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Protein

Peptidyl-prolyl cis-trans isomerase D

Gene

PPID

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:11350175, PubMed:20676357). Proposed to act as a co-chaperone in HSP90 complexes such as in unligated steroid receptors heterocomplexes. Different co-chaperones seem to compete for association with HSP90 thus establishing distinct HSP90-co-chaperone-receptor complexes with the potential to exert tissue-specific receptor activity control. May have a preference for estrogen receptor complexes and is not found in glucocorticoid receptor complexes. May be involved in cytoplasmic dynein-dependent movement of the receptor from the cytoplasm to the nucleus. May regulate MYB by inhibiting its DNA-binding activity. Involved in regulation of AHR signaling by promoting the formation of the AHR:ARNT dimer; the function is independent of HSP90 but requires the chaperone activity. Involved in regulation of UV radiation-induced apoptosis. Promotes cell viability in anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma (ALK+ ALCL) cell lines.6 Publications
(Microbial infection) May be involved in hepatitis C virus (HCV) replication and release.2 Publications

Caution

This protein should not be confused with mitochondrial peptidyl-prolyl cis-trans isomerase F (PPIF) which is often referred to as cyclophilin D or CypD.Curated

Catalytic activityi

Peptidylproline (omega=180) = peptidylproline (omega=0).2 Publications

Enzyme regulationi

Less sensitive to inhibition by cyclosporin A than is CYP-18.1 Publication

GO - Molecular functioni

  • cyclosporin A binding Source: UniProtKB
  • estrogen receptor binding Source: UniProtKB
  • heat shock protein binding Source: UniProtKB
  • Hsp70 protein binding Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • peptidyl-prolyl cis-trans isomerase activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cellular response to UV-A Source: UniProtKB
  • chaperone-mediated protein folding Source: UniProtKB
  • lipid particle organization Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of protein secretion Source: UniProtKB
  • positive regulation of viral genome replication Source: UniProtKB
  • protein-containing complex assembly Source: UniProtKB
  • protein folding Source: UniProtKB
  • protein peptidyl-prolyl isomerization Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • viral release from host cell Source: UniProtKB

Keywordsi

Molecular functionChaperone, Isomerase, Rotamase
Biological processApoptosis, Protein transport, Transport

Enzyme and pathway databases

BRENDAi5.2.1.8 2681
ReactomeiR-HSA-8939211 ESR-mediated signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase DCurated (EC:5.2.1.82 Publications)
Short name:
PPIase DCurated
Alternative name(s):
40 kDa peptidyl-prolyl cis-trans isomerase
Cyclophilin-401 Publication
Short name:
CYP-401 Publication
Cyclophilin-related protein
Rotamase D
Gene namesi
Name:PPIDImported
Synonyms:CYP40, CYPD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000171497.4
HGNCiHGNC:9257 PPID
MIMi601753 gene
neXtProtiNX_Q08752

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

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi227K → A: Abolishes interaction with HSP90AB1 and impairs interaction with HSPA8. 2 Publications1
Mutagenesisi231N → A: Abolishes interaction with HSP90AB1 and impairs interaction with HSPA8. 2 Publications1
Mutagenesisi234F → A: Impairs interaction with HSP90AB1 and HSPA8. 2 Publications1
Mutagenesisi274S → L: Impairs interaction with HSP90AB1 and HSPA8. 2 Publications1
Mutagenesisi278N → A: Abolishes interaction with HSP90AB1. 2 Publications1
Mutagenesisi284L → A: Impairs interaction with HSP90AB1 and HSPA8. 2 Publications1
Mutagenesisi285K → A: Impairs interaction with HSP90AB1 and HSPA8. 2 Publications1
Mutagenesisi308K → A: Abolishes interaction with HSP90AB1 and impairs interaction with HSPA8. 2 Publications1
Mutagenesisi312R → A: Abolishes interaction with HSP90AB1 and impairs interaction with HSPA8. 2 Publications1
Mutagenesisi329D → A: Impairs interaction with HSP90AB1. 1 Publication1

Organism-specific databases

DisGeNETi5481
OpenTargetsiENSG00000171497
PharmGKBiPA33582

Chemistry databases

ChEMBLiCHEMBL1697657

Polymorphism and mutation databases

BioMutaiPPID
DMDMi729274

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000641532 – 370Peptidyl-prolyl cis-trans isomerase DAdd BLAST369

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei5PhosphoserineCombined sources1
Modified residuei171N6-acetyllysineBy similarity1
Modified residuei198PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ08752
MaxQBiQ08752
PaxDbiQ08752
PeptideAtlasiQ08752
PRIDEiQ08752
ProteomicsDBi58647

2D gel databases

REPRODUCTION-2DPAGEiIPI00003927

PTM databases

iPTMnetiQ08752
PhosphoSitePlusiQ08752

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000171497
CleanExiHS_PPID
ExpressionAtlasiQ08752 baseline and differential
GenevisibleiQ08752 HS

