APAF_HUMAN
ID APAF_HUMAN Reviewed; 1248 AA.
AC O14727; B2RMX8; O43297; Q7Z438; Q9BXZ6; Q9UBZ5; Q9UGN8; Q9UGN9; Q9UGP0;
AC Q9UJ58; Q9UJ59; Q9UJ60; Q9UJ61; Q9UJ62; Q9UJ63; Q9UJ64; Q9UJ65; Q9UJ66;
AC Q9UJ67; Q9UNC9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 234.
DE RecName: Full=Apoptotic protease-activating factor 1 {ECO:0000305};
DE Short=APAF-1;
GN Name=APAF1 {ECO:0000312|HGNC:HGNC:576}; Synonyms=KIAA0413;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Cervix carcinoma;
RX PubMed=9267021; DOI=10.1016/s0092-8674(00)80501-2;
RA Zou H., Henzel W.J., Liu X., Lutschg A., Wang X.;
RT "Apaf-1, a human protein homologous to C. elegans CED-4, participates in
RT cytochrome c-dependent activation of caspase-3.";
RL Cell 90:405-413(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 5).
RC TISSUE=Cervix carcinoma, Heart, and Peripheral blood;
RX PubMed=10441496; DOI=10.1006/bbrc.1999.1124;
RA Hahn C., Hirsch B., Jahnke D., Duerkop H., Stein H.;
RT "Three new types of Apaf-1 in mammalian cells.";
RL Biochem. Biophys. Res. Commun. 261:746-749(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=T-cell;
RX PubMed=10364241; DOI=10.1074/jbc.274.25.17941;
RA Saleh A., Srinivasula S.M., Acharya S., Fishel R., Alnemri E.S.;
RT "Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite
RT for procaspase-9 activation.";
RL J. Biol. Chem. 274:17941-17945(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, AND MUTAGENESIS
RP OF LYS-160 AND MET-368.
RC TISSUE=Kidney;
RX PubMed=10393175; DOI=10.1093/emboj/18.13.3586;
RA Hu Y., Benedict M.A., Ding L., Nunez G.;
RT "Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9
RT activation and apoptosis.";
RL EMBO J. 18:3586-3595(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 6), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Prostatic carcinoma;
RX PubMed=12804598; DOI=10.1016/s0006-291x(03)00995-1;
RA Ogawa T., Shiga K., Hashimoto S., Kobayashi T., Horii A., Furukawa T.;
RT "APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially
RT causes impeded ability of undergoing DNA damage-induced apoptosis in the
RT LNCaP human prostate cancer cell line.";
RL Biochem. Biophys. Res. Commun. 306:537-543(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [7]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 810-864 AND 866-883.
RA Roberts D.L., Dalgleish R., Cohen G.M., MacFarlane M.;
RT "The mammalian CED4 homologue, APAF1, exists as two distinct forms in human
RT cells.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-138 (ISOFORMS 1/4/5).
RA Won M., Lee J.-W., Ohr H.-H., Kim D.-U., Chung K.-S., Lee M., Yoo H.-S.;
RT "Cloning of variant Apaf1.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP APAF-1-MEDIATED OLIGOMERIZATION.
RX PubMed=9651578; DOI=10.1016/s1097-2765(00)80095-7;
RA Srinivasula S.M., Ahmad M., Fernandes-Alnemri T., Alnemri E.S.;
RT "Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.";
RL Mol. Cell 1:949-957(1998).
RN [13]
RP INDUCTION BY E2F AND TP53.
RX PubMed=11389439; DOI=10.1038/35078527;
RA Moroni M.C., Hickman E.S., Denchi E.L., Caprara G., Colli E., Cecconi F.,
RA Mueller H., Helin K.;
RT "Apaf-1 is a transcriptional target for E2F and p53.";
RL Nat. Cell Biol. 3:552-558(2001).
RN [14]
RP INTERACTION WITH APIP.
RX PubMed=15262985; DOI=10.1074/jbc.m405747200;
RA Cho D.-H., Hong Y.-M., Lee H.-J., Woo H.-N., Pyo J.-O., Mak T.W.,
RA Jung Y.-K.;
RT "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-
RT interacting protein.";
RL J. Biol. Chem. 279:39942-39950(2004).
RN [15]
RP INHIBITION BY CALCIUM.
RX PubMed=17244527; DOI=10.1016/j.molcel.2006.12.013;
RA Bao Q., Lu W., Rabinowitz J.D., Shi Y.;
RT "Calcium blocks formation of apoptosome by preventing nucleotide exchange
RT in Apaf-1.";
RL Mol. Cell 25:181-192(2007).
RN [16]
RP INTERACTION WITH NAIP/BIRC1.
RX PubMed=21371431; DOI=10.1016/j.bbrc.2011.02.130;
RA Karimpour S., Davoodi J., Ghahremani M.H.;
RT "Integrity of ATP binding site is essential for effective inhibition of the
RT intrinsic apoptosis pathway by NAIP.";
RL Biochem. Biophys. Res. Commun. 407:158-162(2011).
RN [17]
RP INTERACTION WITH CIAO2A.
RX PubMed=25716227; DOI=10.1002/ijc.29498;
RA Schwamb B., Pick R., Fernandez S.B., Voelp K., Heering J., Doetsch V.,
RA Boesser S., Jung J., Beinoraviciute-Kellner R., Wesely J., Zoernig I.,
RA Hammerschmidt M., Nowak M., Penzel R., Zatloukal K., Joos S., Rieker R.J.,
RA Agaimy A., Soeder S., Reid-Lombardo K.M., Kendrick M.L., Bardsley M.R.,
RA Hayashi Y., Asuzu D.T., Syed S.A., Ordog T., Zoernig M.;
RT "FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal
RT stromal tumors.";
RL Int. J. Cancer 137:1318-1329(2015).
RN [18]
RP INDUCTION.
RX PubMed=31498791; DOI=10.1371/journal.pone.0221048;
RA Li M.L., Lin J.Y., Chen B.S., Weng K.F., Shih S.R., Calderon J.D.,
RA Tolbert B.S., Brewer G.;
RT "EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote
RT apaf-1 translation.";
RL PLoS ONE 14:E0221048-E0221048(2019).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 1-97.
RX PubMed=10543941; DOI=10.1006/jmbi.1999.3177;
RA Vaughn D.E., Rodriguez J., Lazebnik Y., Joshua-Tor L.;
RT "Crystal structure of Apaf-1 caspase recruitment domain: an alpha-helical
RT Greek key fold for apoptotic signaling.";
RL J. Mol. Biol. 293:439-447(1999).
RN [20]
RP STRUCTURE BY NMR OF 1-97.
RX PubMed=10578182; DOI=10.1038/sj.cdd.4400584;
RA Day C.L., Dupont C., Lackmann M., Vaux D.L., Hinds M.G.;
RT "Solution structure and mutagenesis of the caspase recruitment domain
RT (CARD) from Apaf-1.";
RL Cell Death Differ. 6:1125-1132(1999).
CC -!- FUNCTION: Oligomeric Apaf-1 mediates the cytochrome c-dependent
CC autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the
CC activation of caspase-3 and apoptosis. This activation requires ATP.
CC Isoform 6 is less effective in inducing apoptosis.
CC {ECO:0000269|PubMed:10393175, ECO:0000269|PubMed:12804598}.
CC -!- SUBUNIT: Monomer. Oligomerizes to a heptameric ring, known as the
CC apoptosome, upon binding of cytochrome c and dATP. Oligomeric Apaf-1
CC and pro-caspase-9 bind to each other via their respective NH2-terminal
CC CARD domains and consecutively mature caspase-9 is released from the
CC complex. Pro-caspase-3 is recruited into the Apaf-1-pro-caspase-9
CC complex via interaction with pro-caspase-9. Interacts with APIP.
