P11598 (PDIA3_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein disulfide-isomerase A3
EC=5.3.4.1

Alternative name(s):
58 kDa glucose-regulated protein
58 kDa microsomal protein
Short name=p58
Disulfide isomerase ER-60
Endoplasmic reticulum resident protein 57
Short name=ER protein 57
Short name=ERp57
Endoplasmic reticulum resident protein 60
Short name=ER protein 60
Short name=ERp60
HIP-70
Q-2

Gene names

Name:	Pdia3
Synonyms:	Erp60, Grp58

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	505 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)

Catalytic activity	Catalyzes the rearrangement of -S-S- bonds in proteins.
Enzyme regulation	Seems to be inhibited by acidic phospholipids.
Subunit structure	Subunit of the TAP complex, also known as the peptide loading complex (PLC). Can form disulfide-linked heterodimers with TAPBP. Interacts with ERP27 and CANX By similarity.
Subcellular location	Endoplasmic reticulum lumen. Melanosome By similarity.
Tissue specificity	In caput epididymal spermatozoa, detected in the head, mid and principal pieces. In cauda epididymal spermatozoa detected only in the acrosome (at protein level). Ref.11
Sequence similarities	Belongs to the protein disulfide isomerase family. Contains 2 thioredoxin domains.
Caution	Was originally (Ref.1) thought to be a phosphatidyl-inositol-4,5-bisphosphate phosphodiesterase type I (phospholipase C-alpha) then was thought (Ref.7 and Ref.10) to be a thiol protease.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Domain	Redox-active center Repeat Signal
Molecular function	Isomerase
PTM	Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from electronic annotation. Source: InterPro glycerol ether metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	electron carrier activity Inferred from electronic annotation. Source: InterPro protein disulfide isomerase activity Inferred from electronic annotation. Source: EC protein disulfide oxidoreductase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Ref.6
	Chain	25 – 505	481	Protein disulfide-isomerase A3		PRO_0000034227
Regions
	Domain	25 – 133	109	Thioredoxin 1
	Domain	343 – 485	143	Thioredoxin 2
	Motif	502 – 505	4	Prevents secretion from ER
Sites
	Active site	57	1	Nucleophile By similarity
	Active site	60	1	Nucleophile By similarity
	Active site	406	1	Nucleophile By similarity
	Active site	409	1	Nucleophile By similarity
	Site	58	1	Contributes to redox potential value By similarity
	Site	59	1	Contributes to redox potential value By similarity
	Site	119	1	Lowers pKa of C-terminal Cys of first active site By similarity
	Site	407	1	Contributes to redox potential value By similarity
	Site	408	1	Contributes to redox potential value By similarity
	Site	471	1	Lowers pKa of C-terminal Cys of second active site By similarity
Amino acid modifications
	Disulfide bond	57 ↔ 60		Redox-active; alternate By similarity
	Disulfide bond	57		Interchain (with C-115 in TAPBP); alternate By similarity
	Disulfide bond	85 ↔ 92		By similarity
	Disulfide bond	406 ↔ 409		Redox-active By similarity
Experimental info
	Mutagenesis	502 – 505	4	QEDL → AAGL: Failure to prevent secretion from ER. Ref.9
	Mutagenesis	502 – 505	4	Missing: Failure to prevent secretion from ER. Ref.9
	Sequence conflict	1 – 13	13	MRFSC…LPGVA → MPSAALRCSRAWR Ref.1
	Sequence conflict	98	1	S → T in CAA30916. Ref.1
	Sequence conflict	232 – 240	9	IKKFIQESI → SRSLFRKA in CAA30916. Ref.1
	Sequence conflict	476	1	F → L in BAA09695. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P11598 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: EAC7F0C0BD4F1471	FASTA	505	56,623
	10 20 30 40 50 60 MRFSCLALLP GVALLLASAL LASASDVLEL TDENFESRVS DTGSAGLMLV EFFAPWCGHC 70 80 90 100 110 120 KRLAPEYEAA ATRLKGIVPL AKVDCTANTN TCNKYGVSGY PTLKIFRDGE EAGAYDGPRT 130 140 150 160 170 180 ADGIVSHLKK QAGPASVPLR TEDEFKKFIS DKDASVVGFF RDLFSDGHSE FLKAASNLRD 190 200 210 220 230 240 NYRFAHTNVE SLVKEYDDNG EGITIFRPLH LANKFEDKIV AYTEKKMTSG KIKKFIQESI 250 260 270 280 290 300 FGLCPHMTED NKDLIQGKDL LTAYYDVDYE KNTKGSNYWR NRVMMVAKTF LDAGHKLNFA 310 320 330 340 350 360 VASRKTFSHE LSDFGLESTT GEIPVVAIRT AKGEKFVMQE EFSRDGKALE RFLQEYFDGN 370 380 390 400 410 420 LKRYLKSEPI PETNEGPVKV VVAESFDDIV NAEDKDVLIE FYAPWCGHCK NLEPKYKELG 430 440 450 460 470 480 EKLSKDPNIV IAKMDATAND VPSPYEVKGF PTIYFSPANK KLTPKKYEGG RELNDFISYL 490 500 QREATNPPII QEEKPKKKKK AQEDL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and complete amino-acid sequence of form-I phosphoinositide-specific phospholipase C." Bennett C.F., Balcarek J.M., Varrichio A., Crooke S.T. Nature 334:268-270(1988) [PubMed: 3398923] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Role of novel microsomal cysteine proteases." Kito M., Urade R. Proc. Jpn. Acad., B, Phys. Biol. Sci. 71:189-192(1995) Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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.
[4]	"A metabolite of halothane covalently binds to an endoplasmic reticulum protein that is highly homologous to phosphatidylinositol-specific phospholipase C-alpha but has no activity." Martin J.L., Pumford N.R., Larosa A.C., Martin B.M., Gonzaga H.M.S., Beaven M.A., Pohl L.R. Biochem. Biophys. Res. Commun. 178:679-685(1991) [PubMed: 1650195] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[5]	"HIP-70: a protein induced by estrogen in the brain and LH-RH in the pituitary." Mobbs C.V., Fink G., Pfaff D.W. Science 247:1477-1479(1990) [PubMed: 2181662] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-43. Tissue: Brain and Pituitary.
[6]	"Purification and characterization of a new isozyme of thiol:protein-disulfide oxidoreductase from rat hepatic microsomes. Relationship of this isozyme to cytosolic phosphatidylinositol-specific phospholipase C form 1A." Srivastava S.P., Chen N.Q., Liu Y.X., Holtzman J.L. J. Biol. Chem. 266:20337-20344(1991) [PubMed: 1657921] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-54; 258-269; 285-310; 347-350; 412-419 AND 434-463. Tissue: Liver.
[7]	"Protein degradation by the phosphoinositide-specific phospholipase C-alpha family from rat liver endoplasmic reticulum." Urade R., Nasu M., Moriyama T., Wada K., Kito M. J. Biol. Chem. 267:15152-15159(1992) [PubMed: 1321829] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-34; 174-193; 433-446 AND 448-458.
[8]	Lubec G., Afjehi-Sadat L. Submitted (DEC-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 105-119; 148-161; 184-214; 259-271; 306-329; 336-344; 352-363; 449-460 AND 472-482, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Spinal cord.
[9]	"Functions of characteristic Cys-Gly-His-Cys (CGHC) and Gln-Glu-Asp-Leu (QEDL) motifs of microsomal ER-60 protease." Urade R., Oda T., Ito H., Moriyama T., Utsumi S., Kito M. J. Biochem. 122:834-842(1997) [PubMed: 9399589] [Abstract] Cited for: MUTAGENESIS OF 502-GLN--LEU-505.
[10]	"Inhibition by acidic phospholipids of protein degradation by ER-60 protease, a novel cysteine protease, of endoplasmic reticulum." Urade R., Kito M. FEBS Lett. 312:83-86(1992) [PubMed: 1330685] [Abstract] Cited for: INHIBITION BY PHOSPHOLIPIDS.
[11]	"Glucose-regulated protein precursor (GRP78) and tumor rejection antigen (GP96) are unique to hamster caput epididymal spermatozoa." Kameshwari D.B., Bhande S., Sundaram C.S., Kota V., Siva A.B., Shivaji S. Asian J. Androl. 12:344-355(2010) [PubMed: 20400973] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X12355 mRNA. Translation: CAA30916.1. D63378 mRNA. Translation: BAA09695.1. BC062393 mRNA. Translation: AAH62393.1.
IPI	IPI00324741.
PIR	A28807. A61354.
RefSeq	NP_059015.1. NM_017319.1.
UniGene	Rn.11527.
3D structure databases
ProteinModelPortal	P11598.
SMR	P11598. Positions 25-488.
ModBase	Search...
Protein-protein interaction databases
IntAct	P11598. 2 interactions.
MINT	MINT-4575564.
STRING	P11598.
PTM databases
PhosphoSite	P11598.
2D gel databases
World-2DPAGE	0004:P11598.
Proteomic databases
PRIDE	P11598.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000020478; ENSRNOP00000020478; ENSRNOG00000015018.
GeneID	29468.
KEGG	rno:29468.
UCSC	NM_017319. rat.
Organism-specific databases
CTD	2923.
RGD	68430. Pdia3.
Phylogenomic databases
eggNOG	roNOG09779.
GeneTree	ENSGT00590000082864.
HOVERGEN	HBG005920.
InParanoid	P11598.
OrthoDB	EOG42Z4PX.
PhylomeDB	P11598.
Gene expression databases
ArrayExpress	P11598.
Genevestigator	P11598.
GermOnline	ENSRNOG00000015018. Rattus norvegicus.
Family and domain databases
InterPro	IPR005788. Disulphide_isomerase. IPR005792. Prot_disulphide_isomerase. IPR005746. Thioredoxin. IPR012336. Thioredoxin-like_fold. IPR017937. Thioredoxin_CS. IPR013766. Thioredoxin_domain. [Graphical view]
Gene3D	G3DSA:3.40.30.10. Thioredoxin_fold. 3 hits.
KO	K08056.
Pfam	PF00085. Thioredoxin. 2 hits. [Graphical view]
PRINTS	PR00421. THIOREDOXIN.
SUPFAM	SSF52833. Thiordxn-like_fd. 4 hits.
TIGRFAMs	TIGR01130. ER_PDI_fam. 1 hit. TIGR01126. Pdi_dom. 2 hits.
PROSITE	PS00194. THIOREDOXIN_1. 2 hits. PS51352. THIOREDOXIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	609284.

Entry information

Entry name

PDIA3_RAT

Accession

Primary (citable) accession number: P11598

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	February 1, 1996
Last modified:	November 16, 2011
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program