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Gene Review

ITIH1  -  inter-alpha-trypsin inhibitor heavy chain 1

Homo sapiens

Synonyms: H1P, IATIH, IGHEP1, ITI heavy chain H1, ITI-HC1, ...
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Disease relevance of ITIH1

  • By using cDNA probes, a recombinant DNA phage has been isolated from a bacteriophage DNA library, which contains sequences flanking the 5' end of the ITIH3 gene and the 3' end of the ITIH1 gene [1].
  • A case of pretibial myxedema associated with Graves' disease: an immunohistochemical study of serum-derived hyaluronan-associated protein [2].

High impact information on ITIH1

  • SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum [3].
  • Leukocytes infiltrated to the synovium were strongly positive for HA, SHAP, and CD44 on their surfaces, suggesting a role for the adhesion-enhancing effect of SHAP in pathogenesis [3].
  • We therefore examined the effect of SHAP on the CD44-HA interaction-mediated lymphocyte adhesion [3].
  • We previously found that a covalent complex of SHAPs (serum-derived hyaluronan-associated proteins), the heavy chains of inter-alpha-trypsin inhibitor family molecules, with hyaluronan (HA) is accumulated in synovial fluid of patients with rheumatoid arthritis, and the complex is circulated in patient plasma at high concentrations [4].
  • We previously showed that serum-derived 85-kDa proteins (SHAPs, serum-derived hyaluronan associated proteins) are firmly bound to hyaluronan (HA) synthesized by cultured fibroblasts [5].

Biological context of ITIH1


Anatomical context of ITIH1

  • The SHAP-HA complex purified from synovial fluid of the patients by three sequential CsCl isopycnic centrifugations was heterogeneous in density, and the fractions with different densities had distinct SHAP-to-HA ratios [4].
  • To clarify the mechanism of the deposition of HA in the dermis, we employed an antibody against serum-derived hyaluronan-associated protein (SHAP) [2].
  • Roentgen manifestations of these disorders include abnormalities of vertebral body shap or density, loss of intervertebral disc space, formation of a paraspinal mass, abnormal curvature and subluxation, disc calcification, and pedicle destruction [9].
  • It was confined to the Epiphysis cerbri and was similar in time course and shap to, though smaller as, the ERP of the isolated retina [10].

Other interactions of ITIH1

  • 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 [11].
  • A reverse-transcriptase polymerase chain reaction mapping analysis of liver mRNA identified the two types of the mRNA for ITI heavy chain H1 [12].
  • We found that the deleted DNA includes the functional epsilon gene, and that the breakpoints are located within a 2 kilobase Bam HI/Sac I region of both the IGHEP1 and IGHE genes [13].

Analytical, diagnostic and therapeutic context of ITIH1

  • Electron microscopy of honeycomb channels inside weathered feldspars of the Shap granite (northwest England) has revealed modern bacteria, perhaps indicative of Archean ones [14].


  1. Tandem orientation of the inter-alpha-trypsin inhibitor heavy chain H1 and H3 genes. Diarra-Mehrpour, M., Bourguignon, J., Sarafan, N., Bost, F., Sesboüé, R., Muschio-Bonnet, F., Martin, J.P. Biochim. Biophys. Acta (1994) [Pubmed]
  2. A case of pretibial myxedema associated with Graves' disease: an immunohistochemical study of serum-derived hyaluronan-associated protein. Shishido, M., Kuroda, K., Tsukifuji, R., Fujita, M., Shinkai, H. J. Dermatol. (1995) [Pubmed]
  3. SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. Zhuo, L., Kanamori, A., Kannagi, R., Itano, N., Wu, J., Hamaguchi, M., Ishiguro, N., Kimata, K. J. Biol. Chem. (2006) [Pubmed]
  4. Molecular heterogeneity of the SHAP-hyaluronan complex. Isolation and characterization of the complex in synovial fluid from patients with rheumatoid arthritis. Yingsung, W., Zhuo, L., Morgelin, M., Yoneda, M., Kida, D., Watanabe, H., Ishiguro, N., Iwata, H., Kimata, K. J. Biol. Chem. (2003) [Pubmed]
  5. Evidence for the covalent binding of SHAP, heavy chains of inter-alpha-trypsin inhibitor, to hyaluronan. Zhao, M., Yoneda, M., Ohashi, Y., Kurono, S., Iwata, H., Ohnuki, Y., Kimata, K. J. Biol. Chem. (1995) [Pubmed]
  6. Linkage studies of cholestasis familiaris groenlandica/Byler-like disease with polymorphic protein and blood group markers. Eiberg, H., Nielsen, I.M. Hum. Hered. (1993) [Pubmed]
  7. The polymorphism of the plasma inter-alpha-trypsin inhibitor (ITI) and its relationship to the heavy chain H1 subunit gene (ITIH1) at 3p211-212. Vogt, U., Sesboüé, R., Bourguignon, J., Diarra-Mehrpour, M., Martin, J.P., Cleve, H. Hum. Genet. (1994) [Pubmed]
  8. Molecular basis of inter-alpha-trypsin inhibitor heavy chain H1 (ITIH1) polymorphism. Ding, M., Umetsu, K., Yuasa, I., Sato, M., Harada, A., Suzuki, T. Hum. Genet. (1995) [Pubmed]
  9. Roentgen signs of emergent spines. Resnick, D. Radiol. Clin. North Am. (1978) [Pubmed]
  10. Early receptor potential from the pineal photoreceptor. Morita, Y., Dodt, E. Pflugers Arch. (1975) [Pubmed]
  11. 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]
  12. Isolation and characterization of the human inter-alpha-trypsin inhibitor heavy-chain H1 gene. Bost, F., Bourguignon, J., Martin, J.P., Sesboüé, R., Thiberville, L., Diarra-Mehrpour, M. Eur. J. Biochem. (1993) [Pubmed]
  13. Defining the breakpoint of a multigene deletion in the immunoglobulin heavy chain gene cluster. Chen, Z.Q., Hofker, M.H., Cox, D.W. Immunogenetics (1995) [Pubmed]
  14. Biochemical evolution III: polymerization on organophilic silica-rich surfaces, crystal-chemical modeling, formation of first cells, and geological clues. Smith, J.V., Arnold, F.P., Parsons, I., Lee, M.R. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
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