Reviewed, UniProtKB/Swiss-Prot O95831 (AIFM1_HUMAN)

Names and origin

Protein names

Recommended name:
    Apoptosis-inducing factor 1, mitochondrial
    EC=1.-.-.-
Alternative name(s):
    Programmed cell death protein 8

Gene names

Name:	AIFM1
Synonyms:	AIF, PDCD8

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	613 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Probable oxidoreductase that acts as a caspase-independent mitochondrial effector of apoptotic cell death. Extramitochondrial AIF induces nuclear chromatin condensation and large scale DNA fragmentation (in vitro). Binds to DNA in a sequence-independent manner.
Cofactor	FAD.
Subunit structure	Interacts with XIAP.
Subcellular location	Mitochondrion intermembrane space. Nucleus. Note= Translocated to the nucleus upon induction of apoptosis.
Sequence similarities	Belongs to the FAD-dependent oxidoreductase family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Ligand	DNA-binding FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction resulting in induction of apoptosis Ref.1 Traceable author statement. Source: ProtInc DNA fragmentation during apoptosis Ref.1 Traceable author statement. Source: ProtInc cell redox homeostasis Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial intermembrane space Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Ref.1 Traceable author statement. Source: ProtInc
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW FAD binding Inferred from electronic annotation. Source: InterPro electron carrier activity Ref.1 Traceable author statement. Source: ProtInc oxidoreductase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRF2	Q9HAW0	1	EBI-356440,EBI-1055224
C20orf24	Q9BUV8	1	EBI-356440,EBI-1050079
MLF2	Q15773	1	EBI-356440,EBI-1051875
PELO	Q9BRX2	1	EBI-356440,EBI-1043580
PTP4A3	O75365	1	EBI-356440,EBI-1043866
TSC22D4	Q9Y3Q8	1	EBI-356440,EBI-739485

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95831-1)

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: O95831-2)

The sequence of this isoform differs from the canonical sequence as follows:
     36-322: Missing.

Isoform 3 (identifier: O95831-3)

The sequence of this isoform differs from the canonical sequence as follows:
     36-82: GNLFQRWHVP...VGLSTVGAGA → VVQSHHLGSP...GATVTGAGVY

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 102

102

Mitochondrion By similarity

Chain

103 – 613

511

Apoptosis-inducing factor 1, mitochondrial

PRO_0000022030

Regions

Nucleotide binding

138 – 142

5

FAD By similarity

Nucleotide binding

164 – 165

2

FAD By similarity

Nucleotide binding

454 – 455

2

FAD By similarity

Region

134 – 483

350

FAD-dependent oxidoreductase By similarity

Motif

446 – 451

6

Nuclear localization signal Potential

Sites

Binding site

172

1

FAD By similarity

Binding site

177

1

FAD By similarity

Binding site

233

1

FAD; via amide nitrogen and carbonyl oxygen By similarity

Binding site

285

1

FAD By similarity

Binding site

438

1

FAD By similarity

Binding site

483

1

FAD; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue

593

1

N6-acetyllysine By similarity

Natural variations

Alternative sequence

36 – 322

287

Missing in isoform 2.

VSP_004357

Alternative sequence

36 – 82

47

GNLFQ…VGAGA → VVQSHHLGSPSRSLASTGAS GKDGSNLVYFLIVGATVTGA GVY in isoform 3.

VSP_022953

Secondary structure

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613

Helix Strand Turn

Details...

Beta strand

130 – 138

9

Helix

141 – 153

13

Beta strand

158 – 167

10

Helix

173 – 176

4

Helix

178 – 180

3

Helix

187 – 190

4

Beta strand

192 – 194

3

Beta strand

200 – 206

7

Helix

208 – 210

3

Turn

214 – 219

6

Beta strand

224 – 229

6

Beta strand

233 – 237

5

Turn

238 – 241

4

Beta strand

242 – 245

4

Beta strand

250 – 258

9

Beta strand

262 – 264

3

Helix

268 – 271

4

Helix

275 – 279

5

Beta strand

281 – 283

3

Helix

287 – 299

13

Beta strand

301 – 306

6

Helix

310 – 326

17

Beta strand

329 – 333

5

Beta strand

335 – 338

4

Turn

339 – 343

5

Helix

346 – 357

12

Turn

358 – 360

3

Beta strand

362 – 364

3

Beta strand

369 – 375

7

Beta strand

378 – 383

6

Beta strand

388 – 396

9

Beta strand

400 – 402

3

Helix

407 – 410

4

Turn

416 – 418

3

Beta strand

420 – 422

3

Beta strand

428 – 430

3

Beta strand

433 – 435

3

Helix

437 – 439

3

Beta strand

440 – 444

5

Turn

445 – 447

3

Beta strand

448 – 450

3

Helix

455 – 469

15

Beta strand

481 – 487

7

Beta strand

491 – 496

6

Beta strand

504 – 509

6

Helix

517 – 524

8

Helix

529 – 532

4

Beta strand

562 – 569

8

Beta strand

572 – 580

9

Helix

585 – 594

10

Helix

604 – 607

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: A156762BC64E6340	FASTA	613	66,901
	10 20 30 40 50 60 MFRCGGLAAG ALKQKLVPLV RTVCVRSPRQ RNRLPGNLFQ RWHVPLELQM TRQMASSGAS 70 80 90 100 110 120 GGKIDNSVLV LIVGLSTVGA GAYAYKTMKE DEKRYNERIS GLGLTPEQKQ KKAALSASEG 130 140 150 160 170 180 EEVPQDKAPS HVPFLLIGGG TAAFAAARSI RARDPGARVL IVSEDPELPY MRPPLSKELW 190 200 210 220 230 240 FSDDPNVTKT LRFKQWNGKE RSIYFQPPSF YVSAQDLPHI ENGGVAVLTG KKVVQLDVRD 250 260 270 280 290 300 NMVKLNDGSQ ITYEKCLIAT GGTPRSLSAI DRAGAEVKSR TTLFRKIGDF RSLEKISREV 310 320 330 340 350 360 KSITIIGGGF LGSELACALG RKARALGTEV IQLFPEKGNM GKILPEYLSN WTMEKVRREG 370 380 390 400 410 420 VKVMPNAIVQ SVGVSSGKLL IKLKDGRKVE TDHIVAAVGL EPNVELAKTG GLEIDSDFGG 430 440 450 460 470 480 FRVNAELQAR SNIWVAGDAA CFYDIKLGRR RVEHHDHAVV SGRLAGENMT GAAKPYWHQS 490 500 510 520 530 540 MFWSDLGPDV GYEAIGLVDS SLPTVGVFAK ATAQDNPKSA TEQSGTGIRS ESETESEASE 550 560 570 580 590 600 ITIPPSTPAV PQAPVQGEDY GKGVIFYLRD KVVVGIVLWN IFNRMPIARK IIKDGEQHED 610 LNEVAKLFNI HED
	Isoform 2 [UniParc]. Checksum: A87ACDC0A0556040		326	35,638
	10 20 30 40 50 60 MFRCGGLAAG ALKQKLVPLV RTVCVRSPRQ RNRLPARALG TEVIQLFPEK GNMGKILPEY 70 80 90 100 110 120 LSNWTMEKVR REGVKVMPNA IVQSVGVSSG KLLIKLKDGR KVETDHIVAA VGLEPNVELA 130 140 150 160 170 180 KTGGLEIDSD FGGFRVNAEL QARSNIWVAG DAACFYDIKL GRRRVEHHDH AVVSGRLAGE 190 200 210 220 230 240 NMTGAAKPYW HQSMFWSDLG PDVGYEAIGL VDSSLPTVGV FAKATAQDNP KSATEQSGTG 250 260 270 280 290 300 IRSESETESE ASEITIPPST PAVPQAPVQG EDYGKGVIFY LRDKVVVGIV LWNIFNRMPI 310 320 ARKIIKDGEQ HEDLNEVAKL FNIHED
	Isoform 3 [UniParc]. Checksum: 313ADD6FA4E5D61A		609	66,295
	10 20 30 40 50 60 MFRCGGLAAG ALKQKLVPLV RTVCVRSPRQ RNRLPVVQSH HLGSPSRSLA STGASGKDGS 70 80 90 100 110 120 NLVYFLIVGA TVTGAGVYYA YKTMKEDEKR YNERISGLGL TPEQKQKKAA LSASEGEEVP 130 140 150 160 170 180 QDKAPSHVPF LLIGGGTAAF AAARSIRARD PGARVLIVSE DPELPYMRPP LSKELWFSDD 190 200 210 220 230 240 PNVTKTLRFK QWNGKERSIY FQPPSFYVSA QDLPHIENGG VAVLTGKKVV QLDVRDNMVK 250 260 270 280 290 300 LNDGSQITYE KCLIATGGTP RSLSAIDRAG AEVKSRTTLF RKIGDFRSLE KISREVKSIT 310 320 330 340 350 360 IIGGGFLGSE LACALGRKAR ALGTEVIQLF PEKGNMGKIL PEYLSNWTME KVRREGVKVM 370 380 390 400 410 420 PNAIVQSVGV SSGKLLIKLK DGRKVETDHI VAAVGLEPNV ELAKTGGLEI DSDFGGFRVN 430 440 450 460 470 480 AELQARSNIW VAGDAACFYD IKLGRRRVEH HDHAVVSGRL AGENMTGAAK PYWHQSMFWS 490 500 510 520 530 540 DLGPDVGYEA IGLVDSSLPT VGVFAKATAQ DNPKSATEQS GTGIRSESET ESEASEITIP 550 560 570 580 590 600 PSTPAVPQAP VQGEDYGKGV IFYLRDKVVV GIVLWNIFNR MPIARKIIKD GEQHEDLNEV AKLFNIHED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of mitochondrial apoptosis-inducing factor." Susin S.A., Lorenzo H.K.,