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O88879 (APAF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Apoptotic protease-activating factor 1

Short name=APAF-1
Gene names
Name:Apaf1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1249 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

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 By similarity.

Subunit structure

Monomer. Oligomerizes to a heptameric ring, known as the apoptosome, 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 By similarity. Interacts with UACA. It may also interact with Bcl-XL. Interacts with APIP. Interacts (via CARD and NACHT domains) with NAIP/BIRC1 (via NACHT domain) By similarity. Ref.4 Ref.5 Ref.6

Subcellular location

Cytoplasm By similarity.

Tissue specificity

Highly expressed in lung and spleen, weakly in brain and kidney and not detectable in liver.

Developmental stage

High levels in embryonic brain and liver from E11.5 to E17.5 day.

Domain

The CARD domain mediates interaction with APIP. Ref.4

The monomeric form is autoinhibited in a closed conformation through a bound ADP at the nucleotide binding site. Exchange of ADP for ATP and binding of cytochrome c trigger a large conformational change where the first WD repeat region swings out, allowing the NB-ARC domain to rotate and expose the contact areas for oligomerization. Ref.4

Miscellaneous

Physiological concentrations of calcium ions negatively affect the assembly of apoptosome by inhibiting nucleotide exchange in the monomeric form By similarity.

Sequence similarities

Contains 1 CARD domain.

Contains 1 NB-ARC domain.

Contains 15 WD repeats.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainRepeat
WD repeat
   LigandATP-binding
Calcium
Nucleotide-binding
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 15703386PubMed 15776018. Source: MGI

activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from mutant phenotype PubMed 9753321. Source: MGI

defense response

Inferred from electronic annotation. Source: InterPro

forebrain development

Inferred from mutant phenotype PubMed 9216040. Source: MGI

multicellular organismal development

Inferred from mutant phenotype Ref.1. Source: MGI

neural tube closure

Inferred from mutant phenotype PubMed 11504943PubMed 9216040. Source: MGI

neuron apoptotic process

Inferred from genetic interaction PubMed 15703386. Source: MGI

positive regulation of apoptotic signaling pathway

Inferred from genetic interaction PubMed 16183742. Source: MGI

regulation of apoptotic DNA fragmentation

Inferred from genetic interaction PubMed 15703386. Source: MGI

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

cytosol

Inferred from direct assay Ref.5. Source: MGI

nucleus

Inferred from direct assay Ref.5. Source: MGI

   Molecular_functionADP binding

Inferred from electronic annotation. Source: InterPro

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cysteine-type endopeptidase activator activity involved in apoptotic process

Inferred from physical interaction PubMed 10830166. Source: MGI

identical protein binding

Inferred from physical interaction PubMed 15907471. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O88879-1)

Also known as: Apaf-1L;

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.
Note: Major isoform.
Isoform 2 (identifier: O88879-2)

The sequence of this isoform differs from the canonical sequence as follows:
     99-110: GKDTDGGITSFV → A

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12491249Apoptotic protease-activating factor 1
PRO_0000050845

Regions

Domain1 – 9090CARD
Domain106 – 415310NB-ARC
Repeat613 – 65240WD 1-1
Repeat655 – 69440WD 1-2
Repeat697 – 73842WD 1-3
Repeat741 – 78040WD 1-4
Repeat796 – 83742WD 1-5
Repeat838 – 87740WD 1-6
Repeat880 – 91031WD 1-7
Repeat922 – 95837WD 2-1
Repeat959 – 99840WD 2-2
Repeat1001 – 104040WD 2-3
Repeat1042 – 108039WD 2-4
Repeat1083 – 112240WD 2-5
Repeat1125 – 116440WD 2-6
Repeat1176 – 121338WD 2-7
Repeat1214 – 124936WD 2-8
Nucleotide binding154 – 1618ATP Potential
Region910 – 92112Interpropeller linker

Sites

Binding site2651ATP

Natural variations

Alternative sequence99 – 11012GKDTD…ITSFV → A in isoform 2.
VSP_006763

Experimental info

Mutagenesis2651R → S: No stimulation of CASP9 activity. Ref.6
Sequence conflict2091E → D in AAC62458. Ref.1
Sequence conflict5921R → P in AAC62458. Ref.1
Sequence conflict7101K → S in AAC62458. Ref.1

