Reviewed, UniProtKB/Swiss-Prot O14727 (APAF_HUMAN)

Names and origin

Protein names

Recommended name:
    Apoptotic protease-activating factor 1
      Short name=Apaf-1

Gene names

Name:	APAF1
Synonyms:	KIAA0413

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1248 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. Isoform 6 is less effective in inducing apoptosis. Ref.4 Ref.5
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. Ref.4 Ref.10 Ref.12
Subcellular location	Cytoplasm. Ref.5
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. Ref.11
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	The sequence AAK28401.1 differs from that shown. Reason: Frameshift at position 108.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	Repeat WD repeat
Ligand	ATP-binding Nucleotide-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	activation of caspase activity by cytochrome c Ref.1 Inferred from direct assay. Source: UniProtKB defense response Inferred from electronic annotation. Source: InterPro nervous system development Traceable author statement. Source: ProtInc
Cellular component	cytosol Ref.1 Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW caspase activator activity Ref.1 Non-traceable author statement. Source: UniProtKB protein binding Ref.1 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP9	P55211	2	EBI-446492,EBI-516799
CYCS	P99999	2	EBI-446492,EBI-446479
PPP1CA	P62136	2	EBI-446492,EBI-357253

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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1248

1248

Apoptotic protease-activating factor 1

PRO_0000050844

Regions

Domain

1 – 90

90

CARD

Domain

104 – 415

312

NB-ARC

Repeat

613 – 652

40

WD 1

Repeat

655 – 694

40

WD 2

Repeat

697 – 738

42

WD 3

Repeat

741 – 780

40

WD 4

Repeat

796 – 836

41

WD 5

Repeat

838 – 877

40

WD 6

Repeat

880 – 919

40

WD 7

Repeat

959 – 998

40

WD 8

Repeat

1001 – 1040

40

WD 9

Repeat

1042 – 1080

39

WD 10

Repeat

1083 – 1122

40

WD 11

Repeat

1125 – 1164

40

WD 12

Repeat

1175 – 1212

38

WD 13

Nucleotide binding

154 – 161

8

ATP Potential

Compositional bias

95 – 98

4

Poly-Ser

Amino acid modifications

Modified residue

204

1

Phosphothreonine Ref.13

Modified residue

238

1

Phosphoserine Ref.13

Modified residue

248

1

Phosphoserine Ref.13

Natural variations

Alternative sequence

99 – 109

11

Missing in isoform 2 and isoform 3.

VSP_006759

Alternative sequence

319 – 338

20

GSPLV…FPNRW → VVERCHWGILTDLLHKWNQS in isoform 6.

VSP_008965

Alternative sequence

339 – 1248

910

Missing in isoform 6.

VSP_008966

Alternative sequence

575

1

E → ETLGFESKK in isoform 5.

VSP_006760

Alternative sequence

824 – 866

43

Missing in isoform 3, isoform 4 and isoform 5.

VSP_006761

Alternative sequence

1113 – 1154

42

Missing in isoform 5.

VSP_006762

Experimental info

Mutagenesis

160

1

K → R: No association with APAF-1. No binding to pro-caspase-9. Ref.4

Mutagenesis

368

1

M → L: Activation of pro-caspase-9 independent of cytochrome c. Increased ability to induce apoptosis. Ref.4

Sequence conflict

134

1

N → S Ref.9

Sequence conflict

145

1

G → C in CAB55587. Ref.2

Sequence conflict

161

1

S → F in CAB55586. Ref.2

Sequence conflict

370

1

I → T in CAB55581. Ref.2

Sequence conflict

383

1

Y → H in CAB55586. Ref.2

Sequence conflict

544

1

F → L in CAB55584. Ref.2

Sequence conflict

580

1

A → T in CAB55580. Ref.2

Sequence conflict

608

1

R → C in CAB55585. Ref.2

Sequence conflict

620

1

H → R in CAB55587. Ref.2

Sequence conflict

639

1

L → F in CAB55583. Ref.2

Sequence conflict

708

1

T → A in CAB55579. Ref.2

Sequence conflict

742

1

H → R in CAB55584. Ref.2

Sequence conflict

746

1

V → A in CAB55586. Ref.2

Sequence conflict

757

1

L → P in CAB56462. Ref.2

Sequence conflict

795

1

E → G in CAB55581. Ref.2

Sequence conflict

798

1

E → G in CAB55587. Ref.2

Sequence conflict

825

1

D → A in CAB55585. Ref.2

Sequence conflict

871

1

S → L in CAB55587. Ref.2

Sequence conflict

876

1

A → T in CAB55581. Ref.2

Sequence conflict

949

1

I → V in CAB55585. Ref.2

Sequence conflict

1008

1

H → R in CAB55582. Ref.2

Sequence conflict

1056

1

S → P in CAB55582. Ref.2

Sequence conflict

1241

1

L → I in BAA24843. Ref.6

Secondary structure

1

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1248

Helix Strand Turn

Details...

Helix

3 – 11

9

Helix

13 – 19

7

Helix

22 – 32

11

Helix

37 – 44

8

Beta strand

46 – 48

3

Helix

49 – 61

13

Helix

65 – 77

13

Helix

81 – 87

7

Helix

88 – 90

3

Helix

108 – 116

9

Helix

130 – 140

11

Beta strand

148 – 153

6

Helix

160 – 168

9

Helix

171 – 177

7

Beta strand

182 – 189

8

Helix

192 – 206

15

Helix

220 – 233

14

Beta strand

239 – 245

7

Helix

248 – 252

5

Beta strand

259 – 265

7

Helix

267 – 270

4

Beta strand

277 – 281

5

Helix

288 – 299

12

Helix

303 – 305

3

Helix

309 – 316

8

Turn

317 – 319

3

Helix

321 – 333

13

Helix

338 – 346

9

Helix

362 – 373

12

Turn

377 – 379

3

Helix

380 – 385

6

Helix

386 – 388

3

Helix

397 – 404

8

Helix

408 – 420

13

Beta strand

423 – 429

7

Beta strand

432 – 436

5

Helix

439 – 448

10

Helix

450 – 452

3

Helix

453 – 464

12

Turn

465 – 467

3

Helix

470 – 472

3

Helix

480 – 493

14

Helix

497 – 504

8

Helix

507 – 517

11

Helix

520 – 528

9

Helix

530 – 532

3

Helix

535 – 550

16

Turn

551 – 556

6

Helix

563 – 567

5

Helix

575 – 585

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Apaf-1XL) [UniParc]. Last modified January 23, 2002. Version 2. Checksum: 0750D05817AC9B3B	FASTA	1,248	141,840
	10 20 30 40 50 60 MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ QRAAMLIKMI 70 80 90 100 110 120 LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSGK DSVSGITSYV RTVLCEGGVP 130 140 150 160 170 180 QRPVVFVTRK KLVNAIQQKL SKLKGEPGWV TIHGMAGCGK SVLAAEAVRD HSLLEGCFPG 190 200 210 220 230 240 GVHWVSVGKQ DKSGLLMKLQ NLCTRLDQDE SFSQRLPLNI EEAKDRLRIL MLRKHPRSLL 250 260 270 280 290 300 ILDDVWDSWV LKAFDSQCQI LLTTRDKSVT DSVMGPKYVV PVESSLGKEK GLEILSLFVN 310 320 330 340 350 360 MKKADLPEQA HSIIKECKGS PLVVSLIGAL LRDFPNRWEY YLKQLQNKQF KRIRKSSSYD 370 380 390 400 410 420 YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL CILWDMETEE VEDILQEFVN 430 440 450 460 470 480 KSLLFCDRNG KSFRYYLHDL QVDFLTEKNC SQLQDLHKKI ITQFQRYHQP HTLSPDQEDC 490 500 510 520 530 540 MYWYNFLAYH MASAKMHKEL CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV 550 560 570 580 590 600 SENFQEFLSL NGHLLGRQPF PNIVQLGLCE PETSEVYQQA KLQAKQEVDN GMLYLEWINK 610 620 630 640 650 660 KNITNLSRLV VRPHTDAVYH ACFSEDGQRI ASCGADKTLQ VFKAETGEKL LEIKAHEDEV 670 680 690 700 710 720 LCCAFSTDDR FIATCSVDKK VKIWNSMTGE LVHTYDEHSE QVNCCHFTNS SHHLLLATGS 730 740 750 760 770 780 SDCFLKLWDL NQKECRNTMF GHTNSVNHCR FSPDDKLLAS CSADGTLKLW DATSANERKS 790 800 810 820 830 840 INVKQFFLNL EDPQEDMEVI VKCCSWSADG ARIMVAAKNK IFLFDIHTSG LLGEIHTGHH 850 860 870 880 890 900 STIQYCDFSP QNHLAVVALS QYCVELWNTD SRSKVADCRG HLSWVHGVMF SPDGSSFLTS 910 920 930 940 950 960 SDDQTIRLWE