Q9BRQ8 (AIFM2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apoptosis-inducing factor 2
EC=1.-.-.-

Alternative name(s):
Apoptosis-inducing factor homologous mitochondrion-associated inducer of death
Apoptosis-inducing factor-like 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 further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Oxidoreductase, which may play a role in mediating a p53/TP53-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 p53/TP53 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 p53/TP53. 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 Transmembrane helix
Ligand	DNA-binding FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Lipoprotein Myristate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	apoptotic mitochondrial changes Non-traceable author statement Ref.2. Source: UniProtKB chromosome condensation Inferred from direct assay Ref.2. Source: UniProtKB induction of apoptosis Inferred from mutant phenotype Ref.2. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay Ref.2. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial outer membrane Inferred from direct assay Ref.2. Source: UniProtKB
Molecular function	DNA binding Inferred from direct assay Ref.9. Source: UniProtKB electron-transferring-flavoprotein dehydrogenase activity Inferred from direct assay Ref.9. Source: UniProtKB flavin adenine dinucleotide binding Inferred from direct assay Ref.9. 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
	Initiator methionine	1	1	Removed
	Chain	2 – 373	372	Apoptosis-inducing factor 2		PRO_0000238922
Regions
	Transmembrane	7 – 27	21	Helical; 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
Amino acid modifications
	Lipidation	2	1	N-myristoyl glycine Ref.10
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. Corresponds to variant rs10999147 [ dbSNP | Ensembl ].		VAR_050651
	Natural variant	288	1	D → N. Corresponds to variant rs2271694 [ dbSNP | Ensembl ].		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 [UniParc]. 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., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder 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.
[10]	"Strategy for comprehensive identification of human N-myristoylated proteins using an insect cell-free protein synthesis system." Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E., Tsunasawa S., Utsumi T. Proteomics 10:1780-1793(2010) [PubMed: 20213681] [Abstract] Cited for: MYRISTOYLATION AT GLY-2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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_001185625.1. NM_001198696.1. NP_116186.1. NM_032797.5.
UniGene	Hs.650680.
3D structure databases
ProteinModelPortal	Q9BRQ8.
SMR	Q9BRQ8. Positions 11-321.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9BRQ8. 1 interaction.
STRING	Q9BRQ8.
PTM databases
PhosphoSite	Q9BRQ8.
Polymorphism databases
DMDM	74752283.
Proteomic databases
PRIDE	Q9BRQ8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307864; ENSP00000312370; ENSG00000042286. ENST00000373248; ENSP00000362345; ENSG00000042286.
GeneID	84883.
KEGG	hsa:84883.
UCSC	uc001jqp.1. human.
Organism-specific databases
CTD	84883.
GeneCards	GC10M071857.
H-InvDB	HIX0008891. HIX0026110.
HGNC	HGNC:21411. AIFM2.
HPA	HPA042309.
MIM	605159. gene.
neXtProt	NX_Q9BRQ8.
PharmGKB	PA162376150.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19494.
GeneTree	ENSGT00390000004582.
HOGENOM	HBG714262.
HOVERGEN	HBG054912.
InParanoid	Q9BRQ8.
OMA	GDCADVR.
OrthoDB	EOG4NZTTT.
PhylomeDB	Q9BRQ8.
Gene expression databases
ArrayExpress	Q9BRQ8.
Bgee	Q9BRQ8.
CleanEx	HS_AIFM2. HS_PRG3.
Genevestigator	Q9BRQ8.
GermOnline	ENSG00000042286. Homo sapiens.
Family and domain databases
InterPro	IPR013027. FAD_pyr_nucl-diS_OxRdtase. IPR023753. Pyr_nucl-diS_OxRdtase_FAD/NAD. IPR001327. Pyr_OxRdtase_NAD-bd_dom. 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.
ProtoNet	Search...
Other
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:	January 25, 2012
This is version 91 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.