CC Interacts (via CARD and NACHT domains) with NAIP/BIRC1 (via NACHT
CC domain). Interacts with CIAO2A (PubMed:25716227).
CC {ECO:0000269|PubMed:10393175, ECO:0000269|PubMed:15262985,
CC ECO:0000269|PubMed:21371431, ECO:0000269|PubMed:25716227}.
CC -!- INTERACTION:
CC O14727; P55211: CASP9; NbExp=22; IntAct=EBI-446492, EBI-516799;
CC O14727; P99999: CYCS; NbExp=6; IntAct=EBI-446492, EBI-446479;
CC O14727; P62136: PPP1CA; NbExp=2; IntAct=EBI-446492, EBI-357253;
CC O14727; P62258: YWHAE; NbExp=2; IntAct=EBI-446492, EBI-356498;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12804598}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=Apaf-1XL;
CC IsoId=O14727-1; Sequence=Displayed;
CC Name=2; Synonyms=Apaf-1L;
CC IsoId=O14727-2; Sequence=VSP_006759;
CC Name=3; Synonyms=Apaf-1S;
CC IsoId=O14727-3; Sequence=VSP_006759, VSP_006761;
CC Name=4; Synonyms=Apaf-1M;
CC IsoId=O14727-4; Sequence=VSP_006761;
CC Name=5; Synonyms=Apaf-1XS;
CC IsoId=O14727-5; Sequence=VSP_006760, VSP_006761, VSP_006762;
CC Name=6; Synonyms=Apaf-1-ALT;
CC IsoId=O14727-6; Sequence=VSP_008965, VSP_008966;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels of expression in adult
CC spleen and peripheral blood leukocytes, and in fetal brain, kidney and
CC lung. Isoform 1 is expressed in heart, kidney and liver.
CC -!- INDUCTION: By E2F and p53/TP53 in apoptotic neurons (PubMed:11389439).
CC Translation is inhibited by HNRPA1, which binds to the IRES of APAF1
CC mRNAs (PubMed:31498791). {ECO:0000269|PubMed:11389439,
CC ECO:0000269|PubMed:31498791}.
CC -!- DOMAIN: The CARD domain mediates interaction with APIP.
CC -!- DOMAIN: The monomeric form is autoinhibited in a closed conformation
CC through a bound ADP at the nucleotide binding site. Exchange of ADP for
CC ATP and binding of cytochrome c trigger a large conformational change
CC where the first WD repeat region swings out, allowing the NB-ARC domain
CC to rotate and expose the contact areas for oligomerization (By
CC similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Physiological concentrations of calcium ions negatively
CC affect the assembly of apoptosome by inhibiting nucleotide exchange in
CC the monomeric form.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK28401.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/APAF1ID422.html";
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DR EMBL; AF013263; AAC51678.1; -; mRNA.
DR EMBL; AJ243003; CAB55579.1; -; mRNA.
DR EMBL; AJ243004; CAB55580.1; -; mRNA.
DR EMBL; AJ243005; CAB55581.1; -; mRNA.
DR EMBL; AJ243006; CAB55582.1; -; mRNA.
DR EMBL; AJ243007; CAB55583.1; -; mRNA.
DR EMBL; AJ243008; CAB55584.1; -; mRNA.
DR EMBL; AJ243009; CAB55585.1; -; mRNA.
DR EMBL; AJ243010; CAB55586.1; -; mRNA.
DR EMBL; AJ243011; CAB55587.1; -; mRNA.
DR EMBL; AJ243048; CAB55588.1; -; mRNA.
DR EMBL; AJ243107; CAB56462.1; -; mRNA.
DR EMBL; AF134397; AAD38344.1; -; mRNA.
DR EMBL; AF149794; AAD34016.1; -; mRNA.
DR EMBL; AB007873; BAA24843.2; -; mRNA.