Secondary structure

........................................................................................................................................................................................................ 1249
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Apaf-1L) [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: AA639E407F9ABC24

FASTA1,249141,003
        10         20         30         40         50         60 
MDAKARNCLL QHREALEKDI KTSYIMDHMI SNGVLSVIEE EKVKSQATQY QRAAALIKMI 

        70         80         90        100        110        120 
LNKDNCAYIS FYNALLHEGY KDLAALLQSG LPLVSSSSGK DTDGGITSFV RTVLCEGGVP 

       130        140        150        160        170        180 
QRPVIFVTRK KLVHAIQQKL WKLNGEPGWV TIYGMAGCGK SVLAAEAVRD HSLLEGCFSG 

       190        200        210        220        230        240 
GVHWVSIGKQ DKSGLLMKLQ NLCMRLDQEE SFSQRLPLNI EEAKDRLRVL MLRKHPRSLL 

       250        260        270        280        290        300 
ILDDVWDPWV LKAFDNQCQI LLTTRDKSVT DSVMGPKHVV PVESGLGREK GLEILSLFVN 

       310        320        330        340        350        360 
MKKEDLPAEA HSIIKECKGS PLVVSLIGAL LRDFPNRWAY YLRQLQNKQF KRIRKSSSYD 

       370        380        390        400        410        420 
YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL CVLWDLETEE VEDILQEFVN 

       430        440        450        460        470        480 
KSLLFCNRNG KSFCYYLHDL QVDFLTEKNR SQLQDLHRKM VTQFQRYYQP HTLSPDQEDC 

       490        500        510        520        530        540 
MYWYNFLAYH MASANMHKEL CALMFSLDWI KAKTELVGPA HLIHEFVAYR HILDEKDCAV 

       550        560        570        580        590        600 
CENFQEFLSL NGHLLGRQPF PNIVQLGLCE PETSEVYRQA KLQAKQEGDT GRLYLEWINK 

       610        620        630        640        650        660 
KTIKNLSRLV VRPHTDAVYH ACFSQDGQRI ASCGADKTLQ VFKAETGEKL LDIKAHEDEV 

       670        680        690        700        710        720 
LCCAFSSDDS YIATCSADKK VKIWDSATGK LVHTYDEHSE QVNCCHFTNK SNHLLLATGS 

       730        740        750        760        770        780 
NDFFLKLWDL NQKECRNTMF GHTNSVNHCR FSPDDELLAS CSADGTLRLW DVRSANERKS 

       790        800        810        820        830        840 
INVKRFFLSS EDPPEDVEVI VKCCSWSADG DKIIVAAKNK VLLFDIHTSG LLAEIHTGHH 

       850        860        870        880        890        900 
STIQYCDFSP YDHLAVIALS QYCVELWNID SRLKVADCRG HLSWVHGVMF SPDGSSFLTA 

       910        920        930        940        950        960 
SDDQTIRVWE TKKVCKNSAI VLKQEIDVVF QENETMVLAV DNIRGLQLIA GKTGQIDYLP 

       970        980        990       1000       1010       1020 
EAQVSCCCLS PHLEYVAFGD EDGAIKIIEL PNNRVFSSGV GHKKAVRHIQ FTADGKTLIS 

      1030       1040       1050       1060       1070       1080 
SSEDSVIQVW NWQTGDYVFL QAHQETVKDF RLLQDSRLLS WSFDGTVKVW NVITGRIERD 

      1090       1100       1110       1120       1130       1140 
FTCHQGTVLS CAISSDATKF SSTSADKTAK IWSFDLLSPL HELKGHNGCV RCSAFSLDGI 

      1150       1160       1170       1180       1190       1200 
LLATGDDNGE IRIWNVSDGQ LLHSCAPISV EEGTATHGGW VTDVCFSPDS KTLVSAGGYL 

      1210       1220       1230       1240 
KWWNVATGDS SQTFYTNGTN LKKIHVSPDF RTYVTVDNLG ILYILQVLE 

« Hide

Isoform 2 [UniParc].

