ID   ARK72_HUMAN             Reviewed;         359 AA.
AC   O43488; O75749; Q5TG63;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   14-NOV-2003, sequence version 3.
DT   24-JAN-2024, entry version 209.
DE   RecName: Full=Aflatoxin B1 aldehyde reductase member 2;
DE            EC=1.1.1.n11;
DE   AltName: Full=AFB1 aldehyde reductase 1;
DE            Short=AFB1-AR 1;
DE   AltName: Full=Aldoketoreductase 7;
DE   AltName: Full=Succinic semialdehyde reductase;
DE            Short=SSA reductase;
DE   Flags: Precursor;
GN   Name=AKR7A2; Synonyms=AFAR, AFAR1, AKR7;
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-359.
RC   TISSUE=Pancreas, Skin, and Uterus;
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 5-359, PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP   SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT THR-142.
RC   TISSUE=Liver;
RX   PubMed=9576847; DOI=10.1042/bj3320021;
RA   Ireland L.S., Harrison D.J., Neal G.E., Hayes J.D.;
RT   "Molecular cloning, expression and catalytic activity of a human AKR7
RT   member of the aldo-keto reductase superfamily: evidence that the major 2-
RT   carboxybenzaldehyde reductase from human liver is a homologue of rat
RT   aflatoxin B1-aldehyde reductase.";
RL   Biochem. J. 332:21-34(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 7-359.
RC   TISSUE=Brain;
RX   PubMed=9823300;
RA   Praml C., Savelyeva L., Perri P., Schwab M.;
RT   "Cloning of the human aflatoxin B1-aldehyde reductase gene at 1p35-1p36.1
RT   in a region frequently altered in human tumor cells.";
RL   Cancer Res. 58:5014-5018(1998).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 30-359.
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   PROTEIN SEQUENCE OF 222-236; 251-261 AND 279-297, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RC   TISSUE=Brain, and Cajal-Retzius cell;
RA   Lubec G., Vishwanath V.;
RL   Submitted (MAR-2007) to UniProtKB.
RN   [7]
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX   PubMed=10510318; DOI=10.1042/bj3430487;
RA   O'Connor T., Ireland L.S., Harrison D.J., Hayes J.D.;
RT   "Major differences exist in the function and tissue-specific expression of
RT   human aflatoxin B1 aldehyde reductase and the principal human aldo-keto
RT   reductase AKR1 family members.";
RL   Biochem. J. 343:487-504(1999).
RN   [8]
RP   GENE STRUCTURE.
RX   PubMed=12071861; DOI=10.1042/bj20020342;
RA   Kelly V.P., Sherratt P.J., Crouch D.H., Hayes J.D.;
RT   "Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases
RT   that associate with the Golgi apparatus define a distinct subclass of aldo-
RT   keto reductase 7 family proteins.";
RL   Biochem. J. 366:847-861(2002).
RN   [9]
RP   FUNCTION.
RX   PubMed=17591773; DOI=10.1074/jbc.m702465200;
RA   Lyon R.C., Johnston S.M., Watson D.G., McGarvie G., Ellis E.M.;
RT   "Synthesis and catabolism of gamma-hydroxybutyrate in SH-SY5Y human
RT   neuroblastoma cells: role of the aldo-keto reductase AKR7A2.";
RL   J. Biol. Chem. 282:25986-25992(2007).
RN   [10]
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   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=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   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255, AND IDENTIFICATION BY
RP   MASS 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   [13]
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   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NADP.
RG   Structural genomics consortium (SGC);
RT   "Structure of the aflatoxin aldehyde reductase in complex with NADPH.";
RL   Submitted (FEB-2009) to the PDB data bank.
RN   [15]
RP   VARIANTS THR-142 AND HIS-157.
RX   PubMed=18752886; DOI=10.1016/j.canlet.2008.07.013;
RA   Praml C., Schulz W., Claas A., Mollenhauer J., Poustka A., Ackermann R.,
RA   Schwab M., Henrich K.-O.;
RT   "Genetic variation of aflatoxin B1 aldehyde reductase genes (AFAR) in human
RT   tumour cells.";
RL   Cancer Lett. 272:160-166(2008).