TKKVCKNSAV MLKQEVDVVF QENEVMVLAV DHIRRLQLIN GRTGQIDYLT 970 980 990 1000 1010 1020 EAQVSCCCLS PHLQYIAFGD ENGAIEILEL VNNRIFQSRF QHKKTVWHIQ FTADEKTLIS 1030 1040 1050 1060 1070 1080 SSDDAEIQVW NWQLDKCIFL RGHQETVKDF RLLKNSRLLS WSFDGTVKVW NIITGNKEKD 1090 1100 1110 1120 1130 1140 FVCHQGTVLS CDISHDATKF SSTSADKTAK IWSFDLLLPL HELRGHNGCV RCSAFSVDST 1150 1160 1170 1180 1190 1200 LLATGDDNGE IRIWNVSNGE LLHLCAPLSE EGAATHGGWV TDLCFSPDGK MLISAGGYIK 1210 1220 1230 1240 WWNVVTGESS QTFYTNGTNL KKIHVSPDFK TYVTVDNLGI LYILQTLE
	Isoform 2 (Apaf-1L). Checksum: 0D3EF9AB2A66FFF5	FASTA	1,237	140,745
	10 20 30 40 50 60 MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ QRAAMLIKMI 70 80 90 100 110 120 LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSVR TVLCEGGVPQ RPVVFVTRKK 130 140 150 160 170 180 LVNAIQQKLS KLKGEPGWVT IHGMAGCGKS VLAAEAVRDH SLLEGCFPGG VHWVSVGKQD 190 200 210 220 230 240 KSGLLMKLQN LCTRLDQDES FSQRLPLNIE EAKDRLRILM LRKHPRSLLI LDDVWDSWVL 250 260 270 280 290 300 KAFDSQCQIL LTTRDKSVTD SVMGPKYVVP VESSLGKEKG LEILSLFVNM KKADLPEQAH 310 320 330 340 350 360 SIIKECKGSP LVVSLIGALL RDFPNRWEYY LKQLQNKQFK RIRKSSSYDY EALDEAMSIS 370 380 390 400 410 420 VEMLREDIKD YYTDLSILQK DVKVPTKVLC ILWDMETEEV EDILQEFVNK SLLFCDRNGK 430 440 450 460 470 480 SFRYYLHDLQ VDFLTEKNCS QLQDLHKKII TQFQRYHQPH TLSPDQEDCM YWYNFLAYHM 490 500 510 520 530 540 ASAKMHKELC ALMFSLDWIK AKTELVGPAH LIHEFVEYRH ILDEKDCAVS ENFQEFLSLN 550 560 570 580 590 600 GHLLGRQPFP NIVQLGLCEP ETSEVYQQAK LQAKQEVDNG MLYLEWINKK NITNLSRLVV 610 620 630 640 650 660 RPHTDAVYHA CFSEDGQRIA SCGADKTLQV FKAETGEKLL EIKAHEDEVL CCAFSTDDRF 670 680 690 700 710 720 IATCSVDKKV KIWNSMTGEL VHTYDEHSEQ VNCCHFTNSS HHLLLATGSS DCFLKLWDLN 730 740 750 760 770 780 QKECRNTMFG HTNSVNHCRF SPDDKLLASC SADGTLKLWD ATSANERKSI NVKQFFLNLE 790 800 810 820 830 840 DPQEDMEVIV KCCSWSADGA RIMVAAKNKI FLFDIHTSGL LGEIHTGHHS TIQYCDFSPQ 850 860 870 880 890 900 NHLAVVALSQ YCVELWNTDS RSKVADCRGH LSWVHGVMFS PDGSSFLTSS DDQTIRLWET 910 920 930 940 950 960 KKVCKNSAVM LKQEVDVVFQ ENEVMVLAVD HIRRLQLING RTGQIDYLTE AQVSCCCLSP 970 980 990 1000 1010 1020 HLQYIAFGDE NGAIEILELV NNRIFQSRFQ HKKTVWHIQF TADEKTLISS SDDAEIQVWN 1030 1040 1050 1060 1070 1080 WQLDKCIFLR GHQETVKDFR LLKNSRLLSW SFDGTVKVWN IITGNKEKDF VCHQGTVLSC 1090 1100 1110 1120 1130 1140 DISHDATKFS STSADKTAKI WSFDLLLPLH ELRGHNGCVR CSAFSVDSTL LATGDDNGEI 1150 1160 1170 1180 1190 1200 RIWNVSNGEL LHLCAPLSEE GAATHGGWVT DLCFSPDGKM LISAGGYIKW WNVVTGESSQ 1210 1220 1230 TFYTNGTNLK KIHVSPDFKT YVTVDNLGIL YILQTLE
	Isoform 3 (Apaf-1S). Checksum: A675EA102DDAAFB7	FASTA	1,194	135,980
