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Gene Review

RCHY1  -  ring finger and CHY zinc finger domain...

Homo sapiens

Synonyms: ARNIP, Androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, CHIMP, DKFZp586C1620, ...
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Disease relevance of RCHY1

  • In addition, overexpression of hPIRH2 protein was detected in 73 of 82 (89%) resected prostate cancers, with a strong correlation between increased hPIRH2 expression and aggressive disease, as signified by high Gleason sum scores and the presence of metastatic disease (P = <0.0001 and 0.0004, respectively) [1].
  • We have previously reported that Pirh2 was overexpressed in human and murine lung cancers as compared to uninvolved lung tissue [2].
  • These studies indicate that infusions of autologous, in vitro-primed CTC are accompanied by little clinical toxicity in the chimp model but that they may be weakly immunogenic [3].
  • We assessed sensitivity and reproducibility on a well-characterized panel of sera (EUROHEP), a Chimp Rodney plasma pool, and samples from IFN-treated and -untreated patients with chronic hepatitis C caused by different HCV genotypes [4].
  • Although there are few shared major histocompatibility complex (MHC) alleles between human and chimp, there is considerable overlap in binding repertoires for epitopes of HIV-1 and HBV [5].

Psychiatry related information on RCHY1


High impact information on RCHY1

  • Furthermore, Pirh2 represses p53 functions including p53-dependent transactivation and growth inhibition [7].
  • Comparative genomics. Gene expression differs in human and chimp brains [8].
  • One milliliter of a 10(-1) dilution containing more than 10 chimp infecting units were inactivated in the presence of 1/2000 formalin or by heating at 100 degrees C for 5 min and then given to four other chimps [9].
  • When they were subsequently challenged, however, by a chimp inoculum containing viruslike particles known to induce non-A, non-B hepatitis with cytoplasmic tubular ultrastructures, they developed high SGPT levels and these characteristic ultrastructures in their hepatocytes [10].
  • We compared human DNA sequences with draft and high-quality versions of the corresponding chimpanzee loci to reveal the overall high quality of the chimp WD sequence [11].

Biological context of RCHY1

  • Differential response between the p53 ubiquitin-protein ligases Pirh2 and MdM2 following DNA damage in human cancer cells [2].
  • In addition, the human ARNIP protein was found to be encoded by nine exons spanning 32 kb on chromosome 4q21 [12].
  • Genomics. Building a case for sequencing the chimp [13].
  • We aligned 7628 chimpanzee virtual transcripts and 5524 chimp ESTs to the 4x chimp draft genome assembly and identified polymorphisms in chimpanzee that also occurred in the human single nucleotide polymorphism database (dbSNP) [14].
  • Moreover, the 3-Mb DNA segment, flanked by the duplications, is inverted in the mouse genome when compared with the orientation in human and chimp [15].

Anatomical context of RCHY1

  • Expression of the approximately 1.7 kb ARNIP mRNA was detected in various tissues by Northern blotting, but was highest in mouse testes, kidney and several neuronal cell lines [12].
  • Baboon bone marrow cDNA was amplified by PCR using primers specific for the signal peptide-encoding region of human CR1 and the 3' region of chimp CR1b [16].
  • HIV-1DH12 tissue culture infections were characterized by extremely rapid replication kinetics, profound cytopathicity, and tropism for chimp and human PBMC, primary human macrophage, and several human T-cell lines [17].
  • Simultaneous probing of multiple endogenous CD33rSiglecs on circulating blood cells of human, chimp, or gorilla suggests that the binding differences observed for Siglec-9 are representative of multiple CD33rSiglecs [18].
  • Pan species are unique in having long metacarpals relative to ulnar length, demonstrating that they probably differ from the common chimp-human ancestor, and also that developmental mechanisms can be altered to results in differential growth of individual forelimb segments [19].

Associations of RCHY1 with chemical compounds

  • Mutation of a single cysteine residue in the ARNIP RING-H2 domain (Cys145Ala) abolished this E3 ubiquitin ligase activity [12].
  • A novel AR N-terminal-interacting protein (ARNIP) was isolated using the yeast two-hybrid system and its interaction with amino acids 11-172 of the normal or corresponding region of the polyglutamine-expanded human AR confirmed by glutathione S-transferase pulldown assays [12].
  • Residue 255 is also Arg in human and chimp [20].
  • Chimp C4A and C4B reacted with human and mouse (monoclonal) anti-C4B and human anti-Ch1 but neither reacted with monoclonal anti-C4A or human anti-Ch2, Ch3, Rg1, or Rg2 [21].
  • During her annual physical examination, while maintained under ketamine anesthesia, the chimp was skin tested intradermally for respiratory allergies prevalent in the Sacramento area, and blood was drawn for "in vitro" evaluation [22].

