DOHH_DROME
ID DOHH_DROME Reviewed; 302 AA.
AC Q9V9U4;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 147.
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};
GN Name=nero {ECO:0000255|HAMAP-Rule:MF_03101}; Synonyms=l(3)s1921;
GN ORFNames=CG2245;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=10471706; DOI=10.1093/genetics/153.1.135;
RA Spradling A.C., Stern D., Beaton A., Rhem E.J., Laverty T., Mozden N.,
RA Misra S., Rubin G.M.;
RT "The Berkeley Drosophila Genome Project gene disruption project: single P-
RT element insertions mutating 25% of vital Drosophila genes.";
RL Genetics 153:135-177(1999).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=19546244; DOI=10.1083/jcb.200904161;
RA Patel P.H., Costa-Mattioli M., Schulze K.L., Bellen H.J.;
RT "The Drosophila deoxyhypusine hydroxylase homologue nero and its target
RT eIF5A are required for cell growth and the regulation of autophagy.";
RL J. Cell Biol. 185:1181-1194(2009).
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 (By similarity).
CC Essential for organismal viability and plays a role in a wide number of
CC important processes such as cell growth and proliferation, and
CC regulates induction of autophagy and protein synthesis. Has a role in
CC eIF-5A-mediated translational control. {ECO:0000255|HAMAP-
CC Rule:MF_03101, ECO:0000269|PubMed:19546244}.
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};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03101};
CC Note=Binds 2 Fe(2+) ions per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_03101};
CC -!- PATHWAY: Protein modification; eIF5A hypusination. {ECO:0000255|HAMAP-
CC Rule:MF_03101}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03101, ECO:0000269|PubMed:19546244};
CC Peripheral membrane protein {ECO:0000255|HAMAP-Rule:MF_03101,
CC ECO:0000269|PubMed:19546244}; Cytoplasmic side {ECO:0000255|HAMAP-
CC Rule:MF_03101, ECO:0000269|PubMed:19546244}. Note=In larval imaginal
CC disk and Garland cells.
CC -!- DISRUPTION PHENOTYPE: Lethality. Mutant clones exhibit bristle loss as
CC well as very small bristles on the thorax. Mutations affect cell and
CC organ size, bromodeoxyuridine incorporation and autophagy.
CC {ECO:0000269|PubMed:10471706, ECO:0000269|PubMed:19546244}.
CC -!- SIMILARITY: Belongs to the deoxyhypusine hydroxylase family.
CC {ECO:0000255|HAMAP-Rule:MF_03101}.
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DR EMBL; AE014297; AAF57189.1; -; Genomic_DNA.
DR EMBL; AY118500; AAM49869.1; -; mRNA.
DR RefSeq; NP_651887.1; NM_143630.2.
DR AlphaFoldDB; Q9V9U4; -.
DR SMR; Q9V9U4; -.
DR BioGRID; 68581; 2.
DR IntAct; Q9V9U4; 1.
DR STRING; 7227.FBpp0085222; -.
DR PaxDb; Q9V9U4; -.
DR PRIDE; Q9V9U4; -.
DR DNASU; 43740; -.
DR EnsemblMetazoa; FBtr0085863; FBpp0085222; FBgn0261479.
DR GeneID; 43740; -.
DR KEGG; dme:Dmel_CG2245; -.
DR CTD; 43740; -.
DR FlyBase; FBgn0261479; nero.
DR VEuPathDB; VectorBase:FBgn0261479; -.
DR eggNOG; KOG0567; Eukaryota.
DR GeneTree; ENSGT00940000165304; -.
DR HOGENOM; CLU_053974_0_0_1; -.
DR InParanoid; Q9V9U4; -.
DR OMA; CIQILNR; -.
DR OrthoDB; 1441854at2759; -.
DR PhylomeDB; Q9V9U4; -.
DR Reactome; R-DME-204626; Hypusine synthesis from eIF5A-lysine.
DR UniPathway; UPA00354; -.
DR BioGRID-ORCS; 43740; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 43740; -.
DR PRO; PR:Q9V9U4; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0261479; Expressed in adult abdomen and 42 other tissues.
DR Genevisible; Q9V9U4; DM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0019135; F:deoxyhypusine monooxygenase activity; IGI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008612; P:peptidyl-lysine modification to peptidyl-hypusine; IGI:UniProtKB.
DR Gene3D; 1.25.10.10; -; 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 SMART; SM00567; EZ_HEAT; 6.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Hypusine biosynthesis; Iron; Membrane;
KW Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome; Repeat.
FT CHAIN 1..302
FT /note="Deoxyhypusine hydroxylase"
FT /id="PRO_0000248582"
FT REPEAT 23..49
FT /note="HEAT-like PBS-type 1"
FT REPEAT 54..80
FT /note="HEAT-like PBS-type 2"
FT REPEAT 87..113
FT /note="HEAT-like PBS-type 3"
FT REPEAT 175..201
FT /note="HEAT-like PBS-type 4"
FT REPEAT 206..232
FT /note="HEAT-like PBS-type 5"
FT REPEAT 239..265
FT /note="HEAT-like PBS-type 6"
FT BINDING 56
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03101"
FT BINDING 57
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03101"
FT BINDING 89
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03101"
FT BINDING 90
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03101"
FT BINDING 208
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03101"
FT BINDING 209
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03101"
FT BINDING 241
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03101"
FT BINDING 242
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03101"
SQ SEQUENCE 302 AA; 33564 MW; 34700E25E0CC5A0F CRC64;
MVSQQQIEAI GGVLNNKERP LKERFRALFT LKNIGGGAAI EAISKAFDDD SALLKHELAY
CLGQMQDAQA LDILTKVLKD TTQEPMVRHE AAEAMGAIGH PDVLPILEEY KQDPVVEVAE
TCAIALDRVR WLQSGQKVDD SNPYASVDPS PPTAGDKSVT ELKAIYLDAQ QSLFDRYRAM
FSLRNLRTEE SVLAIAEGLK DSSALFRHEV AFVLGQLQEP CSIPFLQENL EDRLENEMVR
HECAEALGAI ATEDCIQILN RYAEDDKRVV KESCVIALDM CEYENSPEFQ YADGLAKLDA
TK
