CPLM-001673

Genbank Nucleotide ID

Apoptosis-inducing factor 1, mitochondrial

Protein Synonyms/Alias

Programmed cell death protein 8

Homo sapiens (Human)

Position	Peptide	Type	References
75	KVRREGVKVMPNAIV	ubiquitination	[1]
231	ATAQDNPKSATEQSG	ubiquitination	[1]

[1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]

Functional Description

Functions both as NADH oxidoreductase and as regulator of apoptosis. In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway. In contrast, functions as an antiapoptotic factor in normal mitochondria via its NADH oxidoreductase activity. The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA. Interacts with EIF3G,and thereby inhibits the EIF3 machinery and protein synthesis, and activates casapse-7 to amplify apoptosis. Plays a critical role in caspase- independent, pyknotic cell death in hydrogen peroxide-exposed cells. Binds to DNA in a sequence-independent manner.

NP_BIND 138 142 FAD.
NP_BIND 164 165 FAD.
NP_BIND 454 455 FAD.
REGION 134 483 FAD-dependent oxidoreductase (By
MOTIF 446 451 Nuclear localization signal (Potential).
BINDING 172 172 FAD.
BINDING 177 177 FAD.
BINDING 233 233 FAD; via amide nitrogen and carbonyl
BINDING 285 285 FAD.
BINDING 438 438 FAD.
BINDING 483 483 FAD; via carbonyl oxygen.
MOD_RES 105 105 Phosphothreonine.
MOD_RES 268 268 Phosphoserine.
MOD_RES 593 593 N6-acetyllysine (By similarity).
CROSSLNK 255 255 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Acetylation; Alternative splicing; Apoptosis; Charcot-Marie-Tooth disease; Complete proteome; Cytoplasm; Deafness; Direct protein sequencing; Disease mutation; DNA-binding; FAD; Flavoprotein; Isopeptide bond; Membrane; Mental retardation; Mitochondrion; Mitochondrion inner membrane; NAD; Neurodegeneration; Neuropathy; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; ISS:UniProtKB.
GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
GO:0005634; C:nucleus; IDA:UniProtKB.
GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
GO:0009055; F:electron carrier activity; TAS:ProtInc.
GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
GO:0016651; F:oxidoreductase activity, acting on NAD(P)H; IDA:UniProtKB.
GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
GO:0006309; P:apoptotic DNA fragmentation; TAS:ProtInc.
GO:0045454; P:cell redox homeostasis; IEA:InterPro.
GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
GO:0051402; P:neuron apoptotic process; IEA:Compara.
GO:0030182; P:neuron differentiation; IDA:UniProtKB.

IPR016156; FAD/NAD-linked_Rdtase_dimer.
IPR013027; FAD_pyr_nucl-diS_OxRdtase.
IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
IPR023753; Pyr_nucl-diS_OxRdtase_FAD/NAD.
IPR001327; Pyr_OxRdtase_NAD-bd_dom.

PF00070; Pyr_redox
PF07992; Pyr_redox_2