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O14727

- APAF_HUMAN

UniProt

O14727 - APAF_HUMAN

Protein

Apoptotic protease-activating factor 1

Gene

APAF1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 170 (01 Oct 2014)
      Sequence version 2 (23 Jan 2002)
      Previous versions | rss
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    Functioni

    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.2 Publications

    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

    1. ADP binding Source: InterPro
    2. ATP binding Source: UniProtKB-KW
    3. cysteine-type endopeptidase activator activity involved in apoptotic process Source: UniProtKB
    4. nucleotide binding Source: UniProtKB
    5. protein binding Source: UniProtKB

    GO - Biological processi

    1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    2. activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c Source: UniProtKB
    3. apoptotic DNA fragmentation Source: Ensembl
    4. apoptotic process Source: Reactome
    5. defense response Source: InterPro
    6. forebrain development Source: Ensembl
    7. intrinsic apoptotic signaling pathway Source: UniProtKB
    8. nervous system development Source: ProtInc
    9. neural tube closure Source: Ensembl
    10. neuron apoptotic process Source: Ensembl
    11. positive regulation of apoptotic process Source: UniProtKB
    12. positive regulation of apoptotic signaling pathway Source: Ensembl
    13. regulation of apoptotic process Source: UniProtKB
    14. response to G1 DNA damage checkpoint signaling Source: UniProtKB

    Keywords - Biological processi

    Apoptosis

    Keywords - Ligandi

    ATP-binding, Calcium, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_607. Activation of caspases through apoptosome-mediated cleavage.
    REACT_89. Formation of apoptosome.
    SABIO-RKO14727.
    SignaLinkiO14727.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Apoptotic protease-activating factor 1
    Short name:
    APAF-1
    Gene namesi
    Name:APAF1
    Synonyms:KIAA0413
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:576. APAF1.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. apoptosome Source: UniProtKB
    2. cytosol Source: Reactome
    3. extracellular vesicular exosome Source: UniProt
    4. nucleus Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi160 – 1601K → R: No association with APAF-1. No binding to pro-caspase-9. 1 Publication
    Mutagenesisi368 – 3681M → L: Activation of pro-caspase-9 independent of cytochrome c. Increased ability to induce apoptosis. 1 Publication

    Organism-specific databases

    PharmGKBiPA24868.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 12481248Apoptotic protease-activating factor 1PRO_0000050844Add
    BLAST

    Proteomic databases

    MaxQBiO14727.
    PaxDbiO14727.
    PRIDEiO14727.

    PTM databases

    PhosphoSiteiO14727.

    Miscellaneous databases

    PMAP-CutDBO14727.

    Expressioni

    Tissue specificityi

    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.

    Inductioni

    By E2F and p53/TP53 in apoptotic neurons.1 Publication

    Gene expression databases

    ArrayExpressiO14727.
    BgeeiO14727.
    GenevestigatoriO14727.

    Organism-specific databases

    HPAiHPA031373.

    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 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. Interacts (via CARD and NACHT domains) with NAIP/BIRC1 (via NACHT domain).3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CASP9P5521118EBI-446492,EBI-516799
    CYCSP999996EBI-446492,EBI-446479
    PPP1CAP621362EBI-446492,EBI-357253
    YWHAEP622582EBI-446492,EBI-356498

    Protein-protein interaction databases

    BioGridi106814. 16 interactions.
    DIPiDIP-27624N.
    IntActiO14727. 7 interactions.
    MINTiMINT-96751.

    Structurei

    Secondary structure

    1
    1248
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 119
    Helixi13 – 197
    Helixi22 – 3211
    Helixi37 – 448
    Beta strandi46 – 483
    Helixi49 – 6113
    Helixi65 – 7713
    Helixi81 – 877
    Helixi88 – 903
    Helixi108 – 1169
    Helixi130 – 14011
    Beta strandi148 – 1536
    Helixi160 – 1689
    Helixi171 – 1777
    Beta strandi182 – 1898
    Helixi192 – 20615
    Helixi220 – 23314
    Beta strandi239 – 2457
    Helixi248 – 2525
    Beta strandi259 – 2657
    Helixi267 – 2704
    Beta strandi277 – 2815
    Helixi288 – 29912
    Helixi303 – 3053
    Helixi309 – 3168
    Turni317 – 3193
    Helixi321 – 33313
    Helixi338 – 3469
    Helixi362 – 37312
    Turni377 – 3793
    Helixi380 – 3856
    Helixi386 – 3883
    Helixi397 – 4048
    Helixi408 – 42013
    Beta strandi423 – 4297
    Beta strandi432 – 4365
    Helixi439 – 44810
    Helixi450 – 4523
    Helixi453 – 46412
    Turni465 – 4673
    Helixi470 – 4723
    Helixi480 – 49314
    Helixi497 – 5048
    Helixi507 – 51711
    Helixi520 – 5289
    Helixi530 – 5323
    Helixi535 – 55016
    Turni551 – 5566
    Helixi563 – 5675
    Helixi575 – 58511

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1C15NMR-A1-97[»]
    1CWWNMR-A1-97[»]
    1CY5X-ray1.30A1-97[»]
    1Z6TX-ray2.21A/B/C/D1-591[»]
    2P1HX-ray1.59A1-92[»]
    2YGSX-ray1.60A1-92[»]
    3J2Telectron microscopy9.5A/B/C/D/E/F/G1-1248[»]
    3YGSX-ray2.50C1-95[»]
    ProteinModelPortaliO14727.
    SMRiO14727. Positions 1-1248.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO14727.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 9090CARDPROSITE-ProRule annotationAdd
    BLAST
    Domaini104 – 415312NB-ARCAdd
    BLAST
    Repeati613 – 65240WD 1-1Add
    BLAST
    Repeati655 – 69440WD 1-2Add
    BLAST
    Repeati697 – 73842WD 1-3Add
    BLAST
    Repeati741 – 78040WD 1-4Add
    BLAST
    Repeati796 – 83641WD 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
    Repeati1175 – 121238WD 2-7Add
    BLAST
    Repeati1213 – 124836WD 2-8Add
    BLAST

    Region

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

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi95 – 984Poly-Ser

    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

    eggNOGiCOG2319.
    HOVERGENiHBG018730.
    InParanoidiO14727.
    KOiK02084.
    OMAiETKKVCK.
    OrthoDBiEOG7XWPMS.
    PhylomeDBiO14727.
    TreeFamiTF323866.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    2.130.10.10. 2 hits.
    3.40.50.300. 1 hit.
    InterProiIPR017251. 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]
    PfamiPF00619. CARD. 1 hit.
    PF00931. NB-ARC. 1 hit.
    PF00400. WD40. 10 hits.
    [Graphical view]
    PIRSFiPIRSF037646. Apop_pept_activating-1. 1 hit.
    PRINTSiPR00364. DISEASERSIST.
    PR00320. 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]

    Sequences (6)i

    Sequence statusi: Complete.

    This entry describes 6 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O14727-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ     50
    QRAAMLIKMI LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSGK 100
    DSVSGITSYV RTVLCEGGVP QRPVVFVTRK KLVNAIQQKL SKLKGEPGWV 150
    TIHGMAGCGK SVLAAEAVRD HSLLEGCFPG GVHWVSVGKQ DKSGLLMKLQ 200
    NLCTRLDQDE SFSQRLPLNI EEAKDRLRIL MLRKHPRSLL ILDDVWDSWV 250
    LKAFDSQCQI LLTTRDKSVT DSVMGPKYVV PVESSLGKEK GLEILSLFVN 300
    MKKADLPEQA HSIIKECKGS PLVVSLIGAL LRDFPNRWEY YLKQLQNKQF 350
    KRIRKSSSYD YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL 400
    CILWDMETEE VEDILQEFVN KSLLFCDRNG KSFRYYLHDL QVDFLTEKNC 450
    SQLQDLHKKI ITQFQRYHQP HTLSPDQEDC MYWYNFLAYH MASAKMHKEL 500
    CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV SENFQEFLSL 550
    NGHLLGRQPF PNIVQLGLCE PETSEVYQQA KLQAKQEVDN GMLYLEWINK 600
    KNITNLSRLV VRPHTDAVYH ACFSEDGQRI ASCGADKTLQ VFKAETGEKL 650
    LEIKAHEDEV LCCAFSTDDR FIATCSVDKK VKIWNSMTGE LVHTYDEHSE 700
    QVNCCHFTNS SHHLLLATGS SDCFLKLWDL NQKECRNTMF GHTNSVNHCR 750
    FSPDDKLLAS CSADGTLKLW DATSANERKS INVKQFFLNL EDPQEDMEVI 800
    VKCCSWSADG ARIMVAAKNK IFLFDIHTSG LLGEIHTGHH STIQYCDFSP 850
    QNHLAVVALS QYCVELWNTD SRSKVADCRG HLSWVHGVMF SPDGSSFLTS 900
    SDDQTIRLWE TKKVCKNSAV MLKQEVDVVF QENEVMVLAV DHIRRLQLIN 950
    GRTGQIDYLT EAQVSCCCLS PHLQYIAFGD ENGAIEILEL VNNRIFQSRF 1000
    QHKKTVWHIQ FTADEKTLIS SSDDAEIQVW NWQLDKCIFL RGHQETVKDF 1050
    RLLKNSRLLS WSFDGTVKVW NIITGNKEKD FVCHQGTVLS CDISHDATKF 1100
    SSTSADKTAK IWSFDLLLPL HELRGHNGCV RCSAFSVDST LLATGDDNGE 1150
    IRIWNVSNGE LLHLCAPLSE EGAATHGGWV TDLCFSPDGK MLISAGGYIK 1200
    WWNVVTGESS QTFYTNGTNL KKIHVSPDFK TYVTVDNLGI LYILQTLE 1248
    Length:1,248
    Mass (Da):141,840
    Last modified:January 23, 2002 - v2
    Checksum:i0750D05817AC9B3B
    GO
    Isoform 2 (identifier: O14727-2) [UniParc]FASTAAdd to Basket

    Also known as: Apaf-1L

    The sequence of this isoform differs from the canonical sequence as follows:
         99-109: Missing.

    Show »
    Length:1,237
    Mass (Da):140,745
    Checksum:i0D3EF9AB2A66FFF5
    GO
    Isoform 3 (identifier: O14727-3) [UniParc]FASTAAdd to Basket

    Also known as: Apaf-1S

    The sequence of this isoform differs from the canonical sequence as follows:
         99-109: Missing.
         824-866: Missing.

    Show »
    Length:1,194
    Mass (Da):135,980
    Checksum:iA675EA102DDAAFB7
    GO
    Isoform 4 (identifier: O14727-4) [UniParc]FASTAAdd to Basket

    Also known as: Apaf-1M

    The sequence of this isoform differs from the canonical sequence as follows:
         824-866: Missing.

    Show »
    Length:1,205
    Mass (Da):137,076
    Checksum:iDA57B4E35E79D73A
    GO
    Isoform 5 (identifier: O14727-5) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:1,171
    Mass (Da):133,356
    Checksum:iCA9B14019EAB35BF
    GO
    Isoform 6 (identifier: O14727-6) [UniParc]FASTAAdd to Basket

    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.

    Show »
    Length:338
    Mass (Da):37,976
    Checksum:i29D933A65707ED92
    GO

    Sequence cautioni

    The sequence AAK28401.1 differs from that shown. Reason: Frameshift at position 108.
    The sequence BAA24843.2 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti134 – 1341N → S1 PublicationCurated
    Sequence conflicti145 – 1451G → C in CAB55587. (PubMed:10441496)Curated
    Sequence conflicti161 – 1611S → F in CAB55586. (PubMed:10441496)Curated
    Sequence conflicti370 – 3701I → T in CAB55581. (PubMed:10441496)Curated
    Sequence conflicti383 – 3831Y → H in CAB55586. (PubMed:10441496)Curated
    Sequence conflicti544 – 5441F → L in CAB55584. (PubMed:10441496)Curated
    Sequence conflicti580 – 5801A → T in CAB55580. (PubMed:10441496)Curated
    Sequence conflicti608 – 6081R → C in CAB55585. (PubMed:10441496)Curated
    Sequence conflicti620 – 6201H → R in CAB55587. (PubMed:10441496)Curated
    Sequence conflicti639 – 6391L → F in CAB55583. (PubMed:10441496)Curated
    Sequence conflicti708 – 7081T → A in CAB55579. (PubMed:10441496)Curated
    Sequence conflicti742 – 7421H → R in CAB55584. (PubMed:10441496)Curated
    Sequence conflicti746 – 7461V → A in CAB55586. (PubMed:10441496)Curated
    Sequence conflicti757 – 7571L → P in CAB56462. (PubMed:10441496)Curated
    Sequence conflicti795 – 7951E → G in CAB55581. (PubMed:10441496)Curated
    Sequence conflicti798 – 7981E → G in CAB55587. (PubMed:10441496)Curated
    Sequence conflicti825 – 8251D → A in CAB55585. (PubMed:10441496)Curated
    Sequence conflicti871 – 8711S → L in CAB55587. (PubMed:10441496)Curated
    Sequence conflicti876 – 8761A → T in CAB55581. (PubMed:10441496)Curated
    Sequence conflicti949 – 9491I → V in CAB55585. (PubMed:10441496)Curated
    Sequence conflicti1008 – 10081H → R in CAB55582. (PubMed:10441496)Curated
    Sequence conflicti1056 – 10561S → P in CAB55582. (PubMed:10441496)Curated
    Sequence conflicti1241 – 12411L → I in BAA24843. (PubMed:9455477)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei99 – 10911Missing in isoform 2 and isoform 3. 3 PublicationsVSP_006759Add
    BLAST
    Alternative sequencei319 – 33820GSPLV…FPNRW → VVERCHWGILTDLLHKWNQS in isoform 6. 1 PublicationVSP_008965Add
    BLAST
    Alternative sequencei339 – 1248910Missing in isoform 6. 1 PublicationVSP_008966Add
    BLAST
    Alternative sequencei575 – 5751E → ETLGFESKK in isoform 5. 1 PublicationVSP_006760
    Alternative sequencei824 – 86643Missing in isoform 3, isoform 4 and isoform 5. 2 PublicationsVSP_006761Add
    BLAST
    Alternative sequencei1113 – 115442Missing in isoform 5. 1 PublicationVSP_006762Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF013263 mRNA. Translation: AAC51678.1.
    AJ243003 mRNA. Translation: CAB55579.1.
    AJ243004 mRNA. Translation: CAB55580.1.
    AJ243005 mRNA. Translation: CAB55581.1.
    AJ243006 mRNA. Translation: CAB55582.1.
    AJ243007 mRNA. Translation: CAB55583.1.
    AJ243008 mRNA. Translation: CAB55584.1.
    AJ243009 mRNA. Translation: CAB55585.1.
    AJ243010 mRNA. Translation: CAB55586.1.
    AJ243011 mRNA. Translation: CAB55587.1.
    AJ243048 mRNA. Translation: CAB55588.1.
    AJ243107 mRNA. Translation: CAB56462.1.
    AF134397 mRNA. Translation: AAD38344.1.
    AF149794 mRNA. Translation: AAD34016.1.
    AB007873 mRNA. Translation: BAA24843.2. Different initiation.
    AB103079 mRNA. Translation: BAC77343.1.
    CH471054 Genomic DNA. Translation: EAW97606.1.
    BC136531 mRNA. Translation: AAI36532.1.
    BC136532 mRNA. Translation: AAI36533.1.
    AJ133643 Genomic DNA. Translation: CAB65085.1.
    AJ133644 Genomic DNA. Translation: CAB65086.1.
    AJ133645 Genomic DNA. Translation: CAB65087.1.
    AF248734 mRNA. Translation: AAK28401.1. Frameshift.
    CCDSiCCDS55862.1. [O14727-2]
    CCDS55863.1. [O14727-3]
    CCDS9069.1. [O14727-1]
    CCDS9070.1. [O14727-4]
    CCDS9071.1. [O14727-6]
    PIRiT03818.
    RefSeqiNP_001151.1. NM_001160.2. [O14727-3]
    NP_037361.1. NM_013229.2. [O14727-2]
    NP_863651.1. NM_181861.1. [O14727-1]
    NP_863658.1. NM_181868.1. [O14727-4]
    NP_863659.1. NM_181869.1. [O14727-6]
    UniGeneiHs.552567.

    Genome annotation databases

    EnsembliENST00000333991; ENSP00000334558; ENSG00000120868. [O14727-6]
    ENST00000357310; ENSP00000349862; ENSG00000120868. [O14727-4]
    ENST00000359972; ENSP00000353059; ENSG00000120868. [O14727-3]
    ENST00000547045; ENSP00000449791; ENSG00000120868. [O14727-4]
    ENST00000550527; ENSP00000448449; ENSG00000120868. [O14727-2]
    ENST00000551964; ENSP00000448165; ENSG00000120868. [O14727-1]
    ENST00000552268; ENSP00000448826; ENSG00000120868. [O14727-6]
    GeneIDi317.
    KEGGihsa:317.
    UCSCiuc001tfy.3. human. [O14727-2]
    uc001tfz.3. human. [O14727-1]
    uc001tga.3. human. [O14727-3]
    uc001tgb.3. human. [O14727-4]
    uc001tgc.3. human. [O14727-6]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF013263 mRNA. Translation: AAC51678.1 .
    AJ243003 mRNA. Translation: CAB55579.1 .
    AJ243004 mRNA. Translation: CAB55580.1 .
    AJ243005 mRNA. Translation: CAB55581.1 .
    AJ243006 mRNA. Translation: CAB55582.1 .
    AJ243007 mRNA. Translation: CAB55583.1 .
    AJ243008 mRNA. Translation: CAB55584.1 .
    AJ243009 mRNA. Translation: CAB55585.1 .
    AJ243010 mRNA. Translation: CAB55586.1 .
    AJ243011 mRNA. Translation: CAB55587.1 .
    AJ243048 mRNA. Translation: CAB55588.1 .
    AJ243107 mRNA. Translation: CAB56462.1 .
    AF134397 mRNA. Translation: AAD38344.1 .
    AF149794 mRNA. Translation: AAD34016.1 .
    AB007873 mRNA. Translation: BAA24843.2 . Different initiation.
    AB103079 mRNA. Translation: BAC77343.1 .
    CH471054 Genomic DNA. Translation: EAW97606.1 .
    BC136531 mRNA. Translation: AAI36532.1 .
    BC136532 mRNA. Translation: AAI36533.1 .
    AJ133643 Genomic DNA. Translation: CAB65085.1 .
    AJ133644 Genomic DNA. Translation: CAB65086.1 .
    AJ133645 Genomic DNA. Translation: CAB65087.1 .
    AF248734 mRNA. Translation: AAK28401.1 . Frameshift.
    CCDSi CCDS55862.1. [O14727-2 ]
    CCDS55863.1. [O14727-3 ]
    CCDS9069.1. [O14727-1 ]
    CCDS9070.1. [O14727-4 ]
    CCDS9071.1. [O14727-6 ]
    PIRi T03818.
    RefSeqi NP_001151.1. NM_001160.2. [O14727-3 ]
    NP_037361.1. NM_013229.2. [O14727-2 ]
    NP_863651.1. NM_181861.1. [O14727-1 ]
    NP_863658.1. NM_181868.1. [O14727-4 ]
    NP_863659.1. NM_181869.1. [O14727-6 ]
    UniGenei Hs.552567.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1C15 NMR - A 1-97 [» ]
    1CWW NMR - A 1-97 [» ]
    1CY5 X-ray 1.30 A 1-97 [» ]
    1Z6T X-ray 2.21 A/B/C/D 1-591 [» ]
    2P1H X-ray 1.59 A 1-92 [» ]
    2YGS X-ray 1.60 A 1-92 [» ]
    3J2T electron microscopy 9.5 A/B/C/D/E/F/G 1-1248 [» ]
    3YGS X-ray 2.50 C 1-95 [» ]
    ProteinModelPortali O14727.
    SMRi O14727. Positions 1-1248.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106814. 16 interactions.
    DIPi DIP-27624N.
    IntActi O14727. 7 interactions.
    MINTi MINT-96751.

