PPIF_RAT
ID PPIF_RAT Reviewed; 206 AA.
AC P29117;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase F, mitochondrial;
DE Short=PPIase F;
DE EC=5.2.1.8 {ECO:0000250|UniProtKB:P30405};
DE AltName: Full=Cyclophilin D;
DE Short=CyP-D;
DE Short=CypD;
DE AltName: Full=Cyclophilin F;
DE AltName: Full=Rotamase F;
DE Flags: Precursor;
GN Name=Ppif;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Skeletal muscle;
RA Price N.T., Woodfield K.Y., Halestrap A.P.;
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 30-58.
RC TISSUE=Liver;
RX PubMed=1599421; DOI=10.1042/bj2840381;
RA Connern C.P., Halestrap A.P.;
RT "Purification and N-terminal sequencing of peptidyl-prolyl cis-trans-
RT isomerase from rat liver mitochondrial matrix reveals the existence of a
RT distinct mitochondrial cyclophilin.";
RL Biochem. J. 284:381-385(1992).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8567677; DOI=10.1074/jbc.271.4.2185;
RA Nicolli A., Basso E., Petronilli V., Wenger R.M., Bernardi P.;
RT "Interactions of cyclophilin with the mitochondrial inner membrane and
RT regulation of the permeability transition pore, and cyclosporin A-sensitive
RT channel.";
RL J. Biol. Chem. 271:2185-2192(1996).
RN [5]
RP FUNCTION.
RX PubMed=9309684; DOI=10.1023/a:1006887921810;
RA Scorrano L., Nicolli A., Basso E., Petronilli V., Bernardi P.;
RT "Two modes of activation of the permeability transition pore: the role of
RT mitochondrial cyclophilin.";
RL Mol. Cell. Biochem. 174:181-184(1997).
RN [6]
RP FUNCTION.
RX PubMed=9820802; DOI=10.1042/bj3360287;
RA Woodfield K., Ruck A., Brdiczka D., Halestrap A.P.;
RT "Direct demonstration of a specific interaction between cyclophilin-D and
RT the adenine nucleotide translocase confirms their role in the mitochondrial
RT permeability transition.";
RL Biochem. J. 336:287-290(1998).
RN [7]
RP INTERACTION WITH VDAC1.
RX PubMed=9874241; DOI=10.1046/j.1432-1327.1998.2580729.x;
RA Crompton M., Virji S., Ward J.M.;
RT "Cyclophilin-D binds strongly to complexes of the voltage-dependent anion
RT channel and the adenine nucleotide translocase to form the permeability
RT transition pore.";
RL Eur. J. Biochem. 258:729-735(1998).
RN [8]
RP INTERACTION WITH SLC25A3.
RX PubMed=18667415; DOI=10.1074/jbc.m805235200;
RA Leung A.W., Varanyuwatana P., Halestrap A.P.;
RT "The mitochondrial phosphate carrier interacts with cyclophilin D and may
RT play a key role in the permeability transition.";
RL J. Biol. Chem. 283:26312-26323(2008).
RN [9]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH BCL2.
RX PubMed=19228691; DOI=10.1074/jbc.m808750200;
RA Eliseev R.A., Malecki J., Lester T., Zhang Y., Humphrey J., Gunter T.E.;
RT "Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect.";
RL J. Biol. Chem. 284:9692-9699(2009).
CC -!- FUNCTION: PPIase that catalyzes the cis-trans isomerization of proline
CC imidic peptide bonds in oligopeptides and may therefore assist protein
CC folding (By similarity). Involved in regulation of the mitochondrial
CC permeability transition pore (mPTP) (PubMed:8567677, PubMed:9309684,
CC PubMed:9820802). It is proposed that its association with the mPTP is
CC masking a binding site for inhibiting inorganic phosphate (Pi) and
CC promotes the open probability of the mPTP leading to apoptosis or
CC necrosis; the requirement of the PPIase activity for this function is
CC debated (PubMed:8567677, PubMed:9309684, PubMed:9820802). In
CC cooperation with mitochondrial p53/TP53 is involved in activating
CC oxidative stress-induced necrosis (PubMed:8567677, PubMed:9309684,
CC PubMed:9820802). Involved in modulation of mitochondrial membrane
CC F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix
CC adenine nucleotide levels (PubMed:8567677, PubMed:9309684,
CC PubMed:9820802). Has anti-apoptotic activity independently of mPTP and
CC in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis
CC (PubMed:19228691). {ECO:0000250|UniProtKB:P30405,
CC ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:8567677,
CC ECO:0000269|PubMed:9309684, ECO:0000269|PubMed:9820802}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-peptidylproline (omega=180) = [protein]-
CC peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA-
CC COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833,
CC ChEBI:CHEBI:83834; EC=5.2.1.8;
CC Evidence={ECO:0000250|UniProtKB:P30405};
CC -!- ACTIVITY REGULATION: Binds cyclosporin A (CsA). Is displaced by CsA
CC from the mPTP leading to a lower open probability of the mPTP.
CC {ECO:0000250|UniProtKB:P30405}.
CC -!- SUBUNIT: Associates with the mitochondrial membrane ATP synthase
CC F(1)F(0) ATP synthase; the association is increased by inorganic
CC phosphate (Pi) and decreased by cyclosporin A (CsA) (By similarity).
CC Interacts with ATP5F1B; ATP5PD and ATP5PO (By similarity). Interacts
CC with SLC25A3; the interaction is impaired by CsA (PubMed:18667415).
CC Interacts with BCL2; the interaction is impaired by CsA
CC (PubMed:19228691). Interacts with TP53; the association implicates
CC preferentially tetrameric TP53, is induced by oxidative stress and is
CC impaired by CsA (By similarity). Interacts with C1QBP (By similarity).
CC Interacts with MCUR1 (By similarity). Component of the mitochondrial
CC permeability transition pore complex (mPTPC), at least composed of
CC SPG7, VDAC1 and PPIF (PubMed:9874241). Interacts with SPG7 (By
CC similarity). {ECO:0000250|UniProtKB:P30405,
CC ECO:0000250|UniProtKB:Q99KR7, ECO:0000269|PubMed:18667415,
CC ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:9874241}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:8567677}.
CC -!- PTM: Acetylated at Lys-166; deacetylated at Lys-166 by SIRT3.
CC {ECO:0000250|UniProtKB:Q99KR7}.
CC -!- SIMILARITY: Belongs to the cyclophilin-type PPIase family.
CC {ECO:0000305}.
CC -!- CAUTION: The polyclonal antibody used in PubMed:9820802 and
CC PubMed:9874241 and initially thought to detect SLC25A4/ANT1 in
CC interactions with Ppif/CyP-D is rather detecting SLC25A3.
CC {ECO:0000305|PubMed:18667415}.
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DR EMBL; U68544; AAB08453.1; -; mRNA.
DR EMBL; BC086977; AAH86977.1; -; mRNA.
DR PIR; S23122; S23122.
DR RefSeq; NP_758443.1; NM_172243.1.
DR PDB; 4TOT; X-ray; 2.39 A; A/B/C/D=43-206.
DR PDBsum; 4TOT; -.
DR AlphaFoldDB; P29117; -.
DR BMRB; P29117; -.
DR SMR; P29117; -.
DR BioGRID; 251857; 2.
DR IntAct; P29117; 5.
DR MINT; P29117; -.
DR STRING; 10116.ENSRNOP00000014382; -.
DR iPTMnet; P29117; -.
DR PhosphoSitePlus; P29117; -.
DR jPOST; P29117; -.
DR PaxDb; P29117; -.
DR PRIDE; P29117; -.
DR Ensembl; ENSRNOT00000106999; ENSRNOP00000085863; ENSRNOG00000010558.
DR GeneID; 282819; -.
DR KEGG; rno:282819; -.
DR UCSC; RGD:628670; rat.
DR CTD; 10105; -.
DR RGD; 628670; Ppif.
DR eggNOG; KOG0865; Eukaryota.
DR GeneTree; ENSGT00940000156008; -.
DR HOGENOM; CLU_012062_4_3_1; -.
DR InParanoid; P29117; -.
DR OMA; CKGTVVN; -.
DR OrthoDB; 1403619at2759; -.
DR PhylomeDB; P29117; -.
DR TreeFam; TF312801; -.
DR PRO; PR:P29117; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000010558; Expressed in heart and 20 other tissues.
DR Genevisible; P29117; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:RGD.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:RGD.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0016018; F:cyclosporin A binding; IDA:RGD.
DR GO; GO:0042277; F:peptide binding; IDA:RGD.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:RGD.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; ISO:RGD.
DR GO; GO:0071243; P:cellular response to arsenic-containing substance; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISS:UniProtKB.
DR GO; GO:1902686; P:mitochondrial outer membrane permeabilization involved in programmed cell death; ISS:UniProtKB.
DR GO; GO:0070266; P:necroptotic process; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0032780; P:negative regulation of ATP-dependent activity; ISS:UniProtKB.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0090324; P:negative regulation of oxidative phosphorylation; ISS:UniProtKB.
DR GO; GO:2000276; P:negative regulation of oxidative phosphorylation uncoupler activity; ISS:UniProtKB.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:RGD.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IDA:RGD.
DR GO; GO:1902445; P:regulation of mitochondrial membrane permeability involved in programmed necrotic cell death; ISS:UniProtKB.
DR GO; GO:0010939; P:regulation of necrotic cell death; ISO:RGD.
DR GO; GO:0010849; P:regulation of proton-transporting ATPase activity, rotational mechanism; ISS:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
DR Gene3D; 2.40.100.10; -; 1.
DR InterPro; IPR029000; Cyclophilin-like_dom_sf.
DR InterPro; IPR020892; Cyclophilin-type_PPIase_CS.
DR InterPro; IPR002130; Cyclophilin-type_PPIase_dom.
DR Pfam; PF00160; Pro_isomerase; 1.
DR PRINTS; PR00153; CSAPPISMRASE.
DR SUPFAM; SSF50891; SSF50891; 1.
DR PROSITE; PS00170; CSA_PPIASE_1; 1.
DR PROSITE; PS50072; CSA_PPIASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Direct protein sequencing; Isomerase;
KW Mitochondrion; Necrosis; Reference proteome; Rotamase; S-nitrosylation;
KW Transit peptide.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1599421"
FT CHAIN 30..206
FT /note="Peptidyl-prolyl cis-trans isomerase F,
FT mitochondrial"
FT /id="PRO_0000025491"
FT DOMAIN 48..204
FT /note="PPIase cyclophilin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00156"
FT MOD_RES 66
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 66
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 85
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 166
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 174
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 189
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 202
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT VARIANT 30..39
FT /note="Missing (in a minor form)"
FT VARIANT 31
FT /note="S -> R"
FT CONFLICT 30
FT /note="C -> A (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 56..65
FT /evidence="ECO:0007829|PDB:4TOT"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:4TOT"
FT HELIX 71..82
FT /evidence="ECO:0007829|PDB:4TOT"
FT TURN 83..85
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:4TOT"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 138..141
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:4TOT"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:4TOT"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 169..175
FT /evidence="ECO:0007829|PDB:4TOT"
FT HELIX 177..185
FT /evidence="ECO:0007829|PDB:4TOT"
FT STRAND 197..206
FT /evidence="ECO:0007829|PDB:4TOT"
SQ SEQUENCE 206 AA; 21810 MW; 69048482631B9FAD CRC64;
MLALRCGPRL LGLLSGPRSA PLLLSTTRTC SDGGARGANS SSQNPLVYLD VGADGQPLGR
VVLELKADVV PKTAENFRAL CTGEKGFGYK GSTFHRVIPA FMCQAGDFTN HNGTGGKSIY
GSRFPDENFT LKHVGPGVLS MANAGPNTNG SQFFICTIKT DWLDGKHVVF GHVKEGMDVV
KKIESFGSKS GKTSKKIVIT DCGQLS
