UniProt Accession

 PPIF_HUMAN; P30405; Q5W131 

Genbank Protein ID

 M80254; AL133481; AL391665; AL391665; AL133481; BC005020 

Genbank Nucleotide ID

 AAA58434.1; CAH72725.1; CAH72725.1; CAI40994.1; CAI40994.1; AAH05020.1 

Protein Name

 Peptidyl-prolyl cis-trans isomerase F, mitochondrial 

Protein Synonyms/Alias

 PPIase F; Cyclophilin D; CyP-D; CypD; Cyclophilin F; Mitochondrial cyclophilin; CyP-M; Rotamase F 

Gene Name

 PPIF 

Gene Synonyms/Alias

 CYP3 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
57	LDVDANGKPLGRVVL	acetylation	[1]
73	LKADVVPKTAENFRA	ubiquitination	[2, 3]
167	KTDWLDGKHVVFGHV	acetylation	[1, 4]
190	KIESFGSKSGRTSKK	ubiquitination	[2, 3]

Reference

 [1] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 

Functional Description

 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 F(1)F(0) 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. 

Sequence Annotation

 DOMAIN 49 205 PPIase cyclophilin-type.
 MOD_RES 167 167 N6-acetyllysine (By similarity).
 MOD_RES 203 203 S-nitrosocysteine (By similarity).  

Keyword

 3D-structure; Acetylation; Apoptosis; Complete proteome; Cyclosporin; Isomerase; Mitochondrion; Necrosis; Reference proteome; Rotamase; S-nitrosylation; Transit peptide. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 207 AA 

Protein Sequence

Gene Ontology

 GO:0016020; C:membrane; TAS:ProtInc.
 GO:0005743; C:mitochondrial inner membrane; IEA:Compara.
 GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
 GO:0016018; F:cyclosporin A binding; IEA:Compara.
 GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IEA:UniProtKB-KW.
 GO:0008637; P:apoptotic mitochondrial changes; IEA:Compara.
 GO:0071243; P:cellular response to arsenic-containing substance; ISS:UniProtKB.
 GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
 GO:0070301; P:cellular response to hydrogen peroxide; IMP:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0032780; P:negative regulation of ATPase activity; ISS:UniProtKB.
 GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0090324; P:negative regulation of oxidative phosphorylation; ISS:UniProtKB.
 GO:2000276; P:negative regulation of oxidative phosphorylation uncoupler activity; ISS:UniProtKB.
 GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:UniProtKB.
 GO:0010940; P:positive regulation of necrotic cell death; IMP:UniProtKB.
 GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
 GO:0006457; P:protein folding; IEA:UniProtKB-KW.
 GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB.
 GO:0010849; P:regulation of proton-transporting ATPase activity, rotational mechanism; ISS:UniProtKB.
 GO:0002931; P:response to ischemia; ISS:UniProtKB. 

Interpro

 IPR002130; Cyclophilin-like_PPIase_dom.
 IPR024936; Cyclophilin-type_PPIase.
 IPR020892; Cyclophilin-type_PPIase_CS. 

Pfam

 PF00160; Pro_isomerase 

SMART

  

PROSITE

 PS00170; CSA_PPIASE_1
 PS50072; CSA_PPIASE_2 

PRINTS

 PR00153; CSAPPISMRASE.