    Chemistry

    BindingDBi O14727.
    ChEMBLi CHEMBL1795093.
    DrugBanki DB00171. Adenosine triphosphate.

    PTM databases

    PhosphoSitei O14727.

    Proteomic databases

    MaxQBi O14727.
    PaxDbi O14727.
    PRIDEi O14727.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000333991 ; ENSP00000334558 ; ENSG00000120868 . [O14727-6 ]
    ENST00000357310 ; ENSP00000349862 ; ENSG00000120868 . [O14727-4 ]
    ENST00000359972 ; ENSP00000353059 ; ENSG00000120868 . [O14727-3 ]
    ENST00000547045 ; ENSP00000449791 ; ENSG00000120868 . [O14727-4 ]
    ENST00000550527 ; ENSP00000448449 ; ENSG00000120868 . [O14727-2 ]
    ENST00000551964 ; ENSP00000448165 ; ENSG00000120868 . [O14727-1 ]
    ENST00000552268 ; ENSP00000448826 ; ENSG00000120868 . [O14727-6 ]
    GeneIDi 317.
    KEGGi hsa:317.
    UCSCi uc001tfy.3. human. [O14727-2 ]
    uc001tfz.3. human. [O14727-1 ]
    uc001tga.3. human. [O14727-3 ]
    uc001tgb.3. human. [O14727-4 ]
    uc001tgc.3. human. [O14727-6 ]

    Organism-specific databases

    CTDi 317.
    GeneCardsi GC12P099039.
    HGNCi HGNC:576. APAF1.
    HPAi HPA031373.
    MIMi 602233. gene.
    neXtProti NX_O14727.
    PharmGKBi PA24868.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2319.
    HOVERGENi HBG018730.
    InParanoidi O14727.
    KOi K02084.
    OMAi ETKKVCK.
    OrthoDBi EOG7XWPMS.
    PhylomeDBi O14727.
    TreeFami TF323866.

    Enzyme and pathway databases

    Reactomei REACT_607. Activation of caspases through apoptosome-mediated cleavage.
    REACT_89. Formation of apoptosome.
    SABIO-RK O14727.
    SignaLinki O14727.

    Miscellaneous databases

    EvolutionaryTracei O14727.
    GeneWikii APAF1.
    GenomeRNAii 317.
    NextBioi 1287.
    PMAP-CutDB O14727.
    PROi O14727.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14727.
    Bgeei O14727.
    Genevestigatori O14727.

    Family and domain databases

    Gene3Di 1.10.533.10. 1 hit.
    2.130.10.10. 2 hits.
    3.40.50.300. 1 hit.
    InterProi IPR017251. 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 ]
    Pfami PF00619. CARD. 1 hit.
    PF00931. NB-ARC. 1 hit.
    PF00400. WD40. 10 hits.
    [Graphical view ]
    PIRSFi PIRSF037646. Apop_pept_activating-1. 1 hit.
    PRINTSi PR00364. DISEASERSIST.
    PR00320. GPROTEINBRPT.
    SMARTi SM00320. WD40. 13 hits.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 1 hit.
    SSF50978. SSF50978. 2 hits.
    SSF52540. SSF52540. 1 hit.
    PROSITEi PS50209. CARD. 1 hit.
    PS00678. WD_REPEATS_1. 4 hits.
    PS50082. WD_REPEATS_2. 9 hits.
    PS50294. WD_REPEATS_REGION. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3."
      Zou H., Henzel W.J., Liu X., Lutschg A., Wang X.
      Cell 90:405-413(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PARTIAL PROTEIN SEQUENCE.
      Tissue: Cervix carcinoma.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 5).
      Tissue: Cervix carcinoma, Heart and Peripheral blood.
    3. "Cytochrome c and dATP-mediated oligomerization of Apaf-1 is a prerequisite for procaspase-9 activation."
      Saleh A., Srinivasula S.M., Acharya S., Fishel R., Alnemri E.S.
      J. Biol. Chem. 274:17941-17945(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: T-cell.
    4. "Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis."
      Hu Y., Benedict M.A., Ding L., Nunez G.
      EMBO J. 18:3586-3595(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBUNIT, MUTAGENESIS OF LYS-160 AND MET-368.
      Tissue: Kidney.
    5. "APAF-1-ALT, a novel alternative splicing form of APAF-1, potentially causes impeded ability of undergoing DNA damage-induced apoptosis in the LNCaP human prostate cancer cell line."
      Ogawa T., Shiga K., Hashimoto S., Kobayashi T., Horii A., Furukawa T.
      Biochem. Biophys. Res. Commun. 306:537-543(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 6), FUNCTION, SUBCELLULAR LOCATION.
      Tissue: Prostatic carcinoma.
    6. "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro."
      Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Brain.
    7. "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
      Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
      DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SEQUENCE REVISION.
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "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).
    10. "The mammalian CED4 homologue, APAF1, exists as two distinct forms in human cells."
      Roberts D.L., Dalgleish R., Cohen G.M., MacFarlane M.
      Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 810-864 AND 866-883.
    11. "Cloning of variant Apaf1."
      Won M., Lee J.-W., Ohr H.-H., Kim D.-U., Chung K.-S., Lee M., Yoo H.-S.
      Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-138 (ISOFORMS 1/4/5).
    12. "Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization."
      Srinivasula S.M., Ahmad M., Fernandes-Alnemri T., Alnemri E.S.
      Mol. Cell 1:949-957(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: APAF-1-MEDIATED OLIGOMERIZATION.
    13. Cited for: INDUCTION BY E2F AND TP53.
    14. "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.
    15. "Calcium blocks formation of apoptosome by preventing nucleotide exchange in Apaf-1."
      Bao Q., Lu W., Rabinowitz J.D., Shi Y.
      Mol. Cell 25:181-192(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INHIBITION BY CALCIUM.
    16. "Integrity of ATP binding site is essential for effective inhibition of the intrinsic apoptosis pathway by NAIP."
      Karimpour S., Davoodi J., Ghahremani M.H.
      Biochem. Biophys. Res. Commun. 407:158-162(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NAIP/BIRC1.
    17. "Crystal structure of Apaf-1 caspase recruitment domain: an alpha-helical Greek key fold for apoptotic signaling."
      Vaughn D.E., Rodriguez J., Lazebnik Y., Joshua-Tor L.
      J. Mol. Biol. 293:439-447(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 1-97.
    18. "Solution structure and mutagenesis of the caspase recruitment domain (CARD) from Apaf-1."
      Day C.L., Dupont C., Lackmann M., Vaux D.L., Hinds M.G.
      Cell Death Differ. 6:1125-1132(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-97.

    Entry informationi

    Entry nameiAPAF_HUMAN
    AccessioniPrimary (citable) accession number: O14727
    Secondary accession number(s): B2RMX8
    , O43297, Q7Z438, Q9BXZ6, Q9UBZ5, Q9UGN8, Q9UGN9, Q9UGP0, Q9UJ58, Q9UJ59, Q9UJ60, Q9UJ61, Q9UJ62, Q9UJ63, Q9UJ64, Q9UJ65, Q9UJ66, Q9UJ67, Q9UNC9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: January 23, 2002
    Last modified: October 1, 2014
    This is version 170 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3