O95831 (AIFM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 has a dual role in controlling cellular life and death; during apoptosis, it is translocated from the mitochondria to the nucleus to function as a proapoptotic factor in a caspase-independent pathway, while in normal mitochondria, it functions as an antiapoptotic factor via its 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. Ref.13 Ref.17 Ref.21
Cofactor	FAD.
Subunit structure	Interacts with XIAP/BIRC4. Interacts (via N-terminus) with EIF3G (via C-terminus). Ref.13 Ref.15
Subcellular location	Mitochondrion intermembrane space. Mitochondrion inner membrane. Cytoplasm. Nucleus. Cytoplasm › perinuclear region. Note: Proteolytic cleavage during or just after translocation into the mitochondrial intermembrane space (IMS) results in the formation of an inner-membrane-anchored mature form (AIFmit). During apoptosis, further proteolytic processing leads to a mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis. Colocalizes with EIF3G in the nucleus and perinuclear region. Ref.10 Ref.13 Ref.20
Tissue specificity	Isoform 5 is frequently down-regulated in human cancers. Ref.2
Post-translational modification	Under normal conditions, a 54-residue N-terminal segment is first proteolytically removed during or just after translocation into the mitochondrial intermembrane space (IMS) by the mitochondrial processing peptidase (MPP) to form the inner-membrane-anchored mature form (AIFmit). During apoptosis, it is further proteolytically processed at amino-acid position 101 leading to the generation of the mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis in a caspase-independent manner. Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation. Ubiquitination at Lys-255 by XIAP/BIRC4 blocks its ability to bind DNA and induce chromatin degradation, thereby inhibiting its ability to induce cell death.
Involvement in disease	Combined oxidative phosphorylation deficiency 6 (COXPD6) [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative disorder characterized by psychomotor delay, hypotonia, areflexia, muscle weakness and wasting. Some patients manifest prenatal ventriculomegaly and severe postnatal encephalomyopathy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21 Ref.22
Sequence similarities	Belongs to the FAD-dependent oxidoreductase family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion inner membrane Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Transit peptide
Ligand	DNA-binding FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay Ref.13. Source: UniProtKB apoptotic DNA fragmentation Traceable author statement Ref.1. Source: ProtInc cell redox homeostasis Inferred from electronic annotation. Source: InterPro intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial respiratory chain complex I assembly Inferred from mutant phenotype PubMed 20111043PubMed 20111043. Source: UniProtKB neuron apoptotic process Inferred from electronic annotation. Source: Compara neuron differentiation Inferred from direct assay PubMed 20111043. Source: UniProtKB
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial intermembrane space Inferred from direct assay Ref.10. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW electron carrier activity Traceable author statement Ref.1. Source: ProtInc flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KANK2	Q63ZY3	2	EBI-356440,EBI-2556193
KANK2	Q63ZY3-2	4	EBI-356440,EBI-6244894
TSC22D4	Q9Y3Q8	2	EBI-356440,EBI-739485

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95831-1)

Also known as: AIF;

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)

Also known as: AIF-exB;

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

Isoform 4 (identifier: O95831-4)

Also known as: AIFsh2;

The sequence of this isoform differs from the canonical sequence as follows:
     323-324: AR → DI
     325-613: Missing.

Note: Does not induce nuclear apoptosis.

Isoform 5 (identifier: O95831-5)

Also known as: AIFsh;

The sequence of this isoform differs from the canonical sequence as follows:
     1-352: Missing.

Note: Localizes in the cytoplasm.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 54

54

Mitochondrion Ref.10

Propeptide

55 – 101

47

Removed in mature form

PRO_0000401935

Chain

102 – 613

512

Apoptosis-inducing factor 1, mitochondrial

PRO_0000022030

Regions

Nucleotide binding

138 – 142

5

FAD

Nucleotide binding

164 – 165

2

FAD

Nucleotide binding

454 – 455

2

FAD

Region

134 – 483

350

FAD-dependent oxidoreductase By similarity

Motif

446 – 451

6

Nuclear localization signal Potential

Sites

Binding site

172

1

FAD

Binding site

177

1

FAD

Binding site

233

1

FAD; via amide nitrogen and carbonyl oxygen

Binding site

285

1

FAD

Binding site

438

1

FAD

Binding site

483

1

FAD; via carbonyl oxygen

Amino acid modifications

Modified residue

105

1

Phosphothreonine Ref.14

Modified residue

268

1

Phosphoserine Ref.16

Modified residue

593

1

N6-acetyllysine By similarity

Cross-link

255

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.19

Natural variations

Alternative sequence

1 – 352

352

Missing in isoform 5.

VSP_046248

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

Alternative sequence

323 – 324

2

AR → DI in isoform 4.

VSP_043637

Alternative sequence

325 – 613

289

Missing in isoform 4.

VSP_043638

Natural variant

201

1

Missing in COXPD6; higher DNA binding affinity, partially impaired flavin binding and association with increased parthanatos-linked cell death. Ref.21

VAR_063827

Natural variant

308

1

G → E in COXPD6; with prenatal ventriculomegaly and severe postnatal encephalomyopathy. Ref.22

VAR_067334

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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 (AIF) [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	FASTA	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 (AIF-exB) [UniParc]. Checksum: 313ADD6FA4E5D61A	FASTA	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
	Isoform 4 (AIFsh2) [UniParc]. Checksum: 259AA55812C2F07E	FASTA	324	35,384
	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 KSITIIGGGF LGSELACALG RKDI
	Isoform 5 (AIFsh) [UniParc]. Checksum: B05C9E9F3AA3F2E3	FASTA	261	28,404
	10 20 30 40 50 60 MEKVRREGVK VMPNAIVQSV GVSSGKLLIK LKDGRKVETD HIVAAVGLEP NVELAKTGGL 70 80 90 100 110 120 EIDSDFGGFR VNAELQARSN IWVAGDAACF YDIKLGRRRV EHHDHAVVSG RLAGENMTGA 130 140 150 160 170 180 AKPYWHQSMF WSDLGPDVGY EAIGLVDSSL PTVGVFAKAT AQDNPKSATE QSGTGIRSES 190 200 210 220 230 240 ETESEASEIT IPPSTPAVPQ APVQGEDYGK GVIFYLRDKV VVGIVLWNIF NRMPIARKII 250 260 KDGEQHEDLN EVAKLFNIHE D

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of mitochondrial apoptosis-inducing factor." Susin S.A., Lorenzo H.K., Zamzami N., Marzo I., Snow B.E., Brothers G.M., Mangion J., Jacotot E., Costantini P., Loeffler M., Larochette N., Goodlett D.R., Aebersold R., Siderovski D.P., Penninger J.M., Kroemer G. Nature 397:441-446(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with potential pathological relevance in human cancer." Delettre C., Yuste V.J., Moubarak R.S., Bras M., Lesbordes-Brion J.-C., Petres S., Bellalou J., Susin S.A. J. Biol. Chem. 281:6413-6427(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[3]	"Identification and characterization of AIFsh2, a mitochondrial apoptosis-inducing factor (AIF) isoform with NADH oxidase activity." Delettre C., Yuste V.J., Moubarak R.S., Bras M., Robert N., Susin S.A. J. Biol. Chem. 281:18507-18518(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), ALTERNATIVE SPLICING.
[4]	Rhodes S. Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Kidney.
[6]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Brain.
[10]	"Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space." Otera H., Ohsakaya S., Nagaura Z., Ishihara N., Mihara K. EMBO J. 24:1375-1386(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 55-59, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE.
[11]	Mei G., Yu W., Gibbs R.A. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 171-613. Tissue: Brain.
[12]	"Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis." Daugas E., Nochy D., Ravagnan L., Loeffler M., Susin S.A., Zamzami N., Kroemer G. FEBS Lett. 476:118-123(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[13]	"Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g)." Kim J.T., Kim K.D., Song E.Y., Lee H.G., Kim J.W., Kim J.W., Chae S.K., Kim E., Lee M.S., Yang Y., Lim J.S. FEBS Lett. 580:6375-6383(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF3G.
[14]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-105, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP." Wilkinson J.C., Wilkinson A.S., Galban S., Csomos R.A., Duckett C.S. Mol. Cell. Biol. 28:237-247(2008) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY XIAP/BIRC4, INTERACTION WITH XIAP/BIRC4.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Apoptosis-inducing factor plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells." Son Y.O., Jang Y.S., Heo J.S., Chung W.T., Choi K.C., Lee J.C. Apoptosis 14:796-808(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[18]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation." Lewis E.M., Wilkinson A.S., Davis N.Y., Horita D.A., Wilkinson J.C. Biochemistry 50:11084-11096(2011) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION AT LYS-255 BY XIAP/BIRC4.
[20]	"DNA binding is required for the apoptogenic action of apoptosis inducing factor." Ye H., Cande C., Stephanou N.C., Jiang S., Gurbuxani S., Larochette N., Daugas E., Garrido C., Kroemer G., Wu H. Nat. Struct. Biol. 9:680-684(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 121-613 IN COMPLEX WITH FAD, SUBCELLULAR LOCATION, DNA-BINDING.
[21]	"Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor." Ghezzi D., Sevrioukova I., Invernizzi F., Lamperti C., Mora M., D'Adamo P., Novara F., Zuffardi O., Uziel G., Zeviani M. Am. J. Hum. Genet. 86:639-649(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT COXPD6 ARG-201 DEL, CHARACTERIZATION OF VARIANT COXPD6 ARG-201 DEL, FUNCTION.
[22]	"Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing." Berger I., Ben-Neriah Z., Dor-Wolman T., Shaag A., Saada A., Zenvirt S., Raas-Rothschild A., Nadjari M., Kaestner K.H., Elpeleg O. Mol. Genet. Metab. 104:517-520(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT COXPD6 GLU-308.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF100928 mRNA. Translation: AAD16436.1.
DQ016496 mRNA. Translation: AAY84737.1.
DQ016498 mRNA. Translation: AAY84739.1.
AL049703 mRNA. Translation: CAB41267.1.
AL049704 mRNA. Translation: CAB41268.1.
AK314446 mRNA. Translation: BAG37055.1.
CR457379 mRNA. Translation: CAG33660.1.
AL139234 Genomic DNA. Translation: CAI42778.1.
AL139234 Genomic DNA. Translation: CAI42779.1.
AL139234 Genomic DNA. Translation: CAI42780.1.
CH471107 Genomic DNA. Translation: EAX11811.1.
CH471107 Genomic DNA. Translation: EAX11812.1.
CH471107 Genomic DNA. Translation: EAX11810.1.
BC111065 mRNA. Translation: AAI11066.1.
BC139738 mRNA. Translation: AAI39739.1.
AF131759 mRNA. Translation: AAD20036.1.

IPI

IPI00000690.
IPI00157908.
IPI00300018.
IPI00976931.
IPI01015707.

RefSeq

NP_001124318.1. NM_001130846.2.
NP_001124319.1. NM_001130847.3.
NP_004199.1. NM_004208.3.
NP_665811.1. NM_145812.2.
NP_665812.1. NM_145813.2.

UniGene

Hs.424932.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M6I	X-ray	1.80	A	121-613	[»]
4FDC	X-ray	2.40	B	103-613	[»]

ProteinModelPortal

O95831.

ModBase

Search...

Protein-protein interaction databases

IntAct

O95831. 23 interactions.

MINT

MINT-209209.

STRING

9606.ENSP00000287295.

PTM databases

PhosphoSite

O95831.

2D gel databases

REPRODUCTION-2DPAGE

IPI00157908.

UCD-2DPAGE

O95831.

Proteomic databases

PaxDb

O95831.

PRIDE

O95831.

Protocols and materials databases

DNASU

51060.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000287295; ENSP00000287295; ENSG00000156709.
ENST00000319908; ENSP00000315122; ENSG00000156709.
ENST00000346424; ENSP00000316320; ENSG00000156709.
ENST00000416073; ENSP00000402535; ENSG00000156709.
ENST00000440263; ENSP00000405879; ENSG00000156709.

GeneID

9131.

KEGG

hsa:9131.

UCSC

uc004evg.3. human.
uc004evh.3. human.
uc004evi.3. human.

Organism-specific databases

CTD

9131.

GeneCards

GC0XM129263.

HGNC

HGNC:8768. AIFM1.

HPA

CAB003764.

MIM

300169. gene.
300816. phenotype.

neXtProt

NX_O95831.

Orphanet

238329. Severe X-linked mitochondrial encephalomyopathy.

PharmGKB

PA162376129.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0446.

HOGENOM

HOG000124580.

HOVERGEN

HBG053538.

InParanoid

O95831.

KO

K04727.

OMA

KIGDFRT.

OrthoDB

EOG40S0FD.

PhylomeDB

O95831.

Enzyme and pathway databases

Pathway_Interaction_DB

ceramidepathway. Ceramide signaling pathway.

Gene expression databases

ArrayExpress

O95831.

Bgee

O95831.

CleanEx

HS_AIFM1.

Genevestigator

O95831.

GermOnline

ENSG00000156709. Homo sapiens.

Family and domain databases

Gene3D

3.30.390.30. 1 hit.

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.
[Graphical view]

Pfam

PF00070. Pyr_redox. 1 hit.
PF07992. Pyr_redox_2. 1 hit.
[Graphical view]

PRINTS

PR00368. FADPNR.

SUPFAM

SSF55424. FAD/NAD-linked_reductase_dimer. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

AIFM1. human.

EvolutionaryTrace

O95831.

GenomeRNAi

9131.

NextBio

34229.

SOURCE

Search...

Entry information

Entry name

AIFM1_HUMAN

Accession

Primary (citable) accession number: O95831
Secondary accession number(s): A4QPB4 , B1ALN1, B2RB08, D3DTE9, Q1L6K6, Q2QKE4, Q5JUZ7, Q6I9X6, Q9Y3I3, Q9Y3I4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 136 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.