ID DOHH_CAEEL Reviewed; 298 AA.
AC Q17949;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 157.
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:0000250|UniProtKB:Q9BU89, 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=dohh-1 {ECO:0000255|HAMAP-Rule:MF_03101};
GN Synonyms=tag-242 {ECO:0000312|WormBase:C14A4.1};
GN ORFNames=C14A4.1 {ECO:0000312|WormBase:C14A4.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=24832488; DOI=10.1242/dmm.014449;
RA Sievert H., Paellmann N., Miller K.K., Hermans-Borgmeyer I., Venz S.,
RA Sendoel A., Preukschas M., Schweizer M., Boettcher S., Janiesch P.C.,
RA Streichert T., Walther R., Hengartner M.O., Manz M.G., Bruemmendorf T.H.,
RA Bokemeyer C., Braig M., Hauber J., Duncan K.E., Balabanov S.;
RT "A novel mouse model for inhibition of DOHH-mediated hypusine modification
RT reveals a crucial function in embryonic development, proliferation and
RT oncogenic transformation.";
RL Dis. Model. Mech. 7:963-976(2014).
CC -!- FUNCTION: Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-
CC lysine intermediate produced by deoxyhypusine synthase/DHPS on a
CC critical lysine of the eukaryotic translation initiation factor 5A/eIF-
CC 5A. This is the second step of the post-translational modification of
CC that lysine into an unusual amino acid residue named hypusine.
CC Hypusination is unique to mature eIF-5A factor and is essential for its
CC function. {ECO:0000250|UniProtKB:Q99LN9, ECO:0000255|HAMAP-
CC Rule:MF_03101}.
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;
CC Evidence={ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
CC Rule:MF_03101};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q9BU89,
CC ECO:0000255|HAMAP-Rule:MF_03101};
CC Note=Binds 2 Fe(2+) ions per subunit. {ECO:0000250|UniProtKB:Q9BU89,
CC ECO:0000255|HAMAP-Rule:MF_03101};
CC -!- PATHWAY: Protein modification; eIF5A hypusination.
CC {ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-Rule:MF_03101}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal with the production of
CC multinucleated cells from the one-cell stage of embryogenesis leading
CC to the in utero accumulation of abnormal and enlarged embryos.
CC {ECO:0000269|PubMed:24832488}.
CC -!- SIMILARITY: Belongs to the deoxyhypusine hydroxylase family.
CC {ECO:0000255|HAMAP-Rule:MF_03101}.
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DR EMBL; Z49909; CAA90105.1; -; Genomic_DNA.
DR PIR; T19243; T19243.
DR RefSeq; NP_496279.1; NM_063878.3.
DR AlphaFoldDB; Q17949; -.
DR SMR; Q17949; -.
DR BioGRID; 532896; 7.
DR STRING; 6239.C14A4.1.1; -.
DR EPD; Q17949; -.
DR PaxDb; 6239-C14A4-1; -.
DR PeptideAtlas; Q17949; -.
DR EnsemblMetazoa; C14A4.1.1; C14A4.1.1; WBGene00007555.
DR GeneID; 3565578; -.
DR KEGG; cel:CELE_C14A4.1; -.
DR UCSC; C14A4.1.1; c. elegans.
DR AGR; WB:WBGene00007555; -.
DR WormBase; C14A4.1; CE02138; WBGene00007555; dohh-1.
DR eggNOG; KOG0567; Eukaryota.
DR GeneTree; ENSGT00940000165304; -.
DR HOGENOM; CLU_053974_0_0_1; -.
DR InParanoid; Q17949; -.
DR OMA; GQLQEPC; -.
DR OrthoDB; 5474306at2759; -.
DR PhylomeDB; Q17949; -.
DR Reactome; R-CEL-204626; Hypusine synthesis from eIF5A-lysine.
DR UniPathway; UPA00354; -.
DR PRO; PR:Q17949; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00007555; Expressed in germ line (C elegans) and 4 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IC:WormBase.
DR GO; GO:0019135; F:deoxyhypusine monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0008612; P:peptidyl-lysine modification to peptidyl-hypusine; ISS:UniProtKB.
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; IPR021133; HEAT_type_2.
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 Pfam; PF03130; HEAT_PBS; 1.
DR SMART; SM00567; EZ_HEAT; 6.
DR SUPFAM; SSF48371; ARM repeat; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
PE 3: Inferred from homology;
KW Hypusine biosynthesis; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Repeat.
FT CHAIN 1..298
FT /note="Deoxyhypusine hydroxylase"
FT /id="PRO_0000248581"
FT REPEAT 28..54
FT /note="HEAT-like PBS-type 1"
FT REPEAT 59..85
FT /note="HEAT-like PBS-type 2"
FT REPEAT 92..118
FT /note="HEAT-like PBS-type 3"
FT REPEAT 178..204
FT /note="HEAT-like PBS-type 4"
FT REPEAT 210..236
FT /note="HEAT-like PBS-type 5"
FT REPEAT 243..269
FT /note="HEAT-like PBS-type 6"
FT REGION 140..159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..159
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 61
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 94
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 95
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 212
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 245
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 246
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
SQ SEQUENCE 298 AA; 33240 MW; D92C75F3F63811CB CRC64;
MVASQKFSDA EIDSFGEALN DTKKPLKARF RALFILRNIG CDRSVDWIGK CLNDESALLK
HELAYCLGQM QNKHAIPTLV SVLEDEKQEP MVRHEAGEAL GAIADPSVKD VLRKYAQDPC
PEVSETCQIA LGRVEWVEKS GKDTNSPYDS VDPTPSASTS DVEELAATLI DASLPLFDRY
RAMFSLRNIK TDKSIKALAQ GLYCEDSALF RHEVAYVLGQ LQSPVATQEL KDRLLLSTEN
CMVRHECAEA LGAIANEECT EILKQYVNDE ERVVRESCEV ALDMAEYENS DDLQYAHV
//
