Apoptotic protease-activating factor 1

Details

Name
Apoptotic protease-activating factor 1
Synonyms
  • APAF-1
  • KIAA0413
Gene Name
APAF1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000617|Apoptotic protease-activating factor 1
MDAKARNCLLQHREALEKDIKTSYIMDHMISDGFLTISEEEKVRNEPTQQQRAAMLIKMI
LKKDNDSYVSFYNALLHEGYKDLAALLHDGIPVVSSSSGKDSVSGITSYVRTVLCEGGVP
QRPVVFVTRKKLVNAIQQKLSKLKGEPGWVTIHGMAGCGKSVLAAEAVRDHSLLEGCFPG
GVHWVSVGKQDKSGLLMKLQNLCTRLDQDESFSQRLPLNIEEAKDRLRILMLRKHPRSLL
ILDDVWDSWVLKAFDSQCQILLTTRDKSVTDSVMGPKYVVPVESSLGKEKGLEILSLFVN
MKKADLPEQAHSIIKECKGSPLVVSLIGALLRDFPNRWEYYLKQLQNKQFKRIRKSSSYD
YEALDEAMSISVEMLREDIKDYYTDLSILQKDVKVPTKVLCILWDMETEEVEDILQEFVN
KSLLFCDRNGKSFRYYLHDLQVDFLTEKNCSQLQDLHKKIITQFQRYHQPHTLSPDQEDC
MYWYNFLAYHMASAKMHKELCALMFSLDWIKAKTELVGPAHLIHEFVEYRHILDEKDCAV
SENFQEFLSLNGHLLGRQPFPNIVQLGLCEPETSEVYQQAKLQAKQEVDNGMLYLEWINK
KNITNLSRLVVRPHTDAVYHACFSEDGQRIASCGADKTLQVFKAETGEKLLEIKAHEDEV
LCCAFSTDDRFIATCSVDKKVKIWNSMTGELVHTYDEHSEQVNCCHFTNSSHHLLLATGS
SDCFLKLWDLNQKECRNTMFGHTNSVNHCRFSPDDKLLASCSADGTLKLWDATSANERKS
INVKQFFLNLEDPQEDMEVIVKCCSWSADGARIMVAAKNKIFLFDIHTSGLLGEIHTGHH
STIQYCDFSPQNHLAVVALSQYCVELWNTDSRSKVADCRGHLSWVHGVMFSPDGSSFLTS
SDDQTIRLWETKKVCKNSAVMLKQEVDVVFQENEVMVLAVDHIRRLQLINGRTGQIDYLT
EAQVSCCCLSPHLQYIAFGDENGAIEILELVNNRIFQSRFQHKKTVWHIQFTADEKTLIS
SSDDAEIQVWNWQLDKCIFLRGHQETVKDFRLLKNSRLLSWSFDGTVKVWNIITGNKEKD
FVCHQGTVLSCDISHDATKFSSTSADKTAKIWSFDLLLPLHELRGHNGCVRCSAFSVDST
LLATGDDNGEIRIWNVSNGELLHLCAPLSEEGAATHGGWVTDLCFSPDGKMLISAGGYIK
WWNVVTGESSQTFYTNGTNLKKIHVSPDFKTYVTVDNLGILYILQTLE
Number of residues
1248
Molecular Weight
141838.815
Theoretical pI
6.37
GO Classification
Functions
ADP binding / ATP binding / cysteine-type endopeptidase activator activity involved in apoptotic process / nucleotide binding
Processes
activation of cysteine-type endopeptidase activity involved in apoptotic process / activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c / aging / apoptotic process / cardiac muscle cell apoptotic process / cell differentiation / cellular response to transforming growth factor beta stimulus / forebrain development / glial cell apoptotic process / intrinsic apoptotic signaling pathway / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / nervous system development / neural tube closure / neuron apoptotic process / positive regulation of apoptotic process / positive regulation of apoptotic signaling pathway / programmed cell death / protein homooligomerization / regulation of apoptotic DNA fragmentation / regulation of apoptotic process / response to G1 DNA damage checkpoint signaling / response to hypoxia / response to nutrient
