AIFM1_MOUSE
ID AIFM1_MOUSE Reviewed; 612 AA.
AC Q9Z0X1; Q1L6K5;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Apoptosis-inducing factor 1, mitochondrial {ECO:0000305};
DE EC=1.6.99.- {ECO:0000269|PubMed:19447115};
DE AltName: Full=Programmed cell death protein 8;
DE Flags: Precursor;
GN Name=Aifm1 {ECO:0000312|MGI:MGI:1349419}; Synonyms=Aif, Pdcd8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, PROTEIN
RP SEQUENCE OF 322-336, FUNCTION, COFACTOR, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND SUBCELLULAR LOCATION.
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] {ECO:0000312|EMBL:AAY84740.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2),
RP AND TISSUE SPECIFICITY (ISOFORM 2).
RC STRAIN=C57BL/6J;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP PROTEIN SEQUENCE OF 378-386, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-108, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-387 AND LYS-592, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [8]
RP FUNCTION.
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 [9]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=30830864; DOI=10.1172/jci.insight.124519;
RA Mashimo M., Bu X., Aoyama K., Kato J., Ishiwata-Endo H., Stevens L.A.,
RA Kasamatsu A., Wolfe L.A., Toro C., Adams D., Markello T., Gahl W.A.,
RA Moss J.;
RT "PARP1 inhibition alleviates injury in ARH3-deficient mice and human
RT cells.";
RL JCI Insight 4:0-0(2019).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 108-610 IN COMPLEX WITH FAD,
RP NAD-BINDING, AND MUTAGENESIS OF LYS-176 AND GLU-313.
RX PubMed=11967568; DOI=10.1038/nsb793;
RA Mate M.J., Ortiz-Lombardia M., Boitel B., Haouz A., Tello D., Susin S.A.,
RA Penninger J., Kroemer G., Alzari P.M.;
RT "The crystal structure of the mouse apoptosis-inducing factor AIF.";
RL Nat. Struct. Biol. 9:442-446(2002).
RN [11] {ECO:0007744|PDB:3GD3, ECO:0007744|PDB:3GD4}
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 78-612 IN COMPLEX WITH FAD AND
RP NAD, FAD-BINDING, NAD-BINDING, MUTAGENESIS OF TRP-195, SUBUNIT, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC ACTIVITY.
RX PubMed=19447115; DOI=10.1016/j.jmb.2009.05.013;
RA Sevrioukova I.F.;
RT "Redox-linked conformational dynamics in apoptosis-inducing factor.";
RL J. Mol. Biol. 390:924-938(2009).
CC -!- FUNCTION: Functions both as NADH oxidoreductase and as regulator of
CC apoptosis (By similarity). In response to apoptotic stimuli, it is
CC released from the mitochondrion intermembrane space into the cytosol
CC and to the nucleus, where it functions as a proapoptotic factor in a
CC caspase-independent pathway. The soluble form (AIFsol) found in the
CC nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of
CC chromosomal DNA (PubMed:9989411). Binds to DNA in a sequence-
CC independent manner. Interacts with EIF3G, and thereby inhibits the EIF3
CC machinery and protein synthesis, and activates caspase-7 to amplify
CC apoptosis. Plays a critical role in caspase-independent, pyknotic cell
CC death in hydrogen peroxide-exposed cells (By similarity). In contrast,
CC participates in normal mitochondrial metabolism. Plays an important
CC role in the regulation of respiratory chain biogenesis by interacting
CC with CHCHD4 and controlling CHCHD4 mitochondrial import
CC (PubMed:19447115). {ECO:0000250|UniProtKB:O95831,
CC ECO:0000269|PubMed:19447115, ECO:0000269|PubMed:9989411}.
CC -!- FUNCTION: [Isoform 2]: Has NADH oxidoreductase activity. Does not
CC induce nuclear apoptosis. {ECO:0000250|UniProtKB:O95831}.
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:19447115};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
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:0000250|UniProtKB:O95831};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:19447115, ECO:0000269|PubMed:9989411};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=kcat is 48 min(-1) for dichlorophenolindophenol and 34 min(-1)
CC for cytochrome c. {ECO:0000269|PubMed:19447115};
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:19447115). Also dimerizes with isoform 3 preventing its release
CC from mitochondria. Interacts with XIAP/BIRC4. Interacts (via N-
CC terminus) with EIF3G (via C-terminus). Interacts with PRELID1.
CC Interacts with CHCHD4; the interaction increases in presence of NADH
CC (By similarity). {ECO:0000250|UniProtKB:O95831,
CC ECO:0000269|PubMed:19447115}.
CC -!- INTERACTION:
CC Q9Z0X1; P27661: H2ax; NbExp=3; IntAct=EBI-773597, EBI-495621;
CC Q9Z0X1; Q9EQN3: Tsc22d4; NbExp=4; IntAct=EBI-773597, EBI-7821198;
CC PRO_0000022031; P16104: H2AX; Xeno; NbExp=2; IntAct=EBI-5326677, EBI-494830;
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space
CC {ECO:0000269|PubMed:9989411}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:30830864}. Cytoplasm
CC {ECO:0000250|UniProtKB:O95831}. Nucleus {ECO:0000250|UniProtKB:O95831}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:O95831}.
CC Note=Proteolytic cleavage during or just after translocation into the
CC mitochondrial intermembrane space (IMS) results in the formation of an
CC inner-membrane-anchored mature form (AIFmit). During apoptosis, further
CC proteolytic processing leads to a mature form, which is confined to the
CC mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the
CC cytoplasm in response to specific death signals, and translocated to
CC the nucleus, where it induces nuclear apoptosis. Colocalizes with EIF3G
CC in the nucleus and perinuclear region. {ECO:0000250|UniProtKB:O95831}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion
CC {ECO:0000269|PubMed:16644725}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O95831}. Note=In pro-apoptotic conditions, is
CC released from mitochondria to cytosol in a calpain/cathepsin-dependent
CC manner. {ECO:0000250|UniProtKB:O95831}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Z0X1-1; Sequence=Displayed;
CC Name=2; Synonyms=AIFsh2 {ECO:0000303|PubMed:16644725};
CC IsoId=Q9Z0X1-2; Sequence=VSP_060486, VSP_060487;
CC -!- TISSUE SPECIFICITY: Expressed in cortical neurons (at protein level).
CC {ECO:0000269|PubMed:30830864}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in liver (at protein level).
CC {ECO:0000269|PubMed:16644725}.
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:0000250|UniProtKB:O95831}.
CC -!- PTM: Ubiquitination by XIAP/BIRC4 does not lead to proteasomal
CC degradation. Ubiquitination at Lys-254 by XIAP/BIRC4 blocks its ability
CC to bind DNA and induce chromatin degradation, thereby inhibiting its
CC ability to induce cell death. {ECO:0000250|UniProtKB:O95831}.
CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase family.
CC {ECO:0000305}.
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DR EMBL; AF100927; AAD16435.1; -; mRNA.
DR EMBL; DQ016499; AAY84740.1; -; mRNA.
DR EMBL; BC003292; AAH03292.1; -; mRNA.
DR CCDS; CCDS30109.1; -. [Q9Z0X1-1]
DR RefSeq; NP_001277293.1; NM_001290364.1.
DR RefSeq; NP_036149.1; NM_012019.3. [Q9Z0X1-1]
DR PDB; 1GV4; X-ray; 2.00 A; A/B=122-610.
DR PDB; 3GD3; X-ray; 2.95 A; A/B/C/D=78-612.
DR PDB; 3GD4; X-ray; 2.24 A; A/B=102-612.
DR PDB; 5MIU; X-ray; 3.50 A; A/B=78-612.
DR PDB; 5MIV; X-ray; 3.10 A; A/C=78-612.
DR PDBsum; 1GV4; -.
DR PDBsum; 3GD3; -.
DR PDBsum; 3GD4; -.
DR PDBsum; 5MIU; -.
DR PDBsum; 5MIV; -.
DR AlphaFoldDB; Q9Z0X1; -.
DR SMR; Q9Z0X1; -.
DR BioGRID; 205067; 32.
DR IntAct; Q9Z0X1; 24.
DR MINT; Q9Z0X1; -.
DR STRING; 10090.ENSMUSP00000041104; -.
DR iPTMnet; Q9Z0X1; -.
DR PhosphoSitePlus; Q9Z0X1; -.
DR SwissPalm; Q9Z0X1; -.
DR EPD; Q9Z0X1; -.
DR jPOST; Q9Z0X1; -.
DR MaxQB; Q9Z0X1; -.
DR PaxDb; Q9Z0X1; -.
DR PeptideAtlas; Q9Z0X1; -.
DR PRIDE; Q9Z0X1; -.
DR ProteomicsDB; 296004; -. [Q9Z0X1-1]
DR Antibodypedia; 3528; 876 antibodies from 47 providers.
