| Tbio | Apoptotic protease-activating factor 1 |
Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.
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. [provided by RefSeq, Jul 2008]
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. [provided by RefSeq, Jul 2008]
Comments
Property Summary
| NCBI Gene PubMed Count | 143 |
| Grant Count | 351 |
| R01 Count | 280 |
| Funding | $26,213,583.2 |
| PubMed Score | 541.52 |
| PubTator Score | 341.43 |
| Disease | log2 FC | p |
|---|---|---|
| hepatocellular carcinoma | 1.100 | 0.000 |
| pancreatic cancer | 1.100 | 0.000 |
| osteosarcoma | -1.568 | 0.000 |
| group 3 medulloblastoma | 1.700 | 0.000 |
| adrenocortical carcinoma | 1.173 | 0.000 |
| intraductal papillary-mucinous adenoma (... | 1.300 | 0.006 |
| intraductal papillary-mucinous neoplasm ... | 1.800 | 0.008 |
| pancreatic carcinoma | 1.100 | 0.000 |
| AID | Type | Active / Inconclusive / Inactive | Description |
|---|---|---|---|
| 489030 | screening |
2355 / 0 / 329405 | uHTS Fluorescent assay for identification of inhibitors of Apaf-1 |
| 489031 | screening |
1041 / 0 / 330719 | uHTS Fluorescent assay for identification of activators of Apaf-1 |
| 492945 | summary |
0 / 0 / 0 | Summary assay for inhibitors of Apaf-1 |
| 492946 | summary |
0 / 0 / 0 | Summary assay for activators of Apaf-1 |
| 504614 | screening |
469 / 0 / 1375 | Single concentration confirmation of uHTS Fluorescent assay for identification of inhibitors of Apaf-1 |
| 504615 | screening |
1 / 0 / 1843 | uHTS Fluorescent Interference Counterscreen assay for validation of Inhibitors of Apaf-1 |
| 504616 | screening |
7 / 0 / 977 | uHTS Fluorescent Interference Counterscreen assay for validation of Activators of Apaf-1 |
| 504617 | screening |
45 / 0 / 939 | Single concentration confirmation of uHTS Fluorescent assay for identification of activators of Apaf-1 |
| 588524 | confirmatory |
444 / 0 / 32 | Dose response confirmation of uHTS hits for Apaf-1 in a Fluorescent assay |
| 588538 | confirmatory |
6 / 0 / 456 | Dose Response validation of Inhibitors of Apaf-1 using a Fluorescent Interference Counterscreen assay |
| More... |
| PMID | Text |
|---|---|
| 27141571 | Renal APAF1 expression is increased in diabetes and diabetic nephropathy. |
| 27021436 | miR21 is transferred from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. |
| 26851285 | HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. |
| 26743285 | the markers Ets-1 and APAF-1 relative to p53, Ki-67 and PTEN expression in colon adenomas/polyps, were investigated. |
| 26740177 | These results suggest that CED-4 forms a complex with ced-3 mRNA and delivers it to ribosomes for translation. |
| 26290316 | Inhibition of Caspase-9 restricted, while Apaf-1 promoted, Chlamydia pneumoniae infection in HEp-2, HeLa, and mouse epithelial fibroblast (MEF) cells. |
| 26183023 | NF-kappaB response element, located close to the p53RE#1, mediates APAF1 transcriptional repression by affecting interaction between KAISO and p53 |
| 26179084 | Different selenium concentrations had varying effects on BAK1 and APAF1 levels. APAF1 may play an important role in the pathogenesis of KBD |
| 26014357 | cytochrome c and the WD domains of Apaf-1 interact, with bifurcated salt bridges involved in apoptosome assembly |
| 25895636 | The auto-assembly of truncated Apaf1 molecules disappeared after several hours without any enzyme activation. |
| More... |
MDAKARNCLLQHREALEKDIKTSYIMDHMISDGFLTISEEEKVRNEPTQQQRAAMLIKMILKKDNDSYVS 1 - 70 FYNALLHEGYKDLAALLHDGIPVVSSSSGKDSVSGITSYVRTVLCEGGVPQRPVVFVTRKKLVNAIQQKL 71 - 140 SKLKGEPGWVTIHGMAGCGKSVLAAEAVRDHSLLEGCFPGGVHWVSVGKQDKSGLLMKLQNLCTRLDQDE 141 - 210 SFSQRLPLNIEEAKDRLRILMLRKHPRSLLILDDVWDSWVLKAFDSQCQILLTTRDKSVTDSVMGPKYVV 211 - 280 PVESSLGKEKGLEILSLFVNMKKADLPEQAHSIIKECKGSPLVVSLIGALLRDFPNRWEYYLKQLQNKQF 281 - 350 KRIRKSSSYDYEALDEAMSISVEMLREDIKDYYTDLSILQKDVKVPTKVLCILWDMETEEVEDILQEFVN 351 - 420 KSLLFCDRNGKSFRYYLHDLQVDFLTEKNCSQLQDLHKKIITQFQRYHQPHTLSPDQEDCMYWYNFLAYH 421 - 490 MASAKMHKELCALMFSLDWIKAKTELVGPAHLIHEFVEYRHILDEKDCAVSENFQEFLSLNGHLLGRQPF 491 - 560 PNIVQLGLCEPETSEVYQQAKLQAKQEVDNGMLYLEWINKKNITNLSRLVVRPHTDAVYHACFSEDGQRI 561 - 630 ASCGADKTLQVFKAETGEKLLEIKAHEDEVLCCAFSTDDRFIATCSVDKKVKIWNSMTGELVHTYDEHSE 631 - 700 QVNCCHFTNSSHHLLLATGSSDCFLKLWDLNQKECRNTMFGHTNSVNHCRFSPDDKLLASCSADGTLKLW 701 - 770 DATSANERKSINVKQFFLNLEDPQEDMEVIVKCCSWSADGARIMVAAKNKIFLFDIHTSGLLGEIHTGHH 771 - 840 STIQYCDFSPQNHLAVVALSQYCVELWNTDSRSKVADCRGHLSWVHGVMFSPDGSSFLTSSDDQTIRLWE 841 - 910 TKKVCKNSAVMLKQEVDVVFQENEVMVLAVDHIRRLQLINGRTGQIDYLTEAQVSCCCLSPHLQYIAFGD 911 - 980 ENGAIEILELVNNRIFQSRFQHKKTVWHIQFTADEKTLISSSDDAEIQVWNWQLDKCIFLRGHQETVKDF 981 - 1050 RLLKNSRLLSWSFDGTVKVWNIITGNKEKDFVCHQGTVLSCDISHDATKFSSTSADKTAKIWSFDLLLPL 1051 - 1120 HELRGHNGCVRCSAFSVDSTLLATGDDNGEIRIWNVSNGELLHLCAPLSEEGAATHGGWVTDLCFSPDGK 1121 - 1190 MLISAGGYIKWWNVVTGESSQTFYTNGTNLKKIHVSPDFKTYVTVDNLGILYILQTLE 1191 - 1248 //
| PMID | Year | Title |
|---|---|---|
| 27141571 | Immunohistochemical Aspects of Cell Death in Diabetic Nephropathy. | |
| 27021436 | 2016 | Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. |
| 26851285 | 2016 | Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway. |
| 26743285 | 2015 | Changes in immunoexpression of p53, Ki-67, Ets-1, APAF-1 and PTEN in serrated and conventional colon adenomas. |
| 26740177 | 2016 | CED-4 is an mRNA-binding protein that delivers ced-3 mRNA to ribosomes. |
| 26290316 | 2015 | An epistatic effect of apaf-1 and caspase-9 on chlamydial infection. |
| 26183023 | 2015 | Transcriptional activation of APAF1 by KAISO (ZBTB33) and p53 is attenuated by RelA/p65. |
| 26179084 | 2016 | The Roles of the Interaction of BCL2-Antagonist/Killer 1, Apoptotic Peptidase Activating Factor 1 and Selenium in the Pathogenesis of Kashin-Beck Disease. |
| 26014357 | 2015 | Modeling of interaction between cytochrome c and the WD domains of Apaf-1: bifurcated salt bridges underlying apoptosome assembly. |
| 25895636 | 2015 | Oscillation of apoptosome formation through assembly of truncated Apaf-1. |
| More... |
