AIFM1_HUMAN
ID AIFM1_HUMAN Reviewed; 613 AA.
AC O95831; A4QPB4; B1ALN1; B2RB08; D3DTE9; E9PRR0; Q1L6K4; Q1L6K6; Q2QKE4;
AC Q5JUZ7; Q6I9X6; Q9Y3I3; Q9Y3I4;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Apoptosis-inducing factor 1, mitochondrial {ECO:0000305};
DE EC=1.6.99.- {ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854, ECO:0000269|PubMed:27178839};
DE AltName: Full=Programmed cell death protein 8;
DE Flags: Precursor;
GN Name=AIFM1 {ECO:0000312|HGNC:HGNC:8768}; Synonyms=AIF, PDCD8;
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).
RX PubMed=9989411; DOI=10.1038/17135;
RA Susin S.A., Lorenzo H.K., Zamzami N., Marzo I., Snow B.E., Brothers G.M.,
RA Mangion J., Jacotot E., Costantini P., Loeffler M., Larochette N.,
RA Goodlett D.R., Aebersold R., Siderovski D.P., Penninger J.M., Kroemer G.;
RT "Molecular characterization of mitochondrial apoptosis-inducing factor.";
RL Nature 397:441-446(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), PROTEIN SEQUENCE OF N-TERMINUS,
RP SUBCELLULAR LOCATION (ISOFORM 5), TISSUE SPECIFICITY (ISOFORM 5), FUNCTION
RP (ISOFORM 5), AND INDUCTION BY GAMMA-IRRADIATION (ISOFORM 5).
RX PubMed=16365034; DOI=10.1074/jbc.m509884200;
RA Delettre C., Yuste V.J., Moubarak R.S., Bras M., Lesbordes-Brion J.-C.,
RA Petres S., Bellalou J., Susin S.A.;
RT "AIFsh, a novel apoptosis-inducing factor (AIF) pro-apoptotic isoform with
RT potential pathological relevance in human cancer.";
RL J. Biol. Chem. 281:6413-6427(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 6), ALTERNATIVE SPLICING,
RP FUNCTION (ISOFORM 4), SUBCELLULAR LOCATION (ISOFORM 4), AND TISSUE
RP SPECIFICITY (ISOFORMS 4 AND 6).
RX PubMed=16644725; DOI=10.1074/jbc.m601751200;
RA Delettre C., Yuste V.J., Moubarak R.S., Bras M., Robert N., Susin S.A.;
RT "Identification and characterization of AIFsh2, a mitochondrial apoptosis-
RT inducing factor (AIF) isoform with NADH oxidase activity.";
RL J. Biol. Chem. 281:18507-18518(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RA Rhodes S.;
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Kidney;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Brain;
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).
RN [10]
RP PROTEIN SEQUENCE OF 55-59, SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=15775970; DOI=10.1038/sj.emboj.7600614;
RA Otera H., Ohsakaya S., Nagaura Z., Ishihara N., Mihara K.;
RT "Export of mitochondrial AIF in response to proapoptotic stimuli depends on
RT processing at the intermembrane space.";
RL EMBO J. 24:1375-1386(2005).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 171-613.
RC TISSUE=Brain;
RA Mei G., Yu W., Gibbs R.A.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP REVIEW.
RX PubMed=10913597; DOI=10.1016/s0014-5793(00)01731-2;
RA Daugas E., Nochy D., Ravagnan L., Loeffler M., Susin S.A., Zamzami N.,
RA Kroemer G.;
RT "Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase
RT involved in apoptosis.";
RL FEBS Lett. 476:118-123(2000).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EIF3G.
RX PubMed=17094969; DOI=10.1016/j.febslet.2006.10.049;
RA Kim J.T., Kim K.D., Song E.Y., Lee H.G., Kim J.W., Kim J.W., Chae S.K.,
RA Kim E., Lee M.S., Yang Y., Lim J.S.;
RT "Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting
RT with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g).";
RL FEBS Lett. 580:6375-6383(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-105, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP UBIQUITINATION BY XIAP/BIRC4, AND INTERACTION WITH XIAP/BIRC4.
RX PubMed=17967870; DOI=10.1128/mcb.01065-07;
RA Wilkinson J.C., Wilkinson A.S., Galban S., Csomos R.A., Duckett C.S.;
RT "Apoptosis-inducing factor is a target for ubiquitination through
RT interaction with XIAP.";
RL Mol. Cell. Biol. 28:237-247(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP FUNCTION.
RX PubMed=19418225; DOI=10.1007/s10495-009-0353-7;
RA Son Y.O., Jang Y.S., Heo J.S., Chung W.T., Choi K.C., Lee J.C.;
RT "Apoptosis-inducing factor plays a critical role in caspase-independent,
RT pyknotic cell death in hydrogen peroxide-exposed cells.";
RL Apoptosis 14:796-808(2009).
RN [18]
RP ALTERNATIVE SPLICING (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM 3), AND
RP SUBUNIT.
RX PubMed=20111043; DOI=10.1038/cdd.2009.211;
RA Hangen E., De Zio D., Bordi M., Zhu C., Dessen P., Caffin F., Lachkar S.,
RA Perfettini J.L., Lazar V., Benard J., Fimia G.M., Piacentini M., Harper F.,
RA Pierron G., Vicencio J.M., Benit P., de Andrade A., Hoglinger G.,
RA Culmsee C., Rustin P., Blomgren K., Cecconi F., Kroemer G., Modjtahedi N.;
RT "A brain-specific isoform of mitochondrial apoptosis-inducing factor:
RT AIF2.";
RL Cell Death Differ. 17:1155-1166(2010).
RN [19]
RP INTERACTION WITH PRELID1.
RX PubMed=21364629; DOI=10.1038/cddis.2009.19;
RA McKeller M.R., Herrera-Rodriguez S., Ma W., Ortiz-Quintero B., Rangel R.,
RA Cande C., Sims-Mourtada J.C., Melnikova V., Kashi C., Phan L.M., Chen Z.,
RA Huang P., Dunner K. Jr., Kroemer G., Singh K.K., Martinez-Valdez H.;
RT "Vital function of PRELI and essential requirement of its LEA motif.";
RL Cell Death Dis. 1:E21-E21(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP UBIQUITINATION AT LYS-255 BY XIAP/BIRC4.
RX PubMed=22103349; DOI=10.1021/bi201483g;
RA Lewis E.M., Wilkinson A.S., Davis N.Y., Horita D.A., Wilkinson J.C.;
RT "Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-
RT linked inhibitor of apoptosis at a residue critical for AIF-mediated
RT chromatin degradation.";
RL Biochemistry 50:11084-11096(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-105; SER-116; SER-268 AND
RP SER-292, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116; SER-118; SER-268;
RP SER-371; THR-521; SER-524 AND SER-530, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP FUNCTION, INTERACTION WITH CHCHD4, SUBCELLULAR LOCATION, CHARACTERIZATION
RP OF VARIANT COXPD6 GLU-308, AND CHARACTERIZATION OF VARIANT CMTX4 VAL-493.
RX PubMed=26004228; DOI=10.1016/j.molcel.2015.04.020;
RA Hangen E., Feraud O., Lachkar S., Mou H., Doti N., Fimia G.M., Lam N.V.,
RA Zhu C., Godin I., Muller K., Chatzi A., Nuebel E., Ciccosanti F.,
RA Flamant S., Benit P., Perfettini J.L., Sauvat A., Bennaceur-Griscelli A.,
RA Ser-Le Roux K., Gonin P., Tokatlidis K., Rustin P., Piacentini M., Ruvo M.,
RA Blomgren K., Kroemer G., Modjtahedi N.;
RT "Interaction between AIF and CHCHD4 Regulates Respiratory Chain
RT Biogenesis.";
RL Mol. Cell 58:1001-1014(2015).
RN [25]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER MET-54, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 121-613 IN COMPLEX WITH FAD,
RP SUBCELLULAR LOCATION, AND DNA-BINDING.
RX PubMed=12198487; DOI=10.1038/nsb836;
RA Ye H., Cande C., Stephanou N.C., Jiang S., Gurbuxani S., Larochette N.,
RA Daugas E., Garrido C., Kroemer G., Wu H.;
RT "DNA binding is required for the apoptogenic action of apoptosis inducing
RT factor.";
RL Nat. Struct. Biol. 9:680-684(2002).
RN [27] {ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 121-613 IN COMPLEX WITH FAD AND
RP NAD, SUBUNIT, MUTAGENESIS OF 413-GLU--ARG-430, SUBCELLULAR LOCATION,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, FAD-BINDING, NAD-BINDING, AND
RP CATALYTIC ACTIVITY.
RX PubMed=24914854; DOI=10.1021/bi500343r;
RA Ferreira P., Villanueva R., Martinez-Julvez M., Herguedas B., Marcuello C.,
RA Fernandez-Silva P., Cabon L., Hermoso J.A., Lostao A., Susin S.A.,
RA Medina M.;
RT "Structural insights into the coenzyme mediated monomer-dimer transition of
RT the pro-apoptotic apoptosis inducing factor.";
RL Biochemistry 53:4204-4215(2014).
RN [28] {ECO:0007744|PDB:5FS6, ECO:0007744|PDB:5FS7, ECO:0007744|PDB:5FS8, ECO:0007744|PDB:5FS9}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 103-613 IN COMPLEX WITH FAD,
RP CHARACTERIZATION OF VARIANT SER-262, CHARACTERIZATION OF VARIANTS COXPD6
RP LEU-243; GLU-308 AND GLU-338, FUNCTION, DNA-BINDING, FAD-BINDING, CATALYTIC
RP ACTIVITY, AND COFACTOR.
RX PubMed=27178839; DOI=10.1016/j.jmb.2016.05.004;
RA Sevrioukova I.F.;
RT "Structure/Function Relations in AIFM1 Variants Associated with
RT Neurodegenerative Disorders.";
RL J. Mol. Biol. 428:3650-3665(2016).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 103-613 IN COMPLEX WITH FAD,
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, DNA-BINDING, SUBUNIT,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, VARIANT CMTX4 VAL-493,
RP CHARACTERIZATION OF VARIANT CMTX4 VAL-493, AND CATALYTIC ACTIVITY.
RX PubMed=23217327; DOI=10.1016/j.ajhg.2012.10.008;
RA Rinaldi C., Grunseich C., Sevrioukova I.F., Schindler A.,
RA Horkayne-Szakaly I., Lamperti C., Landoure G., Kennerson M.L.,
RA Burnett B.G., Boennemann C., Biesecker L.G., Ghezzi D., Zeviani M.,
RA Fischbeck K.H.;
RT "Cowchock syndrome is associated with a mutation in apoptosis-inducing
RT factor.";
RL Am. J. Hum. Genet. 91:1095-1102(2012).
RN [30] {ECO:0007744|PDB:5KVH, ECO:0007744|PDB:5KVI}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 78-613 IN COMPLEX WITH FAD,
RP SUBUNIT, MUTAGENESIS OF TRP-196; 443-TYR--ILE-445; HIS-454; TRP-477;
RP SER-480; ASP-485; ARG-529; GLU-531; GLU-533 AND GLU-535, COFACTOR, AND
RP FAD-BINDING.
RX PubMed=27818101; DOI=10.1016/j.str.2016.09.012;
RA Brosey C.A., Ho C., Long W.Z., Singh S., Burnett K., Hura G.L., Nix J.C.,
RA Bowman G.R., Ellenberger T., Tainer J.A.;
RT "Defining NADH-Driven Allostery Regulating Apoptosis-Inducing Factor.";
RL Structure 24:2067-2079(2016).
RN [31]
RP VARIANT COXPD6 ARG-201 DEL, CHARACTERIZATION OF VARIANT COXPD6 ARG-201 DEL,
RP AND FUNCTION.
RX PubMed=20362274; DOI=10.1016/j.ajhg.2010.03.002;
RA Ghezzi D., Sevrioukova I., Invernizzi F., Lamperti C., Mora M., D'Adamo P.,
RA Novara F., Zuffardi O., Uziel G., Zeviani M.;
RT "Severe X-linked mitochondrial encephalomyopathy associated with a mutation
RT in apoptosis-inducing factor.";
RL Am. J. Hum. Genet. 86:639-649(2010).
RN [32]
RP VARIANT COXPD6 GLU-308.
RX PubMed=22019070; DOI=10.1016/j.ymgme.2011.09.020;
RA Berger I., Ben-Neriah Z., Dor-Wolman T., Shaag A., Saada A., Zenvirt S.,
RA Raas-Rothschild A., Nadjari M., Kaestner K.H., Elpeleg O.;
RT "Early prenatal ventriculomegaly due to an AIFM1 mutation identified by
RT linkage analysis and whole exome sequencing.";
RL Mol. Genet. Metab. 104:517-520(2011).
RN [33]
RP INVOLVEMENT IN DFNX5, AND VARIANTS DFNX5 ALA-260; PHE-344; ARG-360;
RP GLN-422; TRP-422; CYS-430; GLN-451; VAL-472; LEU-475; MET-498 AND MET-591.
RX PubMed=25986071; DOI=10.1136/jmedgenet-2014-102961;
RA Zong L., Guan J., Ealy M., Zhang Q., Wang D., Wang H., Zhao Y., Shen Z.,
RA Campbell C.A., Wang F., Yang J., Sun W., Lan L., Ding D., Xie L., Qi Y.,
RA Lou X., Huang X., Shi Q., Chang S., Xiong W., Yin Z., Yu N., Zhao H.,
RA Wang J., Wang J., Salvi R.J., Petit C., Smith R.J., Wang Q.;
RT "Mutations in apoptosis-inducing factor cause X-linked recessive auditory
RT neuropathy spectrum disorder.";
RL J. Med. Genet. 52:523-531(2015).
RN [34]
RP VARIANT COXPD6 LEU-243, AND CHARACTERIZATION OF VARIANT COXPD6 LEU-243.
RX PubMed=25583628; DOI=10.1016/j.mito.2015.01.001;
RA Kettwig M., Schubach M., Zimmermann F.A., Klinge L., Mayr J.A., Biskup S.,
RA Sperl W., Gaertner J., Huppke P.;
RT "From ventriculomegaly to severe muscular atrophy: Expansion of the
RT clinical spectrum related to mutations in AIFM1.";
RL Mitochondrion 21C:12-18(2015).
RN [35]
RP VARIANT SER-262, AND CHARACTERIZATION OF VARIANT SER-262.
RX PubMed=25934856; DOI=10.1212/wnl.0000000000001613;
RA Ardissone A., Piscosquito G., Legati A., Langella T., Lamantea E.,
RA Garavaglia B., Salsano E., Farina L., Moroni I., Pareyson D., Ghezzi D.;
RT "A slowly progressive mitochondrial encephalomyopathy widens the spectrum
RT of AIFM1 disorders.";
RL Neurology 84:2193-2195(2015).
RN [36]
RP VARIANT COXPD6 GLU-338, AND CHARACTERIZATION OF VARIANT COXPD6 GLU-338.
RX PubMed=26173962; DOI=10.1038/ejhg.2015.141;
RA Diodato D., Tasca G., Verrigni D., D'Amico A., Rizza T., Tozzi G.,
RA Martinelli D., Verardo M., Invernizzi F., Nasca A., Bellacchio E.,
RA Ghezzi D., Piemonte F., Dionisi-Vici C., Carrozzo R., Bertini E.;
RT "A novel AIFM1 mutation expands the phenotype to an infantile motor neuron
RT disease.";
RL Eur. J. Hum. Genet. 24:463-466(2016).
RN [37]
RP VARIANTS SEMDHL HIS-235; GLY-237 AND VAL-237, CHARACTERIZATION OF VARIANT
RP SEMDHL HIS-235, INVOLVEMENT IN SEMDHL, AND TISSUE SPECIFICITY.
RX PubMed=28842795; DOI=10.1007/s10048-017-0520-x;
RA Miyake N., Wolf N.I., Cayami F.K., Crawford J., Bley A., Bulas D.,
RA Conant A., Bent S.J., Gripp K.W., Hahn A., Humphray S., Kimura-Ohba S.,
RA Kingsbury Z., Lajoie B.R., Lal D., Micha D., Pizzino A., Sinke R.J.,
RA Sival D., Stolte-Dijkstra I., Superti-Furga A., Ulrick N., Taft R.J.,
RA Ogata T., Ozono K., Matsumoto N., Neubauer B.A., Simons C., Vanderver A.;
RT "X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD)
RT associated with mutations in AIFM1.";
RL Neurogenetics 18:185-194(2017).
CC -!- FUNCTION: Functions both as NADH oxidoreductase and as regulator of
CC apoptosis (PubMed:20362274, PubMed:23217327, PubMed:17094969). In
CC response to apoptotic stimuli, it is released from the mitochondrion
CC intermembrane space into the cytosol and to the nucleus, where it
CC functions as a proapoptotic factor in a caspase-independent pathway.
CC The soluble form (AIFsol) found in the nucleus induces 'parthanatos'
CC i.e. caspase-independent fragmentation of chromosomal DNA (By
CC similarity). Binds to DNA in a sequence-independent manner
CC (PubMed:27178839). Interacts with EIF3G, and thereby inhibits the EIF3
CC machinery and protein synthesis, and activates caspase-7 to amplify
CC apoptosis (PubMed:17094969). Plays a critical role in caspase-
CC independent, pyknotic cell death in hydrogen peroxide-exposed cells
CC (PubMed:19418225). In contrast, participates in normal mitochondrial
CC metabolism. Plays an important role in the regulation of respiratory
CC chain biogenesis by interacting with CHCHD4 and controlling CHCHD4
CC mitochondrial import (PubMed:26004228). {ECO:0000250|UniProtKB:Q9Z0X1,
CC ECO:0000269|PubMed:17094969, ECO:0000269|PubMed:19418225,
CC ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:23217327,
CC ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:27178839}.
CC -!- FUNCTION: [Isoform 4]: Has NADH oxidoreductase activity. Does not
CC induce nuclear apoptosis. {ECO:0000269|PubMed:16644725}.
CC -!- FUNCTION: [Isoform 5]: Pro-apoptotic isoform.
CC {ECO:0000269|PubMed:16365034}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + H(+) + NADH = AH2 + NAD(+); Xref=Rhea:RHEA:11356,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15378, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
CC ECO:0000269|PubMed:27178839};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=A + H(+) + NADH = AH2 + NAD(+); Xref=Rhea:RHEA:11356,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15378, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000269|PubMed:16644725};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
CC ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:27818101};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.53 mM for NADH {ECO:0000269|PubMed:23217327};
CC KM=26 uM for cytochrome c (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:27178839};
CC KM=138 uM for dichlorophenolindophenol (at pH 7.4 and 25 degrees
CC Celsius) {ECO:0000269|PubMed:27178839};
CC KM=0.51 mM for NADH (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:27178839};
CC KM=896 uM for NADPH {ECO:0000269|PubMed:24914854};
CC Note=kcat is 86 min(-1) for dichlorophenolindophenol reduction and 24
CC min(-1) for cytochrome c reduction (PubMed:27178839). kcat is 1.5
CC sec(-1) for dichlorophenolindophenol reduction, 3.1 sec(-1) for
CC ferricyanide and 0.6 sec(-1) for cytochrome c reduction
CC (PubMed:24914854). {ECO:0000269|PubMed:24914854,
CC ECO:0000269|PubMed:27178839};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 4]:
CC Kinetic parameters:
CC KM=102.6 uM for NADH {ECO:0000269|PubMed:16644725};
CC KM=45.3 uM for NADPH {ECO:0000269|PubMed:16644725};
CC -!- SUBUNIT: Monomer (oxidized form). Homodimer (reduced form). Upon
CC reduction with NADH, undergoes dimerization and forms tight, long-lived
CC FADH2-NAD charge transfer complexes (CTC) resistant to oxidation
CC (PubMed:24914854, PubMed:20111043, PubMed:23217327, PubMed:27818101).
CC Also dimerizes with isoform 3 preventing its release from mitochondria
CC (PubMed:20111043). Interacts with XIAP/BIRC4 (PubMed:17967870).
CC Interacts (via N-terminus) with EIF3G (via C-terminus)
CC (PubMed:17094969). Interacts with PRELID1 (PubMed:21364629). Interacts
CC with CHCHD4; the interaction increases in presence of NADH
CC (PubMed:26004228). {ECO:0000269|PubMed:17094969,
CC ECO:0000269|PubMed:17967870, ECO:0000269|PubMed:20111043,
CC ECO:0000269|PubMed:21364629, ECO:0000269|PubMed:23217327,
CC ECO:0000269|PubMed:24914854, ECO:0000269|PubMed:26004228,
CC ECO:0000269|PubMed:27818101}.
CC -!- INTERACTION:
CC O95831; O75821: EIF3G; NbExp=9; IntAct=EBI-356440, EBI-366632;
CC O95831; Q63ZY3: KANK2; NbExp=2; IntAct=EBI-356440, EBI-2556193;
CC O95831; Q63ZY3-2: KANK2; NbExp=4; IntAct=EBI-356440, EBI-6244894;
CC O95831; Q9Y3Q8: TSC22D4; NbExp=2; IntAct=EBI-356440, EBI-739485;
CC O95831; Q5EP34: PA; Xeno; NbExp=8; IntAct=EBI-356440, EBI-25772799;
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:15775970, ECO:0000269|PubMed:24914854,
CC ECO:0000269|PubMed:26004228}. Mitochondrion inner membrane. Cytoplasm
CC {ECO:0000269|PubMed:15775970}. Nucleus {ECO:0000269|PubMed:15775970,
CC ECO:0000269|PubMed:17094969}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:17094969}. Note=Proteolytic cleavage during or just
CC after translocation into the mitochondrial intermembrane space (IMS)
CC results in the formation of an inner-membrane-anchored mature form
CC (AIFmit). During apoptosis, further proteolytic processing leads to a
CC mature form, which is confined to the mitochondrial IMS in a soluble
CC form (AIFsol). AIFsol is released to the cytoplasm in response to
CC specific death signals, and translocated to the nucleus, where it
CC induces nuclear apoptosis (PubMed:15775970). Colocalizes with EIF3G in
CC the nucleus and perinuclear region (PubMed:17094969).
CC {ECO:0000269|PubMed:15775970, ECO:0000269|PubMed:17094969}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:20111043}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:20111043}. Note=Has a stronger membrane anchorage
CC than isoform 1. {ECO:0000269|PubMed:20111043}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Mitochondrion
CC {ECO:0000269|PubMed:16644725}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:16644725}. Note=In pro-apoptotic conditions, is
CC released from mitochondria to cytosol in a calpain/cathepsin-dependent
CC manner. {ECO:0000269|PubMed:16644725}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm
CC {ECO:0000269|PubMed:16365034}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=AIF;
CC IsoId=O95831-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95831-2; Sequence=VSP_004357;
CC Name=3; Synonyms=AIF-exB, AIF2;
CC IsoId=O95831-3; Sequence=VSP_022953;
CC Name=4; Synonyms=AIFsh2 {ECO:0000303|PubMed:16644725};
CC IsoId=O95831-4; Sequence=VSP_043637, VSP_043638;
CC Name=5; Synonyms=AIFsh;
CC IsoId=O95831-5; Sequence=VSP_046248;
CC Name=6; Synonyms=AIFsh3 {ECO:0000303|PubMed:16644725};
CC IsoId=O95831-6; Sequence=VSP_060785, VSP_060786;
CC -!- TISSUE SPECIFICITY: Expressed in all tested tissues (PubMed:16644725).
CC Detected in muscle and skin fibroblasts (at protein level)
CC (PubMed:23217327). Expressed in osteoblasts (at protein level)
CC (PubMed:28842795). {ECO:0000269|PubMed:16644725,
CC ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:28842795}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Brain specific.
CC {ECO:0000269|PubMed:20111043}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Expressed in all tested tissues except
CC brain. {ECO:0000269|PubMed:16644725}.
CC -!- TISSUE SPECIFICITY: [Isoform 5]: Isoform 5 is frequently down-regulated
CC in human cancers. {ECO:0000269|PubMed:16365034}.
CC -!- INDUCTION: [Isoform 5]: Strongly down-regulated in many tumor cells,
CC up-regulated by gamma-irradiation. {ECO:0000269|PubMed:16365034}.
CC -!- PTM: Under normal conditions, a 54-residue N-terminal segment is first
CC proteolytically removed during or just after translocation into the
CC mitochondrial intermembrane space (IMS) by the mitochondrial processing
CC peptidase (MPP) to form the inner-membrane-anchored mature form
CC (AIFmit). During apoptosis, it is further proteolytically processed at
CC amino-acid position 101 leading to the generation of the mature form,
CC which is confined to the mitochondrial IMS in a soluble form (AIFsol).
CC AIFsol is released to the cytoplasm in response to specific death
CC signals, and translocated to the nucleus, where it induces nuclear
CC apoptosis in a caspase-independent manner.
CC {ECO:0000269|PubMed:15775970}.
CC -!- PTM: Ubiquitination by XIAP/BIRC4 does not lead to proteasomal
CC degradation. Ubiquitination at Lys-255 by XIAP/BIRC4 blocks its ability
CC to bind DNA and induce chromatin degradation, thereby inhibiting its
CC ability to induce cell death. {ECO:0000269|PubMed:17967870,
CC ECO:0000269|PubMed:22103349}.
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 6 (COXPD6)
CC [MIM:300816]: A mitochondrial disease resulting in a neurodegenerative
CC disorder characterized by psychomotor delay, hypotonia, areflexia,
CC muscle weakness and wasting. Some patients manifest prenatal
CC ventriculomegaly and severe postnatal encephalomyopathy.
