U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from GEO Profiles

    • Showing Current items.

    APAF1 apoptotic peptidase activating factor 1 [ Homo sapiens (human) ]

    Gene ID: 317, updated on 27-Nov-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    APAF1provided by HGNC
    Official Full Name
    apoptotic peptidase activating factor 1provided by HGNC
    Primary source
    HGNC:HGNC:576
    See related
    Ensembl:ENSG00000120868 MIM:602233; AllianceGenome:HGNC:576
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CED4; APAF-1
    Summary
    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]
    Expression
    Ubiquitous expression in bone marrow (RPKM 6.1), appendix (RPKM 5.1) and 25 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    See APAF1 in Genome Data Viewer
    Location:
    12q23.1
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (98645290..98735433)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (98618230..98708377)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (99039068..99129211)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak1907 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6848 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4754 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31387 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:99037284-99037911 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:99037912-99038538 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:99038539-99039166 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4756 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:99043141-99044340 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:99072005-99072576 Neighboring gene solute carrier family 25 member 3 Neighboring gene small nucleolar RNA, H/ACA box 53 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31421 Neighboring gene MPRA-validated peak1909 silencer Neighboring gene IKBKB interacting protein Neighboring gene ReSE screen-validated silencer GRCh37_chr12:99187754-99187963 Neighboring gene probable ribosome biogenesis protein RLP24 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31455 Neighboring gene ankyrin repeat and sterile alpha motif domain containing 1B Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:99250207-99250805 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:99250806-99251403 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr12:99254871-99255612 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:99288347-99288846 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr12:99303485-99304033 Neighboring gene Sharpr-MPRA regulatory region 15444 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_31475 Neighboring gene RNA, 5S ribosomal pseudogene 366

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    Go to the top of the pageHelp

    Related articles in PubMed

    1. Silencing of APAF-1 in B-CLL results in poor prognosis in the case of concomitant p53 mutation. Sturm I, et al. Int J Cancer, 2006 May 1. PMID 16331630
    2. Reduced Apaf-1 expression in human cutaneous melanomas. Dai DL, et al. Br J Cancer, 2004 Sep 13. PMID 15305193, Free PMC Article
    3. Loss of APAF-1 expression is associated with early recurrence in stage I, II, and III colorectal cancer. Ahn BK, et al. Langenbecks Arch Surg, 2016 Dec. PMID 27480415
    4. Aberrant localization of apoptosis protease activating factor-1 in lipid raft sub-domains of diffuse large B cell lymphomas. Hirpara JL, et al. Oncotarget, 2016 Dec 20. PMID 27863378, Free PMC Article
    5. Variants in Apaf-1 segregating with major depression promote apoptosome function. Harlan J, et al. Mol Psychiatry, 2006 Jan. PMID 16231040

    See all (221) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Exosomal circ_0037104 derived from Hu-MSCs inhibits cholangiocarcinoma progression by sponging miR-620 and targeting AFAP1.
      Title: Exosomal circ_0037104 derived from Hu-MSCs inhibits cholangiocarcinoma progression by sponging miR-620 and targeting AFAP1.
    2. Upregulation of APAF1 and CSF1R in Peripheral Blood Mononuclear Cells of Parkinson's Disease.
      Title: Upregulation of APAF1 and CSF1R in Peripheral Blood Mononuclear Cells of Parkinson's Disease.
    3. APAF1-Binding Long Noncoding RNA Promotes Tumor Growth and Multidrug Resistance in Gastric Cancer by Blocking Apoptosome Assembly.
      Title: APAF1-Binding Long Noncoding RNA Promotes Tumor Growth and Multidrug Resistance in Gastric Cancer by Blocking Apoptosome Assembly.
    4. Apoptotic protease activating factor-1 gene and MicroRNA-484: A possible interplay in relapsing remitting multiple sclerosis.
      Title: Apoptotic protease activating factor-1 gene and MicroRNA-484: A possible interplay in relapsing remitting multiple sclerosis.
    5. Exosomal microRNA rectangle93 rectangle3p secreted by bone marrow mesenchymal stem cells downregulates apoptotic peptidase activating factor 1 to promote wound healing.
      Title: Exosomal microRNA⁃93⁃3p secreted by bone marrow mesenchymal stem cells downregulates apoptotic peptidase activating factor 1 to promote wound healing.
    6. Contribution of Apaf-1 to the pathogenesis of cancer and neurodegenerative diseases.
      Title: Contribution of Apaf-1 to the pathogenesis of cancer and neurodegenerative diseases.
    7. Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition.
      Title: Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition.
    8. Apaf1 nanoLuc biosensors identified lentinan as a potent synergizer of cisplatin in targeting hepatocellular carcinoma cells.
      Title: Apaf1 nanoLuc biosensors identified lentinan as a potent synergizer of cisplatin in targeting hepatocellular carcinoma cells.
    9. Intracellular leucine-rich alpha-2-glycoprotein-1 competes with Apaf-1 for binding cytochrome c in protecting MCF-7 breast cancer cells from apoptosis.
      Title: Intracellular leucine-rich alpha-2-glycoprotein-1 competes with Apaf-1 for binding cytochrome c in protecting MCF-7 breast cancer cells from apoptosis.
    10. The Lumiptosome, an engineered luminescent form of the apoptosome can report cell death by using the same Apaf-1 dependent pathway.
      Title: The Lumiptosome, an engineered luminescent form of the apoptosome can report cell death by using the same Apaf-1 dependent pathway.
    Submit: New GeneRIF Correction See all GeneRIFs (127)

