Reviewed, UniProtKB/Swiss-Prot P04785 (PDIA1_RAT)

Names and origin

Protein names

Recommended name:
    Protein disulfide-isomerase
      Short name=PDI
    EC=5.3.4.1
Alternative name(s):
    Prolyl 4-hydroxylase subunit beta
    Cellular thyroid hormone-binding protein

Gene names

Name:	P4hb
Synonyms:	Pdia1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

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 By similarity.
Catalytic activity	Catalyzes the rearrangement of -S-S- bonds in proteins.
Subunit structure	Homodimer. Monomers and homotetramers may also occur. Also constitutes the structural subunit of prolyl 4-hydroxylase and of the microsomal triacylglycerol transfer protein MTTP in mammalian cells. Stabilizes both enzymes and retain them in the ER without contributing to the catalytic activity. Binds UBQLN1 By similarity.
Subcellular location	Endoplasmic reticulum lumen By similarity. Melanosome By similarity. Cell membrane; Peripheral membrane protein Potential. Note: Highly abundant. In some cell types, seems to be also secreted or associated with the plasma membrane, where it undergoes constant shedding and replacement from intracellular sources. Localizes near CD4-enriched regions on lymphoid cell surfaces By similarity.
Sequence similarities	Belongs to the protein disulfide isomerase family. Contains 2 thioredoxin domains.
Caution	Was originally (Ref.3 and Ref.4) thought to be identical to thyroxine deiodinase but this was later shown (Ref.8) to be incorrect.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Domain	Redox-active center Repeat Signal
Molecular function	Chaperone Isomerase
PTM	Disulfide bond
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	protein disulfide isomerase activity Ref.5 Inferred from mutant phenotype. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Ref.3
	Chain	20 – 509	490	Protein disulfide-isomerase		PRO_0000034199
Regions
	Domain	20 – 136	117	Thioredoxin 1
	Domain	335 – 477	143	Thioredoxin 2
	Motif	506 – 509	4	Prevents secretion from ER
Sites
	Active site	55	1	Nucleophile By similarity
	Active site	58	1	Nucleophile By similarity
	Active site	399	1	Nucleophile By similarity
	Active site	402	1	Nucleophile By similarity
	Site	56	1	Contributes to redox potential value By similarity
	Site	57	1	Contributes to redox potential value By similarity
	Site	122	1	Lowers pKa of C-terminal Cys of first active site By similarity
	Site	400	1	Contributes to redox potential value By similarity
	Site	401	1	Contributes to redox potential value By similarity
	Site	463	1	Lowers pKa of C-terminal Cys of second active site By similarity
Amino acid modifications
	Disulfide bond	55 ↔ 58		Redox-active By similarity
	Disulfide bond	399 ↔ 402		Redox-active By similarity
Experimental info
	Sequence conflict	39 – 40	2	AL → P in CAA26675. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P04785-1 [UniParc]. Last modified October 1, 1989. Version 2. Checksum: 3056107F5E8B1B54	FASTA	509	56,951
	10 20 30 40 50 60 MLSRALLCLA LAWAARVGAD ALEEEDNVLV LKKSNFAEAL AAHNYLLVEF YAPWCGHCKA 70 80 90 100 110 120 LAPEYAKAAA KLKAEGSEIR LAKVDATEES DLAQQYGVRG YPTIKFFKNG DTASPKEYTA 130 140 150 160 170 180 GREADDIVNW LKKRTGPAAT TLSDTAAAES LVDSSEVTVI GFFKDAGSDS AKQFLLAAEA 190 200 210 220 230 240 VDDIPFGITS NSDVFSKYQL DKDGVVLFKK FDEGRNNFEG EITKEKLLDF IKHNQLPLVI 250 260 270 280 290 300 EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY DGKLSNFKKA AEGFKGKILF IFIDSDHTDN 310 320 330 340 350 360 QRILEFFGLK KEECPAVRLI TLEEEMTKYK PESDELTAEK ITQFCHHFLE GKIKPHLMSQ 370 380 390 400 410 420 ELPEDWDKQP VKVLVGKNFE EVAFDEKKNV FVEFYAPWCG HCKQLAPIWD KLGETYKDHE 430 440 450 460 470 480 NIVIAKMDST ANEVEAVKVH SFPTLKFFPA SADRTVIDYN GERTLDGFKK FLESGGQDGA 490 500 GDNDDLDLEE ALEPDMEEDD DQKAVKDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of protein disulphide isomerase and implications of its relationship to thioredoxin." Edman J.C., Ellis L., Blacher R.W., Roth R.A., Rutter W.J. Nature 317:267-270(1985) [PubMed: 3840230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[3]	"Identification of protein disulfide isomerase and calreticulin as autoimmune antigens in LEC strain of rats." Yokoi T., Nagayama S., Kajiwara R., Kawaguchi Y., Horiuchi R., Kamataki T. Biochim. Biophys. Acta 1158:339-344(1993) [PubMed: 8251535] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-34. Strain: LEC. Tissue: Liver.
[4]	"Nucleotide sequence of rat liver iodothyronine 5'-monodeiodinase (5' MD): its identity with the protein disulfide isomerase." Boado R.J., Campbell D.A., Chopra I.J. Biochem. Biophys. Res. Commun. 155:1297-1304(1988) [PubMed: 3178809] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 28-509. Tissue: Liver.
[5]	"Enzyme binding-inhibiting assay for iodothyronine 5'-monodeiodinase (5'-MD) and its application to isolation of complementary deoxyribonucleic acid clones for the 5'-MD in rat liver." Boado R.J., Chopra I.J., Flink I.L., Campbell D.A. Endocrinology 123:1264-1273(1988) [PubMed: 2841089] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 129-394. Tissue: Liver.
[6]	Lubec G., Afjehi-Sadat L., Chen W.-Q. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 233-249; 288-302 AND 341-352, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus and Spinal cord.
[7]	"Peptide binding to protein disulfide isomerase occurs at a site distinct from the active sites." Noiva R., Freedman R.B., Lennarz W.J. J. Biol. Chem. 268:19210-19217(1993) [PubMed: 8366073] [Abstract] Cited for: PROTEIN SEQUENCE OF 471-494.
[8]	"Rat liver type I iodothyronine deiodinase is not identical to protein disulfide isomerase." Schoenmakers C.H.H., Pigmans I.G.A.J., Hawkins H.C., Freedman R.B., Visser T.J. Biochem. Biophys. Res. Commun. 162:857-868(1989) [PubMed: 2757644] [Abstract] Cited for: SHOWS THAT PROTEIN IS NOT IDENTICAL TO THYROXINE DEIODINASE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M21018 mRNA. Translation: AAA40620.1. BC061857 mRNA. Translation: AAH61857.1. X02918 mRNA. Translation: CAA26675.1. M21476 mRNA. Translation: AAA40619.1.
IPI	IPI00198887.
PIR	ISRTSS. A24595. S68028.
RefSeq	NP_037130.1.
UniGene	Rn.4234
3D structure databases
HSSP	HSSP built from PDB template 1MEK based on UniProtKB P07237.
SMR	P04785. Positions 20-139, 370-473.
ModBase	Search...
Protein-protein interaction databases
STRING	P04785.
PTM databases
PhosphoSite	P04785.
Proteomic databases
PRIDE	P04785.
Genome annotation databases
Ensembl	ENSRNOT00000054958; ENSRNOP00000051841; ENSRNOG00000036689; Rattus norvegicus. [Genome view]
GeneID	25506.
KEGG	rno:25506.
UCSC	NM_012998. rat.
Organism-specific databases
CTD	25506.
RGD	3244. P4hb.
Phylogenomic databases
HOVERGEN	P04785.
OMA	EYTAGRE.
Enzyme and pathway databases
BRENDA	5.3.4.1. 248.
Gene expression databases
ArrayExpress	P04785.
Genevestigator	P04785.
GermOnline	ENSRNOG00000036689. Rattus norvegicus.
Family and domain databases
InterPro	IPR005788. Disulphide_isomerase. IPR000886. ER_target_seq_motif. IPR005792. Prot_disulphide_isomerase. IPR017936. Thioredoxin-like. IPR006662. Thioredoxin-like_subdom. IPR017937. Thioredoxin_CS. IPR013766. Thioredoxin_domain. IPR012335. Thioredoxin_fold. [Graphical view]
Gene3D	G3DSA:3.40.30.10. Thioredoxin_fold. 2 hits.
Pfam	PF00085. Thioredoxin. 2 hits. [Graphical view]
PRINTS	PR00421. THIOREDOXIN.
TIGRFAMs	TIGR01130. ER_PDI_fam. 1 hit. TIGR01126. pdi_dom. 2 hits.
PROSITE	PS00014. ER_TARGET. 1 hit. PS00194. THIOREDOXIN_1. 2 hits. PS51352. THIOREDOXIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	606925.

Entry information

Entry name

PDIA1_RAT

Accession

Primary (citable) accession number: P04785
Secondary accession number(s): P13700

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	October 1, 1989
Last modified:	November 3, 2009
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)