CC {ECO:0000269|PubMed:20362274, ECO:0000269|PubMed:22019070,
CC ECO:0000269|PubMed:25583628, ECO:0000269|PubMed:26004228,
CC ECO:0000269|PubMed:26173962, ECO:0000269|PubMed:27178839}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease, X-linked recessive, 4, with or
CC without cerebellar ataxia (CMTX4) [MIM:310490]: A neuromuscular
CC disorder characterized by progressive sensorimotor axonal neuropathy,
CC distal sensory impairment, difficulty walking due to peripheral
CC neuropathy and/or cerebellar ataxia, and deafness due to auditory
CC neuropathy. Additional features include cognitive impairment,
CC cerebellar atrophy, dysarthria, abnormal extraocular movements, tremor,
CC dysmetria and spasticity. The age at onset ranges from infancy to young
CC adulthood. {ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:26004228}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Deafness, X-linked, 5, with peripheral neuropathy (DFNX5)
CC [MIM:300614]: A form of hearing loss characterized by absent or
CC severely abnormal auditory brainstem response, abnormal middle ear
CC reflexes, abnormal speech discrimination, loss of outer hair cell
CC function, and cochlear nerve hypoplasia. DFNX5 patients manifest
CC auditory neuropathy with childhood onset, associated with distal
CC sensory impairment affecting the peripheral nervous system.
CC {ECO:0000269|PubMed:25986071}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Spondyloepimetaphyseal dysplasia, X-linked, with
CC hypomyelinating leukodystrophy (SEMDHL) [MIM:300232]: An X-linked
CC recessive developmental disorder characterized by slowly progressive
CC skeletal and neurologic abnormalities, including short stature, large
CC and deformed joints, significant motor impairment, visual defects, and
CC sometimes cognitive deficits. Affected individuals typically have
CC normal early development in the first year or so of life, followed by
CC development regression and the development of symptoms. Brain imaging
CC shows white matter abnormalities consistent with hypomyelinating
CC leukodystrophy. {ECO:0000269|PubMed:28842795}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 6]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY84741.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AIFM1ID44053chXq25.html";
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DR EMBL; AF100928; AAD16436.1; -; mRNA.
DR EMBL; DQ016496; AAY84737.1; -; mRNA.
DR EMBL; DQ016498; AAY84739.1; -; mRNA.
DR EMBL; DQ016500; AAY84741.1; ALT_SEQ; mRNA.
DR EMBL; AL049703; CAB41267.1; -; mRNA.
DR EMBL; AL049704; CAB41268.1; -; mRNA.
DR EMBL; AK314446; BAG37055.1; -; mRNA.
DR EMBL; CR457379; CAG33660.1; -; mRNA.
DR EMBL; AL139234; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF459397; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF510638; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471107; EAX11811.1; -; Genomic_DNA.
DR EMBL; CH471107; EAX11812.1; -; Genomic_DNA.
DR EMBL; CH471107; EAX11810.1; -; Genomic_DNA.
DR EMBL; BC111065; AAI11066.1; -; mRNA.
DR EMBL; BC139738; AAI39739.1; -; mRNA.
DR EMBL; AF131759; AAD20036.1; -; mRNA.
DR CCDS; CCDS14618.1; -. [O95831-1]
DR CCDS; CCDS14619.1; -. [O95831-3]
DR CCDS; CCDS48167.1; -. [O95831-4]
DR RefSeq; NP_001124318.2; NM_001130846.3.
DR RefSeq; NP_001124319.1; NM_001130847.3. [O95831-4]
DR RefSeq; NP_004199.1; NM_004208.3. [O95831-1]
DR RefSeq; NP_665811.1; NM_145812.2. [O95831-3]
DR PDB; 1M6I; X-ray; 1.80 A; A=121-613.
DR PDB; 4BUR; X-ray; 2.88 A; A/B/C/D=103-613.
DR PDB; 4BV6; X-ray; 1.80 A; A=121-613.
DR PDB; 4FDC; X-ray; 2.40 A; B=103-613.
DR PDB; 4LII; X-ray; 1.88 A; A=100-611.
DR PDB; 5FMH; X-ray; 1.80 A; A=104-613.
DR PDB; 5FS6; X-ray; 1.90 A; A/B=103-613.
DR PDB; 5FS7; X-ray; 1.85 A; A/B=103-613.
DR PDB; 5FS8; X-ray; 1.40 A; A=103-613.
DR PDB; 5FS9; X-ray; 1.75 A; A/B=103-613.
DR PDB; 5KVH; X-ray; 2.27 A; A/B=78-613.
DR PDB; 5KVI; X-ray; 2.00 A; A=78-613.
DR PDBsum; 1M6I; -.
DR PDBsum; 4BUR; -.
DR PDBsum; 4BV6; -.
DR PDBsum; 4FDC; -.
DR PDBsum; 4LII; -.
DR PDBsum; 5FMH; -.
DR PDBsum; 5FS6; -.
DR PDBsum; 5FS7; -.
DR PDBsum; 5FS8; -.
DR PDBsum; 5FS9; -.
DR PDBsum; 5KVH; -.
DR PDBsum; 5KVI; -.
DR AlphaFoldDB; O95831; -.
DR SMR; O95831; -.
DR BioGRID; 114579; 556.
DR CORUM; O95831; -.
DR DIP; DIP-32975N; -.
DR IntAct; O95831; 292.
DR MINT; O95831; -.
DR STRING; 9606.ENSP00000287295; -.
DR ChEMBL; CHEMBL4295688; -.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB05282; MCC.
DR CarbonylDB; O95831; -.
DR GlyGen; O95831; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95831; -.
DR MetOSite; O95831; -.
DR PhosphoSitePlus; O95831; -.
DR SwissPalm; O95831; -.
DR BioMuta; AIFM1; -.
DR REPRODUCTION-2DPAGE; IPI00157908; -.
DR UCD-2DPAGE; O95831; -.
DR EPD; O95831; -.
DR jPOST; O95831; -.
DR MassIVE; O95831; -.
DR MaxQB; O95831; -.
DR PaxDb; O95831; -.
DR PeptideAtlas; O95831; -.
DR PRIDE; O95831; -.
DR ProteomicsDB; 51073; -. [O95831-1]
DR ProteomicsDB; 51074; -. [O95831-2]
DR ProteomicsDB; 51075; -. [O95831-3]
DR ProteomicsDB; 51076; -. [O95831-4]
DR ProteomicsDB; 61222; -.
DR ProteomicsDB; 61439; -.
DR ABCD; O95831; 1 sequenced antibody.
DR Antibodypedia; 3528; 876 antibodies from 47 providers.
DR DNASU; 9131; -.
DR Ensembl; ENST00000287295.8; ENSP00000287295.3; ENSG00000156709.15. [O95831-1]
DR Ensembl; ENST00000346424.6; ENSP00000316320.3; ENSG00000156709.15. [O95831-2]
DR Ensembl; ENST00000527892.5; ENSP00000435955.1; ENSG00000156709.15. [O95831-6]
DR Ensembl; ENST00000535724.6; ENSP00000446113.2; ENSG00000156709.15. [O95831-4]
DR Ensembl; ENST00000674997.1; ENSP00000502124.1; ENSG00000156709.15. [O95831-6]
DR Ensembl; ENST00000675050.1; ENSP00000502606.1; ENSG00000156709.15. [O95831-3]
DR Ensembl; ENST00000675774.1; ENSP00000502690.1; ENSG00000156709.15. [O95831-6]
DR Ensembl; ENST00000676229.1; ENSP00000502184.1; ENSG00000156709.15. [O95831-3]
DR GeneID; 9131; -.
DR KEGG; hsa:9131; -.
DR MANE-Select; ENST00000287295.8; ENSP00000287295.3; NM_004208.4; NP_004199.1.
DR UCSC; uc004evg.4; human. [O95831-1]
DR UCSC; uc065bbv.1; human.
DR CTD; 9131; -.
DR DisGeNET; 9131; -.
DR GeneCards; AIFM1; -.
DR GeneReviews; AIFM1; -.
DR HGNC; HGNC:8768; AIFM1.
DR HPA; ENSG00000156709; Low tissue specificity.
DR MalaCards; AIFM1; -.
DR MIM; 300169; gene.
DR MIM; 300232; phenotype.
DR MIM; 300614; phenotype.
DR MIM; 300816; phenotype.
DR MIM; 310490; phenotype.
DR neXtProt; NX_O95831; -.
DR OpenTargets; ENSG00000156709; -.
DR Orphanet; 83629; Leukoencephalopathy-spondyloepimetaphyseal dysplasia syndrome.
DR Orphanet; 238329; Severe X-linked mitochondrial encephalomyopathy.
DR Orphanet; 101078; X-linked Charcot-Marie-Tooth disease type 4.
DR Orphanet; 139583; X-linked hereditary sensory and autonomic neuropathy with deafness.
DR PharmGKB; PA162376129; -.
DR VEuPathDB; HostDB:ENSG00000156709; -.
DR eggNOG; KOG1346; Eukaryota.
DR GeneTree; ENSGT00940000156455; -.
DR HOGENOM; CLU_1059750_0_0_1; -.
DR InParanoid; O95831; -.
DR OMA; EVRYERC; -.
DR OrthoDB; 830428at2759; -.
DR PhylomeDB; O95831; -.
DR TreeFam; TF314028; -.
DR BRENDA; 7.1.1.2; 2681.
DR PathwayCommons; O95831; -.
DR SABIO-RK; O95831; -.
DR SignaLink; O95831; -.
DR SIGNOR; O95831; -.
DR BioGRID-ORCS; 9131; 156 hits in 721 CRISPR screens.
DR ChiTaRS; AIFM1; human.
DR EvolutionaryTrace; O95831; -.
DR GeneWiki; AIFM1; -.
DR GenomeRNAi; 9131; -.
DR Pharos; O95831; Tbio.
DR PRO; PR:O95831; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O95831; protein.
DR Bgee; ENSG00000156709; Expressed in apex of heart and 181 other tissues.
DR ExpressionAtlas; O95831; baseline and differential.
DR Genevisible; O95831; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; IDA:UniProtKB.
DR GO; GO:0003954; F:NADH dehydrogenase activity; IEA:RHEA.
DR GO; GO:0016651; F:oxidoreductase activity, acting on NAD(P)H; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:1904045; P:cellular response to aldosterone; IEA:Ensembl.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071732; P:cellular response to nitric oxide; IEA:Ensembl.
DR GO; GO:0090650; P:cellular response to oxygen-glucose deprivation; IEA:Ensembl.
DR GO; GO:0030261; P:chromosome condensation; TAS:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; IMP:UniProtKB.
DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0012501; P:programmed cell death; IBA:GO_Central.
DR GO; GO:0045041; P:protein import into mitochondrial intermembrane space; IMP:UniProtKB.
DR GO; GO:1902510; P:regulation of apoptotic DNA fragmentation; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR029324; AIF_C.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR Pfam; PF14721; AIF_C; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR SUPFAM; SSF51905; SSF51905; 2.
DR SUPFAM; SSF55424; SSF55424; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Charcot-Marie-Tooth disease; Cytoplasm; Deafness;
KW Direct protein sequencing; Disease variant; DNA-binding; Dwarfism; FAD;
KW Flavoprotein; Intellectual disability; Isopeptide bond; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; NAD; Neurodegeneration;
KW Neuropathy; Nucleus; Oxidoreductase; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; Transit peptide;
KW Ubl conjugation.