DR EMBL; AB103079; BAC77343.1; -; mRNA.
DR EMBL; CH471054; EAW97606.1; -; Genomic_DNA.
DR EMBL; BC136531; AAI36532.1; -; mRNA.
DR EMBL; BC136532; AAI36533.1; -; mRNA.
DR EMBL; AJ133643; CAB65085.1; -; Genomic_DNA.
DR EMBL; AJ133644; CAB65086.1; -; Genomic_DNA.
DR EMBL; AJ133645; CAB65087.1; -; Genomic_DNA.
DR EMBL; AF248734; AAK28401.1; ALT_FRAME; mRNA.
DR CCDS; CCDS55862.1; -. [O14727-2]
DR CCDS; CCDS55863.1; -. [O14727-3]
DR CCDS; CCDS9069.1; -. [O14727-1]
DR CCDS; CCDS9070.1; -. [O14727-4]
DR CCDS; CCDS9071.1; -. [O14727-6]
DR PIR; T03818; T03818.
DR RefSeq; NP_001151.1; NM_001160.2. [O14727-3]
DR RefSeq; NP_037361.1; NM_013229.2. [O14727-2]
DR RefSeq; NP_863651.1; NM_181861.1. [O14727-1]
DR RefSeq; NP_863658.1; NM_181868.1. [O14727-4]
DR RefSeq; NP_863659.1; NM_181869.1. [O14727-6]
DR PDB; 1C15; NMR; -; A=1-97.
DR PDB; 1CWW; NMR; -; A=1-97.
DR PDB; 1CY5; X-ray; 1.30 A; A=1-97.
DR PDB; 1Z6T; X-ray; 2.21 A; A/B/C/D=1-591.
DR PDB; 2P1H; X-ray; 1.59 A; A=1-92.
DR PDB; 2YGS; X-ray; 1.60 A; A=1-92.
DR PDB; 3J2T; EM; 9.50 A; A/B/C/D/E/F/G=1-1248.
DR PDB; 3JBT; EM; 3.80 A; A/C/E/G/I/K/M=1-1248.
DR PDB; 3YGS; X-ray; 2.50 A; C=1-95.
DR PDB; 4RHW; X-ray; 2.10 A; A/B/C/D=1-97.
DR PDB; 5JUY; EM; 4.10 A; A/B/C/D/E/F/G=1-1248.
DR PDB; 5WVC; X-ray; 2.99 A; A/C/E=1-95.
DR PDB; 5WVE; EM; 4.40 A; A/C/E/G/I/K/M=1-1248, O/P/Q/R/W/X=1-102.
DR PDBsum; 1C15; -.
DR PDBsum; 1CWW; -.
DR PDBsum; 1CY5; -.
DR PDBsum; 1Z6T; -.
DR PDBsum; 2P1H; -.
DR PDBsum; 2YGS; -.
DR PDBsum; 3J2T; -.
DR PDBsum; 3JBT; -.
DR PDBsum; 3YGS; -.
DR PDBsum; 4RHW; -.
DR PDBsum; 5JUY; -.
DR PDBsum; 5WVC; -.
DR PDBsum; 5WVE; -.
DR AlphaFoldDB; O14727; -.
DR BMRB; O14727; -.
DR SMR; O14727; -.
DR BioGRID; 106814; 86.
DR ComplexPortal; CPX-3762; Apoptosome.
DR CORUM; O14727; -.
DR DIP; DIP-27624N; -.
DR IntAct; O14727; 19.
DR MINT; O14727; -.
DR STRING; 9606.ENSP00000448165; -.
DR BindingDB; O14727; -.
DR ChEMBL; CHEMBL1795093; -.
DR DrugBank; DB00171; ATP.
DR TCDB; 8.A.92.1.11; the g-protein AlphaBetaGama complex (gpc) family.
DR iPTMnet; O14727; -.
DR PhosphoSitePlus; O14727; -.
