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 is part of the mitochondrial permeability transition pore in the inner mitochondrial membrane. Activation of this pore is though... See more...

Aliases for PPIF Gene

Aliases for PPIF Gene

  • Peptidylprolyl Isomerase F 2 3 5
  • Cyclophilin D 2 3 4
  • Peptidyl-Prolyl Cis-Trans Isomerase F, Mitochondrial 3 4
  • Mitochondrial Cyclophilin 3 4
  • Cyclophilin F 3 4
  • Rotamase F 3 4
  • EC 5.2.1.8 4 51
  • PPIase F 3 4
  • CyP-M 3 4
  • Cyp-D 2 3
  • CYP3 3 4
  • CypD 3 4
  • Peptidyl-Prolyl Cis-Trans Isomerase, Mitochondrial 3
  • Peptidylprolyl Isomerase F (Cyclophilin F) 2
  • Cyclophilin 3 3
  • HCyP3 2
  • CyP-D 4
  • PPIF 5

External Ids for PPIF Gene

Previous GeneCards Identifiers for PPIF Gene

  • GC10P080064
  • GC10P080316
  • GC10P080999
  • GC10P080451
  • GC10P080777
  • GC10P081107
  • GC10P075101
  • GC10P079349
  • GC10P081949
  • GC10P082113
  • GC10P082154
  • GC10P083194
  • GC10P079465
  • GC10P079466
  • GC10P080330
  • GC10P081513
  • GC10P081845

Summaries for PPIF Gene

Entrez Gene Summary for PPIF 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 is part of the mitochondrial permeability transition pore in the inner mitochondrial membrane. Activation of this pore is thought to be involved in the induction of apoptotic and necrotic cell death. [provided by RefSeq, Jul 2008]

GeneCards Summary for PPIF Gene

PPIF (Peptidylprolyl Isomerase F) is a Protein Coding gene. Diseases associated with PPIF include Ischemia and Ullrich Congenital Muscular Dystrophy 1. Among its related pathways are Calcium signaling pathway and Parkinson disease. Gene Ontology (GO) annotations related to this gene include peptide binding and cyclosporin A binding. An important paralog of this gene is PPIA.

UniProtKB/Swiss-Prot Summary for PPIF Gene

  • PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.

Gene Wiki entry for PPIF Gene

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

Genomics for PPIF Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PPIF 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 PPIF on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the PPIF gene promoter:
  • Arnt
  • ATF6
  • CREB
  • CUTL1
  • E2F
  • E2F-1
  • Lmo2
  • RORalpha1
  • Sp1

Genomic Locations for PPIF Gene

Genomic Locations for PPIF Gene
chr10:79,347,469-79,355,334
(GRCh38/hg38)
Size:
7,866 bases
Orientation:
Plus strand
chr10:81,107,220-81,115,093
(GRCh37/hg19)
Size:
7,874 bases
Orientation:
Plus strand

Genomic View for PPIF Gene

Genes around PPIF on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for PPIF Gene

Proteins for PPIF Gene

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

    Protein Symbol:
    P30405-PPIF_HUMAN
    Recommended name:
    Peptidyl-prolyl cis-trans isomerase F, mitochondrial
    Protein Accession:
    P30405
    Secondary Accessions:
    • Q2YDB7
    • Q5W131

    Protein attributes for PPIF Gene

    Size:
    207 amino acids
    Molecular mass:
    22040 Da
    Quaternary structure:
    • Associates with the mitochondrial membrane ATP synthase F(1)F(0) ATP synthase; the association is increased by inorganic phosphate (Pi) and decreased by cyclosporin A (CsA). Interacts with ATP5F1B; ATP5PD and ATP5PO. Interacts with SLC25A3; the interaction is impaired by CsA. Interacts with BCL2; the interaction is impaired by CsA. Interacts with TP53; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by CsA. Interacts with C1QBP. Interacts with MCUR1 (PubMed:26976564). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735). Interacts with SPG7 (PubMed:26387735).

    Three dimensional structures from OCA and Proteopedia for PPIF Gene

    Alternative splice isoforms for PPIF Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PPIF Gene

Selected DME Specific Peptides for PPIF Gene

P30405:
  • VKKIESFGS
  • LSMANAG
  • TNGSQFF
  • GVLSMAN
  • TAENFRAL
  • TGEKGFGY
  • GDFTNHNGTGG
  • GSTFHRVI
  • GPNTNGSQ
  • DVVPKTA
  • GFGYKGS
  • PKTAENF
  • DENFTLKH
  • GGKSIYG
  • LDGKHVVFG
  • DVVKKIES
  • LCTGEKG

Post-translational modifications for PPIF Gene

Other Protein References for PPIF Gene

Antibody Products

Domains & Families for PPIF Gene

Gene Families for PPIF Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for PPIF Gene

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

Suggested Antigen Peptide Sequences for PPIF Gene

GenScript: Design optimal peptide antigens:
  • Rotamase F (PPIF_HUMAN)
  • Peptidyl-prolyl cis-trans isomerase (Q2YDB7_HUMAN)
  • Peptidyl-prolyl cis-trans isomerase (Q5JSI1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P30405

UniProtKB/Swiss-Prot:

PPIF_HUMAN :
  • Belongs to the cyclophilin-type PPIase family.
Family:
  • Belongs to the cyclophilin-type PPIase family.
genes like me logo Genes that share domains with PPIF: view

Function for PPIF Gene

Molecular function for PPIF 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:20676357). Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.
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:20676357};.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by cyclosporin A (CsA) (PubMed:20676357). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP.

Enzyme Numbers (IUBMB) for PPIF Gene

Phenotypes From GWAS Catalog for PPIF Gene

Gene Ontology (GO) - Molecular Function for PPIF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003755 peptidyl-prolyl cis-trans isomerase activity IEA,IDA 20676357
GO:0005515 protein binding IPI 22726440
GO:0016018 cyclosporin A binding IDA 20676357
GO:0016853 isomerase activity IEA --
GO:0042277 peptide binding IEA --
genes like me logo Genes that share ontologies with PPIF: view
genes like me logo Genes that share phenotypes with PPIF: view

Animal Models for PPIF Gene

MGI Knock Outs for PPIF:

Animal Model Products

  • Taconic Biosciences Mouse Models for PPIF

CRISPR Products

Inhibitory RNA Products

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

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PPIF Gene

Localization for PPIF Gene

Subcellular locations from UniProtKB/Swiss-Prot for PPIF Gene

Mitochondrion matrix.

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 PPIF gene
Compartment Confidence
mitochondrion 5
cytosol 3
plasma membrane 2
extracellular 2
cytoskeleton 2
peroxisome 2
nucleus 2
endoplasmic reticulum 2
lysosome 2
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for PPIF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005739 mitochondrion IDA --
GO:0005743 mitochondrial inner membrane IEA --
GO:0005753 colocalizes_with mitochondrial proton-transporting ATP synthase complex ISS --
GO:0005757 mitochondrial permeability transition pore complex IDA 26387735
genes like me logo Genes that share ontologies with PPIF: view

Pathways & Interactions for PPIF Gene

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

Pathways by source for PPIF Gene

1 Sino Biological pathway for PPIF Gene

Gene Ontology (GO) - Biological Process for PPIF Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000413 protein peptidyl-prolyl isomerization IEA,IDA 20676357
GO:0002931 response to ischemia ISS --
GO:0006457 protein folding IEA,IBA 21873635
GO:0006915 apoptotic process IEA --
GO:0006979 response to oxidative stress IEA --
genes like me logo Genes that share ontologies with PPIF: view

No data available for SIGNOR curated interactions for PPIF Gene

Drugs & Compounds for PPIF Gene

(4) Drugs for PPIF Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cyclosporin A Approved, Investigational, Vet_approved Pharma Antagonist, Inhibitor, Inhibition, Target, binder Immunosuppressive agent, Calcineurin inhibitor 0
Coumarin 120 Experimental Pharma Target 0
Triglyme Experimental Pharma Target 0
Proline Nutra Target 44
genes like me logo Genes that share compounds with PPIF: view

Transcripts for PPIF Gene

mRNA/cDNA for PPIF Gene

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

CRISPR Products

Inhibitory RNA Products

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

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

ExUns: 1 ^ 2 ^ 3a · 3b ^ 4a · 4b · 4c ^ 5 ^ 6a · 6b · 6c
SP1: - - -
SP2: - - -
SP3: - - - -
SP4: - -
SP5: - - - - -
SP6:

Relevant External Links for PPIF Gene

GeneLoc Exon Structure for
PPIF

Expression for PPIF Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PPIF Gene

This gene is overexpressed in Adrenal Gland (x5.2).

Protein differential expression in normal tissues from HIPED for PPIF Gene

This gene is overexpressed in Monocytes (9.1) and Liver, secretome (6.4).

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



Protein tissue co-expression partners for PPIF Gene

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

SOURCE GeneReport for Unigene cluster for PPIF Gene:

Hs.381072

Evidence on tissue expression from TISSUES for PPIF Gene

  • Nervous system(4.8)
  • Blood(4.7)
  • Lung(4)
  • Heart(3.7)
  • Liver(3.7)
  • Muscle(3.5)
  • Intestine(3.4)
  • Skin(3.3)
  • Kidney(3.1)
  • Stomach(2.8)
  • Adrenal gland(2.8)
  • Pancreas(2.6)
  • Bone marrow(2.6)
  • Spleen(2.3)
  • Lymph node(2.2)
  • Thyroid gland(2.1)
  • Eye(2.1)
genes like me logo Genes that share expression patterns with PPIF: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for PPIF Gene

Orthologs for PPIF Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for PPIF Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PPIF 30 31
  • 99.52 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PPIF 30 31
  • 90.61 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PPIF 30 31
  • 88.32 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Ppif 30 17 31
  • 87.86 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Ppif 30
  • 87.86 (n)
Oppossum
(Monodelphis domestica)
Mammalia PPIF 31
  • 81 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia PPIF 31
  • 80 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PPIF 30 31
  • 72.64 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PPIF 31
  • 78 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia ppif 30
  • 68.1 (n)
MGC75715 30
Zebrafish
(Danio rerio)
Actinopterygii ppifb 30 31
  • 71.4 (n)
OneToOne
Dr.26827 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8555 30
Fruit Fly
(Drosophila melanogaster)
Insecta CG7768 31 32
  • 74 (a)
OneToMany
Cyp1 30 31 32
  • 72.67 (n)
OneToMany
ninaA 32
  • 44 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000462 30
  • 70.6 (n)
Worm
(Caenorhabditis elegans)
Secernentea cyp-3 32
  • 68 (a)
cyp-7 32
  • 64 (a)
cyn-13 31
  • 34 (a)
OneToMany
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_AGL177C 30
  • 67.51 (n)
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0D16676g 30
  • 65.2 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes CPR1 30 31 33
  • 64.57 (n)
ManyToMany
CPR3 31
  • 59 (a)
ManyToMany
Thale Cress
(Arabidopsis thaliana)
eudicotyledons CYP5 30
  • 61.64 (n)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.7462 30
Soybean
(Glycine max)
eudicotyledons Gma.5851 30
Rice
(Oryza sativa)
Liliopsida Os06g0708500 30
  • 63.1 (n)
Barley
(Hordeum vulgare)
Liliopsida Hv.3465 30
Wheat
(Triticum aestivum)
Liliopsida Ta.1078 30
Bread mold
(Neurospora crassa)
Ascomycetes NCU00726 30
  • 65.76 (n)
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes ppi1 30
  • 65.61 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.5180 31
  • 61 (a)
ManyToMany
Species where no ortholog for PPIF was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • 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)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for PPIF Gene

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

Paralogs for PPIF Gene

(23) SIMAP similar genes for PPIF Gene using alignment to 4 proteins:

  • PPIF_HUMAN
  • H0Y548_HUMAN
  • Q2YDB7_HUMAN
  • R4GN99_HUMAN

Pseudogenes.org Pseudogenes for PPIF Gene

genes like me logo Genes that share paralogs with PPIF: view

Variants for PPIF Gene

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

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
728878 Benign: not provided 79,353,779(+) C/T SYNONYMOUS_VARIANT
785321 Benign: not provided 79,353,830(+) C/G SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for PPIF Gene

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

Variant ID Type Subtype PubMed ID
nsv1161981 CNV duplication 26073780
nsv819846 CNV loss 19587683

Variation tolerance for PPIF Gene

Residual Variation Intolerance Score: 84.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.93; 19.36% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PPIF Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for PPIF Gene

MalaCards: The human disease database

(7) MalaCards diseases for PPIF Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
ischemia
  • acute coronary syndrome
ullrich congenital muscular dystrophy 1
  • ucmd1
bethlem myopathy 1
  • bthlm1
alzheimer disease
  • ad
optic atrophy 1
  • opa1
- elite association - COSMIC cancer census association via MalaCards
Search PPIF in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PPIF

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with PPIF: view

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

Publications for PPIF Gene

  1. The cyclophilin multigene family of peptidyl-prolyl isomerases. Characterization of three separate human isoforms. (PMID: 1744118) Bergsma DJ … Kasyan K (The Journal of biological chemistry 1991) 2 3 4
  2. SPG7 Is an Essential and Conserved Component of the Mitochondrial Permeability Transition Pore. (PMID: 26387735) Shanmughapriya S … Madesh M (Molecular cell 2015) 3 4
  3. p53 opens the mitochondrial permeability transition pore to trigger necrosis. (PMID: 22726440) Vaseva AV … Moll UM (Cell 2012) 3 4
  4. Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases. (PMID: 20676357) Davis TL … Dhe-Paganon S (PLoS biology 2010) 3 4
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41

Products for PPIF Gene

  • Signalway Proteins for PPIF

Sources for PPIF Gene