The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TM4SF1  -  transmembrane 4 L six family member 1

Homo sapiens

Synonyms: H-L6, L6, M3S1, Membrane component chromosome 3 surface marker 1, TAAL6, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TM4SF1

  • The L6 antigen is mainly expressed in lung, breast, colon, ovarian carcinomas, and healthy epithelial tissue in humans [1].
  • Tumor-associated antigen L6 and the invasion of human lung cancer cells [2].
  • Thus, TAL6 appears to be involved in cancer invasion and metastasis [2].
  • Immunohistology of skin biopsies displayed a strong expression of L6 in follicular epidermis and epidermolytic lesions of autoimmune bullous dermatoses (bullous pemphigoid, pemphigus vulgaris), but not in normal interfollicular epidermis [3].
  • The tumor-associated antigen L6 (TAL6), a distant member of the TM4SF, is expressed on most epithelial cell carcinomas and is a target for antibody-mediated therapy [2].

High impact information on TM4SF1

  • The L6 cell surface antigen, which is highly expressed on lung, breast, colon, and ovarian carcinomas, has attracted attention as a therapeutic target for murine monoclonal antibodies and their humanized counterparts [4].
  • COS cells transfected with this cDNA direct the expression of an approximately 24-kDa surface protein that reacts with the two anti-L6 monoclonal antibodies available [4].
  • The predicted L6 peptide sequence is 202 amino acids long and contains three predicted NH2-terminal hydrophobic transmembrane regions, which are followed by a hydrophilic region containing two potential N-linked glycosylation sites and a COOH-terminal hydrophobic transmembrane region [4].
  • The L6 antigen is related to a number of cell surface proteins with similar predicted membrane topology that have been implicated in cell growth [4].
  • A kinetic study of splenic reconstitution was performed in mice that received hCTLA4-Ig and showed that mature splenic localized CD8+ T-cell repopulation was not significantly different in recipients of hCTLA4-Ig compared with hL6, despite the significant increase in actuarial survival rate in that experiment [5].

Biological context of TM4SF1

  • This cDNA contains one long open reading frame, which encodes a 220-amino acid polypeptide that is 78% homologous to H-L6 [6].
  • After artificial wounding of confluent HaCaT cultures, anti-L6 antibody strongly impaired cell migration velocity and migratory reepithelization of the defect, indicating L6 involvement in keratinocyte migration [3].
  • In contrast to normal keratinocytes, HaCaT cells showed constitutive L6 expression, indicating a constitutively active phenotype [3].
  • The Philadelphia (Ph') chromosome in chronic myelogenous leukemia (CML) results in fusion of the bcr gene and c-abl oncogene, which transcribes into two types of chimeric bcr/abl mRNAs: the L-6 junction and the K-28 junction [7].
  • The L6 rust resistance gene from flax generates at least four transcript classes by alternative splicing of the third intron [8].

Anatomical context of TM4SF1

  • In comparison with 17 other human tissues and cell types by microarray, large adipocytes displayed by far the highest SAA and TM4SF1 expression [9].
  • We have previously demonstrated that the murine L6 mAb recognizes a protein epitope expressed on human tumor-derived cell lines [6].
  • These findings suggest that L6 is an important activation-dependent regulator of keratinocyte function and epidermal tissue regeneration [3].
  • Amount of expression of the tumor-associated antigen L6 gene and transmembrane 4 superfamily member 5 gene in gastric cancers and gastric mucosa [10].
  • Moreover, binding of all four analogues to the IGFBPs secreted by L6 myoblasts and H35B hepatoma cells was greatly decreased compared with the parent IGF [11].

Associations of TM4SF1 with chemical compounds

  • A second transporter, the insulin-sensitive glucose transporter, was also observed to be expressed in the L6 cells [12].
  • Interestingly, the L6 ribosomal protein from L. braziliensis contains a specific region of 14 aa and a tyrosine kinase motif, which is absent in human and C. elegans L6 protein [13].
  • RESULTS: One up-regulated gene, glycoprotein hormone alpha-subunit, and two down-regulated genes coding membrane proteins, human folate receptor and tumor-associated antigen L6, were identified in KB/cDDP cells [14].

Other interactions of TM4SF1


Analytical, diagnostic and therapeutic context of TM4SF1


  1. Chromosomal localization of three human genes coding for A15, L6, and S5.7 (TAPA1): all members of the transmembrane 4 superfamily of proteins. Virtaneva, K.I., Emi, N., Marken, J.S., Aruffo, A., Jones, C., Spurr, N.K., Schröder, J.P. Immunogenetics (1994) [Pubmed]
  2. Tumor-associated antigen L6 and the invasion of human lung cancer cells. Kao, Y.R., Shih, J.Y., Wen, W.C., Ko, Y.P., Chen, B.M., Chan, Y.L., Chu, Y.W., Yang, P.C., Wu, C.W., Roffler, S.R. Clin. Cancer Res. (2003) [Pubmed]
  3. Molecular and functional characterization of the four-transmembrane molecule l6 in epidermal keratinocytes. Storim, J., Friedl, P., Schaefer, B.M., Bechtel, M., Wallich, R., Kramer, M.D., Reinartz, J. Exp. Cell Res. (2001) [Pubmed]
  4. Cloning and expression of the tumor-associated antigen L6. Marken, J.S., Schieven, G.L., Hellström, I., Hellström, K.E., Aruffo, A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  5. In vivo blockade of CD28/CTLA4: B7/BB1 interaction with CTLA4-Ig reduces lethal murine graft-versus-host disease across the major histocompatibility complex barrier in mice. Blazar, B.R., Taylor, P.A., Linsley, P.S., Vallera, D.A. Blood (1994) [Pubmed]
  6. Membrane topology of the L6 antigen and identification of the protein epitope recognized by the L6 monoclonal antibody. Marken, J.S., Bajorath, J., Edwards, C.P., Farr, A.G., Schieven, G.L., Hellström, I., Hellström, K.E., Aruffo, A. J. Biol. Chem. (1994) [Pubmed]
  7. Detection of two alternative bcr/abl mRNA junctions and minimal residual disease in Philadelphia chromosome positive chronic myelogenous leukemia by polymerase chain reaction. Lee, M.S., LeMaistre, A., Kantarjian, H.M., Talpaz, M., Freireich, E.J., Trujillo, J.M., Stass, S.A. Blood (1989) [Pubmed]
  8. Analysis of alternative transcripts of the flax L6 rust resistance gene. Ayliffe, M.A., Frost, D.V., Finnegan, E.J., Lawrence, G.J., Anderson, P.A., Ellis, J.G. Plant J. (1999) [Pubmed]
  9. Separation of human adipocytes by size: hypertrophic fat cells display distinct gene expression. Jernås, M., Palming, J., Sjöholm, K., Jennische, E., Svensson, P.A., Gabrielsson, B.G., Levin, M., Sjögren, A., Rudemo, M., Lystig, T.C., Carlsson, B., Carlsson, L.M., Lönn, M. FASEB J. (2006) [Pubmed]
  10. Amount of expression of the tumor-associated antigen L6 gene and transmembrane 4 superfamily member 5 gene in gastric cancers and gastric mucosa. Kaneko, R., Tsuji, N., Kamagata, C., Endoh, T., Nakamura, M., Kobayashi, D., Yagihashi, A., Watanabe, N. Am. J. Gastroenterol. (2001) [Pubmed]
  11. Insulin-like growth factor (IGF)-II binding to IGF-binding proteins and IGF receptors is modified by deletion of the N-terminal hexapeptide or substitution of arginine for glutamate-6 in IGF-II. Francis, G.L., Aplin, S.E., Milner, S.J., McNeil, K.A., Ballard, F.J., Wallace, J.C. Biochem. J. (1993) [Pubmed]
  12. Monokine regulation of glucose transporter mRNA in L6 myotubes. Cornelius, P., Lee, M.D., Marlowe, M., Pekala, P.H. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  13. Molecular characterization of the Leishmania braziliensis L6 ribosomal protein. Thomas, M.C., Martinez-Carretero, E., Carmelo, E., González, A.C., Valladares, B. J. Parasitol. (2004) [Pubmed]
  14. Differentially expressed genes associated with CIS-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and CDNA microarray. Higuchi, E., Oridate, N., Furuta, Y., Suzuki, S., Hatakeyama, H., Sawa, H., Sunayashiki-Kusuzaki, K., Yamazaki, K., Inuyama, Y., Fukuda, S. Head & neck. (2003) [Pubmed]
  15. Adaptation of estrogen-regulated genes in long-term estradiol deprived MCF-7 breast cancer cells. Santen, R.J., Lobenhofer, E.K., Afshari, C.A., Bao, Y., Song, R.X. Breast Cancer Res. Treat. (2005) [Pubmed]
  16. The carboxy-terminal cysteine of the tetraspanin L6 antigen is required for its interaction with SITAC, a novel PDZ protein. Borrell-Pagès, M., Fernández-Larrea, J., Borroto, A., Rojo, F., Baselga, J., Arribas, J. Mol. Biol. Cell (2000) [Pubmed]
  17. CD13 (aminopeptidase N) can associate with tumor-associated antigen L6 and enhance the motility of human lung cancer cells. Chang, Y.W., Chen, S.C., Cheng, E.C., Ko, Y.P., Lin, Y.C., Kao, Y.R., Tsay, Y.G., Yang, P.C., Wu, C.W., Roffler, S.R. Int. J. Cancer (2005) [Pubmed]
  18. Diagnosis and monitoring of colorectal cancer by L6 blood serum polymerase chain reaction is superior to carcinoembryonic antigen-enzyme-linked immunosorbent assay. Schiedeck, T.H., Wellm, C., Roblick, U.J., Broll, R., Bruch, H.P. Dis. Colon Rectum (2003) [Pubmed]
WikiGenes - Universities