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ITIH4  -  inter-alpha-trypsin inhibitor heavy chain...

Homo sapiens

Synonyms: GP120, Gp120, H4P, IHRP, ITI heavy chain H4, ...
 
 
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Disease relevance of ITIH4

  • Hypercholesterolemia associated with splice-junction variation of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) gene [1].
  • We demonstrate that 2 host response proteins previously identified as candidate markers for early stage ovarian cancer, transthyretin and inter-alpha trypsin inhibitor heavy chain 4 (ITIH4), are posttranslationally modified [2].
  • The serum concentration of the inter-alpha trypsin inhibitor heavy chain 4 protein (ITIH4) increases (from 1.4-3 times) in male patients suffering of different acute-phase processes (myocardial infarction, unstable angina or programmed surgery) [3].
  • A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope [4].
  • Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus [5].
 

Psychiatry related information on ITIH4

 

High impact information on ITIH4

  • HIV-1 entry into cells is mediated by the envelope glycoprotein receptor-binding (gp120) and membrane fusion-promoting (gp41) subunits [4].
  • Molecular mimicry between the rabies virus glycoprotein and human immunodeficiency virus-1 GP120: cross-reacting antibodies induced by rabies vaccination [7].
  • In contrast to the mannose-binding proteins, which have a 50-100-fold decreased antiviral activity against the UDA-exposed mutant viruses, UDA has decreased anti-HIV activity to a very limited extent, even against those mutant virus strains that lack at least 9 of 22 ( approximately 40%) glycosylation sites in their GP120 envelope [8].
  • The selected viruses at passage 8 contained five amino acid substitutions in the V3 loop without any other mutations in GP120 and showed 15-fold resistance compared with the parental virus [9].
  • Serum from mice immunized with MAP-911 had lower titer for oligomannose-9 than those elicited by MAP-D002 under the same conditions, but both immunogens elicited antibodies that can block the binding of GP120 to dendritic cells [10].
 

Chemical compound and disease context of ITIH4

 

Biological context of ITIH4

  • Biochemical, mutagenesis, and fluorescence studies demonstrate that SANT2 binds to a carboxyl-terminal fragment that corresponds to the last third of the new ITIH4 isoform sequence (residues 588-930) [15].
  • These data suggest that genetic variation at ITIH4 locus is one of the likely candidate determinants for plasma cholesterol metabolisms [1].
  • Within the human PRR, a domain that is absent in rat can be transcribed or deleted by alternative splicing which results in two variant forms of human H4P [16].
  • Using the hepatocarcinoma HepG2 cell line we have observed up-regulation of ITIH4 mRNA expression upon dose-response treatments with interleukin-6 (IL-6) [3].
  • A porcine genomic library was screened for clones containing the promoter of the major acute-phase protein in pigs, inter-alpha-trypsin heavy chain 4 (ITIH4) [17].
 

Anatomical context of ITIH4

  • We hypothesize that vaccination with gp120 expressing alpha-gal epitopes (gp120(alphagal)) results in in vivo formation of immune complexes with anti-Gal, which targets vaccines for effective uptake by antigen-presenting cells (APC), due to interaction between the Fc portion of the antibody and Fcgamma receptors on APC [18].
  • This in turn results in effective transport of the vaccine to lymph nodes and effective processing and presentation of gp120 immunogenic peptides by APC for eliciting a strong anti-gp120 immune response [18].
  • Rapid in vivo induction of HIV-specific CD8+ cytotoxic T lymphocytes by a 15-amino acid unmodified free peptide from the immunodominant V3-loop of GP120 [19].
  • In the present experiments the gross behavioural, electrocortical (ECoG) and neuropathological effects of GP120 were studied in rats chronically microinfused into one lateral cerebral ventricle (i.c.v.) via mini-osmotic pumps [20].
  • In addition, acute i.c.v. injection of a subconvulsive dose (500 ng) of N-methyl-D-aspartate (NMDA) did not produce motor and ECoG epileptogenic discharges in rats which received 1 h beforehand a dose of GP120 (900 ng) into the dorsal hippocampus ipsilateral to the injected ventricle; per se this dose of GP120 was ineffective [20].
 

Associations of ITIH4 with chemical compounds

  • The H4P heavy chain of inter-alpha-inhibitor family largely differs in the structure and synthesis of its prolin-rich region from rat to human [16].
  • IL-1beta, although up-regulating the expression of alpha(1)-acid glycoprotein in these cells, did not induce any effect in the expression of ITIH4 [3].
  • IHRP was readily cleaved into 85- and 35-kDa fragments when plasma was incubated at 37 degrees C. The cleaved site, Arg-Arg-Leu, was within a proline-rich region [21].
  • Further, we have identified five electrophoretically distinct renaturable CD40-regulated serine/threonine-specific protein kinases (PK120, PK93, PK76, PK55, and PK48) that showed markedly increased in vitro activity after CD40 stimulation [22].
  • N-glycosidase F digestion of 35SO4(2-)-labelled envelope proteins removed virtually all radiolabel from gp160, gp120, and gp41, indicating that sulfate was linked to the carbohydrate chains of the glycoprotein [23].
 

Physical interactions of ITIH4

  • Here, we identified a new variant of human inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) that also interacts with the SANT2 domain of HTJ1 [15].
 

Regulatory relationships of ITIH4

  • Various drugs targeted to the different steps of viral replication have been selected, but drugs such as soluble CD4 or dextran derivatives aimed to inhibit or interfere with the GP120-CD4 attachment step have shown little or no clinical benefit [24].
 

Other interactions of ITIH4

  • We determined that the human ITIH1, ITIH3, and ITIH4 genes are closely linked within a 45-kilobase pair [25].
  • Therefore, in contrast to what is seen for the ITIH1 to -3 genes, the rat and human ITIH4 gene transcriptions and products thereof present marked differences, which suggests species-specific functions for I alpha IH4P [16].
  • 8. N-Glycanase treatment decreased the molecular weight of GP120 by 15 kDa [26].
  • Role of CD4 hinge region in GP120 utilization by immunoglobulin domain 1 [27].
  • Peptide T blocks GP120/CCR5 chemokine receptor-mediated chemotaxis [28].
 

Analytical, diagnostic and therapeutic context of ITIH4

  • BACKGROUND: Several proteolytically derived fragments from the proline-rich region (PRR) of human inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) have been identified by surface-enhanced or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS or MALDI-TOF-MS) as potential disease markers [29].
  • Assignment of the porcine inter-alpha trypsin inhibitor heavy chain 4 (ITIH4) gene to SSC13q2.1-->q2.2 by fluorescence in situ hybridization and radiation hybrid mapping [30].
  • Western-blot analysis of human plasma revealed that only a 120 kDa protein, GP120, reacted with anti-GP57 antibody [26].
  • Northern blot analysis indicated that IHRP was predominantly synthesized in liver [31].
  • From Southern blot analysis, it was tentatively concluded that ITIHL1 is a single copy gene [31].

