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Protein

Protein disulfide-isomerase

Gene

P4hb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

Catalyzes the rearrangement of -S-S- bonds in proteins.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei55 – 551NucleophileBy similarity
Sitei56 – 561Contributes to redox potential valueBy similarity
Sitei57 – 571Contributes to redox potential valueBy similarity
Active sitei58 – 581NucleophileBy similarity
Sitei122 – 1221Lowers pKa of C-terminal Cys of first active siteBy similarity
Active sitei399 – 3991NucleophileBy similarity
Sitei400 – 4001Contributes to redox potential valueBy similarity
Sitei401 – 4011Contributes to redox potential valueBy similarity
Active sitei402 – 4021NucleophileBy similarity
Sitei463 – 4631Lowers pKa of C-terminal Cys of second active siteBy similarity

GO - Molecular functioni

  1. poly(A) RNA binding Source: MGI
  2. procollagen-proline 4-dioxygenase activity Source: Ensembl
  3. protein disulfide isomerase activity Source: GO_Central

GO - Biological processi

  1. cell redox homeostasis Source: InterPro
  2. cellular response to hypoxia Source: MGI
  3. peptidyl-proline hydroxylation to 4-hydroxy-L-proline Source: MGI
  4. protein folding Source: GO_Central
  5. regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: MGI
  6. response to endoplasmic reticulum stress Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Isomerase

Enzyme and pathway databases

ReactomeiREACT_285754. Collagen biosynthesis and modifying enzymes.
REACT_308972. Detoxification of Reactive Oxygen Species.
REACT_314625. Chylomicron-mediated lipid transport.
REACT_347264. Hedgehog ligand biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein disulfide-isomerase (EC:5.3.4.1)
Short name:
PDI
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 namesi
Name:P4hb
Synonyms:Pdia1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:97464. P4hb.

Subcellular locationi

Endoplasmic reticulum lumen PROSITE-ProRule annotation. Melanosome By similarity. Cell membrane Curated; Peripheral membrane protein Curated
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).By similarity

GO - Cellular componenti

  1. endoplasmic reticulum Source: MGI
  2. endoplasmic reticulum chaperone complex Source: ParkinsonsUK-UCL
  3. endoplasmic reticulum-Golgi intermediate compartment Source: MGI
  4. endoplasmic reticulum lumen Source: UniProtKB-SubCell
  5. extracellular vesicular exosome Source: MGI
  6. focal adhesion Source: MGI
  7. melanosome Source: UniProtKB-SubCell
  8. plasma membrane Source: UniProtKB-SubCell
  9. procollagen-proline 4-dioxygenase complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919By similarityAdd
BLAST
Chaini20 – 509490Protein disulfide-isomerasePRO_0000034196Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi55 ↔ 58Redox-activePROSITE-ProRule annotation
Modified residuei202 – 2021N6-acetyllysine1 Publication
Modified residuei224 – 2241N6-succinyllysine1 Publication
Modified residuei273 – 2731N6-succinyllysine1 Publication
Disulfide bondi399 ↔ 402Redox-activePROSITE-ProRule annotation

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

MaxQBiP09103.
PaxDbiP09103.
PRIDEiP09103.

2D gel databases

COMPLUYEAST-2DPAGEP09103.
REPRODUCTION-2DPAGEP09103.
SWISS-2DPAGEP09103.

PTM databases

PhosphoSiteiP09103.

Expressioni

Gene expression databases

BgeeiP09103.
CleanExiMM_P4HB.
ExpressionAtlasiP09103. baseline and differential.
GenevestigatoriP09103.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi202008. 1 interaction.
IntActiP09103. 12 interactions.
MINTiMINT-4122712.
STRINGi10090.ENSMUSP00000026122.

Structurei

3D structure databases

ProteinModelPortaliP09103.
SMRiP09103. Positions 18-480.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 136117Thioredoxin 1PROSITE-ProRule annotationAdd
BLAST
Domaini348 – 477130Thioredoxin 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi506 – 5094Prevents secretion from ER

Sequence similaritiesi

Belongs to the protein disulfide isomerase family.Curated
Contains 2 thioredoxin domains.PROSITE-ProRule annotation

Keywords - Domaini

Redox-active center, Repeat, Signal

Phylogenomic databases

eggNOGiCOG0526.
GeneTreeiENSGT00760000119201.
HOGENOMiHOG000162459.
HOVERGENiHBG005920.
InParanoidiP09103.
KOiK09580.
OMAiYRDHENI.
OrthoDBiEOG7VHSX1.
TreeFamiTF106381.

Family and domain databases

Gene3Di3.40.30.10. 4 hits.
InterProiIPR005788. Disulphide_isomerase.
IPR005792. Prot_disulphide_isomerase.
IPR012336. Thioredoxin-like_fold.
IPR017937. Thioredoxin_CS.
IPR013766. Thioredoxin_domain.
[Graphical view]
PfamiPF00085. Thioredoxin. 2 hits.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 4 hits.
TIGRFAMsiTIGR01130. ER_PDI_fam. 1 hit.
TIGR01126. pdi_dom. 2 hits.
PROSITEiPS00014. ER_TARGET. 1 hit.
PS00194. THIOREDOXIN_1. 2 hits.
PS51352. THIOREDOXIN_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P09103-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSRALLCLA LAWAARVGAD ALEEEDNVLV LKKSNFEEAL AAHKYLLVEF
60 70 80 90 100
YAPWCGHCKA LAPEYAKAAA KLKAEGSEIR LAKVDATEES DLAQQYGVRG
110 120 130 140 150
YPTIKFFKNG DTASPKEYTA GREADDIVNW LKKRTGPAAT TLSDTAAAES
160 170 180 190 200
LVDSSEVTVI GFFKDVESDS AKQFLLAAEA IDDIPFGITS NSGVFSKYQL
210 220 230 240 250
DKDGVVLFKK FDEGRNNFEG EITKEKLLDF IKHNQLPLVI EFTEQTAPKI
260 270 280 290 300
FGGEIKTHIL LFLPKSVSDY DGKLSSFKRA AEGFKGKILF IFIDSDHTDN
310 320 330 340 350
QRILEFFGLK KEECPAVRLI TLEEEMTKYK PESDELTAEK ITEFCHRFLE
360 370 380 390 400
GKIKPHLMSQ EVPEDWDKQP VKVLVGANFE EVAFDEKKNV FVEFYAPWCG
410 420 430 440 450
HCKQLAPIWD KLGETYKDHE NIIIAKMDST ANEVEAVKVH SFPTLKFFPA
460 470 480 490 500
SADRTVIDYN GERTLDGFKK FLESGGQDGA GDDEDLDLEE ALEPDMEEDD

DQKAVKDEL
Length:509
Mass (Da):57,058
Last modified:July 26, 2011 - v2
Checksum:i1FB0AA8ACCDB13EA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti68 – 681A → R in CAA29759 (PubMed:2830592).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS25742.1.
PIRiA34930. ISMSSS.
RefSeqiNP_035162.1. NM_011032.2.
UniGeneiMm.16660.

Genome annotation databases

EnsembliENSMUST00000026122; ENSMUSP00000026122; ENSMUSG00000025130.
GeneIDi18453.
KEGGimmu:18453.
UCSCiuc007mti.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS25742.1.
PIRiA34930. ISMSSS.
RefSeqiNP_035162.1. NM_011032.2.
UniGeneiMm.16660.

3D structure databases

ProteinModelPortaliP09103.
SMRiP09103. Positions 18-480.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202008. 1 interaction.
IntActiP09103. 12 interactions.
MINTiMINT-4122712.
STRINGi10090.ENSMUSP00000026122.

PTM databases

PhosphoSiteiP09103.

2D gel databases

COMPLUYEAST-2DPAGEP09103.
REPRODUCTION-2DPAGEP09103.
SWISS-2DPAGEP09103.

Proteomic databases

MaxQBiP09103.
PaxDbiP09103.
PRIDEiP09103.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026122; ENSMUSP00000026122; ENSMUSG00000025130.
GeneIDi18453.
KEGGimmu:18453.
UCSCiuc007mti.1. mouse.

Organism-specific databases

CTDi5034.
MGIiMGI:97464. P4hb.

Phylogenomic databases

eggNOGiCOG0526.
GeneTreeiENSGT00760000119201.
HOGENOMiHOG000162459.
HOVERGENiHBG005920.
InParanoidiP09103.
KOiK09580.
OMAiYRDHENI.
OrthoDBiEOG7VHSX1.
TreeFamiTF106381.

Enzyme and pathway databases

ReactomeiREACT_285754. Collagen biosynthesis and modifying enzymes.
REACT_308972. Detoxification of Reactive Oxygen Species.
REACT_314625. Chylomicron-mediated lipid transport.
REACT_347264. Hedgehog ligand biogenesis.

Miscellaneous databases

ChiTaRSiP4hb. mouse.
NextBioi294144.
PROiP09103.
SOURCEiSearch...

Gene expression databases

BgeeiP09103.
CleanExiMM_P4HB.
ExpressionAtlasiP09103. baseline and differential.
GenevestigatoriP09103.

Family and domain databases

Gene3Di3.40.30.10. 4 hits.
InterProiIPR005788. Disulphide_isomerase.
IPR005792. Prot_disulphide_isomerase.
IPR012336. Thioredoxin-like_fold.
IPR017937. Thioredoxin_CS.
IPR013766. Thioredoxin_domain.
[Graphical view]
PfamiPF00085. Thioredoxin. 2 hits.
[Graphical view]
SUPFAMiSSF52833. SSF52833. 4 hits.
TIGRFAMsiTIGR01130. ER_PDI_fam. 1 hit.
TIGR01126. pdi_dom. 2 hits.
PROSITEiPS00014. ER_TARGET. 1 hit.
PS00194. THIOREDOXIN_1. 2 hits.
PS51352. THIOREDOXIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1987) [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(1989) [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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J, DBA/2 and NOD.
    Tissue: Bone marrow and Stomach.
  4. 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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Czech II and FVB/N.
    Tissue: Liver and Mammary tumor.
  6. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-202, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-224 AND LYS-273, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast and Liver.

Entry informationi

Entry nameiPDIA1_MOUSE
AccessioniPrimary (citable) accession number: P09103
Secondary accession number(s): Q922C8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 30, 1989
Last sequence update: July 26, 2011
Last modified: March 31, 2015
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.