Components
apoptosome / cytosol / extracellular exosome / nucleus
General Function
Nucleotide binding
Specific Function
Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010076|Apoptotic protease-activating factor 1 (APAF1)
ATGGATGCAAAAGCTCGAAATTGTTTGCTTCAACATAGAGAAGCTCTGGAAAAGGACATC
AAGACATCCTACATCATGGATCACATGATTAGTGATGGATTTTTAACAATATCAGAAGAG
GAAAAAGTAAGAAATGAGCCCACTCAACAGCAAAGAGCAGCTATGCTGATTAAAATGATA
CTTAAAAAAGATAATGATTCCTACGTATCATTCTACAATGCTCTACTACATGAAGGATAT
AAAGATCTTGCTGCCCTTCTCCATGATGGCATTCCTGTTGTCTCTTCTTCCAGTGTAAGG
ACAGTCCTGTGTGAAGGTGGAGTACCACAGAGGCCAGTTGTTTTTGTCACAAGGAAGAAG
CTGGTGAATGCAATTCAGCAGAAGCTCTCCAAATTGAAAGGTGAACCAGGATGGGTCACC
ATACATGGAATGGCAGGCTGTGGGAAGTCTGTATTAGCTGCAGAAGCTGTTAGAGATCAT
TCCCTTTTAGAAGGTTGTTTCCCAGGGGGAGTGCATTGGGTTTCAGTTGGGAAACAAGAC
AAATCTGGGCTTCTGATGAAACTGCAGAATCTTTGCACACGGTTGGATCAGGATGAGAGT
TTTTCCCAGAGGCTTCCACTTAATATTGAAGAGGCTAAAGACCGTCTCCGCATTCTGATG
CTTCGCAAACACCCAAGGTCTCTCTTGATCTTGGATGATGTTTGGGACTCTTGGGTGTTG
AAAGCTTTTGACAGTCAGTGTCAGATTCTTCTTACAACCAGAGACAAGAGTGTTACAGAT
TCAGTAATGGGTCCTAAATATGTAGTCCCTGTGGAGAGTTCCTTAGGAAAGGAAAAAGGA
CTTGAAATTTTATCCCTTTTTGTTAATATGAAGAAGGCAGATTTGCCAGAACAAGCTCAT
AGTATTATAAAAGAATGTAAAGGCTCTCCCCTTGTAGTATCTTTAATTGGTGCACTTTTA
CGTGATTTTCCCAATCGCTGGGAGTACTACCTCAAACAGCTTCAGAATAAGCAGTTTAAG
AGAATAAGGAAATCTTCGTCTTATGATTATGAGGCTCTAGATGAAGCCATGTCTATAAGT
GTTGAAATGCTCAGAGAAGACATCAAAGATTATTACACAGATCTTTCCATCCTTCAGAAG
GACGTTAAGGTGCCTACAAAGGTGTTATGTATTCTCTGGGACATGGAAACTGAAGAAGTT
GAAGACATACTGCAGGAGTTTGTAAATAAGTCTCTTTTATTCTGTGATCGGAATGGAAAG
TCGTTTCGTTATTATTTACATGATCTTCAAGTAGATTTTCTTACAGAGAAGAATTGCAGC
CAGCTTCAGGATCTACATAAGAAGATAATCACTCAGTTTCAGAGATATCACCAGCCGCAT
ACTCTTTCACCAGATCAGGAAGACTGTATGTATTGGTACAACTTTCTGGCCTATCACATG
GCCAGTGCCAAGATGCACAAGGAACTTTGTGCTTTAATGTTTTCCCTGGATTGGATTAAA
GCAAAAACAGAACTTGTAGGCCCTGCTCATCTGATTCATGAATTTGTGGAATACAGACAT
ATACTAGATGAAAAGGATTGTGCAGTCAGTGAGAATTTTCAGGAGTTTTTATCTTTAAAT
GGACACCTTCTTGGACGACAGCCATTTCCTAATATTGTACAACTGGGTCTCTGTGAGCCG
GAAACTTCAGAAGTTTATCAGCAAGCTAAGCTGCAGGCCAAGCAGGAGGTCGATAATGGA
ATGCTTTACCTGGAATGGATAAACAAAAAAAACATCACGAATCTTTCCCGCTTAGTTGTC
CGCCCCCACACAGATGCTGTTTACCATGCCTGCTTTTCTGAGGATGGTCAGAGAATAGCT
