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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Apoptotic protease activating factor 1''', also known as '''APAF1''', is a human homolog of ''C. elegans'' CED-4 gene.<ref name="entrez"/><ref name="pmid9267021">{{cite journal | vauthors = Zou H, Henzel WJ, Liu X, Lutschg A, Wang X | title = Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3 | journal = Cell | volume = 90 | issue = 3 | pages = 405–13 | date = Aug 1997 | pmid = 9267021 | doi = 10.1016/S0092-8674(00)80501-2 }}</ref><ref name="pmid10702682">{{cite journal | vauthors = Kim H, Jung YK, Kwon YK, Park SH | title = Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome band 12q23 by fluorescence in situ hybridization | journal = Cytogenetics and Cell Genetics | volume = 87 | issue = 3–4 | pages = 252–3 | year = 1999 | pmid = 10702682 | doi = 10.1159/000015436 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_APAF1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1c15.
| PDB = {{PDB2|1c15}}, {{PDB2|1cww}}, {{PDB2|1cy5}}, {{PDB2|1z6t}}, {{PDB2|2p1h}}, {{PDB2|2ygs}}, {{PDB2|3ygs}}
| Name = Apoptotic peptidase activating factor 1
| HGNCid = 576
| Symbol = APAF1
| AltSymbols =; CED4
| OMIM = 602233
| ECnumber = 
| Homologene = 7626
| MGIid = 1306796
| GeneAtlas_image1 = PBB_GE_APAF1_204859_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_APAF1_211553_x_at_tn.png
| GeneAtlas_image3 = PBB_GE_APAF1_211554_s_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0008656 |text = caspase activator activity}} {{GNF_GO|id=GO:0042802 |text = identical protein binding}}
| Component = {{GNF_GO|id=GO:0005622 |text = intracellular}} {{GNF_GO|id=GO:0005625 |text = soluble fraction}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005829 |text = cytosol}}
| Process = {{GNF_GO|id=GO:0001843 |text = neural tube closure}} {{GNF_GO|id=GO:0007275 |text = multicellular organismal development}} {{GNF_GO|id=GO:0007399 |text = nervous system development}} {{GNF_GO|id=GO:0008635 |text = caspase activation via cytochrome c}} {{GNF_GO|id=GO:0030900 |text = forebrain development}} {{GNF_GO|id=GO:0042981 |text = regulation of apoptosis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 317
    | Hs_Ensembl = ENSG00000120868
    | Hs_RefseqProtein = NP_001151
    | Hs_RefseqmRNA = NM_001160
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 97563209
    | Hs_GenLoc_end = 97653335
    | Hs_Uniprot = O14727
    | Mm_EntrezGene = 11783
    | Mm_Ensembl = ENSMUSG00000019979
    | Mm_RefseqmRNA = NM_001042558
    | Mm_RefseqProtein = NP_001036023
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 10
    | Mm_GenLoc_start = 90419117
    | Mm_GenLoc_end = 90512538
    | Mm_Uniprot = Q4VZG8
  }}
}}
'''Apoptotic peptidase activating factor 1''', also known as '''APAF1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: APAF1 apoptotic peptidase activating factor 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=317| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a cytoplasmic protein that forms one of the central hubs in the [[apoptosis]] regulatory network. This protein contains (from the N terminal) a caspase recruitment domain ([[CARD domain|CARD]]), an [[ATPase]] domain (NB-ARC), few short helical domains and then several copies of the [[WD40 repeat]] domain. Upon binding [[cytochrome c]] and [[deoxyadenosine triphosphate|dATP]], this protein forms an oligomeric [[apoptosome]]. The apoptosome binds and cleaves [[Procaspase-9]] protein, releasing its mature, activated form. The precise mechanism for this reaction is still debated though work published by [[Guy Salvesen]] suggests that the apoptosome may induce [[caspase-9]] dimerization and subsequent [[autocatalysis]].<ref name="pmid16630894">{{cite journal | vauthors = Pop C, Timmer J, Sperandio S, Salvesen GS | title = The apoptosome activates caspase-9 by dimerization | journal = Molecular Cell | volume = 22 | issue = 2 | pages = 269–75 | date = Apr 2006 | pmid = 16630894 | doi = 10.1016/j.molcel.2006.03.009 }}</ref> Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.
{{PBB_Summary
| section_title =
| summary_text = This gene encodes a cytoplasmic protein that initiates apoptosis. This protein contains several copies of the WD-40 domain, a caspase recruitment domain (CARD), and an ATPase domain (NB-ARC). Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results in several transcript variants encoding different isoforms.<ref name="entrez">{{cite web | title = Entrez Gene: APAF1 apoptotic peptidase activating factor 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=317| accessdate = }}</ref>
}}


==References==
[[Alternative splicing]] results in several transcript variants encoding different isoforms.<ref name="entrez">{{Cite web| title = Entrez Gene: APAF1 apoptotic peptidase activating factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=317| accessdate = }}</ref>
{{reflist|2}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Smith TF, Gaitatzes C, Saxena K, Neer EJ |title=The WD repeat: a common architecture for diverse functions. |journal=Trends Biochem. Sci. |volume=24 |issue= 5 |pages= 181-5 |year= 1999 |pmid= 10322433 |doi=  }}
*{{cite journal  | author=van Oirschot JT |title=Diva vaccines that reduce virus transmission. |journal=J. Biotechnol. |volume=73 |issue= 2-3 |pages= 195-205 |year= 1999 |pmid= 10486928 |doi=  }}
*{{cite journal  | author=Nakajima D, Okazaki N, Yamakawa H, ''et al.'' |title=Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. |journal=DNA Res. |volume=9 |issue= 3 |pages= 99-106 |year= 2003 |pmid= 12168954 |doi=  }}
*{{cite journal  | author=Campioni M, Santini D, Tonini G, ''et al.'' |title=Role of Apaf-1, a key regulator of apoptosis, in melanoma progression and chemoresistance. |journal=Exp. Dermatol. |volume=14 |issue= 11 |pages= 811-8 |year= 2006 |pmid= 16232302 |doi= 10.1111/j.1600-0625.2005.00360.x }}
*{{cite journal  | author=Zou H, Henzel WJ, Liu X, ''et al.'' |title=Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. |journal=Cell |volume=90 |issue= 3 |pages= 405-13 |year= 1997 |pmid= 9267021 |doi=  }}
*{{cite journal  | author=Li P, Nijhawan D, Budihardjo I, ''et al.'' |title=Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. |journal=Cell |volume=91 |issue= 4 |pages= 479-89 |year= 1997 |pmid= 9390557 |doi=  }}
*{{cite journal  | author=Ishikawa K, Nagase T, Nakajima D, ''et al.'' |title=Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro. |journal=DNA Res. |volume=4 |issue= 5 |pages= 307-13 |year= 1998 |pmid= 9455477 |doi=  }}
*{{cite journal  | author=Pan G, O'Rourke K, Dixit VM |title=Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex. |journal=J. Biol. Chem. |volume=273 |issue= 10 |pages= 5841-5 |year= 1998 |pmid= 9488720 |doi= }}
*{{cite journal  | author=Hu Y, Benedict MA, Wu D, ''et al.'' |title=Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 8 |pages= 4386-91 |year= 1998 |pmid= 9539746 |doi=  }}
*{{cite journal  | author=Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES |title=Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. |journal=Mol. Cell |volume=1 |issue= 7 |pages= 949-57 |year= 1998 |pmid= 9651578 |doi=  }}
*{{cite journal  | author=Cecconi F, Alvarez-Bolado G, Meyer BI, ''et al.'' |title=Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. |journal=Cell |volume=94 |issue= 6 |pages= 727-37 |year= 1998 |pmid= 9753320 |doi=  }}
*{{cite journal  | author=Inohara N, Gourley TS, Carrio R, ''et al.'' |title=Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death. |journal=J. Biol. Chem. |volume=273 |issue= 49 |pages= 32479-86 |year= 1999 |pmid= 9829980 |doi=  }}
*{{cite journal  | author=Hu Y, Ding L, Spencer DM, Núñez G |title=WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation. |journal=J. Biol. Chem. |volume=273 |issue= 50 |pages= 33489-94 |year= 1999 |pmid= 9837928 |doi=  }}
*{{cite journal  | author=Song Q, Kuang Y, Dixit VM, Vincenz C |title=Boo, a novel negative regulator of cell death, interacts with Apaf-1. |journal=EMBO J. |volume=18 |issue= 1 |pages= 167-78 |year= 1999 |pmid= 9878060 |doi= 10.1093/emboj/18.1.167 }}
*{{cite journal  | author=Slee EA, Harte MT, Kluck RM, ''et al.'' |title=Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. |journal=J. Cell Biol. |volume=144 |issue= 2 |pages= 281-92 |year= 1999 |pmid= 9922454 |doi=  }}
*{{cite journal  | author=Zou H, Li Y, Liu X, Wang X |title=An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. |journal=J. Biol. Chem. |volume=274 |issue= 17 |pages= 11549-56 |year= 1999 |pmid= 10206961 |doi=  }}
*{{cite journal  | author=Saleh A, Srinivasula SM, Acharya S, ''et al.'' |title=Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation. |journal=J. Biol. Chem. |volume=274 |issue= 25 |pages= 17941-5 |year= 1999 |pmid= 10364241 |doi=  }}
*{{cite journal  | author=Qin H, Srinivasula SM, Wu G, ''et al.'' |title=Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1. |journal=Nature |volume=399 |issue= 6736 |pages= 549-57 |year= 1999 |pmid= 10376594 |doi= 10.1038/21124 }}
*{{cite journal  | author=Drosopoulos NE, Walsh FS, Doherty P |title=A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade. |journal=Mol. Cell. Neurosci. |volume=13 |issue= 6 |pages= 441-9 |year= 1999 |pmid= 10383829 |doi= 10.1006/mcne.1999.0758 }}
}}
{{refend}}


{{protein-stub}}
== Structure ==
{{WikiDoc Sources}}
 
APAF1 contains a [[CARD domain]] with a [[Beta sheet#Greek key motif|Greek key]] motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.<ref name="pmid15829969">{{cite journal | vauthors = Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y | title = Structure of the apoptotic protease-activating factor 1 bound to ADP | journal = Nature | volume = 434 | issue = 7035 | pages = 926–33 | date = Apr 2005 | pmid = 15829969 | doi = 10.1038/nature03465 }}</ref>
 
== Interactions ==
 
APAF1 has been shown to [[Protein-protein interaction|interact]] with:
* [[APIP]],<ref name = pmid15262985/>
* [[BCL2-like 1 (gene)|BCL2-like 1]]<ref name = pmid9539746/><ref name = pmid9488720/>
* [[Caspase-9]],<ref name = pmid11113115/><ref name = pmid15262985>{{cite journal | vauthors = Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK | title = Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein | journal = The Journal of Biological Chemistry | volume = 279 | issue = 38 | pages = 39942–50 | date = Sep 2004 | pmid = 15262985 | doi = 10.1074/jbc.M405747200 }}</ref><ref name = pmid9390557>{{cite journal | vauthors = Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X | title = Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade | journal = Cell | volume = 91 | issue = 4 | pages = 479–89 | date = Nov 1997 | pmid = 9390557 | doi =  10.1016/s0092-8674(00)80434-1}}</ref><ref name = pmid9539746>{{cite journal | vauthors = Hu Y, Benedict MA, Wu D, Inohara N, Núñez G | title = Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 8 | pages = 4386–91 | date = Apr 1998 | pmid = 9539746 | pmc = 22498 | doi =  10.1073/pnas.95.8.4386}}</ref><ref name = pmid9488720>{{cite journal | vauthors = Pan G, O'Rourke K, Dixit VM | title = Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex | journal = The Journal of Biological Chemistry | volume = 273 | issue = 10 | pages = 5841–5 | date = Mar 1998 | pmid = 9488720 | doi =  10.1074/jbc.273.10.5841}}</ref>
* [[HSPA4]],<ref name = pmid10934467>{{cite journal | vauthors = Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES | title = Negative regulation of the Apaf-1 apoptosome by Hsp70 | journal = Nature Cell Biology | volume = 2 | issue = 8 | pages = 476–83 | date = Aug 2000 | pmid = 10934467 | doi = 10.1038/35019510 }}</ref> and
* [[NLRP1]].<ref name = pmid11113115>{{cite journal | vauthors = Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC | title = A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis | journal = The Journal of Biological Chemistry | volume = 276 | issue = 12 | pages = 9239–45 | date = Mar 2001 | pmid = 11113115 | doi = 10.1074/jbc.M006309200 }}</ref>
 
== References ==
{{Reflist|33em}}
{{-}}
 
==External links==
* {{UCSC gene info|APAF1}}
 
== Further reading ==
{{Refbegin|33em}}
* {{cite journal | vauthors = Smith TF, Gaitatzes C, Saxena K, Neer EJ | title = The WD repeat: a common architecture for diverse functions | journal = Trends in Biochemical Sciences | volume = 24 | issue = 5 | pages = 181–5 | date = May 1999 | pmid = 10322433 | doi = 10.1016/S0968-0004(99)01384-5 }}
* {{cite journal | vauthors = van Oirschot JT | title = Diva vaccines that reduce virus transmission | journal = Journal of Biotechnology | volume = 73 | issue = 2–3 | pages = 195–205 | date = Aug 1999 | pmid = 10486928 | doi = 10.1016/S0168-1656(99)00121-2 }}
* {{cite journal | vauthors = Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T | title = Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones | journal = DNA Research | volume = 9 | issue = 3 | pages = 99–106 | date = Jun 2002 | pmid = 12168954 | doi = 10.1093/dnares/9.3.99 }}
* {{cite journal | vauthors = Campioni M, Santini D, Tonini G, Murace R, Dragonetti E, Spugnini EP, Baldi A | title = Role of Apaf-1, a key regulator of apoptosis, in melanoma progression and chemoresistance | journal = Experimental Dermatology | volume = 14 | issue = 11 | pages = 811–8 | date = Nov 2005 | pmid = 16232302 | doi = 10.1111/j.1600-0625.2005.00360.x }}
* {{cite journal | vauthors = Zou H, Henzel WJ, Liu X, Lutschg A, Wang X | title = Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3 | journal = Cell | volume = 90 | issue = 3 | pages = 405–13 | date = Aug 1997 | pmid = 9267021 | doi = 10.1016/S0092-8674(00)80501-2 }}
* {{cite journal | vauthors = Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X | title = Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade | journal = Cell | volume = 91 | issue = 4 | pages = 479–89 | date = Nov 1997 | pmid = 9390557 | doi = 10.1016/S0092-8674(00)80434-1 }}
* {{cite journal | vauthors = Ishikawa K, Nagase T, Nakajima D, Seki N, Ohira M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Research | volume = 4 | issue = 5 | pages = 307–13 | date = Oct 1997 | pmid = 9455477 | doi = 10.1093/dnares/4.5.307 }}
* {{cite journal | vauthors = Pan G, O'Rourke K, Dixit VM | title = Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex | journal = The Journal of Biological Chemistry | volume = 273 | issue = 10 | pages = 5841–5 | date = Mar 1998 | pmid = 9488720 | doi = 10.1074/jbc.273.10.5841 }}
* {{cite journal | vauthors = Hu Y, Benedict MA, Wu D, Inohara N, Núñez G | title = Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 8 | pages = 4386–91 | date = Apr 1998 | pmid = 9539746 | pmc = 22498 | doi = 10.1073/pnas.95.8.4386 }}
* {{cite journal | vauthors = Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES | title = Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization | journal = Molecular Cell | volume = 1 | issue = 7 | pages = 949–57 | date = Jun 1998 | pmid = 9651578 | doi = 10.1016/S1097-2765(00)80095-7 }}
* {{cite journal | vauthors = Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P | title = Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development | journal = Cell | volume = 94 | issue = 6 | pages = 727–37 | date = Sep 1998 | pmid = 9753320 | doi = 10.1016/S0092-8674(00)81732-8 }}
* {{cite journal | vauthors = Inohara N, Gourley TS, Carrio R, Muñiz M, Merino J, Garcia I, Koseki T, Hu Y, Chen S, Núñez G | title = Diva, a Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death | journal = The Journal of Biological Chemistry | volume = 273 | issue = 49 | pages = 32479–86 | date = Dec 1998 | pmid = 9829980 | doi = 10.1074/jbc.273.49.32479 }}
* {{cite journal | vauthors = Hu Y, Ding L, Spencer DM, Núñez G | title = WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation | journal = The Journal of Biological Chemistry | volume = 273 | issue = 50 | pages = 33489–94 | date = Dec 1998 | pmid = 9837928 | doi = 10.1074/jbc.273.50.33489 }}
* {{cite journal | vauthors = Song Q, Kuang Y, Dixit VM, Vincenz C | title = Boo, a novel negative regulator of cell death, interacts with Apaf-1 | journal = The EMBO Journal | volume = 18 | issue = 1 | pages = 167–78 | date = Jan 1999 | pmid = 9878060 | pmc = 1171112 | doi = 10.1093/emboj/18.1.167 }}
* {{cite journal | vauthors = Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ | title = Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner | journal = The Journal of Cell Biology | volume = 144 | issue = 2 | pages = 281–92 | date = Jan 1999 | pmid = 9922454 | pmc = 2132895 | doi = 10.1083/jcb.144.2.281 }}
* {{cite journal | vauthors = Zou H, Li Y, Liu X, Wang X | title = An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 17 | pages = 11549–56 | date = Apr 1999 | pmid = 10206961 | doi = 10.1074/jbc.274.17.11549 }}
* {{cite journal | vauthors = Saleh A, Srinivasula SM, Acharya S, Fishel R, Alnemri ES | title = Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 25 | pages = 17941–5 | date = Jun 1999 | pmid = 10364241 | doi = 10.1074/jbc.274.25.17941 }}
* {{cite journal | vauthors = Qin H, Srinivasula SM, Wu G, Fernandes-Alnemri T, Alnemri ES, Shi Y | title = Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1 | journal = Nature | volume = 399 | issue = 6736 | pages = 549–57 | date = Jun 1999 | pmid = 10376594 | doi = 10.1038/21124 }}
* {{cite journal | vauthors = Drosopoulos NE, Walsh FS, Doherty P | title = A soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent signaling cascade | journal = Molecular and Cellular Neurosciences | volume = 13 | issue = 6 | pages = 441–9 | date = Jun 1999 | pmid = 10383829 | doi = 10.1006/mcne.1999.0758 }}
{{Refend}}
{{PDB Gallery|geneid=317}}
 
{{DEFAULTSORT:Apaf1}}
[[Category:Programmed cell death]]
[[Category:Apoptosis]]

Latest revision as of 12:07, 24 August 2018

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

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Ensembl

n/a

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UniProt

n/a

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.[1][2][3]

Function

This gene encodes a cytoplasmic protein that forms one of the central hubs in the apoptosis regulatory network. This protein contains (from the N terminal) a caspase recruitment domain (CARD), an ATPase domain (NB-ARC), few short helical domains and then several copies of the WD40 repeat domain. Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves Procaspase-9 protein, releasing its mature, activated form. The precise mechanism for this reaction is still debated though work published by Guy Salvesen suggests that the apoptosome may induce caspase-9 dimerization and subsequent autocatalysis.[4] Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.

Alternative splicing results in several transcript variants encoding different isoforms.[1]

Structure

APAF1 contains a CARD domain with a Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.[5]

Interactions

APAF1 has been shown to interact with:

References

  1. ↑ 1.0 1.1 "Entrez Gene: APAF1 apoptotic peptidase activating factor 1".
  2. ↑ Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (Aug 1997). "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3". Cell. 90 (3): 405–13. doi:10.1016/S0092-8674(00)80501-2. PMID 9267021.
  3. ↑ Kim H, Jung YK, Kwon YK, Park SH (1999). "Assignment of apoptotic protease activating factor-1 gene (APAF1) to human chromosome band 12q23 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 87 (3–4): 252–3. doi:10.1159/000015436. PMID 10702682.
  4. ↑ Pop C, Timmer J, Sperandio S, Salvesen GS (Apr 2006). "The apoptosome activates caspase-9 by dimerization". Molecular Cell. 22 (2): 269–75. doi:10.1016/j.molcel.2006.03.009. PMID 16630894.
  5. ↑ Riedl SJ, Li W, Chao Y, Schwarzenbacher R, Shi Y (Apr 2005). "Structure of the apoptotic protease-activating factor 1 bound to ADP". Nature. 434 (7035): 926–33. doi:10.1038/nature03465. PMID 15829969.
  6. ↑ 6.0 6.1 Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK (Sep 2004). "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein". The Journal of Biological Chemistry. 279 (38): 39942–50. doi:10.1074/jbc.M405747200. PMID 15262985.
  7. ↑ 7.0 7.1 Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of Sciences of the United States of America. 95 (8): 4386–91. doi:10.1073/pnas.95.8.4386. PMC 22498. PMID 9539746.
  8. ↑ 8.0 8.1 Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological Chemistry. 273 (10): 5841–5. doi:10.1074/jbc.273.10.5841. PMID 9488720.
  9. ↑ 9.0 9.1 Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S, Godzik A, Reed JC (Mar 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". The Journal of Biological Chemistry. 276 (12): 9239–45. doi:10.1074/jbc.M006309200. PMID 11113115.
  10. ↑ Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (Nov 1997). "Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade". Cell. 91 (4): 479–89. doi:10.1016/s0092-8674(00)80434-1. PMID 9390557.
  11. ↑ Saleh A, Srinivasula SM, Balkir L, Robbins PD, Alnemri ES (Aug 2000). "Negative regulation of the Apaf-1 apoptosome by Hsp70". Nature Cell Biology. 2 (8): 476–83. doi:10.1038/35019510. PMID 10934467.

External links

Further reading

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