Physical interactions of RCHY1

  • We show that Pirh2-p53 interaction is dependent on the C-terminal zinc binding module of Pirh2, which binds to the tetramerization domain of p53 [23].

Regulatory relationships of RCHY1


Other interactions of RCHY1

  • Collectively, our data establish hPIRH2 as a key modulator of AR function, opening a new direction for targeted therapy in aggressive human prostate cancer [1].
  • There are at least three different ubiquitin ligases that can regulate p53 in an autoregulatory manner: MDM-2, Cop-1 and Pirh-2 [24].
  • We conclude that Pirh2 operates in a distinct manner from MDM2 in response to DNA damage in cancer cells [2].
  • We have previously shown that the AR coregulator TIP60 can interact with human PIRH2 (hPIRH2) [1].
  • The first 6.5 SCRs matched 100% with the predicted human CR1L sequence, while the second half of SCR 7 was homologous to the comparable chimp CR1L sequence but with a stop codon [25].

Analytical, diagnostic and therapeutic context of RCHY1

  • To determine how Pirh2 may mediate lung tumorigenesis, we evaluated Pirh2 expression in human and mouse lung tumor samples and paired normal lung tissues using immunoblot analysis and immunohistochemistry [26].
  • Based on Southern blotting studies of primates and of humans drawn from diverse populations, we conclude that both the X-Y transposition and the subsequent, LINE-mediated Yp inversion occurred after the divergence of hominid and chimp lineages but before the radiation of extant human populations [27].
  • Further sequence analysis suggests that chimp, dog and frog nyctalopins are likely to be GPI anchored but that rat nyctalopin is not [28].
  • The linearity, tested on the chimp Rodney plasma pool, was better with bDNA for high viral load than with NASBA and Monitor, although for low concentration of HCV RNA, bDNA was negative [4].
  • The hPIRH2 binding site was mapped to the C-terminal X domain region of the P protein by using a yeast two-hybrid assay [29].


  1. Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer. Logan, I.R., Gaughan, L., McCracken, S.R., Sapountzi, V., Leung, H.Y., Robson, C.N. Mol. Cell. Biol. (2006) [Pubmed]
  2. Differential response between the p53 ubiquitin-protein ligases Pirh2 and MdM2 following DNA damage in human cancer cells. Duan, W., Gao, L., Wu, X., Zhang, Y., Otterson, G.A., Villalona-Calero, M.A. Exp. Cell Res. (2006) [Pubmed]
  3. Clinical effects of infusions into chimpanzees of primed autologous cultured T-cells. Slease, R.B., Strong, D.M., Gawith, K.E., Bonnard, G.D. J. Natl. Cancer Inst. (1981) [Pubmed]
  4. Comparative evaluation of hepatitis C virus RNA quantitation by branched DNA, NASBA, and monitor assays. Lunel, F., Cresta, P., Vitour, D., Payan, C., Dumont, B., Frangeul, L., Reboul, D., Brault, C., Piette, J.C., Huraux, J.M. Hepatology (1999) [Pubmed]
  5. Chimpanzee models for human disease and immunobiology. Muchmore, E.A. Immunol. Rev. (2001) [Pubmed]
  6. Déjà Vu all over again: chimp-language wars. Gibbons, A. Science (1991) [Pubmed]
  7. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Leng, R.P., Lin, Y., Ma, W., Wu, H., Lemmers, B., Chung, S., Parant, J.M., Lozano, G., Hakem, R., Benchimol, S. Cell (2003) [Pubmed]
  8. Comparative genomics. Gene expression differs in human and chimp brains. Normile, D. Science (2001) [Pubmed]
  9. Non-A, non-B (type 1) hepatitis agent capable of inducing tubular ultrastructures in the hepatocyte cytoplasm of chimpanzees: inactivation by formalin and heat. Yoshizawa, H., Itoh, Y., Iwakiri, S., Kitajima, K., Tanaka, A., Tachibana, T., Nakamura, T., Miyakawa, Y., Mayumi, M. Gastroenterology (1982) [Pubmed]
  10. Demonstration of two different types of non-A, non-B hepatitis by reinjection and cross-challenge studies in chimpanzees. Yoshizawa, H., Itoh, Y., Iwakiri, S., Kitajima, K., Tanaka, A., Nojiri, T., Miyakawa, Y., Mayumi, M. Gastroenterology (1981) [Pubmed]
  11. Should the draft chimpanzee sequence be finished? Taudien, S., Ebersberger, I., Glöckner, G., Platzer, M. Trends Genet. (2006) [Pubmed]
  12. Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity. Beitel, L.K., Elhaji, Y.A., Lumbroso, R., Wing, S.S., Panet-Raymond, V., Gottlieb, B., Pinsky, L., Trifiro, M.A. J. Mol. Endocrinol. (2002) [Pubmed]
  13. Genomics. Building a case for sequencing the chimp. Gibbons, A. Science (2000) [Pubmed]
  14. A limited role for balancing selection. Asthana, S., Schmidt, S., Sunyaev, S. Trends Genet. (2005) [Pubmed]
  15. Segmental duplications flank the multiple sclerosis locus on chromosome 17q. Chen, D.C., Saarela, J., Clark, R.A., Miettinen, T., Chi, A., Eichler, E.E., Peltonen, L., Palotie, A. Genome Res. (2004) [Pubmed]
  16. The baboon erythrocyte complement receptor is a glycophosphatidylinositol-linked protein encoded by a homologue of the human CR1-like genetic element. Birmingham, D.J., Logar, C.M., Shen, X.P., Chen, W. J. Immunol. (1996) [Pubmed]
  17. Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo. Shibata, R., Hoggan, M.D., Broscius, C., Englund, G., Theodore, T.S., Buckler-White, A., Arthur, L.O., Israel, Z., Schultz, A., Lane, H.C. J. Virol. (1995) [Pubmed]
  18. A uniquely human consequence of domain-specific functional adaptation in a sialic acid-binding receptor. Sonnenburg, J.L., Altheide, T.K., Varki, A. Glycobiology (2004) [Pubmed]
  19. Forelimb segment length proportions in extant hominoids and Australopithecus afarensis. Drapeau, M.S., Ward, C.V. Am. J. Phys. Anthropol. (2007) [Pubmed]
  20. Molecular evolution of adrenarche: structural and functional analysis of p450c17 from four primate species. Arlt, W., Martens, J.W., Song, M., Wang, J.T., Auchus, R.J., Miller, W.L. Endocrinology (2002) [Pubmed]
  21. There are two C4 genetic loci and a null allele in the chimpanzee. Granados, J., Awdeh, Z.L., Chen, J.H., Giles, C.M., Balner, H., Yunis, E.J., Alper, C.A. Immunogenetics (1987) [Pubmed]
  22. Diagnosis of inhalant allergy in a chimpanzee using "in vivo" and "in vitro" tests. Halpern, G.M., Gershwin, L.J., Gonzales, G., Fowler, M.E. Allergologia et immunopathologia. (1989) [Pubmed]
  23. Molecular basis of Pirh2-mediated p53 ubiquitylation. Sheng, Y., Laister, R.C., Lemak, A., Wu, B., Tai, E., Duan, S., Lukin, J., Sunnerhagen, M., Srisailam, S., Karra, M., Benchimol, S., Arrowsmith, C.H. Nat. Struct. Mol. Biol. (2008) [Pubmed]
  24. The p53 pathway: positive and negative feedback loops. Harris, S.L., Levine, A.J. Oncogene (2005) [Pubmed]
  25. A human CR1-like transcript containing sequence for a binding protein for iC4 is expressed in hematopoietic and fetal lymphoid tissue. Logar, C.M., Chen, W., Schmitt, H., Yu, C.Y., Birmingham, D.J. Mol. Immunol. (2004) [Pubmed]
  26. Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer. Duan, W., Gao, L., Druhan, L.J., Zhu, W.G., Morrison, C., Otterson, G.A., Villalona-Calero, M.A. J. Natl. Cancer Inst. (2004) [Pubmed]
  27. Reconstructing hominid Y evolution: X-homologous block, created by X-Y transposition, was disrupted by Yp inversion through LINE-LINE recombination. Schwartz, A., Chan, D.C., Brown, L.G., Alagappan, R., Pettay, D., Disteche, C., McGillivray, B., de la Chapelle, A., Page, D.C. Hum. Mol. Genet. (1998) [Pubmed]
  28. Species specific membrane anchoring of nyctalopin, a small leucine-rich repeat protein. O'Connor, E., Eisenhaber, B., Dalley, J., Wang, T., Missen, C., Bulleid, N., Bishop, P.N., Trump, D. Hum. Mol. Genet. (2005) [Pubmed]
  29. Inhibition of ubiquitination and stabilization of human ubiquitin E3 ligase PIRH2 by measles virus phosphoprotein. Chen, M., Cortay, J.C., Logan, I.R., Sapountzi, V., Robson, C.N., Gerlier, D. J. Virol. (2005) [Pubmed]
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