DR BioMuta; APAF1; -.
DR EPD; O14727; -.
DR jPOST; O14727; -.
DR MassIVE; O14727; -.
DR MaxQB; O14727; -.
DR PaxDb; O14727; -.
DR PeptideAtlas; O14727; -.
DR PRIDE; O14727; -.
DR ProteomicsDB; 48182; -. [O14727-1]
DR ProteomicsDB; 48183; -. [O14727-2]
DR ProteomicsDB; 48184; -. [O14727-3]
DR ProteomicsDB; 48185; -. [O14727-4]
DR ProteomicsDB; 48186; -. [O14727-5]
DR ProteomicsDB; 48187; -. [O14727-6]
DR Antibodypedia; 17738; 732 antibodies from 46 providers.
DR DNASU; 317; -.
DR Ensembl; ENST00000333991.5; ENSP00000334558.1; ENSG00000120868.14. [O14727-6]
DR Ensembl; ENST00000357310.5; ENSP00000349862.1; ENSG00000120868.14. [O14727-4]
DR Ensembl; ENST00000359972.6; ENSP00000353059.2; ENSG00000120868.14. [O14727-3]
DR Ensembl; ENST00000547045.5; ENSP00000449791.1; ENSG00000120868.14. [O14727-4]
DR Ensembl; ENST00000550527.5; ENSP00000448449.1; ENSG00000120868.14. [O14727-2]
DR Ensembl; ENST00000551964.6; ENSP00000448165.2; ENSG00000120868.14. [O14727-1]
DR Ensembl; ENST00000552268.5; ENSP00000448826.1; ENSG00000120868.14. [O14727-6]
DR GeneID; 317; -.
DR KEGG; hsa:317; -.
DR MANE-Select; ENST00000551964.6; ENSP00000448165.2; NM_181861.2; NP_863651.1.
DR UCSC; uc001tfz.4; human. [O14727-1]
DR CTD; 317; -.
DR DisGeNET; 317; -.
DR GeneCards; APAF1; -.
DR HGNC; HGNC:576; APAF1.
DR HPA; ENSG00000120868; Tissue enhanced (bone).
DR MIM; 602233; gene.
DR neXtProt; NX_O14727; -.
DR OpenTargets; ENSG00000120868; -.
DR PharmGKB; PA24868; -.
DR VEuPathDB; HostDB:ENSG00000120868; -.
DR eggNOG; KOG4155; Eukaryota.
DR eggNOG; KOG4658; Eukaryota.
DR GeneTree; ENSGT00940000157710; -.
DR HOGENOM; CLU_005071_1_0_1; -.
DR InParanoid; O14727; -.
DR OMA; YHMANAN; -.
DR OrthoDB; 62693at2759; -.
DR PhylomeDB; O14727; -.
DR TreeFam; TF323866; -.
DR PathwayCommons; O14727; -.
DR Reactome; R-HSA-111458; Formation of apoptosome.
DR Reactome; R-HSA-111459; Activation of caspases through apoptosome-mediated cleavage.
DR Reactome; R-HSA-111463; SMAC (DIABLO) binds to IAPs.
DR Reactome; R-HSA-111464; SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR Reactome; R-HSA-9627069; Regulation of the apoptosome activity.
DR SABIO-RK; O14727; -.
DR SignaLink; O14727; -.
DR SIGNOR; O14727; -.
DR BioGRID-ORCS; 317; 15 hits in 1085 CRISPR screens.
DR ChiTaRS; APAF1; human.
DR EvolutionaryTrace; O14727; -.
DR GeneWiki; APAF1; -.
DR GenomeRNAi; 317; -.
DR Pharos; O14727; Tchem.
DR PRO; PR:O14727; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O14727; protein.
DR Bgee; ENSG00000120868; Expressed in monocyte and 172 other tissues.
DR ExpressionAtlas; O14727; baseline and differential.
DR Genevisible; O14727; HS.
DR GO; GO:0043293; C:apoptosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0043531; F:ADP binding; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; TAS:ProtInc.
DR GO; GO:0031072; F:heat shock protein binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0000166; F:nucleotide binding; TAS:UniProtKB.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IDA:ComplexPortal.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; IDA:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:1902510; P:regulation of apoptotic DNA fragmentation; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0072432; P:response to G1 DNA damage checkpoint signaling; TAS:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR CDD; cd08323; CARD_APAF1; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 1.10.8.430; -; 1.
DR Gene3D; 2.130.10.10; -; 2.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR017251; Apaf-1.
DR InterPro; IPR041452; APAF1_C.
DR InterPro; IPR037963; APAF1_CARD_dom.
DR InterPro; IPR042197; Apaf_helical.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR002182; NB-ARC.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF17908; APAF1_C; 1.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF00931; NB-ARC; 1.
DR Pfam; PF00400; WD40; 9.
DR PIRSF; PIRSF037646; Apop_pept_activating-1; 1.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 13.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF50978; SSF50978; 2.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 4.
DR PROSITE; PS50082; WD_REPEATS_2; 9.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Calcium;
KW Cytoplasm; Direct protein sequencing; Nucleotide-binding;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..1248
FT /note="Apoptotic protease-activating factor 1"
FT /id="PRO_0000050844"
FT DOMAIN 1..90
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 104..415
FT /note="NB-ARC"
FT REPEAT 613..652
FT /note="WD 1-1"
FT REPEAT 655..694
FT /note="WD 1-2"
FT REPEAT 697..738
FT /note="WD 1-3"
FT REPEAT 741..780
FT /note="WD 1-4"
FT REPEAT 796..836
FT /note="WD 1-5"
FT REPEAT 838..877
FT /note="WD 1-6"
FT REPEAT 880..910
FT /note="WD 1-7"
FT REPEAT 922..958
FT /note="WD 2-1"
FT REPEAT 959..998
FT /note="WD 2-2"
FT REPEAT 1001..1040
FT /note="WD 2-3"
FT REPEAT 1042..1080
FT /note="WD 2-4"
FT REPEAT 1083..1122
FT /note="WD 2-5"
FT REPEAT 1125..1164
FT /note="WD 2-6"
FT REPEAT 1175..1212
FT /note="WD 2-7"
FT REPEAT 1213..1248
FT /note="WD 2-8"
FT REGION 910..921
FT /note="Interpropeller linker"
FT /evidence="ECO:0000250"
FT BINDING 154..161
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT BINDING 265
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT VAR_SEQ 99..109
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10364241,
FT ECO:0000303|PubMed:9267021, ECO:0000303|PubMed:9455477"
FT /id="VSP_006759"
FT VAR_SEQ 319..338
FT /note="GSPLVVSLIGALLRDFPNRW -> VVERCHWGILTDLLHKWNQS (in
FT isoform 6)"
FT /evidence="ECO:0000303|PubMed:12804598"
FT /id="VSP_008965"
FT VAR_SEQ 339..1248
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:12804598"
FT /id="VSP_008966"
FT VAR_SEQ 575
FT /note="E -> ETLGFESKK (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10441496"
FT /id="VSP_006760"
FT VAR_SEQ 824..866
FT /note="Missing (in isoform 3, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10441496,
FT ECO:0000303|PubMed:9267021"
FT /id="VSP_006761"
FT VAR_SEQ 1113..1154
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10441496"
FT /id="VSP_006762"
FT MUTAGEN 160
FT /note="K->R: No association with APAF-1. No binding to pro-
FT caspase-9."
FT /evidence="ECO:0000269|PubMed:10393175"
FT MUTAGEN 368
FT /note="M->L: Activation of pro-caspase-9 independent of
FT cytochrome c. Increased ability to induce apoptosis."
FT /evidence="ECO:0000269|PubMed:10393175"
FT CONFLICT 134
FT /note="N -> S (in Ref. 11)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="G -> C (in Ref. 2; CAB55587)"
FT /evidence="ECO:0000305"
FT CONFLICT 161
FT /note="S -> F (in Ref. 2; CAB55586)"
FT /evidence="ECO:0000305"
FT CONFLICT 370
FT /note="I -> T (in Ref. 2; CAB55581)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="Y -> H (in Ref. 2; CAB55586)"
FT /evidence="ECO:0000305"
FT CONFLICT 544
FT /note="F -> L (in Ref. 2; CAB55584)"
FT /evidence="ECO:0000305"
FT CONFLICT 580
FT /note="A -> T (in Ref. 2; CAB55580)"
FT /evidence="ECO:0000305"
FT CONFLICT 608
FT /note="R -> C (in Ref. 2; CAB55585)"
FT /evidence="ECO:0000305"
FT CONFLICT 620
FT /note="H -> R (in Ref. 2; CAB55587)"
FT /evidence="ECO:0000305"
FT CONFLICT 639
FT /note="L -> F (in Ref. 2; CAB55583)"
FT /evidence="ECO:0000305"
FT CONFLICT 708
FT /note="T -> A (in Ref. 2; CAB55579)"
FT /evidence="ECO:0000305"
FT CONFLICT 742
FT /note="H -> R (in Ref. 2; CAB55584)"
FT /evidence="ECO:0000305"
FT CONFLICT 746
FT /note="V -> A (in Ref. 2; CAB55586)"
FT /evidence="ECO:0000305"
FT CONFLICT 757
FT /note="L -> P (in Ref. 2; CAB56462)"
FT /evidence="ECO:0000305"
FT CONFLICT 795
FT /note="E -> G (in Ref. 2; CAB55581)"
FT /evidence="ECO:0000305"
FT CONFLICT 798
FT /note="E -> G (in Ref. 2; CAB55587)"
FT /evidence="ECO:0000305"
FT CONFLICT 825
FT /note="D -> A (in Ref. 2; CAB55585)"
FT /evidence="ECO:0000305"
FT CONFLICT 871
FT /note="S -> L (in Ref. 2; CAB55587)"
FT /evidence="ECO:0000305"
FT CONFLICT 876
FT /note="A -> T (in Ref. 2; CAB55581)"
FT /evidence="ECO:0000305"
FT CONFLICT 949
FT /note="I -> V (in Ref. 2; CAB55585)"
FT /evidence="ECO:0000305"
FT CONFLICT 1008
FT /note="H -> R (in Ref. 2; CAB55582)"
FT /evidence="ECO:0000305"
FT CONFLICT 1056
FT /note="S -> P (in Ref. 2; CAB55582)"
FT /evidence="ECO:0000305"
FT CONFLICT 1241
FT /note="L -> I (in Ref. 6; BAA24843)"
FT /evidence="ECO:0000305"
FT HELIX 3..11
FT /evidence="ECO:0007829|PDB:1CY5"
FT HELIX 13..19
FT /evidence="ECO:0007829|PDB:1CY5"
FT HELIX 22..32
FT /evidence="ECO:0007829|PDB:1CY5"
FT HELIX 37..44
FT /evidence="ECO:0007829|PDB:1CY5"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:1CY5"
FT HELIX 49..61
FT /evidence="ECO:0007829|PDB:1CY5"
FT HELIX 65..77
FT /evidence="ECO:0007829|PDB:1CY5"
FT HELIX 81..87
FT /evidence="ECO:0007829|PDB:1CY5"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:1CY5"
FT HELIX 99..104
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 108..116
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 130..140
FT /evidence="ECO:0007829|PDB:1Z6T"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 160..168
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 171..177
FT /evidence="ECO:0007829|PDB:1Z6T"
FT STRAND 182..189
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 192..206
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 220..233
FT /evidence="ECO:0007829|PDB:1Z6T"
FT STRAND 239..245
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 248..252
FT /evidence="ECO:0007829|PDB:1Z6T"
FT STRAND 259..265
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:1Z6T"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 288..299
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 309..316
FT /evidence="ECO:0007829|PDB:1Z6T"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 321..333
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 338..346
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 362..373
FT /evidence="ECO:0007829|PDB:1Z6T"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 380..385
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 386..388
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 397..404
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 408..420
FT /evidence="ECO:0007829|PDB:1Z6T"
FT STRAND 423..429
FT /evidence="ECO:0007829|PDB:1Z6T"
FT STRAND 432..436
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 439..448
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 450..452
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 453..464
FT /evidence="ECO:0007829|PDB:1Z6T"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 480..493
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 497..504
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 507..517
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 520..528
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 530..532
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 535..550
FT /evidence="ECO:0007829|PDB:1Z6T"
FT TURN 551..556
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 563..567
FT /evidence="ECO:0007829|PDB:1Z6T"
FT HELIX 575..585
FT /evidence="ECO:0007829|PDB:1Z6T"
SQ SEQUENCE 1248 AA; 141840 MW; 0750D05817AC9B3B CRC64;
MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ QRAAMLIKMI
LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSGK DSVSGITSYV RTVLCEGGVP
QRPVVFVTRK KLVNAIQQKL SKLKGEPGWV TIHGMAGCGK SVLAAEAVRD HSLLEGCFPG
GVHWVSVGKQ DKSGLLMKLQ NLCTRLDQDE SFSQRLPLNI EEAKDRLRIL MLRKHPRSLL
ILDDVWDSWV LKAFDSQCQI LLTTRDKSVT DSVMGPKYVV PVESSLGKEK GLEILSLFVN
MKKADLPEQA HSIIKECKGS PLVVSLIGAL LRDFPNRWEY YLKQLQNKQF KRIRKSSSYD
YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL CILWDMETEE VEDILQEFVN
KSLLFCDRNG KSFRYYLHDL QVDFLTEKNC SQLQDLHKKI ITQFQRYHQP HTLSPDQEDC
MYWYNFLAYH MASAKMHKEL CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV
SENFQEFLSL NGHLLGRQPF PNIVQLGLCE PETSEVYQQA KLQAKQEVDN GMLYLEWINK
KNITNLSRLV VRPHTDAVYH ACFSEDGQRI ASCGADKTLQ VFKAETGEKL LEIKAHEDEV
LCCAFSTDDR FIATCSVDKK VKIWNSMTGE LVHTYDEHSE QVNCCHFTNS SHHLLLATGS
SDCFLKLWDL NQKECRNTMF GHTNSVNHCR FSPDDKLLAS CSADGTLKLW DATSANERKS
INVKQFFLNL EDPQEDMEVI VKCCSWSADG ARIMVAAKNK IFLFDIHTSG LLGEIHTGHH
STIQYCDFSP QNHLAVVALS QYCVELWNTD SRSKVADCRG HLSWVHGVMF SPDGSSFLTS
SDDQTIRLWE TKKVCKNSAV MLKQEVDVVF QENEVMVLAV DHIRRLQLIN GRTGQIDYLT
EAQVSCCCLS PHLQYIAFGD ENGAIEILEL VNNRIFQSRF QHKKTVWHIQ FTADEKTLIS
SSDDAEIQVW NWQLDKCIFL RGHQETVKDF RLLKNSRLLS WSFDGTVKVW NIITGNKEKD
FVCHQGTVLS CDISHDATKF SSTSADKTAK IWSFDLLLPL HELRGHNGCV RCSAFSVDST
LLATGDDNGE IRIWNVSNGE LLHLCAPLSE EGAATHGGWV TDLCFSPDGK MLISAGGYIK
WWNVVTGESS QTFYTNGTNL KKIHVSPDFK TYVTVDNLGI LYILQTLE
