CKLF-like MARVEL transmembrane domain-containing family explained

The CKLF-like MARVEL transmembrane domain-containing family (CMTM), previously termed the chemokine-like factor superfamily (CKLFSF), consists of 9 proteins, some of which have various isoforms due to alternative splicing of their respective genes. These proteins[1] along with their isoforms[2] are:

All of these proteins have domains (i.e. regions) similar to analogous domains in the chemokine proteins; tetraspanin proteins (also termed transmembrane-4 superfamily proteins); myelin and lymphocyte protein (also termed MAR protein); proteins that direct membrane vesicle trafficking; and other proteins that are embedded in cell membranes.[4] The genes encoding (i.e. directing the production of) these proteins, CKLF, CMTM1, CMTM2, CMTM3, CMTM4, CMTM5, CMTM6, CMTM7, and CMTM8, respectively, also share similar regions that encode the domains just cited for their proteins. (The 8 CMTM genes were formerly termed CKLFSF1, CKLFSF2, CKLFSF3, CKLFSF4, CKLFSF5, CKLFSF6, CKLFSF7, and CKLFSF8.) The CKLF, CMTM1, CMTM2, CTMT3, and CMTM4 genes cluster together in band 22 on the long (i.e. "q") arm of chromosome 16; the CMTM6, CMTM7, and CMTM8 genes form a second cluster in band 22 on the short (i.e. "p") of chromosome 3; and the CMTM5 gene, located in band 11.2 on the q arm of chromosome 14, is not clustered with the other CMTM genes. These structural similarities and clusterings reflect the close relationships of these proteins and genes.[5] Studies suggest that the members of this family may be involved in the development of various cancers[4] autoimmune diseases,[5] cardiovascular diseases,[6] the male reproductive system,[7] and angiogenesis (i.e. development of new blood vessels from pre-existing blood vessels).[8] In most of these cases, however, further studies are needed to determine if these CMTM proteins and/or their corresponding genes and mRNAs will be promising targets to help in the diagnosis, prognosis, and/or treatment of these disorders.[4] [5] [9] [10]

Notes and References

  1. Han W, Ding P, Xu M, Wang L, Rui M, Shi S, Liu Y, Zheng Y, Chen Y, Yang T, Ma D . Identification of eight genes encoding chemokine-like factor superfamily members 1-8 (CKLFSF1-8) by in silico cloning and experimental validation . Genomics . 81 . 6 . 609–17 . June 2003 . 12782130 . 10.1016/s0888-7543(03)00095-8.
  2. Li M, Luo F, Tian X, Yin S, Zhou L, Zheng S . Chemokine-Like Factor-Like MARVEL Transmembrane Domain-Containing Family in Hepatocellular Carcinoma: Latest Advances . Frontiers in Oncology . 10 . 595973 . 2020 . 33282744 . 7691587 . 10.3389/fonc.2020.595973 . free .
  3. Zhang W, Qi H, Mo X, Sun Q, Li T, Song Q, Xu K, Hu H, Ma D, Wang Y . CMTM8 is Frequently Downregulated in Multiple Solid Tumors . Applied Immunohistochemistry & Molecular Morphology . 25 . 2 . 122–128 . February 2017 . 26574634 . 10.1097/PAI.0000000000000274 . 205912507 .
  4. Wu J, Li L, Wu S, Xu B . CMTM family proteins 1-8: roles in cancer biological processes and potential clinical value . Cancer Biology & Medicine . 17 . 3 . 528–542 . August 2020 . 32944388 . 7476098 . 10.20892/j.issn.2095-3941.2020.0032.
  5. Duan HJ, Li XY, Liu C, Deng XL . Chemokine-like factor-like MARVEL transmembrane domain-containing family in autoimmune diseases . Chinese Medical Journal . 133 . 8 . 951–958 . April 2020 . 32195671 . 7176445 . 10.1097/CM9.0000000000000747.
  6. Zhang JW, Liu TF, Chen XH, Liang WY, Feng XR, Wang L, Fu SW, McCaffrey TA, Liu ML . Validation of aspirin response-related transcripts in patients with coronary artery disease and preliminary investigation on CMTM5 function . Gene . 624 . 56–65 . August 2017 . 28457985 . 10.1016/j.gene.2017.04.041.
  7. Liu F, Liu X, Liu X, Li T, Zhu P, Liu Z, Xue H, Wang W, Yang X, Liu J, Han W . Integrated Analyses of Phenotype and Quantitative Proteome of CMTM4 Deficient Mice Reveal Its Association with Male Fertility . Molecular & Cellular Proteomics . 18 . 6 . 1070–1084 . June 2019 . 30867229 . 6553932 . 10.1074/mcp.RA119.001416. free .
  8. Chrifi I, Louzao-Martinez L, Brandt MM, van Dijk CG, Bürgisser PE, Zhu C, Kros JM, Verhaar MC, Duncker DJ, Cheng C . CMTM4 regulates angiogenesis by promoting cell surface recycling of VE-cadherin to endothelial adherens junctions . Angiogenesis . 22 . 1 . 75–93 . February 2019 . 30097810 . 6510885 . 10.1007/s10456-018-9638-1.
  9. Cai X, Deng J, Ming Q, Cai H, Chen Z . Chemokine-like factor 1: A promising therapeutic target in human diseases . Experimental Biology and Medicine . 245 . 16 . 1518–1528 . October 2020 . 32715782 . 7553088 . 10.1177/1535370220945225.
  10. Liang Z, Xie J, Huang L, Huang Y, Zhang Y, Ma R, Zheng Z, Wang Q, Li X . Comprehensive analysis of the prognostic value of the chemokine-like factor-like MARVEL transmembrane domain-containing family in gastric cancer . Journal of Gastrointestinal Oncology . 12 . 2 . 388–406 . April 2021 . 34012634 . 8107618 . 10.21037/jgo-21-78 . free .

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