	10 20 30 40 50 60 MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ QRAAMLIKMI 70 80 90 100 110 120 LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSVR TVLCEGGVPQ RPVVFVTRKK 130 140 150 160 170 180 LVNAIQQKLS KLKGEPGWVT IHGMAGCGKS VLAAEAVRDH SLLEGCFPGG VHWVSVGKQD 190 200 210 220 230 240 KSGLLMKLQN LCTRLDQDES FSQRLPLNIE EAKDRLRILM LRKHPRSLLI LDDVWDSWVL 250 260 270 280 290 300 KAFDSQCQIL LTTRDKSVTD SVMGPKYVVP VESSLGKEKG LEILSLFVNM KKADLPEQAH 310 320 330 340 350 360 SIIKECKGSP LVVSLIGALL RDFPNRWEYY LKQLQNKQFK RIRKSSSYDY EALDEAMSIS 370 380 390 400 410 420 VEMLREDIKD YYTDLSILQK DVKVPTKVLC ILWDMETEEV EDILQEFVNK SLLFCDRNGK 430 440 450 460 470 480 SFRYYLHDLQ VDFLTEKNCS QLQDLHKKII TQFQRYHQPH TLSPDQEDCM YWYNFLAYHM 490 500 510 520 530 540 ASAKMHKELC ALMFSLDWIK AKTELVGPAH LIHEFVEYRH ILDEKDCAVS ENFQEFLSLN 550 560 570 580 590 600 GHLLGRQPFP NIVQLGLCEP ETSEVYQQAK LQAKQEVDNG MLYLEWINKK NITNLSRLVV 610 620 630 640 650 660 RPHTDAVYHA CFSEDGQRIA SCGADKTLQV FKAETGEKLL EIKAHEDEVL CCAFSTDDRF 670 680 690 700 710 720 IATCSVDKKV KIWNSMTGEL VHTYDEHSEQ VNCCHFTNSS HHLLLATGSS DCFLKLWDLN 730 740 750 760 770 780 QKECRNTMFG HTNSVNHCRF SPDDKLLASC SADGTLKLWD ATSANERKSI NVKQFFLNLE 790 800 810 820 830 840 DPQEDMEVIV KCCSWSADGA RIMVAAKNKI FLWNTDSRSK VADCRGHLSW VHGVMFSPDG 850 860 870 880 890 900 SSFLTSSDDQ TIRLWETKKV CKNSAVMLKQ EVDVVFQENE VMVLAVDHIR RLQLINGRTG 910 920 930 940 950 960 QIDYLTEAQV SCCCLSPHLQ YIAFGDENGA IEILELVNNR IFQSRFQHKK TVWHIQFTAD 970 980 990 1000 1010 1020 EKTLISSSDD AEIQVWNWQL DKCIFLRGHQ ETVKDFRLLK NSRLLSWSFD GTVKVWNIIT 1030 1040 1050 1060 1070 1080 GNKEKDFVCH QGTVLSCDIS HDATKFSSTS ADKTAKIWSF DLLLPLHELR GHNGCVRCSA 1090 1100 1110 1120 1130 1140 FSVDSTLLAT GDDNGEIRIW NVSNGELLHL CAPLSEEGAA THGGWVTDLC FSPDGKMLIS 1150 1160 1170 1180 1190 AGGYIKWWNV VTGESSQTFY TNGTNLKKIH VSPDFKTYVT VDNLGILYIL QTLE
	Isoform 4 (Apaf-1M). Checksum: DA57B4E35E79D73A	FASTA	1,205	137,076
	10 20 30 40 50 60 MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ QRAAMLIKMI 70 80 90 100 110 120 LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSGK DSVSGITSYV RTVLCEGGVP 130 140 150 160 170 180 QRPVVFVTRK KLVNAIQQKL SKLKGEPGWV TIHGMAGCGK SVLAAEAVRD HSLLEGCFPG 190 200 210 220 230 240 GVHWVSVGKQ DKSGLLMKLQ NLCTRLDQDE SFSQRLPLNI EEAKDRLRIL MLRKHPRSLL 250 260 270 280 290 300 ILDDVWDSWV LKAFDSQCQI LLTTRDKSVT DSVMGPKYVV PVESSLGKEK GLEILSLFVN 310 320 330 340 350 360 MKKADLPEQA HSIIKECKGS PLVVSLIGAL LRDFPNRWEY YLKQLQNKQF KRIRKSSSYD 370 380 390 400 410 420 YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL CILWDMETEE VEDILQEFVN 430 440 450 460 470 480 KSLLFCDRNG KSFRYYLHDL QVDFLTEKNC SQLQDLHKKI ITQFQRYHQP HTLSPDQEDC 490 500 510 520 530 540 MYWYNFLAYH MASAKMHKEL CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV 550 560 570 580 590 600 SENFQEFLSL NGHLLGRQPF PNIVQLGLCE PETSEVYQQA KLQAKQEVDN GMLYLEWINK 610 620 630 640 650 660 KNITNLSRLV VRPHTDAVYH ACFSEDGQRI ASCGADKTLQ VFKAETGEKL LEIKAHEDEV 670 680 690 700 710 720 LCCAFSTDDR FIATCSVDKK VKIWNSMTGE LVHTYDEHSE QVNCCHFTNS SHHLLLATGS 730 740 750 760 770 780 SDCFLKLWDL NQKECRNTMF GHTNSVNHCR FSPDDKLLAS CSADGTLKLW DATSANERKS 790 800 810 820 830 840 INVKQFFLNL EDPQEDMEVI VKCCSWSADG ARIMVAAKNK IFLWNTDSRS KVADCRGHLS 850 860 870 880 890 900 WVHGVMFSPD GSSFLTSSDD QTIRLWETKK VCKNSAVMLK QEVDVVFQEN EVMVLAVDHI 910 920 930 940 950 960 RRLQLINGRT GQIDYLTEAQ VSCCCLSPHL QYIAFGDENG AIEILELVNN RIFQSRFQHK 970 980 990 1000 1010 1020 KTVWHIQFTA DEKTLISSSD DAEIQVWNWQ LDKCIFLRGH QETVKDFRLL KNSRLLSWSF 1030 1040 1050 1060 1070 1080 DGTVKVWNII TGNKEKDFVC HQGTVLSCDI SHDATKFSST SADKTAKIWS FDLLLPLHEL 1090 1100 1110 1120 1130 1140 RGHNGCVRCS AFSVDSTLLA TGDDNGEIRI WNVSNGELLH LCAPLSEEGA ATHGGWVTDL 1150 1160 1170 1180 1190 1200 CFSPDGKMLI SAGGYIKWWN VVTGESSQTF YTNGTNLKKI HVSPDFKTYV TVDNLGILYI LQTLE
	Isoform 5 (Apaf-1XS). Checksum: CA9B14019EAB35BF	FASTA	1,171	133,356
	10 20 30 40 50 60 MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ QRAAMLIKMI 70 80 90 100 110 120 LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSGK DSVSGITSYV RTVLCEGGVP 130 140 150 160 170 180 QRPVVFVTRK KLVNAIQQKL SKLKGEPGWV TIHGMAGCGK SVLAAEAVRD HSLLEGCFPG 190 200 210 220 230 240 GVHWVSVGKQ DKSGLLMKLQ NLCTRLDQDE SFSQRLPLNI EEAKDRLRIL MLRKHPRSLL 250 260 270 280 290 300 ILDDVWDSWV LKAFDSQCQI LLTTRDKSVT DSVMGPKYVV PVESSLGKEK GLEILSLFVN 310 320 330 340 350 360 MKKADLPEQA HSIIKECKGS PLVVSLIGAL LRDFPNRWEY YLKQLQNKQF KRIRKSSSYD 370 380 390 400 410 420 YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL CILWDMETEE VEDILQEFVN 430 440 450 460 470 480 KSLLFCDRNG KSFRYYLHDL QVDFLTEKNC SQLQDLHKKI ITQFQRYHQP HTLSPDQEDC 490 500 510 520 530 540 MYWYNFLAYH MASAKMHKEL CALMFSLDWI KAKTELVGPA HLIHEFVEYR HILDEKDCAV 550 560 570 580 590 600 SENFQEFLSL NGHLLGRQPF PNIVQLGLCE PETSETLGFE SKKVYQQAKL QAKQEVDNGM 610 620 630 640 650 660 LYLEWINKKN ITNLSRLVVR PHTDAVYHAC FSEDGQRIAS CGADKTLQVF KAETGEKLLE 670 680 690 700 710 720 IKAHEDEVLC CAFSTDDRFI ATCSVDKKVK IWNSMTGELV HTYDEHSEQV NCCHFTNSSH 730 740 750 760 770 780 HLLLATGSSD CFLKLWDLNQ KECRNTMFGH TNSVNHCRFS PDDKLLASCS ADGTLKLWDA 790 800 810 820 830 840 TSANERKSIN VKQFFLNLED PQEDMEVIVK CCSWSADGAR IMVAAKNKIF LWNTDSRSKV 850 860 870 880 890 900 ADCRGHLSWV HGVMFSPDGS SFLTSSDDQT IRLWETKKVC KNSAVMLKQE VDVVFQENEV 910 920 930 940 950 960 MVLAVDHIRR LQLINGRTGQ IDYLTEAQVS CCCLSPHLQY IAFGDENGAI EILELVNNRI 970 980 990 1000 1010 1020 FQSRFQHKKT VWHIQFTADE KTLISSSDDA EIQVWNWQLD KCIFLRGHQE TVKDFRLLKN 1030 1040 1050 1060 1070 1080 SRLLSWSFDG TVKVWNIITG NKEKDFVCHQ GTVLSCDISH DATKFSSTSA DKTAKIWNVS 1090 1100 1110 1120 1130 1140 NGELLHLCAP LSEEGAATHG GWVTDLCFSP DGKMLISAGG YIKWWNVVTG ESSQTFYTNG 1150 1160 1170 TNLKKIHVSP DFKTYVTVDN LGILYILQTL E
