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... See more...

Aliases for CRK Gene

Aliases for CRK Gene

  • CRK Proto-Oncogene, Adaptor Protein 2 3 5
  • V-Crk Avian Sarcoma Virus CT10 Oncogene Homolog 2 3
  • Adapter Molecule Crk 3 4
  • Proto-Oncogene C-Crk 3 4
  • P38 3 4
  • V-Crk Sarcoma Virus CT10 Oncogene-Like Protein 3
  • CRKII 3

External Ids for CRK Gene

Previous GeneCards Identifiers for CRK Gene

  • GC17M001318
  • GC17M001659
  • GC17M001533
  • GC17M001534
  • GC17M001272
  • GC17M001323

Summaries for CRK Gene

Entrez Gene Summary for CRK Gene

  • 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]

GeneCards Summary for CRK Gene

CRK (CRK Proto-Oncogene, Adaptor Protein) is a Protein Coding gene. Diseases associated with CRK include Sarcoma and Chromosome 17P13.3, Centromeric, Duplication Syndrome. Among its related pathways are CCR5 Pathway in Macrophages and NGF Pathway. Gene Ontology (GO) annotations related to this gene include protein domain specific binding and SH3/SH2 adaptor activity. An important paralog of this gene is CRKL.

UniProtKB/Swiss-Prot Summary for CRK Gene

  • [Isoform Crk-II]: Regulates cell adhesion, spreading and migration. Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.

Gene Wiki entry for CRK Gene

Additional gene information for CRK Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CRK Gene

Genomics for CRK Gene

GeneHancer (GH) Regulatory Elements for CRK Gene

Promoters and enhancers for CRK Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17J001484 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 500.3 -25.9 -25865 9.9 RXRA EP300 SIN3A TCF12 POLR2G USF1 SP1 PHF8 JUND PHB2 MYO1C CRK PITPNA HNRNPA1P16 YWHAE DPH1 INPP5K TRARG1 RPS4XP17 TIMM22
GH17J001453 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 512.9 +7.3 7313 3.7 FOXK2 ZBTB40 ZNF217 EP300 CTCF SIN3A NRF1 POLR2G NCOR1 PHF8 CRK PRPF8 HNRNPA1P16 SMYD4 DPH1 RPA1 ENSG00000263345 GEMIN4 SMG6 ENSG00000262228
GH17J001462 Promoter/Enhancer 1.5 Ensembl ENCODE dbSUPER 512.1 +0.1 118 1.8 SP1 ZNF639 ZBTB10 KLF7 HES1 RCOR1 RUNX1 CTBP1 TRIM22 ATF2 CRK lnc-TUSC5-5 MNT ENSG00000262228 GEMIN4 ENSG00000262777 RF00017-2207
GH17J001461 Promoter/Enhancer 0.7 Ensembl ENCODE 511.3 +1.5 1534 0.9 ZNF316 POLR2A SCRT2 CRK TLCD2 ENSG00000262777 RF00017-2207
GH17J001294 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 22.7 +168.8 168813 1.2 RBAK ZNF354C ZNF623 ZNF274 ATF2 ZEB1 GATAD2B CTBP1 ZNF148 KDM1A PRPF8 RPA1 SMYD4 ENSG00000263050 DPH1 WDR81 CRK GEMIN4 MYO1C DBIL5P
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CRK on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CRK

Top Transcription factor binding sites by QIAGEN in the CRK gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • c-Myc
  • Max1

Genomic Locations for CRK Gene

Genomic Locations for CRK Gene
chr17:1,420,689-1,463,162
(GRCh38/hg38)
Size:
42,474 bases
Orientation:
Minus strand
chr17:1,323,983-1,366,456
(GRCh37/hg19)
Size:
42,474 bases
Orientation:
Minus strand

Genomic View for CRK Gene

Genes around CRK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CRK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CRK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CRK Gene

Proteins for CRK Gene

  • Protein details for CRK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P46108-CRK_HUMAN
    Recommended name:
    Adapter molecule crk
    Protein Accession:
    P46108
    Secondary Accessions:
    • A8MWE8
    • B0LPE8
    • D3DTH6
    • Q96GA9
    • Q96HJ0

    Protein attributes for CRK Gene

    Size:
    304 amino acids
    Molecular mass:
    33831 Da
    Quaternary structure:
    • Interacts with ABL1, C3G, DOCK3, DOCK5, MAP4K1, MAPK8 and SOS via its first SH3 domain. Interacts (via SH2 domain) with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1 upon stimulus-induced tyrosine phosphorylation. Interacts (via SH2 domain) with several tyrosine-phosphorylated growth factor receptors such as EGFR and INSR. Interacts with FLT1 (tyrosine-phosphorylated). Interacts with DOCK1 and DOCK4. Interacts with SHB. Interacts with PEAK1. Interacts with FASLG. Isoform Crk-II interacts with KIT. Interacts with EPHA3; upon activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase activity-dependent. Interacts with EPHA3 (phosphorylated); mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. Interacts with FLT4 (tyrosine-phosphorylated). Isoform Crk-II (via SH2 domain) interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and p130cas/BCAR1. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with CBLC. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases.

    Three dimensional structures from OCA and Proteopedia for CRK Gene

    Alternative splice isoforms for CRK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CRK Gene

Post-translational modifications for CRK Gene

  • Phosphorylation of Crk-II (40 kDa) gives rise to a 42 kDa form. Isoform Crk-II is phosphorylated by KIT.
  • Phosphorylated on Tyr-221 upon cell adhesion. Results in the negative regulation of the association with SH2- and SH3-binding partners, possibly by the formation of an intramolecular interaction of phosphorylated Tyr-221 with the SH2 domain. This leads finally to the down-regulation of the Crk signaling pathway.
  • Proline isomerization at Pro-237 by PPIA acts as a switch between two conformations: an autoinhibitory conformation in the cis form, where the tandem SH3 domains interact intramolecularly, and an activated conformation in the trans form.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CRK Gene

Antibody Products

No data available for DME Specific Peptides for CRK Gene

Domains & Families for CRK Gene

Gene Families for CRK Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for CRK Gene

Blocks:
  • SH3 domain signature
  • Variant SH3
  • SH2 domain signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CRK Gene

GenScript: Design optimal peptide antigens:
  • p38 (CRK_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P46108

UniProtKB/Swiss-Prot:

CRK_HUMAN :
  • The C-terminal SH3 domain function as a negative modulator for transformation and the N-terminal SH3 domain appears to function as a positive regulator for transformation.
  • Belongs to the CRK family.
Domain:
  • The C-terminal SH3 domain function as a negative modulator for transformation and the N-terminal SH3 domain appears to function as a positive regulator for transformation.
  • The SH2 domain mediates interaction with tyrosine phosphorylated proteins. Mediates interaction with SHB.
Family:
  • Belongs to the CRK family.
genes like me logo Genes that share domains with CRK: view

Function for CRK Gene

Molecular function for CRK Gene

UniProtKB/Swiss-Prot Function:
[Isoform Crk-II]: Regulates cell adhesion, spreading and migration. Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.
GENATLAS Biochemistry:
avian sarcoma virus CT10 (v-crk) homolog

Phenotypes From GWAS Catalog for CRK Gene

Gene Ontology (GO) - Molecular Function for CRK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine residue binding IPI 20624904
GO:0005070 SH3/SH2 adaptor activity IDA 12384576
GO:0005159 insulin-like growth factor receptor binding IEA --
GO:0005515 protein binding IEA,IPI 7561682
GO:0008092 cytoskeletal protein binding IEA --
genes like me logo Genes that share ontologies with CRK: view
genes like me logo Genes that share phenotypes with CRK: view

Animal Models for CRK Gene

MGI Knock Outs for CRK:
  • Crk Crk<tm1.1Cur>

Animal Model Products

CRISPR Products

miRNA for CRK Gene

miRTarBase miRNAs that target CRK

Clone Products

  • Addgene plasmids for CRK

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CRK Gene

Localization for CRK Gene

Subcellular locations from UniProtKB/Swiss-Prot for CRK Gene

Cytoplasm. Cell membrane. Note=Translocated to the plasma membrane upon cell adhesion. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CRK gene
Compartment Confidence
cytosol 5
plasma membrane 4
cytoskeleton 4
nucleus 4
extracellular 2
mitochondrion 2
endoplasmic reticulum 2
endosome 2
lysosome 2
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CRK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS 10748058
GO:0005737 cytoplasm IC,IEA 11870224
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA --
GO:0015629 actin cytoskeleton IEA --
genes like me logo Genes that share ontologies with CRK: view

Pathways & Interactions for CRK Gene

genes like me logo Genes that share pathways with CRK: view

Pathways by source for CRK Gene

8 GeneGo (Thomson Reuters) pathways for CRK Gene
  • Cell adhesion Integrin-mediated cell adhesion and migration
  • Chemotaxis CXCR4 signaling pathway
  • Cytoskeleton remodeling FAK signaling
  • Development Angiopoietin - Tie2 signaling
  • Development FGFR signaling pathway
15 Qiagen pathways for CRK Gene
  • Chemokine Signaling
  • CXCR4 Pathway
  • Epithelial Adherens Junctions
  • FAK1 Signaling
  • GPCR Pathway
1 Cell Signaling Technology pathway for CRK Gene
1 GeneTex pathway for CRK Gene

SIGNOR curated interactions for CRK Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for CRK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000186 activation of MAPKK activity TAS --
GO:0001764 neuron migration IEA --
GO:0001878 response to yeast IEA --
GO:0002685 regulation of leukocyte migration IEA --
GO:0006357 regulation of transcription by RNA polymerase II TAS 10748058
genes like me logo Genes that share ontologies with CRK: view

Drugs & Compounds for CRK Gene

(9) Drugs for CRK Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(11) Additional Compounds for CRK Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CRK: view

Transcripts for CRK Gene

mRNA/cDNA for CRK Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for CRK

Alternative Splicing Database (ASD) splice patterns (SP) for CRK Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b
SP1: -
SP2:

Relevant External Links for CRK Gene

GeneLoc Exon Structure for
CRK

Expression for CRK Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CRK Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CRK Gene

This gene is overexpressed in Uterus (6.2) and Oral epithelium (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CRK Gene



Protein tissue co-expression partners for CRK Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CRK

SOURCE GeneReport for Unigene cluster for CRK Gene:

Hs.461896

Evidence on tissue expression from TISSUES for CRK Gene

  • Lung(4.4)
  • Liver(4.3)
  • Eye(4.2)
  • Nervous system(3.8)
  • Kidney(2.3)
  • Heart(2.2)
  • Adrenal gland(2.1)
  • Muscle(2.1)
  • Blood(2)
genes like me logo Genes that share expression patterns with CRK: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CRK Gene

Orthologs for CRK Gene

This gene was present in the common ancestor of animals.

Orthologs for CRK Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CRK 31 30
  • 99.55 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CRK 31 30
  • 98.14 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CRK 31 30
  • 97.7 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Crk 17 31 30
  • 96.16 (n)
rat
(Rattus norvegicus)
Mammalia Crk 30
  • 96.05 (n)
oppossum
(Monodelphis domestica)
Mammalia CRK 31
  • 88 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CRK 31
  • 88 (a)
OneToOne
chicken
(Gallus gallus)
Aves CRK 31 30
  • 83.99 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CRK 31
  • 79 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia crk 30
  • 79.62 (n)
Str.6504 30
African clawed frog
(Xenopus laevis)
Amphibia MGC68492 30
zebrafish
(Danio rerio)
Actinopterygii crk 31 30
  • 69.4 (n)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4632 30
fruit fly
(Drosophila melanogaster)
Insecta Crk 31 30
  • 51.25 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP009499 30
  • 49.33 (n)
worm
(Caenorhabditis elegans)
Secernentea ced-2 31 30
  • 45.51 (n)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.6350 31
  • 48 (a)
OneToMany
Species where no ortholog for CRK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CRK Gene

ENSEMBL:
Gene Tree for CRK (if available)
TreeFam:
Gene Tree for CRK (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CRK: view image

Paralogs for CRK Gene

Paralogs for CRK Gene

(6) SIMAP similar genes for CRK Gene using alignment to 3 proteins:

  • CRK_HUMAN
  • I3L297_HUMAN
  • L7RT18_HUMAN

Pseudogenes.org Pseudogenes for CRK Gene

genes like me logo Genes that share paralogs with CRK: view

Variants for CRK Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CRK Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
758881 Likely Benign: not provided 1,436,797(-) C/T SYNONYMOUS_VARIANT
768814 Benign: not provided 1,455,914(-) G/C SYNONYMOUS_VARIANT
775157 Benign: not provided 1,437,022(-) A/G SYNONYMOUS_VARIANT
789896 Benign: not provided 1,455,938(-) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for CRK Gene

Structural Variations from Database of Genomic Variants (DGV) for CRK Gene

Variant ID Type Subtype PubMed ID
esv1931977 CNV deletion 18987734
esv2715463 CNV deletion 23290073
esv3639685 CNV loss 21293372
nsv1057782 CNV gain 25217958
nsv470567 CNV gain 18288195
nsv833334 CNV loss 17160897

Variation tolerance for CRK Gene

Residual Variation Intolerance Score: 18.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.19; 4.32% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CRK Gene

Human Gene Mutation Database (HGMD)
CRK
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CRK

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CRK Gene

Disorders for CRK Gene

MalaCards: The human disease database

(7) MalaCards diseases for CRK Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
sarcoma
  • connective and soft tissue neoplasm
chromosome 17p13.3, centromeric, duplication syndrome
  • chromosome 17p13.3 duplication syndrome
avian influenza
  • avian flu
miller-dieker lissencephaly syndrome
  • mdls
lissencephaly
- elite association - COSMIC cancer census association via MalaCards
Search CRK in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CRK

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Tumor Gene Database
(TGDB)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CRK: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CRK Gene

Publications for CRK Gene

  1. DOCK5 and DOCK1 regulate Caco-2 intestinal epithelial cell spreading and migration on collagen IV. (PMID: 19004829) Sanders MA … Basson MD (The Journal of biological chemistry 2009) 3 4 23 54
  2. Differential interaction of CrkII adaptor protein with platelet-derived growth factor alpha- and beta-receptors is determined by its internal tyrosine phosphorylation. (PMID: 10733900) Matsumoto T … Mori S (Biochemical and biophysical research communications 2000) 3 4 23 54
  3. Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction. (PMID: 9614078) Koval AP … LeRoith D (The Journal of biological chemistry 1998) 3 4 23 54
  4. Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins. (PMID: 8662907) Matsuda M … Kurata T (The Journal of biological chemistry 1996) 3 4 23 54
  5. Two species of human CRK cDNA encode proteins with distinct biological activities. (PMID: 1630456) Matsuda M … Shibuya M (Molecular and cellular biology 1992) 3 4 23 54

Products for CRK Gene

  • Addgene plasmids for CRK

Sources for CRK Gene