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Q99KR7

- PPIF_MOUSE

UniProt

Q99KR7 - PPIF_MOUSE

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Protein

Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Gene
Ppif
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - 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

  1. cyclosporin A binding Source: Ensembl
  2. peptidyl-prolyl cis-trans isomerase activity Source: UniProtKB
  3. protein binding Source: IntAct

GO - Biological processi

  1. apoptotic mitochondrial changes Source: MGI
  2. cellular response to arsenic-containing substance Source: UniProtKB
  3. cellular response to calcium ion Source: UniProtKB
  4. cellular response to hydrogen peroxide Source: UniProtKB
  5. necroptotic process Source: MGI
  6. negative regulation of apoptotic process Source: UniProtKB
  7. negative regulation of ATPase activity Source: UniProtKB
  8. negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  9. negative regulation of oxidative phosphorylation Source: UniProtKB
  10. negative regulation of oxidative phosphorylation uncoupler activity Source: UniProtKB
  11. negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
  12. positive regulation of necrotic cell death Source: Ensembl
  13. positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
  14. protein folding Source: UniProtKB-KW
  15. protein peptidyl-prolyl isomerization Source: UniProtKB
  16. regulation of mitochondrial membrane permeability Source: UniProtKB
  17. regulation of mitochondrial membrane permeability involved in programmed necrotic cell death Source: UniProtKB
  18. regulation of necrotic cell death Source: UniProtKB
  19. regulation of proton-transporting ATPase activity, rotational mechanism Source: UniProtKB
  20. response to ischemia Source: UniProtKB
  21. response to oxidative stress Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Rotamase

Keywords - Biological processi

Apoptosis, Necrosis

Keywords - Ligandi

Cyclosporin

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 14

Organism-specific databases

MGIiMGI:2145814. Ppif.

Subcellular locationi

Mitochondrion matrix By similarity

GO - Cellular componenti

  1. mitochondrial inner membrane Source: Ensembl
  2. mitochondrial matrix Source: UniProtKB-SubCell
  3. mitochondrial permeability transition pore complex Source: UniProtKB
  4. mitochondrion Source: MGI
Complete GO annotation...

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2929Mitochondrion By similarityAdd
BLAST
Chaini30 – 206177Peptidyl-prolyl cis-trans isomerase F, mitochondrialPRO_0000025490Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei66 – 661N6-acetyllysine; alternate1 Publication
Modified residuei66 – 661N6-succinyllysine; alternate1 Publication
Modified residuei85 – 851N6-succinyllysine1 Publication
Modified residuei166 – 1661N6-acetyllysine1 Publication
Modified residuei174 – 1741N6-succinyllysine1 Publication
Modified residuei189 – 1891N6-succinyllysine1 Publication
Modified residuei202 – 2021S-nitrosocysteine1 Publication

Post-translational modificationi

Deacteylated at Lys-166 by SIRT3.

Keywords - PTMi

Acetylation, S-nitrosylation

Proteomic databases

MaxQBiQ99KR7.
PaxDbiQ99KR7.
PRIDEiQ99KR7.

PTM databases

PhosphoSiteiQ99KR7.

Expressioni

Gene expression databases

BgeeiQ99KR7.
CleanExiMM_PPIF.
GenevestigatoriQ99KR7.

Interactioni

Subunit structurei

Believed to associate with the mitochondrial permeability transition pore complex (PTPC). 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 ATP5B; 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.4 Publications

Binary interactionsi

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

Protein-protein interaction databases

IntActiQ99KR7. 7 interactions.
MINTiMINT-1856076.
STRINGi10090.ENSMUSP00000022419.

Structurei

3D structure databases

ProteinModelPortaliQ99KR7.
SMRiQ99KR7. Positions 43-206.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini48 – 204157PPIase cyclophilin-typeAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0652.
GeneTreeiENSGT00750000117619.
HOGENOMiHOG000065981.
HOVERGENiHBG001065.
InParanoidiQ99KR7.
KOiK09565.
OMAiAFMCQAG.
OrthoDBiEOG79GT7W.
PhylomeDBiQ99KR7.
TreeFamiTF312801.

Family and domain databases

Gene3Di2.40.100.10. 1 hit.
InterProiIPR029000. Cyclophilin-like_dom.
IPR024936. Cyclophilin-type_PPIase.
IPR020892. Cyclophilin-type_PPIase_CS.
IPR002130. Cyclophilin-type_PPIase_dom.
[Graphical view]
PfamiPF00160. Pro_isomerase. 1 hit.
[Graphical view]
PIRSFiPIRSF001467. Peptidylpro_ismrse. 1 hit.
PRINTSiPR00153. CSAPPISMRASE.
SUPFAMiSSF50891. SSF50891. 1 hit.
PROSITEiPS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q99KR7-1 [UniParc]FASTAAdd to Basket

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MLALRCGPRL LGLLSGPRSA PLLLSATRTC SDGGARGANS SSGNPLVYLD    50
VGADGQPLGR VVLELKADVV PKTAENFRAL CTGEKGFGYK GSTFHRVIPA 100
FMCQAGDFTN HNGTGGRSIY GSRFPDENFT LKHVGPGVLS MANAGPNTNG 150
SQFFICTIKT DWLDGKHVVF GHVKEGMDVV KKIESFGSKS GKTSKKIVIT 200
DCGQLS 206
Length:206
Mass (Da):21,737
Last modified:June 1, 2001 - v1
Checksum:i6E6BFE4D6B064D6F
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC004041 mRNA. Translation: AAH04041.1.
CCDSiCCDS26874.1.
RefSeqiNP_598845.1. NM_134084.1.
XP_006518453.1. XM_006518390.1.
UniGeneiMm.41656.

Genome annotation databases

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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC004041 mRNA. Translation: AAH04041.1 .
CCDSi CCDS26874.1.
RefSeqi NP_598845.1. NM_134084.1.
XP_006518453.1. XM_006518390.1.
UniGenei Mm.41656.

3D structure databases

ProteinModelPortali Q99KR7.
SMRi Q99KR7. Positions 43-206.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q99KR7. 7 interactions.
MINTi MINT-1856076.
STRINGi 10090.ENSMUSP00000022419.

PTM databases

PhosphoSitei Q99KR7.

Proteomic databases

MaxQBi Q99KR7.
PaxDbi Q99KR7.
PRIDEi Q99KR7.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000022419 ; ENSMUSP00000022419 ; ENSMUSG00000021868 .
GeneIDi 105675.
KEGGi mmu:105675.
UCSCi uc007srr.1. mouse.

Organism-specific databases

CTDi 10105.
MGIi MGI:2145814. Ppif.

Phylogenomic databases

eggNOGi COG0652.
GeneTreei ENSGT00750000117619.
HOGENOMi HOG000065981.
HOVERGENi HBG001065.
InParanoidi Q99KR7.
KOi K09565.
OMAi AFMCQAG.
OrthoDBi EOG79GT7W.
PhylomeDBi Q99KR7.
TreeFami TF312801.

Miscellaneous databases

NextBioi 357826.
PROi Q99KR7.
SOURCEi Search...

Gene expression databases

Bgeei Q99KR7.
CleanExi MM_PPIF.
Genevestigatori Q99KR7.

Family and domain databases

Gene3Di 2.40.100.10. 1 hit.
InterProi IPR029000. Cyclophilin-like_dom.
IPR024936. Cyclophilin-type_PPIase.
IPR020892. Cyclophilin-type_PPIase_CS.
IPR002130. Cyclophilin-type_PPIase_dom.
[Graphical view ]
Pfami PF00160. Pro_isomerase. 1 hit.
[Graphical view ]
PIRSFi PIRSF001467. Peptidylpro_ismrse. 1 hit.
PRINTSi PR00153. CSAPPISMRASE.
SUPFAMi SSF50891. SSF50891. 1 hit.
PROSITEi PS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Mammary tumor.
  2. "Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death."
    Nakagawa T., Shimizu S., Watanabe T., Yamaguchi O., Otsu K., Yamagata H., Inohara H., Kubo T., Tsujimoto Y.
    Nature 434:652-658(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  3. "Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death."
    Baines C.P., Kaiser R.A., Purcell N.H., Blair N.S., Osinska H., Hambleton M.A., Brunskill E.W., Sayen M.R., Gottlieb R.A., Dorn G.W., Robbins J., Molkentin J.D.
    Nature 434:658-662(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  4. "Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia."
    Schinzel A.C., Takeuchi O., Huang Z., Fisher J.K., Zhou Z., Rubens J., Hetz C., Danial N.N., Moskowitz M.A., Korsmeyer S.J.
    Proc. Natl. Acad. Sci. U.S.A. 102:12005-12010(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  5. "Phosphate is essential for inhibition of the mitochondrial permeability transition pore by cyclosporin A and by cyclophilin D ablation."
    Basso E., Petronilli V., Forte M.A., Bernardi P.
    J. Biol. Chem. 283:26307-26311(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Cyclophilin D modulates mitochondrial F0F1-ATP synthase by interacting with the lateral stalk of the complex."
    Giorgio V., Bisetto E., Soriano M.E., Dabbeni-Sala F., Basso E., Petronilli V., Forte M.A., Bernardi P., Lippe G.
    J. Biol. Chem. 284:33982-33988(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy."
    Hafner A.V., Dai J., Gomes A.P., Xiao C.Y., Palmeira C.M., Rosenzweig A., Sinclair D.A.
    Aging (Albany NY) 2:914-923(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT LYS-166, INTERACTION WITH SIRT3.
  8. "Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death."
    McGee A.M., Baines C.P.
    Biochem. J. 433:119-125(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH C1QBP.
  9. "Modulation of F0F1-ATP synthase activity by cyclophilin D regulates matrix adenine nucleotide levels."
    Chinopoulos C., Konrad C., Kiss G., Metelkin E., Torocsik B., Zhang S.F., Starkov A.A.
    FEBS J. 278:1112-1125(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ATP5B.
  10. "Cysteine 203 of cyclophilin D is critical for cyclophilin D activation of the mitochondrial permeability transition pore."
    Nguyen T.T., Stevens M.V., Kohr M., Steenbergen C., Sack M.N., Murphy E.
    J. Biol. Chem. 286:40184-40192(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: S-NITROSYLATION AT CYS-202.
  11. "p53 opens the mitochondrial permeability transition pore to trigger necrosis."
    Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M.
    Cell 149:1536-1548(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TP53.
  12. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-66; LYS-85; LYS-174 AND LYS-189, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  13. "Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
    Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
    Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-66, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiPPIF_MOUSE
AccessioniPrimary (citable) accession number: Q99KR7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: June 1, 2001
Last modified: September 3, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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