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Reviewed, UniProtKB/Swiss-Prot O14727 (APAF_HUMAN)

Last modified July 22, 2008. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Apoptotic protease-activating factor 1
      Short name(s)=Apaf-1
Gene names
Name: APAF1
Synonyms: KIAA0413
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length1248 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.

Subunit structure

Monomer. Oligomerizes upon binding of cytochrome c and dATP. Oligomeric Apaf-1 and pro-caspase-9 bind to each other via their respective NH2-terminal CARD domains and consecutively mature caspase-9 is released from the complex. Pro-caspase-3 is recruited into the Apaf-1-pro-caspase-9 complex via interaction with pro-caspase-9. Interacts with APIP.

Subcellular location

Cytoplasm.

Tissue specificity

Ubiquitous. Highest levels of expression in adult spleen and peripheral blood leukocytes, and in fetal brain, kidney and lung. Isoform 1 is expressed in heart, kidney and liver.

Induction

By E2F and p53 in apoptotic neurons.

Domain

The CARD domain mediates interaction with APIP.

Sequence similarities

Contains 1 CARD domain.

Contains 1 NB-ARC domain.

Contains 13 WD repeats.

Sequence caution

AAK28401.1 sequence differs from that shown. Reason: Frameshift at position 108.

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Ontologies

Keywords

   Biological processApoptosis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainRepeat
WD repeat
   LigandATP-binding
Nucleotide-binding
   PTMPhosphoprotein
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processcaspase activation via cytochrome c Ref.1

Inferred from direct assay. Source: UniProtKB

nervous system development

Traceable author statement. Source: ProtInc

   Cellular componentcytosol Ref.1

Traceable author statement. Source: ProtInc

   Molecular functioncaspase activator activity Ref.1

Non-traceable author statement. Source: UniProtKB

nucleotide binding

Traceable author statement. Source: UniProtKB

protein binding Ref.1

Inferred from physical interaction. Source: UniProtKB

Complete GO annotation...

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

CASP9P552112EBI-446492,EBI-516799
CYCSP999992EBI-446492,EBI-446479
PPP1CAP621362EBI-446492,EBI-357253

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Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14727-1)

Also known as: Apaf-1XL;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O14727-2)

Also known as: Apaf-1L;

The sequence of this isoform differs from the canonical sequence as follows:
     99-109: Missing.
Isoform 3 (identifier: O14727-3)

Also known as: Apaf-1S;

The sequence of this isoform differs from the canonical sequence as follows:
     99-109: Missing.
     824-866: Missing.
Isoform 4 (identifier: O14727-4)

Also known as: Apaf-1M;

The sequence of this isoform differs from the canonical sequence as follows:
     824-866: Missing.
Isoform 5 (identifier: O14727-5)

Also known as: Apaf-1XS;

The sequence of this isoform differs from the canonical sequence as follows:
     575-575: E → ETLGFESKK
     824-866: Missing.
     1113-1154: Missing.
Isoform 6 (identifier: O14727-6)

Also known as: Apaf-1-ALT;

The sequence of this isoform differs from the canonical sequence as follows:
     319-338: GSPLVVSLIGALLRDFPNRW → VVERCHWGILTDLLHKWNQS
     339-1248: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 12481248Apoptotic protease-activating factor 1

Regions

Domain1 – 9090CARD
Domain104 – 415312NB-ARC
Repeat613 – 65240WD 1
Repeat655 – 69440WD 2
Repeat697 – 73842WD 3
Repeat741 – 78040WD 4
Repeat796 – 83641WD 5
Repeat838 – 87740WD 6
Repeat880 – 91940WD 7
Repeat959 – 99840WD 8
Repeat1001 – 104040WD 9
Repeat1042 – 108039WD 10
Repeat1083 – 112240WD 11
Repeat1125 – 116440WD 12
Repeat1175 – 121238WD 13
Nucleotide binding154 – 1618ATP Potential
Compositional bias95 – 984Poly-Ser

Amino acid modifications

Modified residue2041Phosphothreonine
Modified residue2381Phosphoserine
Modified residue2481Phosphoserine

Natural variations

Alternative sequence99 – 10911Missing in isoform 2 and isoform 3.
Alternative sequence319 – 33820GSPLV…FPNRW → VVERCHWGILTDLLHKWNQS in isoform 6.
Alternative sequence339 – 1248910Missing in isoform 6.
Alternative sequence5751E → ETLGFESKK in isoform 5.
Alternative sequence824 – 86643Missing in isoform 3, isoform 4 and isoform 5.
Alternative sequence1113 – 115442Missing in isoform 5.

Experimental info

Mutagenesis1601K → R: No association with APAF-1. No binding to pro-caspase-9
Mutagenesis3681M → L: Activation of pro-caspase-9 independent of cytochrome c. Increased ability to induce apoptosis
Sequence conflict1341N → S Ref.9
Sequence conflict1451G → C in CAB55587. Ref.2
Sequence conflict1611S → F in CAB55586. Ref.2
Sequence conflict3701I → T in CAB55581. Ref.2
Sequence conflict3831Y → H in CAB55586. Ref.2
Sequence conflict5441F → L in CAB55584. Ref.2
Sequence conflict5801A → T in CAB55580. Ref.2
Sequence conflict6081R → C in CAB55585. Ref.2
Sequence conflict6201H → R in CAB55587. Ref.2
Sequence conflict6391L → F in CAB55583. Ref.2
Sequence conflict7081T → A in CAB55579. Ref.2
Sequence conflict7421H → R in CAB55584. Ref.2
Sequence conflict7461V → A in CAB55586. Ref.2
Sequence conflict7571L → P in CAB56462. Ref.2
Sequence conflict7951E → G in CAB55581. Ref.2
Sequence conflict7981E → G in CAB55587. Ref.2
Sequence conflict8251D → A in CAB55585. Ref.2
Sequence conflict8711S → L in CAB55587. Ref.2
Sequence conflict8761A → T in CAB55581. Ref.2
Sequence conflict9491I → V in CAB55585. Ref.2
Sequence conflict10081H → R in CAB55582. Ref.2
Sequence conflict10561S → P in CAB55582. Ref.2
Sequence conflict12411L → I in BAA24843. Ref.6

Secondary structure

1 ............................................................................................. 1248
Helix Strand Turn

Details...