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Gene Review

MIEN1  -  migration and invasion enhancer 1

Homo sapiens

Synonyms: C17orf37, C35, HBV X-transactivated gene 4 protein, HBV XAg-transactivated protein 4, MGC14832, ...
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Disease relevance of C17orf37

  • C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer [1].
  • Immunohistochemical analysis detected robust and frequent expression of C35 protein, including 32% of grade 1 and 66% of grades 2 and 3 infiltrating ductal carcinomas of the breast (in contrast to 20% overexpressing HER-2/neu), 38% of infiltrating lobular carcinoma (typically HER-2/neu negative), as well as tumors arising in other tissues [1].
  • This is similar to the situation in human Trx and Trx m from spinach chloroplasts but differs from Escherichia coli Trx, where it is C35 that moves upon change of the redox state [2].

High impact information on C17orf37

  • Optimization of C35 hydroxyl group protection-deprotection completed the effort, which culminated in the first total synthesis of apratoxin A and will enable analog generation toward improving differential cytotoxicity [3].
  • Further mutation of the A1:U72 base pair, which is conserved in virtually all eukaryotic initiator tRNAs, to G1:C72 in the C35 mutant background yielded tRNAs that were even more active in elongation [4].
  • The diastereomer obtained through cyclization of the unwanted aldol product was subjected to an oxidation/reduction sequence to rectify the C35 stereocenter [5].
  • At physiological pH (7.4), truncation of the two N-terminal SH2 domains [SH-PTP1(delta SH2)] or the last 35 amino acids of the C-terminus [SH-PTP1(delta C35)] activated the phosphatase activity by 30-fold and 20-34-fold relative to the wild-type enzyme, respectively [6].
  • Cochliobolus heterostrophus race T, causal agent of southern corn leaf blight, requires T-toxin (a family of C35 to C49 polyketides) for high virulence on T-cytoplasm maize [7].

Biological context of C17orf37

  • The C35 gene is located on chromosome 17q12, 505 nucleotides from the 3' end of the ERBB2 oncogene, the antigenic target for trastuzumab (Herceptin(TM)) therapy [1].
  • Next to the bound GSH, the orientation of residues C35, H31, and S48 is suggestive of a cysteine-type protein phosphatase active site [8].
  • The consensus sequence of the tRNAs charged by the various Gly-tRNA synthetases reveals conservation of only G1-C72 in the acceptor arm, C35 and C36 in the anticodon, and the (G10-Y25)-G45 triplet involved in tRNA folding [9].
  • The murine anti-human osteoclast monoclonal antibodies 23C6 (vitronectin receptor) and C35 (osteoclast-selective) were used to further identify the osteoclast phenotype [10].
  • The h3 allele contains a C658 to T missense mutation, whereas two missense mutations, C35 to T and A980 to C were identified in the h4 allele [11].

Anatomical context of C17orf37

  • In a study designed to identify genes up-regulated in breast cancer, a cDNA clone corresponding to a novel gene C35 (C17orf37) was selected by representational difference analysis of tumor and normal human mammary cell lines [1].
  • C35 was not detected in 38 different normal human tissues, except Leydig cells in the testes and trace levels in a small percentage of normal breast tissue samples [1].
  • The HN proteins of the two low-fusogenic strains 8389 and 45785, and the highly fusogenic strain C35, were expressed in HeLa T4+ cells and their fusion promotion activities were compared [12].
  • In contrast, C35 reacted with only very occasional giant cells [13].
  • These giant cells and associated mononuclear cells were NSE- and distinctly TRAP+, and expressed osteopontin mRNA, C35, and 23C6 (human osteoclast) reactivity [10].

Associations of C17orf37 with chemical compounds

  • Histidine residues were substituted for two of the Cys residues (C30 and C35), changing a C2C2 type Zn-binding motif to a C2H2 motif [14].
  • Toward the synthesis of reidispongiolide a: stereocontrolled synthesis of the C17-C22 and C23-C35 degradation fragments [15].
  • The structure of CIB1 revealed a complex with a molecule of glutathione in the reduced state bond to the N-terminal domain of one of the two subunits poised to interact with the free thiol of C35 [8].
  • Sanglifehrin A is a novel complex natural product showing strong immunosuppressive activity and remarkably high affinity for cyclophilin A. To assess its pharmacokinetic properties in vivo, an efficient synthetic route was developed to introduce a tritium label in position C35 of sangliferin A via an oxidation/reduction strategy [16].
  • The steady-state spectral properties (absorption and emission) of three structurally similar Coumarin dyes, C151, C500, and C35 were investigated in 13 different solvents [17].

Analytical, diagnostic and therapeutic context of C17orf37


  1. C35 (C17orf37) is a novel tumor biomarker abundantly expressed in breast cancer. Evans, E.E., Henn, A.D., Jonason, A., Paris, M.J., Schiffhauer, L.M., Borrello, M.A., Smith, E.S., Sahasrabudhe, D.M., Zauderer, M. Mol. Cancer Ther. (2006) [Pubmed]
  2. Comparative structural analysis of oxidized and reduced thioredoxin from Drosophila melanogaster. Wahl, M.C., Irmler, A., Hecker, B., Schirmer, R.H., Becker, K. J. Mol. Biol. (2005) [Pubmed]
  3. Total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A. Chen, J., Forsyth, C.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Initiator-elongator discrimination in vertebrate tRNAs for protein synthesis. Drabkin, H.J., Estrella, M., Rajbhandary, U.L. Mol. Cell. Biol. (1998) [Pubmed]
  5. Multigram synthesis of the C29-C51 subunit and completion of the total synthesis of altohyrtin C (spongistatin 2). Heathcock, C.H., McLaughlin, M., Medina, J., Hubbs, J.L., Wallace, G.A., Scott, R., Claffey, M.M., Hayes, C.J., Ott, G.R. J. Am. Chem. Soc. (2003) [Pubmed]
  6. Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains. Pei, D., Lorenz, U., Klingmüller, U., Neel, B.G., Walsh, C.T. Biochemistry (1994) [Pubmed]
  7. Two polyketide synthase-encoding genes are required for biosynthesis of the polyketide virulence factor, T-toxin, by Cochliobolus heterostrophus. Baker, S.E., Kroken, S., Inderbitzin, P., Asvarak, T., Li, B.Y., Shi, L., Yoder, O.C., Turgeon, B.G. Mol. Plant Microbe Interact. (2006) [Pubmed]
  8. The crystal structure of calcium- and integrin-binding protein 1: insights into redox regulated functions. Blamey, C.J., Ceccarelli, C., Naik, U.P., Bahnson, B.J. Protein Sci. (2005) [Pubmed]
  9. Glycyl-tRNA synthetase from Thermus thermophilus--wide structural divergence with other prokaryotic glycyl-tRNA synthetases and functional inter-relation with prokaryotic and eukaryotic glycylation systems. Mazauric, M.H., Keith, G., Logan, D., Kreutzer, R., Giegé, R., Kern, D. Eur. J. Biochem. (1998) [Pubmed]
  10. Human osteoclast and giant cell differentiation: the apparent switch from nonspecific esterase to tartrate resistant acid phosphatase activity coincides with the in situ expression of osteopontin mRNA. Connor, J.R., Dodds, R.A., James, I.E., Gowen, M. J. Histochem. Cytochem. (1995) [Pubmed]
  11. Heterogeneity of the human H blood group alpha(1,2)fucosyltransferase gene among para-Bombay individuals. Yu, L.C., Yang, Y.H., Broadberry, R.E., Chen, Y.H., Lin, M. Vox Sang. (1997) [Pubmed]
  12. A single amino acid changes enhances the fusion promotion activity of human parainfluenza virus type 1 hemagglutinin-neuraminidase glycoprotein. Bousse, T., Takimoto, T., Portner, A. Virology (1995) [Pubmed]
  13. Production and characterization of osteoclast-selective monoclonal antibodies that distinguish between multinucleated cells derived from different human tissues. James, I.E., Walsh, S., Dodds, R.A., Gowen, M. J. Histochem. Cytochem. (1991) [Pubmed]
  14. Mutational analysis of a satellite phage activator. Julien, B., Pountney, D., Christie, G.E., Calendar, R. Gene (1998) [Pubmed]
  15. Toward the synthesis of reidispongiolide a: stereocontrolled synthesis of the C17-C22 and C23-C35 degradation fragments. Paterson, I., Ashton, K., Britton, R., Knust, H. Org. Lett. (2003) [Pubmed]
  16. Efficient synthesis of [3H]-sanglifehrin A via selective oxidation/reduction of alcohols at C31 and C35. Wagner, J., Andres, H., Rohrbach, S., Wagner, D., Oberer, L., France, J. J. Org. Chem. (2005) [Pubmed]
  17. Hydrogen bonding properties of Coumarin 151, 500, and 35: the effect of substitution at the 7-amino position. Das, K., Jain, B., Patel, H.S. The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment & general theory. (2006) [Pubmed]
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