APAF1

APAF1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1C15, 1CWW, 1CY5, 1Z6T, 2P1H, 2YGS, 3J2T, 3YGS, 4RHW, 3JBT
Identifiers
Aliases	APAF1, APAF-1, CED4, apoptotic peptidase activating factor 1
External IDs	MGI: 1306796 HomoloGene: 7626 GeneCards: APAF1
Gene ontology Molecular function • heat shock protein binding • ADP binding • protein binding • identical protein binding • ATP binding • nucleotide binding • cysteine-type endopeptidase activator activity involved in apoptotic process Cellular component • cytoplasm • cytosol • extracellular exosome • nucleus • apoptosome Biological process • cellular response to transforming growth factor beta stimulus • neuron apoptotic process • regulation of apoptotic process • cell differentiation • response to hypoxia • response to nutrient • response to G1 DNA damage checkpoint signaling • aging • 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 • apoptotic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	317	11783
Ensembl	ENSG00000120868	ENSMUSG00000019979
UniProt	O14727	O88879
RefSeq (mRNA)	NM_001160 NM_013229 NM_181861 NM_181868 NM_181869	NM_001042558 NM_001282947 NM_009684
RefSeq (protein)	NP_001151.1 NP_037361.1 NP_863651.1 NP_863658.1 NP_863659.1	NP_001036023.1 NP_033814.2
Location (UCSC)	Chr 12: 98.65 – 98.74 Mb	Chr 10: 90.99 – 91.08 Mb
PubMed search	[1]	[2]
Wikidata

Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.^[3][4][5]

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.^[6] Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.

Alternative splicing results in several transcript variants encoding different isoforms.^[3]

Structure

APAF1 contains a Greek key motif composed of six helices, a Rossman fold nucleotide binding domains, a short helical motif and a winged-helix domain.^[7] It contains a CARD domain with a

Interactions

APAF1 has been shown to interact with:

• APIP,^[8]
• BCL2-like 1^[9][10]
• Caspase-9,^{[11][8][12][9][10]}
• HSPA4,^[13] and
• NLRP1.^[11]

References

Further reading

PDB gallery
1c15: SOLUTION STRUCTURE OF APAF-1 CARD  1cww: SOLUTION STRUCTURE OF THE CASPASE RECRUITMENT DOMAIN (CARD) FROM APAF-1  1cy5: CRYSTAL STRUCTURE OF THE APAF-1 CARD  1z6t: Structure of the apoptotic protease-activating factor 1 bound to ADP  2p1h: Rapid Folding and Unfolding of Apaf-1 CARD  2ygs: CARD DOMAIN FROM APAF-1  3ygs: APAF-1 CARD IN COMPLEX WITH PRODOMAIN OF PROCASPASE-9