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Description

CKLF-like MARVEL transmembrane domain-containing protein 6 (UniProt: Q9NX76, also known as Chemokine-like factor superfamily member 6, CMTM6) is encoded by the CMTM6 gene (Gene ID: 54918) in human. CMTM6 is a ubiquitously expressed, multi-pass membrane protein of the family of MARVEL domain-containing proteins with 3 cytoplasmic domains, 4 transmembrane domains, and 2 extracellular domains. Its MARVEL domain is localized in amino acids 33-160. It serves as a master regulator of recycling and plasma membrane expression of PD-L1. It binds to PD-L1 and maintains its cell surface expression. Although it is not required for PD-L1 maturation, but it co-localizes with PD-L1 at the plasma membrane and in recycling endosomes, where it prevents PD-L1 from being targeted for lysosome-mediated degradation by preventing its STUB-1 mediated ubiquitination. It also stabilizes PD-L1 expression on antigen presenting cells and potentiates inhibitory signaling by PD-1 (CD279), ultimately triggering T-cell anergy. It enhances the ability of PD-L1-expressing tumor cells to inhibit T cell activity. (Ref.: Burr, ML., et al. (2017). Nature. 549(7670), 101-105, Mezzadra, R., et al. (2017). Nature. 549(7670), 106-110).