TM4SF1 explained

Transmembrane 4 L6 family member 1 is a protein that in humans is encoded by the TM4SF1 gene.^{[1] [2]}

Function

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface antigen and is highly expressed in different carcinomas.^[2]

Marker gene for alveolar epithelial progenitors

TM4SF1 has been identified as a marker of Wnt-responsive alveolar epithelial progenitor cells, and a marker of alveolar repair in injured regions of the lungs.^[3] It has also been found hypomethylated and upregulated in asthma, with potential prognostic value (AUROC: 0.769).^[4]

Further reading

• Berditchevski F . Complexes of tetraspanins with integrins: more than meets the eye . Journal of Cell Science . 114 . Pt 23 . 4143–51 . Dec 2001 . 10.1242/jcs.114.23.4143 . 11739647 .
• Marken JS, Bajorath J, Edwards CP, Farr AG, Schieven GL, Hellström I, Hellström KE, Aruffo A . Membrane topology of the L6 antigen and identification of the protein epitope recognized by the L6 monoclonal antibody . The Journal of Biological Chemistry . 269 . 10 . 7397–401 . Mar 1994 . 10.1016/S0021-9258(17)37298-8 . 7510285 . free .
• Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC . Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening . Genomics . 23 . 1 . 42–50 . Sep 1994 . 7829101 . 10.1006/geno.1994.1457 .
• Virtaneva KI, Emi N, Marken JS, Aruffo A, Jones C, Spurr NK, Schröder JP . Chromosomal localization of three human genes coding for A15, L6, and S5.7 (TAPA1): all members of the transmembrane 4 superfamily of proteins . Immunogenetics . 39 . 5 . 329–34 . 1994 . 8168850 . 10.1007/BF00189229 . 22971645 .
• Borrell-Pagès M, Fernández-Larrea J, Borroto A, Rojo F, Baselga J, Arribas J . The carboxy-terminal cysteine of the tetraspanin L6 antigen is required for its interaction with SITAC, a novel PDZ protein . Molecular Biology of the Cell . 11 . 12 . 4217–25 . Dec 2000 . 11102519 . 15068 . 10.1091/mbc.11.12.4217 .
• Storim J, Friedl P, Schaefer BM, Bechtel M, Wallich R, Kramer MD, Reinartz J . Molecular and functional characterization of the four-transmembrane molecule l6 in epidermal keratinocytes . Experimental Cell Research . 267 . 2 . 233–42 . Jul 2001 . 11426942 . 10.1006/excr.2001.5250 .
• Kaneko R, Tsuji N, Kamagata C, Endoh T, Nakamura M, Kobayashi D, Yagihashi A, Watanabe N . Amount of expression of the tumor-associated antigen L6 gene and transmembrane 4 superfamily member 5 gene in gastric cancers and gastric mucosa . The American Journal of Gastroenterology . 96 . 12 . 3457–8 . Dec 2001 . 10.1111/j.1572-0241.2001.05355.x . 11774983 . 31864317 .
• Kao YR, Shih JY, Wen WC, Ko YP, Chen BM, Chan YL, Chu YW, Yang PC, Wu CW, Roffler SR . Tumor-associated antigen L6 and the invasion of human lung cancer cells . Clinical Cancer Research . 9 . 7 . 2807–16 . Jul 2003 . 12855661 .
• Chang YW, Chen SC, Cheng EC, Ko YP, Lin YC, Kao YR, Tsay YG, Yang PC, Wu CW, Roffler SR . CD13 (aminopeptidase N) can associate with tumor-associated antigen L6 and enhance the motility of human lung cancer cells . International Journal of Cancer . 116 . 2 . 243–52 . Aug 2005 . 15812828 . 10.1002/ijc.21089 . 26010618 . free .
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . Sep 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Visintin A, Knowlton K, Tyminski E, Lin CI, Zheng X, Marquette K, Jain S, Tchistiakova L, Li D, O'Donnell CJ, Maderna A, Cao X, Dunn R, Snyder W, Abraham AK, Leal M, Shetty S, Barry A, Zawel L, Coyle AJ, Dvorak HF, Jaminet SC . Novel Anti-TM4SF1 Antibody Drug Conjugates with Activity against Tumor Cells and Tumor Vasculature . Molecular Cancer Therapeutics . 14. 8 . Jun 2015 . 26089370 . 10.1158/1535-7163.MCT-15-0188 . 1868–76. free .

Notes and References

1. Marken JS, Schieven GL, Hellström I, Hellström KE, Aruffo A . Cloning and expression of the tumor-associated antigen L6 . Proceedings of the National Academy of Sciences of the United States of America . 89 . 8 . 3503–7 . Apr 1992 . 1565644 . 48896 . 10.1073/pnas.89.8.3503 . 1992PNAS...89.3503M . free .
2. Web site: Entrez Gene: TM4SF1 transmembrane 4 L six family member 1.
3. Zacharias . William J. . Frank . David B. . Zepp . Jarod A. . Morley . Michael P. . Alkhaleel . Farrah A. . Kong . Jun . Zhou . Su . Cantu . Edward . Morrisey . Edward E. . 2018-03-08 . Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor . Nature . 555 . 7695 . 251–255 . 10.1038/nature25786 . 1476-4687 . 6020060 . 29489752. 2018Natur.555..251Z .
4. Wang . Zongling . Wang . Lizhi . Dai . Lina . Wang . Yanan . Li . Erhong . An . Shuyuan . Wang . Fengliang . Liu . Dan . Pan . Wen . 2022-12-22 . Identification of candidate aberrant differentially methylated/expressed genes in asthma . Allergy, Asthma, and Clinical Immunology . 18 . 1 . 108 . 10.1186/s13223-022-00744-5 . 1710-1484 . 9784293 . 36550577 . free .