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Gene Review

P4hb  -  prolyl 4-hydroxylase, beta polypeptide

Mus musculus

Synonyms: Cellular thyroid hormone-binding protein, ER protein 59, ERp59, Endoplasmic reticulum resident protein 59, PDI, ...
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Disease relevance of P4hb


High impact information on P4hb

  • Edman degradation of MTPv1 isolated from transfected cells revealed three unique residues; however, recombinant MTP and MTPv1 had an equivalent protein disulfide isomerase association, subcellular localization, triglyceride transfer, phospholipid transfer, response to inhibitors, and ability to support apoB secretion [6].
  • Internuclear exchange of an inner nuclear membrane protein (p55) in heterokaryons: in vivo evidence for the interaction of p55 with the nuclear lamina [7].
  • When rat/mouse heterokaryons were constructed using an undifferentiated murine embryonal carcinoma (P19), which lacks lamins A and C, no accumulation of p55 in the mouse cell nucleus was observed [7].
  • However, P19 nuclei could be rendered competent to accumulate p55 by transfecting the parent cells with human lamin A before cell fusion, supporting the notion that p55 may interact with the nuclear lamina [7].
  • After incubation of the detergent-insoluble matrix of these cells with [gamma-32P]ATP, several alkali-resistant phosphoproteins, including a very heavily labelled 55 000 mol. wt. protein ( p55 ), have been detected in LSTRA, reflecting the activity of a protein kinase specific to this cell line [8].

Chemical compound and disease context of P4hb


Biological context of P4hb

  • Infectibility measured by nuclear T antigen expression was reduced commensurately with the degree of PDI downregulation [1].
  • Infectibility was restored by transfection with a plasmid expressing PDI but not with a control expressing catalytically inactive enzyme [1].
  • Tissue distribution of three members of the murine protein disulfide isomerase (PDI) family [11].
  • We detected a single linkage at the telomeric end of chromosome 11, where the Pdi gene itself resides (logarithm of odds score >30.0) [12].
  • A genetic analysis was carried out to determine whether there is a causal relationship between elevated Pdi expression and diabetes phenotype in BTBR-ob/ob mice [12].

Anatomical context of P4hb


Associations of P4hb with chemical compounds


Regulatory relationships of P4hb


Other interactions of P4hb


Analytical, diagnostic and therapeutic context of P4hb

  • The gene array results were verified by quantitative real-time PCR that showed highly elevated transcript levels of genes involved in unfolded protein response such as ER and cytoplasmic chaperones, oxidoreductases, protein disulfide isomerase (PDI) family, and ER-associated degradation system such as ubiquitin [23].
  • A strong correlation emerged between the experimental results on epitope mapping and predictions of potential antigenicity of murine p55 IL-2R [24].
  • In particular, an unconjugated HIV1-p24 peptide containing both B- and T-cell epitopes in tandem plus Freund's adjuvant induced a strong antibody response in both mice and rabbits against p24 and its precursor p55 as judged by immunoblotting [25].
  • Animals immunized with these gag particles produced high titer antibodies and Western blot analyses showed that anti-gag pr45 rabbit sera react with p17, p24 and p55 gag proteins of HIV-1 [26].


  1. Downregulation of protein disulfide isomerase inhibits infection by the mouse polyomavirus. Gilbert, J., Ou, W., Silver, J., Benjamin, T. J. Virol. (2006) [Pubmed]
  2. Cloning, baculovirus expression, and characterization of a second mouse prolyl 4-hydroxylase alpha-subunit isoform: formation of an alpha 2 beta 2 tetramer with the protein disulfide-isomerase/beta subunit. Helaakoski, T., Annunen, P., Vuori, K., MacNeil, I.A., Pihlajaniemi, T., Kivirikko, K.I. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Induction of the Unfolded Protein Response in Familial Amyotrophic Lateral Sclerosis and Association of Protein-disulfide Isomerase with Superoxide Dismutase 1. Atkin, J.D., Farg, M.A., Turner, B.J., Tomas, D., Lysaght, J.A., Nunan, J., Rembach, A., Nagley, P., Beart, P.M., Cheema, S.S., Horne, M.K. J. Biol. Chem. (2006) [Pubmed]
  4. Structure and assembly of the endoplasmic reticulum: biosynthesis and intracellular sorting of ERp61, ERp59, and ERp49, three protein components of murine endoplasmic reticulum. Lewis, M.J., Mazzarella, R.A., Green, M. Arch. Biochem. Biophys. (1986) [Pubmed]
  5. The expression of murine protein disulfide isomerase in Escherichia coli. Haugejorden, S.M., Srinivasan, M., Green, M. DNA Cell Biol. (1992) [Pubmed]
  6. MTP regulated by an alternate promoter is essential for NKT cell development. Dougan, S.K., Rava, P., Hussain, M.M., Blumberg, R.S. J. Exp. Med. (2007) [Pubmed]
  7. Internuclear exchange of an inner nuclear membrane protein (p55) in heterokaryons: in vivo evidence for the interaction of p55 with the nuclear lamina. Powell, L., Burke, B. J. Cell Biol. (1990) [Pubmed]
  8. High level of tyrosine protein kinase in a murine lymphoma cell line induced by Moloney leukemia virus. Gacon, G., Gisselbrecht, S., Piau, J.P., Boissel, J.P., Tolle, J., Fischer, S. EMBO J. (1982) [Pubmed]
  9. Overexpression of protein disulfide isomerase-like protein in a mouse leukemia L1210 cell line selected for resistance to 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone, a ribonucleotide reductase inhibitor. Crenshaw, T.R., Cory, J.G. Adv. Enzyme Regul. (2002) [Pubmed]
  10. cDNA cloning and baculovirus expression of the human liver endoplasmic reticulum P58: characterization as a protein disulfide isomerase isoform, but not as a protease or a carnitine acyltransferase. Bourdi, M., Demady, D., Martin, J.L., Jabbour, S.K., Martin, B.M., George, J.W., Pohl, L.R. Arch. Biochem. Biophys. (1995) [Pubmed]
  11. Tissue distribution of three members of the murine protein disulfide isomerase (PDI) family. Marcus, N., Shaffer, D., Farrar, P., Green, M. Biochim. Biophys. Acta (1996) [Pubmed]
  12. Distinguishing covariation from causation in diabetes: a lesson from the protein disulfide isomerase mRNA abundance trait. Lan, H., Rabaglia, M.E., Schueler, K.L., Mata, C., Yandell, B.S., Attie, A.D. Diabetes (2004) [Pubmed]
  13. Tissue distribution of ERp61 and association of its increased expression with IgG production in hybridoma cells. Kozaki, K., Miyaishi, O., Asai, N., Iida, K., Sakata, K., Hayashi, M., Nishida, T., Matsuyama, M., Shimizu, S., Kaneda, T. Exp. Cell Res. (1994) [Pubmed]
  14. A role for sperm surface protein disulfide isomerase activity in gamete fusion: evidence for the participation of ERp57. Ellerman, D.A., Myles, D.G., Primakoff, P. Dev. Cell (2006) [Pubmed]
  15. ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase. Mazzarella, R.A., Srinivasan, M., Haugejorden, S.M., Green, M. J. Biol. Chem. (1990) [Pubmed]
  16. Endogenous substrates of sphingosine-dependent kinases (SDKs) are chaperone proteins: heat shock proteins, glucose-regulated proteins, protein disulfide isomerase, and calreticulin. Megidish, T., Takio, K., Titani, K., Iwabuchi, K., Hamaguchi, A., Igarashi, Y., Hakomori, S. Biochemistry (1999) [Pubmed]
  17. Corneal keratocytes: phenotypic and species differences in abundant protein expression and in vitro light-scattering. Jester, J.V., Budge, A., Fisher, S., Huang, J. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  18. Protein disulfide isomerase suppresses the transcriptional activity of NF-kappaB. Higuchi, T., Watanabe, Y., Waga, I. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  19. Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides. Nair, S., Wearsch, P.A., Mitchell, D.A., Wassenberg, J.J., Gilboa, E., Nicchitta, C.V. J. Immunol. (1999) [Pubmed]
  20. Protein degradation by ERp72 from rat and mouse liver endoplasmic reticulum. Urade, R., Takenaka, Y., Kito, M. J. Biol. Chem. (1993) [Pubmed]
  21. Comparative proteomic analysis identifies protein disulfide isomerase and peroxiredoxin 1 as new players involved in embryonic interdigital cell death. Shan, S.W., Tang, M.K., Cai, D.Q., Chui, Y.L., Chow, P.H., Grotewold, L., Lee, K.K. Dev. Dyn. (2005) [Pubmed]
  22. Dietary energy tissue-specifically regulates endoplasmic reticulum chaperone gene expression in the liver of mice. Dhahbi, J.M., Mote, P.L., Tillman, J.B., Walford, R.L., Spindler, S.R. J. Nutr. (1997) [Pubmed]
  23. Activation of endoplasmic reticulum stress response during the development of ischemic heart disease. Azfer, A., Niu, J., Rogers, L.M., Adamski, F.M., Kolattukudy, P.E. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  24. Structure-function study of the p55 subunit of murine IL-2 receptor by epitope mapping. Lorenzo, F., Jaulin, C., Vita, N., Froussard, P., Ferrara, P., Jankovic, D.L., Theze, J. J. Immunol. (1991) [Pubmed]
  25. Identification of a potent synthetic HIV1 immunogen compromising gag-P24 tandem T- and B-cell epitopes. Chong, P., Sia, C., Sydor, M., Klein, M. FEBS Lett. (1990) [Pubmed]
  26. Development of HIV/AIDS vaccine using chimeric gag-env virus-like particles. Kang, C.Y., Luo, L., Wainberg, M.A., Li, Y. Biol. Chem. (1999) [Pubmed]
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