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Protein

Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Gene

Ppif

Organism
Mus musculus (Mouse)
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.7 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: UniProtKB

GO - Biological processi

  • apoptotic mitochondrial changes Source: MGI
  • 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: MGI
  • 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
  • protein peptidyl-prolyl isomerization Source: UniProtKB
  • 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: UniProtKB
  • regulation of proton-transporting ATPase activity, rotational mechanism Source: UniProtKB
  • response to ischemia Source: UniProtKB
  • response to oxidative stress Source: MGI

Keywordsi

Molecular functionIsomerase, Rotamase
Biological processApoptosis, Necrosis

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
Rotamase F
Gene namesi
Name:Ppif
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:2145814 Ppif

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

Disruption phenotypei

Mice are developmentally normal and show no apparent anomalies. Mitochondria do not undergo cyclosporin A-sensitive mitochondrial permeability transtition. Cells show resistance to necrotic cell death induced by reactive oxygen species and Ca2+ overload, and animals show a high level of resistance to ischaemia/reperfusion-induced cardiac injury. Mice show a dramatic reduction in brain infarct size after acute middle cerebral artery occlusion and reperfusion.3 Publications

Chemistry databases

ChEMBLiCHEMBL3804752

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 29MitochondrionBy similarityAdd BLAST29
ChainiPRO_000002549030 – 206Peptidyl-prolyl cis-trans isomerase F, mitochondrialAdd BLAST177

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei66N6-acetyllysine; alternateCombined sources1
Modified residuei66N6-succinyllysine; alternateCombined sources1
Modified residuei85N6-succinyllysineCombined sources1
Modified residuei166N6-acetyllysine1 Publication1
Modified residuei174N6-succinyllysineCombined sources1
Modified residuei189N6-succinyllysineCombined sources1
Modified residuei202S-nitrosocysteine1 Publication1

Post-translational modificationi

Deacteylated at Lys-166 by SIRT3.

Keywords - PTMi

Acetylation, S-nitrosylation

Proteomic databases

EPDiQ99KR7
MaxQBiQ99KR7
PaxDbiQ99KR7
PeptideAtlasiQ99KR7
PRIDEiQ99KR7

PTM databases

iPTMnetiQ99KR7
PhosphoSitePlusiQ99KR7

Expressioni

Gene expression databases

BgeeiENSMUSG00000021868
CleanExiMM_PPIF
GenevisibleiQ99KR7 MM

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. Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF. Interacts with SPG7 (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Tp53P023402EBI-6455001,EBI-474016

Protein-protein interaction databases

IntActiQ99KR7 8 interactors.
MINTiQ99KR7
STRINGi10090.ENSMUSP00000022419

Structurei

3D structure databases

ProteinModelPortaliQ99KR7
SMRiQ99KR7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini48 – 204PPIase 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
InParanoidiQ99KR7
KOiK09565
OMAiELKHTGS
OrthoDBiEOG091G0BGL
PhylomeDBiQ99KR7
TreeFamiTF312801

Family and domain databases

Gene3Di2.40.100.101 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

Sequencei

Sequence statusi: Complete.

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

Q99KR7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLALRCGPRL LGLLSGPRSA PLLLSATRTC SDGGARGANS SSGNPLVYLD
60 70 80 90 100
VGADGQPLGR VVLELKADVV PKTAENFRAL CTGEKGFGYK GSTFHRVIPA
110 120 130 140 150
FMCQAGDFTN HNGTGGRSIY GSRFPDENFT LKHVGPGVLS MANAGPNTNG
160 170 180 190 200
SQFFICTIKT DWLDGKHVVF GHVKEGMDVV KKIESFGSKS GKTSKKIVIT

DCGQLS
Length:206
Mass (Da):21,737
Last modified:June 1, 2001 - v1
Checksum:i6E6BFE4D6B064D6F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC004041 mRNA Translation: AAH04041.1
CCDSiCCDS26874.1
RefSeqiNP_598845.1, NM_134084.1
UniGeneiMm.41656

Genome annotation databases

EnsembliENSMUST00000022419; ENSMUSP00000022419; ENSMUSG00000021868
GeneIDi105675
KEGGimmu:105675
UCSCiuc007srr.1 mouse

Similar proteinsi

Entry informationi

Entry nameiPPIF_MOUSE
AccessioniPrimary (citable) accession number: Q99KR7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: June 1, 2001
Last modified: March 28, 2018
This is version 125 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome