PPID Gene

HGNC Family	Peptidylprolyl isomerases, Tetratricopeptide repeat domain containing (TTC)
Name	peptidylprolyl isomerase D
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPID, which encodes Cyclophilin 40, is a multifunctional peptidyl‐prolyl cis–trans isomerase that operates as an immunophilin co‐chaperone. It facilitates the proper folding and regulation of client proteins by interacting with chaperone systems, such as Hsp90, and plays an important role in modulating receptor‐mediated signaling. For example, PPID participates in the formation of transcriptionally active complexes by promoting the assembly of the aryl hydrocarbon receptor (AhR) and its partner factors, thereby enhancing downstream signaling responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in receptor signaling, Cyclophilin 40 contributes to protein homeostasis through its chaperone activity. It has been shown to dissolve pathogenic protein aggregates, such as tau amyloids implicated in neurodegeneration, thereby preserving neuronal function. PPID also interacts with several proteins involved in tumorigenesis—for instance, by modulating androgen receptor activity in prostate cancer—and facilitates the uptake and refolding of bacterial ADP‐ribosylating toxin components. These functions underscore its involvement in diverse cellular contexts including cancer, neurodegenerative disorders, and host–pathogen interactions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and biophysical studies of PPID have revealed that its chaperone function depends not only on its cyclophilin (PPIase) domain but also on its tetratricopeptide repeat (TPR) domain and the intervening linker region. This interdomain segment forms a binding cleft crucial for substrate interaction and allosteric regulation—its association with Hsp90‑derived peptides (e.g., MEEVD motifs) can modulate its catalytic activity. Such insights into PPID’s structural dynamics further explain how the enzyme fine-tunes its isomerase function to impact protein folding and signaling under physiological and stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Danny Mok, Rudi K Allan, Amerigo Carrello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The chaperone function of cyclophilin 40 maps to a cleft between the prolyl isomerase and tetratricopeptide repeat domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2006.04.039"}], "href": "https://doi.org/10.1016/j.febslet.2006.04.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16650407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16650407"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tony C Luu, Pompeya Bhattacharya, William K Chan "}, {"type": "b", "children": [{"type": "t", "text": "Cyclophilin-40 has a cellular role in the aryl hydrocarbon receptor signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2008.08.007"}], "href": "https://doi.org/10.1016/j.febslet.2008.08.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18708059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18708059"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "S Periyasamy, T Hinds, L Shemshedini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FKBP51 and Cyp40 are positive regulators of androgen-dependent prostate cancer cell growth and the targets of FK506 and cyclosporin A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2009.458"}], "href": "https://doi.org/10.1038/onc.2009.458"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20023700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20023700"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Joel D Pearson, Zubair Mohammed, Julinor T C Bacani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-12-229"}], "href": "https://doi.org/10.1186/1471-2407-12-229"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22681779"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22681779"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alexander E Lang, Katharina Ernst, Haram Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The chaperone Hsp90 and PPIases of the cyclophilin and FKBP families facilitate membrane translocation of Photorhabdus luminescens ADP-ribosyltransferases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cmi.12228"}], "href": "https://doi.org/10.1111/cmi.12228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24138221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24138221"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Katharina Ernst, Simon Langer, Eva Kaiser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclophilin-facilitated membrane translocation as pharmacological target to prevent intoxication of mammalian cells by binary clostridial actin ADP-ribosylated toxins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2014.07.013"}], "href": "https://doi.org/10.1016/j.jmb.2014.07.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25058685"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25058685"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Elizabeth A Blackburn, Martin A Wear, Vivian Landré, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclophilin40 isomerase activity is regulated by a temperature-dependent allosteric interaction with Hsp90."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20150124"}], "href": "https://doi.org/10.1042/BSR20150124"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26330616"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26330616"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jeremy D Baker, Lindsey B Shelton, Dali Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human cyclophilin 40 unravels neurotoxic amyloids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Biol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pbio.2001336"}], "href": "https://doi.org/10.1371/journal.pbio.2001336"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28654636"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28654636"}]}]}]}
Synonyms	CYPD, CYP-40
Proteins	PPID_HUMAN
NCBI Gene ID	5481
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPID has 7,815 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 125 datasets.

Click the + buttons to view associations for PPID from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPID Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PPID gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPID gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPID gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PPID gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PPID gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PPID gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPID gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PPID gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PPID gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PPID gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PPID gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPID gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PPID gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPID protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PPID gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPID gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPID gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PPID gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PPID gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PPID protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PPID gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPID protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPID protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PPID protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PPID protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PPID protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PPID protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPID gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPID gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPID gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPID gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PPID gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PPID protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PPID gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for PPID protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PPID gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PPID gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PPID gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPID gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PPID gene from the ENCODE Histone Modification Site Profiles dataset.