Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

CRK (v-crk sarcoma virus CT10 oncogene homolog (avian))

Written2012-03Shinya Tanaka
Laboratory of Cancer Research, Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias_namesv-crk avian sarcoma virus CT10 oncogene homolog
Other aliasCRKII
p38
HGNC (Hugo) CRK
LocusID (NCBI) 1398
Atlas_Id 40149
Location 17p13.3  [Link to chromosome band 17p13]
Location_base_pair Starts at 1421353 and ends at 1456267 bp from pter ( according to hg19-Feb_2009)  [Mapping CRK.png]
Fusion genes
(updated 2016)
ABR (17p13.3) / CRK (17p13.3)CDS2 (20p12.3) / CRK (17p13.3)CRK (17p13.3) / CRK (17p13.3)
CRK (17p13.3) / WDR47 (1p13.3)CYP19A1 (15q21.2) / CRK (17p13.3)FABP6 (5q33.3) / CRK (17p13.3)
FAM20B (1q25.2) / CRK (17p13.3)LHFPL2 (5q14.1) / CRK (17p13.3)MYO1C (17p13.3) / CRK (17p13.3)
PLA2R1 (2q24.2) / CRK (17p13.3)TAF8 (6p21.1) / CRK (17p13.3)TUSC5 (17p13.3) / CRK (17p13.3)
WDR6 (3p21.31) / CRK (17p13.3)
Note CT10 regulator of kinase.

DNA/RNA

Note Crk belongs to an adaptor family of protein mostly composed of SH2 (src homology 2) and SH3 domains.
 
  Crk-II gene comprises of three exons spanning on chromosome 17p13.3.
Description The human genomic DNA sequence contains 3 exons.
Transcription The length of open reading frame of transcript is 912 mer and translated to a 304 residues protein referred as c-Crk-II. By alternative splicing, 610-778 were deleted and truncated protein encoding 203 amino acids protein as c-Crk-I was generated. Recently, Crk-III which comprises 283 amino acids was reported.
Pseudogene Not identified.

Protein

Note Crk was originally isolated as avian retrovirus (CT10, chicken tumor No. 10) encoding oncoprotein as v-Crk (viral Crk, CT10 regulator of kinase).
Crk-II is composed of SH2-SH3(N)-SH3(C) and alternative splicing product Crk-I which deleted SH3(C) as SH2-SH3(N).
 
  Tyrosine Y221 (human) of CrkII can be tyrosine phosphorylated and SH2 domain of CrkII binds to pY221 intramolecularly.
Description NMR analysis of Crk-I, Crk-II, and phosphorylated form of Crk-II (aa 1-231). Crk-I has flexible structure of the linker region, thus individual SH2 or SH3 domain freely access to the targets (data not shown). Unphosphorylated form of Crk-II exhibits compact structure, and each SH domains were relatively fixed around inter SH3 region (designated as ISC: inter SH3 core; yellow in the figure below). In this form, interaction surface of SH3(N) is in the semi-closed status. Upon tyrosine phosphorylation of Y221, SH2 binds to pY221 and structure is dramatically altered and SH3(N) surface is completely blocked by internal structure. Thus, pCrk-II is signaling-OFF form.
 
  Structure of signaling adaptor protein CrkII. Adapted from Kobashigawa et al. (2007).
Expression Ubiquitous.
Localisation Mostly cytoplasm.
Function Signaling adaptor protein which links tyrosine kinases and small G proteins.
Crk transmits signals from extracellular stimuli such as growth factors and extracellular matrices. SH2 domain of Crk bound to tyrosine phosphorylated peptide motif as YXXP. In focal adhesion complex, Crk binds to p130Cas which possesses six Crk binding consensus sequences and to paxillin. Crk activates Fak and transmit signals to PI3 kinase. Crk also binds to growth factor receptors such as EGFR or FGF, in addition to downstream signaling scaffold protein Gab1 which is mainly activated by HGF. CRK transmits signals to small G proteins through its SH3 domain binding target C3G and DOCK180 those can activate Rap/R-Ras and Rac, respectively, and regulates cell growth, adhesion, and motility.
Crk plays various roles including cell growth, differentiation, phagocytosis, glucose transport, and infectious diseases.
Homology CrkL (Crk-like).

