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Protein

Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Gene

Ppif

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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.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: RGD
  • peptide binding Source: RGD
  • peptidyl-prolyl cis-trans isomerase activity Source: RGD

GO - Biological processi

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 16

Organism-specific databases

RGDi628670. Ppif.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial inner membrane Source: RGD
  • mitochondrial matrix Source: RGD
  • mitochondrion Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 29Mitochondrion1 PublicationAdd BLAST29
ChainiPRO_000002549130 – 206Peptidyl-prolyl cis-trans isomerase F, mitochondrialAdd BLAST177

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei66N6-acetyllysine; alternateBy similarity1
Modified residuei66N6-succinyllysine; alternateBy similarity1
Modified residuei85N6-succinyllysineBy similarity1
Modified residuei166N6-acetyllysineBy similarity1
Modified residuei174N6-succinyllysineBy similarity1
Modified residuei189N6-succinyllysineBy similarity1
Modified residuei202S-nitrosocysteineBy similarity1

Post-translational modificationi

Deacteylated at Lys-166 by SIRT3 (By similarity). Interacts with BCL2; the interaction is impaired by CsA.By similarity

Keywords - PTMi

Acetylation, S-nitrosylation

Proteomic databases

PaxDbiP29117.
PRIDEiP29117.

PTM databases

iPTMnetiP29117.
PhosphoSitePlusiP29117.

Expressioni

Gene expression databases

BgeeiENSRNOG00000010558.
GenevisibleiP29117. RN.

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. Interacts with MCUR1 (By similarity).By similarity3 Publications

Protein-protein interaction databases

IntActiP29117. 5 interactors.
MINTiMINT-1542363.
STRINGi10116.ENSRNOP00000014382.

Structurei

Secondary structure

1206
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi46 – 53Combined sources8
Beta strandi56 – 65Combined sources10
Turni67 – 69Combined sources3
Helixi71 – 82Combined sources12
Turni83 – 85Combined sources3
Beta strandi96 – 98Combined sources3
Turni99 – 101Combined sources3
Beta strandi102 – 105Combined sources4
Beta strandi109 – 114Combined sources6
Beta strandi119 – 122Combined sources4
Beta strandi138 – 141Combined sources4
Beta strandi143 – 145Combined sources3
Beta strandi153 – 158Combined sources6
Helixi161 – 163Combined sources3
Turni164 – 166Combined sources3
Beta strandi169 – 175Combined sources7
Helixi177 – 185Combined sources9
Beta strandi197 – 206Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4TOTX-ray2.39A/B/C/D43-206[»]
ProteinModelPortaliP29117.
SMRiP29117.
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
Contains 1 PPIase cyclophilin-type domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0865. Eukaryota.
COG0652. LUCA.
GeneTreeiENSGT00760000119119.
HOGENOMiHOG000065981.
HOVERGENiHBG001065.
InParanoidiP29117.
KOiK09565.
OMAiVIPAFMC.
OrthoDBiEOG091G0BGL.
PhylomeDBiP29117.
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]
PANTHERiPTHR11071. PTHR11071. 1 hit.
PfamiPF00160. Pro_isomerase. 1 hit.
[Graphical view]
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.

P29117-1 [UniParc]FASTAAdd to basket

« Hide

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

DCGQLS
Length:206
Mass (Da):21,810
Last modified:November 1, 1997 - v2
Checksum:i69048482631B9FAD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti30C → A AA sequence (PubMed:1599421).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti30 – 39Missing in a minor form. 10
Natural varianti31S → R.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68544 mRNA. Translation: AAB08453.1.
BC086977 mRNA. Translation: AAH86977.1.
PIRiS23122.
RefSeqiNP_758443.1. NM_172243.1.
UniGeneiRn.2923.

Genome annotation databases

EnsembliENSRNOT00000014382; ENSRNOP00000014382; ENSRNOG00000010558.
GeneIDi282819.
KEGGirno:282819.
UCSCiRGD:628670. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U68544 mRNA. Translation: AAB08453.1.
BC086977 mRNA. Translation: AAH86977.1.
PIRiS23122.
RefSeqiNP_758443.1. NM_172243.1.
UniGeneiRn.2923.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4TOTX-ray2.39A/B/C/D43-206[»]
ProteinModelPortaliP29117.
SMRiP29117.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP29117. 5 interactors.
MINTiMINT-1542363.
STRINGi10116.ENSRNOP00000014382.

PTM databases

iPTMnetiP29117.
PhosphoSitePlusiP29117.

Proteomic databases

PaxDbiP29117.
PRIDEiP29117.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000014382; ENSRNOP00000014382; ENSRNOG00000010558.
GeneIDi282819.
KEGGirno:282819.
UCSCiRGD:628670. rat.

Organism-specific databases

CTDi10105.
RGDi628670. Ppif.

Phylogenomic databases

eggNOGiKOG0865. Eukaryota.
COG0652. LUCA.
GeneTreeiENSGT00760000119119.
HOGENOMiHOG000065981.
HOVERGENiHBG001065.
InParanoidiP29117.
KOiK09565.
OMAiVIPAFMC.
OrthoDBiEOG091G0BGL.
PhylomeDBiP29117.
TreeFamiTF312801.

Miscellaneous databases

PROiP29117.

Gene expression databases

BgeeiENSRNOG00000010558.
GenevisibleiP29117. RN.

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]
PANTHERiPTHR11071. PTHR11071. 1 hit.
PfamiPF00160. Pro_isomerase. 1 hit.
[Graphical view]
PRINTSiPR00153. CSAPPISMRASE.
SUPFAMiSSF50891. SSF50891. 1 hit.
PROSITEiPS00170. CSA_PPIASE_1. 1 hit.
PS50072. CSA_PPIASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPPIF_RAT
AccessioniPrimary (citable) accession number: P29117
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The polyclonal antibody used in PubMed:9820802 and PubMed:9874241 and initially thought to detect SLC25A4/ANT1 in interactions with Ppif/CyP-D is rather detecting SLC25A3.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.