Crk-like protein (CRKL)
The protein contains 303 amino acids for an estimated molecular weight of 33777 Da.
May mediate the transduction of intracellular signals. (updated: March 4, 2015)
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.
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Biological Process
Acetylcholine receptor signaling pathway
Activation of GTPase activity
Activation of MAPK activity
Activation of MAPKK activity
Animal organ morphogenesis
Anterior/posterior pattern specification
B cell apoptotic process
Blood vessel development
Cell chemotaxis
Cellular response to drug
Cellular response to interleukin-7
Cellular response to transforming growth factor beta stimulus
Cerebellar neuron development
Cerebral cortex development
Cranial skeletal system development
Cytokine-mediated signaling pathway
Dendrite development
Endothelin receptor signaling pathway
Establishment of cell polarity
Fibroblast growth factor receptor signaling pathway
Heart development
Helper T cell diapedesis
Hippocampus development
Intracellular signal transduction
JNK cascade
Lipid metabolic process
Male gonad development
Negative regulation of gene expression
Negative regulation of protein phosphorylation
Neuron migration
Neurotrophin TRK receptor signaling pathway
Outflow tract morphogenesis
Parathyroid gland development
Pharynx development
Positive regulation of cell population proliferation
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of glial cell migration
Positive regulation of protein phosphorylation
Positive regulation of Ras protein signal transduction
Positive regulation of substrate adhesion-dependent cell spreading
Ras protein signal transduction
Reelin-mediated signaling pathway
Regulation of cell adhesion mediated by integrin
Regulation of cell growth
Regulation of dendrite development
Regulation of skeletal muscle acetylcholine-gated channel clustering
Regulation of T cell migration
Retinoic acid receptor signaling pathway
Single fertilization
Spermatogenesis
Synapse assembly
T cell receptor signaling pathway
Thymus development
Urogenital system development
The reference OMIM entry for this protein is 602007
V-crk avian sarcoma virus ct10 oncogene homolog-like; crkl
Oncogene crkl
CLONING
CRK (164762) was originally identified as an oncogene transduced by the avian sarcoma virus CT10. Ten Hoeve et al. (1993) identified and characterized a gene, which they called CRKL for CRK-like, from a human K562 lambda gt10 cDNA library. CRKL encodes a 303-amino acid polypeptide with a predicted molecular mass of 36 kD. While CRKL is not the human homolog of CRK, it is similar to protein-tyrosine kinases with SH2 and SH3 (src homology) domains.GENE FUNCTION
Senechal et al. (1996) showed that CRKL becomes phosphorylated when overexpressed, activates Ras-dependent and JNK (601158) pathways, and transforms fibroblasts. The authors also found CRKL to be a substrate for the BCR-ABL tyrosine kinase (ABL; 189980), leading them to conclude that CRKL is a tyrosine kinase and an oncogene. Sasahara et al. (2002) showed that the adaptor protein CRKL binds directly to WIP (602357) and that, following T-cell receptor ligation, a CRKL-WIP-WASP (300392) complex is recruited by ZAP70 (176947) to lipid rafts and immunologic synapses. Since Fgf8 (600483) deletion in mice, like Crkl deletion, results in many of the phenotypic features of DiGeorge syndrome (DGS; 188400)/velocardiofacial syndrome (VCFS; 192430), Moon et al. (2006) investigated whether Crkl mediates Fgf8 signaling. In addition to finding interactions between Crkl and Fgf8 during the development of structures affected in DGS/VCFS, Moon et al. (2006) found that Fgf8 induced tyrosine phosphorylation of Fgfr1 (136350) and Fgfr2 (176943) and their binding to Crkl. Crkl was required for normal cellular responses to Fgf8, including survival and migration, Erk (see MAPK3; 601795) activation, and target gene expression. Hallock et al. (2010) found that Crk and Crkl 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.MAPPING
By fluorescence in situ hybridization, ten Hoeve et al. (1993) localized the CRKL gene to chromosome 22q11, centromeric of the chronic myelogenous leukemia breakpoint region.ANIMAL MODEL
Since the CRKL gene maps within the common deletion region for DGS/VCFS, Guris et al. (2001) created mice homozygous for a targeted null mutation at the Crkl locus (symbolized Crkol in mice) and found that they exhibited defects in multiple cranial and cardiac neural crest derivatives including the cranial ganglia, aortic arch arteries, cardiac outflow tract, thymus, parathyroid glands, and craniofacial structures. They showed that the migration and early expansion of neural crest cells was unaffected in Crkol -/- embryos. These results therefore indicated an essential stage- and tissue-specific role for Crkol in the function, differentiation, and/or survival of neural crest cells during development. The similarity between the Crkol -/- phenotype and the clinical manifestations of DGS/VCFS implicated defects in CRKL-mediated signaling pathways as part of the molecular mechanism underlying this syndrome. Guris et al. (2006) found that compound heterozygosity for null alleles of the mouse Crkl and Tbx1 (602054) genes recapitulated thymic, parathyroid, and cardiovascular defects characteristic of DGS at a penetrance far greater than that generated by heterozygosity of Crkl or Tbx1 alon ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602007 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed