UniProtKB - P30405 (PPIF_HUMAN)
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Protein
Peptidyl-prolyl cis-trans isomerase F, mitochondrial
Gene
PPIF
Organism
Homo sapiens (Human)
Status
Functioni
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. 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 F1F0 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.3 Publications
Catalytic activityi
Peptidylproline (omega=180) = peptidylproline (omega=0).
Enzyme regulationi
Binds cyclosporin A (CsA). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP.
GO - Molecular functioni
- cyclosporin A binding Source: Ensembl
- peptidyl-prolyl cis-trans isomerase activity Source: GO_Central
GO - Biological processi
- apoptotic mitochondrial changes Source: Ensembl
- cellular response to arsenic-containing substance Source: UniProtKB
- cellular response to calcium ion Source: UniProtKB
- cellular response to hydrogen peroxide Source: UniProtKB
- mitochondrial outer membrane permeabilization involved in programmed cell death Source: UniProtKB
- necroptotic process Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of ATPase activity Source: UniProtKB
- negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- negative regulation of oxidative phosphorylation Source: UniProtKB
- negative regulation of oxidative phosphorylation uncoupler activity Source: UniProtKB
- negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
- positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
- protein folding Source: InterPro
- regulation of mitochondrial membrane permeability Source: UniProtKB
- regulation of mitochondrial membrane permeability involved in programmed necrotic cell death Source: UniProtKB
- regulation of necrotic cell death Source: Ensembl
- regulation of proton-transporting ATPase activity, rotational mechanism Source: UniProtKB
- response to ischemia Source: UniProtKB
Keywordsi
Molecular function | Isomerase, Rotamase |
Biological process | Apoptosis, Necrosis |
Enzyme and pathway databases
BRENDAi | 5.2.1.8. 2681. |
Names & Taxonomyi
Protein namesi | Recommended name: Peptidyl-prolyl cis-trans isomerase F, mitochondrial (EC:5.2.1.8)Short name: PPIase F Alternative name(s): Cyclophilin D Short name: CyP-D Short name: CypD Cyclophilin F Mitochondrial cyclophilin Short name: CyP-M Rotamase F |
Gene namesi | Name:PPIF Synonyms:CYP3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000108179.13. |
HGNCi | HGNC:9259. PPIF. |
MIMi | 604486. gene. |
neXtProti | NX_P30405. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 203 | C → S: Blocks Ca(2+)-induced mPTP opening and reduces hydrogen peroxide-induced cell death. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 10105. |
OpenTargetsi | ENSG00000108179. |
PharmGKBi | PA33584. |
Chemistry databases
ChEMBLi | CHEMBL3325306. |
DrugBanki | DB02078. 1-Methoxy-2-[2-(2-Methoxy-Ethoxy]-Ethane. DB08168. 7-AMINO-4-METHYL-CHROMEN-2-ONE. DB00091. Cyclosporine. DB00172. L-Proline. |
Polymorphism and mutation databases
BioMutai | PPIF. |
DMDMi | 231968. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 29 | MitochondrionSequence analysisAdd BLAST | 29 | |
ChainiPRO_0000025489 | 30 – 207 | Peptidyl-prolyl cis-trans isomerase F, mitochondrialAdd BLAST | 178 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 67 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 67 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 86 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 167 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 175 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 190 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 203 | S-nitrosocysteineBy similarity | 1 |
Post-translational modificationi
Deacteylated at Lys-167 by SIRT3.By similarity
Keywords - PTMi
Acetylation, S-nitrosylationProteomic databases
EPDi | P30405. |
MaxQBi | P30405. |
PaxDbi | P30405. |
PeptideAtlasi | P30405. |
PRIDEi | P30405. |
TopDownProteomicsi | P30405-1. [P30405-1] |
2D gel databases
OGPi | P30405. |
UCD-2DPAGEi | P30405. |
PTM databases
iPTMneti | P30405. |
PhosphoSitePlusi | P30405. |
SwissPalmi | P30405. |
Expressioni
Gene expression databases
Bgeei | ENSG00000108179. |
CleanExi | HS_PPIF. |
ExpressionAtlasi | P30405. baseline and differential. |
Genevisiblei | P30405. HS. |
Organism-specific databases
HPAi | HPA077416. |
Interactioni
Subunit structurei
Associates with the mitochondrial membrane ATP synthase F1F0 ATP synthase; the association is increased by inorganic phosphate (Pi) and decreased by cyclosporin A (CsA). Interacts with ATP5F1B; ATP5H and ATP5O. 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).6 Publications
Binary interactionsi
Protein-protein interaction databases
BioGridi | 115411. 35 interactors. |
CORUMi | P30405. |
IntActi | P30405. 14 interactors. |
STRINGi | 9606.ENSP00000225174. |
Chemistry databases
BindingDBi | P30405. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 47 – 54 | Combined sources | 8 | |
Beta strandi | 57 – 66 | Combined sources | 10 | |
Turni | 68 – 70 | Combined sources | 3 | |
Helixi | 72 – 83 | Combined sources | 12 | |
Turni | 84 – 86 | Combined sources | 3 | |
Beta strandi | 94 – 99 | Combined sources | 6 | |
Turni | 100 – 102 | Combined sources | 3 | |
Beta strandi | 103 – 106 | Combined sources | 4 | |
Turni | 109 – 111 | Combined sources | 3 | |
Beta strandi | 112 – 115 | Combined sources | 4 | |
Beta strandi | 120 – 123 | Combined sources | 4 | |
Beta strandi | 139 – 142 | Combined sources | 4 | |
Beta strandi | 144 – 146 | Combined sources | 3 | |
Beta strandi | 150 – 152 | Combined sources | 3 | |
Beta strandi | 154 – 159 | Combined sources | 6 | |
Helixi | 162 – 164 | Combined sources | 3 | |
Turni | 165 – 167 | Combined sources | 3 | |
Beta strandi | 170 – 176 | Combined sources | 7 | |
Helixi | 178 – 186 | Combined sources | 9 | |
Beta strandi | 198 – 205 | Combined sources | 8 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2BIT | X-ray | 1.71 | X | 43-207 | [»] | |
2BIU | X-ray | 1.71 | X | 43-207 | [»] | |
2Z6W | X-ray | 0.96 | A/B | 44-207 | [»] | |
3QYU | X-ray | 1.54 | A | 44-207 | [»] | |
3R49 | X-ray | 1.77 | A | 43-207 | [»] | |
3R4G | X-ray | 1.05 | A | 43-207 | [»] | |
3R54 | X-ray | 1.35 | A | 43-207 | [»] | |
3R56 | X-ray | 1.40 | A | 43-207 | [»] | |
3R57 | X-ray | 1.71 | A | 43-207 | [»] | |
3R59 | X-ray | 1.10 | A | 43-207 | [»] | |
3RCF | X-ray | 1.15 | A | 43-207 | [»] | |
3RCG | X-ray | 0.97 | A | 43-207 | [»] | |
3RCI | X-ray | 1.44 | X | 43-207 | [»] | |
3RCK | X-ray | 1.26 | X | 43-207 | [»] | |
3RCL | X-ray | 1.70 | A | 43-207 | [»] | |
3RD9 | X-ray | 1.40 | X | 43-207 | [»] | |
3RDA | X-ray | 1.07 | X | 43-207 | [»] | |
3RDB | X-ray | 1.55 | A | 43-207 | [»] | |
3RDC | X-ray | 1.94 | A | 43-207 | [»] | |
4J58 | X-ray | 1.28 | A | 44-207 | [»] | |
4J59 | X-ray | 1.92 | A | 44-207 | [»] | |
4J5A | X-ray | 1.58 | X | 44-207 | [»] | |
4J5B | X-ray | 2.01 | A | 44-207 | [»] | |
4J5C | X-ray | 1.03 | X | 44-207 | [»] | |
4J5D | X-ray | 1.32 | X | 44-207 | [»] | |
4J5E | X-ray | 0.99 | X | 44-207 | [»] | |
4O8H | X-ray | 0.85 | A | 43-207 | [»] | |
4O8I | X-ray | 1.45 | A | 43-207 | [»] | |
4XNC | X-ray | 2.23 | A | 44-207 | [»] | |
4ZSC | X-ray | 1.50 | A | 44-207 | [»] | |
4ZSD | X-ray | 1.45 | A | 44-207 | [»] | |
5A0E | X-ray | 1.25 | A/B | 43-207 | [»] | |
5CBT | X-ray | 1.45 | A | 44-207 | [»] | |
5CBU | X-ray | 1.40 | A | 44-207 | [»] | |
5CBV | X-ray | 1.80 | A | 44-207 | [»] | |
5CBW | X-ray | 1.80 | A | 44-207 | [»] | |
5CCN | X-ray | 1.80 | A | 44-207 | [»] | |
5CCQ | X-ray | 1.80 | A | 44-207 | [»] | |
5CCR | X-ray | 1.90 | A | 44-207 | [»] | |
5CCS | X-ray | 2.10 | X | 44-207 | [»] | |
ProteinModelPortali | P30405. | |||||
SMRi | P30405. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P30405. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 49 – 205 | PPIase cyclophilin-typePROSITE-ProRule annotationAdd BLAST | 157 |
Sequence similaritiesi
Belongs to the cyclophilin-type PPIase family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG0865. Eukaryota. COG0652. LUCA. |
GeneTreei | ENSGT00760000119119. |
HOGENOMi | HOG000065981. |
HOVERGENi | HBG001065. |
InParanoidi | P30405. |
KOi | K09565. |
OMAi | ELKHTGS. |
OrthoDBi | EOG091G0BGL. |
PhylomeDBi | P30405. |
TreeFami | TF312801. |
Family and domain databases
Gene3Di | 2.40.100.10. 1 hit. |
InterProi | View protein in InterPro IPR029000. Cyclophilin-like_dom_sf. IPR024936. Cyclophilin-type_PPIase. IPR020892. Cyclophilin-type_PPIase_CS. IPR002130. Cyclophilin-type_PPIase_dom. |
PANTHERi | PTHR11071. PTHR11071. 1 hit. |
Pfami | View protein in Pfam PF00160. Pro_isomerase. 1 hit. |
PIRSFi | PIRSF001467. Peptidylpro_ismrse. 1 hit. |
PRINTSi | PR00153. CSAPPISMRASE. |
SUPFAMi | SSF50891. SSF50891. 1 hit. |
PROSITEi | View protein in PROSITE PS00170. CSA_PPIASE_1. 1 hit. PS50072. CSA_PPIASE_2. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1 (identifier: P30405-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MLALRCGSRW LGLLSVPRSV PLRLPAARAC SKGSGDPSSS SSSGNPLVYL
60 70 80 90 100
DVDANGKPLG RVVLELKADV VPKTAENFRA LCTGEKGFGY KGSTFHRVIP
110 120 130 140 150
SFMCQAGDFT NHNGTGGKSI YGSRFPDENF TLKHVGPGVL SMANAGPNTN
160 170 180 190 200
GSQFFICTIK TDWLDGKHVV FGHVKEGMDV VKKIESFGSK SGRTSKKIVI
TDCGQLS
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056286 | 139 – 207 | VLSMA…CGQLS → WMASMLCSVTSKRAWTS in isoform 2. 2 PublicationsAdd BLAST | 69 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M80254 mRNA. Translation: AAA58434.1. AK296669 mRNA. Translation: BAG59266.1. AL133481, AL391665 Genomic DNA. Translation: CAH72725.1. AL391665, AL133481 Genomic DNA. Translation: CAI40994.1. CH471083 Genomic DNA. Translation: EAW54645.1. BC005020 mRNA. Translation: AAH05020.1. BC110299 mRNA. Translation: AAI10300.1. |
CCDSi | CCDS7358.1. [P30405-1] |
PIRi | A41581. |
RefSeqi | NP_005720.1. NM_005729.3. [P30405-1] |
UniGenei | Hs.381072. |
Genome annotation databases
Ensembli | ENST00000225174; ENSP00000225174; ENSG00000108179. [P30405-1] |
GeneIDi | 10105. |
KEGGi | hsa:10105. |
UCSCi | uc001kai.4. human. [P30405-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
Entry namei | PPIF_HUMAN | |
Accessioni | P30405Primary (citable) accession number: P30405 Secondary accession number(s): Q2YDB7, Q5W131 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1993 |
Last sequence update: | April 1, 1993 | |
Last modified: | March 28, 2018 | |
This is version 171 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |