ID   ETHE1_HUMAN             Reviewed;         254 AA.
AC   O95571; Q96HR0; Q9H001;
DT   30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 2.
DT   27-MAR-2024, entry version 174.
DE   RecName: Full=Persulfide dioxygenase ETHE1, mitochondrial;
DE            EC=1.13.11.18 {ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459, ECO:0000269|PubMed:25596185};
DE   AltName: Full=Ethylmalonic encephalopathy protein 1;
DE   AltName: Full=Hepatoma subtracted clone one protein;
DE   AltName: Full=Sulfur dioxygenase ETHE1;
DE   Flags: Precursor;
GN   Name=ETHE1; Synonyms=HSCO;
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], SUBCELLULAR LOCATION, INTERACTION WITH RELA,
RP   FUNCTION, AND ABSENCE OF GLYOXALASE II ACTIVITY.
RC   TISSUE=Liver;
RX   PubMed=12398897; DOI=10.1016/s1535-6108(02)00152-6;
RA   Higashitsuji H., Higashitsuji H., Nagao T., Nonoguchi K., Fujii S.,
RA   Itoh K., Fujita J.;
RT   "A novel protein overexpressed in hepatoma accelerates export of NF-kappa B
RT   from the nucleus and inhibits p53-dependent apoptosis.";
RL   Cancer Cell 2:335-346(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   FUNCTION, ABSENCE OF GLYOXALASE II ACTIVITY, AND VARIANTS EE CYS-38;
RP   ALA-136; TRP-163 AND ARG-185.
RX   PubMed=14732903; DOI=10.1086/381653;
RA   Tiranti V., D'Adamo P., Briem E., Ferrari G., Mineri R., Lamantea E.,
RA   Mandel H., Balestri P., Garcia-Silva M.-T., Vollmer B., Rinaldo P.,
RA   Hahn S.H., Leonard J., Rahman S., Dionisi-Vici C., Garavaglia B.,
RA   Gasparini P., Zeviani M.;
RT   "Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene
RT   encoding a mitochondrial matrix protein.";
RL   Am. J. Hum. Genet. 74:239-252(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057824; DOI=10.1038/nature02399;
RA   Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA   Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA   Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA   Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA   Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA   Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA   Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA   Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA   Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA   McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA   Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA   Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA   She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA   Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA   Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA   Rubin E.M., Lucas S.M.;
RT   "The DNA sequence and biology of human chromosome 19.";
RL   Nature 428:529-535(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
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   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ROLE IN DISEASE, SUBCELLULAR
RP   LOCATION, TRANSIT PEPTIDE CLEAVAGE SITE, IDENTIFICATION BY MASS
RP   SPECTROMETRY, AND INTERACTION WITH TST.
RX   PubMed=19136963; DOI=10.1038/nm.1907;
RA   Tiranti V., Viscomi C., Hildebrandt T., Di Meo I., Mineri R., Tiveron C.,
RA   Levitt M.D., Prelle A., Fagiolari G., Rimoldi M., Zeviani M.;
RT   "Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity
RT   in ethylmalonic encephalopathy.";
RL   Nat. Med. 15:200-205(2009).
RN   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-66, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [7]
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   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP   SUBUNIT, ACTIVITY REGULATION, AND CHARACTERIZATION OF VARIANTS EE ILE-152
RP   AND ASN-196.
RX   PubMed=23144459; DOI=10.1074/jbc.m112.407411;
RA   Kabil O., Banerjee R.;
RT   "Characterization of patient mutations in human persulfide dioxygenase
RT   (ETHE1) involved in H2S catabolism.";
RL   J. Biol. Chem. 287:44561-44567(2012).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, 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   [10]
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   [11] {ECO:0007744|PDB:4CHL}
RP   X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 21-254 IN COMPLEX WITH IRON,
RP   CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, AND DISULFIDE BONDS.
RX   PubMed=25596185; DOI=10.1093/hmg/ddv007;
RA   Pettinati I., Brem J., McDonough M.A., Schofield C.J.;
RT   "Crystal structure of human persulfide dioxygenase: structural basis of
RT   ethylmalonic encephalopathy.";
RL   Hum. Mol. Genet. 24:2458-2469(2015).
RN   [12]
RP   VARIANTS EE PRO-55; ALA-136; ILE-152; GLN-163; TRP-163; LYS-164; ARG-185
RP   AND ASN-196, AND CHARACTERIZATION OF VARIANTS EE PRO-55 AND LYS-164.
RX   PubMed=18593870; DOI=10.1136/jmg.2008.058271;
RA   Mineri R., Rimoldi M., Burlina A.B., Koskull S., Perletti C., Heese B.,
RA   von Dobeln U., Mereghetti P., Di Meo I., Invernizzi F., Zeviani M.,
RA   Uziel G., Tiranti V.;
RT   "Identification of new mutations in the ETHE1 gene in a cohort of 14
RT   patients presenting with ethylmalonic encephalopathy.";
RL   J. Med. Genet. 45:473-478(2008).
CC   -!- FUNCTION: Sulfur dioxygenase that plays an essential role in hydrogen
CC       sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide
CC       (H(2)S) is first oxidized by SQRDL, giving rise to cysteine persulfide
CC       residues. ETHE1 consumes molecular oxygen to catalyze the oxidation of
CC       the persulfide, once it has been transferred to a thiophilic acceptor,
CC       such as glutathione (R-SSH). Plays an important role in metabolic
CC       homeostasis in mitochondria by metabolizing hydrogen sulfide and
CC       preventing the accumulation of supraphysiological H(2)S levels that
CC       have toxic effects, due to the inhibition of cytochrome c oxidase.
CC       First described as a protein that can shuttle between the nucleus and
CC       the cytoplasm and suppress p53-induced apoptosis by sequestering the
CC       transcription factor RELA/NFKB3 in the cytoplasm and preventing its
CC       accumulation in the nucleus (PubMed:12398897).
CC       {ECO:0000269|PubMed:12398897, ECO:0000269|PubMed:14732903,
CC       ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + O2 + S-sulfanylglutathione = glutathione + 2 H(+) +
CC         sulfite; Xref=Rhea:RHEA:12981, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17359, ChEBI:CHEBI:57925,
CC         ChEBI:CHEBI:58905; EC=1.13.11.18;
CC         Evidence={ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459,
CC         ECO:0000269|PubMed:25596185};
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC         Evidence={ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459,
CC         ECO:0000269|PubMed:25596185};
CC       Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:19136963,
CC       ECO:0000269|PubMed:23144459, ECO:0000269|PubMed:25596185};
CC   -!- ACTIVITY REGULATION: Glutathione increases enzyme activity.
CC       {ECO:0000269|PubMed:23144459}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.34 mM for glutathione persulfide (GSSH)
CC         {ECO:0000269|PubMed:23144459};
CC         Vmax=113 umol/min/mg enzyme (in the presence of equimolar amounts of
CC         GSSH and GSH and at 22 degrees Celsius)
CC         {ECO:0000269|PubMed:23144459};
CC   -!- SUBUNIT: Homodimer (PubMed:25596185). Monomer (PubMed:23144459).
CC       Interacts with TST (PubMed:19136963). May interact with RELA
CC       (PubMed:12398897). {ECO:0000269|PubMed:12398897,
CC       ECO:0000269|PubMed:19136963, ECO:0000269|PubMed:23144459,
CC       ECO:0000269|PubMed:25596185}.
CC   -!- INTERACTION:
CC       O95571; Q7Z3C6-3: ATG9A; NbExp=3; IntAct=EBI-715318, EBI-12006308;
CC       O95571; O95571: ETHE1; NbExp=3; IntAct=EBI-715318, EBI-715318;
CC       O95571; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-715318, EBI-739467;
CC       O95571; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-715318, EBI-12196745;
CC       O95571; Q99757: TXN2; NbExp=3; IntAct=EBI-715318, EBI-2932492;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12398897}. Nucleus
CC       {ECO:0000269|PubMed:12398897}. Mitochondrion matrix
CC       {ECO:0000269|PubMed:14732903}.
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC       {ECO:0000269|PubMed:14732903}.
CC   -!- DISEASE: Ethylmalonic encephalopathy (EE) [MIM:602473]: Autosomal
CC       recessive disorder characterized by neurodevelopmental delay and
CC       regression, recurrent petechiae, acrocyanosis, diarrhea, leading to
CC       death in the first decade of life. It is also associated with
CC       persistent lactic acidemia and ethylmalonic and methylsuccinic
CC       aciduria. {ECO:0000269|PubMed:14732903, ECO:0000269|PubMed:18593870,
CC       ECO:0000269|PubMed:23144459}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC       Glyoxalase II family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAG09063.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; D83198; BAA34595.2; -; mRNA.
DR   EMBL; AC018758; AAG09063.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BC008250; AAH08250.1; -; mRNA.
DR   CCDS; CCDS12622.1; -.
DR   RefSeq; NP_001307796.1; NM_001320867.1.
DR   RefSeq; NP_001307797.1; NM_001320868.1.
DR   RefSeq; NP_001307798.1; NM_001320869.1.
DR   RefSeq; NP_055112.2; NM_014297.4.
DR   RefSeq; XP_005258744.1; XM_005258687.3.
DR   PDB; 4CHL; X-ray; 2.61 A; A/B=21-254.
DR   PDBsum; 4CHL; -.
DR   AlphaFoldDB; O95571; -.
DR   SASBDB; O95571; -.
DR   SMR; O95571; -.
DR   BioGRID; 117034; 53.
DR   IntAct; O95571; 12.
DR   MINT; O95571; -.
DR   STRING; 9606.ENSP00000292147; -.
DR   iPTMnet; O95571; -.
DR   MetOSite; O95571; -.
DR   PhosphoSitePlus; O95571; -.
DR   SwissPalm; O95571; -.
DR   BioMuta; ETHE1; -.
DR   EPD; O95571; -.
DR   jPOST; O95571; -.
DR   MassIVE; O95571; -.
DR   MaxQB; O95571; -.
DR   PaxDb; 9606-ENSP00000292147; -.
DR   PeptideAtlas; O95571; -.
DR   ProteomicsDB; 50945; -.
DR   Pumba; O95571; -.
DR   Antibodypedia; 31059; 292 antibodies from 26 providers.
DR   DNASU; 23474; -.
DR   Ensembl; ENST00000292147.7; ENSP00000292147.1; ENSG00000105755.8.
DR   GeneID; 23474; -.
DR   KEGG; hsa:23474; -.
DR   MANE-Select; ENST00000292147.7; ENSP00000292147.1; NM_014297.5; NP_055112.2.
DR   UCSC; uc002owp.3; human.
DR   AGR; HGNC:23287; -.
DR   CTD; 23474; -.
DR   DisGeNET; 23474; -.
DR   GeneCards; ETHE1; -.
DR   GeneReviews; ETHE1; -.
DR   HGNC; HGNC:23287; ETHE1.
DR   HPA; ENSG00000105755; Tissue enhanced (intestine).
DR   MalaCards; ETHE1; -.
DR   MIM; 602473; phenotype.
DR   MIM; 608451; gene.
DR   neXtProt; NX_O95571; -.
DR   OpenTargets; ENSG00000105755; -.
DR   Orphanet; 51188; Ethylmalonic encephalopathy.
DR   PharmGKB; PA134879650; -.
DR   VEuPathDB; HostDB:ENSG00000105755; -.
DR   eggNOG; KOG0814; Eukaryota.
DR   GeneTree; ENSGT00940000159046; -.
DR   HOGENOM; CLU_030571_7_0_1; -.
DR   InParanoid; O95571; -.
DR   OMA; DYKGDTV; -.
DR   OrthoDB; 5471651at2759; -.
DR   PhylomeDB; O95571; -.
DR   TreeFam; TF312952; -.
DR   BioCyc; MetaCyc:ENSG00000105755-MONOMER; -.
DR   PathwayCommons; O95571; -.
DR   Reactome; R-HSA-1614517; Sulfide oxidation to sulfate.
DR   SABIO-RK; O95571; -.
DR   SignaLink; O95571; -.
DR   BioGRID-ORCS; 23474; 17 hits in 1163 CRISPR screens.
DR   ChiTaRS; ETHE1; human.
DR   GeneWiki; ETHE1; -.
DR   GenomeRNAi; 23474; -.
DR   Pharos; O95571; Tbio.
DR   PRO; PR:O95571; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; O95571; Protein.
DR   Bgee; ENSG00000105755; Expressed in mucosa of transverse colon and 194 other cell types or tissues.
DR   ExpressionAtlas; O95571; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR   GO; GO:0050313; F:sulfur dioxygenase activity; IDA:UniProtKB.
DR   GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB.
DR   GO; GO:0070813; P:hydrogen sulfide metabolic process; IDA:UniProtKB.
DR   CDD; cd07724; POD-like_MBL-fold; 1.
DR   Gene3D; 3.60.15.10; Ribonuclease Z/Hydroxyacylglutathione hydrolase-like; 1.
DR   InterPro; IPR001279; Metallo-B-lactamas.
DR   InterPro; IPR044528; POD-like_MBL-fold.
DR   InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR   PANTHER; PTHR43084; PERSULFIDE DIOXYGENASE ETHE1; 1.
DR   PANTHER; PTHR43084:SF1; PERSULFIDE DIOXYGENASE ETHE1, MITOCHONDRIAL; 1.
DR   Pfam; PF00753; Lactamase_B; 1.
DR   SMART; SM00849; Lactamase_B; 1.
DR   SUPFAM; SSF56281; Metallo-hydrolase/oxidoreductase; 1.
DR   UCD-2DPAGE; O95571; -.
DR   Genevisible; O95571; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Cytoplasm; Dioxygenase; Disease variant; Iron;
KW   Metal-binding; Mitochondrion; Nucleus; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Transit peptide.
FT   TRANSIT         1..7
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:19136963"
FT   CHAIN           8..254
FT                   /note="Persulfide dioxygenase ETHE1, mitochondrial"
FT                   /id="PRO_0000012289"
FT   BINDING         79
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:25596185,
FT                   ECO:0007744|PDB:4CHL"
FT   BINDING         135
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:25596185,
FT                   ECO:0007744|PDB:4CHL"
FT   BINDING         154
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:25596185,
FT                   ECO:0007744|PDB:4CHL"
FT   MOD_RES         14
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9DCM0"
FT   MOD_RES         19
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         66
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         172
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9DCM0"
FT   MOD_RES         172
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9DCM0"
FT   VARIANT         38
FT                   /note="Y -> C (in EE; dbSNP:rs1555765564)"
FT                   /evidence="ECO:0000269|PubMed:14732903"
FT                   /id="VAR_023395"
FT   VARIANT         55
FT                   /note="L -> P (in EE; reduces protein stability;
FT                   dbSNP:rs182983506)"
FT                   /evidence="ECO:0000269|PubMed:18593870"
FT                   /id="VAR_069507"
FT   VARIANT         136
FT                   /note="T -> A (in EE; dbSNP:rs1284200516)"
FT                   /evidence="ECO:0000269|PubMed:14732903,
FT                   ECO:0000269|PubMed:18593870"
FT                   /id="VAR_023396"
FT   VARIANT         152
FT                   /note="T -> I (in EE; reduces protein stability, iron
FT                   content and enzyme activity; dbSNP:rs1317633085)"
FT                   /evidence="ECO:0000269|PubMed:18593870,
FT                   ECO:0000269|PubMed:23144459"
FT                   /id="VAR_069508"
FT   VARIANT         163
FT                   /note="R -> Q (in EE; dbSNP:rs745656120)"
FT                   /evidence="ECO:0000269|PubMed:18593870"
FT                   /id="VAR_069509"
FT   VARIANT         163
FT                   /note="R -> W (in EE; dbSNP:rs28940289)"
FT                   /evidence="ECO:0000269|PubMed:14732903,
FT                   ECO:0000269|PubMed:18593870"
FT                   /id="VAR_023397"
FT   VARIANT         164
FT                   /note="T -> K (in EE; reduces protein stability;
FT                   dbSNP:rs1268640442)"
FT                   /evidence="ECO:0000269|PubMed:18593870"
FT                   /id="VAR_069510"
FT   VARIANT         185
FT                   /note="L -> R (in EE; dbSNP:rs387906987)"
FT                   /evidence="ECO:0000269|PubMed:14732903,
FT                   ECO:0000269|PubMed:18593870"
FT                   /id="VAR_023398"
FT   VARIANT         196
FT                   /note="D -> N (in EE; reduces protein stability and
FT                   affinity for substrate; dbSNP:rs763799125)"
FT                   /evidence="ECO:0000269|PubMed:18593870,
FT                   ECO:0000269|PubMed:23144459"
FT                   /id="VAR_069511"
FT   STRAND          24..30
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   TURN            31..34
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          35..41
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   TURN            43..45
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          47..52
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   HELIX           55..57
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   HELIX           58..68
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          71..76
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          82..84
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   HELIX           88..94
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          99..103
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   HELIX           104..106
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          111..114
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          119..122
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          125..131
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          134..136
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          140..144
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          147..153
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   HELIX           171..181
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   TURN            182..184
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          190..195
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   STRAND          197..199
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   HELIX           205..211
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   TURN            213..216
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   HELIX           219..228
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   HELIX           237..245
FT                   /evidence="ECO:0007829|PDB:4CHL"
FT   TURN            246..248
FT                   /evidence="ECO:0007829|PDB:4CHL"
SQ   SEQUENCE   254 AA;  27873 MW;  52073D52A487ACD4 CRC64;
     MAEAVLRVAR RQLSQRGGSG APILLRQMFE PVSCTFTYLL GDRESREAVL IDPVLETAPR
     DAQLIKELGL RLLYAVNTHC HADHITGSGL LRSLLPGCQS VISRLSGAQA DLHIEDGDSI
     RFGRFALETR ASPGHTPGCV TFVLNDHSMA FTGDALLIRG CGRTDFQQGC AKTLYHSVHE
     KIFTLPGDCL IYPAHDYHGF TVSTVEEERT LNPRLTLSCE EFVKIMGNLN LPKPQQIDFA
     VPANMRCGVQ TPTA
//