Reviewed, UniProtKB/Swiss-Prot Q9BRQ8 (AIFM2_HUMAN)

Names and origin

Protein names

Recommended name:
    Apoptosis-inducing factor 2
    EC=1.-.-.-
Alternative name(s):
    Apoptosis-inducing factor-like mitochondrion-associated inducer of death
    Apoptosis-inducing factor homologous mitochondrion-associated inducer of death
    p53-responsive gene 3 protein

Gene names

Name:	AIFM2
Synonyms:	AMID, PRG3

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	373 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Oxidoreductase, which may play a role in mediating a TP53/p53-dependent apoptosis response. Probable oxidoreductase that acts as a caspase-independent mitochondrial effector of apoptotic cell death. Binds to DNA in a sequence-independent manner. May contribute to genotoxin-induced growth arrest. Ref.1 Ref.2 Ref.9
Cofactor	FAD. Binds 6-hydroxy-FAD non-covalently. Ref.9
Subcellular location	Cytoplasm. Mitochondrion outer membrane. Ref.1 Ref.2
Tissue specificity	Detected in most normal tissues as two transcripts of 1.8 and 4.0 kb in length, respectively. Highly expressed in heart, moderately in liver and skeletal muscles, and expressed at low levels in placenta, lung, kidney, and pancreas. Both transcripts expressed following TP53/p53 induction. The shorter 1.8 kb transcript seems to be the major transcript in EB1 colon cancer cells. Ref.1
Induction	Expression detected at 4 hours after induction by TP53/p53. Down-regulated in a wide range of human tumors. Ref.1 Ref.8
Sequence similarities	Belongs to the FAD-dependent oxidoreductase family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Ligand	DNA-binding FAD Flavoprotein
Molecular function	Oxidoreductase
Gene Ontology (GO)
Biological process	apoptotic mitochondrial changes Ref.2 Non-traceable author statement. Source: UniProtKB chromosome condensation Ref.2 Inferred from direct assay. Source: UniProtKB induction of apoptosis Ref.2 Inferred from mutant phenotype. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Ref.2 Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Ref.2 Inferred from direct assay. Source: UniProtKB
Molecular function	DNA binding Ref.9 Inferred from direct assay. Source: UniProtKB FAD binding Ref.9 Inferred from direct assay. Source: UniProtKB electron-transferring-flavoprotein dehydrogenase activity Ref.2 Ref.9 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 Ref.1 Ref.2 (identifier: Q9BRQ8-1)

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 Ref.6 (identifier: Q9BRQ8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     99-138: Missing.
     206-206: S → SLLG

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 373	373	Apoptosis-inducing factor 2		PRO_0000238922
Regions
	Transmembrane	7 – 27	21	Potential
	Nucleotide binding	18 – 22	5	FAD Potential
Sites
	Binding site	54	1	FAD Potential
	Binding site	82	1	FAD; via amide nitrogen and carbonyl oxygen Potential
	Binding site	285	1	FAD Potential
Natural variations
	Alternative sequence	99 – 138	40	Missing in isoform 2. Ref.6		VSP_052047
	Alternative sequence	206	1	S → SLLG in isoform 2. Ref.6		VSP_052048
	Natural variant	135	1	M → T: dbSNP rs10999147.		VAR_050651
	Natural variant	288	1	D → N: dbSNP rs2271694.		VAR_050652

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 47F2E6F682D4C060	FASTA	373	40,527
	10 20 30 40 50 60 MGSQVSVESG ALHVVIVGGG FGGIAAASQL QALNVPFMLV DMKDSFHHNV AALRASVETG 70 80 90 100 110 120 FAKKTFISYS VTFKDNFRQG LVVGIDLKNQ MVLLQGGEAL PFSHLILATG STGPFPGKFN 130 140 150 160 170 180 EVSSQQAAIQ AYEDMVRQVQ RSRFIVVVGG GSAGVEMAAE IKTEYPEKEV TLIHSQVALA 190 200 210 220 230 240 DKELLPSVRQ EVKEILLRKG VQLLLSERVS NLEELPLNEY REYIKVQTDK GTEVATNLVI 250 260 270 280 290 300 LCTGIKINSS AYRKAFESRL ASSGALRVNE HLQVEGHSNV YAIGDCADVR TPKMAYLAGL 310 320 330 340 350 360 HANIAVANIV NSVKQRPLQA YKPGALTFLL SMGRNDGVGQ ISGFYVGRLM VRLTKSRDLF 370 VSTSWKTMRQ SPP
	Isoform 2. Checksum: 30E3D34AE9CE8EFA	FASTA	336	36,520
	10 20 30 40 50 60 MGSQVSVESG ALHVVIVGGG FGGIAAASQL QALNVPFMLV DMKDSFHHNV AALRASVETG 70 80 90 100 110 120 FAKKTFISYS VTFKDNFRQG LVVGIDLKNQ MVLLQGGEVQ RSRFIVVVGG GSAGVEMAAE 130 140 150 160 170 180 IKTEYPEKEV TLIHSQVALA DKELLPSVRQ EVKEILLRKG VQLLLSLLGE RVSNLEELPL 190 200 210 220 230 240 NEYREYIKVQ TDKGTEVATN LVILCTGIKI NSSAYRKAFE SRLASSGALR VNEHLQVEGH 250 260 270 280 290 300 SNVYAIGDCA DVRTPKMAYL AGLHANIAVA NIVNSVKQRP LQAYKPGALT FLLSMGRNDG 310 320 330 VGQISGFYVG RLMVRLTKSR DLFVSTSWKT MRQSPP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)." Ohiro Y., Garkavtsev I., Kobayashi S., Sreekumar K.R., Nantz R., Higashikubo B.T., Duffy S.L., Higashikubo R., Usheva A., Gius D., Kley N., Horikoshi N. FEBS Lett. 524:163-171(2002) [PubMed: 12135761] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
[2]	"AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis." Wu M., Xu L.-G., Li X., Zhai Z., Shu H.-B. J. Biol. Chem. 277:25617-25623(2002) [PubMed: 11980907] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Hippocampus.
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Kidney and Lung.
[7]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 23-373 (ISOFORM 2). Tissue: Oesophageal carcinoma.
[8]	"AMID is a p53-inducible gene downregulated in tumors." Wu M., Xu L.-G., Su T., Tian Y., Zhai Z., Shu H.-B. Oncogene 23:6815-6819(2004) [PubMed: 15273740] [Abstract] Cited for: INDUCTION.
[9]	"The human apoptosis-inducing protein AMID is an oxidoreductase with a modified flavin cofactor and DNA binding activity." Marshall K.R., Gong M., Wodke L., Lamb J.H., Jones D.J., Farmer P.B., Scrutton N.S., Munro A.W. J. Biol. Chem. 280:30735-30740(2005) [PubMed: 15958387] [Abstract] Cited for: FUNCTION, COFACTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF337957 mRNA. Translation: AAL73229.1. AF506757 mRNA. Translation: AAM77596.1. AK027403 mRNA. Translation: BAB55089.1. AK127353 mRNA. Translation: BAG54492.1. AL731540 Genomic DNA. Translation: CAI13684.1. CH471083 Genomic DNA. Translation: EAW54376.1. BC006121 mRNA. Translation: AAH06121.1. BC023601 mRNA. Translation: AAH23601.1. BX537621 mRNA. Translation: CAH56481.1.
IPI	IPI00013909. IPI00759583.
RefSeq	NP_116186.1.
UniGene	Hs.655377
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	Q9BRQ8.
Genome annotation databases
Ensembl	ENSG00000042286. Homo sapiens. [Contig view]
GeneID	84883.
KEGG	hsa:84883.
Organism-specific databases
GeneCards	GC10M071528.
H-InvDB	HIX0008891. HIX0026110.
HGNC	HGNC:21411. AIFM2.
MIM	605159. gene.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9BRQ8.
OMA	Q9BRQ8. ISRIIHP.
Gene expression databases
ArrayExpress	Q9BRQ8.
Bgee	Q9BRQ8.
CleanEx	HS_AIFM2. HS_PRG3.
GermOnline	ENSG00000042286. Homo sapiens.
Family and domain databases
InterPro	IPR013027. FAD_pyr_nucl-diS_OxRdtase. IPR001327. Pyr_OxRdtase_NAD_bd. IPR000103. Pyridine_nuc-diS_OxRdtase_2. [Graphical view]
Pfam	PF00070. Pyr_redox. 1 hit. PF07992. Pyr_redox_2. 1 hit. [Graphical view]
PRINTS	PR00368. FADPNR. PR00469. PNDRDTASEII.
ProDom	PD000139. FAD_pyr_redox. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...
Other Resources
NextBio	75197.
SOURCE	Search...

Entry information

Entry name

AIFM2_HUMAN

Accession

Primary (citable) accession number: Q9BRQ8
Secondary accession number(s): B3KXI0, Q63Z39

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2006
Last sequence update:	June 1, 2001
Last modified:	June 16, 2009
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)