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Identification
HMDB Protein ID HMDBP02284
Secondary Accession Numbers
  • 7769
Name Apoptotic protease-activating factor 1
Synonyms
  1. APAF-1
Gene Name APAF1
Protein Type Enzyme
Biological Properties
General Function Involved in protein 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular
Function
binding
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein binding
Process
defense response
response to stimulus
response to stress
cellular process
biological regulation
regulation of biological process
programmed cell death
apoptosis
regulation of cell death
regulation of programmed cell death
regulation of apoptosis
regulation of cellular process
cell death
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location Chromosome:1
Locus 12q23
SNPs APAF1
Gene Sequence
>3747 bp
ATGGATGCAAAAGCTCGAAATTGTTTGCTTCAACATAGAGAAGCTCTGGAAAAGGACATC
AAGACATCCTACATCATGGATCACATGATTAGTGATGGATTTTTAACAATATCAGAAGAG
GAAAAAGTAAGAAATGAGCCCACTCAACAGCAAAGAGCAGCTATGCTGATTAAAATGATA
CTTAAAAAAGATAATGATTCCTACGTATCATTCTACAATGCTCTACTACATGAAGGATAT
AAAGATCTTGCTGCCCTTCTCCATGATGGCATTCCTGTTGTCTCTTCTTCCAGTGGTAAA
GATTCAGTTAGTGGAATAACTTCGTATGTAAGGACAGTCCTGTGTGAAGGTGGAGTACCA
CAGAGGCCAGTTGTTTTTGTCACAAGGAAGAAGCTGGTGAATGCAATTCAGCAGAAGCTC
TCCAAATTGAAAGGTGAACCAGGATGGGTCACCATACATGGAATGGCAGGCTGTGGGAAG
TCTGTATTAGCTGCAGAAGCTGTTAGAGATCATTCCCTTTTAGAAGGTTGTTTCCCAGGG
GGAGTGCATTGGGTTTCAGTTGGGAAACAAGACAAATCTGGGCTTCTGATGAAACTGCAG
AATCTTTGCACACGGTTGGATCAGGATGAGAGTTTTTCCCAGAGGCTTCCACTTAATATT
GAAGAGGCTAAAGACCGTCTCCGCATTCTGATGCTTCGCAAACACCCAAGGTCTCTCTTG
ATCTTGGATGATGTTTGGGACTCTTGGGTGTTGAAAGCTTTTGACAGTCAGTGTCAGATT
CTTCTTACAACCAGAGACAAGAGTGTTACAGATTCAGTAATGGGTCCTAAATATGTAGTC
CCTGTGGAGAGTTCCTTAGGAAAGGAAAAAGGACTTGAAATTTTATCCCTTTTTGTTAAT
ATGAAGAAGGCAGATTTGCCAGAACAAGCTCATAGTATTATAAAAGAATGTAAAGGCTCT
CCCCTTGTAGTATCTTTAATTGGTGCACTTTTACGTGATTTTCCCAATCGCTGGGAGTAC
TACCTCAAACAGCTTCAGAATAAGCAGTTTAAGAGAATAAGGAAATCTTCGTCTTATGAT
TATGAGGCTCTAGATGAAGCCATGTCTATAAGTGTTGAAATGCTCAGAGAAGACATCAAA
GATTATTACACAGATCTTTCCATCCTTCAGAAGGACGTTAAGGTGCCTACAAAGGTGTTA
TGTATTCTCTGGGACATGGAAACTGAAGAAGTTGAAGACATACTGCAGGAGTTTGTAAAT
AAGTCTCTTTTATTCTGTGATCGGAATGGAAAGTCGTTTCGTTATTATTTACATGATCTT
CAAGTAGATTTTCTTACAGAGAAGAATTGCAGCCAGCTTCAGGATCTACATAAGAAGATA
ATCACTCAGTTTCAGAGATATCACCAGCCGCATACTCTTTCACCAGATCAGGAAGACTGT
ATGTATTGGTACAACTTTCTGGCCTATCACATGGCCAGTGCCAAGATGCACAAGGAACTT
TGTGCTTTAATGTTTTCCCTGGATTGGATTAAAGCAAAAACAGAACTTGTAGGCCCTGCT
CATCTGATTCATGAATTTGTGGAATACAGACATATACTAGATGAAAAGGATTGTGCAGTC
AGTGAGAATTTTCAGGAGTTTTTATCTTTAAATGGACACCTTCTTGGACGACAGCCATTT
CCTAATATTGTACAACTGGGTCTCTGTGAGCCGGAAACTTCAGAAGTTTATCAGCAAGCT
