Reviewed, UniProtKB/Swiss-Prot Q2HWU2 (PDIA1_MACFU)

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

Gene names

Name:	P4HB
Synonyms:	PDI, PDIA1

Organism

Macaca fuscata fuscata (Japanese macaque)

Taxonomic identifier

9543 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca

Protein attributes

Sequence length	510 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Domain	Redox-active center Repeat Signal
Molecular function	Chaperone Isomerase
PTM	Disulfide bond
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 Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	By similarity
	Chain	20 – 510	491	Protein disulfide-isomerase		PRO_0000246155
Regions
	Domain	20 – 136	117	Thioredoxin 1
	Domain	351 – 477	127	Thioredoxin 2
	Motif	507 – 510	4	Prevents secretion from ER By similarity
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

Sequences

	Sequence		Length	Mass (Da)
	Q2HWU2-1 [UniParc]. Last modified March 21, 2006. Version 1. Checksum: 5F917B017F418BE2	FASTA	510	57,304
	10 20 30 40 50 60 MLRRALLCLA VAAAPGLYAD APEEEDHVLV LRKSNFAEAL AAHKYLLVEF YAPWCGHCKA 70 80 90 100 110 120 LAPEYAKAAG KLKAEGSEIR LAKVDATEES DLAQQYGVRG YPTIKFFRNG DTASPKEYTA 130 140 150 160 170 180 GREADDIVNW LKKRTGPAAT TLPDGAAAES LVESSEVAVI GFFKDVESDS AKQFLQAAEA 190 200 210 220 230 240 IDDIPFGITS NSDVFSKYQL DKDGVVLFKK FDEGRNNFEG EVTKENLLDF IKYNQLPLVI 250 260 270 280 290 300 EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY DGKLSNFKTA AESFKGKILF IFIDSDHTDN 310 320 330 340 350 360 QRILEFFGLK KEECPAVRLI TLEEEMTKYK PESDELTAER ITEFCHRFLE GKIKPHLMSQ 370 380 390 400 410 420 ELPEDWDKQP VKVLVGKNFE EVAFDENKNV FVEFYAPWCG HCKQLAPIWD KLGETYKDHE 430 440 450 460 470 480 NIVIAKMDST ANEVEAIKVH SFPTLKFFPA SVDRTVIDYN GERTLDGFKK FLESGGQDGA 490 500 510 GDDDDLEDLE EAEEPDMEED DDQKAVKDEL

References

[1]	"Molecular cloning and gene expression of endoplasmic reticulum stress proteins in Japanese monkey, Macaca fuscata." Higashino A., Fukuhara R., Tezuka T., Kageyama T. J. Med. Primatol. 35:376-383(2006) [PubMed: 17214666] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB232156 mRNA. Translation: BAE79726.1.
3D structure databases
SMR	Q2HWU2. Positions 20-139, 24-475.
ModBase	Search...
Phylogenomic databases
HOVERGEN	Q2HWU2.
Enzyme and pathway databases
BRENDA	5.3.4.1. 276174.
Family and domain databases
InterPro	IPR005788. Disulphide_isomerase. IPR005792. Prot_disulphide_isomerase. IPR017936. Thioredoxin-like. IPR012336. Thioredoxin-like_fold. 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...

Entry information

Entry name

PDIA1_MACFU

Accession

Primary (citable) accession number: Q2HWU2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	March 21, 2006
Last modified:	February 9, 2010
This is version 34 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)