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Protein

Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Gene

PPIF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. 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

GO - Biological processi

Keywordsi

Molecular functionIsomerase, Rotamase
Biological processApoptosis, Necrosis

Enzyme and pathway databases

BRENDAi5.2.1.8 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000108179.13
HGNCiHGNC:9259 PPIF
MIMi604486 gene
neXtProtiNX_P30405

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi203C → S: Blocks Ca(2+)-induced mPTP opening and reduces hydrogen peroxide-induced cell death. 1 Publication1

Organism-specific databases

DisGeNETi10105
OpenTargetsiENSG00000108179
PharmGKBiPA33584

Chemistry databases

ChEMBLiCHEMBL3325306
DrugBankiDB02078 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

BioMutaiPPIF
DMDMi231968

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 29MitochondrionSequence analysisAdd BLAST29
ChainiPRO_000002548930 – 207Peptidyl-prolyl cis-trans isomerase F, mitochondrialAdd BLAST178

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei67N6-acetyllysine; alternateBy similarity1
Modified residuei67N6-succinyllysine; alternateBy similarity1
Modified residuei86N6-succinyllysineBy similarity1
Modified residuei167N6-acetyllysineBy similarity1
Modified residuei175N6-succinyllysineBy similarity1
Modified residuei190N6-succinyllysineBy similarity1
Modified residuei203S-nitrosocysteineBy similarity1

Post-translational modificationi

Deacteylated at Lys-167 by SIRT3.By similarity

Keywords - PTMi

Acetylation, S-nitrosylation

Proteomic databases

EPDiP30405
MaxQBiP30405
PaxDbiP30405
PeptideAtlasiP30405
PRIDEiP30405
TopDownProteomicsiP30405-1 [P30405-1]

2D gel databases

OGPiP30405
UCD-2DPAGEiP30405

PTM databases

iPTMnetiP30405
PhosphoSitePlusiP30405
SwissPalmiP30405

Expressioni

Gene expression databases

BgeeiENSG00000108179
CleanExiHS_PPIF
ExpressionAtlasiP30405 baseline and differential
GenevisibleiP30405 HS

Organism-specific databases

HPAiHPA077416

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

Show more details

Protein-protein interaction databases

BioGridi115411, 36 interactors
CORUMiP30405
IntActiP30405, 19 interactors
STRINGi9606.ENSP00000225174

Chemistry databases

BindingDBiP30405

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi47 – 54Combined sources8
Beta strandi57 – 66Combined sources10
Turni68 – 70Combined sources3
Helixi72 – 83Combined sources12
Turni84 – 86Combined sources3
Beta strandi94 – 99Combined sources6
Turni100 – 102Combined sources3
Beta strandi103 – 106Combined sources4
Turni109 – 111Combined sources3
Beta strandi112 – 115Combined sources4
Beta strandi120 – 123Combined sources4
Beta strandi139 – 142Combined sources4
Beta strandi144 – 146Combined sources3
Beta strandi150 – 152Combined sources3
Beta strandi154 – 159Combined sources6
Helixi162 – 164Combined sources3
Turni165 – 167Combined sources3
Beta strandi170 – 176Combined sources7
Helixi178 – 186Combined sources9
Beta strandi198 – 205Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BITX-ray1.71X43-207[»]
2BIUX-ray1.71X43-207[»]
2Z6WX-ray0.96A/B44-207[»]
3QYUX-ray1.54A44-207[»]
3R49X-ray1.77A43-207[»]
3R4GX-ray1.05A43-207[»]
3R54X-ray1.35A43-207[»]
3R56X-ray1.40A43-207[»]
3R57X-ray1.71A43-207[»]
3R59X-ray1.10A43-207[»]
3RCFX-ray1.15A43-207[»]
3RCGX-ray0.97A43-207[»]
3RCIX-ray1.44X43-207[»]
3RCKX-ray1.26X43-207[»]
3RCLX-ray1.70A43-207[»]
3RD9X-ray1.40X43-207[»]
3RDAX-ray1.07X43-207[»]
3RDBX-ray1.55A43-207[»]
3RDCX-ray1.94A43-207[»]
4J58X-ray1.28A44-207[»]
4J59X-ray1.92A44-207[»]
4J5AX-ray1.58X44-207[»]
4J5BX-ray2.01A44-207[»]
4J5CX-ray1.03X44-207[»]
4J5DX-ray1.32X44-207[»]
4J5EX-ray0.99X44-207[»]
4O8HX-ray0.85A43-207[»]
4O8IX-ray1.45A43-207[»]
4XNCX-ray2.23A44-207[»]
4ZSCX-ray1.50A44-207[»]
4ZSDX-ray1.45A44-207[»]
5A0EX-ray1.25A/B43-207[»]
5CBTX-ray1.45A44-207[»]
5CBUX-ray1.40A44-207[»]
5CBVX-ray1.80A44-207[»]
5CBWX-ray1.80A44-207[»]
5CCNX-ray1.80A44-207[»]
5CCQX-ray1.80A44-207[»]
5CCRX-ray1.90A44-207[»]
5CCSX-ray2.10X44-207[»]
ProteinModelPortaliP30405
SMRiP30405
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30405

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini49 – 205PPIase cyclophilin-typePROSITE-ProRule annotationAdd BLAST157

Sequence similaritiesi

Belongs to the cyclophilin-type PPIase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0865 Eukaryota
COG0652 LUCA
GeneTreeiENSGT00760000119119
HOGENOMiHOG000065981
HOVERGENiHBG001065
InParanoidiP30405
KOiK09565
OMAiELKHTGS
OrthoDBiEOG091G0BGL
PhylomeDBiP30405
TreeFamiTF312801

Family and domain databases

Gene3Di2.40.100.10, 1 hit
InterProiView protein in InterPro
IPR029000 Cyclophilin-like_dom_sf
IPR024936 Cyclophilin-type_PPIase
IPR020892 Cyclophilin-type_PPIase_CS
IPR002130 Cyclophilin-type_PPIase_dom
PANTHERiPTHR11071 PTHR11071, 1 hit
PfamiView protein in Pfam
PF00160 Pro_isomerase, 1 hit
PIRSFiPIRSF001467 Peptidylpro_ismrse, 1 hit
PRINTSiPR00153 CSAPPISMRASE
SUPFAMiSSF50891 SSF50891, 1 hit
PROSITEiView protein in PROSITE
PS00170 CSA_PPIASE_1, 1 hit
PS50072 CSA_PPIASE_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative 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.

« Hide

        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
Length:207
Mass (Da):22,040
Last modified:April 1, 1993 - v1
Checksum:iD7C76F1D4049F16A
GO
Isoform 2 (identifier: P30405-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     139-207: VLSMANAGPN...IVITDCGQLS → WMASMLCSVTSKRAWTS

Show »
Length:155
Mass (Da):16,541
Checksum:iBA0C086F1899B2DF
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056286139 – 207VLSMA…CGQLS → WMASMLCSVTSKRAWTS in isoform 2. 2 PublicationsAdd BLAST69

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M80254 mRNA Translation: AAA58434.1
AK296669 mRNA Translation: BAG59266.1
AL133481 Genomic DNA No translation available.
AL391665 Genomic DNA No translation available.
CH471083 Genomic DNA Translation: EAW54645.1
BC005020 mRNA Translation: AAH05020.1
BC110299 mRNA Translation: AAI10300.1
CCDSiCCDS7358.1 [P30405-1]
PIRiA41581
RefSeqiNP_005720.1, NM_005729.3 [P30405-1]
UniGeneiHs.381072

Genome annotation databases

EnsembliENST00000225174; ENSP00000225174; ENSG00000108179 [P30405-1]
GeneIDi10105
KEGGihsa:10105
UCSCiuc001kai.4 human [P30405-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPPIF_HUMAN
AccessioniPrimary (citable) accession number: P30405
Secondary accession number(s): Q2YDB7, Q5W131
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: May 23, 2018
This is version 172 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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