Adapter molecule crk (CRK)
The protein contains 304 amino acids for an estimated molecular weight of 33831 Da.
Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1.', 'Regulates cell adhesion, spreading and migration (PubMed:31311869). 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 (PubMed:19004829). May regulate the EFNA5-EPHA3 signaling (By similarity). (updated: April 22, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Actin cytoskeleton organization
Activation of GTPase activity
Activation of MAPKK activity
Blood coagulation
Cell chemotaxis
Cellular response to endothelin
Cellular response to insulin-like growth factor stimulus
Cellular response to nerve growth factor stimulus
Cellular response to nitric oxide
Cellular response to transforming growth factor beta stimulus
Cerebellar neuron development
Cerebral cortex development
Cytokine-mediated signaling pathway
Dendrite development
Ephrin receptor signaling pathway
Establishment of cell polarity
Fc-gamma receptor signaling pathway involved in phagocytosis
Helper T cell diapedesis
Hippocampus development
Innate immune response
Insulin receptor signaling pathway
Lipid metabolic process
Negative regulation of cell motility
Negative regulation of natural killer cell mediated cytotoxicity
Negative regulation of wound healing
Neuron migration
Neurotrophin TRK receptor signaling pathway
Platelet activation
Positive regulation of cell growth
Positive regulation of smooth muscle cell migration
Positive regulation of substrate adhesion-dependent cell spreading
Reelin-mediated signaling pathway
Regulation of actin cytoskeleton organization
Regulation of cell adhesion mediated by integrin
Regulation of cell shape
Regulation of dendrite development
Regulation of GTPase activity
Regulation of intracellular signal transduction
Regulation of protein binding
Regulation of Rac protein signal transduction
Regulation of signal transduction
Regulation of T cell migration
Regulation of transcription by RNA polymerase II
Response to cholecystokinin
Response to hepatocyte growth factor
Response to hydrogen peroxide
Response to yeast
SH2 domain-mediated complex assembly
Vascular endothelial growth factor receptor signaling pathway
Cellular Component
Actin cytoskeleton
Cytoplasm
Cytosol
Extracellular exosome
Membrane
Membrane raft
Nucleus
Plasma membrane
Protein complex
Protein-containing complex
Molecular Function
Cytoskeletal protein binding
Ephrin receptor binding
Insulin-like growth factor receptor binding
Kinase binding
Obsolete SH3/SH2 adaptor activity
Phosphotyrosine residue binding
Protein phosphorylated amino acid binding
Protein self-association
Protein tyrosine kinase binding
Scaffold protein binding
SH2 domain binding
SH3 domain binding
Signaling adaptor activity
Signaling receptor complex adaptor activity
Ubiquitin protein ligase binding
The reference OMIM entry for this protein is 164762
V-crk avian sarcoma virus ct10 oncogene homolog; crk
Oncogene crk
Crkii
CLONING
The CRK oncogene was originally identified as a transforming component of the avian sarcoma virus CT10. A cDNA encoding the chicken cellular homolog of v-crk was isolated by Reichman et al. (1992) and shown to consist primarily of the SRC (190090) homology domains SH2 and SH3. Matsuda et al. (1992) isolated 2 distinct human CRK cDNA species and showed that the deduced amino acid sequences of the corresponding polypeptides differed in their C termini. The 2 cDNA species were considered to derive from the same genomic locus by alternative splicing.MAPPING
Fioretos et al. (1993) used fluorescence in situ hybridization to map the CRK gene to chromosome 17p13. Deletion of this region of chromosome 17 is one of the most frequent chromosomal abnormalities in human cancer. The TP53 gene (191170) maps to 17p13.1; Fioretos et al. (1993) mapped the CRK oncogene to 17p13.3, which is a second region on 17p that has been shown to manifest frequent loss of heterozygosity (LOH) in a number of different tumor types. Thus, the region is presumed to harbor a tumor suppressor gene.GENE FUNCTION
Feller et al. (1994) described the SRC homology domains SH2 and SH3 as molecular adhesives on many proteins involved in signal transduction. They reviewed the interactions of ABL (189980) and CRK as a model of SH2 and SH3 interaction. Hallock et al. (2010) found that Crk and Crkl (602007) were recruited to mouse skeletal muscle synapses and played redundant roles in synaptic differentiation. Crk and Crkl bound the same tyrosine-phosphorylated sequences in Dok7 (610285), a protein that functions downstream of agrin (AGRN; 103320) and muscle-specific receptor kinase (MUSK; 601296) in synapse formation.MOLECULAR GENETICS
Cardoso et al. (2003) completed a physical and transcriptional map of the 17p13.3 region from LIS1 to the telomere. Using Cardoso et al. (2003), they mapped the deletion size in 19 children with ILS (607432), 11 children with Miller-Dieker syndrome (MDS; 164762), and 4 children with 17p13.3 deletions not involving LIS1. They showed that the critical region that differentiates ILS from MDS at the molecular level can be reduced to 400 kb. Using somatic cell hybrids from selected patients, the authors identified 8 genes that are consistently deleted in patients classified as having MDS. These genes include ABR (600365), 14-3-3-epsilon (605066), CRK, MYO1C (606538), SKIP (603055), PITPNA (600174), SCARF1, RILP, PRP8 (607300), and SERPINF1 (172860). In addition, deletion of the genes CRK and 14-3-3-epsilon delineates patients with the most severe lissencephaly grade. On the basis of recent functional data and the creation of a mouse model suggesting a role for 14-3-3-epsilon in cortical development, Cardoso et al. (2003) suggested that deletion of 1 or both of these genes in combination with deletion of LIS1 may contribute to the more severe form of lissencephaly seen only in patients with MDS.ANIMAL MODEL
Hallock et al. (2010) found that knockout of both Crk and Crkl in mouse skeletal muscle, but not of either gene alone, caused perinatal lethality. Lungs from Crk- and Crkl-deficient newborns failed to expand. Embryonic day-18.5 muscle from Crk- and Crkl-deficient mice lacked innervation and showed severe defects in presynaptic and postsynaptic differentiation. ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 164762 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed