P4HB

Prolyl 4-hydroxylase, beta polypeptide
PDB rendering based on 1bjx.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BJX​, 1MEK​, 1X5C​, 2BJX​, 2K18​, 3BJ5​, 3UEM​, 4EKZ​, 4EL1​, 4JU5​
Identifiers
Symbols	P4HB ; CLCRP1; DSI; ERBA2L; GIT; P4Hbeta; PDI; PDIA1; PHDB; PO4DB; PO4HB; PROHB
External IDs	OMIM: 176790 MGI: 97464 HomoloGene: 55495 ChEMBL: 5422 GeneCards: P4HB Gene
EC number	5.3.4.1
Gene ontology Molecular function • protein disulfide isomerase activity • endopeptidase activity • procollagen-proline 4-dioxygenase activity • protein binding • enzyme binding • poly(A) RNA binding • protein heterodimerization activity Cellular component • extracellular region • endoplasmic reticulum • endoplasmic reticulum lumen • endoplasmic reticulum-Golgi intermediate compartment • focal adhesion • external side of plasma membrane • procollagen-proline 4-dioxygenase complex • endoplasmic reticulum chaperone complex • melanosome • extracellular exosome Biological process • response to reactive oxygen species • protein folding • proteolysis • peptidyl-proline hydroxylation to 4-hydroxy-L-proline • extracellular matrix organization • response to endoplasmic reticulum stress • lipoprotein metabolic process • small molecule metabolic process • cell redox homeostasis • positive regulation of viral entry into host cell • cellular response to hypoxia • regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5034	18453
Ensembl	ENSG00000185624	ENSMUSG00000025130
UniProt	P07237	P09103
RefSeq (mRNA)	NM_000918	NM_011032
RefSeq (protein)	NP_000909	NP_035162
Location (UCSC)	Chr 17: 81.84 – 81.86 Mb	Chr 11: 120.56 – 120.57 Mb
PubMed search

Protein disulfide-isomerase is an enzyme that in humans is encoded by the P4HB gene.^[1][2][3]

Function

This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol-bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex.^[2]

Interactions

P4HB has been shown to interact with UBQLN1,^[4] ERO1LB^[5][6] and ERO1L.^[5][6]

References

1. Shoulders CC, Brett DJ, Bayliss JD, Narcisi TM, Jarmuz A, Grantham TT, Leoni PR, Bhattacharya S, Pease RJ, Cullen PM (Dec 1993). "Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein". Human Molecular Genetics 2 (12): 2109–16. doi:10.1093/hmg/2.12.2109. PMID 8111381.
2. "Entrez Gene: P4HB procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), beta polypeptide".
3. Galligan JJ, Petersen DR (July 2012). "The human protein disulfide isomerase gene family". Human Genomics 6 (6): 6. doi:10.1186/1479-7364-6-6. PMC 3500226. PMID 23245351.
4. Ko HS, Uehara T, Nomura Y (Sep 2002). "Role of ubiquilin associated with protein-disulfide isomerase in the endoplasmic reticulum in stress-induced apoptotic cell death". The Journal of Biological Chemistry 277 (38): 35386–92. doi:10.1074/jbc.M203412200. PMID 12095988.
5. Anelli T, Alessio M, Mezghrani A, Simmen T, Talamo F, Bachi A, Sitia R (Feb 2002). "ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family". The EMBO Journal 21 (4): 835–44. doi:10.1093/emboj/21.4.835. PMC 125352. PMID 11847130.
6. Mezghrani A, Fassio A, Benham A, Simmen T, Braakman I, Sitia R (Nov 2001). "Manipulation of oxidative protein folding and PDI redox state in mammalian cells". The EMBO Journal 20 (22): 6288–96. doi:10.1093/emboj/20.22.6288. PMC 125306. PMID 11707400.

Further reading

• Galligan JJ, Petersen DR (July 2012). "The human protein disulfide isomerase gene family". Human Genomics 6 (6): 6. doi:10.1186/1479-7364-6-6. PMC 3500226. PMID 23245351.
• Wilkinson B, Gilbert HF (Jun 2004). "Protein disulfide isomerase". Biochimica Et Biophysica Acta 1699 (1-2): 35–44. doi:10.1016/j.bbapap.2004.02.017. PMID 15158710.
• Pihlajaniemi T, Myllylä R, Kivirikko KI (1992). "Prolyl 4-hydroxylase and its role in collagen synthesis". Journal of Hepatology. 13 Suppl 3: S2–7. doi:10.1016/0168-8278(91)90002-S. PMID 1667665.
• Wilkinson B, Gilbert HF (Jun 2004). "Protein disulfide isomerase". Biochimica Et Biophysica Acta 1699 (1-2): 35–44. doi:10.1016/j.bbapap.2004.02.017. PMID 15158710.
• Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R (Dec 1992). "Human liver protein map: a reference database established by microsequencing and gel comparison". Electrophoresis 13 (12): 992–1001. doi:10.1002/elps.11501301201. PMID 1286669.
• Chessler SD, Byers PH (Apr 1992). "Defective folding and stable association with protein disulfide isomerase/prolyl hydroxylase of type I procollagen with a deletion in the pro alpha 2(I) chain that preserves the Gly-X-Y repeat pattern". The Journal of Biological Chemistry 267 (11): 7751–7. PMID 1339453.
• Vuori K, Myllylä R, Pihlajaniemi T, Kivirikko KI (Apr 1992). "Expression and site-directed mutagenesis of human protein disulfide isomerase in Escherichia coli. This multifunctional polypeptide has two independently acting catalytic sites for the isomerase activity". The Journal of Biological Chemistry 267 (11): 7211–4. PMID 1559965.
• Tasanen K, Oikarinen J, Kivirikko KI, Pihlajaniemi T (Jun 1992). "Promoter of the gene for the multifunctional protein disulfide isomerase polypeptide. Functional significance of the six CCAAT boxes and other promoter elements". The Journal of Biological Chemistry 267 (16): 11513–9. PMID 1597478.
• Bauw G, Rasmussen HH, van den Bulcke M, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J (Jul 1990). "Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes". Electrophoresis 11 (7): 528–36. doi:10.1002/elps.1150110703. PMID 1699755.
• Ward LD, Hong J, Whitehead RH, Simpson RJ (Oct 1990). "Development of a database of amino acid sequences for human colon carcinoma proteins separated by two-dimensional polyacrylamide gel electrophoresis". Electrophoresis 11 (10): 883–91. doi:10.1002/elps.1150111019. PMID 2079031.
• Tasanen K, Parkkonen T, Chow LT, Kivirikko KI, Pihlajaniemi T (Nov 1988). "Characterization of the human gene for a polypeptide that acts both as the beta subunit of prolyl 4-hydroxylase and as protein disulfide isomerase". The Journal of Biological Chemistry 263 (31): 16218–24. PMID 2846539.
• Koivu J, Myllylä R, Helaakoski T, Pihlajaniemi T, Tasanen K, Kivirikko KI (May 1987). "A single polypeptide acts both as the beta subunit of prolyl 4-hydroxylase and as a protein disulfide-isomerase". The Journal of Biological Chemistry 262 (14): 6447–9. PMID 3032969.
• Pihlajaniemi T, Helaakoski T, Tasanen K, Myllylä R, Huhtala ML, Koivu J, Kivirikko KI (Mar 1987). "Molecular cloning of the beta-subunit of human prolyl 4-hydroxylase. This subunit and protein disulphide isomerase are products of the same gene". The EMBO Journal 6 (3): 643–9. PMC 553446. PMID 3034602.
• Morris JI, Varandani PT (Feb 1988). "Characterization of a cDNA for human glutathione-insulin transhydrogenase (protein-disulfide isomerase/oxidoreductase)". Biochimica Et Biophysica Acta 949 (2): 169–80. doi:10.1016/0167-4781(88)90080-2. PMID 3342239.
• Gosden JR, Middleton PG, Rout D, De Angelis C (1987). "Chromosomal localization of the human oncogene ERBA2". Cytogenetics and Cell Genetics 43 (3-4): 150–3. doi:10.1159/000132313. PMID 3467900.
• Cheng SY, Gong QH, Parkison C, Robinson EA, Appella E, Merlino GT, Pastan I (Aug 1987). "The nucleotide sequence of a human cellular thyroid hormone binding protein present in endoplasmic reticulum". The Journal of Biological Chemistry 262 (23): 11221–7. PMID 3611107.
• Helaakoski T, Annunen P, Vuori K, MacNeil IA, Pihlajaniemi T, Kivirikko KI (May 1995). "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". Proceedings of the National Academy of Sciences of the United States of America 92 (10): 4427–31. doi:10.1073/pnas.92.10.4427. PMC 41957. PMID 7753822.
• Kemmink J, Darby NJ, Dijkstra K, Scheek RM, Creighton TE (Dec 1995). "Nuclear magnetic resonance characterization of the N-terminal thioredoxin-like domain of protein disulfide isomerase". Protein Science 4 (12): 2587–93. doi:10.1002/pro.5560041216. PMC 2143042. PMID 8580850.
• Kemmink J, Darby NJ, Dijkstra K, Nilges M, Creighton TE (Jun 1996). "Structure determination of the N-terminal thioredoxin-like domain of protein disulfide isomerase using multidimensional heteronuclear 13C/15N NMR spectroscopy". Biochemistry 35 (24): 7684–91. doi:10.1021/bi960335m. PMID 8672469.
• Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ (1997). "A two-dimensional gel database of human colon carcinoma proteins". Electrophoresis 18 (3-4): 605–13. doi:10.1002/elps.1150180344. PMID 9150948.