Reviewed, UniProtKB/Swiss-Prot P21195 (PDIA1_RABIT)

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
    p55

Gene names

Name:	P4HB
Synonyms:	PDIA1

Organism

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

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 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 – 18	18	By similarity
	Chain	19 – 509	491	Protein disulfide-isomerase		PRO_0000034198
Regions
	Domain	19 – 135	117	Thioredoxin 1
	Domain	347 – 476	130	Thioredoxin 2
	Motif	506 – 509	4	Prevents secretion from ER
Sites
	Active site	54	1	Nucleophile By similarity
	Active site	57	1	Nucleophile By similarity
	Active site	398	1	Nucleophile By similarity
	Active site	401	1	Nucleophile By similarity
	Site	55	1	Contributes to redox potential value By similarity
	Site	56	1	Contributes to redox potential value By similarity
	Site	121	1	Lowers pKa of C-terminal Cys of first active site By similarity
	Site	399	1	Contributes to redox potential value By similarity
	Site	400	1	Contributes to redox potential value By similarity
	Site	462	1	Lowers pKa of C-terminal Cys of second active site By similarity
Amino acid modifications
	Disulfide bond	54 ↔ 57		Redox-active By similarity
	Disulfide bond	398 ↔ 401		Redox-active By similarity

Sequences

	Sequence		Length	Mass (Da)
	P21195-1 [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 093C8C18E209BAB5	FASTA	509	56,808
	10 20 30 40 50 60 MLRRAVLCLA LAVTAGWAWA AEEEDNVLVL KSSNFAEELA AHKHLLVEFY APWCGHCKAL 70 80 90 100 110 120 APEYAKAAGK LKAEGSDIRL AKVDATEESD LAQQYGVRGY PTIKFFKNGD TASPKEYTAG 130 140 150 160 170 180 READDIVNWL KKRTGPAATT LADSAAAESL VESSEVAVIG FFKDVESDAA KQFLLAAEAT 190 200 210 220 230 240 DDIPFGLTAS SDVFSRYQVH QDGVVLFKKF DEGRNNFEGE VTKEKLLDFI KHNQLPLVIE 250 260 270 280 290 300 FTEQTAPKIF GGEIKTHILL FLPRSAADHD GKLSGFKQAA EGFKGKILFI FIDSDHADNQ 310 320 330 340 350 360 RILEFFGLKK EECPAVRLIT LEEEMTKYKP ESDELTAEGI TEFCQRFLEG KIKPHLMSQE 370 380 390 400 410 420 LPEDWDRQPV KVLVGKNFEE VAFDEKKNVF VEFYAPWCGH CKQLAPIWDK LGETYKEHQD 430 440 450 460 470 480 IVIAKMDSTA NEVEAVKVHS FPTLKFFPAG PGRTVIDYNG ERTLDGFKKF LESGGQDGAG 490 500 DEDGLEDLEE AEEPDLEEDD DQKAVRDEL

References

[1]	"Molecular cloning of cDNA encoding a 55-kDa multifunctional thyroid hormone binding protein of skeletal muscle sarcoplasmic reticulum." Fliegel L., Newton E., Burns K., Michalak M. J. Biol. Chem. 265:15496-15502(1990) [PubMed: 1697592] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBLGenBankDDBJ	J05602 mRNA. Translation: AAA31476.1.
PIR	A38362.
3D structure databases
HSSP	HSSP built from PDB template 1MEK based on UniProtKB P07237.
SMR	P21195. Positions 20-138, 369-472.
ModBase	Search...
Protein-protein interaction databases
STRING	P21195.
Phylogenomic databases
HOVERGEN	P21195.
Enzyme and pathway databases
BRENDA	5.3.4.1. 255.
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...

Entry information

Entry name

PDIA1_RABIT

Accession

Primary (citable) accession number: P21195

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	October 13, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)