Implicated in

Note
  
Entity Various diseases
Note Crk is overexpressed in various human cancers especially in lung adenocarcinoma and in brain tumor. Crk knockdown study demonstrates the essential roles for Crk in malignant potentials of various human cancers including ovarian cancer, sarcoma, and brain tumor. Recently, microRNA-126 was shown to suppress lung cancer growth by the suppression of Crk expression. Crk has been reported to bind to NS1 protein of influenza virus type H5N1, CagA protein of Helicobacter pylori, and also known to regulate the infection of Pseudomonas aeruginosa and Shigella flexneri. Therefore, Crk can be a therapeutic target molecule for cancer and infectious diseases.
  
  
Entity Lung cancer
Note 96 cases of lung adenocarcinoma were analyzed by using Gene chip and in the cases of stage III, mRNA levels of Crk were increased comparing to those of in stage I (Beer et al., 2002).
Affymetrix oligonucleotide arrays were used to analyze 86 lung adenocarcinomas and 10 uninvolved lung tissues, and Crk mRNA expression was increased in more advanced (stage III versus stage I), larger (T2-4 versus T1), and poorly differentiated tumors and in tumors from patients demonstrating poor survival (Miller et al., 2003).
Immunohistochemical analysis of Crk-II demonstrated that the levels of Crk-II were significantly elevated in most of the tumors, particularly in the colon and lung cancers. Furthermore, immunoblot analysis using human lung cancer cell lines revealed that the expression levels of Crk-II were correlated to growth rates of cells (Nishihara et al., 2002).
Prognosis Expression of Crk mRNA was increased in patients with poor prognosis (P=0.00034) (Miller et al., 2003).
  
  
Entity Brain tumor
Note CrkII mRNA was detected both in normal brain and glioblastoma tissues, whereas crkI mRNA levels were quite low in normal brain and up-regulated in glioblastoma tissues. Expression of CrkI but not CrkII in glioblastoma U87MG cells induced transformation that stimulated cell migration and invasion concomitant with tyrosine phosphorylation of p130 Cas (Takino et al., 2003).
Crk-knockdown cell lines of glioblastoma KMG4 was established by siRNA, and early phase of cell adhesion to laminin was found to be suppressed. Wound healing assay revealed the decreased cell motility in Crk knockdown cells, and suppression of both anchorage-dependent and -independent growth were demonstrated in these cells. Furthermore, in vivo tumor forming potential was also markedly suppressed (Wang et al., 2007).
  
  
Entity Ovarian cancer
Note Crk expression was targeted in the human ovarian cancer cell line MCAS through RNA interference, resulting in disorganized actin fibers, reduced number of focal adhesions, and decreased Rac activity in association with suppression of cell motility and invasion, and anchorage-dependent growth in soft agar. Tumor forming potential in nude mice was attenuated and intraperitoneal dissemination was not observed when Crk knockdown cells were injected into the peritoneal cavity (Linghu et al., 2006).
  
  
Entity Breast cancer
Note CrkI/II knockdown resulted in a significant decrease in migration and invasion of multiple malignant breast and other human cancer cell lines (MDA-231, MDA-435s, H1299, KB, and HeLa). Moreover, CrkI/II knockdown decreased cell spreading on extracellular matrix and led to a decrease in actin stress fibers and the formation of mature focal adhesions. Using immunohistochemistry, we show elevated CrkI/II protein levels in patients with breast adenocarcinoma (Rodrigues et al., 2005).
  
  
Entity Synovial sarcoma
Note Crk adaptor protein is required for the sustained phosphorylation of Gab1 in response to HGF, leading to the enhanced cell motility of human synovial sarcoma cell lines SYO-1, HS-SY-II, and Fuji. Crk knockdown by RNA interference disturbed this HGF-induced tyrosine phosphorylation of Gab1. The elimination of Crk in these cells induced the disorganization of actin cytoskeleton and complete abolishment of HGF-mediated Rac1 activation and cell motility. Furthermore, the depletion of Crk remarkably inhibited the tumor formation and its invasive growth in vivo (Watanabe et al., 2006).
  
  
Entity Oral cancer
Note The expression of CRKII in 71 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of CRKII overexpression with clinicopathological factors was evaluated. Overexpression of CRKII was detected in 41 of 70 oral squamous cell carcinomas, the frequency being more significant than in normal oral mucosa. In addition, CRKII overexpression was more frequent in higher-grade cancers according to the T classification, N classification, and invasive pattern. Moreover, RNAi-mediated suppression of CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20 (Yamada et al., 2011).
  
  
Entity Endometriosis
Note The expression levels of miR-126 and and its putative target Crk mRNA were quantified using real time PCR in ectopic endometrium and eutopic endometrium in patients with endometriosis. The expression level of miR-126 was significantly downregulated in ectopic endometrium whereas the protein levels of Crk was increased. Thus, miR-126 may play an initial role in the development and progression of endometriosis (Liu et al., 2012).
  

Bibliography

Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling.
Heikkinen LS, Kazlauskas A, Melen K, Wagner R, Ziegler T, Julkunen I, Saksela K.
J Biol Chem. 2008 Feb 29;283(9):5719-27. Epub 2007 Dec 28.
PMID 18165234
 
v-Crk activates the phosphoinositide 3-kinase/AKT pathway in transformation.
Akagi T, Shishido T, Murata K, Hanafusa H.
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7290-5.
PMID 10852971
 
Gene-expression profiles predict survival of patients with lung adenocarcinoma.
Beer DG, Kardia SL, Huang CC, Giordano TJ, Levin AM, Misek DE, Lin L, Chen G, Gharib TG, Thomas DG, Lizyness ML, Kuick R, Hayasaka S, Taylor JM, Iannettoni MD, Orringer MB, Hanash S.
Nat Med. 2002 Aug;8(8):816-24. Epub 2002 Jul 15.
PMID 12118244
 
c-Abl kinase regulates the protein binding activity of c-Crk.
Feller SM, Knudsen B, Hanafusa H.
EMBO J. 1994 May 15;13(10):2341-51.
PMID 8194526
 
Crk family adaptors-signalling complex formation and biological roles.
Feller SM.
Oncogene. 2001 Oct 1;20(44):6348-71. (REVIEW)
PMID 11607838
 
Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling.
Heikkinen LS, Kazlauskas A, Melen K, Wagner R, Ziegler T, Julkunen I, Saksela K.
J Biol Chem. 2008 Feb 29;283(9):5719-27. Epub 2007 Dec 28.
PMID 18165234
 
CrkII regulates focal adhesion kinase activation by making a complex with Crk-associated substrate, p130Cas.
Iwahara T, Akagi T, Fujitsuka Y, Hanafusa H.
Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17693-8. Epub 2004 Dec 14.
PMID 15598735
 
Activation of Rac1 by a Crk SH3-binding protein, DOCK180.
Kiyokawa E, Hashimoto Y, Kobayashi S, Sugimura H, Kurata T, Matsuda M.
Genes Dev. 1998 Nov 1;12(21):3331-6.
PMID 9808620
 
Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.
Kobashigawa Y, Sakai M, Naito M, Yokochi M, Kumeta H, Makino Y, Ogura K, Tanaka S, Inagaki F.
Nat Struct Mol Biol. 2007 Jun;14(6):503-10. Epub 2007 May 21.
PMID 17515907
 
Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS.
Linghu H, Tsuda M, Makino Y, Sakai M, Watanabe T, Ichihara S, Sawa H, Nagashima K, Mochizuki N, Tanaka S.
Oncogene. 2006 Jun 15;25(25):3547-56. Epub 2006 Feb 20.
PMID 16491127
 
Expression of miR-126 and Crk in endometriosis: miR-126 may affect the progression of endometriosis by regulating Crk expression.
Liu S, Gao S, Wang XY, Wang DB.
Arch Gynecol Obstet. 2012 Apr;285(4):1065-72. Epub 2011 Oct 20.
PMID 22012249
 
Elmo1 inhibits ubiquitylation of Dock180.
Makino Y, Tsuda M, Ichihara S, Watanabe T, Sakai M, Sawa H, Nagashima K, Hatakeyama S, Tanaka S.
J Cell Sci. 2006 Mar 1;119(Pt 5):923-32.
PMID 16495483
 
Two species of human CRK cDNA encode proteins with distinct biological activities.
Matsuda M, Tanaka S, Nagata S, Kojima A, Kurata T, Shibuya M.
Mol Cell Biol. 1992 Aug;12(8):3482-9.
PMID 1630456
 
A novel viral oncogene with structural similarity to phospholipase C.
Mayer BJ, Hamaguchi M, Hanafusa H.
Nature. 1988 Mar 17;332(6161):272-5.
PMID 2450282
 
Increased C-CRK proto-oncogene expression is associated with an aggressive phenotype in lung adenocarcinomas.
Miller CT, Chen G, Gharib TG, Wang H, Thomas DG, Misek DE, Giordano TJ, Yee J, Orringer MB, Hanash SM, Beer DG.
Oncogene. 2003 Sep 11;22(39):7950-7.
PMID 12970743
 
Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers.
Nishihara H, Tanaka S, Tsuda M, Oikawa S, Maeda M, Shimizu M, Shinomiya H, Tanigami A, Sawa H, Nagashima K.
Cancer Lett. 2002 Jun 6;180(1):55-61.
PMID 11911970
 
CrkIII: a novel and biologically distinct member of the Crk family of adaptor proteins.
Prosser S, Sorokina E, Pratt P, Sorokin A.
Oncogene. 2003 Jul 31;22(31):4799-806.
PMID 12894221
 
Sustained formation of focal adhesions with paxillin in morphological differentiation of PC12 cells.
Rhee S, Lee KH, Kim D, Kwon YK, Kang MS, Kwon H.
Mol Cells. 2000 Apr 30;10(2):169-79.
PMID 10850658
 
CrkI and CrkII function as key signaling integrators for migration and invasion of cancer cells.
Rodrigues SP, Fathers KE, Chan G, Zuo D, Halwani F, Meterissian S, Park M.
Mol Cancer Res. 2005 Apr;3(4):183-94.
PMID 15831672
 
Proline cis-trans isomerization controls autoinhibition of a signaling protein.
Sarkar P, Reichman C, Saleh T, Birge RB, Kalodimos CG.
Mol Cell. 2007 Feb 9;25(3):413-26.
PMID 17289588
 
pp125FAK-dependent tyrosine phosphorylation of paxillin creates a high-affinity binding site for Crk.
Schaller MD, Parsons JT.
Mol Cell Biol. 1995 May;15(5):2635-45.
PMID 7537852
 
Crk protein binds to PDGF receptor and insulin receptor substrate-1 with different modulating effects on PDGF- and insulin-dependent signaling pathways.
Sorokin A, Reed E, Nnkemere N, Dulin NO, Schlessinger J.
Oncogene. 1998 May 14;16(19):2425-34.
PMID 9627109
 
CrkI adapter protein modulates cell migration and invasion in glioblastoma.
Takino T, Nakada M, Miyamori H, Yamashita J, Yamada KM, Sato H.
Cancer Res. 2003 May 1;63(9):2335-7.
PMID 12727859
 
