T3DB: Apoptotic protease-activating factor 1

Name	Apoptotic protease-activating factor 1
Synonyms	APAF-1 KIAA0413
Gene Name	APAF1
Organism	Human
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 nucleotide binding ATP binding ADP binding cysteine-type endopeptidase activator activity involved in apoptotic process Processes intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress cellular response to transforming growth factor beta stimulus neural tube closure apoptotic process positive regulation of apoptotic signaling pathway response to hypoxia protein homooligomerization nervous system development regulation of apoptotic DNA fragmentation neuron apoptotic process response to G1 DNA damage checkpoint signaling response to nutrient aging programmed cell death activation of cysteine-type endopeptidase activity involved in apoptotic process regulation of apoptotic process activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c cardiac muscle cell apoptotic process forebrain development glial cell apoptotic process cell differentiation intrinsic apoptotic signaling pathway positive regulation of apoptotic process Components apoptosome nucleus cytosol extracellular exosome
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	CARD (PF00619 ) NB-ARC (PF00931 ) WD40 (PF00400 )
Transmembrane Regions	Not Available
GenBank Protein ID	2330015
UniProtKB ID	O14727
UniProtKB Entry Name	APAF_HUMAN
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
GenBank Gene ID	AF013263
GeneCard ID	Not Available
GenAtlas ID	APAF1
HGNC ID	HGNC:576
Chromosome Location	12
Locus	12q23
References	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. 9267021 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. 10441496 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. 10364241 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. 10393175 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. 12804598 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. 9455477 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. 12168954 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. 15489334 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. 9651578 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. 11389439 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. 15262985 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. 17244527 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. 21371431 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. 10543941 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. 10578182