CD2-associated protein (CD2AP)
The protein contains 639 amino acids for an estimated molecular weight of 71451 Da.
Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton (PubMed:10339567). In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation (By similarity). May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell (By similarity). May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis (PubMed:15800069). Plays a role in epithelial cell junctions formation (PubMed:22891260). (updated: Nov. 22, 2017)
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.
- 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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
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| Variant | Description |
|---|---|
| dbSNP:rs34069459 |
Biological Process
Actin filament organization
Cell cycle
Cell division
Cell-cell adhesion
Mitotic nuclear division
Negative regulation of small GTPase mediated signal transduction
Negative regulation of transforming growth factor beta1 production
Positive regulation of protein localization to nucleus
Positive regulation of protein secretion
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein complex assembly
Protein-containing complex assembly
Regulation of actin cytoskeleton reorganization
Regulation of receptor-mediated endocytosis
Signal transduction
Substrate-dependent cell migration, cell extension
Vesicle organization
The reference OMIM entry for this protein is 604241
Cd2-associated protein; cd2ap
Cas ligand with multiple sh3 domains; cms
CLONING
P130(Cas) (602941) is a docking protein that is tyrosine-phosphorylated in response to a variety of extracellular stimuli, such as growth factors, cell-cell interaction, and cell-matrix interaction, and appears to play a critical role in the integrin-linked formation of focal complexes. To understand the growth regulatory pathway of p130(Cas), Kirsch et al. (1999) used the yeast 2-hybrid system to search for interacting molecules. They identified a human protein, which they called CMS for p130(Cas) ligand with multiple SH3 domains, as a direct binding protein of p130(Cas). CMS is a multifunctional adapter-type molecule, which is localized in the cytoplasm, membrane ruffles, and leading edges of cells. Its structure and colocalization with F-actin (see 102610) and p130(Cas) suggested a function as a scaffolding protein involved in the dynamic regulation of the actin cytoskeleton. The cDNA corresponding to CMS encodes a protein of 639 amino acids with a deduced molecular mass of approximately 70 kD. Amino acid analysis revealed that CMS contains in its N terminus 3 SH3 domains followed by a proline-rich region containing binding sites for SH3 domains. Putative actin-binding sites and a coiled-coil domain are located at the C terminus of the protein, which also contains a putative leucine zipper motif. CMS mRNA is ubiquitously expressed in adult and fetal human tissues as an approximately 5.4-kb transcript, as detected by Northern blot analysis. Dustin et al. (1998) cloned the mouse homolog of CMS, which they called CD2AP, that binds the cytoplasmic tail of the adhesion molecule CD2 (186990). Kirsch et al. (1999) stated that the mouse CD2AP protein is 86% identical to human CMS.GENE FUNCTION
Kirsch et al. (1999) demonstrated that CMS induces vesicle formation and colocalizes with p130(Cas) and F-actin to membrane ruffles. It also associates with and is phosphorylated by tyrosine kinases. CMS is able to homodimerize through the coiled-coil domain located in its C terminus. There was no evidence for intermolecular or intramolecular binding via the SH3 domains and PXXP binding. Dustin et al. (1998) demonstrated that ligand engagement of the adhesion molecule CD2 initiates the process of protein segregation, CD2 clustering, and cytoskeletal polarization. Although protein segregation was not dependent on the cytoplasmic domain of CD2, CD2 clustering and cytoskeletal polarization required an interaction with the CD2 cytoplasmic domain with a novel SH3-containing protein.MOLECULAR GENETICS
Kim et al. (2003) found the same mutation (604241.0001) in the CD2AP gene in 2 African Americans with primary focal segmental glomerulosclerosis (FSGS3; 607832). The mutation affects the splice acceptor of exon 7 on one allele, replacing 2 nucleotides, GC, with CT. No stable truncated protein was produced from the alternatively spliced transcript. Kim et al. (2003) suggested that haploinsufficiency for CD2AP is a determinant of human susceptibility to glomerular disease. In a boy with severe early-onset nephrotic syndrome associated with focal segmental glomerulosclerosis, Lowik et al. (2007) identified a homozygous mutation in the CD2AP gene (R612X; 604241.0002). There was no expression of the mutant protein in patient lymphocytes, consistent with a complete loss of function. Each unaffected parent was heterozygous for the mutation, indicating that heterozygosity for this mutation does not result in renal disease.
Feb. 10, 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 604241 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed