UniProt Accession

 PDIA1_HUMAN; P07237; B2RDQ2; P30037; P32079; Q15205; Q6LDE5 

Genbank Protein ID

 X05130; J02783; M22806; M22803; M22804; M22805; AK315631; CH471099; BC010859; BC029617; BC071892; S37207; X07077 

Genbank Nucleotide ID

 CAA28775.1; AAA61169.1; AAC13652.1; AAC13652.1; AAC13652.1; AAC13652.1; BAG37999.1; EAW89690.1; AAH10859.1; AAH29617.1; AAH71892.1; AAB22262.2; CAA30112.1 

Protein Name

 Protein disulfide-isomerase 

Protein Synonyms/Alias

 PDI; Cellular thyroid hormone-binding protein; Prolyl 4-hydroxylase subunit beta; p55 

Gene Name

 P4HB 

Gene Synonyms/Alias

 ERBA2L; PDI; PDIA1; PO4DB 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
81	GSEIRLAKVDATEES	ubiquitination	[1, 2, 3]
103	VRGYPTIKFFRNGDT	ubiquitination	[2, 4, 5, 6]
130	DDIVNWLKKRTGPAA	ubiquitination	[4, 6]
200	FSKYQLDKDGVVLFK	ubiquitination	[4, 5, 6]
222	NFEGEVTKENLLDFI	ubiquitination	[1, 4, 6]
247	FTEQTAPKIFGGEIK	ubiquitination	[4, 6]
271	SVSDYDGKLSNFKTA	ubiquitination	[4, 5, 6]
308	ILEFFGLKKEECPAV	ubiquitination	[1, 3]
375	PVKVLVGKNFEDVAF	ubiquitination	[4, 5, 6]
409	QLAPIWDKLGETYKD	acetylation	[7]
444	VHSFPTLKFFPASAD	ubiquitination	[4, 5, 6]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 18 134 Thioredoxin 1.
 DOMAIN 349 475 Thioredoxin 2.
 MOTIF 505 508 Prevents secretion from ER.
 ACT_SITE 53 53 Nucleophile.
 ACT_SITE 56 56 Nucleophile.
 ACT_SITE 397 397 Nucleophile (By similarity).
 ACT_SITE 400 400 Nucleophile (By similarity).
 DISULFID 53 56 Redox-active.
 DISULFID 397 400 Redox-active (By similarity).  

Keyword

 3D-structure; Cell membrane; Chaperone; Complete proteome; Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Isomerase; Membrane; Redox-active center; Reference proteome; Repeat; Signal. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 508 AA 

Protein Sequence

Gene Ontology

 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
 GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
 GO:0005576; C:extracellular region; NAS:UniProtKB.
 GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0009055; F:electron carrier activity; IEA:InterPro.
 GO:0004656; F:procollagen-proline 4-dioxygenase activity; IDA:MGI.
 GO:0003756; F:protein disulfide isomerase activity; TAS:ProtInc.
 GO:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
 GO:0045454; P:cell redox homeostasis; IEA:InterPro.
 GO:0030198; P:extracellular matrix organization; TAS:Reactome.
 GO:0006662; P:glycerol ether metabolic process; IEA:InterPro.
 GO:0006629; P:lipid metabolic process; TAS:Reactome.
 GO:0042157; P:lipoprotein metabolic process; TAS:Reactome.
 GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IDA:MGI. 

Interpro

 IPR005788; Disulphide_isomerase.
 IPR005792; Prot_disulphide_isomerase.
 IPR005746; Thioredoxin.
 IPR012336; Thioredoxin-like_fold.
 IPR017937; Thioredoxin_CS.
 IPR013766; Thioredoxin_domain. 

Pfam

 PF00085; Thioredoxin 

SMART

  

PROSITE

 PS00014; ER_TARGET
 PS00194; THIOREDOXIN_1
 PS51352; THIOREDOXIN_2 

PRINTS

 PR00421; THIOREDOXIN.