CKLF-like MARVEL transmembrane domain-containing family

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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]

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<span class="mw-page-title-main">CKLF like MARVEL transmembrane domain containing 7</span>

CKLF like MARVEL transmembrane domain-containing 7, previously termed chemokine-like factor superfamily 7, is a protein that in humans is encoded by the CMTM7 gene. This gene, which is located in band 22 on the short arm of chromosome 3, and the protein that it encodes belong to the CKLF-like MARVEL transmembrane domain-containing family. Through the process of alternative splicing, the CMTM7 gene encodes two isoforms, CMTM7-v1 and CMTM7-v2, with CMTM7-v1 being the main form expressed and studied. CMTM7 proteins are widely expressed in normal human tissues.

<span class="mw-page-title-main">CKLF like MARVEL transmembrane domain containing 6</span> Transmembrane protein

CKLF like MARVEL transmembrane domain-containing 6, previously termed chemokine-like factor superfamily 6, is a transmembrane protein encoded in humans by the CMTM6 gene. This gene is located in band 22.3 on the short arm of chromosome 3. CMTM6 protein belongs to the CKLF-like MARVEL transmembrane domain-containing family of proteins. This family consist of 9 member proteins: CKLF and CMTM1 through CMTM8. The CMTM family proteins are involved in autoimmune diseases, cardiovascular diseases, the male reproductive system, haematopoiesis, and cancer development. CMTM6 protein regulates immune responses to normal and abnormal cells.

<span class="mw-page-title-main">CMTM3</span> Protein-coding gene in the species Homo sapiens

CKLF-like MARVEL transmembrane domain-containing protein 3, also termed chemokine-like factor superfamily 3, is a member of the CKLF-like MARVEL transmembrane domain-containing family of proteins. In humans, CMTM2 protein is encoded by the CMTM3 gene located in band 22.1 on the long arm of chromosome 16. This protein is expressed in a wide range of tissues, including fetal tissues. It is highly expressed in the male reproductive system, particularly testicular tissues and may play a role in the development of this tissue. It is also highly expressed in the immune system including circulating blood cells, i.e. B lymphocytes, CD4+ T lymphocytes, and monocytes. However, CMTM3 protein is weakly expressed or unexpressed in the malignant tissues of several types of cancers. In many but not all of theses cancers, this decreased or lack of expression appears due to methylation of the GpC islands in the promoter region, and thereby the silencing, of the CMTM3 gene.

Transmembrane protein 39B (TMEM39B) is a protein that in humans is encoded by the gene TMEM39B. TMEM39B is a multi-pass membrane protein with eight transmembrane domains. The protein localizes to the plasma membrane and vesicles. The precise function of TMEM39B is not yet well-understood by the scientific community, but differential expression is associated with survival of B cell lymphoma, and knockdown of TMEM39B is associated with decreased autophagy in cells infected with the Sindbis virus. Furthermore, the TMEM39B protein been found to interact with the SARS-CoV-2 ORF9C protein. TMEM39B is expressed at moderate levels in most tissues, with higher expression in the testis, placenta, white blood cells, adrenal gland, thymus, and fetal brain.

CKLF-like MARVEL transmembrane domain-containing 5 (CMTM5), previously termed chemokine-like factor superfamily 5, designates any one of the six protein isoforms encoded by six different alternative splices of its gene, CMTM5; CMTM5-v1 is the most studied of these isoforms. The CMTM5 gene is located in band 11.2 on the long arm of chromosome 14.

CKLF like MARVEL transmembrane domain-containing 8, previously termed chemokine-like factor superfamily 8 has at least two isoforms, the CMTM8 and CMTM8-v2 proteins. Protein isoforms are variant products that are made by the alternative splicing of a single gene. The gene for these isoforms, CMTM8, is located in band 22 on the short arm of chromosome 3. The CMTM8 gene and its CMTM8 and CMTM8-v2 proteins belong to the CKLF-like MARVEL transmembrane domain-containing family of structurally and functionally related genes and proteins. The CMTM8 protein is the full-length and predominant product of the CMTM8 gene. This protein is expressed in a wide range of normal adult and fetal tissues while relatively little is known about the CMTM8-v2 protein. Studies suggest that the CMTM8 protein may be involved in the development of various cancers.

CKLF like MARVEL transmembrane domain-containing 1, formerly termed chemokine-like factor superfamily 1, has 23 known isoforms, the CMTM1-v1 to CMTM1-v23 proteins. Protein isoforms are variant products that are made by alternative splicing of a single gene. The gene for these isoforms, CMTM1, is located in band 22 on the long arm of chromosome 16. The CMTM1 gene and its 23 isoforms belong to the CKLF-like MARVEL transmembrane domain-containing family of structurally and functionally related genes and proteins. CMTM1 proteins are weakly express in a wide range of normal tissues but are far more highly expressed in normal testes as well as the malignant cells of certain types of cancer.

