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

HAVCR1  -  hepatitis A virus cellular receptor 1

Homo sapiens

Synonyms: HAVCR, HAVCR-1, HAVcr-1, Hepatitis A virus cellular receptor 1, KIM-1, ...
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 HAVCR1


High impact information on HAVCR1


Chemical compound and disease context of HAVCR1


Biological context of HAVCR1

  • These features suggest that patterns of variation in HAVCR1 have been shaped by both positive and balancing natural selection in the course of primate evolution [14].
  • We describe the generation of 10 monoclonal antibodies against the extracellular domain of human KIM-1, the mapping of their binding sites, and their use in identifying various forms of the protein [15].
  • The extracellular domain of KIM-1 is composed of an immunoglobulin-like domain topping a long mucin-like domain, a structure that points to a possible role in cell adhesion by homology to several known adhesion proteins [15].
  • Two splice variants (a and b), of the human KIM-1 having identical extracellular domains, differ in their cytoplasmic domains and tissue distributions [15].
  • Nucleotide sequence analysis revealed that the amplified liver and kidney huHAVcr-1 cDNAs were identical and that they coded for a 359-amino-acid glycoprotein, termed huhavcr-1, which was approximately 79% identical to havcr-1 [16].

Anatomical context of HAVCR1

  • We show that human KIM-1b is expressed in adult kidney cell lines, and we demonstrate that a soluble form of KIM-1 is shed constitutively into the culture medium of the cell lines expressing endogenous or recombinant KIM-1b by membrane-proximal cleavage [15].
  • KIM-1 (kidney injury molecule-1) is a type I transmembrane glycoprotein expressed on dedifferentiated renal proximal tubule epithelial cells undergoing regeneration after toxic or ischemic injury [15].
  • We propose that the shedding of KIM-1 in the kidney undergoing regeneration constitutes an active mechanism allowing dedifferentiated regenerating cells to scatter on denuded patches of the basement membrane and reconstitute a continuous epithelial layer [15].
  • Hepatitis A virus receptor (HAVcr-1) and T-cell immunoglobulin- and mucin-domain-containing molecule (TIM)-3 were recently implicated as asthma susceptibility genes in the study of congenic mice [17].
  • A member of Tim family, TIM-1, is considered as a membrane protein that is associated with the development of Th2 biased immune responses and may be selectively expressed on Th2 cells [18].

Associations of HAVCR1 with chemical compounds

  • Release of soluble KIM-1 is enhanced by activating the cells with phorbol 12-myristate 13-acetate and can be inhibited with two metalloproteinase inhibitors, BB-94 (Batimastat) and GM6001 (Ilomastat), suggesting that the cleavage is mediated by a metalloproteinase [15].
  • These results indicate that the Cys-rich region of havcr-1 and its first N-glycosylation site are required for binding of protective MAb 190/4 and HAV receptor function [1].
  • Treatment of AGMK and cr5 cells with tunicamycin reduced binding of protective monoclonal Ab (MAb) 190/4, which suggested that N-glycans are required for binding of MAb 190/4 to havcr-1 [1].
  • Fifty % effective doses on day 3 of exposure to sho-saiko-to were 353.5 +/- 32.4 micrograms/ml for KIM-1 and 236.3 +/- 26.5 micrograms/ml for KMC-1 [4].
  • The addition of insulin increased the growth rate of all examined cell lines and partially inhibited the AFP secretion in those cell lines except KIM-1/c-4, while the addition of dexamethasone inhibited the growth and stimulated the AFP secretion in all of the cell lines [19].

Physical interactions of HAVCR1

  • Taken together, these data show that the activation of PKCtheta by the TCR and CD28 plays an important role in the assembly and activation of IKK complexes in the T cell membrane [20].
  • Beta 2-microglobulin-bound T-cell membrane components containing both human TL-like antigens and HLA(A, B, C) antigens were partially purified from Renex 30-solubilized membrane material of cells of a human T-cell-type leukemia cell line, HPB-ALL [21].