TCTTGTGGAGCTGATAAAACCTTACAGGTGTTCAAAGCTGAAACAGGAGAGAAACTTCTA
GAAATCAAGGCTCATGAGGATGAAGTGCTTTGTTGTGCATTCTCTACAGATGACAGATTT
ATAGCAACCTGCTCAGTGGATAAAAAAGTGAAGATTTGGAATTCTATGACTGGGGAACTA
GTACACACCTATGATGAGCACTCAGAGCAAGTCAATTGCTGCCATTTCACCAACAGTAGT
CATCATCTTCTCTTAGCCACTGGGTCAAGTGACTGCTTCCTCAAACTTTGGGATTTGAAT
CAAAAAGAATGTCGAAATACCATGTTTGGTCATACAAATTCAGTCAATCACTGCAGATTT
TCACCAGATGATAAGCTTTTGGCTAGTTGTTCAGCTGATGGAACCTTAAAGCTTTGGGAT
GCGACATCAGCAAATGAGAGGAAAAGCATTAATGTGAAACAGTTCTTCCTAAATTTGGAG
GACCCTCAAGAGGATATGGAAGTGATAGTGAAGTGTTGTTCGTGGTCTGCTGATGGTGCA
AGGATAATGGTGGCAGCAAAAAATAAAATCTTTTTGTGGAATACAGACTCACGTTCAAAG
GTGGCTGATTGCAGAGGACATTTAAGTTGGGTTCATGGTGTGATGTTTTCTCCTGATGGA
TCATCATTTTTGACATCTTCTGATGACCAGACAATCAGGCTCTGGGAGACAAAGAAAGTA
TGTAAGAACTCTGCTGTAATGTTAAAGCAAGAAGTAGATGTTGTGTTTCAAGAAAATGAA
GTGATGGTCCTTGCAGTTGACCATATAAGACGTCTGCAACTCATTAATGGAAGAACAGGT
CAGATTGATTATCTGACTGAAGCTCAAGTTAGCTGCTGTTGCTTAAGTCCACATCTTCAG
TACATTGCATTTGGAGATGAAAATGGAGCCATTGAGATTTTAGAACTTGTAAACAATAGA
ATCTTCCAGTCCAGGTTTCAGCACAAGAAAACTGTATGGCACATCCAGTTCACAGCCGAT
GAGAAGACTCTTATTTCAAGTTCTGATGATGCTGAAATTCAGGTATGGAATTGGCAATTG
GACAAATGTATCTTTCTACGAGGCCATCAGGAAACAGTGAAAGACTTTAGACTCTTGAAA
AATTCAAGACTGCTTTCTTGGTCATTTGATGGAACAGTGAAGGTATGGAATATTATTACT
GGAAATAAAGAAAAAGACTTTGTCTGTCACCAGGGTACAGTACTTTCTTGTGACATTTCT
CACGATGCTACCAAGTTTTCATCTACCTCTGCTGACAAGACTGCAAAGATCTGGAGTTTT
GATCTCCTTTTGCCACTTCATGAATTGAGGGGCCACAACGGCTGTGTGCGCTGCTCTGCC
TTCTCTGTGGACAGTACCCTGCTGGCAACGGGAGATGACAATGGAGAAATCAGGATATGG
AATGTCTCAAACGGTGAGCTTCTTCATTTGTGTGCTCCGCTTTCAGAAGAAGGAGCTGCT
ACCCATGGAGGCTGGGTGACTGACCTTTGCTTTTCTCCAGATGGCAAAATGCTTATCTCT
GCTGGAGGATATATTAAGTGGTGGAACGTTGTCACTGGGGAATCCTCACAGACCTTCTAC
ACAAATGGAACCAATCTTAAGAAAATACACGTGTCCCCTGACTTCAAAACATATGTGACT
GTGGATAATCTTGGTATTTTATATATTTTACAGACTTTAGAATAA
Chromosome Location
12
Locus
12q23
External Identifiers
ResourceLink
UniProtKB IDO14727
UniProtKB Entry NameAPAF_HUMAN
GenBank Protein ID2330015
GenBank Gene IDAF013263
GenAtlas IDAPAF1
HGNC IDHGNC:576
General References
  1. Zou H, Henzel WJ, Liu X, Lutschg A, Wang X: Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell. 1997 Aug 8;90(3):405-13. [PubMed:9267021]
  2. Hahn C, Hirsch B, Jahnke D, Durkop H, Stein H: Three new types of Apaf-1 in mammalian cells. Biochem Biophys Res Commun. 1999 Aug 11;261(3):746-9. [PubMed:10441496]
  3. Saleh A, Srinivasula SM, Acharya S, Fishel R, Alnemri ES: Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation. J Biol Chem. 1999 Jun 18;274(25):17941-5. [PubMed:10364241]
