U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Gene ID: 317, updated on 7-Apr-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_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (98645290..98735433)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (98618230..98708377)
105.20220307 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. Apoptotic protease activating factor-1 gene and MicroRNA-484: A possible interplay in relapsing remitting multiple sclerosis. Mohamed DAW, et al. Mult Scler Relat Disord, 2022 Feb. PMID 35030371
  2. Apaf1 nanoLuc biosensors identified lentinan as a potent synergizer of cisplatin in targeting hepatocellular carcinoma cells. Wang Z, et al. Biochem Biophys Res Commun, 2021 Nov 5. PMID 34507064
  3. Loss of WD2 subdomain of Apaf-1 forms an apoptosome structure which blocks activation of caspase-3 and caspase-9. Noori AR, et al. Biochimie, 2021 Jan. PMID 33132160
  4. The Lumiptosome, an engineered luminescent form of the apoptosome can report cell death by using the same Apaf-1 dependent pathway. Hosseini ES, et al. J Cell Sci, 2020 May 27. PMID 32461338
  5. Apoptotic protease activating factor-1 negatively regulates Wnt signaling in hepatocellular carcinoma. Han R, et al. Kaohsiung J Med Sci, 2019 Aug. PMID 31094091

See all (219) 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)

Genotypes

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 activation of cysteine-type endopeptidase activity involved in apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c IDA
Inferred from Direct Assay
more info
 PubMed 
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 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_2023_10

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