Regulatory relationships of HAVCR1


Other interactions of HAVCR1


Analytical, diagnostic and therapeutic context of HAVCR1

  • Western blot analysis with anti-GST2 Ab detected 62- and 65-kDa bands in AGMK cells and 59-, 62-, and 65-kDa bands in dog cells transfected with the HAVcr-1 cDNA (cr5 cells) but not in dog cells transfected with the vector alone (DR2 cells) [1].
  • METHODS: This work reports on the identification of human hepatitis A virus cellular receptor 1 (hHAVcr-1) as a differentially expressed gene in ccRCC using RNA-based arbitrarily primed polymerase chain reaction (RAP-PCR) [2].
  • Analysis of eluted material by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, and two-dimensional electrophoresis demonstrated the major proteins to be of Mr 56,000, pI 4.8-5.1 and Mr 60,000, pI 5.0-5.6, and these were radiolabeled, indicating an origin in part from the T-cell membrane [28].
  • Forty renal cell carcinoma (RCC) and 484 nonrenal tumors were analyzed by immunohistochemistry for expression of hKIM-1 (group 1) [29].
  • Tissue was examined for expression of hKIM-1, and cell-free urine supernatants were analyzed for hKIM-1 by ELISA [29].


  1. The Cys-rich region of hepatitis A virus cellular receptor 1 is required for binding of hepatitis A virus and protective monoclonal antibody 190/4. Thompson, P., Lu, J., Kaplan, G.G. J. Virol. (1998) [Pubmed]
  2. Hepatitis A virus receptor blocks cell differentiation and is overexpressed in clear cell renal cell carcinoma. Vilà, M.R., Kaplan, G.G., Feigelstock, D., Nadal, M., Morote, J., Porta, R., Bellmunt, J., Meseguer, A. Kidney Int. (2004) [Pubmed]
  3. Genetic Association Studies between the T Cell Immunoglobulin Mucin (TIM) Gene Locus and Childhood Atopic Dermatitis. Page, N.S., Jones, G., Stewart, G.J. Int. Arch. Allergy Immunol. (2006) [Pubmed]
  4. The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Yano, H., Mizoguchi, A., Fukuda, K., Haramaki, M., Ogasawara, S., Momosaki, S., Kojiro, M. Cancer Res. (1994) [Pubmed]
  5. Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. Liangos, O., Perianayagam, M.C., Vaidya, V.S., Han, W.K., Wald, R., Tighiouart, H., MacKinnon, R.W., Li, L., Balakrishnan, V.S., Pereira, B.J., Bonventre, J.V., Jaber, B.L. J. Am. Soc. Nephrol. (2007) [Pubmed]
  6. Cotransfection of ICAM-1 and HLA-DR reconstitutes human antigen-presenting cell function in mouse L cells. Altmann, D.M., Hogg, N., Trowsdale, J., Wilkinson, D. Nature (1989) [Pubmed]
  7. TIM Family of Genes in Immunity and Tolerance. Kuchroo, V.K., Meyers, J.H., Umetsu, D.T., Dekruyff, R.H. Adv. Immunol. (2006) [Pubmed]
  8. Structures of T Cell Immunoglobulin Mucin Receptors 1 and 2 Reveal Mechanisms for Regulation of Immune Responses by the TIM Receptor Family. Santiago, C., Ballesteros, A., Tami, C., Martínez-Muñoz, L., Kaplan, G.G., Casasnovas, J.M. Immunity (2007) [Pubmed]
  9. Prevention of acute allograft rejection by antibody targeting of TIRC7, a novel T cell membrane protein. Utku, N., Heinemann, T., Tullius, S.G., Bulwin, G.C., Beinke, S., Blumberg, R.S., Beato, F., Randall, J., Kojima, R., Busconi, L., Robertson, E.S., Schülein, R., Volk, H.D., Milford, E.L., Gullans, S.R. Immunity (1998) [Pubmed]
  10. The 26-kD transmembrane form of tumor necrosis factor alpha on activated CD4+ T cell clones provides a costimulatory signal for human B cell activation. Aversa, G., Punnonen, J., de Vries, J.E. J. Exp. Med. (1993) [Pubmed]
  11. Reactivity of antisera to endogenous primate retrovirus with a human T cell membrane protein: recognition of a nonviral glycoprotein by antibodies directed only against carbohydrate components. Markenson, J.A., Snyder, H.W. J. Immunol. (1984) [Pubmed]
