Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Apoptotic protease-activating factor 1

Gene

Apaf1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulates progammed cell death; necessary for normal brain development. Participates with pro-caspase-9 (Apaf-3) in the cytochrome c-dependent activation of caspase-3, leading to apoptosis. This activation requires ATP (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei265 – 2651ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi154 – 1618ATPSequence analysis

GO - Molecular functioni

  • ADP binding Source: InterPro
  • ATP binding Source: UniProtKB-KW
  • cysteine-type endopeptidase activator activity involved in apoptotic process Source: Ensembl
  • heat shock protein binding Source: RGD
  • identical protein binding Source: RGD

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c Source: Ensembl
  • aging Source: RGD
  • brain development Source: RGD
  • cardiac muscle cell apoptotic process Source: RGD
  • cell differentiation Source: RGD
  • cellular response to transforming growth factor beta stimulus Source: RGD
  • forebrain development Source: Ensembl
  • glial cell apoptotic process Source: RGD
  • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: Ensembl
  • neural tube closure Source: Ensembl
  • neuron apoptotic process Source: Ensembl
  • positive regulation of apoptotic signaling pathway Source: Ensembl
  • protein homooligomerization Source: RGD
  • regulation of apoptotic DNA fragmentation Source: Ensembl
  • response to hypoxia Source: RGD
  • response to nutrient Source: RGD
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Calcium, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-111458. Formation of apoptosome.
R-RNO-111459. Activation of caspases through apoptosome-mediated cleavage.

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptotic protease-activating factor 1
Short name:
APAF-1
Gene namesi
Name:Apaf1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi620575. Apaf1.

Subcellular locationi

GO - Cellular componenti

  • apoptosome Source: RGD
  • extracellular exosome Source: Ensembl
  • nucleus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12491249Apoptotic protease-activating factor 1PRO_0000050846Add
BLAST

Proteomic databases

PRIDEiQ9EPV5.

Expressioni

Developmental stagei

Highly expressed in brain cortex in embryos (E17) and newborn rats up to day 7. Very low expression thereafter.1 Publication

Inductioni

By brain injury.1 Publication

Gene expression databases

ExpressionAtlasiQ9EPV5. baseline and differential.
GenevisibleiQ9EPV5. RN.

Interactioni

Subunit structurei

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. Interacts with UACA. Interacts with APIP (By similarity). Interacts (via CARD and NACHT domains) with NAIP/BIRC1 (via NACHT domain) (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
HIP1O002912EBI-6978501,EBI-473886From a different organism.

GO - Molecular functioni

  • heat shock protein binding Source: RGD
  • identical protein binding Source: RGD

Protein-protein interaction databases

IntActiQ9EPV5. 2 interactions.
MINTiMINT-3370020.

Structurei

3D structure databases

ProteinModelPortaliQ9EPV5.
SMRiQ9EPV5. Positions 1-586.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 9090CARDPROSITE-ProRule annotationAdd
BLAST
Domaini106 – 415310NB-ARCAdd
BLAST
Repeati613 – 65240WD 1-1Add
BLAST
Repeati655 – 69440WD 1-2Add
BLAST
Repeati697 – 73842WD 1-3Add
BLAST
Repeati741 – 78040WD 1-4Add
BLAST
Repeati796 – 83742WD 1-5Add
BLAST
Repeati838 – 87740WD 1-6Add
BLAST
Repeati880 – 91031WD 1-7Add
BLAST
Repeati922 – 95837WD 2-1Add
BLAST
Repeati959 – 99840WD 2-2Add
BLAST
Repeati1001 – 104040WD 2-3Add
BLAST
Repeati1042 – 108039WD 2-4Add
BLAST
Repeati1083 – 112240WD 2-5Add
BLAST
Repeati1125 – 116440WD 2-6Add
BLAST
Repeati1176 – 121338WD 2-7Add
BLAST
Repeati1214 – 124936WD 2-8Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni910 – 92112Interpropeller linkerBy similarityAdd
BLAST

Domaini

The CARD domain mediates interaction with APIP.
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 (By similarity).By similarity

Sequence similaritiesi

Contains 1 CARD domain.PROSITE-ProRule annotation
Contains 1 NB-ARC domain.Curated
Contains 15 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

GeneTreeiENSGT00810000125363.
HOVERGENiHBG018730.
InParanoidiQ9EPV5.
KOiK02084.
PhylomeDBiQ9EPV5.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
2.130.10.10. 2 hits.
3.40.50.300. 1 hit.
InterProiIPR017251. Apaf-1.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
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]
PfamiPF00619. CARD. 1 hit.
PF00931. NB-ARC. 1 hit.
PF00400. WD40. 9 hits.
[Graphical view]
PIRSFiPIRSF037646. Apop_pept_activating-1. 1 hit.
PRINTSiPR00320. GPROTEINBRPT.
SMARTiSM00320. WD40. 13 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF50978. SSF50978. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS00678. WD_REPEATS_1. 4 hits.
PS50082. WD_REPEATS_2. 9 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9EPV5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDAKARNCLL QHKEALEKDI KTSYIMDHMI SNGVLTVVEE EKVKSQATQY
60 70 80 90 100
QRAAALIKMI LNKDNYAYIS FYNALLHEGY KDLAGLLHSG LPLVSSSSGK
110 120 130 140 150
DTDGGNTSFV RTVLCEGGVP QRPVIFVTRK KLVSAIQQKL WKLNGEPGWV
160 170 180 190 200
TIYGMAGCGK SVLAAEAVRD HALLEGCFSG GVHWVSIGKQ DKSGLLMKLQ
210 220 230 240 250
NLCTRLGQEE SFSQRLPLNI EEAKDRLRVL MLRKHPRSLL ILDDVWDPWV
260 270 280 290 300
LKAFDNQCQI LLTTRDKSVT DSVMGPKYVI PVESGLGKEK GLEILSLFVN
310 320 330 340 350
MKKEDLPVEA HSIIKECKGS PLVVSLVGAL LRDFPNRWAY YLRQLQNKQF
360 370 380 390 400
KRIRKSSSYD YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL
410 420 430 440 450
CVLWDLETEE VEDILQEFVN KSLLFCNRNG KSFCYYLHDL QVDFLTEKNR
460 470 480 490 500
SQLQDLHRKM VTQFQRYHQP HTLSPGQEDC MYWYNFLAYH MASAGMHKEL
510 520 530 540 550
CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV CENFQEFLSL
560 570 580 590 600
NGHLLGRQPF PNIVQLGLCE PETSEVYQQA KLQAKQEVDT GRLYLEWINK
610 620 630 640 650
KTIKNLSRLV VRPHTDAVYH ACFSQDGQRI ASCGADKTLQ VFKAETGEKL
660 670 680 690 700
LDIKAHEDEV LCCAFSSDDS YIATCSVDKK VKIWDSGTGK LVHTYEEHSE
710 720 730 740 750
QVNCCHFTNK SNHLLLATGS NDSFLKLWDL NQKECRNTMF GHTNSVTHCR
760 770 780 790 800
FSPDDELLAS CSADGTLKLW DVRSANEKKS INVKRFFLSS EDPPEDVEVI
810 820 830 840 850
VKCCSWSADG DRIIVAAKNK VLLLDIHTSG LLTEIHTGHH STIQYCDFSP
860 870 880 890 900
YDHLAVIALS QYCVELWNID SRVKVADCRG HLSWVHGVMF SPDGSSFLTA
910 920 930 940 950
SDDQTIRVWE TRKVCKNSAI VLKQEIDVVF QENEMMVLAV DNIRGLQLIA
960 970 980 990 1000
GKTGQIDYLP EAQVSCCCLS PHLEYVAFGD EEGAIKIIEL PNNRVFSSGI
1010 1020 1030 1040 1050
GHKKAVRHIQ FTADGKTLIS SSEDSVIQVW NWQTEEYVFL QAHQETVKDF
1060 1070 1080 1090 1100
RLLRDSRLLS WSFDGTVKVW NVITGRIERD FTCHQGTVLS CAISSDATKF
1110 1120 1130 1140 1150
SSTSADKTAK IWSFELPSPL HELKGHNSCV RCSAFSLDGI LLATGDDNGE
1160 1170 1180 1190 1200
IRIWNVSDGQ LLHLCAPISI EEGTATHGGW VTDVCFSPDR KMLVSAGGYL
1210 1220 1230 1240
KWWNVVTGES SQTFYTNGTN LKKIHVSPDF RTYVTVDNLG ILYILQVLE
Length:1,249
Mass (Da):141,152
Last modified:March 1, 2001 - v1
Checksum:i7B4A8116FAD008E9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF320222 mRNA. Translation: AAG35067.1.
RefSeqiNP_076469.1. NM_023979.1.
UniGeneiRn.64522.

Genome annotation databases

EnsembliENSRNOT00000010869; ENSRNOP00000010869; ENSRNOG00000008022.
GeneIDi78963.
KEGGirno:78963.
UCSCiRGD:620575. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF320222 mRNA. Translation: AAG35067.1.
RefSeqiNP_076469.1. NM_023979.1.
UniGeneiRn.64522.

3D structure databases

ProteinModelPortaliQ9EPV5.
SMRiQ9EPV5. Positions 1-586.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9EPV5. 2 interactions.
MINTiMINT-3370020.

Proteomic databases

PRIDEiQ9EPV5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000010869; ENSRNOP00000010869; ENSRNOG00000008022.
GeneIDi78963.
KEGGirno:78963.
UCSCiRGD:620575. rat.

Organism-specific databases

CTDi317.
RGDi620575. Apaf1.

Phylogenomic databases

GeneTreeiENSGT00810000125363.
HOVERGENiHBG018730.
InParanoidiQ9EPV5.
KOiK02084.
PhylomeDBiQ9EPV5.

Enzyme and pathway databases

ReactomeiR-RNO-111458. Formation of apoptosome.
R-RNO-111459. Activation of caspases through apoptosome-mediated cleavage.

Miscellaneous databases

NextBioi614396.
PROiQ9EPV5.

Gene expression databases

ExpressionAtlasiQ9EPV5. baseline and differential.
GenevisibleiQ9EPV5. RN.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
2.130.10.10. 2 hits.
3.40.50.300. 1 hit.
InterProiIPR017251. Apaf-1.
IPR001315. CARD.
IPR011029. DEATH-like_dom.
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]
PfamiPF00619. CARD. 1 hit.
PF00931. NB-ARC. 1 hit.
PF00400. WD40. 9 hits.
[Graphical view]
PIRSFiPIRSF037646. Apop_pept_activating-1. 1 hit.
PRINTSiPR00320. GPROTEINBRPT.
SMARTiSM00320. WD40. 13 hits.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF50978. SSF50978. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS00678. WD_REPEATS_1. 4 hits.
PS50082. WD_REPEATS_2. 9 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Itoh T., Itoh A., Pleasure D.
    Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
  2. "Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury."
    Yakovlev A.G., Ota K., Wang G., Movsesyan V., Bao W.-L., Yoshihara K., Faden A.I.
    J. Neurosci. 21:7439-7446(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEVELOPMENTAL STAGE, INDUCTION BY BRAIN INJURY.

Entry informationi

Entry nameiAPAF_RAT
AccessioniPrimary (citable) accession number: Q9EPV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: March 1, 2001
Last modified: May 11, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.