CKLF like MARVEL transmembrane domain-containing 4

Last updated
CKLF-like MARVEL transmembrane domain-containing protein 4
Identifiers
SymbolCMTM4
Alt. symbolsCKLFSF4
Alt. namesChemokine-like factor superfamily member 4
HGNC 19175
OMIM 607887
RefSeq NM_178818.3
UniProt Q8IZR5
Other data
Locus Chr. 16 q21-q22.1
Search for
Structures Swiss-model
Domains InterPro

CKLF like MARVEL transmembrane domain-containing 4 (i.e. CMTM4), formerly termed chemokine-like factor superfamily 4 (i.e. CKLFSF4), is a small transmembrane protein which passes the plasma membrane four times. It has 3 known isoforms, the CMTM4-v1 to CMTM4-v3 proteins. [1] 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 (i.e. "q") arm of chromosome 16. [2] 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. [3] 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. [4] [5]

The Cancer Genome Atlas indicates that CMTM4 protein is frequently reduced in colorectal cancer and its high expression is associated with increased overall survival rates in individuals with this cancer. [6] CMTM4 protein was also found to be greatly reduced in the tissues of clear cell renal cell carcinoma compared to nearby normal renal (i.e. kidney) tissues and the forced overexpression of this protein in 786-O cells (a renal cancer cell line) inhibited their growth in culture as well as in a xenograph nude mouse model. [7] Finally, CMTM4 protein levels were lower in several brain cancers, such as glioblastomas, [7] [8] neuroblastomas, and medulloblastomas, compared to their levels in nearby normal, non-tumorous brain tissues. [7] [9] These studies suggest CMTM4 may act to suppress these malignancies. Further studies are needed to confirm these relationships and determine if CMTM4 protein can be used as a marker for the severity of these malignancies and/or serve as a therapeutic target for treating them. [4] [9] [10]

CMTM4 in IL-17A signaling

Recently, CMTM4 has been identified to play a critical role in IL-17A signaling. [11] The IL-17 receptor consists of two subunits: IL-17 receptor subunit A and C (IL-17RA, IL-17RC). [12] [13] CMTM4 was reported to be associated with the transmembrane domain of IL-17RC. This association proved to be critical for IL-17 signaling as CMTM4 knockout cells were unresponsive to IL-17A stimulation. Interestingly, lack of CMTM4 in cells caused an overall decrease in IL-17RC surface expression and impaired IL-17RC glycosylation. Altogether, CMTM4 regulates IL-17RC glycosylation status and its cellular localization. [11]

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<span class="mw-page-title-main">CMTM2</span> Protein-coding gene in the species Homo sapiens

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<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.

<span class="mw-page-title-main">TMEM171</span> Protein-coding gene in the species Homo sapiens

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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 along with their isoforms are:

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.

References

  1. ↑ Zhang W, Qi H, Mo X, Sun Q, Li T, Song Q, et al. (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.
  2. ↑ 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.
  3. ↑ Han W, Ding P, Xu M, Wang L, Rui M, Shi S, et al. (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): 609–617. doi:10.1016/s0888-7543(03)00095-8. PMID   12782130.
  4. 1 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.
  5. ↑ Ge YY, Duan HJ, Deng XL (April 2021). "Possible effects of chemokine-like factor-like MARVEL transmembrane domain-containing family on antiphospholipid syndrome". Chinese Medical Journal. 134 (14): 1661–1668. doi:10.1097/CM9.0000000000001449. PMC   8318642 . PMID   33813507.
  6. ↑ Xue H, Li T, Wang P, Mo X, Zhang H, Ding S, et al. (September 2019). "CMTM4 inhibits cell proliferation and migration via AKT, ERK1/2, and STAT3 pathway in colorectal cancer". Acta Biochimica et Biophysica Sinica. 51 (9): 915–924. doi:10.1093/abbs/gmz084. PMID   31435638.
  7. 1 2 3 Li T, Cheng Y, Wang P, Wang W, Hu F, Mo X, et al. (October 2015). "CMTM4 is frequently downregulated and functions as a tumour suppressor in clear cell renal cell carcinoma". Journal of Experimental & Clinical Cancer Research. 34: 122. doi: 10.1186/s13046-015-0236-4 . PMC   4609138 . PMID   26474560.
  8. ↑ Delic S, Thuy A, Schulze M, Proescholdt MA, Dietrich P, Bosserhoff AK, Riemenschneider MJ (July 2015). "Systematic investigation of CMTM family genes suggests relevance to glioblastoma pathogenesis and CMTM1 and CMTM3 as priority targets". Genes, Chromosomes & Cancer. 54 (7): 433–443. doi:10.1002/gcc.22255. PMID   25931111. S2CID   25545349.
  9. 1 2 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.
  10. ↑ Liang Z, Xie J, Huang L, Huang Y, Zhang Y, Ma R, et al. (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.
  11. 1 2 Knizkova D, Pribikova M, Draberova H, Semberova T, Trivic T, Synackova A, et al. (November 2022). "CMTM4 is a subunit of the IL-17 receptor and mediates autoimmune pathology". Nature Immunology. 23 (11): 1644–1652. doi:10.1038/s41590-022-01325-9. PMC   9663306 . PMID   36271145.
  12. ↑ Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, et al. (July 2006). "Cutting edge: interleukin 17 signals through a heteromeric receptor complex". Journal of Immunology. 177 (1): 36–39. doi: 10.4049/jimmunol.177.1.36 . PMID   16785495. S2CID   45096063.
  13. ↑ Yao Z, Fanslow WC, Seldin MF, Rousseau AM, Painter SL, Comeau MR, et al. (December 1995). "Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor". Immunity. 3 (6): 811–821. doi: 10.1016/1074-7613(95)90070-5 . PMID   8777726.
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