DOHH_MOUSE
ID DOHH_MOUSE Reviewed; 302 AA.
AC Q99LN9; Q8BNT3; Q8BTD5;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 151.
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, ECO:0000269|PubMed:24832488};
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 {ECO:0000312|MGI:MGI:1915964};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain cortex;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II; TISSUE=Mammary tumor;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
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:0000255|HAMAP-Rule:MF_03101,
CC ECO:0000269|PubMed:24832488}.
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:24832488};
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. {ECO:0000255|HAMAP-
CC Rule:MF_03101, ECO:0000269|PubMed:24832488}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99LN9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99LN9-2; Sequence=VSP_020315, VSP_020316;
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal between E3.5 and E9.5.
CC {ECO:0000269|PubMed:24832488}.
CC -!- SIMILARITY: Belongs to the deoxyhypusine hydroxylase family.
CC {ECO:0000255|HAMAP-Rule:MF_03101}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC25064.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK004052; BAC25064.1; ALT_FRAME; mRNA.
DR EMBL; AK080664; BAC37972.1; -; mRNA.
DR EMBL; BC002295; AAH02295.1; -; mRNA.
DR CCDS; CCDS35997.1; -. [Q99LN9-1]
DR RefSeq; NP_598725.2; NM_133964.2. [Q99LN9-1]
DR AlphaFoldDB; Q99LN9; -.
DR SMR; Q99LN9; -.
DR BioGRID; 221799; 5.
DR STRING; 10090.ENSMUSP00000072534; -.
DR PhosphoSitePlus; Q99LN9; -.
DR EPD; Q99LN9; -.
DR MaxQB; Q99LN9; -.
DR PaxDb; Q99LN9; -.
DR PeptideAtlas; Q99LN9; -.
DR PRIDE; Q99LN9; -.
DR ProteomicsDB; 277487; -. [Q99LN9-1]
DR ProteomicsDB; 277488; -. [Q99LN9-2]
DR Antibodypedia; 23208; 47 antibodies from 16 providers.
DR Ensembl; ENSMUST00000072751; ENSMUSP00000072534; ENSMUSG00000078440. [Q99LN9-1]
DR Ensembl; ENSMUST00000144647; ENSMUSP00000116074; ENSMUSG00000113262. [Q99LN9-2]
DR GeneID; 102115; -.
DR KEGG; mmu:102115; -.
DR UCSC; uc007ghu.2; mouse. [Q99LN9-1]
DR CTD; 83475; -.
DR MGI; MGI:1915964; Dohh.
DR VEuPathDB; HostDB:ENSMUSG00000078440; -.
DR VEuPathDB; HostDB:ENSMUSG00000113262; -.
DR eggNOG; KOG0567; Eukaryota.
DR GeneTree; ENSGT00500000044957; -.
DR HOGENOM; CLU_053974_0_0_1; -.
DR InParanoid; Q99LN9; -.
DR OMA; CIQILNR; -.
DR OrthoDB; 1441854at2759; -.
DR PhylomeDB; Q99LN9; -.
DR TreeFam; TF105626; -.
DR Reactome; R-MMU-204626; Hypusine synthesis from eIF5A-lysine.
DR UniPathway; UPA00354; -.
DR BioGRID-ORCS; 102115; 25 hits in 70 CRISPR screens.
DR ChiTaRS; Dohh; mouse.
DR PRO; PR:Q99LN9; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q99LN9; protein.
DR Bgee; ENSMUSG00000078440; Expressed in ectoplacental cone and 63 other tissues.
DR ExpressionAtlas; Q99LN9; baseline and differential.
DR Genevisible; Q99LN9; MM.
DR GO; GO:0019135; F:deoxyhypusine monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008612; P:peptidyl-lysine modification to peptidyl-hypusine; IMP:MGI.
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 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Hypusine biosynthesis; Iron;
KW Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome; Repeat.
FT CHAIN 1..302
FT /note="Deoxyhypusine hydroxylase"
FT /id="PRO_0000248576"
FT REPEAT 54..80
FT /note="HEAT-like PBS-type 1"
FT REPEAT 87..113
FT /note="HEAT-like PBS-type 2"
FT REPEAT 175..201
FT /note="HEAT-like PBS-type 3"
FT REPEAT 206..232
FT /note="HEAT-like PBS-type 4"
FT REPEAT 239..265
FT /note="HEAT-like PBS-type 5"
FT BINDING 56
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 89
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 90
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 208
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 241
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 242
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 MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89"
FT VAR_SEQ 199..200
FT /note="LQ -> SC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020315"
FT VAR_SEQ 201..302
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_020316"
FT CONFLICT 68
FT /note="A -> V (in Ref. 2; AAH02295)"
FT /evidence="ECO:0000305"
FT CONFLICT 75..76
FT /note="AD -> VG (in Ref. 2; AAH02295)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="L -> V (in Ref. 1; BAC25064)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 302 AA; 32905 MW; 524712E1EABF90C9 CRC64;
MVTEQEIEAI GKTLVDPKQP LQARFRALFT LRGLGGPDAI SWISRGFEDS SALLKHELAY
CLGQMRDARA IPVLADVLQD TSQEPMVRHE AGEALGAIGN PEVLGLLKQY STDPVVEVAE
TCQLAVGRLE WLQQHPGEAT CAGPYLSVDP APPAAEQDVG RLREALLDEA RPLFERYRAM
FALRNVGGKE AALALAEGLQ CGSALFRHEV GYVLGQLQHE AAVPGLAATL ARTTESPMVR
HECAEALGAI ARPACLAALR EHIEDPEQVV RESCEVALDM YEYESSQDFQ YADGLERLRP
PP
