ID   DOHH_YEAST              Reviewed;         325 AA.
AC   P47120; D6VWP1;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 192.
DE   RecName: Full=Deoxyhypusine hydroxylase {ECO:0000255|HAMAP-Rule:MF_03101};
DE            Short=DOHH {ECO:0000255|HAMAP-Rule:MF_03101};
DE            EC=1.14.99.29 {ECO:0000255|HAMAP-Rule:MF_03101};
DE   AltName: Full=Deoxyhypusine dioxygenase {ECO:0000255|HAMAP-Rule:MF_03101};
DE   AltName: Full=Deoxyhypusine monooxygenase {ECO:0000255|HAMAP-Rule:MF_03101};
DE   AltName: Full=Ligand of eIF5A protein 1 {ECO:0000255|HAMAP-Rule:MF_03101};
GN   Name=LIA1 {ECO:0000255|HAMAP-Rule:MF_03101}; Synonyms=MMD1;
GN   OrderedLocusNames=YJR070C; ORFNames=J1814;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8840504;
RX   DOI=10.1002/(sici)1097-0061(199607)12:9<869::aid-yea964>3.0.co;2-1;
RA   Huang M.-E., Manus V., Chuat J.-C., Galibert F.;
RT   "Analysis of a 62 kb DNA sequence of chromosome X reveals 36 open reading
RT   frames and a gene cluster with a counterpart on chromosome XI.";
RL   Yeast 12:869-875(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=8962070; DOI=10.1073/pnas.93.25.14440;
RA   Shevchenko A., Jensen O.N., Podtelejnikov A.V., Sagliocco F., Wilm M.,
RA   Vorm O., Mortensen P., Shevchenko A., Boucherie H., Mann M.;
RT   "Linking genome and proteome by mass spectrometry: large-scale
RT   identification of yeast proteins from two dimensional gels.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:14440-14445(1996).
RN   [5]
RP   ACETYLATION AT SER-2.
RX   PubMed=9298649; DOI=10.1002/elps.1150180810;
RA   Garrels J.I., McLaughlin C.S., Warner J.R., Futcher B., Latter G.I.,
RA   Kobayashi R., Schwender B., Volpe T., Anderson D.S., Mesquita-Fuentes R.,
RA   Payne W.E.;
RT   "Proteome studies of Saccharomyces cerevisiae: identification and
RT   characterization of abundant proteins.";
RL   Electrophoresis 18:1347-1360(1997).
RN   [6]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [7]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [8]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=16371467; DOI=10.1073/pnas.0509348102;
RA   Park J.-H., Aravind L., Wolff E.C., Kaevel J., Kim Y.S., Park M.H.;
RT   "Molecular cloning, expression, and structural prediction of deoxyhypusine
RT   hydroxylase: a HEAT-repeat-containing metalloenzyme.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:51-56(2006).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ADR376;
RX   PubMed=17330950; DOI=10.1021/pr060559j;
RA   Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA   Elias J.E., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of alpha-factor-arrested
RT   Saccharomyces cerevisiae.";
RL   J. Proteome Res. 6:1190-1197(2007).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126; THR-187 AND SER-281, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
RN   [12]
RP   FUNCTION, COFACTOR, MUTAGENESIS OF HIS-79; GLU-80; HIS-112; GLU-113;
RP   GLU-116; HIS-237; GLU-238; HIS-270; GLU-271 AND GLU-274, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=19956996; DOI=10.1007/s00726-009-0407-8;
RA   Cano V.S., Medrano F.J., Park M.H., Valentini S.R.;
RT   "Evidence for conformational changes in the yeast deoxyhypusine hydroxylase
RT   Lia1 upon iron displacement from its active site.";
RL   Amino Acids 38:479-490(2010).
CC   -!- FUNCTION: Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-
CC       lysine intermediate to form hypusine, an essential post-translational
CC       modification only found in mature eIF-5A factor. {ECO:0000255|HAMAP-
CC       Rule:MF_03101, ECO:0000269|PubMed:16371467,
CC       ECO:0000269|PubMed:19956996}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[eIF5A protein]-deoxyhypusine + AH2 + O2 = [eIF5A protein]-
CC         hypusine + A + H2O; Xref=Rhea:RHEA:14101, Rhea:RHEA-COMP:10144,
CC         Rhea:RHEA-COMP:12592, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:82657,
CC         ChEBI:CHEBI:91175; EC=1.14.99.29; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03101, ECO:0000269|PubMed:16371467};
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03101, ECO:0000269|PubMed:19956996};
CC       Note=Binds 2 Fe(2+) ions per subunit. {ECO:0000255|HAMAP-Rule:MF_03101,
CC       ECO:0000269|PubMed:19956996};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7.5. Active from pH 6 to 10.
CC         {ECO:0000269|PubMed:19956996};
CC   -!- PATHWAY: Protein modification; eIF5A hypusination. {ECO:0000255|HAMAP-
CC       Rule:MF_03101}.
CC   -!- INTERACTION:
CC       P47120; P23301: HYP2; NbExp=2; IntAct=EBI-25526, EBI-9033;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03101,
CC       ECO:0000269|PubMed:14562095}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03101,
CC       ECO:0000269|PubMed:14562095}.
CC   -!- MISCELLANEOUS: Present with 39900 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the deoxyhypusine hydroxylase family.
CC       {ECO:0000255|HAMAP-Rule:MF_03101}.
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DR   EMBL; Z49570; CAA89598.1; -; Genomic_DNA.
DR   EMBL; L47993; AAB39296.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08857.1; -; Genomic_DNA.
DR   PIR; S57089; S57089.
DR   RefSeq; NP_012604.1; NM_001181728.1.
DR   AlphaFoldDB; P47120; -.
DR   SMR; P47120; -.
DR   BioGRID; 33827; 255.
DR   DIP; DIP-2829N; -.
DR   IntAct; P47120; 10.
DR   MINT; P47120; -.
DR   STRING; 4932.YJR070C; -.
DR   iPTMnet; P47120; -.
DR   MaxQB; P47120; -.
DR   PaxDb; 4932-YJR070C; -.
DR   PeptideAtlas; P47120; -.
DR   EnsemblFungi; YJR070C_mRNA; YJR070C; YJR070C.
DR   GeneID; 853534; -.
DR   KEGG; sce:YJR070C; -.
DR   AGR; SGD:S000003831; -.
DR   SGD; S000003831; LIA1.
DR   VEuPathDB; FungiDB:YJR070C; -.
DR   eggNOG; KOG0567; Eukaryota.
DR   HOGENOM; CLU_053974_0_0_1; -.
DR   InParanoid; P47120; -.
DR   OMA; GQLQEPC; -.
DR   OrthoDB; 5474306at2759; -.
DR   BioCyc; YEAST:G3O-31703-MONOMER; -.
DR   Reactome; R-SCE-204626; Hypusine synthesis from eIF5A-lysine.
DR   UniPathway; UPA00354; -.
DR   BioGRID-ORCS; 853534; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P47120; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P47120; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0019135; F:deoxyhypusine monooxygenase activity; IDA:SGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:SGD.
DR   GO; GO:0008612; P:peptidyl-lysine modification to peptidyl-hypusine; IDA:SGD.
DR   Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 2.
DR   HAMAP; MF_03101; Deoxyhypusine_hydroxylase; 1.
DR   InterPro; IPR011989; ARM-like.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR027517; Deoxyhypusine_hydroxylase.
DR   InterPro; IPR004155; PBS_lyase_HEAT.
DR   PANTHER; PTHR12697:SF5; DEOXYHYPUSINE HYDROXYLASE; 1.
DR   PANTHER; PTHR12697; PBS LYASE HEAT-LIKE PROTEIN; 1.
DR   Pfam; PF13646; HEAT_2; 2.
DR   SMART; SM00567; EZ_HEAT; 5.
DR   SUPFAM; SSF48371; ARM repeat; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Hypusine biosynthesis; Iron; Metal-binding;
KW   Monooxygenase; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome;
KW   Repeat.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03101,
FT                   ECO:0000269|PubMed:9298649"
FT   CHAIN           2..325
FT                   /note="Deoxyhypusine hydroxylase"
FT                   /id="PRO_0000203100"
FT   REPEAT          77..103
FT                   /note="HEAT-like PBS-type 1"
FT   REPEAT          110..136
FT                   /note="HEAT-like PBS-type 2"
FT   REPEAT          202..231
FT                   /note="HEAT-like PBS-type 3"
FT   REPEAT          235..261
FT                   /note="HEAT-like PBS-type 4"
FT   REPEAT          268..294
FT                   /note="HEAT-like PBS-type 5"
FT   BINDING         79
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="1"
FT   BINDING         80
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="1"
FT   BINDING         112
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="1"
FT   BINDING         113
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="1"
FT   BINDING         237
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="2"
FT   BINDING         238
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="2"
FT   BINDING         270
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="2"
FT   BINDING         271
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_label="2"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03101,
FT                   ECO:0000269|PubMed:9298649"
FT   MOD_RES         126
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         187
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         281
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17330950,
FT                   ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT   MUTAGEN         79
FT                   /note="H->A: Abolishes both iron-binding and enzyme
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         80
FT                   /note="E->A: Abolishes enzyme activity and impairs
FT                   iron-binding."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         112
FT                   /note="H->A: Abolishes both iron-binding and enzyme
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         113
FT                   /note="E->A: Abolishes iron-binding, substrate-binding, and
FT                   enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         116
FT                   /note="E->A: Abolishes substrate-binding and enzyme
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         116
FT                   /note="E->D: Reduces enzyme activity by 97%."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         237
FT                   /note="H->A: Abolishes both iron-binding and enzyme
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         238
FT                   /note="E->A: Abolishes substrate-binding, enzyme activity,
FT                   and impairs iron-binding."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         270
FT                   /note="H->A: Abolishes iron-binding, substrate-binding, and
FT                   enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         271
FT                   /note="E->A: Abolishes iron-binding, substrate-binding, and
FT                   enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:19956996"
FT   MUTAGEN         274
FT                   /note="E->A: Abolishes substrate-binding."
FT                   /evidence="ECO:0000269|PubMed:19956996"
SQ   SEQUENCE   325 AA;  36165 MW;  AB36A73B40466CD5 CRC64;
     MSTNFEKHFQ ENVDECTLEQ LRDILVNKSG KTVLANRFRA LFNLKTVAEE FATKPEEAKK
     AIEYIAESFV NDKSELLKHE VAYVLGQTKN LDAAPTLRHV MLDQNQEPMV RHEAAEALGA
     LGDKDSLDDL NKAAKEDPHV AVRETCELAI NRINWTHGGA KDKENLQQSL YSSIDPAPPL
     PLEKDATIPE LQALLNDPKQ PLFQRYRAMF RLRDIGTDEA ILALATGFSA ESSLFKHEIA
     YVFGQIGSPA AVPSLIEVLG RKEEAPMVRH EAAEALGAIA SPEVVDVLKS YLNDEVDVVR
     ESCIVALDMY DYENSNELEY APTAN
//