AIFM3_HUMAN
ID AIFM3_HUMAN Reviewed; 605 AA.
AC Q96NN9; B7WP37; D3DX37; D3DX38; Q6ZT44; Q8N1V3; Q8N5E0;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Apoptosis-inducing factor 3;
DE EC=1.-.-.-;
DE AltName: Full=Apoptosis-inducing factor-like protein;
GN Name=AIFM3; Synonyms=AIFL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=15764604; DOI=10.1074/jbc.m409517200;
RA Xie Q., Lin T., Zhang Y., Zheng J., Bonanno J.A.;
RT "Molecular cloning and characterization of a human AIF-like gene with
RT ability to induce apoptosis.";
RL J. Biol. Chem. 280:19673-19681(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Induces apoptosis through a caspase dependent pathway.
CC Reduces mitochondrial membrane potential.
CC {ECO:0000269|PubMed:15764604}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:15764604}.
CC Note=Does not translocate to the nucleus upon induction of apoptosis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96NN9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96NN9-2; Sequence=VSP_021300, VSP_021303;
CC Name=3;
CC IsoId=Q96NN9-3; Sequence=VSP_021303;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in bone marrow, cerebral
CC cortex, liver, ovary, thymus, thyroid gland and tongue (at protein
CC level). {ECO:0000269|PubMed:15764604}.
CC -!- DOMAIN: The Rieske domain induces apoptosis.
CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase family.
CC {ECO:0000305}.
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DR EMBL; CR456342; CAG30228.1; -; mRNA.
DR EMBL; AK055035; BAB70841.1; -; mRNA.
DR EMBL; AK094844; BAC04434.1; -; mRNA.
DR EMBL; AC002470; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471176; EAX02924.1; -; Genomic_DNA.
DR EMBL; CH471176; EAX02925.1; -; Genomic_DNA.
DR EMBL; CH471176; EAX02926.1; -; Genomic_DNA.
DR EMBL; CH471176; EAX02927.1; -; Genomic_DNA.
DR EMBL; CH471176; EAX02930.1; -; Genomic_DNA.
DR EMBL; CH471176; EAX02931.1; -; Genomic_DNA.
DR EMBL; BC032485; AAH32485.1; -; mRNA.
DR CCDS; CCDS13786.1; -. [Q96NN9-1]
DR CCDS; CCDS33605.1; -. [Q96NN9-3]
DR CCDS; CCDS54503.1; -. [Q96NN9-2]
DR RefSeq; NP_001018070.1; NM_001018060.2. [Q96NN9-3]
DR RefSeq; NP_001139760.1; NM_001146288.1. [Q96NN9-2]
DR RefSeq; NP_653305.1; NM_144704.2. [Q96NN9-1]
DR PDB; 5O9V; X-ray; 2.20 A; C/D=2-9.
DR PDB; 6QRM; X-ray; 2.30 A; C/D=2-11.
DR PDB; 6SJZ; X-ray; 2.00 A; E/F=2-9.
DR PDB; 6SK3; X-ray; 2.70 A; C/D=2-9.
DR PDB; 6SK8; X-ray; 1.87 A; C/D=2-9.
DR PDB; 6SKJ; X-ray; 2.80 A; C/D=2-9.
DR PDBsum; 5O9V; -.
DR PDBsum; 6QRM; -.
DR PDBsum; 6SJZ; -.
DR PDBsum; 6SK3; -.
DR PDBsum; 6SK8; -.
DR PDBsum; 6SKJ; -.
DR AlphaFoldDB; Q96NN9; -.
DR SMR; Q96NN9; -.
DR BioGRID; 127270; 16.
DR IntAct; Q96NN9; 6.
DR MINT; Q96NN9; -.
DR STRING; 9606.ENSP00000382120; -.
DR iPTMnet; Q96NN9; -.
DR PhosphoSitePlus; Q96NN9; -.
DR BioMuta; AIFM3; -.
DR DMDM; 74732608; -.
DR MassIVE; Q96NN9; -.
DR PaxDb; Q96NN9; -.
DR PeptideAtlas; Q96NN9; -.
DR PRIDE; Q96NN9; -.
DR ProteomicsDB; 77540; -. [Q96NN9-1]
DR ProteomicsDB; 77541; -. [Q96NN9-2]
DR ProteomicsDB; 77542; -. [Q96NN9-3]
DR Antibodypedia; 231; 217 antibodies from 30 providers.
DR DNASU; 150209; -.
DR Ensembl; ENST00000399163.6; ENSP00000382116.2; ENSG00000183773.16. [Q96NN9-3]
DR Ensembl; ENST00000399167.6; ENSP00000382120.2; ENSG00000183773.16. [Q96NN9-1]
DR Ensembl; ENST00000405089.5; ENSP00000385800.1; ENSG00000183773.16. [Q96NN9-2]
DR Ensembl; ENST00000440238.4; ENSP00000390798.2; ENSG00000183773.16. [Q96NN9-1]
DR Ensembl; ENST00000683034.1; ENSP00000507958.1; ENSG00000183773.16. [Q96NN9-3]
DR GeneID; 150209; -.
