Descriptions
CRK regulates transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 and nSH3 domains are used to recruit their target proteins. The interaction between SH2 and inter-domain linker between nSH3 and cSH3 detaches the SH2-targeting proteins. In mouse CRK mutant experiments, it was discovered that cSH3 negatively regulates the function of nSH3.
Autoinhibitory domains (AIDs)
Target domain |
125-185 (N-terminal SH3 domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Kobashigawa Y et al. (2007) "Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK", Nature structural & molecular biology, 14, 503-10
- Ogawa S et al. (1994) "The C-terminal SH3 domain of the mouse c-Crk protein negatively regulates tyrosine-phosphorylation of Crk associated p130 in rat 3Y1 cells", Oncogene, 9, 1669-78
- Sriram G et al. (2012) "Commentary: The carboxyl-terminal Crk SH3 domain: Regulatory strategies and new perspectives", FEBS letters, 586, 2615-8
Autoinhibited structure
Activated structure
4 structures for Q04929
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 2L3P | NMR | - | A | 220-297 | PDB |
| 2L3Q | NMR | - | A | 220-297 | PDB |
| 2L3S | NMR | - | A | 135-297 | PDB |
| AF-Q04929-F1 | Predicted | AlphaFoldDB |
5 variants for Q04929
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs741480070 | 210 | H>P | No | Ensembl | |
| rs734736643 | 214 | L>R | No | Ensembl | |
| rs738605604 | 231 | L>P | No | Ensembl | |
| rs740791728 | 233 | N>T | No | Ensembl | |
| rs740062743 | 276 | W>G | No | Ensembl |
No associated diseases with Q04929
4 regional properties for Q04929
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | SH2 domain | 11 - 119 | IPR000980 |
| domain | SH3 domain | 133 - 193 | IPR001452-1 |
| domain | SH3 domain | 236 - 297 | IPR001452-2 |
| domain | CRK, C-terminal SH3 domain | 238 - 294 | IPR035458 |
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| protein-containing complex | A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. |
7 GO annotations of molecular function
| Name | Definition |
|---|---|
| ephrin receptor binding | Binding to an ephrin receptor. |
| phosphotyrosine residue binding | Binding to a phosphorylated tyrosine residue within a protein. |
| protein self-association | Binding to a domain within the same polypeptide. |
| receptor tyrosine kinase binding | Binding to a receptor that possesses protein tyrosine kinase activity. |
| SH2 domain binding | Binding to a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class. |
| SH3 domain binding | Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins. |
| signaling adaptor activity | The binding activity of a molecule that brings together two or more molecules in a signaling pathway, permitting those molecules to function in a coordinated way. Adaptor molecules themselves do not have catalytic activity. |
12 GO annotations of biological process
| Name | Definition |
|---|---|
| actin cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins. |
| cell migration | The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms. |
| ephrin receptor signaling pathway | The series of molecular signals initiated by ephrin binding to its receptor, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| negative regulation of cell motility | Any process that stops, prevents, or reduces the frequency, rate or extent of cell motility. |
| negative regulation of wound healing | Any process that decreases the rate, frequency, or extent of the series of events that restore integrity to a damaged tissue, following an injury. |
| positive regulation of substrate adhesion-dependent cell spreading | Any process that activates or increases the frequency, rate or extent of substrate adhesion-dependent cell spreading. |
| regulation of actin cytoskeleton organization | Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins. |
| regulation of cell shape | Any process that modulates the surface configuration of a cell. |
| regulation of GTPase activity | Any process that modulates the rate of GTP hydrolysis by a GTPase. |
| regulation of intracellular signal transduction | Any process that modulates the frequency, rate or extent of intracellular signal transduction. |
| regulation of protein binding | Any process that modulates the frequency, rate or extent of protein binding. |
| signal transduction | The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell. |
8 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q9XYM0 | Crk | Adapter molecule Crk | Drosophila melanogaster (Fruit fly) | SS |
| P46109 | CRKL | Crk-like protein | Homo sapiens (Human) | SS |
| P46108 | CRK | Adapter molecule crk | Homo sapiens (Human) | EV |
| P47941 | Crkl | Crk-like protein | Mus musculus (Mouse) | SS |
| Q64010 | Crk | Adapter molecule crk | Mus musculus (Mouse) | EV SS |
| Q5U2U2 | Crkl | Crk-like protein | Rattus norvegicus (Rat) | SS |
| Q63768 | Crk | Adapter molecule crk | Rattus norvegicus (Rat) | SS |
| Q9NHC3 | ced-2 | Cell death abnormality protein 2 | Caenorhabditis elegans | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MAGQFDSEDR | GSWYWGRLSR | GDAVSLLQGQ | RHGTFLVRDS | GSIPGDFVLS | VSESSRVSHY |
| 70 | 80 | 90 | 100 | 110 | 120 |
| IVNSLGPAGG | RRAGGEGPGA | PGLNPTRFRI | GDQEFDSLPS | LLEFYKIHYL | DTTTLIEPVS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| RSRQNSGVIL | RQEEVEYVRA | LFDFNGNDDE | DLPFKKGDIL | KIRDKPEEQW | WNAEDMDGKR |
| 190 | 200 | 210 | 220 | 230 | 240 |
| GMIPVPYVEK | CRPSSASVST | LTGGNQDSSH | PQPLGGPEPG | PYAQPSINTP | LPNLQNGPFY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| ARVIQKRVPN | AYDKTALALE | VGELVKVTKI | NMSGQWEGEC | NGKRGHFPFT | HVRLLDQQNP |
| DEDFS |