Both the SH2 and SH3 domains of human CRK protein are required for neuronal differentiation of PC12 cells.
Tanaka S, Hattori S, Kurata T, Nagashima K, Fukui Y, Nakamura S, Matsuda M.
Mol Cell Biol. 1993 Jul;13(7):4409-15.
PMID 8321240
 
C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins.
Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M, Matuoka K, Takenawa T, Kurata T, Nagashima K, et al.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3443-7.
PMID 7512734
 
Downstream of Crk adaptor signaling pathway: activation of Jun kinase by v-Crk through the guanine nucleotide exchange protein C3G.
Tanaka S, Ouchi T, Hanafusa H.
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2356-61.
PMID 9122199
 
Signaling adaptor protein v-Crk activates Rho and regulates cell motility in 3Y1 rat fibroblast cell line.
Tsuda M, Tanaka S, Sawa H, Hanafusa H, Nagashima K.
Cell Growth Differ. 2002 Mar;13(3):131-9.
PMID 11959814
 
Signaling adaptor protein Crk is indispensable for malignant feature of glioblastoma cell line KMG4.
Wang L, Tabu K, Kimura T, Tsuda M, Linghu H, Tanino M, Kaneko S, Nishihara H, Tanaka S.
Biochem Biophys Res Commun. 2007 Nov 3;362(4):976-81. Epub 2007 Aug 27.
PMID 17825249
 
Adaptor molecule Crk is required for sustained phosphorylation of Grb2-associated binder 1 and hepatocyte growth factor-induced cell motility of human synovial sarcoma cell lines.
Watanabe T, Tsuda M, Makino Y, Ichihara S, Sawa H, Minami A, Mochizuki N, Nagashima K, Tanaka S.
Mol Cancer Res. 2006 Jul;4(7):499-510.
PMID 16849525
 
Overexpression of CRKII increases migration and invasive potential in oral squamous cell carcinoma.
Yamada S, Yanamoto S, Kawasaki G, Rokutanda S, Yonezawa H, Kawakita A, Nemoto TK.
Cancer Lett. 2011 Apr 28;303(2):84-91. Epub 2011 Feb 19.
PMID 21339045
 
Isolation and chromosomal localization of CRKL, a human crk-like gene.
ten Hoeve J, Morris C, Heisterkamp N, Groffen J.
Oncogene. 1993 Sep;8(9):2469-74.
PMID 8361759
 

Citation

This paper should be referenced as such :
Tanaka, S
CRK (v-crk sarcoma virus CT10 oncogene homolog (avian))
Atlas Genet Cytogenet Oncol Haematol. 2012;16(8):521-525.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CRKID40149ch17p13.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(3;11)(p25;p15) ANKRD28/NUP98


External links

Nomenclature
HGNC (Hugo)CRK   2362
Cards
AtlasCRKID40149ch17p13
Entrez_Gene (NCBI)CRK  1398  CRK proto-oncogene, adaptor protein
AliasesCRKII; p38
GeneCards (Weizmann)CRK
Ensembl hg19 (Hinxton)ENSG00000167193 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000167193 [Gene_View]  chr17:1421353-1456267 [Contig_View]  CRK [Vega]
ICGC DataPortalENSG00000167193
TCGA cBioPortalCRK
AceView (NCBI)CRK
Genatlas (Paris)CRK
WikiGenes1398
SOURCE (Princeton)CRK
Genetics Home Reference (NIH)CRK
Genomic and cartography
GoldenPath hg38 (UCSC)CRK  -     chr17:1421353-1456267 -  17p13.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CRK  -     17p13.3   [Description]    (hg19-Feb_2009)
EnsemblCRK - 17p13.3 [CytoView hg19]  CRK - 17p13.3 [CytoView hg38]
Mapping of homologs : NCBICRK [Mapview hg19]  CRK [Mapview hg38]
OMIM164762   
Gene and transcription
Genbank (Entrez)AK095449 AK291060 AU125411 BC001718 BC008506
RefSeq transcript (Entrez)NM_005206 NM_016823
RefSeq genomic (Entrez)NC_000017 NC_018928 NG_029008 NT_187613
Consensus coding sequences : CCDS (NCBI)CRK
Cluster EST : UnigeneHs.461896 [ NCBI ]
CGAP (NCI)Hs.461896
Alternative Splicing GalleryENSG00000167193
Gene ExpressionCRK [ NCBI-GEO ]   CRK [ EBI - ARRAY_EXPRESS ]   CRK [ SEEK ]   CRK [ MEM ]
Gene Expression Viewer (FireBrowse)CRK [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1398
GTEX Portal (Tissue expression)CRK
Protein : pattern, domain, 3D structure
UniProt/SwissProtP46108   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP46108  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP46108
Splice isoforms : SwissVarP46108
PhosPhoSitePlusP46108
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)    SH3 (PS50002)   
Domains : Interpro (EBI)SH2    SH3_2    SH3_domain   
Domain families : Pfam (Sanger)SH2 (PF00017)    SH3_1 (PF00018)    SH3_2 (PF07653)   
Domain families : Pfam (NCBI)pfam00017    pfam00018    pfam07653   
Domain families : Smart (EMBL)SH2 (SM00252)  SH3 (SM00326)  
Conserved Domain (NCBI)CRK
DMDM Disease mutations1398
Blocks (Seattle)CRK
PDB (SRS)1JU5    2DVJ    2EYV    2EYW    2EYX    2EYY    2EYZ    2MS4   
PDB (PDBSum)1JU5    2DVJ    2EYV    2EYW    2EYX    2EYY    2EYZ    2MS4   
PDB (IMB)1JU5    2DVJ    2EYV    2EYW    2EYX    2EYY    2EYZ    2MS4   
PDB (RSDB)1JU5    2DVJ    2EYV    2EYW    2EYX    2EYY    2EYZ    2MS4   
Structural Biology KnowledgeBase1JU5    2DVJ    2EYV    2EYW    2EYX    2EYY    2EYZ    2MS4   
SCOP (Structural Classification of Proteins)1JU5    2DVJ    2EYV    2EYW    2EYX    2EYY    2EYZ    2MS4   
CATH (Classification of proteins structures)1JU5    2DVJ    2EYV    2EYW    2EYX    2EYY    2EYZ    2MS4   
SuperfamilyP46108
Human Protein AtlasENSG00000167193
Peptide AtlasP46108
HPRD01267
IPIIPI00004838   IPI00399054   
Protein Interaction databases
DIP (DOE-UCLA)P46108
IntAct (EBI)P46108
FunCoupENSG00000167193
BioGRIDCRK
STRING (EMBL)CRK
ZODIACCRK
Ontologies - Pathways
QuickGOP46108
Ontology : AmiGOactivation of MAPKK activity  phosphotyrosine binding  response to yeast  SH3/SH2 adaptor activity  insulin-like growth factor receptor binding  protein binding  nucleus  cytoplasm  cytosol  plasma membrane  regulation of transcription from RNA polymerase II promoter  cytoskeletal protein binding  regulation of cell shape  regulation of signal transduction  positive regulation of smooth muscle cell migration  actin cytoskeleton  SH3 domain binding  regulation of actin cytoskeleton organization  regulation of Rac protein signal transduction  response to hepatocyte growth factor  Fc-gamma receptor signaling pathway involved in phagocytosis  SH2 domain binding  response to hydrogen peroxide  regulation of GTPase activity  protein complex  regulation of protein binding  protein self-association  membrane raft  protein phosphorylated amino acid binding  negative regulation of natural killer cell mediated cytotoxicity  ephrin receptor binding  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  negative regulation of wound healing  negative regulation of wound healing  response to cholecystokinin  extracellular exosome  SH2 domain-mediated complex assembly  cellular response to transforming growth factor beta stimulus  cellular response to nitric oxide  scaffold protein binding  positive regulation of substrate adhesion-dependent cell spreading  cellular response to nerve growth factor stimulus  cellular response to insulin-like growth factor stimulus  protein tyrosine kinase binding  cellular response to endothelin  negative regulation of cell motility  negative regulation of cell motility  
Ontology : EGO-EBIactivation of MAPKK activity  phosphotyrosine binding  response to yeast  SH3/SH2 adaptor activity  insulin-like growth factor receptor binding  protein binding  nucleus  cytoplasm  cytosol  plasma membrane  regulation of transcription from RNA polymerase II promoter  cytoskeletal protein binding  regulation of cell shape  regulation of signal transduction  positive regulation of smooth muscle cell migration  actin cytoskeleton  SH3 domain binding  regulation of actin cytoskeleton organization  regulation of Rac protein signal transduction  response to hepatocyte growth factor  Fc-gamma receptor signaling pathway involved in phagocytosis  SH2 domain binding  response to hydrogen peroxide  regulation of GTPase activity  protein complex  regulation of protein binding  protein self-association  membrane raft  protein phosphorylated amino acid binding  negative regulation of natural killer cell mediated cytotoxicity  ephrin receptor binding  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  negative regulation of wound healing  negative regulation of wound healing  response to cholecystokinin  extracellular exosome  SH2 domain-mediated complex assembly  cellular response to transforming growth factor beta stimulus  cellular response to nitric oxide  scaffold protein binding  positive regulation of substrate adhesion-dependent cell spreading  cellular response to nerve growth factor stimulus  cellular response to insulin-like growth factor stimulus  protein tyrosine kinase binding  cellular response to endothelin  negative regulation of cell motility  negative regulation of cell motility  
Pathways : BIOCARTASignaling of Hepatocyte Growth Factor Receptor [Genes]    CXCR4 Signaling Pathway [Genes]   
Pathways : KEGG   
REACTOMEP46108 [protein]
REACTOME PathwaysR-HSA-912631 [pathway]   
NDEx NetworkCRK
Atlas of Cancer Signalling NetworkCRK
Wikipedia pathwaysCRK
Orthology - Evolution
OrthoDB1398
GeneTree (enSembl)ENSG00000167193
Phylogenetic Trees/Animal Genes : TreeFamCRK
HOVERGENP46108
HOGENOMP46108
Homologs : HomoloGeneCRK
Homology/Alignments : Family Browser (UCSC)CRK
Gene fusions - Rearrangements
Fusion : MitelmanABR/CRK [17p13.3/17p13.3]  [t(17;17)(p13;p13)]  
Fusion: TCGAABR 17p13.3 CRK 17p13.3 LUAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCRK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CRK
dbVarCRK
ClinVarCRK
1000_GenomesCRK 
Exome Variant ServerCRK
ExAC (Exome Aggregation Consortium)CRK (select the gene name)
Genetic variants : HAPMAP1398
Genomic Variants (DGV)CRK [DGVbeta]
DECIPHERCRK [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCRK 
Mutations
ICGC Data PortalCRK 
TCGA Data PortalCRK 
Broad Tumor PortalCRK
OASIS PortalCRK [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCRK  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCRK
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CRK
DgiDB (Drug Gene Interaction Database)CRK
DoCM (Curated mutations)CRK (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CRK (select a term)
intoGenCRK
NCG5 (London)CRK
Cancer3DCRK(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM164762   
Orphanet
MedgenCRK
Genetic Testing Registry CRK
NextProtP46108 [Medical]
TSGene1398
GENETestsCRK
Target ValidationCRK
Huge Navigator CRK [HugePedia]
snp3D : Map Gene to Disease1398
BioCentury BCIQCRK
ClinGenCRK
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1398
Chemical/Pharm GKB GenePA26880
Clinical trialCRK
Miscellaneous
canSAR (ICR)CRK (select the gene name)
Probes
Litterature
PubMed253 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCRK
EVEXCRK
GoPubMedCRK
iHOPCRK
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Jun 30 11:03:57 CEST 2017

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.