRK proto-oncogene, adaptor protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: CRKprovided by HGNC
Official Full Name: CRK proto-oncogene, adaptor proteinprovided by HGNC
Primary source: HGNC:HGNC:2362
See related: Ensembl:ENSG00000167193 MIM:164762; AllianceGenome:HGNC:2362
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
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]
Expression: Ubiquitous expression in fat (RPKM 27.5), thyroid (RPKM 27.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p13.3

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (1420693..1456232, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (1309416..1344954, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (1323987..1359526, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Gab2 plays a carcinogenic role in ovarian cancer by regulating CrkII.
Title: Gab2 plays a carcinogenic role in ovarian cancer by regulating CrkII.
Crk proteins activate the Rap1 guanine nucleotide exchange factor C3G by segregated adaptor-dependent and -independent mechanisms.
Title: Crk proteins activate the Rap1 guanine nucleotide exchange factor C3G by segregated adaptor-dependent and -independent mechanisms.
MicroRNA-215-5p Inhibits the Proliferation and Migration of Wilm's Tumor Cells by Targeting CRK.
Title: MicroRNA-215-5p Inhibits the Proliferation and Migration of Wilm's Tumor Cells by Targeting CRK.
Quantitative assessment of glioblastoma phenotypes in vitro establishes cell migration as a robust readout of Crk and CrkL activity.
Title: Quantitative assessment of glioblastoma phenotypes in vitro establishes cell migration as a robust readout of Crk and CrkL activity.
Prenatal diagnosis of Miller-Dieker syndrome by chromosomal microarray.
Title: Prenatal diagnosis of Miller-Dieker syndrome by chromosomal microarray.
Cyclophilin A Inhibitor Debio-025 Targets Crk, Reduces Metastasis, and Induces Tumor Immunogenicity in Breast Cancer.
Title: Cyclophilin A Inhibitor Debio-025 Targets Crk, Reduces Metastasis, and Induces Tumor Immunogenicity in Breast Cancer.
17p13.3 microdeletion including YWHAE and CRK genes: towards a clinical characterization.
Title: 17p13.3 microdeletion including YWHAE and CRK genes: towards a clinical characterization.
Novel role for CRK adaptor proteins as essential components of SRC/FAK signaling for epithelial-mesenchymal transition and colorectal cancer aggressiveness.
Title: Novel role for CRK adaptor proteins as essential components of SRC/FAK signaling for epithelial-mesenchymal transition and colorectal cancer aggressiveness.
Signaling adaptor protein Crk is involved in malignant feature of pancreatic cancer associated with phosphorylation of c-Met.
Title: Signaling adaptor protein Crk is involved in malignant feature of pancreatic cancer associated with phosphorylation of c-Met.
ACAP4 physically interacts with CrkII. Functional characterization showed that the interaction is required for the recruitment of ACAP4 to the plasma membrane where ACAP4 functions to regulate the recycling of the signal transducer integrin beta1.
Title: ACAP4 interacts with CrkII to promote the recycling of integrin β1.

Submit: New GeneRIF Correction See all GeneRIFs (87)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WIAF-1540 (e-PCR)
- UniSTS:42060

L18426 (e-PCR)
- UniSTS:34648

RH17363 (e-PCR)
- UniSTS:33714

CRK (e-PCR)
- UniSTS:266693

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH2 domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables SH3 domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables cytoskeletal protein binding	IEA Inferred from Electronic Annotation more info
enables ephrin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin-like growth factor receptor binding	IEA Inferred from Electronic Annotation more info
enables kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphorylated amino acid binding	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables scaffold protein binding	IEA Inferred from Electronic Annotation more info
enables signaling adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables signaling adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor complex adaptor activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to endothelin	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin-like growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to nerve growth factor stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to nitric oxide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to transforming growth factor beta stimulus	IEA Inferred from Electronic Annotation more info
involved_in cerebellar neuron development	IEA Inferred from Electronic Annotation more info
involved_in cerebral cortex development	IEA Inferred from Electronic Annotation more info
involved_in dendrite development	IEA Inferred from Electronic Annotation more info
involved_in enzyme-linked receptor protein signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ephrin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in establishment of cell polarity	IEA Inferred from Electronic Annotation more info
involved_in helper T cell diapedesis	IEA Inferred from Electronic Annotation more info
involved_in hippocampus development	IEA Inferred from Electronic Annotation more info
involved_in lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell motility	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell motility	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of natural killer cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of wound healing	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of wound healing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of Rac protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of skeletal muscle acetylcholine-gated channel clustering	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of smooth muscle cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of substrate adhesion-dependent cell spreading	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in postsynaptic specialization assembly	IEA Inferred from Electronic Annotation more info
involved_in protein localization to membrane	IEA Inferred from Electronic Annotation more info
involved_in reelin-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of T cell migration	IEA Inferred from Electronic Annotation more info
involved_in regulation of actin cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell adhesion mediated by integrin	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell shape	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of dendrite development	IEA Inferred from Electronic Annotation more info
involved_in regulation of intracellular signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
involved_in response to cholecystokinin	IEA Inferred from Electronic Annotation more info
involved_in response to hepatocyte growth factor	IEA Inferred from Electronic Annotation more info
involved_in response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
involved_in response to yeast	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in actin cytoskeleton	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IC Inferred by Curator more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in neuromuscular junction	IEA Inferred from Electronic Annotation more info
located_in nucleus	TAS Traceable Author Statement more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: adapter molecule crk

Names: proto-oncogene c-Crk; v-crk avian sarcoma virus CT10 oncogene homolog; v-crk sarcoma virus CT10 oncogene-like protein

NCBI Reference Sequences (RefSeq)

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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

5019..40558

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005206.5 → NP_005197.3 adapter molecule crk isoform b

See identical proteins and their annotated locations for NP_005197.3

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

Consensus CDS

CCDS45561.1

UniProtKB/TrEMBL

A0A0S2Z3K9

Related

ENSP00000381942.5, ENST00000398970.5

Conserved Domains (2) summary

cd09926
Location:5 → 122

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

cd11758
Location:135 → 189

SH3_CRK_N; N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins
NM_016823.4 → NP_058431.2 adapter molecule crk isoform a

See identical proteins and their annotated locations for NP_058431.2

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

A8MWE8, B0LPE8, D3DTH6, P46108, Q96GA9, Q96HJ0

UniProtKB/TrEMBL

A0A0S2Z3Q4, L7RT18

Related

ENSP00000300574.2, ENST00000300574.3

Conserved Domains (3) summary

cd09926
Location:5 → 122

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

cd11758
Location:135 → 189

SH3_CRK_N; N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins

cd11759
Location:237 → 293

SH3_CRK_C; C-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins