P09103 (PDIA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein disulfide-isomerase
Short name=PDI
EC=5.3.4.1

Alternative name(s):
Cellular thyroid hormone-binding protein
Endoplasmic reticulum resident protein 59
Short name=ER protein 59
Short name=ERp59
Prolyl 4-hydroxylase subunit beta
p55

Gene names

Name:	P4hb
Synonyms:	Pdia1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Domain	Redox-active center Repeat Signal
Molecular function	Chaperone Isomerase
PTM	Disulfide bond
Technical term	Complete proteome 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 peptidyl-proline hydroxylation to 4-hydroxy-L-proline Inferred from sequence orthology PubMed 7753822. Source: MGI protein folding Inferred from electronic annotation. Source: GOC
Cellular_component	cell surface Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from direct assay PubMed 15767459PubMed 15767678PubMed 18094359PubMed 9493907PubMed 9806833. Source: MGI endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum-Golgi intermediate compartment Inferred from electronic annotation. Source: Compara melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro procollagen-proline 4-dioxygenase activity Inferred from sequence orthology PubMed 7753822. Source: MGI 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 – 19	19	By similarity
	Chain	20 – 509	490	Protein disulfide-isomerase		PRO_0000034196
Regions
	Domain	20 – 136	117	Thioredoxin 1
	Domain	348 – 477	130	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	68	1	A → R in CAA29759. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P09103 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 1FB0AA8ACCDB13EA	FASTA	509	57,058
	10 20 30 40 50 60 MLSRALLCLA LAWAARVGAD ALEEEDNVLV LKKSNFEEAL AAHKYLLVEF YAPWCGHCKA 70 80 90 100 110 120 LAPEYAKAAA KLKAEGSEIR LAKVDATEES DLAQQYGVRG YPTIKFFKNG DTASPKEYTA 130 140 150 160 170 180 GREADDIVNW LKKRTGPAAT TLSDTAAAES LVDSSEVTVI GFFKDVESDS AKQFLLAAEA 190 200 210 220 230 240 IDDIPFGITS NSGVFSKYQL DKDGVVLFKK FDEGRNNFEG EITKEKLLDF IKHNQLPLVI 250 260 270 280 290 300 EFTEQTAPKI FGGEIKTHIL LFLPKSVSDY DGKLSSFKRA AEGFKGKILF IFIDSDHTDN 310 320 330 340 350 360 QRILEFFGLK KEECPAVRLI TLEEEMTKYK PESDELTAEK ITEFCHRFLE GKIKPHLMSQ 370 380 390 400 410 420 EVPEDWDKQP VKVLVGANFE EVAFDEKKNV FVEFYAPWCG HCKQLAPIWD KLGETYKDHE 430 440 450 460 470 480 NIIIAKMDST ANEVEAVKVH SFPTLKFFPA SADRTVIDYN GERTLDGFKK FLESGGQDGA 490 500 GDDEDLDLEE ALEPDMEEDD DQKAVKDEL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of a full-length cDNA clone encoding a mouse cellular thyroid hormone binding protein (p55) that is homologous to protein disulfide isomerase and the beta-subunit of prolyl-4-hydroxylase." Gong Q.-H., Fukuda T., Parkison C., Cheng S.-Y. Nucleic Acids Res. 16:1203-1203(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase." Mazzarella R.A., Srinivasan M., Haugejorden S.M., Green M. J. Biol. Chem. 265:1094-1101(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J, DBA/2 and NOD. Tissue: Bone marrow and Stomach.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Czech II and FVB/N. Tissue: Liver and Mammary tumor.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X06453 mRNA. Translation: CAA29759.1. J05185 mRNA. Translation: AAA39906.1. AK150002 mRNA. Translation: BAE29230.1. AK150422 mRNA. Translation: BAE29545.1. AK150805 mRNA. Translation: BAE29868.1. AK152141 mRNA. Translation: BAE30979.1. AK152217 mRNA. Translation: BAE31045.1. AK159606 mRNA. Translation: BAE35225.1. AK159965 mRNA. Translation: BAE35520.1. AK168330 mRNA. Translation: BAE40268.1. AK168893 mRNA. Translation: BAE40710.1. AK170603 mRNA. Translation: BAE41907.1. AL663030 Genomic DNA. Translation: CAM27084.1. BC008549 mRNA. Translation: AAH08549.1. BC093512 mRNA. Translation: AAH93512.1.
IPI	IPI00133522.
PIR	ISMSSS. A34930.
RefSeq	NP_035162.1. NM_011032.2.
UniGene	Mm.16660. Mm.490258.
3D structure databases
HSSP	HSSP built from PDB template 1MEK based on UniProtKB P07237.
ProteinModelPortal	P09103.
SMR	P09103. Positions 20-480.
ModBase	Search...
Protein-protein interaction databases
IntAct	P09103. 4 interactions.
MINT	MINT-1177082.
STRING	10090.ENSMUSP00000026122.
PTM databases
PhosphoSite	P09103.
2D gel databases
COMPLUYEAST-2DPAGE	P09103.
REPRODUCTION-2DPAGE	P09103.
SWISS-2DPAGE	P09103.
Proteomic databases
PaxDb	P09103.
PRIDE	P09103.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000026122; ENSMUSP00000026122; ENSMUSG00000025130.
GeneID	18453.
KEGG	mmu:18453.
Organism-specific databases
CTD	5034.
MGI	MGI:97464. P4hb.
Phylogenomic databases
eggNOG	COG0526.
GeneTree	ENSGT00700000104429.
HOGENOM	HOG000162459.
HOVERGEN	HBG005920.
InParanoid	Q922C8.
KO	K09580.
OMA	AEDIVNW.
OrthoDB	EOG4JWVDB.
Gene expression databases
ArrayExpress	P09103.
Bgee	P09103.
CleanEx	MM_P4HB.
Genevestigator	P09103.
GermOnline	ENSMUSG00000025130. Mus musculus.
Family and domain databases
Gene3D	3.40.30.10. 4 hits.
InterPro	IPR005788. Disulphide_isomerase. IPR005792. Prot_disulphide_isomerase. IPR005746. Thioredoxin. IPR012336. Thioredoxin-like_fold. IPR017937. Thioredoxin_CS. IPR013766. Thioredoxin_domain. [Graphical view]
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	PS00014. ER_TARGET. 1 hit. PS00194. THIOREDOXIN_1. 2 hits. PS51352. THIOREDOXIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	P4HB. mouse.
NextBio	294144.
SOURCE	Search...

Entry information

Entry name

PDIA1_MOUSE

Accession

Primary (citable) accession number: P09103
Secondary accession number(s): Q922C8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program