Peptidyl-prolyl cis-trans isomerase F, mitochondrial

Details

Name
Peptidyl-prolyl cis-trans isomerase F, mitochondrial
Synonyms
  • 5.2.1.8
  • Cyclophilin D
  • Cyclophilin F
  • CyP-D
  • CyP-M
  • CYP3
  • CypD
  • Mitochondrial cyclophilin
  • PPIase F
  • Rotamase F
Gene Name
PPIF
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002777|Peptidyl-prolyl cis-trans isomerase F, mitochondrial
MLALRCGSRWLGLLSVPRSVPLRLPAARACSKGSGDPSSSSSSGNPLVYLDVDANGKPLG
RVVLELKADVVPKTAENFRALCTGEKGFGYKGSTFHRVIPSFMCQAGDFTNHNGTGGKSI
YGSRFPDENFTLKHVGPGVLSMANAGPNTNGSQFFICTIKTDWLDGKHVVFGHVKEGMDV
VKKIESFGSKSGRTSKKIVITDCGQLS
Number of residues
207
Molecular Weight
22040.09
Theoretical pI
9.95
GO Classification
Functions
cyclosporin A binding / peptidyl-prolyl cis-trans isomerase activity
Processes
apoptotic mitochondrial changes / cellular response to arsenic-containing substance / cellular response to calcium ion / cellular response to hydrogen peroxide / necroptotic process / negative regulation of apoptotic process / negative regulation of ATPase activity / negative regulation of intrinsic apoptotic signaling pathway / negative regulation of oxidative phosphorylation / negative regulation of oxidative phosphorylation uncoupler activity / negative regulation of release of cytochrome c from mitochondria / positive regulation of release of cytochrome c from mitochondria / protein folding / protein peptidyl-prolyl isomerization / regulation of mitochondrial membrane permeability / regulation of mitochondrial membrane permeability involved in programmed necrotic cell death / regulation of necrotic cell death / regulation of proton-transporting ATPase activity, rotational mechanism / response to ischemia
Components
membrane / mitochondrial inner membrane / mitochondrial matrix / mitochondrion
General Function
Peptidyl-prolyl cis-trans isomerase activity
Specific Function
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 probability 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion matrix
Gene sequence
>lcl|BSEQ0021846|Peptidyl-prolyl cis-trans isomerase F, mitochondrial (PPIF)
ATGCTGGCGCTGCGCTGCGGCTCCCGCTGGCTCGGCCTGCTCTCCGTCCCGCGCTCCGTG
CCGCTGCGCCTCCCCGCGGCCCGCGCCTGCAGCAAGGGCTCCGGCGACCCGTCCTCTTCC
TCCTCCTCCGGGAACCCGCTCGTGTACCTGGACGTGGACGCCAACGGGAAGCCGCTCGGC
CGCGTGGTGCTGGAGCTGAAGGCAGATGTCGTCCCAAAGACAGCTGAGAACTTCAGAGCC
CTGTGCACTGGTGAGAAGGGCTTCGGCTACAAAGGCTCCACCTTCCACAGGGTGATCCCT
TCCTTCATGTGCCAGGCGGGCGACTTCACCAACCACAATGGCACAGGCGGGAAGTCCATC
TACGGAAGCCGCTTTCCTGACGAGAACTTTACACTGAAGCACGTGGGGCCAGGTGTCCTG
TCCATGGCTAATGCTGGTCCTAACACCAACGGCTCCCAGTTCTTCATCTGCACCATAAAG
ACAGACTGGTTGGATGGCAAGCATGTTGTGTTCGGTCACGTCAAAGAGGGCATGGACGTC
GTGAAGAAAATAGAATCTTTCGGCTCTAAGAGTGGGAGGACATCCAAGAAGATTGTCATC
ACAGACTGTGGCCAGTTGAGCTAA
Chromosome Location
10
Locus
10q22-q23
External Identifiers
ResourceLink
UniProtKB IDP30405
UniProtKB Entry NamePPIF_HUMAN
GenBank Protein ID181274
GenBank Gene IDM80254
GenAtlas IDPPIF
HGNC IDHGNC:9259
General References
  1. Bergsma DJ, Eder C, Gross M, Kersten H, Sylvester D, Appelbaum E, Cusimano D, Livi GP, McLaughlin MM, Kasyan K, et al.: The cyclophilin multigene family of peptidyl-prolyl isomerases. Characterization of three separate human isoforms. J Biol Chem. 1991 Dec 5;266(34):23204-14. [Article]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Johnson N, Khan A, Virji S, Ward JM, Crompton M: Import and processing of heart mitochondrial cyclophilin D. Eur J Biochem. 1999 Jul;263(2):353-9. [Article]
  6. Eliseev RA, Malecki J, Lester T, Zhang Y, Humphrey J, Gunter TE: Cyclophilin D interacts with Bcl2 and exerts an anti-apoptotic effect. J Biol Chem. 2009 Apr 10;284(15):9692-9. doi: 10.1074/jbc.M808750200. Epub 2009 Feb 19. [Article]
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  8. McGee AM, Baines CP: Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death. Biochem J. 2011 Jan 1;433(1):119-25. doi: 10.1042/BJ20101431. [Article]
  9. Nguyen TT, Stevens MV, Kohr M, Steenbergen C, Sack MN, Murphy E: Cysteine 203 of cyclophilin D is critical for cyclophilin D activation of the mitochondrial permeability transition pore. J Biol Chem. 2011 Nov 18;286(46):40184-92. doi: 10.1074/jbc.M111.243469. Epub 2011 Sep 19. [Article]
  10. Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM: p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012 Jun 22;149(7):1536-48. doi: 10.1016/j.cell.2012.05.014. [Article]
  11. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  12. Schlatter D, Thoma R, Kung E, Stihle M, Muller F, Borroni E, Cesura A, Hennig M: Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2005 May;61(Pt 5):513-9. Epub 2005 Apr 20. [Article]
  13. Kajitani K, Fujihashi M, Kobayashi Y, Shimizu S, Tsujimoto Y, Miki K: Crystal structure of human cyclophilin D in complex with its inhibitor, cyclosporin A at 0.96-A resolution. Proteins. 2008 Mar;70(4):1635-9. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00172ProlinenutraceuticalunknownDetails
DB08168Coumarin 120experimentalunknownDetails
DB02078TriglymeexperimentalunknownDetails
DB00091Cyclosporineapproved, investigational, vet_approvedyesbinderDetails