CC   -!- FUNCTION: Catalyzes the NADPH-dependent reduction of succinic
CC       semialdehyde to gamma-hydroxybutyrate. May have an important role in
CC       producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad
CC       substrate specificity. Has NADPH-dependent aldehyde reductase activity
CC       towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-
CC       aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-
CC       phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-
CC       binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol.
CC       May be involved in protection of liver against the toxic and
CC       carcinogenic effects of AFB1, a potent hepatocarcinogen.
CC       {ECO:0000269|PubMed:17591773, ECO:0000269|PubMed:9576847}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-hydroxybutanoate + NADP(+) = H(+) + NADPH + succinate
CC         semialdehyde; Xref=Rhea:RHEA:26381, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16724, ChEBI:CHEBI:57706, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349; EC=1.1.1.n11;
CC         Evidence={ECO:0000269|PubMed:10510318};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=20 uM for succinic semialdehyde {ECO:0000269|PubMed:10510318};
CC         KM=17 uM for 2-carboxybenzaldehyde {ECO:0000269|PubMed:10510318};
CC         KM=8 uM for 9,10-phenanthrenequinone {ECO:0000269|PubMed:10510318};
CC         KM=102 uM for 1,2-naphthoquinone {ECO:0000269|PubMed:10510318};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9576847, ECO:0000269|Ref.14}.
CC   -!- INTERACTION:
CC       O43488; O95154: AKR7A3; NbExp=6; IntAct=EBI-748855, EBI-748869;
CC       O43488; Q92870-2: APBB2; NbExp=3; IntAct=EBI-748855, EBI-21535880;
CC       O43488; P54252: ATXN3; NbExp=3; IntAct=EBI-748855, EBI-946046;
CC       O43488; Q8WWM9: CYGB; NbExp=3; IntAct=EBI-748855, EBI-6309037;
CC       O43488; Q9Y2K1: ZBTB1; NbExp=4; IntAct=EBI-748855, EBI-2682961;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255}. Golgi apparatus
CC       {ECO:0000250|UniProtKB:Q8CG45}. Cytoplasm {ECO:0000269|PubMed:9576847}.
CC   -!- TISSUE SPECIFICITY: Detected in brain, liver, small intestine and
CC       testis, and at lower levels in heart, prostate, skeletal muscle and
CC       spleen. Detected in kidney proximal and distal tubules, endothelial
CC       cells lining the Bowman's capsules and some cysts. Detected at low
CC       levels in lung and pancreas (at protein level). Widely expressed.
CC       {ECO:0000269|PubMed:10510318, ECO:0000269|PubMed:9576847}.
CC   -!- SIMILARITY: Belongs to the aldo/keto reductase family. Aldo/keto
CC       reductase 2 subfamily. {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-30 is the initiator.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC52104.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAH04111.3; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAH10852.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAH11586.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAH12171.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAH13996.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=AAP36011.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAA76347.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AL035413; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC004111; AAH04111.3; ALT_INIT; mRNA.
DR   EMBL; BC007352; AAH07352.2; -; mRNA.
DR   EMBL; BC010852; AAH10852.1; ALT_INIT; mRNA.
DR   EMBL; BC011586; AAH11586.1; ALT_INIT; mRNA.
DR   EMBL; BC012171; AAH12171.1; ALT_INIT; mRNA.
DR   EMBL; BC013996; AAH13996.1; ALT_INIT; mRNA.
DR   EMBL; AF026947; AAC52104.1; ALT_INIT; mRNA.
DR   EMBL; Y16675; CAA76347.1; ALT_INIT; mRNA.
DR   EMBL; BT007347; AAP36011.1; ALT_INIT; mRNA.
DR   EMBL; BK000395; DAA00088.1; -; mRNA.
DR   CCDS; CCDS194.1; -.
DR   RefSeq; NP_003680.2; NM_003689.3.
DR   PDB; 2BP1; X-ray; 2.40 A; A/B/C/D=1-359.
DR   PDBsum; 2BP1; -.
DR   AlphaFoldDB; O43488; -.
