UniProt functional annotation for P30405



	UniProt functional annotation for P30405

UniProt code: P30405.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Involved in regulation of the mitochondrial permeability transition pore (mPTP) (PubMed:26387735). 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 (PubMed:26387735). In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis (PubMed:22726440). Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels (By similarity). Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis (PubMed:19228691). {ECO:0000250|UniProtKB:Q99KR7, ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:26387735}.

Catalytic activity: Reaction=[protein]-peptidylproline (omega=180) = [protein]- peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269|PubMed:20676357};

Activity regulation: Inhibited by cyclosporin A (CsA) (PubMed:20676357). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP. {ECO:0000269|PubMed:20676357}.

Subunit: Associates with the mitochondrial membrane ATP synthase F(1)F(0) ATP synthase; the association is increased by inorganic phosphate (Pi) and decreased by cyclosporin A (CsA) (By similarity). Interacts with ATP5F1B; ATP5PD and ATP5PO (By similarity). Interacts with SLC25A3; the interaction is impaired by CsA (By similarity). Interacts with BCL2; the interaction is impaired by CsA (PubMed:19228691). Interacts with TP53; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by CsA (PubMed:22726440). Interacts with C1QBP (PubMed:20950273). Interacts with MCUR1 (PubMed:26976564). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735). Interacts with SPG7 (PubMed:26387735). {ECO:0000250|UniProtKB:P29117, ECO:0000250|UniProtKB:P30404, ECO:0000250|UniProtKB:Q99KR7, ECO:0000269|PubMed:19228691, ECO:0000269|PubMed:20950273, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:26387735, ECO:0000269|PubMed:26976564}.

Subcellular location: Mitochondrion matrix {ECO:0000269|PubMed:10406942}.

Ptm: Acetylated at Lys-167; deacetylated at Lys-167 by SIRT3. {ECO:0000250|UniProtKB:Q99KR7}.

Similarity: Belongs to the cyclophilin-type PPIase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (PubMed:20676357). Involved in regulation of the mitochondrial permeability transition pore (mPTP) (PubMed:26387735). 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 (PubMed:26387735). In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis (PubMed:22726440). Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels (By similarity). Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis (PubMed:19228691). {ECO:0000250\|UniProtKB:Q99KR7, ECO:0000269\|PubMed:19228691, ECO:0000269\|PubMed:20676357, ECO:0000269\|PubMed:22726440, ECO:0000269\|PubMed:26387735}.


Catalytic activity:		Reaction=[protein]-peptidylproline (omega=180) = [protein]- peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269\|PubMed:20676357};
Activity regulation:		Inhibited by cyclosporin A (CsA) (PubMed:20676357). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP. {ECO:0000269\|PubMed:20676357}.
Subunit:		Associates with the mitochondrial membrane ATP synthase F(1)F(0) ATP synthase; the association is increased by inorganic phosphate (Pi) and decreased by cyclosporin A (CsA) (By similarity). Interacts with ATP5F1B; ATP5PD and ATP5PO (By similarity). Interacts with SLC25A3; the interaction is impaired by CsA (By similarity). Interacts with BCL2; the interaction is impaired by CsA (PubMed:19228691). Interacts with TP53; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by CsA (PubMed:22726440). Interacts with C1QBP (PubMed:20950273). Interacts with MCUR1 (PubMed:26976564). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735). Interacts with SPG7 (PubMed:26387735). {ECO:0000250\|UniProtKB:P29117, ECO:0000250\|UniProtKB:P30404, ECO:0000250\|UniProtKB:Q99KR7, ECO:0000269\|PubMed:19228691, ECO:0000269\|PubMed:20950273, ECO:0000269\|PubMed:22726440, ECO:0000269\|PubMed:26387735, ECO:0000269\|PubMed:26976564}.
Subcellular location:		Mitochondrion matrix {ECO:0000269\|PubMed:10406942}.
Ptm:		Acetylated at Lys-167; deacetylated at Lys-167 by SIRT3. {ECO:0000250\|UniProtKB:Q99KR7}.
Similarity:		Belongs to the cyclophilin-type PPIase family. {ECO:0000305}.