O88879

EV
Gene name
Apaf1
Protein name
Apoptotic protease-activating factor 1
Names
APAF-1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:11783
EC number
Protein Class
APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 (PTHR22845)

Descriptions

Apoptotic protease-activating factor 1 (Apaf-1) is a key player in the mitochondrial pathway of apoptosis and composed of three main domains: the N-terminal caspase recruitment domain (CARD), the nucleotide-binding and oligomerization domain (NOD), and the C-terminal WD40-repeat domain (two b-propellers, WD1 and WD2). The NOD is subdivided into the NB-ARC domain and the helical domain. Apaf-1 forms fully inhibited conformation in the absence of cytochrome c with ADP bound in the nucleotide binding site. The NB-ARC domain is held in place through interactions with the b-propeller WD1 and with the helical domain of the NOD, respectively. The presence of a gamma-phosphate in the nucleotide binding site leads to the formation of a salt bridge between R265 and ATP, which is a prerequisite for subsequent rotation of the NB-ARC domain. Binding of cytochrome c between the b-propellers causes propeller WD1 to swing out of its resting position, thereby releasing the attachment of the NB-ARC domain to the regulatory domain. Rotation of the NB-ARC domain exposes the contact areas for oligomerization and relocates the CARD. Apoptotic oligomerization of open Apaf-1 monomers arranges the flexibly tethered CARDs in the central hub of the apoptosomal wheel, where they bind procaspase-9 molecules for activation of the death cascade.

Autoinhibitory domains (AIDs)

593-1246 (WD40 repeats) EV

Target domain

130-374 (NB-ARC domain)

Relief mechanism

Ligand binding, Partner binding

Assay

Structural analysis

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

3 structures for O88879

Entry ID Method Resolution Chain Position Source
3SFZ X-ray 300 A A 1-1249 PDB
3SHF X-ray 355 A A 1-1249 PDB
AF-O88879-F1 Predicted AlphaFoldDB

11 variants for O88879

Variant ID(s) Position Change Description Diseaes Association Provenance
rs1134374437 69 I>V No Ensembl
rs36503066 369 S>L No Ensembl
rs264570704 408 T>M No Ensembl
rs220086528 588 G>V No Ensembl
rs238694428 598 I>M No Ensembl
rs36862062 645 E>K No Ensembl
rs264787327 952 K>Q No Ensembl
rs258437295 1000 V>I No Ensembl
rs244864145 1093 I>V No Ensembl
rs39345271 1097 A>S No Ensembl
rs38241400 1168 I>V No Ensembl

No associated diseases with O88879

40 regional properties for O88879

Type Name Position InterPro Accession
domain Protein kinase domain 1606 - 1859 IPR000719-1
domain Protein kinase domain 2961 - 3213 IPR000719-2
domain Immunoglobulin subtype 2 57 - 117 IPR003598-1
domain Immunoglobulin subtype 2 739 - 806 IPR003598-2
domain Immunoglobulin subtype 2 886 - 954 IPR003598-3
domain Immunoglobulin subtype 2 985 - 1053 IPR003598-4
domain Immunoglobulin subtype 2 1081 - 1148 IPR003598-5
domain Immunoglobulin subtype 2 1205 - 1272 IPR003598-6
domain Immunoglobulin subtype 2 1502 - 1569 IPR003598-7
domain Immunoglobulin subtype 2 2599 - 2667 IPR003598-8
domain Immunoglobulin subtype 51 - 128 IPR003599-1
domain Immunoglobulin subtype 733 - 817 IPR003599-2
domain Immunoglobulin subtype 880 - 965 IPR003599-3
domain Immunoglobulin subtype 979 - 1064 IPR003599-4
domain Immunoglobulin subtype 1075 - 1159 IPR003599-5
domain Immunoglobulin subtype 1199 - 1283 IPR003599-6
domain Immunoglobulin subtype 1401 - 1487 IPR003599-7
domain Immunoglobulin subtype 1496 - 1580 IPR003599-8
domain Immunoglobulin subtype 2593 - 2678 IPR003599-9
domain Fibronectin type III 1287 - 1387 IPR003961-1
domain Fibronectin type III 2681 - 2777 IPR003961-2
domain Immunoglobulin-like domain 45 - 126 IPR007110-1
domain Immunoglobulin-like domain 727 - 815 IPR007110-2
domain Immunoglobulin-like domain 874 - 963 IPR007110-3
domain Immunoglobulin-like domain 968 - 1062 IPR007110-4
domain Immunoglobulin-like domain 1069 - 1157 IPR007110-5
domain Immunoglobulin-like domain 1193 - 1283 IPR007110-6
domain Immunoglobulin-like domain 1490 - 1578 IPR007110-7
domain Immunoglobulin-like domain 2586 - 2676 IPR007110-8
active_site Serine/threonine-protein kinase, active site 1720 - 1732 IPR008271-1
active_site Serine/threonine-protein kinase, active site 3076 - 3088 IPR008271-2
domain Immunoglobulin I-set 45 - 127 IPR013098-1
domain Immunoglobulin I-set 727 - 816 IPR013098-2
domain Immunoglobulin I-set 874 - 964 IPR013098-3
domain Immunoglobulin I-set 976 - 1063 IPR013098-4
domain Immunoglobulin I-set 1070 - 1158 IPR013098-5
domain Immunoglobulin I-set 1193 - 1282 IPR013098-6
domain Immunoglobulin I-set 1490 - 1579 IPR013098-7
domain Immunoglobulin I-set 2587 - 2677 IPR013098-8
binding_site Protein kinase, ATP binding site 1612 - 1635 IPR017441

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
PANTHER Family PTHR22845 APOPTOTIC PROTEASE-ACTIVATING FACTOR 1
PANTHER Subfamily PTHR22845:SF5 APOPTOTIC PROTEASE-ACTIVATING FACTOR 1
PANTHER Protein Class
PANTHER Pathway Category p53 pathway
Apaf
Apoptosis signaling pathway
Apaf-1
FAS signaling pathway
Apaf1
Huntington disease
Apaf-1

5 GO annotations of cellular component

Name Definition
apoptosome A multisubunit protein complex involved in the signaling phase of the apoptotic process. In mammals it is typically composed of seven Apaf-1 subunits bound to cytochrome c and caspase-9. A similar complex to promote apoptosis is formed from homologous gene products in other eukaryotic organisms.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
protein-containing complex A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.

5 GO annotations of molecular function

Name Definition
ADP binding Binding to ADP, adenosine 5'-diphosphate.
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
cysteine-type endopeptidase activator activity involved in apoptotic process Binds to and increases the rate of proteolysis catalyzed by a cysteine-type endopeptidase involved in the apoptotic process.
heat shock protein binding Binding to a heat shock protein, a protein synthesized or activated in response to heat shock.
identical protein binding Binding to an identical protein or proteins.

17 GO annotations of biological process

Name Definition
activation of cysteine-type endopeptidase activity Any process that initiates the activity of the inactive enzyme cysteine-type endopeptidase.
activation of cysteine-type endopeptidase activity involved in apoptotic process Any process that initiates the activity of the inactive enzyme cysteine-type endopeptidase in the context of an apoptotic process.
activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c Any process that initiates the activity of the inactive enzyme cysteine-type endopeptidase in the context of an apoptotic process and is mediated by cytochrome c.
aging A developmental process that is a deterioration and loss of function over time. Aging includes loss of functions such as resistance to disease, homeostasis, and fertility, as well as wear and tear. Aging includes cellular senescence, but is more inclusive. May precede death and may succeed developmental maturation (GO:0021700).
brain development The process whose specific outcome is the progression of the brain over time, from its formation to the mature structure. Brain development begins with patterning events in the neural tube and ends with the mature structure that is the center of thought and emotion. The brain is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
cardiac muscle cell apoptotic process A form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases, whose actions dismantle a cardiac muscle cell and result in its death. Cardiac muscle cells are striated muscle cells that are responsible for heart contraction.
cell differentiation The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
cellular response to transforming growth factor beta stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a transforming growth factor beta stimulus.
forebrain development The process whose specific outcome is the progression of the forebrain over time, from its formation to the mature structure. The forebrain is the anterior of the three primary divisions of the developing chordate brain or the corresponding part of the adult brain (in vertebrates, includes especially the cerebral hemispheres, the thalamus, and the hypothalamus and especially in higher vertebrates is the main control center for sensory and associative information processing, visceral functions, and voluntary motor functions).
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to a stimulus indicating endoplasmic reticulum (ER) stress, and ends when the execution phase of apoptosis is triggered. ER stress usually results from the accumulation of unfolded or misfolded proteins in the ER lumen.
kidney development The process whose specific outcome is the progression of the kidney over time, from its formation to the mature structure. The kidney is an organ that filters the blood and/or excretes the end products of body metabolism in the form of urine.
neural tube closure The last step in the formation of the neural tube, where the paired neural folds are brought together and fuse at the dorsal midline.
neuron apoptotic process Any apoptotic process in a neuron, the basic cellular unit of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system.
positive regulation of apoptotic signaling pathway Any process that activates or increases the frequency, rate or extent of apoptotic signaling pathway.
regulation of apoptotic DNA fragmentation Any process that modulates the frequency, rate or extent of apoptotic DNA fragmentation.
response to hypoxia Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
response to nutrient Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nutrient stimulus.

4 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q3MJ13 WDR72 WD repeat-containing protein 72 Homo sapiens (Human) PR
O14727 APAF1 Apoptotic protease-activating factor 1 Homo sapiens (Human) EV
Q9EPV5 Apaf1 Apoptotic protease-activating factor 1 Rattus norvegicus (Rat) SS
Q9I9H8 apaf1 Apoptotic protease-activating factor 1 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MDAKARNCLL QHREALEKDI KTSYIMDHMI SNGVLSVIEE EKVKSQATQY QRAAALIKMI
70 80 90 100 110 120
LNKDNCAYIS FYNALLHEGY KDLAALLQSG LPLVSSSSGK DTDGGITSFV RTVLCEGGVP
130 140 150 160 170 180
QRPVIFVTRK KLVHAIQQKL WKLNGEPGWV TIYGMAGCGK SVLAAEAVRD HSLLEGCFSG
190 200 210 220 230 240
GVHWVSIGKQ DKSGLLMKLQ NLCMRLDQEE SFSQRLPLNI EEAKDRLRVL MLRKHPRSLL
250 260 270 280 290 300
ILDDVWDPWV LKAFDNQCQI LLTTRDKSVT DSVMGPKHVV PVESGLGREK GLEILSLFVN
310 320 330 340 350 360
MKKEDLPAEA HSIIKECKGS PLVVSLIGAL LRDFPNRWAY YLRQLQNKQF KRIRKSSSYD
370 380 390 400 410 420
YEALDEAMSI SVEMLREDIK DYYTDLSILQ KDVKVPTKVL CVLWDLETEE VEDILQEFVN
430 440 450 460 470 480
KSLLFCNRNG KSFCYYLHDL QVDFLTEKNR SQLQDLHRKM VTQFQRYYQP HTLSPDQEDC
490 500 510 520 530 540
MYWYNFLAYH MASANMHKEL CALMFSLDWI KAKTELVGPA HLIHEFVAYR HILDEKDCAV
550 560 570 580 590 600
CENFQEFLSL NGHLLGRQPF PNIVQLGLCE PETSEVYRQA KLQAKQEGDT GRLYLEWINK
610 620 630 640 650 660
KTIKNLSRLV VRPHTDAVYH ACFSQDGQRI ASCGADKTLQ VFKAETGEKL LDIKAHEDEV
670 680 690 700 710 720
LCCAFSSDDS YIATCSADKK VKIWDSATGK LVHTYDEHSE QVNCCHFTNK SNHLLLATGS
730 740 750 760 770 780
NDFFLKLWDL NQKECRNTMF GHTNSVNHCR FSPDDELLAS CSADGTLRLW DVRSANERKS
790 800 810 820 830 840
INVKRFFLSS EDPPEDVEVI VKCCSWSADG DKIIVAAKNK VLLFDIHTSG LLAEIHTGHH
850 860 870 880 890 900
STIQYCDFSP YDHLAVIALS QYCVELWNID SRLKVADCRG HLSWVHGVMF SPDGSSFLTA
910 920 930 940 950 960
SDDQTIRVWE TKKVCKNSAI VLKQEIDVVF QENETMVLAV DNIRGLQLIA GKTGQIDYLP
970 980 990 1000 1010 1020
EAQVSCCCLS PHLEYVAFGD EDGAIKIIEL PNNRVFSSGV GHKKAVRHIQ FTADGKTLIS
1030 1040 1050 1060 1070 1080
SSEDSVIQVW NWQTGDYVFL QAHQETVKDF RLLQDSRLLS WSFDGTVKVW NVITGRIERD
1090 1100 1110 1120 1130 1140
FTCHQGTVLS CAISSDATKF SSTSADKTAK IWSFDLLSPL HELKGHNGCV RCSAFSLDGI
1150 1160 1170 1180 1190 1200
LLATGDDNGE IRIWNVSDGQ LLHSCAPISV EEGTATHGGW VTDVCFSPDS KTLVSAGGYL
1210 1220 1230 1240
KWWNVATGDS SQTFYTNGTN LKKIHVSPDF RTYVTVDNLG ILYILQVLE