PPIF_BOVIN
ID PPIF_BOVIN Reviewed; 208 AA.
AC P30404; Q6PMK8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 3.
DT 03-AUG-2022, entry version 145.
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; Synonyms=CYP3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang W., Xiao Y., Ren Z., Wang J., Wu Z., Cheng J., Wang Y.;
RT "Bos taurus peptidylprolyl isomerase F.";
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Colon;
RA Moore S., Alexander L., Brownstein M., Guan L., Lobo S., Meng Y.,
RA Tanaguchi M., Wang Z., Yu J., Prange C., Schreiber K., Shenmen C.,
RA Wagner L., Bala M., Barbazuk S., Barber S., Babakaiff R., Beland J.,
RA Chun E., Del Rio L., Gibson S., Hanson R., Kirkpatrick R., Liu J.,
RA Matsuo C., Mayo M., Santos R.R., Stott J., Tsai M., Wong D., Siddiqui A.,
RA Holt R., Jones S.J., Marra M.A.;
RT "Bovine genome sequencing program: Full-length cDNA sequencing.";
RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19390049; DOI=10.1126/science.1169588;
RG The bovine genome sequencing and analysis consortium;
RT "The genome sequence of taurine cattle: a window to ruminant biology and
RT evolution.";
RL Science 324:522-528(2009).
RN [4]
RP PRELIMINARY PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Heart;
RX PubMed=7679902; DOI=10.1006/bbrc.1993.1127;
RA Inoue T., Yoshida Y., Isaka Y., Tagawa K.;
RT "Isolation of mitochondrial cyclophilin from bovine heart.";
RL Biochem. Biophys. Res. Commun. 190:857-863(1993).
RN [5]
RP INTERACTION WITH ATP5F1B; ATP5PD AND ATP5PO.
RX PubMed=19801635; DOI=10.1074/jbc.m109.020115;
RA Giorgio V., Bisetto E., Soriano M.E., Dabbeni-Sala F., Basso E.,
RA Petronilli V., Forte M.A., Bernardi P., Lippe G.;
RT "Cyclophilin D modulates mitochondrial F0F1-ATP synthase by interacting
RT with the lateral stalk of the complex.";
RL J. Biol. Chem. 284:33982-33988(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. Involved in regulation of the mitochondrial permeability
CC transition pore (mPTP). It is proposed that its association with the
CC mPTP is masking a binding site for inhibiting inorganic phosphate (Pi)
CC and 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. In cooperation with mitochondrial p53/TP53 is involved in
CC activating oxidative stress-induced necrosis (By similarity). Involved
CC in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity
CC and regulation of mitochondrial matrix adenine nucleotide levels (By
CC similarity). Has anti-apoptotic activity independently of mPTP and in
CC cooperation with BCL2 inhibits cytochrome c-dependent apoptosis (By
CC similarity). {ECO:0000250|UniProtKB:P30405,
CC ECO:0000250|UniProtKB:Q99KR7}.
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 (By
CC similarity). {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 (PubMed:19801635). Interacts
CC with SLC25A3; the interaction is impaired by CsA (By similarity).
CC Interacts with BCL2; the interaction is impaired by CsA. Interacts with
CC TP53; the association implicates preferentially tetrameric TP53, is
CC induced by oxidative stress and is impaired by CsA. Interacts with
CC C1QBP. Interacts with MCUR1. Component of the mitochondrial
CC permeability transition pore complex (mPTPC), at least composed of
CC SPG7, VDAC1 and PPIF. Interacts with SPG7 (By similarity).
CC {ECO:0000250|UniProtKB:P29117, ECO:0000250|UniProtKB:P30405,
CC ECO:0000250|UniProtKB:Q99KR7, ECO:0000269|PubMed:19801635}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P29117}.
CC -!- PTM: Acetylated at Lys-168; deacetylated at Lys-168 by SIRT3.
CC {ECO:0000250|UniProtKB:Q99KR7}.
CC -!- SIMILARITY: Belongs to the cyclophilin-type PPIase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAT02663.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY594335; AAT02663.1; ALT_SEQ; mRNA.
DR EMBL; EH176460; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AAFC03123307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; PC1237; PC1237.
DR RefSeq; NP_001001597.1; NM_001001597.1.
DR AlphaFoldDB; P30404; -.
DR BMRB; P30404; -.
DR SMR; P30404; -.
DR STRING; 9913.ENSBTAP00000022213; -.
DR PaxDb; P30404; -.
DR PeptideAtlas; P30404; -.
DR PRIDE; P30404; -.
DR DNASU; 414346; -.
DR GeneID; 414346; -.
DR KEGG; bta:414346; -.
DR CTD; 10105; -.
DR eggNOG; KOG0865; Eukaryota.
DR HOGENOM; CLU_012062_4_3_1; -.
DR InParanoid; P30404; -.
DR OrthoDB; 1403619at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0016018; F:cyclosporin A binding; ISS:UniProtKB.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
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: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; ISS:UniProtKB.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB.
DR GO; GO:1902445; P:regulation of mitochondrial membrane permeability involved in programmed necrotic cell death; ISS:UniProtKB.
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 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 Acetylation; Apoptosis; Direct protein sequencing; Isomerase;
KW Mitochondrion; Necrosis; Reference proteome; Rotamase; S-nitrosylation;
KW Transit peptide.
FT TRANSIT 1..30
FT /note="Mitochondrion"
FT CHAIN 31..208
FT /note="Peptidyl-prolyl cis-trans isomerase F,
FT mitochondrial"
FT /id="PRO_0000064149"
FT DOMAIN 50..206
FT /note="PPIase cyclophilin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00156"
FT MOD_RES 68
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 68
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 87
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 168
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 176
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 191
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT MOD_RES 204
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q99KR7"
FT CONFLICT 30
FT /note="A -> V (in Ref. 1; AAT02663 and 2; EH176460)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 208 AA; 22019 MW; 087239A93D68A512 CRC64;
MMLALRCGPR LLGLLSGPRS AHLRLPAVRA CSSGSGSHGS SSSSGNPLVY LDVGADGQPL
GRVVLELKAD VVPKTAENFR ALCTGEKGFG YKGSTFHRVI PSFMCQAGDF TNHNGTGGKS
IYGSRFPDEN FKLKHEGPGV LSMANAGPNT NGSQFFICTI KTDWLDGKHV VFGHVKEGMD
VVKKIESFGS KSGKTSKKIV ITDCGQLS
