Cytotoxic and regulatory T-cell molecule (CRTAM)
The protein contains 393 amino acids for an estimated molecular weight of 44641 Da.
Mediates heterophilic cell-cell adhesion which regulates the activation, differentiation and tissue retention of various T-cell subsets (By similarity). Interaction with CADM1 promotes natural killer (NK) cell cytotoxicity and IFNG/interferon-gamma secretion by CD8+ T-cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM1 in vivo (PubMed:15811952). Regulates CD8+ T-cell proliferation in response to T-cell receptor (TCR) activation (By similarity). Appears to be dispensable for CD8+ T-cell-mediated cytotoxicity (By similarity). Interaction with SCRIB promotes the late phase of cellular polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG, IL17 and IL22 production (By similarity). By interacting with CADM1 on CD8+ dendritic cells, regulates the retention of activated CD8+ T-cells within the draining lymph node (By similarity). Required for the intestinal retention of intraepithelial CD4+ CD8+ T-cells and, to a lesser extent, intraepithelial and lamina propria CD8+ T-cells and CD4+ T-cells (By similarity). Interaction with CADM1 promotes the adhesion to gut-associated CD103+ dendritic cells, which may facilitate the expression of gut-homing and adhesion molecules on T-cells and the conversion of CD4+ T-cells into CD4+ CD8+ T-cells (By similarity). (updated: April 22, 2020)
Protein identification was indicated in the following studies:
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, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs35411582 | |
| dbSNP:rs34397316 | |
| dbSNP:rs35136295 | |
| dbSNP:rs2272094 | |
| dbSNP:rs1916036 |
No binding partner found
Biological Process
Adaptive immune response
Cell recognition
Detection of stimulus
Detection of tumor cell
Establishment of T cell polarity
Heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
Homophilic cell adhesion via plasma membrane adhesion molecules
Lymphocyte migration into lymphoid organs
Negative regulation of activated T cell proliferation
Positive regulation of cytokine production
Positive regulation of cytokine secretion
Positive regulation of interferon-gamma production
Positive regulation of natural killer cell mediated cytotoxicity
Positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target
Regulation of CD8-positive, alpha-beta T cell activation
Regulation of immune response
Regulation of T cell activation
Regulation of T cell differentiation
The reference OMIM entry for this protein is 612597
Cytotoxic and regulatory t-cell molecule; crtam
Class i major histocompatibility complex-restricted t-cell-associated molecule
DESCRIPTION
The CRTAM gene is upregulated in CD4 (see 186940)-positive and CD8 (see CD8A; 186910)-positive T cells and encodes a type I transmembrane protein with V and C1-like Ig domains (Yeh et al., 2008).CLONING
By screening a CD8-positive T-cell cDNA library with mouse Crtam, Kennedy et al. (2000) cloned human CRTAM. The deduced 393-amino acid human protein shares 72% amino acid identity with mouse Crtam. It contains a 17-amino acid leader sequence, followed by a 269-amino acid extracellular region, a 25-amino acid transmembrane domain, and an 82-amino acid cytoplasmic domain. The extracellular region has 5 potential N-glycosylation sites and 5 conserved cysteines, 4 of which appear to form 2 Ig-like domains. The cytoplasmic region has 3 conserved phosphorylation sites. Northern blot analysis detected high expression of 2.5- and 1.8-kb CRTAM transcripts in activated human CD8-positive cells, with lower levels in unactivated CD8-positive cells and CD4-positive cells. Among human tissues, CRTAM was abundantly expressed in spleen, thymus, small intestine, and peripheral blood leukocytes, with lower levels in testis, ovary, and colon.GENE FUNCTION
Using antibody phage display to identify cell-surface epitopes expressed on human BDCA3-positive dendritic cells (DCs), Galibert et al. (2005) identified a fragment that bound NECL2 (IGSF4; 605686) on both human BDCA3-positive DCs and mouse Cd8a-positive DCs. In turn, they found that NECL2 bound CRTAM, a receptor primarily expressed on activated cytotoxic lymphocytes.MAPPING
By analysis of genomic DNA from mouse/human hybrid cell lines, Kennedy et al. (2000) mapped the CRTAM gene to chromosome 11q22-q23. They mapped the mouse gene to a region of chromosome 9 that shows homology of synteny to human chromosome 11q22-q23.ANIMAL MODEL
Using flow cytometry, Yeh et al. (2008) found that Crtam was transiently upregulated in mouse Cd4-positive T cells following activation. Yeh et al. (2008) generated Crtam -/- mice, which were born at the expected mendelian ratio and showed no thymic developmental defects. Crtam -/- T cells had reduced production of Ifng (147570), Il22 (605330), and Il17 (see 603149), but increased T-cell receptor-mediated proliferation. Crtam -/- mice exhibited compromised resistance to Citrobacter rodentium infection. Crtam -/- T cells were unable to assemble a Scrib (607733)-containing complex to control T-cell polarity. The Crtam-Scrib interaction, which was mediated by the Crtam extracellular domain, was required for Ifng and Il22 production. Yeh et al. (2008) concluded that CRTAM organizes a molecular scaffold through SCRIB to regulate a later phase of T-cell activation. Takeuchi et al. (2009) generated Crtam -/- mice and observed that they had reduced protective immunity against influenza virus infection and impaired autoimmune diabetes induction. Mice lacking Crtam had normal in vitro CD8-positive cytotoxic lymphocyte function, but cytotoxic lymphocyte numbers were reduced in draining lymph nodes. Immunohistologic analysis revealed wide Necl2 expression in the T-cell area of lymph nodes, particularly on CD11c-positive (ITGAX; 151510)/CD8-positive dendritic cells. Cell adhesion assays demonstrated that T-cell-dendritic cell conjugate formation is Crtam-dependent and does not require dendritic cell activation or antigen presentation. Takeuchi et al. (2009) concluded that CRTAM is critically involved in in vivo cytotoxic ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 612597 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).