Recombinant Human Cytotoxic and regulatory T-cell molecule (CRTAM), partial (Active)

Function

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)

Subcellular Location

Cell membrane (Single-pass type I membrane protein)

Tissue Specificity

In the immune system, expression is restricted to activated class-I MHC-restricted cells, including NKT and CD8 T-cells (PubMed:10811014, PubMed:15811952, PubMed:16300832). Strongly expressed in spleen, thymus, small intestine, peripheral blood leukocyte, and in Purkinje neurons in cerebellum. Expressed at much lower levels in testis, ovary, colon, lung and lymphoid tissues (PubMed:16300832)

Subunit

Monomer (PubMed:23583034). May form homodimer (via Ig-like V-type domain) (PubMed:23583034, PubMed:23871486). Interacts (via Ig-like V-type domain) with CADM1 (via Ig-like V-type domain); the interaction competes with CRTAM homodimerization and CADM1 homodimerization (PubMed:15781451, PubMed:15811952, PubMed:23871486). Interacts (via PDZ-binding motif) with SCRIB (via PDZ domain 3); the interaction promotes CRTAM and SCRIB polarization in a subset of CD4+ T-cells (By similarity)

• Kennedy J. et al. A molecular analysis of NKT cells: identification of a class-I restricted T cell-associated molecule (CRTAM). — J. Leukoc. Biol. (2000)
• Totoki Y. et al. PubMed: CI-6FM9UGIHPC7GG (MAR-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Boles K.S. et al. The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM. — Blood (2005)
• Galibert L. et al. Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule. — J. Biol. Chem. (2005)
• Patino-Lopez G. et al. Human class-I restricted T cell associated molecule is highly expressed in the cerebellum and is a marker for activated NKT and CD8+ T lymphocytes. — J. Neuroimmunol. (2006)
• Rubinstein R. et al. Functional classification of immune regulatory proteins. — Structure (2013)
• Zhang S. et al. Competition of cell adhesion and immune recognition: insights into the interaction between CRTAM and nectin-like 2. — Structure (2013)