  4. Hu Y, Benedict MA, Ding L, Nunez G: Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis. EMBO J. 1999 Jul 1;18(13):3586-95. [PubMed:10393175]
  5. Ogawa T, Shiga K, Hashimoto S, Kobayashi T, Horii A, Furukawa T: APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially causes impeded ability of undergoing DNA damage-induced apoptosis in the LNCaP human prostate cancer cell line. Biochem Biophys Res Commun. 2003 Jun 27;306(2):537-43. [PubMed:12804598]
  6. Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1997 Oct 31;4(5):307-13. [PubMed:9455477]
  7. Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. DNA Res. 2002 Jun 30;9(3):99-106. [PubMed:12168954]
  8. 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. [PubMed:15489334]
  9. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES: Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. Mol Cell. 1998 Jun;1(7):949-57. [PubMed:9651578]
  10. Moroni MC, Hickman ES, Lazzerini Denchi E, Caprara G, Colli E, Cecconi F, Muller H, Helin K: Apaf-1 is a transcriptional target for E2F and p53. Nat Cell Biol. 2001 Jun;3(6):552-8. [PubMed:11389439]
  11. Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK: Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein. J Biol Chem. 2004 Sep 17;279(38):39942-50. Epub 2004 Jul 15. [PubMed:15262985]
  12. Bao Q, Lu W, Rabinowitz JD, Shi Y: Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1. Mol Cell. 2007 Jan 26;25(2):181-92. [PubMed:17244527]
  13. Karimpour S, Davoodi J, Ghahremani MH: Integrity of ATP binding site is essential for effective inhibition of the intrinsic apoptosis pathway by NAIP. Biochem Biophys Res Commun. 2011 Apr 1;407(1):158-62. doi: 10.1016/j.bbrc.2011.02.130. Epub 2011 Mar 1. [PubMed:21371431]
  14. Vaughn DE, Rodriguez J, Lazebnik Y, Joshua-Tor L: Crystal structure of Apaf-1 caspase recruitment domain: an alpha-helical Greek key fold for apoptotic signaling. J Mol Biol. 1999 Oct 29;293(3):439-47. [PubMed:10543941]
  15. Day CL, Dupont C, Lackmann M, Vaux DL, Hinds MG: Solution structure and mutagenesis of the caspase recruitment domain (CARD) from Apaf-1. Cell Death Differ. 1999 Nov;6(11):1125-32. [PubMed:10578182]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00171ATPinvestigational, nutraceuticalunknownDetails