APAF1

Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of C. elegans CED-4 gene.^[5][6][7]

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	OMIM: 602233; MGI: 1306796; HomoloGene: 7626; GeneCards: APAF1; OMA:APAF1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q23.1 Start 98,645,290 bp[1] End 98,735,433 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 C2|10 45.47 cM Start 90,989,311 bp[2] End 91,082,770 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte ventricular zone blood bone marrow cells ganglionic eminence epithelium of colon granulocyte Achilles tendon trabecular bone testicle Top expressed in granulocyte dermis migratory enteric neural crest cell ureter jejunum vas deferens otic vesicle stroma of bone marrow gastrula ileum More reference expression data BioGPS More reference expression data
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 extracellular region secretory granule lumen ficolin-1-rich granule lumen protein-containing complex 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 ageing 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 neutrophil degranulation negative regulation of G0 to G1 transition kidney development Sources:Amigo / QuickGO
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 NP_037361 NP_863651 NP_863658 NP_863659 NP_001036023 NP_001269876 NP_033814 Location (UCSC) Chr 12: 98.65 – 98.74 Mb Chr 10: 90.99 – 91.08 Mb PubMed search [3] [4]
Wikidata
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Function

The protein was identified in the laboratory of Xiaodong Wang as an activator of caspase-3 in the presence of cytochromeC and dATP.^[8] 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.^[9] Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis.^{[citation needed]}

Alternative splicing results in several transcript variants encoding different isoforms.^[5]

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.^[10]

Interactions

APAF1 has been shown to interact with:

• APIP,^[11]
• BCL2-like 1^[12][13]
• Caspase-9,^{[14][11][15][12][13]}
• HSPA4,^[16] and
• NLRP1.^[14]