Q96NN9 (AIFM3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apoptosis-inducing factor 3
EC=1.-.-.-

Alternative name(s):
Apoptosis-inducing factor-like protein

Gene names

Name:	AIFM3
Synonyms:	AIFL

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	605 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Induces apoptosis through a caspase dependent pathway. Reduces mitochondrial membrane potential. Ref.1
Subcellular location	Mitochondrion. Note: Does not translocate to the nucleus upon induction of apoptosis. Ref.1
Tissue specificity	Ubiquitous. Expressed in bone marrow, cerebral cortex, liver, ovary, thymus, thyroid gland and tongue (at protein level). Ref.1
Domain	The Rieske domain induces apoptosis.
Sequence similarities	Belongs to the FAD-dependent oxidoreductase family. Contains 1 Rieske domain.

Ontologies

Keywords
Biological process	Apoptosis Electron transport Transport
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	2Fe-2S FAD Flavoprotein Iron Iron-sulfur Metal-binding
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c Inferred from direct assay Ref.1. Source: HGNC cell redox homeostasis Inferred from electronic annotation. Source: InterPro electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Inferred from direct assay Ref.1. Source: HGNC mitochondrial depolarization Inferred from direct assay Ref.1. Source: HGNC transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from direct assay Ref.1. Source: HGNC mitochondrial inner membrane Inferred from direct assay Ref.1. Source: HGNC
Molecular function	2 iron, 2 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activator activity involved in apoptotic process Inferred from direct assay Ref.1. Source: HGNC flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q96NN9-1)

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: Q96NN9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     10-10: P → PGAALPT
     587-593: Missing.

Isoform 3 (identifier: Q96NN9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     587-593: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 605	605	Apoptosis-inducing factor 3		PRO_0000255660
Regions
	Domain	70 – 165	96	Rieske
	Nucleotide binding	201 – 205	5	FAD Potential
Sites
	Metal binding	109	1	Iron-sulfur (2Fe-2S) By similarity
	Metal binding	111	1	Iron-sulfur (2Fe-2S); via pros nitrogen
	Metal binding	128	1	Iron-sulfur (2Fe-2S) By similarity
	Metal binding	131	1	Iron-sulfur (2Fe-2S); via pros nitrogen
	Binding site	235	1	FAD Potential
	Binding site	240	1	FAD Potential
	Binding site	270	1	FAD; via amide nitrogen and carbonyl oxygen Potential
	Binding site	467	1	FAD Potential
	Binding site	514	1	FAD; via carbonyl oxygen Potential
Natural variations
	Alternative sequence	10	1	P → PGAALPT in isoform 2.		VSP_021300
	Alternative sequence	587 – 593	7	Missing in isoform 2 and isoform 3.		VSP_021303
	Natural variant	508	1	S → T. Corresponds to variant rs61356271 [ dbSNP | Ensembl ].		VAR_061553
Experimental info
	Sequence conflict	165	1	V → A in BAC04434. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: C1DF20AE2AF2E262	FASTA	605	66,791
	10 20 30 40 50 60 MGGCFSKPKP VELKIEVVLP EKERGKEELS ASGKGSPRAY QGNGTARHFH TEERLSTPHP 70 80 90 100 110 120 YPSPQDCVEA AVCHVKDLEN GQMREVELGW GKVLLVKDNG EFHALGHKCP HYGAPLVKGV 130 140 150 160 170 180 LSRGRVRCPW HGACFNISTG DLEDFPGLDS LHKFQVKIEK EKVYVRASKQ ALQLQRRTKV 190 200 210 220 230 240 MAKCISPSAG YSSSTNVLIV GAGAAGLVCA ETLRQEGFSD RIVLCTLDRH LPYDRPKLSK 250 260 270 280 290 300 SLDTQPEQLA LRPKEFFRAY GIEVLTEAQV VTVDVRTKKV VFKDGFKLEY SKLLLAPGSS 310 320 330 340 350 360 PKTLSCKGKE VENVFTIRTP EDANRVVRLA RGRNVVVVGA GFLGMEVAAY LTEKAHSVSV 370 380 390 400 410 420 VELEETPFRR FLGERVGRAL MKMFENNRVK FYMQTEVSEL RGQEGKLKEV VLKSSKVVRA 430 440 450 460 470 480 DVCVVGIGAV PATGFLRQSG IGLDSRGFIP VNKMMQTNVP GVFAAGDAVT FPLAWRNNRK 490 500 510 520 530 540 VNIPHWQMAH AQGRVAAQNM LAQEAEMSTV PYLWTAMFGK SLRYAGYGEG FDDVIIQGDL 550 560 570 580 590 600 EELKFVAFYT KGDEVIAVAS MNYDPIVSKV AEVLASGRAI RKREVELFVL HSKTGDMSWL TGKGS
	Isoform 2 [UniParc]. Checksum: AEF75FBE911988A6	FASTA	604	66,477
	10 20 30 40 50 60 MGGCFSKPKP GAALPTVELK IEVVLPEKER GKEELSASGK GSPRAYQGNG TARHFHTEER 70 80 90 100 110 120 LSTPHPYPSP QDCVEAAVCH VKDLENGQMR EVELGWGKVL LVKDNGEFHA LGHKCPHYGA 130 140 150 160 170 180 PLVKGVLSRG RVRCPWHGAC FNISTGDLED FPGLDSLHKF QVKIEKEKVY VRASKQALQL 190 200 210 220 230 240 QRRTKVMAKC ISPSAGYSSS TNVLIVGAGA AGLVCAETLR QEGFSDRIVL CTLDRHLPYD 250 260 270 280 290 300 RPKLSKSLDT QPEQLALRPK EFFRAYGIEV LTEAQVVTVD VRTKKVVFKD GFKLEYSKLL 310 320 330 340 350 360 LAPGSSPKTL SCKGKEVENV FTIRTPEDAN RVVRLARGRN VVVVGAGFLG MEVAAYLTEK 370 380 390 400 410 420 AHSVSVVELE ETPFRRFLGE RVGRALMKMF ENNRVKFYMQ TEVSELRGQE GKLKEVVLKS 430 440 450 460 470 480 SKVVRADVCV VGIGAVPATG FLRQSGIGLD SRGFIPVNKM MQTNVPGVFA AGDAVTFPLA 490 500 510 520 530 540 WRNNRKVNIP HWQMAHAQGR VAAQNMLAQE AEMSTVPYLW TAMFGKSLRY AGYGEGFDDV 550 560 570 580 590 600 IIQGDLEELK FVAFYTKGDE VIAVASMNYD PIVSKVAEVL ASGRAIRKRE VETGDMSWLT GKGS
	Isoform 3 [UniParc]. Checksum: E49D7ED5BBF7F30E	FASTA	598	65,966
	10 20 30 40 50 60 MGGCFSKPKP VELKIEVVLP EKERGKEELS ASGKGSPRAY QGNGTARHFH TEERLSTPHP 70 80 90 100 110 120 YPSPQDCVEA AVCHVKDLEN GQMREVELGW GKVLLVKDNG EFHALGHKCP HYGAPLVKGV 130 140 150 160 170 180 LSRGRVRCPW HGACFNISTG DLEDFPGLDS LHKFQVKIEK EKVYVRASKQ ALQLQRRTKV 190 200 210 220 230 240 MAKCISPSAG YSSSTNVLIV GAGAAGLVCA ETLRQEGFSD RIVLCTLDRH LPYDRPKLSK 250 260 270 280 290 300 SLDTQPEQLA LRPKEFFRAY GIEVLTEAQV VTVDVRTKKV VFKDGFKLEY SKLLLAPGSS 310 320 330 340 350 360 PKTLSCKGKE VENVFTIRTP EDANRVVRLA RGRNVVVVGA GFLGMEVAAY LTEKAHSVSV 370 380 390 400 410 420 VELEETPFRR FLGERVGRAL MKMFENNRVK FYMQTEVSEL RGQEGKLKEV VLKSSKVVRA 430 440 450 460 470 480 DVCVVGIGAV PATGFLRQSG IGLDSRGFIP VNKMMQTNVP GVFAAGDAVT FPLAWRNNRK 490 500 510 520 530 540 VNIPHWQMAH AQGRVAAQNM LAQEAEMSTV PYLWTAMFGK SLRYAGYGEG FDDVIIQGDL 550 560 570 580 590 EELKFVAFYT KGDEVIAVAS MNYDPIVSKV AEVLASGRAI RKREVETGDM SWLTGKGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of a human AIF-like gene with ability to induce apoptosis." Xie Q., Lin T., Zhang Y., Zheng J., Bonanno J.A. J. Biol. Chem. 280:19673-19681(2005) [PubMed: 15764604] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed: 15461802] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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] (ISOFORMS 1 AND 2). Tissue: Brain and Caudate nucleus.
[4]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [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 (SEP-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 3). Tissue: Pancreas.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	CR456342 mRNA. Translation: CAG30228.1. AK055035 mRNA. Translation: BAB70841.1. AK094844 mRNA. Translation: BAC04434.1. AC002470 Genomic DNA. No translation available. CH471176 Genomic DNA. Translation: EAX02924.1. CH471176 Genomic DNA. Translation: EAX02925.1. CH471176 Genomic DNA. Translation: EAX02926.1. CH471176 Genomic DNA. Translation: EAX02927.1. CH471176 Genomic DNA. Translation: EAX02930.1. CH471176 Genomic DNA. Translation: EAX02931.1. BC032485 mRNA. Translation: AAH32485.1.
IPI	IPI00043760. IPI00384348. IPI00793477.
RefSeq	NP_001018070.1. NM_001018060.2. NP_001139760.1. NM_001146288.1. NP_653305.1. NM_144704.2.
UniGene	Hs.723246.
3D structure databases
ProteinModelPortal	Q96NN9.
SMR	Q96NN9. Positions 68-170, 193-593.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96NN9. 1 interaction.
STRING	Q96NN9.
PTM databases
PhosphoSite	Q96NN9.
Polymorphism databases
DMDM	74732608.
Proteomic databases
PRIDE	Q96NN9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000335375; ENSP00000335369; ENSG00000183773. ENST00000399167; ENSP00000382120; ENSG00000183773.
GeneID	150209.
KEGG	hsa:150209.
UCSC	uc002ztj.1. human. uc002ztk.1. human. uc002ztl.1. human.
Organism-specific databases
CTD	150209.
GeneCards	GC22P021321.
HGNC	HGNC:26398. AIFM3.
HPA	HPA001271.
neXtProt	NX_Q96NN9.
PharmGKB	PA162376173.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG10819.
GeneTree	ENSGT00530000063416.
HOGENOM	HBG644911.
HOVERGEN	HBG052926.
InParanoid	Q96NN9.
OMA	CHVKDLE.
OrthoDB	EOG4STS46.
PhylomeDB	Q96NN9.
Gene expression databases
ArrayExpress	Q96NN9.
Bgee	Q96NN9.
CleanEx	HS_AIFM3.
Genevestigator	Q96NN9.
GermOnline	ENSG00000183773. Homo sapiens.
Family and domain databases
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. IPR000103. Pyridine_nuc-diS_OxRdtase_2. IPR017941. Rieske_2Fe-2S. [Graphical view]
Gene3D	G3DSA:3.30.390.30. Pyr_redox_dim. 1 hit. G3DSA:2.102.10.10. Rieske_reg. 1 hit.
Pfam	PF00070. Pyr_redox. 1 hit. PF07992. Pyr_redox_2. 1 hit. PF00355. Rieske. 1 hit. [Graphical view]
PRINTS	PR00368. FADPNR. PR00469. PNDRDTASEII.
SUPFAM	SSF55424. FAD/NAD-linked_reductase_dimer. 1 hit. SSF50022. Rieske_dom. 1 hit.
PROSITE	PS51296. RIESKE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	86362.

Entry information

Entry name

AIFM3_HUMAN

Accession

Primary (citable) accession number: Q96NN9
Secondary accession number(s): B7WP37 , D3DX37, D3DX38, Q6ZT44, Q8N1V3, Q8N5E0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 87 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.