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Gene Review

Cig40  -  cold inducible glycoprotein 40

Mus musculus

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Disease relevance of Cig40

  • We now report the expression of the complete p40x coding sequence as a 40-kDa protein in Escherichia coli [1].
  • This open reading frame encodes a 40-kDa protein (designated p40x) that has been implicated as a positive control element for transcription from the HTLV-I LTR in a phenomenon known as trans-activation [1].
  • Immunotoxins were made using five different murine monoclonal antibodies to the human erbB2 gene product and LysPE40, a 40-kDa recombinant form of Pseudomonas exotoxin (PE) lacking its cell-binding domain [2].
  • In Western blot analyses, the purified polyclonal antibody recognized a specific signal with a molecular mass of approximately 40 kDa in RL and HT lymphomas [3].
  • Many IDDM sera are known to immunoprecipitate 37-kDa and 40-kDa tryptic fragments from islet cells, but the identity of the precursor protein(s) has remained elusive [4].

Psychiatry related information on Cig40

  • The different isozymes -100, 69, 46 and 40 kDa expressed in human cells, or the 105, 71 and 43 kDa expressed in mouse cells--are induced by IFNs with cell type specificity, and exhibit individual differences in their biochemical and enzymatic properties [5].

High impact information on Cig40

  • The responsible gene m152, encoding a type I transmembrane glycoprotein of 40 kDa, is a member of a gene family located in the right-hand terminal region of the 230 kb virus genome [6].
  • The mDab1 PTB domain binds to phosphotyrosine-containing proteins of 200, 120 and 40 kDa from extracts of embryonic mouse heads [7].
  • 5. Several BEN-encoded polypeptides of different sizes ranging from 165 to 40 kDa were identified by Western blot analysis using BEN-specific polyclonal Abs [8].
  • We show that the 40-kDa GATA-1 (GATA-1s) is produced by the use of an internal AUG initiation codon in the GATA-1 transcript [9].
  • (iii) The protein derived from our cDNA but not from an unrelated control cDNA clone can block immunoprecipitation of the 37/40-kDa antigen from a labeled rat insulinoma cell extract [10].

Chemical compound and disease context of Cig40

  • The full-length cDNA baculovirus recombinant directed the expression of a 40-kDa glycoprotein that was confined to infected Spodoptera frugiperda cells, whereas cells infected with the truncated cDNA baculovirus recombinant abundantly secreted a 31-kDa glycoprotein into the culture medium [11].
  • RESULTS: GTP gamma S, as opposed to other nucleotides, caused optimal and virtually instantaneous release of soluble 40 kDa [32P]ADP ribosylated protein in pertussis toxin treated membranes [12].
  • We have identified and characterized the 40 kDa immunoreactive UTI (UTI(40)) and 8 kDa degradation fragment (UTI(8)) in ascites fluid [13].
  • Endotoxemia was associated with hepatobiliary epithelial barrier dysfunction, as evidenced by increased plasma-to-bile leakage of FITC-labeled dextran (relative molecular mass 40 kDa) and increased circulating levels of bile acids and conjugated bilirubin [14].
  • In contrast, in membranes from other origins, only two PT substrates at 41 and 40 kDa were resolved; the latter being the most abundant ADP-ribosylated substrate in human platelets and C6 glioma cells [15].

Biological context of Cig40

  • It encodes isoforms of a highly hydrophilic 40 kDa protein, homologous to its human counterpart and containing several potential phosphorylation sites [16].
  • Interleukin 12 (IL-12) is an inducible cytokine composed of 35- and 40-kDa subunits that is critical for promoting T helper type 1 development and cell-mediated immunity against pathogens [17].
  • On SDS-polyacrylamide gel electrophoresis, a 40-kDa band was identified as the enzyme, and its partial amino acid sequence (27 amino acids) was determined [18].
  • Both kinases consisted of a 40-kDa catalytic subunit and a 44-kDa regulatory subunit [19].
  • Serologic analysis showed that the humoral responses to the major surface 29-kDa glycoprotein of adult parasites and a 40-kDa Ag from the surface of the microfilarial stage were restricted to mice with H-2k alleles (B10.BR, CBA/Ca, and CBA/N), whereas mice of the H-2d haplotype (B10.D2/n and BALB/c) were nonresponsive to these Ag [20].

Anatomical context of Cig40

  • In vitro binding experiments suggest that the 40-kDa protein that binds to this element (NF-alpha P) is a member of the Ets family present in both B-cell and plasma-cell nuclei [21].
  • In human and murine erythroid cells a previously undescribed 40-kDa protein is detected with GATA-1-specific antibodies [9].
  • Tax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) that activates nuclear expression of the NF-kappaB/Rel family of transcription factors by an unknown mechanism [22].
  • All human cell lines so far examined expressed the 40-kDa protein; however, expression of the 28- and the 42-kDa proteins was variable [23].
  • The 40-kDa subunit, expressed by activated macrophages and B cells, is induced by several pathogens in vivo and in vitro and is augmented or inhibited by gamma interferon (IFN-gamma) or IL-10, respectively [17].

Associations of Cig40 with chemical compounds

  • We have generated a polyclonal antibody against a peptide from a unique region within retinoschisin, which detects a protein of approximately 28 kDa in retinal samples reduced with dithiothreitol, but multimers sized >40 kDa under non-reducing conditions [24].
  • Upon incubation of WEHI 231 cells with the reversible chemical cross-linking agent dithiobis(succinimidyl propionate), the 40-kDa protein could be cross-linked to c-Myc protein intracellularly [25].
  • ADP-ribosylation with 32P-NAD and PTX of choroid plexus revealed an intense labeling at the 40 kDa level in addition to the known PTX-substrates at 41 kDa (Gi alpha) and 39 kDa (Go alpha) [26].
  • Ag-mimicking cross-linked anti-CD3 mAb stimulated suspension of thymocytes from adult (6 to 8 wk old) mice for a brisk free cytoplasmic calcium ion ([Ca2+]i) rise, low level of inositol phosphate production, and marginal increase in tyrosine-specific phosphorylation of 110/120-kDa and 40-kDa cellular proteins [27].
  • A novel 40-kDa protein containing six repeats of an epidermal growth factor-like domain functions as a pattern recognition protein for lipopolysaccharide [28].

Physical interactions of Cig40

  • Identification of the 40-kDa protein as the TATA-binding protein (TBP) of the TFIID transcription initiation complex was made by comigration and V-8 protease mapping, which yielded identical peptide fragments upon digestion of the 40-kDa protein and material immunoprecipitated with an anti-TBP specific antibody [25].
  • Previous work demonstrates that PNK-E mAb binds to a 205-kDa tetrameric molecule composed of two 47-kDa peptides and two 50-kDa peptides and G7 mAb binds to a distinct 40-kDa heterodispersed monomeric peptide on porcine NK cells [29].
  • The 97 kDa receptor in cytosol from wild type cells was digested by chymotrypsin to a 40 kDa steroid-binding receptor fragment but the 48 kDa receptor in cytosol from nti mutants was resistant to digestion by chymotrypsin [30].

Regulatory relationships of Cig40

  • In particular, as shown in mice with the recombinant H-2 haplotype and in class II mutant bm12 mice, the I-A heterodimer controls the recognition of the immunodominant 40-kDa antigen [31].
  • Thy-1/CD3-mediated activation enhanced mostly tyrosine phosphorylation of a 40 kDa protein which was identified as a transmembrane protein lacking N-linked oligosaccharides [32].
  • To further understand CSF-1 regulation of macrophages in vivo, we developed a neutralizing anti-mouse CSF-1 antibody which was expressed as a recombinant Fab' fragment and coupled to 40 kDa polyethylene glycol [33].
  • In addition, the keratin polypeptide composition within the low molecular weight range showed further alterations with regard to the corresponding keratin subset of normal tissues in that both tumors expressed a 40-kDa protein, and a 56-kDa protein was selectively found in the forestomach tumor [34].

Other interactions of Cig40


Analytical, diagnostic and therapeutic context of Cig40


  1. Expression of the complete human T-cell leukemia virus type I pX coding sequence as a functional protein in Escherichia coli. Giam, C.Z., Nerenberg, M., Khoury, G., Jay, G. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  2. Recombinant anti-erbB2 immunotoxins containing Pseudomonas exotoxin. Batra, J.K., Kasprzyk, P.G., Bird, R.E., Pastan, I., King, C.R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  3. Development of a polyclonal antiserum for the detection of the isoforms of the receptors for human growth hormone-releasing hormone on tumors. Toller, G.L., Horvath, J.E., Schally, A.V., Halmos, G., Varga, J.L., Groot, K., Chism, D., Zarandi, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Identification of a second transmembrane protein tyrosine phosphatase, IA-2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor of the 37-kDa tryptic fragment. Lu, J., Li, Q., Xie, H., Chen, Z.J., Borovitskaya, A.E., Maclaren, N.K., Notkins, A.L., Lan, M.S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. Specific regulation of the 100 kDa 2-5 A synthetase by protein kinase C. Raber, J., Eldar, H., Lehrer, R., Chebath, J., Livneh, E. Eur. Cytokine Netw. (1991) [Pubmed]
  6. A mouse cytomegalovirus glycoprotein retains MHC class I complexes in the ERGIC/cis-Golgi compartments. Ziegler, H., Thale, R., Lucin, P., Muranyi, W., Flohr, T., Hengel, H., Farrell, H., Rawlinson, W., Koszinowski, U.H. Immunity (1997) [Pubmed]
  7. Mouse disabled (mDab1): a Src binding protein implicated in neuronal development. Howell, B.W., Gertler, F.B., Cooper, J.A. EMBO J. (1997) [Pubmed]
  8. Isolation and characterization of BEN, a member of the TFII-I family of DNA-binding proteins containing distinct helix-loop-helix domains. Bayarsaihan, D., Ruddle, F.H. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. Alternative translation initiation site usage results in two functionally distinct forms of the GATA-1 transcription factor. Calligaris, R., Bottardi, S., Cogoi, S., Apezteguia, I., Santoro, C. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  10. The 37/40-kilodalton autoantigen in insulin-dependent diabetes mellitus is the putative tyrosine phosphatase IA-2. Passini, N., Larigan, J.D., Genovese, S., Appella, E., Sinigaglia, F., Rogge, L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  11. Baculovirus recombinant expressing a secreted form of a transmembrane carcinoma-associated antigen. Strassburg, C.P., Kasai, Y., Seng, B.A., Miniou, P., Zaloudik, J., Herlyn, D., Koprowski, H., Linnenbach, A.J. Cancer Res. (1992) [Pubmed]
  12. Release of guanosine triphosphate binding protein alpha subunits from mouse myocardial membranes: basic properties and their alterations in acute murine Chagas disease. Huang, H., Wittner, M., Tanowitz, H., Bilezikian, J.P., Morris, S.A., Huan, H. Cardiovasc. Res. (1995) [Pubmed]
  13. Identification and characterization of a Kunitz-type protease inhibitor in ascites fluid from patients with ovarian carcinoma. Kobayashi, H., Hirashima, Y., Sun, G.W., Ohi, H., Fujie, M., Terao, T. Int. J. Cancer (2000) [Pubmed]
  14. Increased iNOS activity is essential for hepatic epithelial tight junction dysfunction in endotoxemic mice. Han, X., Fink, M.P., Uchiyama, T., Yang, R., Delude, R.L. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  15. Multiple species and isoforms of Bordetella pertussis toxin substrates. Brabet, P., Pantaloni, C., Rouot, B., Toutant, M., Garcia-Sainz, A., Bockaert, J., Homburger, V. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  16. Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2+-dependent signaling protein which is mutated in human X-linked neuronal migration defects. Sossey-Alaoui, K., Hartung, A.J., Guerrini, R., Manchester, D.K., Posar, A., Puche-Mira, A., Andermann, E., Dobyns, W.B., Srivastava, A.K. Hum. Mol. Genet. (1998) [Pubmed]
  17. Regulation of interleukin 12 p40 expression through an NF-kappa B half-site. Murphy, T.L., Cleveland, M.G., Kulesza, P., Magram, J., Murphy, K.M. Mol. Cell. Biol. (1995) [Pubmed]
  18. Molecular cloning and expression of mammalian peroxisomal trans-2-enoyl-coenzyme A reductase cDNAs. Das, A.K., Uhler, M.D., Hajra, A.K. J. Biol. Chem. (2000) [Pubmed]
  19. Cyclic AMP-dependent protein kinase in Paramecium tetraurelia. Its purification and the production of monoclonal antibodies against both subunits. Hochstrasser, M., Nelson, D.L. J. Biol. Chem. (1989) [Pubmed]
  20. MHC and non-MHC-restricted recognition of filarial surface antigens in mice transplanted with adult Brugia malayi parasites. Kwan-Lim, G.E., Maizels, R.M. J. Immunol. (1990) [Pubmed]
  21. Pax5 (BSAP) regulates the murine immunoglobulin 3' alpha enhancer by suppressing binding of NF-alpha P, a protein that controls heavy chain transcription. Neurath, M.F., Max, E.E., Strober, W. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  22. Human T-cell leukemia virus type 1 Tax induction of NF-kappaB involves activation of the IkappaB kinase alpha (IKKalpha) and IKKbeta cellular kinases. Geleziunas, R., Ferrell, S., Lin, X., Mu, Y., Cunningham, E.T., Grant, M., Connelly, M.A., Hambor, J.E., Marcu, K.B., Greene, W.C. Mol. Cell. Biol. (1998) [Pubmed]
  23. Two species of human CRK cDNA encode proteins with distinct biological activities. Matsuda, M., Tanaka, S., Nagata, S., Kojima, A., Kurata, T., Shibuya, M. Mol. Cell. Biol. (1992) [Pubmed]
  24. Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor protein, and is expressed and released by Weri-Rb1 cells. Grayson, C., Reid, S.N., Ellis, J.A., Rutherford, A., Sowden, J.C., Yates, J.R., Farber, D.B., Trump, D. Hum. Mol. Genet. (2000) [Pubmed]
  25. Intracellular association of the protein product of the c-myc oncogene with the TATA-binding protein. Maheswaran, S., Lee, H., Sonenshein, G.E. Mol. Cell. Biol. (1994) [Pubmed]
  26. Apical localization of the alpha subunit of GTP-binding protein Go in choroidal and ciliated ependymocytes. Péraldi, S., Nguyen Than Dao, B., Brabet, P., Homburger, V., Rouot, B., Toutant, M., Bouille, C., Assenmacher, I., Bockaert, J., Gabrion, J. J. Neurosci. (1989) [Pubmed]
  27. Evidence of synergy between Thy-1 and CD3/TCR complex in signal delivery to murine thymocytes for cell death. Nakashima, I., Zhang, Y.H., Rahman, S.M., Yoshida, T., Isobe, K., Ding, L.N., Iwamoto, T., Hamaguchi, M., Ikezawa, H., Taguchi, R. J. Immunol. (1991) [Pubmed]
  28. A novel 40-kDa protein containing six repeats of an epidermal growth factor-like domain functions as a pattern recognition protein for lipopolysaccharide. Ju, J.S., Cho, M.H., Brade, L., Kim, J.H., Park, J.W., Ha, N.C., Söderhäll, I., Söderhäll, K., Brade, H., Lee, B.L. J. Immunol. (2006) [Pubmed]
  29. Two distinct porcine natural killer lytic trigger molecules as PNK-E/G7 molecular complex. Wierda, W.G., Johnson, B.D., Dato, M.E., Kim, Y.B. Cell. Immunol. (1993) [Pubmed]
  30. Characterization of glucocorticoid receptors in S49 mouse lymphoma cells by affinity labeling with [3H]dexamethasone 21-mesylate. Distelhorst, C.W., Kullman, L., Wasson, J. J. Steroid Biochem. (1987) [Pubmed]
  31. Influence of genes from the major histocompatibility complex on the antibody repertoire against culture filtrate antigens in mice infected with live Mycobacterium bovis BCG. Huygen, K., Drowart, A., Harboe, M., ten Berg, R., Cogniaux, J., Van Vooren, J.P. Infect. Immun. (1993) [Pubmed]
  32. Thy-1/CD3 coengagement promotes TCR signaling and enhances particularly tyrosine phosphorylation of the raft molecule LAT. Leyton, L., Quest, A.F., Bron, C. Mol. Immunol. (1999) [Pubmed]
  33. Modulation of CSF-1-regulated post-natal development with anti-CSF-1 antibody. Wei, S., Lightwood, D., Ladyman, H., Cross, S., Neale, H., Griffiths, M., Adams, R., Marshall, D., Lawson, A., McKnight, A.J., Stanley, E.R. Immunobiology (2005) [Pubmed]
  34. Keratin biosynthesis in normal mouse epithelia and in squamous cell carcinomas. mRNA-dependent alterations of the primary structure of distinct keratin subunits in tumors. Schweizer, J., Winter, H. J. Biol. Chem. (1983) [Pubmed]
  35. A 40-kDa epidermal growth factor/transforming growth factor alpha-binding domain produced by limited proteolysis of the extracellular domain of the epidermal growth factor receptor. Kohda, D., Odaka, M., Lax, I., Kawasaki, H., Suzuki, K., Ullrich, A., Schlessinger, J., Inagaki, F. J. Biol. Chem. (1993) [Pubmed]
  36. Agonist but not antagonist ligands induce conformational change in the mouse aryl hydrocarbon receptor as detected by partial proteolysis. Henry, E.C., Gasiewicz, T.A. Mol. Pharmacol. (2003) [Pubmed]
  37. Characterization of the non-functional Fas ligand of gld mice. Hahne, M., Peitsch, M.C., Irmler, M., Schröter, M., Lowin, B., Rousseau, M., Bron, C., Renno, T., French, L., Tschopp, J. Int. Immunol. (1995) [Pubmed]
  38. Insulin-like growth factor (IGF) binding proteins and insulin-like growth factor secretion by cultured chondrocyte cells: identification, characterization and ontogeny during cell differentiation. Bhaumick, B. Regul. Pept. (1993) [Pubmed]
  39. Activation of latent transforming growth factor-beta1 is induced by mannose 6-phosphate/insulin-like growth factor-II receptor. Yang, L., Tredget, E.E., Ghahary, A. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. (2000) [Pubmed]
  40. Insulin-stimulated microtubule-associated protein kinase is phosphorylated on tyrosine and threonine in vivo. Ray, L.B., Sturgill, T.W. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  41. Monoclonal, antigen-specific, T cell contrasuppressor factor expresses determinants of TCR alpha-chain (not necessarily TCR beta-chain), having a molecular mass of about 40 kDa. Paliwal, V., Friedman, A.M., Ptak, W., Askenase, P.W. J. Immunol. (1994) [Pubmed]
  42. A pertussis toxin-sensitive G-protein mediates some aspects of insulin action in BC3H-1 murine myocytes. Luttrell, L., Kilgour, E., Larner, J., Romero, G. J. Biol. Chem. (1990) [Pubmed]
  43. Purification and expression of gCap39. An intracellular and secreted Ca2(+)-dependent actin-binding protein enriched in mononuclear phagocytes. Johnston, P.A., Yu, F.X., Reynolds, G.A., Yin, H.L., Moomaw, C.R., Slaughter, C.A., Südhof, T.C. J. Biol. Chem. (1990) [Pubmed]
  44. Interaction of the erythrocyte lactate transporter (monocarboxylate transporter 1) with an integral 70-kDa membrane glycoprotein of the immunoglobulin superfamily. Poole, R.C., Halestrap, A.P. J. Biol. Chem. (1997) [Pubmed]
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