DR KEGG; hsa:150209; -.
DR MANE-Select; ENST00000440238.4; ENSP00000390798.2; NM_001386814.1; NP_001373743.1.
DR UCSC; uc002ztj.3; human. [Q96NN9-1]
DR CTD; 150209; -.
DR DisGeNET; 150209; -.
DR GeneCards; AIFM3; -.
DR HGNC; HGNC:26398; AIFM3.
DR HPA; ENSG00000183773; Group enriched (brain, choroid plexus).
DR MIM; 617298; gene.
DR neXtProt; NX_Q96NN9; -.
DR OpenTargets; ENSG00000183773; -.
DR PharmGKB; PA162376173; -.
DR VEuPathDB; HostDB:ENSG00000183773; -.
DR eggNOG; KOG1336; Eukaryota.
DR GeneTree; ENSGT00940000160448; -.
DR InParanoid; Q96NN9; -.
DR OMA; IATYPYH; -.
DR OrthoDB; 405030at2759; -.
DR PhylomeDB; Q96NN9; -.
DR TreeFam; TF314028; -.
DR PathwayCommons; Q96NN9; -.
DR SignaLink; Q96NN9; -.
DR BioGRID-ORCS; 150209; 21 hits in 1069 CRISPR screens.
DR ChiTaRS; AIFM3; human.
DR GenomeRNAi; 150209; -.
DR Pharos; Q96NN9; Tbio.
DR PRO; PR:Q96NN9; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q96NN9; protein.
DR Bgee; ENSG00000183773; Expressed in mucosa of transverse colon and 112 other tissues.
DR ExpressionAtlas; Q96NN9; baseline and differential.
DR Genevisible; Q96NN9; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:HGNC-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:HGNC-UCL.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016651; F:oxidoreductase activity, acting on NAD(P)H; IBA:GO_Central.
DR GO; GO:0097194; P:execution phase of apoptosis; IDA:BHF-UCL.
DR Gene3D; 2.102.10.10; -; 1.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR InterPro; IPR028202; Reductase_C.
DR InterPro; IPR017941; Rieske_2Fe-2S.
DR InterPro; IPR036922; Rieske_2Fe-2S_sf.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF14759; Reductase_C; 1.
DR Pfam; PF00355; Rieske; 1.
DR SUPFAM; SSF50022; SSF50022; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR PROSITE; PS51296; RIESKE; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; 3D-structure; Alternative splicing; Apoptosis; Electron transport;
KW FAD; Flavoprotein; Iron; Iron-sulfur; Metal-binding; Mitochondrion;
KW Oxidoreductase; Reference proteome; Transport.
FT CHAIN 1..605
FT /note="Apoptosis-inducing factor 3"
FT /id="PRO_0000255660"
FT DOMAIN 70..165
FT /note="Rieske"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT REGION 22..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 109
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT BINDING 111
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT BINDING 128
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT BINDING 131
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00628"
FT BINDING 201..205
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 235
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 240
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 270
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 467
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT BINDING 514
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT VAR_SEQ 10
FT /note="P -> PGAALPT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021300"
FT VAR_SEQ 587..593
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_021303"
FT VARIANT 508
FT /note="S -> T (in dbSNP:rs61356271)"
FT /id="VAR_061553"
FT CONFLICT 165
FT /note="V -> A (in Ref. 3; BAC04434)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 605 AA; 66791 MW; C1DF20AE2AF2E262 CRC64;
MGGCFSKPKP VELKIEVVLP EKERGKEELS ASGKGSPRAY QGNGTARHFH TEERLSTPHP
YPSPQDCVEA AVCHVKDLEN GQMREVELGW GKVLLVKDNG EFHALGHKCP HYGAPLVKGV
LSRGRVRCPW HGACFNISTG DLEDFPGLDS LHKFQVKIEK EKVYVRASKQ ALQLQRRTKV
MAKCISPSAG YSSSTNVLIV GAGAAGLVCA ETLRQEGFSD RIVLCTLDRH LPYDRPKLSK
SLDTQPEQLA LRPKEFFRAY GIEVLTEAQV VTVDVRTKKV VFKDGFKLEY SKLLLAPGSS
PKTLSCKGKE VENVFTIRTP EDANRVVRLA RGRNVVVVGA GFLGMEVAAY LTEKAHSVSV
VELEETPFRR FLGERVGRAL MKMFENNRVK FYMQTEVSEL RGQEGKLKEV VLKSSKVVRA
DVCVVGIGAV PATGFLRQSG IGLDSRGFIP VNKMMQTNVP GVFAAGDAVT FPLAWRNNRK
VNIPHWQMAH AQGRVAAQNM LAQEAEMSTV PYLWTAMFGK SLRYAGYGEG FDDVIIQGDL
EELKFVAFYT KGDEVIAVAS MNYDPIVSKV AEVLASGRAI RKREVELFVL HSKTGDMSWL
TGKGS
