Hmdb loader

Showing Protein Protein disulfide-isomerase (HMDBP02802)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 39931 metabolites
Identification
HMDB Protein ID HMDBP02802
Secondary Accession Numbers
  • 8308
  • HMDBP03678
Name Protein disulfide-isomerase
Synonyms
  1. Cellular thyroid hormone-binding protein
  2. PDI
  3. Prolyl 4-hydroxylase subunit beta
  4. p55
Gene Name P4HB
Protein Type Enzyme
Biological Properties
General Function Involved in isomerase activity
Specific Function This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP
Pathways Not Available
Reactions Not Available
GO Classification
Component
endoplasmic reticulum
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
Function
catalytic activity
isomerase activity
Process
cellular process
cellular homeostasis
cell redox homeostasis
Cellular Location
  1. Cell membrane
  2. Melanosome
  3. Endoplasmic reticulum lumen
  4. Peripheral membrane protein (Potential)
Gene Properties
Chromosome Location Chromosome:1
Locus 17q25
SNPs P4HB
Gene Sequence 
>1527 bp
ATGCTGCGCCGCGCTCTGCTGTGCCTGCCGTGGNCCGCCCTGGTGCGCGCCGACGCCCCC
GAGGAGGAGGACCACGTCTTGGTGCTGCGGAAAAGCAACTTCGCGGAGGCGCTGGCGGCC
CACAAGTACCCGCCGGTGGAGTTCCATGCCCCCTGGTGTGGCCACTGCAAGGCTCTGGCC
CCTGAGTATGCCAAAGCCGCTGGGAAGCTGAAGGCAGAAGGTTCCGAGATCAGGTTGGCC
AAGGTGGACGCCACGGAGGAGTCTGACCTAGCCCAGCAGTACGGCGTGCGCGGCTATCCC
ACCATCAAGTTCTTCAGGAATGGAGACACGGCTTCCCCCAAGGAATATACAGCTGGCAGA
GAGGCTGATGACATCGTGAACTGGCTGAAGAAGCGCACGGGCCCGGCTGCCACCACCCTG
CCTGACGGCGCAGCTGCAGAGTCCTTGGTGGAGTCCAGCGAGGTGGCCGTCATCGGCTTC
TTCAAGGACGTGGAGTCGGACTCTGCCAAGCAGTTTTTGCAGGCAGCAGAGGCCATCGAT
GACATACCATTTGGGATCACTTCCAACAGTGACGTGTTCTCCAAATACCAGCTCGACAAA
GATGGGGTTGTCCTCTTTAAGAAGTTTGATGAAGGCCGGAACAACTTTGAAGGGGAGGTC
ACCAAGGAGAACCTGCTGGACTTTATCAAACACAACCAGCTGCCCCTTGTCATCGAGTTC
ACCGAGCAGACAGCCCCGAAGATTTTTGGAGGTGAAATCAAGACTCACATCCTGCTGTTC
TTGCCCAAGAGTGTGTCTGACTATGACGGCAAACTGAGCAACTTCAAAACAGCAGCCGAG
AGCTTCAAGGGCAAGATCCTGTTCATCTTCATCGACAGCGACCACACCGACAACCAGCGC
ATCCTCGAGTTCTTTGGCCTGAAGAAGGAAGAGTGCCCGGCCGTGCGCCTCATCACCTTG
GAGGAGGAGATGACCAAGTACAAGCCCGAATCGGAGGAGCTGACGGCAGAGAGGATCACA
GAGTTCTGCCACCGCTTCCTGGAGGGCAAAATCAAGCCCCACCTGATGAGCCAGGAGCTG
CCGGAGGACTGGGACAAGCAGCCTGTCAAGGTGCTTGTTGGGAAGAACTTTGAAGACGTG
GCTTTTGATGAGAAAAAAAACGTCTTTGTGGAGTTCTATGCCCCATGGTGTGGTCACTGC
AAACAGTTGGCTCCCATTTGGGATAAACTGGGAGAGACGTACAAGGACCATGAGAACATC
GTCATCGCCAAGATGGACTCGACTGCCAACGAGGTGGAGGCCGTCAAAGTGCACGGCTTC
CCCACACTCGGGTTCTTTCCTGCCAGTGCCGACAGGACGGTCATTGATTACAACGGGGAA
CGCACGCTGGATGGTTTTAAGAAATTCCTAGAGAGCGGTGGCCAAGATGGGGCAGGGGAT
GTTGACGACCTCGAGGACCTCGAAGAAGCAGAGGAGCCAGACATGGAGGAAGACGATGAC
CAGAAAGCTGTGAAAGATGAACTGTAA
Protein Properties
Number of Residues 508
Molecular Weight 57115.8
Theoretical pI 4.49
Pfam Domain Function
Signals
  • 1-17
Transmembrane Regions
  • None
Protein Sequence 
>Protein disulfide-isomerase
MLRRALLCLAVAALVRADAPEEEDHVLVLRKSNFAEALAAHKYLLVEFYAPWCGHCKALA
PEYAKAAGKLKAEGSEIRLAKVDATEESDLAQQYGVRGYPTIKFFRNGDTASPKEYTAGR
EADDIVNWLKKRTGPAATTLPDGAAAESLVESSEVAVIGFFKDVESDSAKQFLQAAEAID
DIPFGITSNSDVFSKYQLDKDGVVLFKKFDEGRNNFEGEVTKENLLDFIKHNQLPLVIEF
TEQTAPKIFGGEIKTHILLFLPKSVSDYDGKLSNFKTAAESFKGKILFIFIDSDHTDNQR
ILEFFGLKKEECPAVRLITLEEEMTKYKPESEELTAERITEFCHRFLEGKIKPHLMSQEL
PEDWDKQPVKVLVGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGETYKDHENI
VIAKMDSTANEVEAVKVHSFPTLKFFPASADRTVIDYNGERTLDGFKKFLESGGQDGAGD
DDDLEDLEEAEEPDMEEDDDQKAVKDEL
GenBank ID Protein 35655
UniProtKB/Swiss-Prot ID P07237
UniProtKB/Swiss-Prot Entry Name PDIA1_HUMAN
PDB IDs
GenBank Gene ID X05130
GeneCard ID P4HB
GenAtlas ID P4HB
HGNC ID HGNC:8548
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R, et al.: Human liver protein map: a reference database established by microsequencing and gel comparison. Electrophoresis. 1992 Dec;13(12):992-1001. [PubMed:1286669 ]
  4. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [PubMed:17081065 ]
  5. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed:12665801 ]
  6. Basrur V, Yang F, Kushimoto T, Higashimoto Y, Yasumoto K, Valencia J, Muller J, Vieira WD, Watabe H, Shabanowitz J, Hearing VJ, Hunt DF, Appella E: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. J Proteome Res. 2003 Jan-Feb;2(1):69-79. [PubMed:12643545 ]
  7. Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ: A two-dimensional gel database of human colon carcinoma proteins. Electrophoresis. 1997 Mar-Apr;18(3-4):605-13. [PubMed:9150948 ]
  8. Pihlajaniemi T, Helaakoski T, Tasanen K, Myllyla R, Huhtala ML, Koivu J, Kivirikko KI: Molecular cloning of the beta-subunit of human prolyl 4-hydroxylase. This subunit and protein disulphide isomerase are products of the same gene. EMBO J. 1987 Mar;6(3):643-9. [PubMed:3034602 ]
  9. Cheng SY, Gong QH, Parkison C, Robinson EA, Appella E, Merlino GT, Pastan I: The nucleotide sequence of a human cellular thyroid hormone binding protein present in endoplasmic reticulum. J Biol Chem. 1987 Aug 15;262(23):11221-7. [PubMed:3611107 ]
  10. Tasanen K, Parkkonen T, Chow LT, Kivirikko KI, Pihlajaniemi T: Characterization of the human gene for a polypeptide that acts both as the beta subunit of prolyl 4-hydroxylase and as protein disulfide isomerase. J Biol Chem. 1988 Nov 5;263(31):16218-24. [PubMed:2846539 ]
  11. Tasanen K, Oikarinen J, Kivirikko KI, Pihlajaniemi T: Promoter of the gene for the multifunctional protein disulfide isomerase polypeptide. Functional significance of the six CCAAT boxes and other promoter elements. J Biol Chem. 1992 Jun 5;267(16):11513-9. [PubMed:1597478 ]
  12. Ward LD, Hong J, Whitehead RH, Simpson RJ: Development of a database of amino acid sequences for human colon carcinoma proteins separated by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis. 1990 Oct;11(10):883-91. [PubMed:2079031 ]
  13. Urade R, Oda T, Ito H, Moriyama T, Utsumi S, Kito M: Functions of characteristic Cys-Gly-His-Cys (CGHC) and Gln-Glu-Asp-Leu (QEDL) motifs of microsomal ER-60 protease. J Biochem. 1997 Oct;122(4):834-42. [PubMed:9399589 ]
  14. Morris JI, Varandani PT: Characterization of a cDNA for human glutathione-insulin transhydrogenase (protein-disulfide isomerase/oxidoreductase). Biochim Biophys Acta. 1988 Feb 28;949(2):169-80. [PubMed:3342239 ]
  15. Bauw G, Rasmussen HH, van den Bulcke M, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J: Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes. Electrophoresis. 1990 Jul;11(7):528-36. [PubMed:1699755 ]
  16. Mezghrani A, Courageot J, Mani JC, Pugniere M, Bastiani P, Miquelis R: Protein-disulfide isomerase (PDI) in FRTL5 cells. pH-dependent thyroglobulin/PDI interactions determine a novel PDI function in the post-endoplasmic reticulum of thyrocytes. J Biol Chem. 2000 Jan 21;275(3):1920-9. [PubMed:10636893 ]
  17. Fenouillet E, Barbouche R, Courageot J, Miquelis R: The catalytic activity of protein disulfide isomerase is involved in human immunodeficiency virus envelope-mediated membrane fusion after CD4 cell binding. J Infect Dis. 2001 Mar 1;183(5):744-52. Epub 2001 Jan 25. [PubMed:11181151 ]
  18. Lumb RA, Bulleid NJ: Is protein disulfide isomerase a redox-dependent molecular chaperone? EMBO J. 2002 Dec 16;21(24):6763-70. [PubMed:12485997 ]
  19. Ko HS, Uehara T, Nomura Y: Role of ubiquilin associated with protein-disulfide isomerase in the endoplasmic reticulum in stress-induced apoptotic cell death. J Biol Chem. 2002 Sep 20;277(38):35386-92. Epub 2002 Jul 2. [PubMed:12095988 ]
  20. Gallina A, Hanley TM, Mandel R, Trahey M, Broder CC, Viglianti GA, Ryser HJ: Inhibitors of protein-disulfide isomerase prevent cleavage of disulfide bonds in receptor-bound glycoprotein 120 and prevent HIV-1 entry. J Biol Chem. 2002 Dec 27;277(52):50579-88. Epub 2002 Sep 5. [PubMed:12218051 ]
  21. Barbouche R, Miquelis R, Jones IM, Fenouillet E: Protein-disulfide isomerase-mediated reduction of two disulfide bonds of HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for fusion. J Biol Chem. 2003 Jan 31;278(5):3131-6. Epub 2002 Sep 5. [PubMed:12218052 ]
  22. Wilkinson B, Gilbert HF: Protein disulfide isomerase. Biochim Biophys Acta. 2004 Jun 1;1699(1-2):35-44. [PubMed:15158710 ]
  23. Markovic I, Stantchev TS, Fields KH, Tiffany LJ, Tomic M, Weiss CD, Broder CC, Strebel K, Clouse KA: Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry. Blood. 2004 Mar 1;103(5):1586-94. Epub 2003 Oct 30. [PubMed:14592831 ]
  24. Barbouche R, Lortat-Jacob H, Jones IM, Fenouillet E: Glycosaminoglycans and protein disulfide isomerase-mediated reduction of HIV Env. Mol Pharmacol. 2005 Apr;67(4):1111-8. Epub 2005 Jan 11. [PubMed:15644496 ]
  25. Kemmink J, Darby NJ, Dijkstra K, Scheek RM, Creighton TE: Nuclear magnetic resonance characterization of the N-terminal thioredoxin-like domain of protein disulfide isomerase. Protein Sci. 1995 Dec;4(12):2587-93. [PubMed:8580850 ]
  26. Kemmink J, Darby NJ, Dijkstra K, Nilges M, Creighton TE: Structure determination of the N-terminal thioredoxin-like domain of protein disulfide isomerase using multidimensional heteronuclear 13C/15N NMR spectroscopy. Biochemistry. 1996 Jun 18;35(24):7684-91. [PubMed:8672469 ]
  27. Kemmink J, Dijkstra K, Mariani M, Scheek RM, Penka E, Nilges M, Darby NJ: The structure in solution of the b domain of protein disulfide isomerase. J Biomol NMR. 1999 Apr;13(4):357-68. [PubMed:10383197 ]