APAF1

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APAF1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1C15, 1CWW, 1CY5, 1Z6T, 2P1H, 2YGS, 3J2T, 3YGS, 4RHW, 3JBT

Identifikatori
AliasiAPAF1
Vanjski ID-jeviOMIM: 602233 MGI: 1306796 HomoloGene: 7626 GeneCards: APAF1
Lokacija gena (čovjek)
Hromosom 12 (čovjek)
Hrom.Hromosom 12 (čovjek)[1]
Hromosom 12 (čovjek)
Genomska lokacija za APAF1
Genomska lokacija za APAF1
Bend12q23.1Početak98,645,290 bp[1]
Kraj98,735,433 bp[1]
Lokacija gena (miš)
Hromosom 10 (miš)
Hrom.Hromosom 10 (miš)[2]
Hromosom 10 (miš)
Genomska lokacija za APAF1
Genomska lokacija za APAF1
Bend10 C2|10 45.47 cMPočetak90,989,311 bp[2]
Kraj91,082,770 bp[2]
Obrazac RNK ekspresije




Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija heat shock protein binding
ADP binding
GO:0001948, GO:0016582 protein binding
identical protein binding
ATP binding
nucleotide binding
cysteine-type endopeptidase activator activity involved in apoptotic process
Ćelijska komponenta citoplazma
citosol
Egzosom
Jedro
apoptosome
extracellular region
secretory granule lumen
ficolin-1-rich granule lumen
GO:0009327 protein-containing complex
Biološki proces cellular response to transforming growth factor beta stimulus
neuron apoptotic process
regulation of apoptotic process
Ćelijska diferencijacija
response to hypoxia
response to nutrient
response to G1 DNA damage checkpoint signaling
GO:0010260 Starenje
positive regulation of apoptotic signaling pathway
glial cell apoptotic process
nervous system development
multicellular organism development
cardiac muscle cell apoptotic process
intrinsic apoptotic signaling pathway
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
neural tube closure
brain development
positive regulation of apoptotic process
apoptotic signaling pathway
forebrain development
regulation of apoptotic DNA fragmentation
protein homooligomerization
activation of cysteine-type endopeptidase activity involved in apoptotic process
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c
GO:0097285 Apoptoza
neutrophil degranulation
negative regulation of G0 to G1 transition
Nefrogeneza
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001160
NM_013229
NM_181861
NM_181868
NM_181869

NM_001042558
NM_001282947
NM_009684

RefSeq (bjelančevina)

NP_001151
NP_037361
NP_863651
NP_863658
NP_863659

NP_001036023
NP_001269876
NP_033814

Lokacija (UCSC)Chr 12: 98.65 – 98.74 MbChr 10: 90.99 – 91.08 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Apoptotski faktor aktiviranja proteaze 1, također poznat kao APAF1, je ljudski homolog CED-4 gena C. elegans. To jest protein koji je kod ljudi kodiran genom APAF1 sa hromosoma 12.[5][6][7]

Funkcija[uredi | uredi izvor]

Protein je identifikovan u laboratoriji Xiaodonga Wanga kao aktivator kaspaze-3 u prisustvu citohroma C i dATP.<.[8] Ovaj gen kodira citoplazmatski protein koji čini jedno od centralnih čvorišta u regulatornoj mreži apoptoza. Ovaj protein sadrži (sa N terminala) domen za regrutaciju kaspaznog (CARD), ATPazni domen (NB-ARC), nekoliko kratkih spiralnih domena i zatim nekoliko kopija domena zvanog WD40 ponavljanje. Nakon vezivanja citohroma c i dATP, ovaj protein formira oligomerni apoptosom. Apoptosom veže i cijepa prokaspazni-9 protein, oslobađajući njegov zreli, aktivirani oblik. O preciznom mehanizmu za ovu reakciju se još uvijek raspravlja iako rad koji je objavio Guy Salvesen sugerira da apoptosom može inducirati dimerizaciju kaspaza-9 i naknadnu autokatalizu.[9] Aktivirana kaspaza-9 stimulira kaspaznu kaskadu koja dopušta ćeliju apoptozi.

Alternativna prerada rezultira u nekoliko varijanti transkripta koje kodiraju različite izoforme.[5]

Struktura[uredi | uredi izvor]

Dužina polipeptidnog lanca je 1.248 aminokiselina, a molekulska težina 141.840 Da.[5] APAF1 sadrži CARD domen sa motivom sa motivom grčkog ključa koji se sastoji od šest spirala, domena Rossmanovog nabora za vezivanje nukleotida, kratkog spiralnog motiva i domene krilate spirale.[10]

Struktura apoptosomskog kompleksa

Interakcije[uredi | uredi izvor]

Pokazalo se da je APAF1 u interakciji sa:

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000120868 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019979 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c "Entrez Gene: APAF1 apoptotic peptidase activating factor 1".
  6. ^ 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. S2CID 18105320.
  7. ^ 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. S2CID 10377371.
  8. ^ a b 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. S2CID 14321446.
  9. ^ 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.
  10. ^ 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. Bibcode:2005Natur.434..926R. doi:10.1038/nature03465. PMID 15829969. S2CID 4355459.
  11. ^ a b 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.
  12. ^ a b 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. Bibcode:1998PNAS...95.4386H. doi:10.1073/pnas.95.8.4386. PMC 22498. PMID 9539746.
  13. ^ a b 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.
  14. ^ a b 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.
  15. ^ 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. S2CID 20374981.

Vanjski linkovi[uredi | uredi izvor]

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]