    Phenotypes

    Go to the top of the page Help

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

    Go to the top of the page Help

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env The mRNA expression levels for alpha-tubulin, TRADD, IFN-gamma R2, GAS1, MADD, NF-kappaB, I-kappa B, 14-3-3 protein, APaf1, PARP, IGF-1 receptor, RB1, Rb2/p130, ARC, and caspase 6 are upregulated in human neuronal cells after treatment with HIV-1 gp120 PubMed
    Tat tat HIV-1 Tat 47-59 peptide upregulates gene expression of apoptotic peptidase activating factor 1 (APAF1) in U-937 macrophages PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Clone Names

    • DKFZp781B1145

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ADP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables cysteine-type endopeptidase activator activity involved in apoptotic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables heat shock protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nucleotide binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in apoptotic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cardiac muscle cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to transforming growth factor beta stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in forebrain development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intrinsic apoptotic signaling pathway NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in intrinsic apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in kidney development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nervous system development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in neural tube closure IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of apoptotic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of apoptotic signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of apoptotic DNA fragmentation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of apoptotic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in response to G1 DNA damage checkpoint signaling TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to nutrient IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of apoptosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of apoptosome IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    part_of apoptosome TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in ficolin-1-rich granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in secretory granule lumen TAS
    Traceable Author Statement
    more info
    		  

    General protein information

    Go to the top of the page Help
    Preferred Names
    apoptotic protease-activating factor 1

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029094.1 RefSeqGene

      Range
      4991..95134
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001160.3 → NP_001151.1  apoptotic protease-activating factor 1 isoform b

      See identical proteins and their annotated locations for NP_001151.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site and lacks an exon in the coding region but maintains the reading frame, compared to variant 3. Variant 2 encodes isoform b, which is shorter than isoform c.
      Source sequence(s)
      AC011248, AC013283, AF013263
      Consensus CDS
      CCDS55863.1
      UniProtKB/TrEMBL
      A5YM44
      Related
      ENSP00000353059.2, ENST00000359972.6
      Conserved Domains (6) summary
      COG2319
      Location:698 → 1180
      WD40; WD40 repeat [General function prediction only]
      cd00200
      Location:596 → 859
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
      cd08323
      Location:7 → 92
      CARD_APAF1; Caspase activation and recruitment domain similar to that found in Apoptotic Protease-Activating Factor 1
      pfam00931
      Location:118 → 403
      NB-ARC; NB-ARC domain
      pfam13191
      Location:115 → 234
      AAA_16; AAA ATPase domain
      sd00039
      Location:649 → 686
      7WD40; WD40 repeat [structural motif]

    2. NM_013229.3 → NP_037361.1  apoptotic protease-activating factor 1 isoform a

      See identical proteins and their annotated locations for NP_037361.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) uses an alternate splice site in the coding region but maintains the reading frame, compared to variant 3. Variant 1 encodes isoform a, which is shorter than isoform c.
      Source sequence(s)
      AC011248, AC013283, AF013263, AF134397
      Consensus CDS
      CCDS55862.1
      UniProtKB/TrEMBL
      A7E2A2
      Related
      ENSP00000448449.1, ENST00000550527.5
      Conserved Domains (6) summary
      COG2319
      Location:698 → 1223
      WD40; WD40 repeat [General function prediction only]
      cd00200
      Location:596 → 899
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
      cd08323
      Location:7 → 92
      CARD_APAF1; Caspase activation and recruitment domain similar to that found in Apoptotic Protease-Activating Factor 1
      pfam00931
      Location:118 → 403
      NB-ARC; NB-ARC domain
      pfam13191
      Location:115 → 234
      AAA_16; AAA ATPase domain
      sd00039
      Location:649 → 686
      7WD40; WD40 repeat [structural motif]

    3. NM_181861.2 → NP_863651.1  apoptotic protease-activating factor 1 isoform c

      See identical proteins and their annotated locations for NP_863651.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), also known as Apaf-1L, encodes the longest isoform (c) of this protein.
      Source sequence(s)
      AC011248, AC013283, AF013263, AF149794
      Consensus CDS
      CCDS9069.1
      UniProtKB/Swiss-Prot
      B2RMX8, O14727, O43297, Q7Z438, Q9BXZ6, Q9UBZ5, Q9UGN8, Q9UGN9, Q9UGP0, Q9UJ58, Q9UJ59, Q9UJ60, Q9UJ61, Q9UJ62, Q9UJ63, Q9UJ64, Q9UJ65, Q9UJ66, Q9UJ67, Q9UNC9
      UniProtKB/TrEMBL
      A7E2A2
      Related
      ENSP00000448165.2, ENST00000551964.6
      Conserved Domains (5) summary
      cd00200
      Location:607 → 910
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
      cd08323
      Location:7 → 92
      CARD_APAF1; Caspase activation and recruitment domain similar to that found in Apoptotic Protease-Activating Factor 1
      sd00039
      Location:660 → 697
      7WD40; WD40 repeat [structural motif]
      pfam00931
      Location:129 → 374
      NB-ARC; NB-ARC domain
      pfam17908
      Location:453 → 587
      APAF1_C; APAF-1 helical domain

    4. NM_181868.2 → NP_863658.1  apoptotic protease-activating factor 1 isoform d

      See identical proteins and their annotated locations for NP_863658.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), also known as Apaf-1M, lacks an in-frame exon in the coding region, compared to variant 3. Variant 4 encodes isoform d, which is shorter than isoform c.
      Source sequence(s)
      AC011248, AC013283, AF013263, AJ243003
      Consensus CDS
      CCDS9070.1
      UniProtKB/TrEMBL
      A5YM44
      Related
      ENSP00000349862.1, ENST00000357310.5
      Conserved Domains (6) summary
      COG2319
      Location:709 → 1191
      WD40; WD40 repeat [General function prediction only]
      cd00200
      Location:607 → 870
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
      cd08323
      Location:7 → 92
      CARD_APAF1; Caspase activation and recruitment domain similar to that found in Apoptotic Protease-Activating Factor 1
      pfam00931
      Location:129 → 414
      NB-ARC; NB-ARC domain
      pfam13191
      Location:126 → 245
      AAA_16; AAA ATPase domain
      sd00039
      Location:660 → 697
      7WD40; WD40 repeat [structural motif]

    5. NM_181869.2 → NP_863659.1  apoptotic protease-activating factor 1 isoform e

      See identical proteins and their annotated locations for NP_863659.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5), also known as APAF-1-ALT, lacks several exons in the coding sequence, resulting in a frameshift and an early termination codon compared to variant 3. Variant 5 encodes isoform e, which is shorter and has a distinct C-terminus compared to isoform c.
      Source sequence(s)
      AB103079, AC011248, AC013283, AF013263
      Consensus CDS
      CCDS9071.1
      UniProtKB/Swiss-Prot
      O14727
      Related
      ENSP00000334558.1, ENST00000333991.5
      Conserved Domains (2) summary
      cd08323
      Location:7 → 92
      CARD_APAF1; Caspase activation and recruitment domain similar to that found in Apoptotic Protease-Activating Factor 1
      pfam13191
      Location:126 → 245
      AAA_16; AAA ATPase domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      98645290..98735433
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047428759.1 → XP_047284715.1  apoptotic protease-activating factor 1 isoform X2

    2. XM_047428760.1 → XP_047284716.1  apoptotic protease-activating factor 1 isoform X3

    3. XM_017019250.2 → XP_016874739.1  apoptotic protease-activating factor 1 isoform X4

    4. XM_047428758.1 → XP_047284714.1  apoptotic protease-activating factor 1 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      98618230..98708377
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054371909.1 → XP_054227884.1  apoptotic protease-activating factor 1 isoform X2

    2. XM_054371910.1 → XP_054227885.1  apoptotic protease-activating factor 1 isoform X3

    3. XM_054371911.1 → XP_054227886.1  apoptotic protease-activating factor 1 isoform X4

    4. XM_054371908.1 → XP_054227883.1  apoptotic protease-activating factor 1 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14727.2 GenPept UniProtKB/Swiss-Prot:O14727

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous