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Protein

Apoptotic protease-activating factor 1

Gene

APAF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

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 process Source: Reactome
  4. forebrain development Source: Ensembl
  5. intrinsic apoptotic signaling pathway Source: UniProtKB
  6. nervous system development Source: ProtInc
  7. neural tube closure Source: Ensembl
  8. neuron apoptotic process Source: Ensembl
  9. positive regulation of apoptotic process Source: UniProtKB
  10. positive regulation of apoptotic signaling pathway Source: Ensembl
  11. regulation of apoptotic DNA fragmentation Source: Ensembl
  12. regulation of apoptotic process Source: UniProtKB
  13. response to G1 DNA damage checkpoint signaling Source: UniProtKB
Complete GO annotation...

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: UniProtKB
  4. nucleus Source: Ensembl
Complete GO annotation...

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

BgeeiO14727.
ExpressionAtlasiO14727. baseline and differential.
GenevestigatoriO14727.

Organism-specific databases

HPAiCAB069399.
HPA031373.

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. 18 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 – 119Combined sources
Helixi13 – 197Combined sources
Helixi22 – 3211Combined sources
Helixi37 – 448Combined sources
Beta strandi46 – 483Combined sources
Helixi49 – 6113Combined sources
Helixi65 – 7713Combined sources
Helixi81 – 877Combined sources
Helixi88 – 903Combined sources
Helixi108 – 1169Combined sources
Helixi130 – 14011Combined sources
Beta strandi148 – 1536Combined sources
Helixi160 – 1689Combined sources
Helixi171 – 1777Combined sources
Beta strandi182 – 1898Combined sources
Helixi192 – 20615Combined sources
Helixi220 – 23314Combined sources
Beta strandi239 – 2457Combined sources
Helixi248 – 2525Combined sources
Beta strandi259 – 2657Combined sources
Helixi267 – 2704Combined sources
Beta strandi277 – 2815Combined sources
Helixi288 – 29912Combined sources
Helixi303 – 3053Combined sources
Helixi309 – 3168Combined sources
Turni317 – 3193Combined sources
Helixi321 – 33313Combined sources
Helixi338 – 3469Combined sources
Helixi362 – 37312Combined sources
Turni377 – 3793Combined sources
Helixi380 – 3856Combined sources
Helixi386 – 3883Combined sources
Helixi397 – 4048Combined sources
Helixi408 – 42013Combined sources
Beta strandi423 – 4297Combined sources
Beta strandi432 – 4365Combined sources
Helixi439 – 44810Combined sources
Helixi450 – 4523Combined sources
Helixi453 – 46412Combined sources
Turni465 – 4673Combined sources
Helixi470 – 4723Combined sources
Helixi480 – 49314Combined sources
Helixi497 – 5048Combined sources
Helixi507 – 51711Combined sources
Helixi520 – 5289Combined sources
Helixi530 – 5323Combined sources
Helixi535 – 55016Combined sources
Turni551 – 5566Combined sources
Helixi563 – 5675Combined sources
Helixi575 – 58511Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
4RHWX-ray2.10A/B/C/D1-97[»]
ProteinModelPortaliO14727.
SMRiO14727. Positions 1-586.
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.
GeneTreeiENSGT00780000121899.
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. 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. 10 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]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

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

        10         20         30         40         50
MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ
60 70 80 90 100
QRAAMLIKMI LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSGK
110 120 130 140 150
DSVSGITSYV RTVLCEGGVP QRPVVFVTRK KLVNAIQQKL SKLKGEPGWV
160 170 180 190 200
TIHGMAGCGK SVLAAEAVRD HSLLEGCFPG GVHWVSVGKQ DKSGLLMKLQ
210 220 230 240 250
NLCTRLDQDE SFSQRLPLNI EEAKDRLRIL MLRKHPRSLL ILDDVWDSWV
260 270 280 290 300
LKAFDSQCQI LLTTRDKSVT DSVMGPKYVV PVESSLGKEK GLEILSLFVN
310 320 330 340 350
MKKADLPEQA HSIIKECKGS PLVVSLIGAL LRDFPNRWEY YLKQLQNKQF
360 370 380 390 400
KRIRKSSSYD YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL
410 420 430 440 450
CILWDMETEE VEDILQEFVN KSLLFCDRNG KSFRYYLHDL QVDFLTEKNC
460 470 480 490 500
SQLQDLHKKI ITQFQRYHQP HTLSPDQEDC MYWYNFLAYH MASAKMHKEL
510 520 530 540 550
CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV SENFQEFLSL
560 570 580 590 600
NGHLLGRQPF PNIVQLGLCE PETSEVYQQA KLQAKQEVDN GMLYLEWINK
610 620 630 640 650
KNITNLSRLV VRPHTDAVYH ACFSEDGQRI ASCGADKTLQ VFKAETGEKL
660 670 680 690 700
LEIKAHEDEV LCCAFSTDDR FIATCSVDKK VKIWNSMTGE LVHTYDEHSE
710 720 730 740 750
QVNCCHFTNS SHHLLLATGS SDCFLKLWDL NQKECRNTMF GHTNSVNHCR
760 770 780 790 800
FSPDDKLLAS CSADGTLKLW DATSANERKS INVKQFFLNL EDPQEDMEVI
810 820 830 840 850
VKCCSWSADG ARIMVAAKNK IFLFDIHTSG LLGEIHTGHH STIQYCDFSP
860 870 880 890 900
QNHLAVVALS QYCVELWNTD SRSKVADCRG HLSWVHGVMF SPDGSSFLTS
910 920 930 940 950
SDDQTIRLWE TKKVCKNSAV MLKQEVDVVF QENEVMVLAV DHIRRLQLIN
960 970 980 990 1000
GRTGQIDYLT EAQVSCCCLS PHLQYIAFGD ENGAIEILEL VNNRIFQSRF
1010 1020 1030 1040 1050
QHKKTVWHIQ FTADEKTLIS SSDDAEIQVW NWQLDKCIFL RGHQETVKDF
1060 1070 1080 1090 1100
RLLKNSRLLS WSFDGTVKVW NIITGNKEKD FVCHQGTVLS CDISHDATKF
1110 1120 1130 1140 1150
SSTSADKTAK IWSFDLLLPL HELRGHNGCV RCSAFSVDST LLATGDDNGE
1160 1170 1180 1190 1200
IRIWNVSNGE LLHLCAPLSE EGAATHGGWV TDLCFSPDGK MLISAGGYIK
1210 1220 1230 1240
WWNVVTGESS QTFYTNGTNL KKIHVSPDFK TYVTVDNLGI LYILQTLE
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. Curated
The sequence BAA24843.2 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti134 – 1341N → S (Ref. 11) Curated
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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[»]
4RHWX-ray2.10A/B/C/D1-97[»]
ProteinModelPortaliO14727.
SMRiO14727. Positions 1-586.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106814. 18 interactions.
DIPiDIP-27624N.
IntActiO14727. 7 interactions.
MINTiMINT-96751.

Chemistry

BindingDBiO14727.
ChEMBLiCHEMBL1795093.
DrugBankiDB00171. Adenosine triphosphate.

PTM databases

PhosphoSiteiO14727.

Proteomic databases

MaxQBiO14727.
PaxDbiO14727.
PRIDEiO14727.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi317.
GeneCardsiGC12P099039.
HGNCiHGNC:576. APAF1.
HPAiCAB069399.
HPA031373.
MIMi602233. gene.
neXtProtiNX_O14727.
PharmGKBiPA24868.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2319.
GeneTreeiENSGT00780000121899.
HOVERGENiHBG018730.
InParanoidiO14727.
KOiK02084.
OMAiETKKVCK.
OrthoDBiEOG7XWPMS.
PhylomeDBiO14727.
TreeFamiTF323866.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiO14727.
GeneWikiiAPAF1.
GenomeRNAii317.
NextBioi1287.
PMAP-CutDBO14727.
PROiO14727.
SOURCEiSearch...

Gene expression databases

BgeeiO14727.
ExpressionAtlasiO14727. baseline and differential.
GenevestigatoriO14727.

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. 10 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

« Hide 'large scale' publications
  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: March 4, 2015
This is version 175 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

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 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.