The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant cyclosporin A.... See more...

Aliases for PPID Gene

Aliases for PPID Gene

  • Peptidylprolyl Isomerase D 2 3 5
  • CYP-40 2 3 4
  • Peptidyl-Prolyl Cis-Trans Isomerase D 3 4
  • Cyclophilin-Related Protein 3 4
  • Cyclophilin 40 2 3
  • Rotamase D 3 4
  • EC 5.2.1.8 4 51
  • PPIase D 3 4
  • CYPD 3 4
  • 40 KDa Peptidyl-Prolyl Cis-Trans Isomerase D 3
  • Peptidylprolyl Isomerase D (Cyclophilin D) 2
  • 40 KDa Peptidyl-Prolyl Cis-Trans Isomerase 4
  • Testicular Tissue Protein Li 147 3
  • Cyclophilin-40 4
  • Cyclophilin D 3
  • CYP40 4
  • PPID 5

External Ids for PPID Gene

Previous GeneCards Identifiers for PPID Gene

  • GC04M160480
  • GC04M160059
  • GC04M160207
  • GC04M159987
  • GC04M159849
  • GC04M159630
  • GC04M155380

Summaries for PPID Gene

Entrez Gene Summary for PPID Gene

  • The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant cyclosporin A. [provided by RefSeq, Jul 2008]

GeneCards Summary for PPID Gene

PPID (Peptidylprolyl Isomerase D) is a Protein Coding gene. Diseases associated with PPID include Anaplastic Large Cell Lymphoma and Amyotrophic Lateral Sclerosis 1. Among its related pathways are Shigellosis and Pathways of neurodegeneration - multiple diseases. Gene Ontology (GO) annotations related to this gene include transcription factor binding and heat shock protein binding. An important paralog of this gene is NKTR.

UniProtKB/Swiss-Prot Summary for PPID Gene

  • 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.
  • (Microbial infection) May be involved in hepatitis C virus (HCV) replication and release.

Gene Wiki entry for PPID Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PPID Gene

Genomics for PPID Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PPID Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PPID on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PPID

Top Transcription factor binding sites by QIAGEN in the PPID gene promoter:
  • AML1a
  • FOXL1
  • POU3F2
  • POU3F2 (N-Oct-5a)
  • POU3F2 (N-Oct-5b)
  • PPAR-alpha
  • STAT1
  • STAT1alpha
  • STAT1beta
  • STAT2

Genomic Locations for PPID Gene

Latest Assembly
chr4:158,709,127-158,723,396
(GRCh38/hg38)
Size:
14,270 bases
Orientation:
Minus strand

Previous Assembly
chr4:159,630,279-159,644,548
(GRCh37/hg19 by Entrez Gene)
Size:
14,270 bases
Orientation:
Minus strand

chr4:159,630,286-159,644,548
(GRCh37/hg19 by Ensembl)
Size:
14,263 bases
Orientation:
Minus strand

Genomic View for PPID Gene

Genes around PPID on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PPID Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PPID Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PPID Gene

Proteins for PPID Gene

  • Protein details for PPID Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q08752-PPID_HUMAN
    Recommended name:
    Peptidyl-prolyl cis-trans isomerase D
    Protein Accession:
    Q08752
    Secondary Accessions:
    • B2R9V2

    Protein attributes for PPID Gene

    Size:
    370 amino acids
    Molecular mass:
    40764 Da
    Quaternary structure:
    • 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).

neXtProt entry for PPID Gene

Selected DME Specific Peptides for PPID Gene

Q08752:
  • GLLSMAN
  • FMIQGGD
  • LSMANAG
  • NGSQFFITTV
  • KFEDENF
  • TNGSQFF
  • TAENFRAL
  • KHVVFGQV
  • SIYGEKF
  • ALSCVLNIGACKLKMS
  • PKTAENF
  • LDGKHVVFG
  • GGESIYG
  • LCTGEKG

Post-translational modifications for PPID Gene

  • Ubiquitination at Lys218, Lys283, and Lys341
  • Modification sites at PhosphoSitePlus

Other Protein References for PPID Gene

Domains & Families for PPID Gene

Gene Families for PPID Gene

Protein Domains for PPID Gene

InterPro:
Blocks:
  • Peptidyl-prolyl cis-trans isomerase, cyclophilin type
ProtoNet:

Suggested Antigen Peptide Sequences for PPID Gene

GenScript: Design optimal peptide antigens:
  • Rotamase D (PPID_HUMAN)
  • Peptidyl-prolyl cis-trans isomerase (Q05DH6_HUMAN)
  • PPID protein (Q6FGM6_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q08752

UniProtKB/Swiss-Prot:

PPID_HUMAN :
  • Belongs to the cyclophilin-type PPIase family. PPIase D subfamily.
Family:
  • Belongs to the cyclophilin-type PPIase family. PPIase D subfamily.
genes like me logo Genes that share domains with PPID: view

Function for PPID Gene

Molecular function for PPID Gene

UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot Function:
(Microbial infection) May be involved in hepatitis C virus (HCV) replication and release.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA-COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269|PubMed:11350175, ECO:0000269|PubMed:20676357};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Less sensitive to inhibition by cyclosporin A than is CYP-18.
GENATLAS Biochemistry:
cyclophilin 40kDa,with intrinsic peptidyl-prolyl cis-trans isomerase activity,component of an unactivated steroid hormone receptor complex (see FKBP2)

Enzyme Numbers (IUBMB) for PPID Gene

Phenotypes From GWAS Catalog for PPID Gene

Gene Ontology (GO) - Molecular Function for PPID Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003755 peptidyl-prolyl cis-trans isomerase activity IBA,IDA 11350175
GO:0005515 protein binding IEA,IPI 9659917
GO:0008134 transcription factor binding IDA 9659917
GO:0016018 cyclosporin A binding TAS 7744028
GO:0016853 isomerase activity IEA --
genes like me logo Genes that share ontologies with PPID: view
genes like me logo Genes that share phenotypes with PPID: view

Animal Models for research

  • Taconic Biosciences Mouse Models for PPID

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPID

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for PPID Gene

Localization for PPID Gene

Subcellular locations from UniProtKB/Swiss-Prot for PPID Gene

Cytoplasm. Nucleus, nucleolus. Nucleus, nucleoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PPID gene
Compartment Confidence
nucleus 5
cytosol 5
mitochondrion 3
plasma membrane 2
cytoskeleton 2
endoplasmic reticulum 2
extracellular 1
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoli (3)
  • Nucleoli rim (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for PPID Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 11525244
GO:0005654 nucleoplasm TAS --
GO:0005730 nucleolus IEA,IDA 11525244
GO:0005737 cytoplasm IBA,IDA 11525244
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with PPID: view

Pathways & Interactions for PPID Gene

genes like me logo Genes that share pathways with PPID: view

Pathways by source for PPID Gene

1 GeneGo (Thomson Reuters) pathway for PPID Gene
  • Cholesterol and Sphingolipids transport / Transport from Golgi and ER to the apical membrane (normal and CF)
2 Qiagen pathways for PPID Gene
  • Cellular Apoptosis Pathway
  • Mitochondrial Apoptosis

Gene Ontology (GO) - Biological Process for PPID Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 18708059
GO:0000413 protein peptidyl-prolyl isomerization IDA 20676357
GO:0006457 protein folding IBA,ISS --
GO:0006915 apoptotic process IEA --
GO:0015031 protein transport IEA --
genes like me logo Genes that share ontologies with PPID: view

No data available for SIGNOR curated interactions for PPID Gene

Drugs & Compounds for PPID Gene

(2) Drugs for PPID Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for PPID Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PPID: view

Transcripts for PPID Gene

mRNA/cDNA for PPID Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PPID

Alternative Splicing Database (ASD) splice patterns (SP) for PPID Gene

No ASD Table

Relevant External Links for PPID Gene

GeneLoc Exon Structure for
PPID

Expression for PPID Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PPID Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PPID Gene

This gene is overexpressed in Peripheral blood mononuclear cells (8.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PPID Gene



Protein tissue co-expression partners for PPID Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PPID

SOURCE GeneReport for Unigene cluster for PPID Gene:

Hs.183958

mRNA Expression by UniProt/SwissProt for PPID Gene:

Q08752-PPID_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for PPID Gene

  • Nervous system(4.6)
  • Liver(4.5)
  • Blood(4.5)
  • Pancreas(4.4)
  • Heart(2.7)
  • Muscle(2.7)
  • Lung(2.5)
  • Kidney(2.4)
  • Skin(2.3)
  • Adrenal gland(2.1)
  • Intestine(2.1)
  • Spleen(2)
genes like me logo Genes that share expression patterns with PPID: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for PPID Gene

Orthologs for PPID Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for PPID Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PPID 30 31
  • 99.64 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PPID 30 31
  • 92.97 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ppid 30
  • 90.72 (n)
Mouse
(Mus musculus)
Mammalia Ppid 30 17 31
  • 90.45 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PPID 30 31
  • 90 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia PPID 31
  • 81 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PPID 30 31
  • 76.58 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PPID 31
  • 78 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ppid 30
  • 73.42 (n)
MGC75854 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.4643 30
Zebrafish
(Danio rerio)
Actinopterygii ppid 30 31
  • 67.66 (n)
OneToOne
wufb18b07 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003265 30
  • 47.79 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG8336 30 31 32
  • 47.23 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea cyp-3 32
  • 66 (a)
cyp-7 32
  • 62 (a)
cyp-8 32
  • 51 (a)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CPR6 30 31 33
  • 53.41 (n)
OneToMany
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F05093g 30
  • 52.94 (n)
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_ADR087C 30
  • 46.8 (n)
Thale Cress
(Arabidopsis thaliana)
eudicotyledons SQN 30
  • 53.98 (n)
Rice
(Oryza sativa)
Liliopsida Os06g0216800 30
  • 53.06 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes wis2 30
  • 53.69 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU03853 30
  • 53.62 (n)
Species where no ortholog for PPID was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for PPID Gene

ENSEMBL:
Gene Tree for PPID (if available)
TreeFam:
Gene Tree for PPID (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PPID: view image

Paralogs for PPID Gene

(22) SIMAP similar genes for PPID Gene using alignment to 5 proteins:

  • PPID_HUMAN
  • H0Y8J0_HUMAN
  • H0Y969_HUMAN
  • Q05DH6_HUMAN
  • Q6FGM6_HUMAN
genes like me logo Genes that share paralogs with PPID: view

Variants for PPID Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PPID Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
974730 Uncertain Significance: Aganglionic megacolon 158,620,033(-) ACTCAGATTTTACAAC
NG_031835.1(PPID):g.103322_138659del
rs116191398 Benign: not provided 158,719,171(-) C/G
NM_005038.3(PPID):c.333+9G>C
INTRON
rs368268182 Likely Benign: not provided 158,717,095(-) CAT/C
NM_005038.3(PPID):c.437_438del (p.His146fs)
FRAMESHIFT
rs61756415 Benign: not provided 158,715,678(-) C/T
NM_005038.3(PPID):c.529G>A (p.Val177Ile)
MISSENSE
rs17843956 - p.Gly335Glu

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for PPID Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for PPID Gene

Variant ID Type Subtype PubMed ID
nsv830125 CNV gain 17160897

Variation tolerance for PPID Gene

Residual Variation Intolerance Score: 53.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.51; 88.81% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PPID Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PPID

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PPID Gene

Disorders for PPID Gene

MalaCards: The human disease database

(2) MalaCards diseases for PPID Gene - From: COP and GCD

Disorder Aliases PubMed IDs
anaplastic large cell lymphoma
  • alcl
amyotrophic lateral sclerosis 1
  • als1
- elite association - COSMIC cancer census association via MalaCards
Search PPID in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PPID

Genetic Association Database
(GAD)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with PPID: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PPID Gene

Publications for PPID Gene

  1. Functional analysis of the Hsp90-associated human peptidyl prolyl cis/trans isomerases FKBP51, FKBP52 and Cyp40. (PMID: 11350175) Pirkl F … Buchner J (Journal of molecular biology 2001) 3 4 23
  2. Cyclophilin-40, a protein with homology to the P59 component of the steroid receptor complex. Cloning of the cDNA and further characterization. (PMID: 8509368) Kieffer LJ … Bayney RM (The Journal of biological chemistry 1993) 2 3 4
  3. Cyclophilin 40 alters UVA-induced apoptosis and mitochondrial ROS generation in keratinocytes. (PMID: 23220213) Jandova J … Sligh JE (Experimental cell research 2013) 3 4
  4. The heat shock protein-90 co-chaperone, Cyclophilin 40, promotes ALK-positive, anaplastic large cell lymphoma viability and its expression is regulated by the NPM-ALK oncoprotein. (PMID: 22681779) Pearson JD … Ingham RJ (BMC cancer 2012) 3 4
  5. Inhibition of cyclophilins alters lipid trafficking and blocks hepatitis C virus secretion. (PMID: 21711559) Anderson LJ … Wiedmann B (Virology journal 2011) 3 4

Products for PPID Gene