Organism-specific databases

HPAiHPA019520
HPA019692

Interactioni

Subunit structurei

Identified in ESR1 or NR3C1/GCR steroid receptor-chaperone complexes. Found in HSP90 chaperone complexes with kinase clients LCK or EIF2AK1. Two monomers associate with one HSP90 homodimer. Interacts with HSP90AA1. Interacts with HSP90AB1; PPID and FKBP4 compete for binding to HSP90AB1 and the interaction is mutually exclusive with the PPID:HSPA8 interaction. Interacts with HSPA8; PPID and STIP1 but not FKBP4 compete for binding to HSPA8 and the interaction is mutually exclusive with the PPID:HSP90AB1 interaction. Interacts with S100A1 and S100A2; the interactions dissociate the PPID:HSP90AA1 interaction. Interacts with S100A6. Interacts with MYB, ILF2, XRCC6, RACK1 and RPS3. Interacts with cytoplasmic dynein 1 intermediate chain (DYNC1I1 or DYNC1I2).6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • estrogen receptor binding Source: UniProtKB
  • heat shock protein binding Source: UniProtKB
  • Hsp70 protein binding Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111477, 60 interactors
DIPiDIP-34893N
IntActiQ08752, 26 interactors
MINTiQ08752
STRINGi9606.ENSP00000303754

Chemistry databases

BindingDBiQ08752

Structurei

3D structure databases

ProteinModelPortaliQ08752
SMRiQ08752
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 183PPIase cyclophilin-typePROSITE-ProRule annotationAdd BLAST165
Repeati223 – 256TPR 1Add BLAST34
Repeati273 – 306TPR 2Add BLAST34
Repeati307 – 340TPR 3Add BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni185 – 215Chaperone activityBy similarityAdd BLAST31
Regioni214 – 370Interaction with HSP90AB1By similarityAdd BLAST157

Sequence similaritiesi

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0546 Eukaryota
COG0652 LUCA
GeneTreeiENSGT00550000074595
HOGENOMiHOG000065980
HOVERGENiHBG053654
InParanoidiQ08752
KOiK05864
OMAiAMCAIKL
OrthoDBiEOG091G0BGL
PhylomeDBiQ08752
TreeFamiTF324493

Family and domain databases

Gene3Di1.25.40.10, 1 hit
2.40.100.10, 1 hit
InterProiView protein in InterPro
IPR029000 Cyclophilin-like_dom_sf
IPR024936 Cyclophilin-type_PPIase
IPR020892 Cyclophilin-type_PPIase_CS
IPR002130 Cyclophilin-type_PPIase_dom
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
PANTHERiPTHR11071 PTHR11071, 1 hit
PfamiView protein in Pfam
PF00160 Pro_isomerase, 1 hit
PF13176 TPR_7, 1 hit
PRINTSiPR00153 CSAPPISMRASE
SMARTiView protein in SMART
SM00028 TPR, 3 hits
SUPFAMiSSF48452 SSF48452, 1 hit
SSF50891 SSF50891, 1 hit
PROSITEiView protein in PROSITE
PS00170 CSA_PPIASE_1, 1 hit
PS50072 CSA_PPIASE_2, 1 hit
PS50005 TPR, 3 hits
PS50293 TPR_REGION, 2 hits

Sequencei

Sequence statusi: Complete.

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

Q08752-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSHPSPQAKP SNPSNPRVFF DVDIGGERVG RIVLELFADI VPKTAENFRA
60 70 80 90 100
LCTGEKGIGH TTGKPLHFKG CPFHRIIKKF MIQGGDFSNQ NGTGGESIYG
110 120 130 140 150
EKFEDENFHY KHDREGLLSM ANAGRNTNGS QFFITTVPTP HLDGKHVVFG
160 170 180 190 200
QVIKGIGVAR ILENVEVKGE KPAKLCVIAE CGELKEGDDG GIFPKDGSGD
210 220 230 240 250
SHPDFPEDAD IDLKDVDKIL LITEDLKNIG NTFFKSQNWE MAIKKYAEVL
260 270 280 290 300
RYVDSSKAVI ETADRAKLQP IALSCVLNIG ACKLKMSNWQ GAIDSCLEAL
310 320 330 340 350
ELDPSNTKAL YRRAQGWQGL KEYDQALADL KKAQGIAPED KAIQAELLKV
360 370
KQKIKAQKDK EKAVYAKMFA
Length:370
Mass (Da):40,764
Last modified:January 23, 2007 - v3
Checksum:i39D4100748B35D48
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02102149R → C1 PublicationCorresponds to variant dbSNP:rs2070631Ensembl.1
Natural variantiVAR_051771196D → V. Corresponds to variant dbSNP:rs2230222Ensembl.1
Natural variantiVAR_021022302L → I1 PublicationCorresponds to variant dbSNP:rs9410Ensembl.1
Natural variantiVAR_021023335G → E1 PublicationCorresponds to variant dbSNP:rs17843956Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11667 mRNA Translation: AAA35731.1
D63861 Genomic DNA Translation: BAA09923.1
AY714221 Genomic DNA Translation: AAT97986.1
AK313929 mRNA Translation: BAG36649.1
CH471056 Genomic DNA Translation: EAX04853.1
BC030707 mRNA Translation: AAH30707.1
CCDSiCCDS3801.1
PIRiA45981
RefSeqiNP_005029.1, NM_005038.2
UniGeneiHs.183958

Genome annotation databases

EnsembliENST00000307720; ENSP00000303754; ENSG00000171497
GeneIDi5481
KEGGihsa:5481
UCSCiuc003iqc.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPPID_HUMAN
AccessioniPrimary (citable) accession number: Q08752
Secondary accession number(s): B2R9V2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 178 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

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

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