AAGCTGCAGGCCAAGCAGGAGGTCGATAATGGAATGCTTTACCTGGAATGGATAAACAAA
AAAAACATCACGAATCTTTCCCGCTTAGTTGTCCGCCCCCACACAGATGCTGTTTACCAT
GCCTGCTTTTCTGAGGATGGTCAGAGAATAGCTTCTTGTGGAGCTGATAAAACCTTACAG
GTGTTCAAAGCTGAAACAGGAGAGAAACTTCTAGAAATCAAGGCTCATGAGGATGAAGTG
CTTTGTTGTGCATTCTCTACAGATGACAGATTTATAGCAACCTGCTCAGTGGATAAAAAA
GTGAAGATTTGGAATTCTATGACTGGGGAACTAGTACACACCTATGATGAGCACTCAGAG
CAAGTCAATTGCTGCCATTTCACCAACAGTAGTCATCATCTTCTCTTAGCCACTGGGTCA
AGTGACTGCTTCCTCAAACTTTGGGATTTGAATCAAAAAGAATGTCGAAATACCATGTTT
GGTCATACAAATTCAGTCAATCACTGCAGATTTTCACCAGATGATAAGCTTTTGGCTAGT
TGTTCAGCTGATGGAACCTTAAAGCTTTGGGATGCGACATCAGCAAATGAGAGGAAAAGC
ATTAATGTGAAACAGTTCTTCCTAAATTTGGAGGACCCTCAAGAGGATATGGAAGTGATA
GTGAAGTGTTGTTCGTGGTCTGCTGATGGTGCAAGGATAATGGTGGCAGCAAAAAATAAA
ATCTTTCTTTTTGACATTCATACTAGTGGCCTATTGGGAGAAATCCACACGGGCCATCAC
AGCACCATCCAGTACTGTGACTTCTCCCCACAAAACCATTTGGCAGTGGTTGCTTTGTCC
CAGTACTGTGTAGAGTTGTGGAATACAGACTCACGTTCAAAGGTGGCTGATTGCAGAGGA
CATTTAAGTTGGGTTCATGGTGTGATGTTTTCTCCTGATGGATCATCATTTTTGACATCT
TCTGATGACCAGACAATCAGGCTCTGGGAGACAAAGAAAGTATGTAAGAACTCTGCTGTA
ATGTTAAAGCAAGAAGTAGATGTTGTGTTTCAAGAAAATGAAGTGATGGTCCTTGCAGTT
GACCATATAAGACGTCTGCAACTCATTAATGGAAGAACAGGTCAGATTGATTATCTGACT
GAAGCTCAAGTTAGCTGCTGTTGCTTAAGTCCACATCTTCAGTACATTGCATTTGGAGAT
GAAAATGGAGCCATTGAGATTTTAGAACTTGTAAACAATAGAATCTTCCAGTCCAGGTTT
CAGCACAAGAAAACTGTATGGCACATCCAGTTCACAGCCGATGAGAAGACTCTTATTTCA
AGTTCTGATGATGCTGAAATTCAGGTATGGAATTGGCAATTGGACAAATGTATCTTTCTA
CGAGGCCATCAGGAAACAGTGAAAGACTTTAGACTCTTGAAAAATTCAAGACTGCTTTCT
TGGTCATTTGATGGAACAGTGAAGGTATGGAATATTATTACTGGAAATAAAGAAAAAGAC
TTTGTCTGTCACCAGGGTACAGTACTTTCTTGTGACATTTCTCACGATGCTACCAAGTTT
TCATCTACCTCTGCTGACAAGACTGCAAAGATCTGGAGTTTTGATCTCCTTTTGCCACTT
CATGAATTGAGGGGCCACAACGGCTGTGTGCGCTGCTCTGCCTTCTCTGTGGACAGTACC
CTGCTGGCAACGGGAGATGACAATGGAGAAATCAGGATATGGAATGTCTCAAACGGTGAG
CTTCTTCATTTGTGTGCTCCGCTTTCAGAAGAAGGAGCTGCTACCCATGGAGGCTGGGTG
ACTGACCTTTGCTTTTCTCCAGATGGCAAAATGCTTATCTCTGCTGGAGGATATATTAAG
TGGTGGAACGTTGTCACTGGGGAATCCTCACAGACCTTCTACACAAATGGAACCAATCTT
AAGAAAATACACGTGTCCCCTGACTTCAAAACATATGTGACTGTGGATAATCTTGGTATT
TTATATATTTTACAGACTTTAGAATAA
Protein Properties
Number of Residues 1248
Molecular Weight 141838.8
Theoretical pI 6.37
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>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
GenBank ID Protein 32483359
UniProtKB/Swiss-Prot ID O14727
UniProtKB/Swiss-Prot Entry Name APAF_HUMAN
PDB IDs
GenBank Gene ID NM_181861.1
GeneCard ID APAF1
GenAtlas ID APAF1
HGNC ID HGNC:576
References
General References
  1. 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 ]
  2. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]