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Protein

Protein disulfide-isomerase

Gene

P4HB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307).3 Publications

Miscellaneous

Reduces and may activate fusogenic properties of HIV-1 gp120 surface protein, thereby enabling HIV-1 entry into the cell.

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei53Nucleophile1
Sitei54Contributes to redox potential value1
Sitei55Contributes to redox potential value1
Active sitei56Nucleophile1
Sitei120Lowers pKa of C-terminal Cys of first active site1
Active sitei397NucleophileBy similarity1
Sitei398Contributes to redox potential valueBy similarity1
Sitei399Contributes to redox potential valueBy similarity1
Active sitei400NucleophileBy similarity1
Sitei461Lowers pKa of C-terminal Cys of second active siteBy similarity1

GO - Molecular functioni

  • enzyme binding Source: Ensembl
  • integrin binding Source: UniProtKB
  • peptide disulfide oxidoreductase activity Source: UniProtKB
  • procollagen-proline 4-dioxygenase activity Source: ProtInc
  • protein disulfide isomerase activity Source: CACAO
  • protein heterodimerization activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionChaperone, Isomerase

Enzyme and pathway databases

BioCyciMetaCyc:HS06845-MONOMER
BRENDAi5.3.4.1 2681
ReactomeiR-HSA-1650814 Collagen biosynthesis and modifying enzymes
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-8866423 VLDL assembly
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-8963888 Chylomicron assembly
R-HSA-9020591 Interleukin-12 signaling
R-HSA-9020933 Interleukin-23 signaling

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
Prolyl 4-hydroxylase subunit beta
p55
Gene namesi
Name:P4HB
Synonyms:ERBA2L, PDI, PDIA1, PO4DB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000185624.14
HGNCiHGNC:8548 P4HB
MIMi176790 gene
neXtProtiNX_P07237

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Cole-Carpenter syndrome 1 (CLCRP1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Cole-Carpenter syndrome, a disorder characterized by features of osteogenesis imperfecta such as bone deformities and severe bone fragility with frequent fractures, in association with craniosynostosis, ocular proptosis, hydrocephalus, growth failure and distinctive facial features. Craniofacial findings include marked frontal bossing, midface hypoplasia, and micrognathia. Despite the craniosynostosis and hydrocephalus, intellectual development is normal. CLCRP1 inheritance is autosomal dominant.
See also OMIM:112240
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073440393Y → C in CLCRP1; impairs ability to act as a disulfide isomerase enzyme. 1 PublicationCorresponds to variant dbSNP:rs786204843EnsemblClinVar.1

Keywords - Diseasei

Craniosynostosis, Disease mutation, Osteogenesis imperfecta

Organism-specific databases

DisGeNETi5034
MalaCardsiP4HB
MIMi112240 phenotype
OpenTargetsiENSG00000185624
PharmGKBiPA32876

Chemistry databases

ChEMBLiCHEMBL5422
DrugBankiDB03615 Ribostamycin

Polymorphism and mutation databases

BioMutaiP4HB
DMDMi2507460

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Combined sources4 PublicationsAdd BLAST17
ChainiPRO_000003419518 – 508Protein disulfide-isomeraseAdd BLAST491

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi53 ↔ 56Redox-activePROSITE-ProRule annotation1 Publication
Modified residuei200N6-acetyllysineBy similarity1
Modified residuei222N6-succinyllysineBy similarity1
Modified residuei271N6-succinyllysineBy similarity1
Modified residuei357Phosphoserine; by FAM20C1 Publication1
Disulfide bondi397 ↔ 400Redox-activePROSITE-ProRule annotation

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP07237
MaxQBiP07237
PaxDbiP07237
PeptideAtlasiP07237
PRIDEiP07237
ProteomicsDBi51976
TopDownProteomicsiP07237

2D gel databases

DOSAC-COBS-2DPAGEiP07237
OGPiP07237
REPRODUCTION-2DPAGEiIPI00010796
P07237
SWISS-2DPAGEiP07237

PTM databases

iPTMnetiP07237
PhosphoSitePlusiP07237
SwissPalmiP07237

Miscellaneous databases

PMAP-CutDBiP07237

Expressioni

Gene expression databases

BgeeiENSG00000185624 Expressed in 235 organ(s), highest expression level in right lobe of liver
CleanExiHS_P4HB
ExpressionAtlasiP07237 baseline and differential
GenevisibleiP07237 HS

Organism-specific databases

HPAiCAB012463
HPA018884

Interactioni

Subunit structurei

Heterodimer; heterodimerizes with the protein microsomal triglyceride transfer MTTP (PubMed:23475612, PubMed:26224785). 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 (By similarity). Binds UBQLN1 (PubMed:12095988). Interacts with ERO1B (PubMed:11707400). Binds to CD4, and upon HIV-1 binding to the cell membrane, is part of a P4HB/PDI-CD4-CXCR4-gp120 complex.By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111073, 145 interactors
CORUMiP07237
DIPiDIP-32979N
IntActiP07237, 93 interactors
MINTiP07237
STRINGi9606.ENSP00000327801

Chemistry databases

BindingDBiP07237

Structurei

Secondary structure

1508
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP07237
SMRiP07237
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07237

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 134Thioredoxin 1PROSITE-ProRule annotationAdd BLAST117
Domaini349 – 475Thioredoxin 2PROSITE-ProRule annotationAdd BLAST127

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi505 – 508Prevents secretion from ER4

Sequence similaritiesi

Belongs to the protein disulfide isomerase family.Curated

Keywords - Domaini

Redox-active center, Repeat, Signal

Phylogenomic databases

eggNOGiKOG0190 Eukaryota
COG0526 LUCA
GeneTreeiENSGT00860000133691
HOGENOMiHOG000162459
HOVERGENiHBG005920
InParanoidiP07237
KOiK09580
OMAiQYGVRGY
OrthoDBiEOG091G08WM
PhylomeDBiP07237
TreeFamiTF106381

Family and domain databases

InterProiView protein in InterPro
IPR005788 Disulphide_isomerase
IPR005792 Prot_disulphide_isomerase
IPR036249 Thioredoxin-like_sf
IPR017937 Thioredoxin_CS
IPR013766 Thioredoxin_domain
PfamiView protein in Pfam
PF00085 Thioredoxin, 2 hits
SUPFAMiSSF52833 SSF52833, 4 hits
TIGRFAMsiTIGR01130 ER_PDI_fam, 1 hit
TIGR01126 pdi_dom, 2 hits
PROSITEiView protein in PROSITE
PS00014 ER_TARGET, 1 hit
PS00194 THIOREDOXIN_1, 2 hits
PS51352 THIOREDOXIN_2, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 11 potential isoforms that are computationally mapped.Show allAlign All

P07237-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLRRALLCLA VAALVRADAP EEEDHVLVLR KSNFAEALAA HKYLLVEFYA
60 70 80 90 100
PWCGHCKALA PEYAKAAGKL KAEGSEIRLA KVDATEESDL AQQYGVRGYP
110 120 130 140 150
TIKFFRNGDT ASPKEYTAGR EADDIVNWLK KRTGPAATTL PDGAAAESLV
160 170 180 190 200
ESSEVAVIGF FKDVESDSAK QFLQAAEAID DIPFGITSNS DVFSKYQLDK
210 220 230 240 250
DGVVLFKKFD EGRNNFEGEV TKENLLDFIK HNQLPLVIEF TEQTAPKIFG
260 270 280 290 300
GEIKTHILLF LPKSVSDYDG KLSNFKTAAE SFKGKILFIF IDSDHTDNQR
310 320 330 340 350
ILEFFGLKKE ECPAVRLITL EEEMTKYKPE SEELTAERIT EFCHRFLEGK
360 370 380 390 400
IKPHLMSQEL PEDWDKQPVK VLVGKNFEDV AFDEKKNVFV EFYAPWCGHC
410 420 430 440 450
KQLAPIWDKL GETYKDHENI VIAKMDSTAN EVEAVKVHSF PTLKFFPASA
460 470 480 490 500
DRTVIDYNGE RTLDGFKKFL ESGGQDGAGD DDDLEDLEEA EEPDMEEDDD

QKAVKDEL
Length:508
Mass (Da):57,116
Last modified:November 1, 1997 - v3
Checksum:i906CE6D9900B8FCE
GO

Computationally mapped potential isoform sequencesi

There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7BZ94H7BZ94_HUMAN
Protein disulfide-isomerase
P4HB
464Annotation score:
I3NI03I3NI03_HUMAN
Protein disulfide-isomerase
P4HB
166Annotation score:
I3L0S0I3L0S0_HUMAN
Protein disulfide-isomerase
P4HB
148Annotation score:
I3L3U6I3L3U6_HUMAN
Protein disulfide-isomerase
P4HB
188Annotation score:
H0Y3Z3H0Y3Z3_HUMAN
Protein disulfide-isomerase
P4HB
274Annotation score:
I3L514I3L514_HUMAN
Protein disulfide-isomerase
P4HB
106Annotation score:
I3L3P5I3L3P5_HUMAN
Protein disulfide-isomerase
P4HB
156Annotation score:
I3L398I3L398_HUMAN
Protein disulfide-isomerase
P4HB
200Annotation score:
I3L312I3L312_HUMAN
Protein disulfide-isomerase
P4HB
208Annotation score:
I3L1Y5I3L1Y5_HUMAN
Protein disulfide-isomerase
P4HB
54Annotation score:
There is more potential isoformShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti10 – 11AV → PW in CAA28775 (PubMed:3034602).Curated2
Sequence conflicti21E → D AA sequence (PubMed:9399589).Curated1
Sequence conflicti24D → V AA sequence (PubMed:9399589).Curated1
Sequence conflicti44 – 45LL → PP in CAA28775 (PubMed:3034602).Curated2
Sequence conflicti49Y → H in CAA28775 (PubMed:3034602).Curated1
Sequence conflicti141P → R in AAA61169 (PubMed:3611107).Curated1
Sequence conflicti360 – 362LPE → RAG in AAA61169 (PubMed:3611107).Curated3
Sequence conflicti372L → P in AAA61169 (PubMed:3611107).Curated1
Sequence conflicti439S → G in CAA28775 (PubMed:3034602).Curated1
Sequence conflicti444K → G in CAA28775 (PubMed:3034602).Curated1
Sequence conflicti460E → Q in CAA30112 (PubMed:3342239).Curated1
Sequence conflicti481D → V in CAA28775 (PubMed:3034602).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073440393Y → C in CLCRP1; impairs ability to act as a disulfide isomerase enzyme. 1 PublicationCorresponds to variant dbSNP:rs786204843EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05130 mRNA Translation: CAA28775.1
J02783 mRNA Translation: AAA61169.1
M22806
, M22803, M22804, M22805 Genomic DNA Translation: AAC13652.1
AK315631 mRNA Translation: BAG37999.1
CH471099 Genomic DNA Translation: EAW89690.1
BC010859 mRNA Translation: AAH10859.1
BC029617 mRNA Translation: AAH29617.1
BC071892 mRNA Translation: AAH71892.1
S37207 Genomic DNA Translation: AAB22262.2
X07077 mRNA Translation: CAA30112.1
CCDSiCCDS11787.1
PIRiA31913 ISHUSS
RefSeqiNP_000909.2, NM_000918.3
UniGeneiHs.464336

Genome annotation databases

EnsembliENST00000331483; ENSP00000327801; ENSG00000185624
GeneIDi5034
KEGGihsa:5034
UCSCiuc002kbn.2 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05130 mRNA Translation: CAA28775.1
J02783 mRNA Translation: AAA61169.1
M22806
, M22803, M22804, M22805 Genomic DNA Translation: AAC13652.1
AK315631 mRNA Translation: BAG37999.1
CH471099 Genomic DNA Translation: EAW89690.1
BC010859 mRNA Translation: AAH10859.1
BC029617 mRNA Translation: AAH29617.1
BC071892 mRNA Translation: AAH71892.1
S37207 Genomic DNA Translation: AAB22262.2
X07077 mRNA Translation: CAA30112.1
CCDSiCCDS11787.1
PIRiA31913 ISHUSS
RefSeqiNP_000909.2, NM_000918.3
UniGeneiHs.464336

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BJXNMR-A136-245[»]
1MEKNMR-A18-137[»]
1X5CNMR-A368-475[»]
2BJXNMR-A136-245[»]
2K18NMR-A135-357[»]
3BJ5X-ray2.20A230-368[»]
3UEMX-ray2.29A137-479[»]
4EKZX-ray2.51A18-479[»]
4EL1X-ray2.88A/B18-479[»]
4JU5X-ray2.28A/B135-367[»]
ProteinModelPortaliP07237
SMRiP07237
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111073, 145 interactors
CORUMiP07237
DIPiDIP-32979N
IntActiP07237, 93 interactors
MINTiP07237
STRINGi9606.ENSP00000327801

Chemistry databases

BindingDBiP07237
ChEMBLiCHEMBL5422
DrugBankiDB03615 Ribostamycin

PTM databases

iPTMnetiP07237
PhosphoSitePlusiP07237
SwissPalmiP07237

Polymorphism and mutation databases

BioMutaiP4HB
DMDMi2507460

2D gel databases

DOSAC-COBS-2DPAGEiP07237
OGPiP07237
REPRODUCTION-2DPAGEiIPI00010796
P07237
SWISS-2DPAGEiP07237

Proteomic databases

EPDiP07237
MaxQBiP07237
PaxDbiP07237
PeptideAtlasiP07237
PRIDEiP07237
ProteomicsDBi51976
TopDownProteomicsiP07237

Protocols and materials databases

DNASUi5034
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000331483; ENSP00000327801; ENSG00000185624
GeneIDi5034
KEGGihsa:5034
UCSCiuc002kbn.2 human

Organism-specific databases

CTDi5034
DisGeNETi5034
EuPathDBiHostDB:ENSG00000185624.14
GeneCardsiP4HB
HGNCiHGNC:8548 P4HB
HPAiCAB012463
HPA018884
MalaCardsiP4HB
MIMi112240 phenotype
176790 gene
neXtProtiNX_P07237
OpenTargetsiENSG00000185624
PharmGKBiPA32876
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0190 Eukaryota
COG0526 LUCA
GeneTreeiENSGT00860000133691
HOGENOMiHOG000162459
HOVERGENiHBG005920
InParanoidiP07237
KOiK09580
OMAiQYGVRGY
OrthoDBiEOG091G08WM
PhylomeDBiP07237
TreeFamiTF106381

Enzyme and pathway databases

BioCyciMetaCyc:HS06845-MONOMER
BRENDAi5.3.4.1 2681
ReactomeiR-HSA-1650814 Collagen biosynthesis and modifying enzymes
R-HSA-3299685 Detoxification of Reactive Oxygen Species
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-8866423 VLDL assembly
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-8963888 Chylomicron assembly
R-HSA-9020591 Interleukin-12 signaling
R-HSA-9020933 Interleukin-23 signaling

Miscellaneous databases

ChiTaRSiP4HB human
EvolutionaryTraceiP07237
GeneWikiiP4HB
GenomeRNAii5034
PMAP-CutDBiP07237
PROiPR:P07237
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185624 Expressed in 235 organ(s), highest expression level in right lobe of liver
CleanExiHS_P4HB
ExpressionAtlasiP07237 baseline and differential
GenevisibleiP07237 HS

Family and domain databases

InterProiView protein in InterPro
IPR005788 Disulphide_isomerase
IPR005792 Prot_disulphide_isomerase
IPR036249 Thioredoxin-like_sf
IPR017937 Thioredoxin_CS
IPR013766 Thioredoxin_domain
PfamiView protein in Pfam
PF00085 Thioredoxin, 2 hits
SUPFAMiSSF52833 SSF52833, 4 hits
TIGRFAMsiTIGR01130 ER_PDI_fam, 1 hit
TIGR01126 pdi_dom, 2 hits
PROSITEiView protein in PROSITE
PS00014 ER_TARGET, 1 hit
PS00194 THIOREDOXIN_1, 2 hits
PS51352 THIOREDOXIN_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiPDIA1_HUMAN
AccessioniPrimary (citable) accession number: P07237
Secondary accession number(s): B2RDQ2
, P30037, P32079, Q15205, Q6LDE5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: November 1, 1997
Last modified: October 10, 2018
This is version 238 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
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