FT TRANSIT 1..54
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:15775970,
FT ECO:0000269|PubMed:16365034, ECO:0007744|PubMed:25944712"
FT PROPEP 55..101
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:16365034"
FT /id="PRO_0000401935"
FT CHAIN 102..613
FT /note="Apoptosis-inducing factor 1, mitochondrial"
FT /id="PRO_0000022030"
FT REGION 100..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 134..483
FT /note="FAD-dependent oxidoreductase"
FT /evidence="ECO:0000250"
FT REGION 513..554
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1..31
FT /note="Mitochondrial localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X1"
FT MOTIF 63..89
FT /note="Mitochondrial localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X1"
FT MOTIF 446..451
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 514..546
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 138..142
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
FT ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:27818101,
FT ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6,
FT ECO:0007744|PDB:5FS7, ECO:0007744|PDB:5FS8,
FT ECO:0007744|PDB:5FS9, ECO:0007744|PDB:5KVI"
FT BINDING 164..165
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
FT ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:27818101,
FT ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6,
FT ECO:0007744|PDB:5FS7, ECO:0007744|PDB:5FS8,
FT ECO:0007744|PDB:5FS9, ECO:0007744|PDB:5KVH,
FT ECO:0007744|PDB:5KVI"
FT BINDING 172
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
FT ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:27818101,
FT ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6,
FT ECO:0007744|PDB:5FS7, ECO:0007744|PDB:5FS8,
FT ECO:0007744|PDB:5FS9, ECO:0007744|PDB:5KVH,
FT ECO:0007744|PDB:5KVI"
FT BINDING 177
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:24914854, ECO:0000269|PubMed:27178839,
FT ECO:0000269|PubMed:27818101, ECO:0007744|PDB:4BUR,
FT ECO:0007744|PDB:4BV6, ECO:0007744|PDB:5FS7,
FT ECO:0007744|PDB:5FS8, ECO:0007744|PDB:5FS9,
FT ECO:0007744|PDB:5KVI"
FT BINDING 196
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24914854,
FT ECO:0007744|PDB:4BUR"
FT BINDING 233
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
FT ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:27818101,
FT ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6,
FT ECO:0007744|PDB:5FS7, ECO:0007744|PDB:5FS8,
FT ECO:0007744|PDB:5FS9, ECO:0007744|PDB:5KVH,
FT ECO:0007744|PDB:5KVI"
FT BINDING 285
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
FT ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:27818101,
FT ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6,
FT ECO:0007744|PDB:5FS7, ECO:0007744|PDB:5FS8,
FT ECO:0007744|PDB:5FS9, ECO:0007744|PDB:5KVH"
FT BINDING 308..311
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24914854,
FT ECO:0007744|PDB:4BUR"
FT BINDING 336
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24914854,
FT ECO:0007744|PDB:4BUR"
FT BINDING 342
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X1"
FT BINDING 399
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24914854,
FT ECO:0007744|PDB:4BUR"
FT BINDING 438
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
FT ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:27818101,
FT ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6,
FT ECO:0007744|PDB:5FS7, ECO:0007744|PDB:5FS8,
FT ECO:0007744|PDB:5FS9, ECO:0007744|PDB:5KVH,
FT ECO:0007744|PDB:5KVI"
FT BINDING 453..454
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24914854,
FT ECO:0007744|PDB:4BUR"
FT BINDING 454..455
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:24914854, ECO:0000269|PubMed:27178839,
FT ECO:0000269|PubMed:27818101, ECO:0007744|PDB:4BUR,
FT ECO:0007744|PDB:4BV6, ECO:0007744|PDB:5FS7,
FT ECO:0007744|PDB:5FS8, ECO:0007744|PDB:5FS9,
FT ECO:0007744|PDB:5KVH, ECO:0007744|PDB:5KVI"
FT BINDING 483
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:12198487,
FT ECO:0000269|PubMed:23217327, ECO:0000269|PubMed:24914854,
FT ECO:0000269|PubMed:27178839, ECO:0000269|PubMed:27818101,
FT ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6,
FT ECO:0007744|PDB:5FS7, ECO:0007744|PDB:5FS8,
FT ECO:0007744|PDB:5FS9, ECO:0007744|PDB:5KVH,
FT ECO:0007744|PDB:5KVI"
FT BINDING 483
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24914854,
FT ECO:0007744|PDB:4BUR, ECO:0007744|PDB:4BV6"
FT BINDING 493
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24914854,
FT ECO:0007744|PDB:4BUR"
FT BINDING 583
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24914854,
FT ECO:0007744|PDB:4BUR"
FT MOD_RES 105
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 109
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X1"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 388
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X1"
FT MOD_RES 521
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 530
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 593
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0X1"
FT CROSSLNK 255
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:22103349"
FT VAR_SEQ 1..352
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:16365034"
FT /id="VSP_046248"
FT VAR_SEQ 36..322
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_004357"
FT VAR_SEQ 36..82
FT /note="GNLFQRWHVPLELQMTRQMASSGASGGKIDNSVLVLIVGLSTVGAGA -> V
FT VQSHHLGSPSRSLASTGASGKDGSNLVYFLIVGATVTGAGVY (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.4"
FT /id="VSP_022953"
FT VAR_SEQ 37..43
FT /note="NLFQRWH -> LQDYERG (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_060785"
FT VAR_SEQ 44..613
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_060786"
FT VAR_SEQ 323..324
FT /note="AR -> DI (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16644725"
FT /id="VSP_043637"
FT VAR_SEQ 325..613
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16644725"
FT /id="VSP_043638"
FT VARIANT 201
FT /note="Missing (in COXPD6; higher DNA binding affinity,
FT partially impaired flavin binding and association with
FT increased parthanatos-linked cell death;
FT dbSNP:rs387906500)"
FT /evidence="ECO:0000269|PubMed:20362274"
FT /id="VAR_063827"
FT VARIANT 235
FT /note="Q -> H (in SEMDHL; severe decrease of protein
FT expression; dbSNP:rs377527583)"
FT /evidence="ECO:0000269|PubMed:28842795"
FT /id="VAR_083739"
FT VARIANT 237
FT /note="D -> G (in SEMDHL; dbSNP:rs1202786652)"
FT /evidence="ECO:0000269|PubMed:28842795"
FT /id="VAR_083740"
FT VARIANT 237
FT /note="D -> V (in SEMDHL; dbSNP:rs1202786652)"
FT /evidence="ECO:0000269|PubMed:28842795"
FT /id="VAR_083741"
FT VARIANT 243
FT /note="V -> L (in COXPD6; reduced protein amount in muscle
FT compared to controls; no effect on reduction with NADH;
FT strongly decreased NADH oxidase activity; no effect on
FT dimerization; no effect on DNA-binding;
FT dbSNP:rs1603225138)"
FT /evidence="ECO:0000269|PubMed:25583628,
FT ECO:0000269|PubMed:27178839"
FT /id="VAR_072791"
FT VARIANT 260
FT /note="T -> A (in DFNX5; dbSNP:rs863225432)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076211"
FT VARIANT 262
FT /note="G -> S (probable disease-associated variant found in
FT patient with mitochondrial encephalomyopathy with moderate
FT clinical severity and slow progressive course despite early
FT onset as well as and cerebellar involvement; decreased
FT protein level; strongly decreased redox potential; strongly
FT decreased NADH oxidase activity; no effect on DNA-binding;
FT dbSNP:rs1603224817)"
FT /evidence="ECO:0000269|PubMed:25934856,
FT ECO:0000269|PubMed:27178839"
FT /id="VAR_083067"
FT VARIANT 308
