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UniProtKB/Swiss-Prot entry P46108

[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name CRK_HUMAN
Primary accession number P46108
Secondary accession number Q96HJ0
Integrated into Swiss-Prot on November 1, 1995
Sequence was last modified on July 24, 2007 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 99)
Name and origin of the protein
Protein name Proto-oncogene C-crk
Synonyms p38
Adapter molecule crk
Gene name
Name: CRK
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
 NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND ALTERNATIVE SPLICING.
TISSUE=Embryonic lung, and Placenta;
PubMed=1630456 [NCBI, ExPASy, EBI, Israel, Japan]
Matsuda M., Tanaka S., Nagata S., Kojima A., Kurata T., Shibuya M.;
"Two species of human CRK cDNA encode proteins with distinct biological activities.";
Mol. Cell. Biol. 12:3482-3489(1992).
[2]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=8378094 [NCBI, ExPASy, EBI, Israel, Japan]
Fioretos T., Heisterkamp N., Groffen J., Benjes S., Morris C.;
"CRK proto-oncogene maps to human chromosome band 17p13.";
Oncogene 8:2853-2855(1993).
[3]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[4]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Eye, and Placenta;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
 INTERACTION WITH DOCK1.
PubMed=8657152 [NCBI, ExPASy, EBI, Israel, Japan]
Hasegawa H., Kiyokawa E., Tanaka S., Nagashima K., Gotoh N., Shibuya M., Kurata T., Matsuda M.;
"DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane.";
Mol. Cell. Biol. 16:1770-1776(1996).
[6]
 INTERACTION WITH DOCK1; C3G AND EPS15, AND MUTAGENESIS OF ASP-150.
DOI=10.1074/jbc.271.24.14468; PubMed=8662907 [NCBI, ExPASy, EBI, Israel, Japan]
Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T., Nagashima K., Kurata T.;
"Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins.";
J. Biol. Chem. 271:14468-14472(1996).
[7]
 INTERACTION WITH IRS4.
DOI=10.1074/jbc.273.24.14780; PubMed=9614078 [NCBI, ExPASy, EBI, Israel, Japan]
Koval A.P., Karas M., Zick Y., LeRoith D.;
"Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction.";
J. Biol. Chem. 273:14780-14787(1998).
[8]
 INTERACTION WITH SHB.
DOI=10.1006/excr.2000.4984; PubMed=10964504 [NCBI, ExPASy, EBI, Israel, Japan]
Lu L., Anneren C., Reedquist K.A., Bos J.L., Welsh M.;
"NGF-dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway.";
Exp. Cell Res. 259:370-377(2000).
[9]
 INTERACTION WITH DOCK4.
DOI=10.1016/S0092-8674(03)00155-7; PubMed=12628187 [NCBI, ExPASy, EBI, Israel, Japan]
Yajnik V., Paulding C., Sordella R., McClatchey A.I., Saito M., Wahrer D.C.R., Reynolds P., Bell D.W., Lake R., van den Heuvel S., Settleman J., Haber D.A.;
"DOCK4, a GTPase activator, is disrupted during tumorigenesis.";
Cell 112:673-684(2003).
[10]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-239, AND MASS SPECTROMETRY.
DOI=10.1038/nbt1046; PubMed=15592455 [NCBI, ExPASy, EBI, Israel, Japan]
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.;
"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
Nat. Biotechnol. 23:94-101(2005).
[11]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-221, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[12]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74 AND SER-83, AND MASS SPECTROMETRY.
DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan]
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[13]
 IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
Colinge J., Superti-Furga G., Bennett K.L.;
Submitted (OCT-2008) to UniProtKB.
[14]
 STRUCTURE BY NMR OF 12-120 IN COMPLEX WITH ABL1, AND INTERACTION OF THE CRK SH2 DOMAIN WITH PHOSPHORYLATED TYR-221.
DOI=10.1073/pnas.212518799; PubMed=12384576 [NCBI, ExPASy, EBI, Israel, Japan]
Donaldson L.W., Gish G., Pawson T., Kay L.E., Forman-Kay J.D.;
"Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.";
Proc. Natl. Acad. Sci. U.S.A. 99:14053-14058(2002).
[15]
 STRUCTURE BY NMR (ISOFORMS CRK-I AND CRK-II), FUNCTION, AND PHOSPHORYLATION.
DOI=10.1038/nsmb1241; PubMed=17515907 [NCBI, ExPASy, EBI, Israel, Japan]
Kobashigawa Y., Sakai M., Naito M., Yokochi M., Kumeta H., Makino Y., Ogura K., Tanaka S., Inagaki F.;
"Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.";
Nat. Struct. Mol. Biol. 14:503-510(2007).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
D10656; BAA01505.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S65701; AAB28213.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT007277; AAP35941.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC001718; AAH01718.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC008506; AAH08506.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00004838; -.
IPI00399054; -.
PIR A45022; A45022.
RefSeq NP_005197.3; -.
NP_058431.2; -.
UniGene Hs.638121
3D structure databases
PDB
1JU5; NMR; -; A=12-120.[ExPASy / RCSB / EBI]
2DVJ; NMR; -; A=1-228.[ExPASy / RCSB / EBI]
2EYV; NMR; -; A=6-124.[ExPASy / RCSB / EBI]
2EYW; NMR; -; A=124-198.[ExPASy / RCSB / EBI]
2EYX; NMR; -; A=232-298.[ExPASy / RCSB / EBI]
2EYY; NMR; -; A=1-204.[ExPASy / RCSB / EBI]
2EYZ; NMR; -; A=1-304.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1JU5; -.
2DVJ; -.
2EYV; -.
2EYW; -.
2EYX; -.
2EYY; -.
2EYZ; -.
ModBase P46108.
Protein-protein interaction databases
DIP DIP:199N; -.
IntAct P46108; 123.
PTM databases
PhosphoSite P46108; -.
Enzyme and pathway databases
Pathway_Interaction_DB angiopoietinreceptor_pathway; Angiopoietin receptor Tie2-mediated signaling.
endothelinpathway; Endothelins.
epha_fwdpathway; EPHA forward signaling.
ephbfwdpathway; EPHB forward signaling.
igf1_pathway; IGF1 pathway.
insulin_pathway; Insulin Pathway.
tcrjnkpathway; JNK signaling in the CD4+ TCR pathway.
lysophospholipid_pathway; LPA receptor mediated events.
trkrpathway; Neurotrophic factor-mediated Trk receptor signaling.
a4b1_paxdep_pathway; Paxillin-dependent events mediated by a4b1.
a4b1_paxindep_pathway; Paxillin-independent events mediated by a4b1 and a4b7.
pdgfrapathway; PDGFR-alpha signaling pathway.
met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
ptp1bpathway; Signaling events mediated by PTP1B.
ret_pathway; Signaling events regulated by Ret tyrosine kinase.
lymphangiogenesis_pathway; VEGFR3 signaling in lymphatic endothelium.
Reactome REACT_11061; Signalling by NGF.
REACT_508; Signal attenuation.
2D gel databases
SWISS-2DPAGE P46108; -.
REPRODUCTION-2DPAGE IPI00399054; -.
Organism-specific databases
GeneCards GC17M001272; -.
HGNC HGNC:2362; CRK.
GenAtlas CRK.
HPA CAB010485; -.
MIM 164762; gene. [NCBI / EBI]
PharmGKB PA134991422; -.
Gene expression databases
ArrayExpress P46108; -.
Bgee P46108; -.
CleanEx HS_CRK; -.
GermOnline ENSG00000167193; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005768; Cellular component: endosome (inferred from experiment from Reactome).
GO:0005634; Cellular component: nucleus (traceable author statement from ProtInc).
GO:0005886; Cellular component: plasma membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0042169; Molecular function: SH2 domain binding (inferred from physical interaction from UniProtKB).
GO:0030036; Biological process: actin cytoskeleton organization (traceable author statement from ProtInc).
GO:0007242; Biological process: intracellular signaling cascade (inferred from experiment from Reactome).
GO:0006357; Biological process: regulation of transcription from RNA polymerase II promoter (traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR000980; SH2.
IPR011511; SH3_2.
IPR001452; SH3_domain.
Graphical view of domain structure.
Pfam PF00017; SH2; 1.
PF00018; SH3_1; 1.
PF07653; SH3_2; 1.
Pfam graphical view of domain structure.
PRINTS PR00401; SH2DOMAIN.
ProDom PD000093; SH2; 1.
PD000066; SH3; 2.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00252; SH2; 1.
SM00326; SH3; 2.
SMART graphical view of domain structure.
PROSITE PS50001; SH2; 1.
PS50002; SH3; 1.
PROSITE graphical view of domain structure (profiles).
Proteomic databases
PRIDE P46108; -.
Genome annotation databases
Ensembl ENSG00000167193; Homo sapiens. [Contig view]
GeneID 1398; -.
KEGG hsa:1398; -.
Phylogenomic databases
HOGENOM P46108; -.
HOVERGEN P46108; -.
OMA P46108; ILRPEEA.
Other
NextBio 5721; -.
SOURCE CRK; Homo sapiens.
ProtoNet P46108.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Cell membrane; Cytoplasm; Membrane; Phosphoprotein; Proto-oncogene; Repeat; SH2 domain; SH3 domain.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   304  304     Proto-oncogene C-crk. PRO_0000079351
DOMAIN   13   118  106     SH2. 
DOMAIN   132   192  61     SH3 1. 
DOMAIN   256   296  41     SH3 2. 
MOD_RES   41    41        Phosphoserine (By similarity). 
MOD_RES   42    42        Phosphothreonine (By similarity). 
MOD_RES   74    74        Phosphoserine. 
MOD_RES   83    83        Phosphoserine. 
MOD_RES   221   221        Phosphotyrosine. 
MOD_RES   239   239        Phosphotyrosine. 
VAR_SEQ   205   304        Missing (in isoform Crk-I). VSP_004173
MUTAGEN   150   150        D->K: Abolishes interaction with DOCK1. 
CONFLICT   109   109        L -> W (in Ref. 1; BAA01505 and 2; AAB28213). 
CONFLICT   215   215        G -> P (in Ref. 1; BAA01505 and 2; AAB28213). 
CONFLICT   278   278        E -> G (in Ref. 1; BAA01505 and 2; AAB28213). 
HELIX   20    27  8      
STRAND   34    39  6      
STRAND   41    43  3      
STRAND   46    52  7      
STRAND   57    63  7      
STRAND   66    69  4      
STRAND   87    89  3      
STRAND   92    96  5      
HELIX   97   106  10      
STRAND   109   112  4      
STRAND   116   118  3      
STRAND   121   123  3      
STRAND   165   168  4      
STRAND   171   173  3      
STRAND   187   189  3      
STRAND   224   227  4      
STRAND   229   231  3      
STRAND   239   242  4      
STRAND   253   255  3      
STRAND   260   269  10      
STRAND   273   279  7      
STRAND   282   287  6      
HELIX   288   290  3      
Sequence information
Length: 304 AA [This is the length of the unprocessed precursor] Molecular weight: 33831 Da [This is the MW of the unprocessed precursor] CRC64: 4CFBFB65BFC2E265 [This is a checksum on the sequence] 
        10         20         30         40         50         60 
MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS VSENSRVSHY 

        70         80         90        100        110        120 
IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL LEFYKIHYLD TTTLIEPVSR 

       130        140        150        160        170        180 
SRQGSGVILR QEEAEYVRAL FDFNGNDEED LPFKKGDILR IRDKPEEQWW NAEDSEGKRG 

       190        200        210        220        230        240 
MIPVPYVEKY RPASASVSAL IGGNQEGSHP QPLGGPEPGP YAQPSVNTPL PNLQNGPIYA 

       250        260        270        280        290        300 
RVIQKRVPNA YDKTALALEV GELVKVTKIN VSGQWEGECN GKRGHFPFTH VRLLDQQNPD 


EDFS
P46108 in FASTA format

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