DR DNASU; 26926; -.
DR Ensembl; ENSMUST00000037349; ENSMUSP00000041104; ENSMUSG00000036932. [Q9Z0X1-1]
DR GeneID; 26926; -.
DR KEGG; mmu:26926; -.
DR UCSC; uc009tcg.1; mouse. [Q9Z0X1-1]
DR CTD; 9131; -.
DR MGI; MGI:1349419; Aifm1.
DR VEuPathDB; HostDB:ENSMUSG00000036932; -.
DR eggNOG; KOG1346; Eukaryota.
DR GeneTree; ENSGT00940000156455; -.
DR HOGENOM; CLU_003291_5_3_1; -.
DR InParanoid; Q9Z0X1; -.
DR OrthoDB; 830428at2759; -.
DR PhylomeDB; Q9Z0X1; -.
DR TreeFam; TF314028; -.
DR SABIO-RK; Q9Z0X1; -.
DR BioGRID-ORCS; 26926; 11 hits in 72 CRISPR screens.
DR ChiTaRS; Aifm1; mouse.
DR EvolutionaryTrace; Q9Z0X1; -.
DR PRO; PR:Q9Z0X1; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9Z0X1; protein.
DR Bgee; ENSMUSG00000036932; Expressed in ileal epithelium and 260 other tissues.
DR ExpressionAtlas; Q9Z0X1; baseline and differential.
DR Genevisible; Q9Z0X1; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
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:0004174; F:electron-transferring-flavoprotein dehydrogenase activity; TAS:MGI.
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; ISO:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0019153; F:protein-disulfide reductase (glutathione) activity; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; TAS:MGI.
DR GO; GO:0006915; P:apoptotic process; IBA:GO_Central.
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:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0033108; P:mitochondrial respiratory chain complex assembly; IMP:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IGI:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
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; IGI:MGI.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; TAS:UniProtKB.
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; Cytoplasm;
KW Direct protein sequencing; DNA-binding; FAD; Flavoprotein; Isopeptide bond;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; NAD; Nucleus;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide;
KW Ubl conjugation.
FT TRANSIT 1..54
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT PROPEP 55..101
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:9989411"
FT /id="PRO_0000401936"
FT CHAIN 102..612
FT /note="Apoptosis-inducing factor 1, mitochondrial"
FT /id="PRO_0000022031"
FT REGION 133..482
FT /note="FAD-dependent oxidoreductase"
FT REGION 512..551
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1..30
FT /note="Mitochondrial localization signal"
FT /evidence="ECO:0000305|PubMed:9989411"
FT MOTIF 62..88
FT /note="Mitochondrial localization signal"
FT /evidence="ECO:0000305|PubMed:9989411"
FT MOTIF 445..450
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 513..540
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 137..141
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:11967568,
FT ECO:0000269|PubMed:19447115, ECO:0007744|PDB:3GD3,
FT ECO:0007744|PDB:3GD4"
FT BINDING 163..164
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:11967568,
FT ECO:0000269|PubMed:19447115, ECO:0007744|PDB:3GD4"
FT BINDING 171
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:11967568,
FT ECO:0000269|PubMed:19447115, ECO:0007744|PDB:3GD3,
FT ECO:0007744|PDB:3GD4"
FT BINDING 176
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:11967568,
FT ECO:0000269|PubMed:19447115, ECO:0007744|PDB:3GD3"
FT BINDING 195
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT BINDING 232
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:11967568,
FT ECO:0000269|PubMed:19447115, ECO:0007744|PDB:3GD3,
FT ECO:0007744|PDB:3GD4"
FT BINDING 284
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:11967568,
FT ECO:0000269|PubMed:19447115, ECO:0007744|PDB:3GD3,
FT ECO:0007744|PDB:3GD4"
FT BINDING 307..310
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19447115,
FT ECO:0007744|PDB:3GD4"
FT BINDING 335
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19447115,
FT ECO:0007744|PDB:3GD4"
FT BINDING 341
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19447115,
FT ECO:0007744|PDB:3GD4"
FT BINDING 398
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19447115,
FT ECO:0007744|PDB:3GD4"
FT BINDING 437
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:19447115,
FT ECO:0007744|PDB:3GD3, ECO:0007744|PDB:3GD4"
FT BINDING 452..453
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19447115,
FT ECO:0007744|PDB:3GD4"
FT BINDING 453..454
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:11967568,
FT ECO:0000269|PubMed:19447115, ECO:0007744|PDB:3GD4"
FT BINDING 482
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:11967568,
FT ECO:0000269|PubMed:19447115, ECO:0007744|PDB:3GD3,
FT ECO:0007744|PDB:3GD4"
FT BINDING 482
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19447115,
FT ECO:0007744|PDB:3GD4"
FT BINDING 492
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT BINDING 582
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT MOD_RES 108
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT MOD_RES 387
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 520
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT MOD_RES 523
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT MOD_RES 529
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT MOD_RES 592
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT CROSSLNK 254
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O95831"
FT VAR_SEQ 322..324
FT /note="SQA -> CEY (in isoform 2)"
FT /id="VSP_060486"
FT VAR_SEQ 325..612
FT /note="Missing (in isoform 2)"
FT /id="VSP_060487"
FT MUTAGEN 176
FT /note="K->A: Increases catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11967568"
FT MUTAGEN 195
FT /note="W->A: Increases redox potential, reacts faster to
FT NADH and forms two-fold longer-lived CTC."
FT /evidence="ECO:0000269|PubMed:19447115"
FT MUTAGEN 313
FT /note="E->A: Increases catalytic efficiency 30-fold.
FT Increases affinity for NADH 20-fold."
FT /evidence="ECO:0000269|PubMed:11967568"
FT STRAND 129..137
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 140..152
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 157..166
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 199..205
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 213..218
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 223..229
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 232..236
FT /evidence="ECO:0007829|PDB:1GV4"
FT TURN 237..240
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 241..244
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 249..257
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 286..296
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 300..305
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 309..325
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 328..332
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:1GV4"
FT TURN 338..342
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 345..356
FT /evidence="ECO:0007829|PDB:1GV4"
FT TURN 357..359
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 368..374
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 377..382
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 387..395
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 404..406
FT /evidence="ECO:0007829|PDB:1GV4"
FT TURN 407..410
FT /evidence="ECO:0007829|PDB:1GV4"
FT TURN 415..417
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 426..429
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 432..434
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 436..438
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 439..443
FT /evidence="ECO:0007829|PDB:1GV4"
FT TURN 444..446
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 454..468
FT /evidence="ECO:0007829|PDB:1GV4"
FT TURN 469..471
FT /evidence="ECO:0007829|PDB:3GD3"
FT STRAND 480..486
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 490..495
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 499..501
FT /evidence="ECO:0007829|PDB:5MIU"
FT STRAND 503..508
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 516..523
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 528..532
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 539..542
FT /evidence="ECO:0007829|PDB:3GD4"
FT HELIX 556..558
FT /evidence="ECO:0007829|PDB:1GV4"
FT STRAND 561..579
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 584..593
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 600..604
FT /evidence="ECO:0007829|PDB:1GV4"
FT HELIX 605..607
FT /evidence="ECO:0007829|PDB:1GV4"
SQ SEQUENCE 612 AA; 66765 MW; A17EDFD5CF77BB85 CRC64;
MFRCGGLAGA FKQKLVPLVR TVYVQRPKQR NRLPGNLFQQ WRVPLELQMA RQMASSGSSG
GKMDNSVLVL IVGLSTIGAG AYAYKTIKED QKRYNERVMG LGLSPEEKQR RAIASATEGG
SVPQIRAPSH VPFLLIGGGT AAFAAARSIR ARDPGARVLI VSEDPELPYM RPPLSKELWF
SDDPNVTKTL QFRQWNGKER SIYFQPPSFY VSAQDLPNIE NGGVAVLTGK KVVHLDVRGN
MVKLNDGSQI TFEKCLIATG GTPRSLSAID RAGAEVKSRT TLFRKIGDFR ALEKISREVK
SITVIGGGFL GSELACALGR KSQASGIEVI QLFPEKGNMG KILPQYLSNW TMEKVKREGV
KVMPNAIVQS VGVSGGRLLI KLKDGRKVET DHIVTAVGLE PNVELAKTGG LEIDSDFGGF
RVNAELQARS NIWVAGDAAC FYDIKLGRRR VEHHDHAVVS GRLAGENMTG AAKPYWHQSM
FWSDLGPDVG YEAIGLVDSS LPTVGVFAKA TAQDNPKSAT EQSGTGIRSE SETESEASEI
TIPPSAPAVP QVPVEGEDYG KGVIFYLRDK VVVGIVLWNV FNRMPIARKI IKDGEQHEDL
NEVAKLFNIH ED