FT /note="G -> E (in COXPD6; with prenatal ventriculomegaly
FT and severe postnatal encephalomyopathy; no effect on redox
FT potential; slowered reduction with NADH; strongly decreased
FT NADH oxidase activity; strongly decreased NADH oxidase
FT activity; no effect on DNA-binding; decreased interaction
FT with CHCHDE; dbSNP:rs1603224226)"
FT /evidence="ECO:0000269|PubMed:22019070,
FT ECO:0000269|PubMed:26004228, ECO:0000269|PubMed:27178839"
FT /id="VAR_067334"
FT VARIANT 338
FT /note="G -> E (in COXPD6; with early-onset severe motor
FT neuron involvement; decreased protein levels; decreased
FT oxidoreductase activity on cytochrome C; slowered reduction
FT with NADH; strongly decreased NADH oxidase activity;
FT strongly decreased NADH oxidase activity; no effect on DNA-
FT binding; dbSNP:rs1603223152)"
FT /evidence="ECO:0000269|PubMed:26173962,
FT ECO:0000269|PubMed:27178839"
FT /id="VAR_083068"
FT VARIANT 344
FT /note="L -> F (in DFNX5; unknown pathological significance;
FT dbSNP:rs184474885)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076212"
FT VARIANT 360
FT /note="G -> R (in DFNX5; unknown pathological significance;
FT dbSNP:rs724160026)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076213"
FT VARIANT 422
FT /note="R -> Q (in DFNX5; dbSNP:rs724160021)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076214"
FT VARIANT 422
FT /note="R -> W (in DFNX5; dbSNP:rs724160020)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076215"
FT VARIANT 430
FT /note="R -> C (in DFNX5; unknown pathological significance;
FT dbSNP:rs1223488720)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076216"
FT VARIANT 451
FT /note="R -> Q (in DFNX5; dbSNP:rs863225431)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076217"
FT VARIANT 472
FT /note="A -> V (in DFNX5; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076218"
FT VARIANT 475
FT /note="P -> L (in DFNX5; unknown pathological significance;
FT dbSNP:rs724160022)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076219"
FT VARIANT 493
FT /note="E -> V (in CMTX4; increases affinity for NADH and
FT electron transfer activity; increases affinity for DNA,
FT resulting in increased apoptosis; no effect on interaction
FT with CHCHD4; dbSNP:rs281864468)"
FT /evidence="ECO:0000269|PubMed:23217327,
FT ECO:0000269|PubMed:26004228"
FT /id="VAR_069468"
FT VARIANT 498
FT /note="V -> M (in DFNX5; unknown pathological significance;
FT dbSNP:rs724160023)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076220"
FT VARIANT 591
FT /note="I -> M (in DFNX5; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:25986071"
FT /id="VAR_076221"
FT MUTAGEN 196
FT /note="W->A: Increases protein dimerization at lower NADH
FT levels."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 413..430
FT /note="EIDSDFGGFRVNAELQAR->AIDSDFGGFAVNAELQAA: Disrupts
FT dimerization. Lower efficiency in stabilizing charge-
FT transfer complexes upon coenzyme reduction."
FT /evidence="ECO:0000269|PubMed:24914854"
FT MUTAGEN 443..445
FT /note="YDI->ADA: Disrupts dimerization. Disrupts
FT dimerization; when associated with A-477."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 454
FT /note="H->A: Allows dimerization in absence of NADH."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 477
FT /note="W->A: Disrupts dimerization; when associated with A-
FT 443--445-A."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 480
FT /note="S->A: Allows dimerization in absence of NADH."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 485
FT /note="D->A: Increases protein dimerization at lower NADH
FT levels."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 529
FT /note="R->A: Increases protein dimerization at lower NADH
FT levels."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 531
FT /note="E->A: Increases protein dimerization at lower NADH
FT levels."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 533
FT /note="E->A: Increases protein dimerization at lower NADH
FT levels."
FT /evidence="ECO:0000269|PubMed:27818101"
FT MUTAGEN 535
FT /note="E->A: Increases protein dimerization at lower NADH
FT levels."
FT /evidence="ECO:0000269|PubMed:27818101"
FT STRAND 130..138
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 141..153
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 158..162
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 187..190
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 200..206
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:5FS8"
FT TURN 214..219
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 233..237
FT /evidence="ECO:0007829|PDB:5FS8"
FT TURN 238..241
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 242..245
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 250..258
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 268..271
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 275..279
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 287..299
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 301..306
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 310..326
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 335..338
FT /evidence="ECO:0007829|PDB:5FS8"
FT TURN 339..343
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 346..358
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 362..364
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 369..375
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 378..383
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 388..396
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 407..410
FT /evidence="ECO:0007829|PDB:5FS8"
FT TURN 416..418
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 420..422
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 427..430
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 433..435
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 437..439
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 440..444
FT /evidence="ECO:0007829|PDB:5FS8"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 448..450
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 455..468
FT /evidence="ECO:0007829|PDB:5FS8"
FT TURN 469..471
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 481..487
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 491..496
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 504..509
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 513..515
FT /evidence="ECO:0007829|PDB:4BUR"
FT HELIX 517..524
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 529..533
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 538..542
FT /evidence="ECO:0007829|PDB:5KVI"
FT STRAND 562..569
FT /evidence="ECO:0007829|PDB:5FS8"
FT STRAND 572..580
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 585..594
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 601..605
FT /evidence="ECO:0007829|PDB:5FS8"
FT HELIX 606..608
FT /evidence="ECO:0007829|PDB:5FS8"
SQ SEQUENCE 613 AA; 66901 MW; A156762BC64E6340 CRC64;
MFRCGGLAAG ALKQKLVPLV RTVCVRSPRQ RNRLPGNLFQ RWHVPLELQM TRQMASSGAS
GGKIDNSVLV LIVGLSTVGA GAYAYKTMKE DEKRYNERIS GLGLTPEQKQ KKAALSASEG
EEVPQDKAPS HVPFLLIGGG TAAFAAARSI RARDPGARVL IVSEDPELPY MRPPLSKELW
FSDDPNVTKT LRFKQWNGKE RSIYFQPPSF YVSAQDLPHI ENGGVAVLTG KKVVQLDVRD
NMVKLNDGSQ ITYEKCLIAT GGTPRSLSAI DRAGAEVKSR TTLFRKIGDF RSLEKISREV
KSITIIGGGF LGSELACALG RKARALGTEV IQLFPEKGNM GKILPEYLSN WTMEKVRREG
VKVMPNAIVQ SVGVSSGKLL IKLKDGRKVE TDHIVAAVGL EPNVELAKTG GLEIDSDFGG
FRVNAELQAR SNIWVAGDAA CFYDIKLGRR RVEHHDHAVV SGRLAGENMT GAAKPYWHQS
MFWSDLGPDV GYEAIGLVDS SLPTVGVFAK ATAQDNPKSA TEQSGTGIRS ESETESEASE
ITIPPSTPAV PQAPVQGEDY GKGVIFYLRD KVVVGIVLWN IFNRMPIARK IIKDGEQHED
LNEVAKLFNI HED