DR   SMR; O43488; -.
DR   BioGRID; 114142; 77.
DR   IntAct; O43488; 47.
DR   STRING; 9606.ENSP00000235835; -.
DR   GlyGen; O43488; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O43488; -.
DR   MetOSite; O43488; -.
DR   PhosphoSitePlus; O43488; -.
DR   SwissPalm; O43488; -.
DR   BioMuta; AKR7A2; -.
DR   REPRODUCTION-2DPAGE; IPI00305978; -.
DR   REPRODUCTION-2DPAGE; O43488; -.
DR   EPD; O43488; -.
DR   jPOST; O43488; -.
DR   MassIVE; O43488; -.
DR   PaxDb; 9606-ENSP00000235835; -.
DR   PeptideAtlas; O43488; -.
DR   ProteomicsDB; 48966; -.
DR   Pumba; O43488; -.
DR   Antibodypedia; 29614; 303 antibodies from 31 providers.
DR   DNASU; 8574; -.
DR   Ensembl; ENST00000235835.8; ENSP00000235835.3; ENSG00000053371.13.
DR   GeneID; 8574; -.
DR   KEGG; hsa:8574; -.
DR   MANE-Select; ENST00000235835.8; ENSP00000235835.3; NM_003689.4; NP_003680.2.
DR   AGR; HGNC:389; -.
DR   CTD; 8574; -.
DR   DisGeNET; 8574; -.
DR   GeneCards; AKR7A2; -.
DR   HGNC; HGNC:389; AKR7A2.
DR   HPA; ENSG00000053371; Low tissue specificity.
DR   MIM; 603418; gene.
DR   neXtProt; NX_O43488; -.
DR   OpenTargets; ENSG00000053371; -.
DR   PharmGKB; PA24682; -.
DR   VEuPathDB; HostDB:ENSG00000053371; -.
DR   eggNOG; ENOG502QU2T; Eukaryota.
DR   GeneTree; ENSGT00940000164191; -.
DR   HOGENOM; CLU_023205_1_1_1; -.
DR   InParanoid; O43488; -.
DR   OMA; APNYWHL; -.
DR   OrthoDB; 1379250at2759; -.
DR   PhylomeDB; O43488; -.
DR   TreeFam; TF329173; -.
DR   BioCyc; MetaCyc:ENSG00000053371-MONOMER; -.
DR   PathwayCommons; O43488; -.
DR   Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
DR   SABIO-RK; O43488; -.
DR   SignaLink; O43488; -.
DR   BioGRID-ORCS; 8574; 9 hits in 1164 CRISPR screens.
DR   ChiTaRS; AKR7A2; human.
DR   EvolutionaryTrace; O43488; -.
DR   GeneWiki; AKR7A2; -.
DR   GenomeRNAi; 8574; -.
DR   Pharos; O43488; Tbio.
DR   PRO; PR:O43488; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; O43488; Protein.
DR   Bgee; ENSG00000053371; Expressed in mucosa of transverse colon and 201 other cell types or tissues.
DR   ExpressionAtlas; O43488; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; TAS:ProtInc.
DR   GO; GO:0004033; F:aldo-keto reductase (NADP) activity; IBA:GO_Central.
DR   GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR   GO; GO:0019119; F:phenanthrene-9,10-epoxide hydrolase activity; IDA:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR   GO; GO:0006081; P:cellular aldehyde metabolic process; TAS:ProtInc.
DR   GO; GO:0044597; P:daunorubicin metabolic process; IMP:UniProtKB.
DR   GO; GO:0044598; P:doxorubicin metabolic process; IMP:UniProtKB.
DR   GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR   CDD; cd19075; AKR_AKR7A1-5; 1.
DR   Gene3D; 3.20.20.100; NADP-dependent oxidoreductase domain; 1.
DR   InterPro; IPR023210; NADP_OxRdtase_dom.
DR   InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR   PANTHER; PTHR43364:SF4; NAD(P)-LINKED OXIDOREDUCTASE SUPERFAMILY PROTEIN; 1.
DR   PANTHER; PTHR43364; NADH-SPECIFIC METHYLGLYOXAL REDUCTASE-RELATED; 1.
DR   Pfam; PF00248; Aldo_ket_red; 1.
DR   SUPFAM; SSF51430; NAD(P)-linked oxidoreductase; 1.
DR   UCD-2DPAGE; O43488; -.
DR   Genevisible; O43488; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW   Golgi apparatus; Lipid metabolism; Mitochondrion; NADP; Oxidoreductase;
KW   Phosphoprotein; Reference proteome; Transit peptide.
FT   TRANSIT         1..38
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           39..359
FT                   /note="Aflatoxin B1 aldehyde reductase member 2"
FT                   /id="PRO_0000070375"
FT   ACT_SITE        77
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   BINDING         72
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.14"
FT   BINDING         141
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         171..172
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.14"
FT   BINDING         197
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.14"
FT   BINDING         226..236
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.14"
FT   BINDING         250
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.14"
FT   BINDING         260
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         263
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         318..326
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000269|Ref.14"
FT   BINDING         359
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   SITE            105
FT                   /note="Lowers pKa of active site Tyr"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         40
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT   MOD_RES         128
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT   MOD_RES         236
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8CG76"
FT   MOD_RES         255
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163,
FT                   ECO:0007744|PubMed:24275569"
FT   VARIANT         135
FT                   /note="V -> M (in dbSNP:rs6670759)"
FT                   /id="VAR_048209"
FT   VARIANT         142
FT                   /note="A -> T (in dbSNP:rs1043657)"
FT                   /evidence="ECO:0000269|PubMed:18752886,
FT                   ECO:0000269|PubMed:9576847"
FT                   /id="VAR_017413"
FT   VARIANT         157
FT                   /note="Q -> H (in dbSNP:rs859208)"
FT                   /evidence="ECO:0000269|PubMed:18752886"
FT                   /id="VAR_017414"
FT   VARIANT         180
FT                   /note="E -> K (in dbSNP:rs859210)"
FT                   /id="VAR_060222"
FT   VARIANT         198
FT                   /note="G -> S (in dbSNP:rs2231200)"
FT                   /id="VAR_048210"
FT   VARIANT         214
FT                   /note="C -> Y (in dbSNP:rs2235794)"
FT                   /id="VAR_017415"
FT   VARIANT         255
FT                   /note="S -> N (in dbSNP:rs2231203)"
FT                   /id="VAR_048211"
FT   STRAND          39..43
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   TURN            48..50
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           53..65
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   STRAND          70..72
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           77..80
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           81..87
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   STRAND          101..106
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           116..130
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   STRAND          135..140
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           149..161
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   STRAND          164..172
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           175..188
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   STRAND          193..199
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           206..208
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           211..218
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   STRAND          221..225
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           229..234
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           239..242
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   TURN            243..245
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   STRAND          252..254
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           257..264
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           267..284
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           285..287
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           291..302
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           307..309
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   STRAND          312..315
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           320..330
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           337..350
FT                   /evidence="ECO:0007829|PDB:2BP1"
FT   HELIX           351..353
FT                   /evidence="ECO:0007829|PDB:2BP1"
SQ   SEQUENCE   359 AA;  39589 MW;  2C9775FE4B977D2A CRC64;
     MLSAASRVVS RAAVHCALRS PPPEARALAM SRPPPPRVAS VLGTMEMGRR MDAPASAAAV
     RAFLERGHTE LDTAFMYSDG QSETILGGLG LGLGGGDCRV KIATKANPWD GKSLKPDSVR
     SQLETSLKRL QCPQVDLFYL HAPDHGTPVE ETLHACQRLH QEGKFVELGL SNYASWEVAE
     ICTLCKSNGW ILPTVYQGMY NATTRQVETE LFPCLRHFGL RFYAYNPLAG GLLTGKYKYE
     DKDGKQPVGR FFGNSWAETY RNRFWKEHHF EAIALVEKAL QAAYGASAPS VTSAALRWMY
     HHSQLQGAHG DAVILGMSSL EQLEQNLAAT EEGPLEPAVV DAFNQAWHLV AHECPNYFR
//