References

  1. Hypercholesterolemia associated with splice-junction variation of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) gene. Fujita, Y., Ezura, Y., Emi, M., Sato, K., Takada, D., Iino, Y., Katayama, Y., Takahashi, K., Kamimura, K., Bujo, H., Saito, Y. J. Hum. Genet. (2004) [Pubmed]
  2. Classification of cancer types by measuring variants of host response proteins using SELDI serum assays. Fung, E.T., Yip, T.T., Lomas, L., Wang, Z., Yip, C., Meng, X.Y., Lin, S., Zhang, F., Zhang, Z., Chan, D.W., Weinberger, S.R. Int. J. Cancer (2005) [Pubmed]
  3. ITIH4 serum concentration increases during acute-phase processes in human patients and is up-regulated by interleukin-6 in hepatocarcinoma HepG2 cells. Piñeiro, M., Alava, M.A., González-Ramón, N., Osada, J., Lasierra, P., Larrad, L., Piñeiro, A., Lampreave, F. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  4. A human monoclonal antibody neutralizes diverse HIV-1 isolates by binding a critical gp41 epitope. Miller, M.D., Geleziunas, R., Bianchi, E., Lennard, S., Hrin, R., Zhang, H., Lu, M., An, Z., Ingallinella, P., Finotto, M., Mattu, M., Finnefrock, A.C., Bramhill, D., Cook, J., Eckert, D.M., Hampton, R., Patel, M., Jarantow, S., Joyce, J., Ciliberto, G., Cortese, R., Lu, P., Strohl, W., Schleif, W., McElhaugh, M., Lane, S., Lloyd, C., Lowe, D., Osbourn, J., Vaughan, T., Emini, E., Barbato, G., Kim, P.S., Hazuda, D.J., Shiver, J.W., Pessi, A. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus. Chirmule, N., Kalyanaraman, V.S., Oyaizu, N., Slade, H.B., Pahwa, S. Blood (1990) [Pubmed]
  6. Effect of GP120 on glutathione peroxidase activity in cortical cultures and the interaction with steroid hormones. Brooke, S.M., McLaughlin, J.R., Cortopassi, K.M., Sapolsky, R.M. J. Neurochem. (2002) [Pubmed]
  7. Molecular mimicry between the rabies virus glycoprotein and human immunodeficiency virus-1 GP120: cross-reacting antibodies induced by rabies vaccination. Bracci, L., Ballas, S.K., Spreafico, A., Neri, P. Blood (1997) [Pubmed]
  8. Carbohydrate-binding agents cause deletions of highly conserved glycosylation sites in HIV GP120: a new therapeutic concept to hit the achilles heel of HIV. Balzarini, J., Van Laethem, K., Hatse, S., Froeyen, M., Peumans, W., Van Damme, E., Schols, D. J. Biol. Chem. (2005) [Pubmed]
  9. Isolation of TAK-779-resistant HIV-1 from an R5 HIV-1 GP120 V3 loop library. Yusa, K., Maeda, Y., Fujioka, A., Monde, K., Harada, S. J. Biol. Chem. (2005) [Pubmed]
  10. Antigenic properties of peptide mimotopes of HIV-1-associated carbohydrate antigens. Pashov, A., Canziani, G., Monzavi-Karbassi, B., Kaveri, S.V., Macleod, S., Saha, R., Perry, M., Vancott, T.C., Kieber-Emmons, T. J. Biol. Chem. (2005) [Pubmed]
  11. Brucella abortus conjugated with a gp120 or V3 loop peptide derived from human immunodeficiency virus (HIV) type 1 induces neutralizing anti-HIV antibodies, and the V3-B. abortus conjugate is effective even after CD4+ T-cell depletion. Golding, B., Inman, J., Highet, P., Blackburn, R., Manischewitz, J., Blyveis, N., Angus, R.D., Golding, H. J. Virol. (1995) [Pubmed]
  12. Interferon-gamma decreases cell surface expression of galactosyl ceramide, the receptor for HIV-1 GP120 on human colonic epithelial cells. Yahi, N., Spitalnik, S.L., Stefano, K.A., De Micco, P., Gonzalez-Scarano, F., Fantini, J. Virology (1994) [Pubmed]
  13. Role of the V2, V3, and CD4-binding domains of GP120 in curdlan sulfate neutralization sensitivity of HIV-1 during infection of T lymphocytes. Jagodzinski, P.P., Wustner, J., Kmieciak, D., Wasik, T.J., Fertala, A., Sieron, A.L., Takahashi, M., Tsuji, T., Mimura, T., Fung, M.S., Gorny, M.K., Kloczewiak, M., Kaneko, Y., Kozbor, D. Virology (1996) [Pubmed]
  14. Macrophage behavior associated with acute and chronic exposure to HIV GP120, morphine and anandamide: endothelial implications. Stefano, G.B., Salzet, M., Rialas, C.M., Mattocks, D., Fimiani, C., Bilfinger, T.V. International journal of cardiology. (1998) [Pubmed]
  15. BIP co-chaperone MTJ1/ERDJ1 interacts with inter-alpha-trypsin inhibitor heavy chain 4. Kroczynska, B., King-Simmons, L., Alloza, L., Alava, M.A., Elguindi, E.C., Blond, S.Y. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  16. The H4P heavy chain of inter-alpha-inhibitor family largely differs in the structure and synthesis of its prolin-rich region from rat to human. Soury, E., Olivier, E., Daveau, M., Hiron, M., Claeyssens, S., Risler, J.L., Salier, J.P. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  17. Isolation and characterization of the promoter and partial enhancer region of the porcine inter-alpha-trypsin inhibitor heavy chain 4 gene. Harraghy, N., Mitchell, T.J. Clin. Diagn. Lab. Immunol. (2005) [Pubmed]
  18. Increased immunogenicity of human immunodeficiency virus gp120 engineered to express Galalpha1-3Galbeta1-4GlcNAc-R epitopes. Abdel-Motal, U., Wang, S., Lu, S., Wigglesworth, K., Galili, U. J. Virol. (2006) [Pubmed]
  19. Rapid in vivo induction of HIV-specific CD8+ cytotoxic T lymphocytes by a 15-amino acid unmodified free peptide from the immunodominant V3-loop of GP120. Sastry, K.J., Nehete, P.N., Venkatnarayanan, S., Morkowski, J., Platsoucas, C.D., Arlinghaus, R.B. Virology (1992) [Pubmed]
  20. Intracerebral injection of human immunodeficiency virus type 1 coat glycoprotein GP120 does not produce neurodegeneration in rats. Bagetta, G., Finazzi-Agrò, A., Palma, E., Nisticò, G. Neurosci. Lett. (1994) [Pubmed]
  21. Cloning and characterization of cDNA for inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP), a novel human plasma glycoprotein. Saguchi, K., Tobe, T., Hashimoto, K., Sano, Y., Nakano, Y., Miura, N.H., Tomita, M. J. Biochem. (1995) [Pubmed]
  22. Stimulation of protein tyrosine phosphorylation, phosphoinositide turnover, and multiple previously unidentified serine/threonine-specific protein kinases by the Pan-B-cell receptor CD40/Bp50 at discrete developmental stages of human B-cell ontogeny. Uckun, F.M., Schieven, G.L., Dibirdik, I., Chandan-Langlie, M., Tuel-Ahlgren, L., Ledbetter, J.A. J. Biol. Chem. (1991) [Pubmed]
  23. Sulfation of the human immunodeficiency virus envelope glycoprotein. Bernstein, H.B., Compans, R.W. J. Virol. (1992) [Pubmed]
  24. Current use of anti-HIV drugs in AIDS. Clumeck, N. J. Antimicrob. Chemother. (1993) [Pubmed]
  25. Human inter-alpha-trypsin inhibitor heavy chain H3 gene. Genomic organization, promoter analysis, and gene linkage. Diarra-Mehrpour, M., Sarafan, N., Bourguignon, J., Bonnet, F., Bost, F., Martin, J.P. J. Biol. Chem. (1998) [Pubmed]
  26. Purification and characterization of a novel glycoprotein which has significant homology to heavy chains of inter-alpha-trypsin inhibitor family from human plasma. Choi-Miura, N.H., Sano, Y., Oda, E., Nakano, Y., Tobe, T., Yanagishita, T., Taniyama, M., Katagiri, T., Tomita, M. J. Biochem. (1995) [Pubmed]
  27. Role of CD4 hinge region in GP120 utilization by immunoglobulin domain 1. Murray, J.L., Hu, Q.X., Navenot, J.M., Peiper, S.C. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  28. Peptide T blocks GP120/CCR5 chemokine receptor-mediated chemotaxis. Redwine, L.S., Pert, C.B., Rone, J.D., Nixon, R., Vance, M., Sandler, B., Lumpkin, M.D., Dieter, D.J., Ruff, M.R. Clin. Immunol. (1999) [Pubmed]
  29. Quantification of fragments of human serum inter-alpha-trypsin inhibitor heavy chain 4 by a surface-enhanced laser desorption/ionization-based immunoassay. Song, J., Patel, M., Rosenzweig, C.N., Chan-Li, Y., Sokoll, L.J., Fung, E.T., Choi-Miura, N.H., Goggins, M., Chan, D.W., Zhang, Z. Clin. Chem. (2006) [Pubmed]
  30. Assignment of the porcine inter-alpha trypsin inhibitor heavy chain 4 (ITIH4) gene to SSC13q2.1-->q2.2 by fluorescence in situ hybridization and radiation hybrid mapping. Kuiper, H., Spötter, A., Drögemüller, C., Brenig, B., Leeb, T., Distl, O. Cytogenet. Cell Genet. (2001) [Pubmed]
  31. Mapping of human inter-alpha-trypsin inhibitor family heavy chain-related protein gene (ITIHL1) to human chromosome 3p21-->p14. Tobe, T., Saguchi, K., Hashimoto, K., Miura, N.H., Tomita, M., Li, F., Wang, Y., Minoshima, S., Shimizu, N. Cytogenet. Cell Genet. (1995) [Pubmed]
 
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