CKLF like MARVEL transmembrane domain-containing 4, formerly termed chemokine-like factor superfamily 4, is a small transmembrane protein which passes the plasma membrane four times. It has 3 known isoforms, the CMTM4-v1 to CMTM4-v3 proteins. Protein isoforms are variant products that are made by alternative splicing of a single gene. The gene for the CMTM4 isoforms is located in band 22 on the long arm of chromosome 16. The CMTM4 gene and its 3 isoform proteins belong to the CKLF-like MARVEL transmembrane domain-containing family of structurally and functionally related genes and proteins. CMTM4-v1 and CMTM4-v2 are widely expressed in multiple human tissue while CMTM4-v3 has been detected only in the kidney and placental tissues.

References

  1. ↑ Han W, Ding P, Xu M, Wang L, Rui M, Shi S, Liu Y, Zheng Y, Chen Y, Yang T, Ma D (June 2003). "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. doi:10.1016/s0888-7543(03)00095-8. PMID   12782130.
  2. ↑ Li M, Luo F, Tian X, Yin S, Zhou L, Zheng S (2020). "Chemokine-Like Factor-Like MARVEL Transmembrane Domain-Containing Family in Hepatocellular Carcinoma: Latest Advances". Frontiers in Oncology. 10: 595973. doi: 10.3389/fonc.2020.595973 . PMC   7691587 . PMID   33282744.
  3. ↑ Zhang W, Qi H, Mo X, Sun Q, Li T, Song Q, Xu K, Hu H, Ma D, Wang Y (February 2017). "CMTM8 is Frequently Downregulated in Multiple Solid Tumors". Applied Immunohistochemistry & Molecular Morphology. 25 (2): 122–128. doi:10.1097/PAI.0000000000000274. PMID   26574634. S2CID   205912507.
  4. 1 2 3 Wu J, Li L, Wu S, Xu B (August 2020). "CMTM family proteins 1-8: roles in cancer biological processes and potential clinical value". Cancer Biology & Medicine. 17 (3): 528–542. doi:10.20892/j.issn.2095-3941.2020.0032. PMC   7476098 . PMID   32944388.
  5. 1 2 3 Duan HJ, Li XY, Liu C, Deng XL (April 2020). "Chemokine-like factor-like MARVEL transmembrane domain-containing family in autoimmune diseases". Chinese Medical Journal. 133 (8): 951–958. doi:10.1097/CM9.0000000000000747. PMC   7176445 . PMID   32195671.
  6. ↑ Zhang JW, Liu TF, Chen XH, Liang WY, Feng XR, Wang L, Fu SW, McCaffrey TA, Liu ML (August 2017). "Validation of aspirin response-related transcripts in patients with coronary artery disease and preliminary investigation on CMTM5 function". Gene. 624: 56–65. doi:10.1016/j.gene.2017.04.041. PMID   28457985.
  7. ↑ Liu F, Liu X, Liu X, Li T, Zhu P, Liu Z, Xue H, Wang W, Yang X, Liu J, Han W (June 2019). "Integrated Analyses of Phenotype and Quantitative Proteome of CMTM4 Deficient Mice Reveal Its Association with Male Fertility". Molecular & Cellular Proteomics. 18 (6): 1070–1084. doi: 10.1074/mcp.RA119.001416 . PMC   6553932 . PMID   30867229.
  8. ↑ Chrifi I, Louzao-Martinez L, Brandt MM, van Dijk CG, Bürgisser PE, Zhu C, Kros JM, Verhaar MC, Duncker DJ, Cheng C (February 2019). "CMTM4 regulates angiogenesis by promoting cell surface recycling of VE-cadherin to endothelial adherens junctions". Angiogenesis. 22 (1): 75–93. doi:10.1007/s10456-018-9638-1. PMC   6510885 . PMID   30097810.
  9. ↑ Cai X, Deng J, Ming Q, Cai H, Chen Z (October 2020). "Chemokine-like factor 1: A promising therapeutic target in human diseases". Experimental Biology and Medicine. 245 (16): 1518–1528. doi:10.1177/1535370220945225. PMC   7553088 . PMID   32715782.
  10. ↑ Liang Z, Xie J, Huang L, Huang Y, Zhang Y, Ma R, Zheng Z, Wang Q, Li X (April 2021). "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. doi: 10.21037/jgo-21-78 . PMC   8107618 . PMID   34012634.
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