Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Peptidyl-prolyl cis-trans isomerase D

Gene

PPID

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. 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. May be involved in hepatitis C virus (HCV) replication and release.7 Publications

Catalytic activityi

Peptidylproline (omega=180) = peptidylproline (omega=0).1 Publication

Enzyme regulationi

Less sensitive to inhibition by cyclosporin A than is CYP-18.

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 from RNA polymerase II promoter 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 complex assembly Source: UniProtKB
  • protein folding Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • viral release from host cell Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Isomerase, Rotamase

Keywords - Biological processi

Apoptosis, Protein transport, Transport

Keywords - Ligandi

Cyclosporin

Enzyme and pathway databases

BioCyciZFISH:HS10323-MONOMER.
BRENDAi5.2.1.8. 2681.

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase D (EC:5.2.1.81 Publication)
Short name:
PPIase D
Alternative name(s):
40 kDa peptidyl-prolyl cis-trans isomerase
Cyclophilin-40
Short name:
CYP-40
Cyclophilin-related protein
Rotamase D
Gene namesi
Name:PPID
Synonyms:CYP40, CYPD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:9257. PPID.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

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.

2D gel databases

REPRODUCTION-2DPAGEIPI00003927.

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

WithEntry#Exp.IntActNotes
ILF2Q129054EBI-716596,EBI-357925
MYBP011032EBI-716596,EBI-6502562From a different organism.
RACK1P632444EBI-716596,EBI-296739
RPS3P233964EBI-716596,EBI-351193
XRCC6P129564EBI-716596,EBI-353208

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. 55 interactors.
DIPiDIP-34893N.
IntActiQ08752. 24 interactors.
MINTiMINT-1399772.
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

Contains 1 PPIase cyclophilin-type domain.PROSITE-ProRule annotation
Contains 3 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
2.40.100.10. 1 hit.
InterProiIPR029000. Cyclophilin-like_dom.
IPR024936. Cyclophilin-type_PPIase.
IPR020892. Cyclophilin-type_PPIase_CS.
IPR002130. Cyclophilin-type_PPIase_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR11071. PTHR11071. 1 hit.
PfamiPF00160. Pro_isomerase. 1 hit.
PF13176. TPR_7. 1 hit.
[Graphical view]
PRINTSiPR00153. CSAPPISMRASE.
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
SSF50891. SSF50891. 1 hit.
PROSITEiPS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]

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 → C.1 PublicationCorresponds to variant rs2070631dbSNPEnsembl.1
Natural variantiVAR_051771196D → V.Corresponds to variant rs2230222dbSNPEnsembl.1
Natural variantiVAR_021022302L → I.1 PublicationCorresponds to variant rs9410dbSNPEnsembl.1
Natural variantiVAR_021023335G → E.1 PublicationCorresponds to variant rs17843956dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Cyclophilin entry

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.

3D structure databases

ProteinModelPortaliQ08752.
SMRiQ08752.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111477. 55 interactors.
DIPiDIP-34893N.
IntActiQ08752. 24 interactors.
MINTiMINT-1399772.
STRINGi9606.ENSP00000303754.

Chemistry databases

BindingDBiQ08752.
ChEMBLiCHEMBL1697657.

PTM databases

iPTMnetiQ08752.
PhosphoSitePlusiQ08752.

Polymorphism and mutation databases

BioMutaiPPID.
DMDMi729274.

2D gel databases

REPRODUCTION-2DPAGEIPI00003927.

Proteomic databases

EPDiQ08752.
MaxQBiQ08752.
PaxDbiQ08752.
PeptideAtlasiQ08752.
PRIDEiQ08752.

Protocols and materials databases

DNASUi5481.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5481.
DisGeNETi5481.
GeneCardsiPPID.
HGNCiHGNC:9257. PPID.
HPAiHPA019520.
HPA019692.
MIMi601753. gene.
neXtProtiNX_Q08752.
OpenTargetsiENSG00000171497.
PharmGKBiPA33582.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS10323-MONOMER.
BRENDAi5.2.1.8. 2681.

Miscellaneous databases

ChiTaRSiPPID. human.
GeneWikiiPPID.
GenomeRNAii5481.
PROiQ08752.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171497.
CleanExiHS_PPID.
ExpressionAtlasiQ08752. baseline and differential.
GenevisibleiQ08752. HS.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
2.40.100.10. 1 hit.
InterProiIPR029000. Cyclophilin-like_dom.
IPR024936. Cyclophilin-type_PPIase.
IPR020892. Cyclophilin-type_PPIase_CS.
IPR002130. Cyclophilin-type_PPIase_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR11071. PTHR11071. 1 hit.
PfamiPF00160. Pro_isomerase. 1 hit.
PF13176. TPR_7. 1 hit.
[Graphical view]
PRINTSiPR00153. CSAPPISMRASE.
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
SSF50891. SSF50891. 1 hit.
PROSITEiPS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPPID_HUMAN
AccessioniPrimary (citable) accession number: Q08752
Secondary accession number(s): B2R9V2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 163 of the entry and version 3 of the sequence. [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

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

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

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 one 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.