| General information | | DisProt: | DP00748_A002 | | Name: | Adapter molecule crk [Isoform 2] | | Synonym(s): | CRK_HUMAN
CrkI or CRKI
Proto-oncogene c-Crk
p38
| | First appeared in release: | Release 6.02 (05/24/2013) | | UniProt: | P46108 | | UniGene: | Hs.461896 | | SwissProt: | CRK_HUMAN | | TrEMBL: | | | NCBI (GI): | | | Source organism: | Homo sapiens (Human) | | Sequence length: | 204 | | Percent disordered: | 100% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
| | | | | |
MAGNFDSEER SSWYWGRLSR QEAVALLQGQ RHGVFLVRDS STSPGDYVLS VSENSRVSHY - 60
IINSSGPRPP VPPSPAQPPP GVSPSRLRIG DQEFDSLPAL LEFYKIHYLD TTTLIEPVSR - 120
SRQGSGVILR QEEAEYVRAL FDFNGNDEED LPFKKGDILR IRDKPEEQWW NAEDSEGKRG - 180
MIPVPYVEKY RPASASVSAL IGGR
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| Functional narrative |
Adapter molecule crk is a proto-oncogene existing in two isoforms, Crk-II and Crk-I. Crk-II is the UniProt canonical sequence [DP00748], comprising aa 1-304. Crk-I is UniProt alternatively-spliced product 2 [DP00748_A002], comprising aa 1-204 of canonical sequence and including a variation at N204R.
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"CRK regulates transcription and cytoskeletal reorganization during cell growth, motility, proliferation, adhesion, differentiation and apoptosis by acting as an adaptor to link tyrosine kinases and small G proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK." (Kobashigawa et al, 2007, and references therein)
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From UniProt: 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. May regulate the EFNA5-EPHA3 signaling.
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|
| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | N-terminal | | Location: | 1 - 9 | | Length: | 9 | | Region sequence: |
MAGNFDSEE | | Modification type: | Native
| | PDB: | 2EYY:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Modification site
| | Functional subclasses: | Acetylation
| Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.8; Crk-I 1 mM; EDTA 1 mM; DTT 2 mM; NaCl 150 mM; 90% H2O/10% D2O; Phosphate buffer 20 mM)
- Small-angle X-ray scattering (SAXS) (298 K; pH: 8; Crk-I 20 mg/mL; NaCl 150 mM; Tris-HCl buffer 20 mM)
| References:
- 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.. 2007; 14(6): 503-10. PubMed: 17515907
| Comments:
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| Region 2 | | Type: | Disordered - Extended | | Name: | SH2 domain | | Location: | 10 - 120 | | Length: | 111 | | Region sequence: |
RSSWYWGRLSRQEAVALLQGQRHGVFLVRDSSTSPGDYVLSVSENSRVSHYIINSSGPRP
PVPPSPAQPPPGVSPSRLRIGDQEFDSLPALLEFYKIHYLDTTTLIEPVSR | | Modification type: | Native
| | PDB: | 2EYY:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Modification site
Molecular recognition effectors
| | Functional subclasses: | Phosphorylation
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.8; 90% H2O/10% D2O; Crk-I 1 mM; DTT 2 mM; EDTA 1 mM; NaCl 150 mM; Phosphate buffer 20 mM)
- Small-angle X-ray scattering (SAXS) (298 K; pH: 8; Crk-I 20 mg/mL; NaCl 150 mM; Tris-HCl buffer 20 mM)
| References:
- 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.. 2007; 14(6): 503-10. PubMed: 17515907
| Comments:
|
| Region 3 | | Type: | Disordered | | Name: | linker | | Location: | 121 - 133 | | Length: | 13 | | Region sequence: |
SRQGSGVILRQEE | | Modification type: | Native
| | PDB: | 2EYY:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Entropic chain
| | Functional subclasses: | Flexible linkers/spacers
| Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.8; 90% H2O/10% D2O; Crk-I 1 mM; DTT 2 mM; EDTA 1 mM; NaCl 150 mM; Phosphate buffer 20 mM)
- Small-angle X-ray scattering (SAXS) (298 K; pH: 8; Crk-I 20 mg/mL; NaCl 150 mM; Tris-HCl buffer 20 mM)
| References:
- 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.. 2007; 14(6): 503-10. PubMed: 17515907
| Comments:
|
| Region 4 | | Type: | Disordered - Extended | | Name: | SH3 domain | | Location: | 134 - 191 | | Length: | 58 | | Region sequence: |
AEYVRALFDFNGNDEEDLPFKKGDILRIRDKPEEQWWNAEDSEGKRGMIPVPYVEKYR | | Modification type: | Native
| | PDB: | 2EYY:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Modification site
Molecular recognition effectors
| | Functional subclasses: | Phosphorylation
Protein-protein binding
| Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.8; 90% H2O/10% D2O; Crk-I 1 mM; DTT 2 mM; EDTA 1 mM; NaCl 150 mM; Phosphate buffer 20 mM)
- Small-angle X-ray scattering (SAXS) (298 K; pH: 8; Crk-I 20 mg/mL; NaCl 150 mM; Tris-HCl buffer 20 mM)
| References:
- 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.. 2007; 14(6): 503-10. PubMed: 17515907
| Comments:Kobashigawa et al (2007) also refer to this segment as "nSH3" when comparing Crk-I with Crk-II. Crk-II contains two SH3 domains labelled nSH3 and cSH3. The Crk-I SH3 domain and Crk-II nSH3 domains are the same domain.
|
| Region 5 | | Type: | Disordered | | Name: | C-terminal | | Location: | 192 - 204 | | Length: | 13 | | Region sequence: |
PASASVSALIGGR | | Modification type: | Native
| | PDB: | 2EYY:A | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- Nuclear magnetic resonance (NMR) (298 K; pH: 6.8; 90% H2O/10% D2O; Crk-I 1 mM; DTT 2 mM; EDTA 1 mM; NaCl 150 mM; Phosphate buffer 20 mM)
- Small-angle X-ray scattering (SAXS) (298 K; pH: 8; Crk-I 20 mg/mL; NaCl 150 mM; Tris-HCl buffer 20 mM)
| References:
- 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.. 2007; 14(6): 503-10. PubMed: 17515907
| Comments:
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| Comments |
According to Kobashigawa et al (2007), Crk-I is "an extended structure in which both SH2 and nSH3 are freely accessible for interactions with target proteins." They further describe that, by contrast, Crk-II (the long isoform; DP00748) folds into a compact, stable structure. Crk-II adds a long linker containing a hydrophobic core and a second SH3 domain at the C-terminal. The compact structure of Crk-II is produced by intramolecular interactions of the additional segments.
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