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P30405 (PPIF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Short name=PPIase F
EC=5.2.1.8
Alternative name(s):
Cyclophilin D
Short name=CyP-D
Short name=CypD
Cyclophilin F
Mitochondrial cyclophilin
Short name=CyP-M
Rotamase F
Gene names
Name:PPIF
Synonyms:CYP3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length207 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 probablity 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. Ref.5 Ref.9

Catalytic activity

Peptidylproline (omega=180) = peptidylproline (omega=0).

Enzyme regulation

Binds cyclosporin A (CsA). Is displaced by CsA from the mPTP leading to a lower open probablity of the mPTP.

Subunit structure

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. Ref.5 Ref.7 Ref.9

Subcellular location

Mitochondrion matrix Ref.4.

Post-translational modification

Deacteylated at Lys-167 by SIRT3 By similarity.

Sequence similarities

Belongs to the cyclophilin-type PPIase family.

Contains 1 PPIase cyclophilin-type domain.

Ontologies

Keywords
   Biological processApoptosis
Necrosis
   Cellular componentMitochondrion
   DomainTransit peptide
   LigandCyclosporin
   Molecular functionIsomerase
Rotamase
   PTMAcetylation
S-nitrosylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic mitochondrial changes

Inferred from electronic annotation. Source: Ensembl

cellular response to arsenic-containing substance

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to calcium ion

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to hydrogen peroxide

Inferred from mutant phenotype Ref.9. Source: UniProtKB

negative regulation of ATPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from direct assay Ref.5. Source: UniProtKB

negative regulation of intrinsic apoptotic signaling pathway

Inferred from mutant phenotype Ref.5. Source: UniProtKB

negative regulation of oxidative phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of oxidative phosphorylation uncoupler activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of release of cytochrome c from mitochondria

Inferred from direct assay Ref.5. Source: UniProtKB

positive regulation of necrotic cell death

Inferred from mutant phenotype. Source: UniProtKB

positive regulation of release of cytochrome c from mitochondria

Inferred from sequence or structural similarity. Source: UniProtKB

protein folding

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of mitochondrial membrane permeability

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of proton-transporting ATPase activity, rotational mechanism

Inferred from sequence or structural similarity. Source: UniProtKB

response to ischemia

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentmembrane

Traceable author statement Ref.1. Source: ProtInc

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncyclosporin A binding

Inferred from electronic annotation. Source: Ensembl

peptidyl-prolyl cis-trans isomerase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TP53P046374EBI-5544229,EBI-366083

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2929Mitochondrion Potential
Chain30 – 207178Peptidyl-prolyl cis-trans isomerase F, mitochondrial
PRO_0000025489

Regions

Domain49 – 205157PPIase cyclophilin-type

Amino acid modifications

Modified residue671N6-acetyllysine; alternate By similarity
Modified residue671N6-succinyllysine; alternate By similarity
Modified residue861N6-succinyllysine By similarity
Modified residue1671N6-acetyllysine By similarity
Modified residue1751N6-succinyllysine By similarity
Modified residue1901N6-succinyllysine By similarity
Modified residue2031S-nitrosocysteine By similarity

Experimental info

Mutagenesis2031C → S: Blocks Ca(2+)-induced mPTP opening and reduces hydrogen peroxide-induced cell death. Ref.8

Secondary structure

.................................... 207
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P30405 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: D7C76F1D4049F16A

FASTA20722,040
        10         20         30         40         50         60 
MLALRCGSRW LGLLSVPRSV PLRLPAARAC SKGSGDPSSS SSSGNPLVYL DVDANGKPLG 

        70         80         90        100        110        120 
RVVLELKADV VPKTAENFRA LCTGEKGFGY KGSTFHRVIP SFMCQAGDFT NHNGTGGKSI 

       130        140        150        160        170        180 
YGSRFPDENF TLKHVGPGVL SMANAGPNTN GSQFFICTIK TDWLDGKHVV FGHVKEGMDV 

       190        200 
VKKIESFGSK SGRTSKKIVI TDCGQLS 

« Hide

References

« Hide 'large scale' references
[1]"The cyclophilin multigene family of peptidyl-prolyl isomerases. Characterization of three separate human isoforms."
Bergsma D.J., Eder C., Gross M., Kersten H., Sylvester D., Appelbaum E., Cusimano D., Livi G.P., McLauglin M.M., Kasyan K., Porter T.G., Silverman C., Dunnington D., Hand A., Prichett W.P., Bossard M.J., Brandt M., Levy M.A.
J. Biol. Chem. 266:23204-23214(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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: Ovary.
[4]"Import and processing of heart mitochondrial cyclophilin D."
Johnson N., Khan A., Virji S., Ward J.M., Crompton M.
Eur. J. Biochem. 263:353-359(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[5]"Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect."
Eliseev R.A., Malecki J., Lester T., Zhang Y., Humphrey J., Gunter T.E.
J. Biol. Chem. 284:9692-9699(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BCL2.
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"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.
[8]"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: MUTAGENESIS OF CYS-203.
[9]"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.
[10]"Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A resolution."
Schlatter D., Thoma R., Kung E., Stihle M., Muller F., Borroni E., Cesura A., Hennig M.
Acta Crystallogr. D 61:513-519(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 43-207.
[11]"Crystal structure of human cyclophilin D in complex with its inhibitor, cyclosporin A at 0.96-A resolution."
Kajitani K., Fujihashi M., Kobayashi Y., Shimizu S., Tsujimoto Y., Miki K.
Proteins 70:1635-1639(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (0.96 ANGSTROMS) OF 44-207 IN COMPLEX WITH CYCLOSPORIN A.
[12]"In-plate protein crystallization, in situ ligand soaking and X-ray diffraction."
le Maire A., Gelin M., Pochet S., Hoh F., Pirocchi M., Guichou J.F., Ferrer J.L., Labesse G.
Acta Crystallogr. D 67:747-755(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 44-207.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M80254 mRNA. Translation: AAA58434.1.
AL133481, AL391665 Genomic DNA. Translation: CAH72725.1.
AL391665, AL133481 Genomic DNA. Translation: CAI40994.1.
BC005020 mRNA. Translation: AAH05020.1.
PIRA41581.
RefSeqNP_005720.1. NM_005729.3.
UniGeneHs.381072.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP30405.
SMRP30405. Positions 44-207.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115411. 24 interactions.
IntActP30405. 5 interactions.
MINTMINT-3011711.
STRING9606.ENSP00000225174.

Chemistry

DrugBankDB01093. Dimethyl sulfoxide.
DB00172. L-Proline.

PTM databases

PhosphoSiteP30405.

Polymorphism databases

DMDM231968.

2D gel databases

OGPP30405.
UCD-2DPAGEP30405.

Proteomic databases

PaxDbP30405.
PeptideAtlasP30405.
PRIDEP30405.

Protocols and materials databases

DNASU10105.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000225174; ENSP00000225174; ENSG00000108179.
GeneID10105.
KEGGhsa:10105.
UCSCuc001kai.3. human.

Organism-specific databases

CTD10105.
GeneCardsGC10P081107.
HGNCHGNC:9259. PPIF.
MIM604486. gene.
neXtProtNX_P30405.
PharmGKBPA33584.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0652.
HOGENOMHOG000065981.
HOVERGENHBG001065.
InParanoidP30405.
KOK09565.
OMAAFMCQAG.
OrthoDBEOG79GT7W.
PhylomeDBP30405.
TreeFamTF312801.

Gene expression databases

ArrayExpressP30405.
BgeeP30405.
CleanExHS_PPIF.
GenevestigatorP30405.

Family and domain databases

InterProIPR024936. Cyclophilin-type_PPIase.
IPR020892. Cyclophilin-type_PPIase_CS.
IPR002130. Cyclophilin-type_PPIase_dom.
[Graphical view]
PfamPF00160. Pro_isomerase. 1 hit.
[Graphical view]
PIRSFPIRSF001467. Peptidylpro_ismrse. 1 hit.
PRINTSPR00153. CSAPPISMRASE.
PROSITEPS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPIF. human.
EvolutionaryTraceP30405.
GeneWikiPPIF.
GenomeRNAi10105.
NextBio38221.
PROP30405.
SOURCESearch...

Entry information

Entry namePPIF_HUMAN
AccessionPrimary (citable) accession number: P30405
Secondary accession number(s): Q5W131
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: April 16, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM