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

Summary

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
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Genomic context

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition.
Title: Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition.
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.
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.
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

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

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

A009H22 (e-PCR)
- UniSTS:47888

GDB:434012 (e-PCR)
- UniSTS:157204

GDB:313557 (e-PCR)
- UniSTS:8230

RH69665 (e-PCR)
- UniSTS:12332

PMC156606P1 (e-PCR)
- UniSTS:271408

D8S2279 (e-PCR)
- UniSTS:473907

PMC310794P40 (e-PCR)
- UniSTS:272731

G32545 (e-PCR)
- UniSTS:117129

SHGC-79800 (e-PCR)
- UniSTS:101101

L17791 (e-PCR)
- UniSTS:42740

SHGC-79820 (e-PCR)
- UniSTS:101109

SHGC-79823 (e-PCR)
- UniSTS:101111

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 more info	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

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Preferred Names: apoptotic protease-activating factor 1

NCBI Reference Sequences (RefSeq)

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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

NG_029094.1 RefSeqGene

Range

4991..95134

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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]
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]
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
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]
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

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

98645290..98735433

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047428759.1 → XP_047284715.1 apoptotic protease-activating factor 1 isoform X2
XM_047428760.1 → XP_047284716.1 apoptotic protease-activating factor 1 isoform X3
XM_017019250.2 → XP_016874739.1 apoptotic protease-activating factor 1 isoform X4
XM_047428758.1 → XP_047284714.1 apoptotic protease-activating factor 1 isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

98618230..98708377

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054371909.1 → XP_054227884.1 apoptotic protease-activating factor 1 isoform X2
XM_054371910.1 → XP_054227885.1 apoptotic protease-activating factor 1 isoform X3
XM_054371911.1 → XP_054227886.1 apoptotic protease-activating factor 1 isoform X4
XM_054371908.1 → XP_054227883.1 apoptotic protease-activating factor 1 isoform X1