CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-019911
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Peptidyl-prolyl cis-trans isomerase F, mitochondrial 
Protein Synonyms/Alias
 PPIase F; Cyclophilin D; CyP-D; CypD; Cyclophilin F; Rotamase F 
Gene Name
 Ppif 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
66GRVVLELKADVVPKTacetylation[1, 2, 3, 4, 5]
66GRVVLELKADVVPKTsuccinylation[5]
85RALCTGEKGFGYKGSacetylation[4, 5, 6, 7, 8]
85RALCTGEKGFGYKGSsuccinylation[5]
166KTDWLDGKHVVFGHVacetylation[4, 5, 7, 8, 9]
166KTDWLDGKHVVFGHVsuccinylation[5]
174HVVFGHVKEGMDVVKacetylation[4, 5]
174HVVFGHVKEGMDVVKsuccinylation[5]
181KEGMDVVKKIESFGSacetylation[4, 7, 8]
182EGMDVVKKIESFGSKacetylation[4, 5]
182EGMDVVKKIESFGSKsuccinylation[5]
189KIESFGSKSGKTSKKacetylation[5]
189KIESFGSKSGKTSKKsuccinylation[5]
189KIESFGSKSGKTSKKsuccinylation[5]
Reference
 [1] The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching.
 Yang L, Vaitheesvaran B, Hartil K, Robinson AJ, Hoopmann MR, Eng JK, Kurland IJ, Bruce JE.
 J Proteome Res. 2011 Sep 2;10(9):4134-49. [PMID: 21728379]
 [2] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
 Simon GM, Cheng J, Gordon JI.
 Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
 [3] 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]
 [4] Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways.
 Rardin MJ, Newman JC, Held JM, Cusack MP, Sorensen DJ, Li B, Schilling B, Mooney SD, Kahn CR, Verdin E, Gibson BW.
 Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6601-6. [PMID: 23576753]
 [5] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [6] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [7] Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.
 Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ.
 Mol Cell. 2013 Jan 10;49(1):186-99. [PMID: 23201123]
 [8] Quantification of mitochondrial acetylation dynamics highlights prominent sites of metabolic regulation.
 Still AJ, Floyd BJ, Hebert AS, Bingman CA, Carson JJ, Gunderson DR, Dolan BK, Grimsrud PA, Dittenhafer-Reed KE, Stapleton DS, Keller MP, Westphall MS, Denu JM, Attie AD, Coon JJ, Pagliarini DJ.
 J Biol Chem. 2013 Jul 17;. [PMID: 23864654]
 [9] Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy.
 Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A, Sinclair DA.
 Aging (Albany NY). 2010 Dec;2(12):914-23. [PMID: 21212461] 
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 48 204 PPIase cyclophilin-type.
 MOD_RES 166 166 N6-acetyllysine.
 MOD_RES 202 202 S-nitrosocysteine.  
Keyword
 Acetylation; Apoptosis; Complete proteome; Cyclosporin; Isomerase; Mitochondrion; Necrosis; Reference proteome; Rotamase; S-nitrosylation; Transit peptide. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 206 AA 
Protein Sequence
MLALRCGPRL LGLLSGPRSA PLLLSATRTC SDGGARGANS SSGNPLVYLD VGADGQPLGR 60
VVLELKADVV PKTAENFRAL CTGEKGFGYK GSTFHRVIPA FMCQAGDFTN HNGTGGRSIY 120
GSRFPDENFT LKHVGPGVLS MANAGPNTNG SQFFICTIKT DWLDGKHVVF GHVKEGMDVV 180
KKIESFGSKS GKTSKKIVIT DCGQLS 206 
Gene Ontology
 GO:0005743; C:mitochondrial inner membrane; IEA:Compara.
 GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; IDA:MGI.
 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; IGI:MGI.
 GO:0071243; P:cellular response to arsenic-containing substance; IMP:UniProtKB.
 GO:0071277; P:cellular response to calcium ion; IMP:UniProtKB.
 GO:0070301; P:cellular response to hydrogen peroxide; IMP:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
 GO:0032780; P:negative regulation of ATPase activity; IMP:UniProtKB.
 GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
 GO:0090324; P:negative regulation of oxidative phosphorylation; IMP:UniProtKB.
 GO:2000276; P:negative regulation of oxidative phosphorylation uncoupler activity; IMP:UniProtKB.
 GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
 GO:0010940; P:positive regulation of necrotic cell death; IMP:UniProtKB.
 GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IMP:UniProtKB.
 GO:0006457; P:protein folding; IEA:UniProtKB-KW.
 GO:0046902; P:regulation of mitochondrial membrane permeability; IMP:UniProtKB.
 GO:0010849; P:regulation of proton-transporting ATPase activity, rotational mechanism; IMP:UniProtKB.
 GO:0002931; P:response to ischemia; IMP: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.