UniProt Accession

 AIFM1_HUMAN; O95831; A4QPB4; B1ALN1; B2RB08; D3DTE9; Q1L6K4; Q1L6K6; Q2QKE4; Q5JUZ7; Q6I9X6; Q9Y3I3; Q9Y3I4 

Genbank Protein ID

 AF100928; DQ016496; DQ016498; DQ016500; AL049703; AL049704; AK314446; CR457379; AL139234; AL139234; AL139234; CH471107; CH471107; CH471107; BC111065; BC139738; AF131759 

Genbank Nucleotide ID

 AAD16436.1; AAY84737.1; AAY84739.1; AAY84741.1; CAB41267.1; CAB41268.1; BAG37055.1; CAG33660.1; CAI42778.1; CAI42779.1; CAI42780.1; EAX11811.1; EAX11812.1; EAX11810.1; AAI11066.1; AAI39739.1; AAD20036.1 

Protein Name

 Apoptosis-inducing factor 1, mitochondrial 

Protein Synonyms/Alias

 Programmed cell death protein 8 

Gene Name

 AIFM1 

Gene Synonyms/Alias

 AIF; PDCD8 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
109	LGLTPEQKQKKAALS	ubiquitination	[1, 2, 3]
189	SDDPNVTKTLRFKQW	ubiquitination	[2, 3, 4]
194	VTKTLRFKQWNGKER	ubiquitination	[4]
232	VAVLTGKKVVQLDVR	ubiquitination	[4]
255	GSQITYEKCLIATGG	ubiquitination	[3, 4]
295	GDFRSLEKISREVKS	acetylation	[5]
337	VIQLFPEKGNMGKIL	ubiquitination	[4]
518	ATAQDNPKSATEQSG	ubiquitination	[4, 6]

Reference

 [1] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 

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. 

Sequence Annotation

 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)  

Keyword

 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. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 613 AA 

Protein Sequence

Gene Ontology

 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. 

Interpro

 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. 

Pfam

 PF00070; Pyr_redox
 PF07992; Pyr_redox_2 

SMART

  

PROSITE

  

PRINTS

 PR00368; FADPNR.