	Isoform 6 (Apaf-1-ALT). Checksum: 29D933A65707ED92	FASTA	338	37,976
	10 20 30 40 50 60 MDAKARNCLL QHREALEKDI KTSYIMDHMI SDGFLTISEE EKVRNEPTQQ QRAAMLIKMI 70 80 90 100 110 120 LKKDNDSYVS FYNALLHEGY KDLAALLHDG IPVVSSSSGK DSVSGITSYV RTVLCEGGVP 130 140 150 160 170 180 QRPVVFVTRK KLVNAIQQKL SKLKGEPGWV TIHGMAGCGK SVLAAEAVRD HSLLEGCFPG 190 200 210 220 230 240 GVHWVSVGKQ DKSGLLMKLQ NLCTRLDQDE SFSQRLPLNI EEAKDRLRIL MLRKHPRSLL 250 260 270 280 290 300 ILDDVWDSWV LKAFDSQCQI LLTTRDKSVT DSVMGPKYVV PVESSLGKEK GLEILSLFVN 310 320 330 MKKADLPEQA HSIIKECKVV ERCHWGILTD LLHKWNQS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 9267021] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PARTIAL PROTEIN SEQUENCE. Tissue: Cervix carcinoma.
[2]	"Three new types of Apaf-1 in mammalian cells." Hahn C., Hirsch B., Jahnke D., Duerkop H., Stein H. Biochem. Biophys. Res. Commun. 261:746-749(1999) [PubMed: 10441496] [Abstract] 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: 10364241] [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: 10393175] [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: 12804598] [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: 9455477] [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: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[8]	"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.
[9]	"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).
[10]	"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: 9651578] [Abstract] Cited for: APAF-1-MEDIATED OLIGOMERIZATION.
[11]	"Apaf-1 is a transcriptional target for E2F and p53." Moroni M.C., Hickman E.S., Denchi E.L., Caprara G., Colli E., Cecconi F., Mueller H., Helin K. Nat. Cell Biol. 3:552-558(2001) [PubMed: 11389439] [Abstract] Cited for: INDUCTION BY E2F AND P53.
[12]	"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: 15262985] [Abstract] Cited for: INTERACTION WITH APIP.
[13]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-204; SER-238 AND SER-248, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"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: 10543941] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 1-97.
[15]	"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: 10578182] [Abstract] Cited for: STRUCTURE BY NMR OF 1-97.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.
AJ133643 Genomic DNA. Translation: CAB65085.1.
AJ133644 Genomic DNA. Translation: CAB65086.1.
AJ133645 Genomic DNA. Translation: CAB65087.1.
AF248734 mRNA. Translation: AAK28401.1. Frameshift.

IPI

IPI00023630.
IPI00217460.
IPI00217461.
IPI00217462.
IPI00217463.
IPI00375875.

PIR

T03818.

RefSeq

NP_001151.1.
NP_037361.1.
NP_863651.1.
NP_863658.1.
NP_863659.1.

UniGene

Hs.708112

3D structure databases

PDBPDBe

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	[»]
3YGS	X-ray	2.50	C	1-95	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:27624N.

IntAct

O14727. 3 interactions.

STRING

O14727.

PTM databases

PhosphoSite

O14727.

Proteomic databases

PRIDE

O14727.

Genome annotation databases

Ensembl

ENST00000333991; ENSP00000334558; ENSG00000120868; Homo sapiens. [Genome view]
ENST00000339433; ENSP00000341830; ENSG00000120868; Homo sapiens. [Genome view]
ENST00000357310; ENSP00000349862; ENSG00000120868; Homo sapiens. [Genome view]
ENST00000359972; ENSP00000353059; ENSG00000120868; Homo sapiens. [Genome view]

GeneID

317.

KEGG

hsa:317.

UCSC

uc001tfy.1. human.
uc001tfz.1. human.
uc001tga.1. human.
uc001tgb.1. human.
uc001tgc.1. human.

Organism-specific databases

CTD

317.

GeneCards

GC12P097541.

H-InvDB

HIX0010910.

HGNC

HGNC:576. APAF1.

MIM

602233. gene.

PharmGKB

PA24868.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O14727.

OMA

SSYDYEA.

Enzyme and pathway databases

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
p75ntrpathway. p75(NTR)-mediated signaling.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

O14727.

Bgee

O14727.

Genevestigator

O14727.

GermOnline

ENSG00000120868. Homo sapiens.

Family and domain databases

InterPro

IPR017251. Apoptotic_pept-activating_1.
IPR001315. CARD.
IPR011029. DEATH-like.
IPR000767. Disease_R.
IPR020472. G-protein_beta_WD-40_rep_reg.
IPR002182. NB-ARC.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019782. WD40_repeat_2.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
IPR019781. WD40_repeat_sg.
[Graphical view]

Gene3D

G3DSA:1.10.533.10. DEATH_like. 1 hit.
G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 2 hits.

Pfam

PF00619. CARD. 1 hit.
PF00931. NB-ARC. 1 hit.
PF00400. WD40. 10 hits.
[Graphical view]

PIRSF

PIRSF037646. Apop_pept_activating-1. 1 hit.

PRINTS

PR00364. DISEASERSIST.
PR00320. GPROTEINBRPT.

ProDom

PD000018. WD40. 4 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00320. WD40. 13 hits.
[Graphical view]

PROSITE

PS50209. CARD. 1 hit.
PS00678. WD_REPEATS_1. 4 hits.
PS50082. WD_REPEATS_2. 9 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00171. Adenosine triphosphate.

NextBio

1287.

PMAP-CutDB

O14727.

SOURCE

Search...

Entry information

Entry name

APAF_HUMAN

Accession

Primary (citable) accession number: O14727
Secondary accession number(s): O43297 , Q7Z438, Q9BXZ6, Q9UBZ5, Q9UGN8, Q9UGN9, Q9UGP0, Q9UJ58, Q9UJ59, Q9UJ60, Q9UJ61, Q9UJ62, Q9UJ63, Q9UJ64, Q9UJ65, Q9UJ66, Q9UJ67, Q9UNC9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 23, 2002
Last modified:	November 3, 2009
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.