Checksum: CC9BE41A95B20ADF
Show »

FASTA1,238139,896

References

« Hide 'large scale' references
[1]"Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development."
Cecconi F., Alvarez-Bolado G., Meyer B.I., Roth K.A., Gruss P.
Cell 94:727-737(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: Swiss Webster / NIH.
Tissue: Embryo.
[2]"A comparison of the expression and properties of Apaf-1 and Apaf-1L."
Walke D.W., Morgan J.I.
Brain Res. 886:73-81(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Spleen.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein."
Cho D.-H., Hong Y.-M., Lee H.-J., Woo H.-N., Pyo J.-O., Mak T.W., Jung Y.-K.
J. Biol. Chem. 279:39942-39950(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APIP, DOMAIN.
[5]"Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis."
Sakai T., Liu L., Teng X., Mukai-Sakai R., Shimada H., Kaji R., Mitani T., Matsumoto M., Toida K., Ishimura K., Shishido Y., Mak T.W., Fukui K.
J. Biol. Chem. 279:41131-41140(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UACA.
[6]"Crystal structure of full-length Apaf-1: how the death signal is relayed in the mitochondrial pathway of apoptosis."
Reubold T.F., Wohlgemuth S., Eschenburg S.
Structure 19:1074-1083(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS), WD REPEATS, SUBUNIT, MUTAGENESIS OF ARG-265.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF064071 mRNA. Translation: AAC62458.1.
BC131683 mRNA. Translation: AAI31684.1.
BC131684 mRNA. Translation: AAI31685.1.
RefSeqNP_001036023.1. NM_001042558.1.
NP_033814.2. NM_009684.2.
UniGeneMm.220289.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3SFZX-ray3.00A1-1249[»]
3SHFX-ray3.55A1-1249[»]
ProteinModelPortalO88879.
SMRO88879. Positions 1-586.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198139. 1 interaction.
IntActO88879. 1 interaction.
MINTMINT-104429.

PTM databases

PhosphoSiteO88879.

Proteomic databases

PaxDbO88879.
PRIDEO88879.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020157; ENSMUSP00000020157; ENSMUSG00000019979. [O88879-1]
ENSMUST00000159110; ENSMUSP00000125291; ENSMUSG00000019979. [O88879-1]
GeneID11783.
KEGGmmu:11783.
UCSCuc007gtg.1. mouse. [O88879-1]

Organism-specific databases

CTD317.
MGIMGI:1306796. Apaf1.

Phylogenomic databases

eggNOGCOG2319.
GeneTreeENSGT00750000117677.
HOVERGENHBG018730.
InParanoidA2RRK8.
KOK02084.
OMAKVCKNSA.
OrthoDBEOG7XWPMS.
PhylomeDBO88879.
TreeFamTF323866.

Gene expression databases

ArrayExpressO88879.
BgeeO88879.
CleanExMM_APAF1.
GenevestigatorO88879.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
2.130.10.10. 2 hits.
3.40.50.300. 1 hit.
InterProIPR017251. Apoptotic_pept-activating_1.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
IPR000767. Disease_R.
IPR020472. G-protein_beta_WD-40_rep.
IPR002182. NB-ARC.
IPR027417. P-loop_NTPase.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF00619. CARD. 1 hit.
PF00931. NB-ARC. 1 hit.
PF00400. WD40. 10 hits.
[Graphical view]
PIRSFPIRSF037646. Apop_pept_activating-1. 1 hit.
PRINTSPR00364. DISEASERSIST.
PR00320. GPROTEINBRPT.
SMARTSM00320. WD40. 13 hits.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF50978. SSF50978. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEPS50209. CARD. 1 hit.
PS00678. WD_REPEATS_1. 4 hits.
PS50082. WD_REPEATS_2. 9 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAPAF1. mouse.
NextBio279591.
PROO88879.
SOURCESearch...

Entry information

Entry nameAPAF_MOUSE
AccessionPrimary (citable) accession number: O88879
Secondary accession number(s): A2RRK8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 122 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot