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Database: UniProt
Entry: O14727
LinkDB: O14727
Original site: O14727 
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   07-APR-2021, entry version 229.
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; 9.5 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   BMRB; O14727; -.
DR   SMR; O14727; -.
DR   BioGRID; 106814; 40.
DR   ComplexPortal; CPX-3762; Apoptosome.
DR   CORUM; O14727; -.
DR   DIP; DIP-27624N; -.
DR   IntAct; O14727; 18.
DR   MINT; O14727; -.
DR   STRING; 9606.ENSP00000448165; -.
DR   BindingDB; O14727; -.
DR   ChEMBL; CHEMBL1795093; -.
DR   DrugBank; DB00171; ATP.
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; 716 antibodies.
DR   Ensembl; ENST00000333991; ENSP00000334558; ENSG00000120868. [O14727-6]
DR   Ensembl; ENST00000357310; ENSP00000349862; ENSG00000120868. [O14727-4]
DR   Ensembl; ENST00000359972; ENSP00000353059; ENSG00000120868. [O14727-3]
DR   Ensembl; ENST00000547045; ENSP00000449791; ENSG00000120868. [O14727-4]
DR   Ensembl; ENST00000550527; ENSP00000448449; ENSG00000120868. [O14727-2]
DR   Ensembl; ENST00000551964; ENSP00000448165; ENSG00000120868. [O14727-1]
DR   Ensembl; ENST00000552268; ENSP00000448826; ENSG00000120868. [O14727-6]
DR   GeneID; 317; -.
DR   KEGG; hsa:317; -.
DR   UCSC; uc001tfz.4; human. [O14727-1]
DR   CTD; 317; -.
DR   DisGeNET; 317; -.
DR   GeneCards; APAF1; -.
DR   HGNC; HGNC:576; APAF1.
DR   HPA; ENSG00000120868; Low tissue specificity.
DR   MIM; 602233; gene.
DR   neXtProt; NX_O14727; -.
DR   OpenTargets; ENSG00000120868; -.
DR   PharmGKB; PA24868; -.
DR   VEuPathDB; HostDB:ENSG00000120868.13; -.
DR   eggNOG; KOG4155; Eukaryota.
DR   eggNOG; KOG4658; Eukaryota.
DR   GeneTree; ENSGT00940000157710; -.
DR   HOGENOM; CLU_005071_1_0_1; -.
DR   InParanoid; O14727; -.
DR   OMA; VQHCRFT; -.
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; 5 hits in 1000 CRISPR screens.
DR   ChiTaRS; APAF1; human.
DR   EvolutionaryTrace; O14727; -.
DR   GeneWiki; APAF1; -.
DR   GenomeRNAi; 317; -.
DR   Pharos; O14727; Tbio.
DR   PRO; PR:O14727; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; O14727; protein.
DR   Bgee; ENSG00000120868; Expressed in caudate nucleus and 209 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: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:0070317; P:negative regulation of G0 to G1 transition; TAS:Reactome.
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:0043312; P:neutrophil degranulation; TAS:Reactome.
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; 2.130.10.10; -; 2.
DR   InterPro; IPR017251; Apaf-1.
DR   InterPro; IPR041452; APAF1_C.
DR   InterPro; IPR037963; APAF1_CARD_dom.
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; IPR017986; WD40_repeat_dom.
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   NP_BIND         154..161
FT                   /note="ATP"
FT                   /evidence="ECO:0000255"
FT   REGION          910..921
FT                   /note="Interpropeller linker"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        95..98
FT                   /note="Poly-Ser"
FT   BINDING         265
FT                   /note="ATP"
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:0007744|PDB:1CY5"
FT   HELIX           13..19
FT                   /evidence="ECO:0007744|PDB:1CY5"
FT   HELIX           22..32
FT                   /evidence="ECO:0007744|PDB:1CY5"
FT   HELIX           37..44
FT                   /evidence="ECO:0007744|PDB:1CY5"
FT   STRAND          46..48
FT                   /evidence="ECO:0007744|PDB:1CY5"
FT   HELIX           49..61
FT                   /evidence="ECO:0007744|PDB:1CY5"
FT   HELIX           65..77
FT                   /evidence="ECO:0007744|PDB:1CY5"
FT   HELIX           81..87
FT                   /evidence="ECO:0007744|PDB:1CY5"
FT   HELIX           88..90
FT                   /evidence="ECO:0007744|PDB:1CY5"
FT   HELIX           99..104
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           108..116
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           130..140
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   STRAND          148..153
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           160..168
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           171..177
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   STRAND          182..189
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           192..206
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           220..233
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   STRAND          239..245
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           248..252
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   STRAND          259..265
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           267..270
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   STRAND          277..281
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           288..299
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           303..305
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           309..316
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   TURN            317..319
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           321..333
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           338..346
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           362..373
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   TURN            377..379
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           380..385
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           386..388
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           397..404
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           408..420
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   STRAND          423..429
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   STRAND          432..436
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           439..448
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           450..452
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           453..464
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   TURN            465..467
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           470..472
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           480..493
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           497..504
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           507..517
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           520..528
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           530..532
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           535..550
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   TURN            551..556
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           563..567
FT                   /evidence="ECO:0007744|PDB:1Z6T"
FT   HELIX           575..585
FT                   /evidence="ECO:0007744|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
//
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