Protein disulfide-isomerase A3

Details

Name
Protein disulfide-isomerase A3
Kind
protein
Synonyms
  • 5.3.4.1
  • 58 kDa glucose-regulated protein
  • 58 kDa microsomal protein
  • Disulfide isomerase ER-60
  • Endoplasmic reticulum resident protein 57
  • Endoplasmic reticulum resident protein 60
  • ER protein 57
  • ER protein 60
  • ERP57
  • ERP60
  • GRP58
  • p58
Gene Name
PDIA3
UniProtKB Entry
P30101Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0049675|Protein disulfide-isomerase A3
MRLRRLALFPGVALLLAAARLAAASDVLELTDDNFESRISDTGSAGLMLVEFFAPWCGHC
KRLAPEYEAAATRLKGIVPLAKVDCTANTNTCNKYGVSGYPTLKIFRDGEEAGAYDGPRT
ADGIVSHLKKQAGPASVPLRTEEEFKKFISDKDASIVGFFDDSFSEAHSEFLKAASNLRD
NYRFAHTNVESLVNEYDDNGEGIILFRPSHLTNKFEDKTVAYTEQKMTSGKIKKFIQENI
FGICPHMTEDNKDLIQGKDLLIAYYDVDYEKNAKGSNYWRNRVMMVAKKFLDAGHKLNFA
VASRKTFSHELSDFGLESTAGEIPVVAIRTAKGEKFVMQEEFSRDGKALERFLQDYFDGN
LKRYLKSEPIPESNDGPVKVVVAENFDEIVNNENKDVLIEFYAPWCGHCKNLEPKYKELG
EKLSKDPNIVIAKMDATANDVPSPYEVRGFPTIYFSPANKKLNPKKYEGGRELSDFISYL
QREATNPPVIQEEKPKKKKKAQEDL
Number of residues
505
Molecular Weight
56781.84
Theoretical pI
Not Available
GO Classification
Functions
identical protein binding / protein-disulfide reductase activity
Processes
adaptive immune response / cellular response to interleukin-7 / extrinsic apoptotic signaling pathway / peptide antigen assembly with MHC class I protein complex / platelet aggregation
Components
MHC class I peptide loading complex / Tapasin-ERp57 complex
General Function
Protein disulfide isomerase that catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins and functions as a protein folding chaperone (PubMed:11825568, PubMed:16193070, PubMed:27897272, PubMed:36104323, PubMed:7487104). Core component of the major histocompatibility complex class I (MHC I) peptide loading complex where it functions as an essential folding chaperone for TAPBP. Through TAPBP, assists the dynamic assembly of the MHC I complex with high affinity antigens in the endoplasmic reticulum. Therefore, plays a crucial role in the presentation of antigens to cytotoxic T cells in adaptive immunity (PubMed:35948544, PubMed:36104323)
Specific Function
Cysteine-type endopeptidase activity
Pfam Domain Function
Signal Regions
1-24
Transmembrane Regions
Not Available
Cellular Location
Endoplasmic reticulum
Gene sequence
>lcl|BSEQ0049676|Protein disulfide-isomerase A3 (PDIA3)
ATGCGCCTCCGCCGCCTAGCGCTGTTCCCGGGTGTGGCGCTGCTTCTTGCCGCGGCCCGC
CTCGCCGCTGCCTCCGACGTGCTAGAACTCACGGACGACAACTTCGAGAGTCGCATCTCC
GACACGGGCTCTGCGGGCCTCATGCTCGTCGAGTTCTTCGCCCCCTGGTGTGGACACTGC
AAGAGACTTGCACCTGAGTATGAAGCTGCAGCTACCAGATTAAAAGGAATAGTCCCATTA
GCAAAGGTTGATTGCACTGCCAACACTAACACCTGTAATAAATATGGAGTCAGTGGATAT
CCAACCCTGAAGATATTTAGAGATGGTGAAGAAGCAGGTGCTTATGATGGACCTAGGACT
GCTGATGGAATTGTCAGCCACTTGAAGAAGCAGGCAGGACCAGCTTCAGTGCCTCTCAGG
ACTGAGGAAGAATTTAAGAAATTCATTAGTGATAAAGATGCCTCTATAGTAGGTTTTTTC
GATGATTCATTCAGTGAGGCTCACTCCGAGTTCCTAAAAGCAGCCAGCAACTTGAGGGAT
AACTACCGATTTGCACATACGAATGTTGAGTCTCTGGTGAACGAGTATGATGATAATGGA
GAGGGTATCATCTTATTTCGTCCTTCACATCTCACTAACAAGTTTGAGGACAAGACTGTG
GCATATACAGAGCAAAAAATGACCAGTGGCAAAATTAAAAAGTTTATCCAGGAAAACATT
TTTGGTATCTGCCCTCACATGACAGAAGACAATAAAGATTTGATACAGGGCAAGGACTTA
CTTATTGCTTACTATGATGTGGACTATGAAAAGAACGCTAAAGGTTCCAACTACTGGAGA
AACAGGGTAATGATGGTGGCAAAGAAATTCCTGGATGCTGGGCACAAACTCAACTTTGCT
GTAGCTAGCCGCAAAACCTTTAGCCATGAACTTTCTGATTTTGGCTTGGAGAGCACTGCT
GGAGAGATTCCTGTTGTTGCTATCAGAACTGCTAAAGGAGAGAAGTTTGTCATGCAGGAG
GAGTTCTCGCGTGATGGGAAGGCTCTGGAGAGGTTCCTGCAGGATTACTTTGATGGCAAT
CTGAAGAGATACCTGAAGTCTGAACCTATCCCAGAGAGCAATGATGGGCCTGTGAAGGTA
GTGGTAGCAGAGAATTTTGATGAAATAGTGAATAATGAAAATAAAGATGTGCTGATTGAA
TTTTATGCCCCTTGGTGTGGTCACTGTAAGAACCTGGAGCCCAAGTATAAAGAACTTGGC
GAGAAGCTCAGCAAAGACCCAAATATCGTCATAGCCAAGATGGATGCCACAGCCAATGAT
GTGCCTTCTCCATATGAAGTCAGAGGTTTTCCTACCATATACTTCTCTCCAGCCAACAAG
AAGCTAAATCCAAAGAAATATGAAGGTGGCCGTGAATTAAGTGATTTTATTAGCTATCTA
CAAAGAGAAGCTACAAACCCCCCTGTAATTCAAGAAGAAAAACCCAAGAAGAAGAAGAAG
GCACAGGAGGATCTCTAA
Chromosome Location
15
Locus
15q15.3
External Identifiers
ResourceLink
UniProtKB IDP30101
UniProtKB Entry NamePDIA3_HUMAN
GeneCard IDPDIA3
HGNC IDHGNC:4606
PDB ID(s)2ALB, 2DMM, 2H8L, 3F8U, 6ENY, 7QNG, 7QPD
KEGG IDhsa:2923
NCBI Gene ID2923
General References
  1. Hirano N, Shibasaki F, Kato H, Sakai R, Tanaka T, Nishida J, Yazaki Y, Takenawa T, Hirai H: Molecular cloning and characterization of a cDNA for bovine phospholipase C-alpha: proposal of redesignation of phospholipase C-alpha. Biochem Biophys Res Commun. 1994 Oct 14;204(1):375-82. [Article]
  2. Bourdi M, Demady D, Martin JL, Jabbour SK, Martin BM, George JW, Pohl LR: 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. Arch Biochem Biophys. 1995 Nov 10;323(2):397-403. [Article]
  3. Koivunen P, Helaakoski T, Annunen P, Veijola J, Raisanen S, Pihlajaniemi T, Kivirikko KI: ERp60 does not substitute for protein disulphide isomerase as the beta-subunit of prolyl 4-hydroxylase. Biochem J. 1996 Jun 1;316 ( Pt 2):599-605. [Article]
  4. Charnock-Jones DS, Day K, Smith SK: Cloning, expression and genomic organization of human placental protein disulfide isomerase (previously identified as phospholipase C alpha). Int J Biochem Cell Biol. 1996 Jan;28(1):81-9. [Article]
  5. Koivunen P, Horelli-Kuitunen N, Helaakoski T, Karvonen P, Jaakkola M, Palotie A, Kivirikko KI: Structures of the human gene for the protein disulfide isomerase-related polypeptide ERp60 and a processed gene and assignment of these genes to 15q15 and 1q21. Genomics. 1997 Jun 15;42(3):397-404. [Article]
  6. 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. [Article]
  7. 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. [Article]
  8. 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. [Article]
  9. 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. [Article]
  10. 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. [Article]
  11. Rasmussen RK, Ji H, Eddes JS, Moritz RL, Reid GE, Simpson RJ, Dorow DS: Two-dimensional electrophoretic analysis of human breast carcinoma proteins: mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2. Electrophoresis. 1997 Mar-Apr;18(3-4):588-98. [Article]
  12. Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J: Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. Electrophoresis. 1992 Dec;13(12):960-9. [Article]
  13. Harris RA, Yang A, Stein RC, Lucy K, Brusten L, Herath A, Parekh R, Waterfield MD, O'Hare MJ, Neville MA, Page MJ, Zvelebil MJ: Cluster analysis of an extensive human breast cancer cell line protein expression map database. Proteomics. 2002 Feb;2(2):212-23. [Article]
  14. 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. [Article]
  15. Alanen HI, Williamson RA, Howard MJ, Hatahet FS, Salo KE, Kauppila A, Kellokumpu S, Ruddock LW: ERp27, a new non-catalytic endoplasmic reticulum-located human protein disulfide isomerase family member, interacts with ERp57. J Biol Chem. 2006 Nov 3;281(44):33727-38. Epub 2006 Aug 28. [Article]
  16. 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. [Article]
  17. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  18. Kameshwari DB, Bhande S, Sundaram CS, Kota V, Siva AB, Shivaji S: Glucose-regulated protein precursor (GRP78) and tumor rejection antigen (GP96) are unique to hamster caput epididymal spermatozoa. Asian J Androl. 2010 May;12(3):344-55. doi: 10.1038/aja.2010.19. Epub 2010 Apr 19. [Article]
  19. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  20. Rosenow A, Noben JP, Jocken J, Kallendrusch S, Fischer-Posovszky P, Mariman EC, Renes J: Resveratrol-induced changes of the human adipocyte secretion profile. J Proteome Res. 2012 Sep 7;11(9):4733-43. doi: 10.1021/pr300539b. Epub 2012 Aug 27. [Article]
  21. Marques PI, Ferreira Z, Martins M, Figueiredo J, Silva DI, Castro P, Morales-Hojas R, Simoes-Correia J, Seixas S: SERPINA2 is a novel gene with a divergent function from SERPINA1. PLoS One. 2013 Jun 24;8(6):e66889. doi: 10.1371/journal.pone.0066889. Print 2013. [Article]
  22. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  23. Guo A, Gu H, Zhou J, Mulhern D, Wang Y, Lee KA, Yang V, Aguiar M, Kornhauser J, Jia X, Ren J, Beausoleil SA, Silva JC, Vemulapalli V, Bedford MT, Comb MJ: Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol Cell Proteomics. 2014 Jan;13(1):372-87. doi: 10.1074/mcp.O113.027870. Epub 2013 Oct 15. [Article]
  24. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  25. Silvennoinen L, Koivunen P, Myllyharju J, Kilpelainen I, Permi P: NMR assignment of the N-terminal domain a of the glycoprotein chaperone ERp57. J Biomol NMR. 2005 Oct;33(2):136. [Article]
  26. Kozlov G, Maattanen P, Schrag JD, Pollock S, Cygler M, Nagar B, Thomas DY, Gehring K: Crystal structure of the bb' domains of the protein disulfide isomerase ERp57. Structure. 2006 Aug;14(8):1331-9. [Article]
  27. Dong G, Wearsch PA, Peaper DR, Cresswell P, Reinisch KM: Insights into MHC class I peptide loading from the structure of the tapasin-ERp57 thiol oxidoreductase heterodimer. Immunity. 2009 Jan 16;30(1):21-32. doi: 10.1016/j.immuni.2008.10.018. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Copperapproved, investigationalunknowntargetDetails
Zincapproved, investigationalunknowntargetDetails
Zinc acetateapproved, investigationalunknowntargetDetails
Zinc chlorideapproved, investigationalunknowntargetbinderDetails
Zinc sulfate, unspecified formapproved, experimentalunknowntargetbinderDetails