  12. Effect of ASTA Z 7557 (INN mafosfamide) a precursor of 4-hydroxy-cyclophosphamide on human T-lymphocytes' Fc-receptors and immunoregulatory functions. Saal, J.G., Hadam, M., Frank, F., Rautenstrauch, H., Fritz, P. Investigational new drugs. (1984) [Pubmed]
  13. T-cell membrane-associated serine protease, tryptase TL2, binds human immunodeficiency virus type 1 gp120 and cleaves the third-variable-domain loop of gp120. Neutralizing antibodies of human immunodeficiency virus type 1 inhibit cleavage of gp120. Niwa, Y., Yano, M., Futaki, S., Okumura, Y., Kido, H. Eur. J. Biochem. (1996) [Pubmed]
  14. Evidence for natural selection in the HAVCR1 gene: high degree of amino-acid variability in the mucin domain of human HAVCR1 protein. Nakajima, T., Wooding, S., Satta, Y., Jinnai, N., Goto, S., Hayasaka, I., Saitou, N., Guan-Jun, J., Tokunaga, K., Jorde, L.B., Emi, M., Inoue, I. Genes Immun. (2005) [Pubmed]
  15. Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration. Bailly, V., Zhang, Z., Meier, W., Cate, R., Sanicola, M., Bonventre, J.V. J. Biol. Chem. (2002) [Pubmed]
  16. The human homolog of HAVcr-1 codes for a hepatitis A virus cellular receptor. Feigelstock, D., Thompson, P., Mattoo, P., Zhang, Y., Kaplan, G.G. J. Virol. (1998) [Pubmed]
  17. Insertion/deletion coding polymorphisms in hHAVcr-1 are not associated with atopic asthma in the Japanese population. Noguchi, E., Nakayama, J., Kamioka, M., Ichikawa, K., Shibasaki, M., Arinami, T. Genes Immun. (2003) [Pubmed]
  18. The association of the exon 4 variations of Tim-1 gene with allergic diseases in a Korean population. Chae, S.C., Song, J.H., Lee, Y.C., Kim, J.W., Chung, H.T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. Hormonal control of alpha-fetoprotein secretion in human hepatoma cell lines proliferating in chemically defined medium. Nakabayashi, H., Taketa, K., Yamane, T., Oda, M., Sato, J. Cancer Res. (1985) [Pubmed]
  20. The physical association of protein kinase C theta with a lipid raft-associated inhibitor of kappa B factor kinase (IKK) complex plays a role in the activation of the NF-kappa B cascade by TCR and CD28. Khoshnan, A., Bae, D., Tindell, C.A., Nel, A.E. J. Immunol. (2000) [Pubmed]
  21. Separation and comparison of human TL-like antigens and HLA(A, B, C) antigens expressed on cultured T cells. Tokuyama, H., Tanigaki, N. Immunogenetics (1981) [Pubmed]
  22. Contact with T cells modulates monocyte IL-10 production: role of T cell membrane TNF-alpha. Parry, S.L., Sebbag, M., Feldmann, M., Brennan, F.M. J. Immunol. (1997) [Pubmed]
  23. Human recombinant interleukin-2 is mitogenic to human lymphocytes. Mookerjee, B.K., Pauly, J.L. J. Leukoc. Biol. (1985) [Pubmed]
  24. T helper cells. Noelle, R., Snow, E.C. Curr. Opin. Immunol. (1992) [Pubmed]
  25. Human mast cells release metalloproteinase-9 on contact with activated T cells: juxtacrine regulation by TNF-alpha. Baram, D., Vaday, G.G., Salamon, P., Drucker, I., Hershkoviz, R., Mekori, Y.A. J. Immunol. (2001) [Pubmed]
  26. Inhibition of in vitro and in vivo T cell responses by recombinant human Tim-1 extracellular domain proteins. Mesri, M., Smithson, G., Ghatpande, A., Chapoval, A., Shenoy, S., Boldog, F., Hackett, C., Pena, C.E., Burgess, C., Bendele, A., Shimkets, R.A., Starling, G.C. Int. Immunol. (2006) [Pubmed]
  27. T cell receptor/CD3 and CD28 use distinct intracellular signaling pathways. Van Lier, R.A., Brouwer, M., De Groot, E.D., Kramer, I., Aarden, L.A., Verhoeven, A.J. Eur. J. Immunol. (1991) [Pubmed]
  28. Structural studies of T lymphocyte Fc receptors. Association of Gc protein with IgG binding to Fc gamma. Petrini, M., Galbraith, R.M., Emerson, D.L., Nel, A.E., Arnaud, P. J. Biol. Chem. (1985) [Pubmed]
  29. Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. Han, W.K., Alinani, A., Wu, C.L., Michaelson, D., Loda, M., McGovern, F.J., Thadhani, R., Bonventre, J.V. J. Am. Soc. Nephrol. (2005) [Pubmed]
WikiGenes - Universities