APAF_RAT
ID APAF_RAT Reviewed; 1249 AA.
AC Q9EPV5;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Apoptotic protease-activating factor 1;
DE Short=APAF-1;
GN Name=Apaf1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Itoh T., Itoh A., Pleasure D.;
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP DEVELOPMENTAL STAGE, AND INDUCTION BY BRAIN INJURY.
RX PubMed=11567033; DOI=10.1523/jneurosci.21-19-07439.2001;
RA Yakovlev A.G., Ota K., Wang G., Movsesyan V., Bao W.-L., Yoshihara K.,
RA Faden A.I.;
RT "Differential expression of apoptotic protease-activating factor-1 and
RT caspase-3 genes and susceptibility to apoptosis during brain development
RT and after traumatic brain injury.";
RL J. Neurosci. 21:7439-7446(2001).
CC -!- FUNCTION: Regulates programmed cell death; necessary for normal brain
CC development. Participates with pro-caspase-9 (Apaf-3) in the cytochrome
CC c-dependent activation of caspase-3, leading to apoptosis. This
CC activation requires ATP (By similarity). {ECO:0000250}.
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. Interacts with UACA. Interacts with APIP (By similarity).
CC Interacts (via CARD and NACHT domains) with NAIP/BIRC1 (via NACHT
CC domain) (By similarity). Interacts with CIAO2A (By similarity).
CC {ECO:0000250|UniProtKB:O14727}.
CC -!- INTERACTION:
CC Q9EPV5; O00291: HIP1; Xeno; NbExp=2; IntAct=EBI-6978501, EBI-473886;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in brain cortex in embryos (E17)
CC and newborn rats up to day 7. Very low expression thereafter.
CC {ECO:0000269|PubMed:11567033}.
CC -!- INDUCTION: By brain injury. {ECO:0000269|PubMed:11567033}.
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. {ECO:0000250}.
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DR EMBL; AF320222; AAG35067.1; -; mRNA.
DR RefSeq; NP_076469.1; NM_023979.1.
DR AlphaFoldDB; Q9EPV5; -.
DR SMR; Q9EPV5; -.
DR IntAct; Q9EPV5; 2.
DR MINT; Q9EPV5; -.
DR STRING; 10116.ENSRNOP00000010869; -.
DR iPTMnet; Q9EPV5; -.
DR PhosphoSitePlus; Q9EPV5; -.
DR jPOST; Q9EPV5; -.
DR PRIDE; Q9EPV5; -.
DR Ensembl; ENSRNOT00000010869; ENSRNOP00000010869; ENSRNOG00000008022.
DR GeneID; 78963; -.
DR KEGG; rno:78963; -.
DR UCSC; RGD:620575; rat.
DR CTD; 317; -.
DR RGD; 620575; Apaf1.
DR eggNOG; KOG4155; Eukaryota.
DR eggNOG; KOG4658; Eukaryota.
DR GeneTree; ENSGT00940000157710; -.
DR HOGENOM; CLU_005071_1_0_1; -.
DR InParanoid; Q9EPV5; -.
DR OMA; YHMANAN; -.
DR OrthoDB; 62693at2759; -.
DR PhylomeDB; Q9EPV5; -.
DR Reactome; R-RNO-111458; Formation of apoptosome.
DR Reactome; R-RNO-111459; Activation of caspases through apoptosome-mediated cleavage.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-9627069; Regulation of the apoptosome activity.
DR PRO; PR:Q9EPV5; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000008022; Expressed in jejunum and 19 other tissues.
DR Genevisible; Q9EPV5; RN.
DR GO; GO:0043293; C:apoptosome; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0031072; F:heat shock protein binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0008635; P:activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IMP:RGD.
DR GO; GO:0030154; P:cell differentiation; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:1902510; P:regulation of apoptotic DNA fragmentation; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
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 Apoptosis; ATP-binding; Calcium; Cytoplasm; Nucleotide-binding;
KW Reference proteome; Repeat; WD repeat.
FT CHAIN 1..1249
FT /note="Apoptotic protease-activating factor 1"
FT /id="PRO_0000050846"
FT DOMAIN 1..90
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 106..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..837
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 1176..1213
FT /note="WD 2-7"
FT REPEAT 1214..1249
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"
SQ SEQUENCE 1249 AA; 141152 MW; 7B4A8116FAD008E9 CRC64;
MDAKARNCLL QHKEALEKDI KTSYIMDHMI SNGVLTVVEE EKVKSQATQY QRAAALIKMI
LNKDNYAYIS FYNALLHEGY KDLAGLLHSG LPLVSSSSGK DTDGGNTSFV RTVLCEGGVP
QRPVIFVTRK KLVSAIQQKL WKLNGEPGWV TIYGMAGCGK SVLAAEAVRD HALLEGCFSG
GVHWVSIGKQ DKSGLLMKLQ NLCTRLGQEE SFSQRLPLNI EEAKDRLRVL MLRKHPRSLL
ILDDVWDPWV LKAFDNQCQI LLTTRDKSVT DSVMGPKYVI PVESGLGKEK GLEILSLFVN
MKKEDLPVEA HSIIKECKGS PLVVSLVGAL LRDFPNRWAY YLRQLQNKQF KRIRKSSSYD
YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL CVLWDLETEE VEDILQEFVN
KSLLFCNRNG KSFCYYLHDL QVDFLTEKNR SQLQDLHRKM VTQFQRYHQP HTLSPGQEDC
MYWYNFLAYH MASAGMHKEL CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV
CENFQEFLSL NGHLLGRQPF PNIVQLGLCE PETSEVYQQA KLQAKQEVDT GRLYLEWINK
KTIKNLSRLV VRPHTDAVYH ACFSQDGQRI ASCGADKTLQ VFKAETGEKL LDIKAHEDEV
LCCAFSSDDS YIATCSVDKK VKIWDSGTGK LVHTYEEHSE QVNCCHFTNK SNHLLLATGS
NDSFLKLWDL NQKECRNTMF GHTNSVTHCR FSPDDELLAS CSADGTLKLW DVRSANEKKS
INVKRFFLSS EDPPEDVEVI VKCCSWSADG DRIIVAAKNK VLLLDIHTSG LLTEIHTGHH
STIQYCDFSP YDHLAVIALS QYCVELWNID SRVKVADCRG HLSWVHGVMF SPDGSSFLTA
SDDQTIRVWE TRKVCKNSAI VLKQEIDVVF QENEMMVLAV DNIRGLQLIA GKTGQIDYLP
EAQVSCCCLS PHLEYVAFGD EEGAIKIIEL PNNRVFSSGI GHKKAVRHIQ FTADGKTLIS
SSEDSVIQVW NWQTEEYVFL QAHQETVKDF RLLRDSRLLS WSFDGTVKVW NVITGRIERD
FTCHQGTVLS CAISSDATKF SSTSADKTAK IWSFELPSPL HELKGHNSCV RCSAFSLDGI
LLATGDDNGE IRIWNVSDGQ LLHLCAPISI EEGTATHGGW VTDVCFSPDR KMLVSAGGYL
KWWNVVTGES SQTFYTNGTN LKKIHVSPDF RTYVTVDNLG ILYILQVLE
