Reviewed,
UniProtKB/Swiss-Prot P46108 (CRK_HUMAN)
Last modified
November 25, 2008.
Version 90.
History...
Clusters with 100%,
90%,
50% identity |
 Documents (5) |
 Third-party data |
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Names and origin
| Protein names | Recommended name: Proto-oncogene C-crk Alternative name(s): p38 Adapter molecule crk | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 304 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II 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. |
| Subunit structure | Interacts with ABL1, C3G, SOS, MAP4K1, MAPK8 and DOCK3 via its first SH3 domain. Interacts with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1 via its SH2 domain upon stimulus-induced tyrosine phosphorylation. Interacts with several tyrosine-phosphorylated growth factor receptors such as EGFR, PDGFR and INSR via its SH2 domain By similarity. Interacts with DOCK1 and DOCK4. Interacts with SHB. |
| Subcellular location | CytoplasmBy similarity. Cell membraneBy similarity. Note= Translocated to the plasma membrane upon cell adhesion By similarity. |
| 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 By similarity. The SH2 domain mediates interaction with SHB. |
| Post-translational modification | Phosphorylation of Crk-II (40 kDa) gives rise to a 42 kDa form. 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. |
| Sequence similarities | Contains 1 SH2 domain. Contains 2 SH3 domains. |
Ontologies
Keywords | |
|---|---|
| Cellular component | Cell membrane Cytoplasm Membrane |
| Coding sequence diversity | Alternative splicing |
| Disease | Proto-oncogene |
| Domain | Repeat SH2 domain SH3 domain |
| PTM | Phosphoprotein |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Biological process | actin cytoskeleton organization Traceable author statement. Source: ProtInc intracellular signaling cascadeInferred from Experiment. Source: Reactome regulation of transcription from RNA polymerase II promoterTraceable author statement. Source: ProtInc |
| Cellular component | cytosol Inferred from Experiment. Source: Reactome endosomeInferred from Experiment. Source: Reactome nucleusTraceable author statement. Source: ProtInc plasma membraneInferred from electronic annotation. Source: UniProtKB-KW |
| Molecular function | SH2 domain binding Inferred from physical interaction. Source: UniProtKB |
| Complete GO annotation... | |
Binary interactions
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform Crk-II (identifier: P46108-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform Crk-I (identifier: P46108-2) The sequence of this isoform differs from the canonical sequence as follows: 205-304: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 304 | 304 | Proto-oncogene C-crk | PRO_0000079351 | |||||||||||||||||||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Domain | 13 – 118 | 106 | SH2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Domain | 132 – 192 | 61 | SH3 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Domain | 256 – 296 | 41 | SH3 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 41 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 42 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 74 | 1 | Phosphoserine | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 83 | 1 | Phosphoserine | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 221 | 1 | Phosphotyrosine | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 239 | 1 | Phosphotyrosine | ||||||||||||||||||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 205 – 304 | 100 | Missing in isoform Crk-I. | VSP_004173 | |||||||||||||||||||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 150 | 1 | D → K: Abolishes interaction with DOCK1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 109 | 1 | L → W in BAA01505. Ref.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 109 | 1 | L → W in AAB28213. Ref.2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 215 | 1 | G → P in BAA01505. Ref.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 215 | 1 | G → P in AAB28213. Ref.2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 278 | 1 | E → G in BAA01505. Ref.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 278 | 1 | E → G in AAB28213. Ref.2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 20 – 27 | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 34 – 39 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 41 – 43 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 46 – 52 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 57 – 63 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 66 – 69 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 87 – 89 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 92 – 96 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 97 – 106 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 109 – 112 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 116 – 118 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 121 – 123 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 165 – 168 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 171 – 173 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 187 – 189 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 224 – 227 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 229 – 231 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 239 – 242 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 253 – 255 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 260 – 269 | 10 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 273 – 279 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 282 – 287 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 288 – 290 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "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. 12:3482-3489(1992) [PubMed: 1630456] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ALTERNATIVE SPLICING. Tissue: Embryonic lung and Placenta. |
| [2] | "CRK proto-oncogene maps to human chromosome band 17p13." Fioretos T., Heisterkamp N., Groffen J., Benjes S., Morris C. Oncogene 8:2853-2855(1993) [PubMed: 8378094] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "Cloning of human full-length CDSs in BD Creator(TM) system donor vector." 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. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye and Placenta. |
| [5] | "DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane." Hasegawa H., Kiyokawa E., Tanaka S., Nagashima K., Gotoh N., Shibuya M., Kurata T., Matsuda M. Mol. Cell. Biol. 16:1770-1776(1996) [PubMed: 8657152] [Abstract] Cited for: INTERACTION WITH DOCK1. |
| [6] | "Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins." Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T., Nagashima K., Kurata T. J. Biol. Chem. 271:14468-14472(1996) [PubMed: 8662907] [Abstract] Cited for: INTERACTION WITH DOCK1; C3G AND EPS15, MUTAGENESIS OF ASP-150. |
| [7] | "Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction." Koval A.P., Karas M., Zick Y., LeRoith D. J. Biol. Chem. 273:14780-14787(1998) [PubMed: 9614078] [Abstract] Cited for: INTERACTION WITH IRS4. |
| [8] | "NGF-dependent neurite outgrowth in PC12 cells overexpressing the Src homology 2-domain protein shb requires activation of the Rap1 pathway." Lu L., Anneren C., Reedquist K.A., Bos J.L., Welsh M. Exp. Cell Res. 259:370-377(2000) [PubMed: 10964504] [Abstract] Cited for: INTERACTION WITH SHB. |
| [9] | "DOCK4, a GTPase activator, is disrupted during tumorigenesis." 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. Cell 112:673-684(2003) [PubMed: 12628187] [Abstract] Cited for: INTERACTION WITH DOCK4. |
| [10] | "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." 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. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-239, MASS SPECTROMETRY. |
| [11] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-221, MASS SPECTROMETRY. Tissue: Epithelium. |
| [12] | "A quantitative atlas of mitotic phosphorylation." Dephoure N. |