Full text data of DOHH
DOHH
(HLRC1)
[Confidence: low (only semi-automatic identification from reviews)]
Deoxyhypusine hydroxylase; hDOHH; 1.14.99.29 (Deoxyhypusine dioxygenase; Deoxyhypusine monooxygenase; HEAT-like repeat-containing protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Deoxyhypusine hydroxylase; hDOHH; 1.14.99.29 (Deoxyhypusine dioxygenase; Deoxyhypusine monooxygenase; HEAT-like repeat-containing protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9BU89
ID DOHH_HUMAN Reviewed; 302 AA.
AC Q9BU89; O75265;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Deoxyhypusine hydroxylase;
DE Short=hDOHH;
DE EC=1.14.99.29;
DE AltName: Full=Deoxyhypusine dioxygenase;
DE AltName: Full=Deoxyhypusine monooxygenase;
DE AltName: Full=HEAT-like repeat-containing protein 1;
GN Name=DOHH; Synonyms=HLRC1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
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.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Lymph;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 1-7, COFACTOR, AND MUTAGENESIS OF HIS-56; GLU-57;
RP HIS-89; GLU-90; HIS-207; GLU-208; HIS-240 AND GLU-241.
RX PubMed=16533814; DOI=10.1074/jbc.M601081200;
RA Kim Y.S., Kang K.R., Wolff E.C., Bell J.K., McPhie P., Park M.H.;
RT "Deoxyhypusine hydroxylase is an Fe(II)-dependent, HEAT-repeat enzyme.
RT Identification of amino acid residues critical for Fe(II) binding and
RT catalysis.";
RL J. Biol. Chem. 281:13217-13225(2006).
RN [4]
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
RT deoxyhypusine hydroxylase: a HEAT-repeat-containing metalloenzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:51-56(2006).
RN [5]
RP FUNCTION, AND COFACTOR.
RX PubMed=19706422; DOI=10.1073/pnas.0904553106;
RA Vu V.V., Emerson J.P., Martinho M., Kim Y.S., Munck E., Park M.H.,
RA Que L. Jr.;
RT "Human deoxyhypusine hydroxylase, an enzyme involved in regulating
RT cell growth, activates O(2) with a nonheme diiron center.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14814-14819(2009).
RN [6]
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.,
RA Buerckstuemmer T., 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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-
CC L-lysine intermediate to form hypusine, an essential post-
CC translational modification only found in mature eIF-5A factor.
CC -!- CATALYTIC ACTIVITY: [eIF5A]-deoxyhypusine + AH(2) + O(2) =
CC [eIF5A]-hypusine + A + H(2)O.
CC -!- COFACTOR: Binds 2 Fe(2+) ions per subunit.
CC -!- PATHWAY: Protein modification; eIF5A hypusination.
CC -!- SIMILARITY: Belongs to the deoxyhypusine hydroxylase family.
CC -!- SIMILARITY: Contains 5 HEAT-like PBS-type repeats.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AC005551; AAC33193.1; -; Genomic_DNA.
DR EMBL; AC093052; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002817; AAH02817.1; -; mRNA.
DR EMBL; BC009863; AAH09863.1; -; mRNA.
DR RefSeq; NP_001138637.1; NM_001145165.1.
DR RefSeq; NP_112594.1; NM_031304.4.
DR UniGene; Hs.515064; -.
DR UniGene; Hs.609012; -.
DR ProteinModelPortal; Q9BU89; -.
DR SMR; Q9BU89; 47-226.
DR IntAct; Q9BU89; 1.
DR STRING; 9606.ENSP00000250937; -.
DR PhosphoSite; Q9BU89; -.
DR DMDM; 74733193; -.
DR PaxDb; Q9BU89; -.
DR PeptideAtlas; Q9BU89; -.
DR PRIDE; Q9BU89; -.
DR Ensembl; ENST00000250937; ENSP00000250937; ENSG00000129932.
DR Ensembl; ENST00000427575; ENSP00000398882; ENSG00000129932.
DR GeneID; 83475; -.
DR KEGG; hsa:83475; -.
DR UCSC; uc002lxs.3; human.
DR CTD; 83475; -.
DR GeneCards; GC19M003443; -.
DR HGNC; HGNC:28662; DOHH.
DR HPA; HPA041953; -.
DR MIM; 611262; gene.
DR neXtProt; NX_Q9BU89; -.
DR PharmGKB; PA142671678; -.
DR eggNOG; COG1413; -.
DR HOGENOM; HOG000248665; -.
DR HOVERGEN; HBG081460; -.
DR InParanoid; Q9BU89; -.
DR KO; K06072; -.
DR OMA; RESCQVA; -.
DR OrthoDB; EOG75TMCH; -.
DR PhylomeDB; Q9BU89; -.
DR BioCyc; MetaCyc:HS05318-MONOMER; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR UniPathway; UPA00354; -.
DR GenomeRNAi; 83475; -.
DR NextBio; 72407; -.
DR PRO; PR:Q9BU89; -.
DR ArrayExpress; Q9BU89; -.
DR Bgee; Q9BU89; -.
DR CleanEx; HS_DOHH; -.
DR Genevestigator; Q9BU89; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0019135; F:deoxyhypusine monooxygenase activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008612; P:peptidyl-lysine modification to hypusine; IMP:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR Gene3D; 1.25.10.10; -; 1.
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 SMART; SM00567; EZ_HEAT; 6.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Direct protein sequencing;
KW Hypusine biosynthesis; Iron; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Repeat.
FT CHAIN 1 302 Deoxyhypusine hydroxylase.
FT /FTId=PRO_0000248575.
FT REPEAT 54 80 HEAT-like PBS-type 1.
FT REPEAT 87 113 HEAT-like PBS-type 2.
FT REPEAT 174 200 HEAT-like PBS-type 3.
FT REPEAT 205 231 HEAT-like PBS-type 4.
FT REPEAT 238 264 HEAT-like PBS-type 5.
FT METAL 56 56 Iron 1.
FT METAL 57 57 Iron 1.
FT METAL 89 89 Iron 1.
FT METAL 90 90 Iron 1.
FT METAL 207 207 Iron 2.
FT METAL 208 208 Iron 2.
FT METAL 240 240 Iron 2.
FT METAL 241 241 Iron 2.
FT MOD_RES 1 1 N-acetylmethionine.
FT MUTAGEN 56 56 H->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 57 57 E->A: Abolishes enzyme activity and
FT impairs iron-binding.
FT MUTAGEN 89 89 H->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 90 90 E->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 207 207 H->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 208 208 E->A: Abolishes enzyme activity and
FT impairs iron-binding.
FT MUTAGEN 240 240 H->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 241 241 E->A: Abolishes both iron-binding and
FT enzyme activity.
SQ SEQUENCE 302 AA; 32904 MW; CDA86E5549B98A2F CRC64;
MVTEQEVDAI GQTLVDPKQP LQARFRALFT LRGLGGPGAI AWISQAFDDD SALLKHELAY
CLGQMQDARA IPMLVDVLQD TRQEPMVRHE AGEALGAIGD PEVLEILKQY SSDPVIEVAE
TCQLAVRRLE WLQQHGGEPA AGPYLSVDPA PPAEERDVGR LREALLDESR PLFERYRAMF
ALRNAGGEEA ALALAEGLHC GSALFRHEVG YVLGQLQHEA AVPQLAAALA RCTENPMVRH
ECAEALGAIA RPACLAALQA HADDPERVVR ESCEVALDMY EHETGRAFQY ADGLEQLRGA
PS
//
ID DOHH_HUMAN Reviewed; 302 AA.
AC Q9BU89; O75265;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=Deoxyhypusine hydroxylase;
DE Short=hDOHH;
DE EC=1.14.99.29;
DE AltName: Full=Deoxyhypusine dioxygenase;
DE AltName: Full=Deoxyhypusine monooxygenase;
DE AltName: Full=HEAT-like repeat-containing protein 1;
GN Name=DOHH; Synonyms=HLRC1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
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.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Lymph;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 1-7, COFACTOR, AND MUTAGENESIS OF HIS-56; GLU-57;
RP HIS-89; GLU-90; HIS-207; GLU-208; HIS-240 AND GLU-241.
RX PubMed=16533814; DOI=10.1074/jbc.M601081200;
RA Kim Y.S., Kang K.R., Wolff E.C., Bell J.K., McPhie P., Park M.H.;
RT "Deoxyhypusine hydroxylase is an Fe(II)-dependent, HEAT-repeat enzyme.
RT Identification of amino acid residues critical for Fe(II) binding and
RT catalysis.";
RL J. Biol. Chem. 281:13217-13225(2006).
RN [4]
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
RT deoxyhypusine hydroxylase: a HEAT-repeat-containing metalloenzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:51-56(2006).
RN [5]
RP FUNCTION, AND COFACTOR.
RX PubMed=19706422; DOI=10.1073/pnas.0904553106;
RA Vu V.V., Emerson J.P., Martinho M., Kim Y.S., Munck E., Park M.H.,
RA Que L. Jr.;
RT "Human deoxyhypusine hydroxylase, an enzyme involved in regulating
RT cell growth, activates O(2) with a nonheme diiron center.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14814-14819(2009).
RN [6]
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.,
RA Buerckstuemmer T., 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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-
CC L-lysine intermediate to form hypusine, an essential post-
CC translational modification only found in mature eIF-5A factor.
CC -!- CATALYTIC ACTIVITY: [eIF5A]-deoxyhypusine + AH(2) + O(2) =
CC [eIF5A]-hypusine + A + H(2)O.
CC -!- COFACTOR: Binds 2 Fe(2+) ions per subunit.
CC -!- PATHWAY: Protein modification; eIF5A hypusination.
CC -!- SIMILARITY: Belongs to the deoxyhypusine hydroxylase family.
CC -!- SIMILARITY: Contains 5 HEAT-like PBS-type repeats.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AC005551; AAC33193.1; -; Genomic_DNA.
DR EMBL; AC093052; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002817; AAH02817.1; -; mRNA.
DR EMBL; BC009863; AAH09863.1; -; mRNA.
DR RefSeq; NP_001138637.1; NM_001145165.1.
DR RefSeq; NP_112594.1; NM_031304.4.
DR UniGene; Hs.515064; -.
DR UniGene; Hs.609012; -.
DR ProteinModelPortal; Q9BU89; -.
DR SMR; Q9BU89; 47-226.
DR IntAct; Q9BU89; 1.
DR STRING; 9606.ENSP00000250937; -.
DR PhosphoSite; Q9BU89; -.
DR DMDM; 74733193; -.
DR PaxDb; Q9BU89; -.
DR PeptideAtlas; Q9BU89; -.
DR PRIDE; Q9BU89; -.
DR Ensembl; ENST00000250937; ENSP00000250937; ENSG00000129932.
DR Ensembl; ENST00000427575; ENSP00000398882; ENSG00000129932.
DR GeneID; 83475; -.
DR KEGG; hsa:83475; -.
DR UCSC; uc002lxs.3; human.
DR CTD; 83475; -.
DR GeneCards; GC19M003443; -.
DR HGNC; HGNC:28662; DOHH.
DR HPA; HPA041953; -.
DR MIM; 611262; gene.
DR neXtProt; NX_Q9BU89; -.
DR PharmGKB; PA142671678; -.
DR eggNOG; COG1413; -.
DR HOGENOM; HOG000248665; -.
DR HOVERGEN; HBG081460; -.
DR InParanoid; Q9BU89; -.
DR KO; K06072; -.
DR OMA; RESCQVA; -.
DR OrthoDB; EOG75TMCH; -.
DR PhylomeDB; Q9BU89; -.
DR BioCyc; MetaCyc:HS05318-MONOMER; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR UniPathway; UPA00354; -.
DR GenomeRNAi; 83475; -.
DR NextBio; 72407; -.
DR PRO; PR:Q9BU89; -.
DR ArrayExpress; Q9BU89; -.
DR Bgee; Q9BU89; -.
DR CleanEx; HS_DOHH; -.
DR Genevestigator; Q9BU89; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0019135; F:deoxyhypusine monooxygenase activity; IMP:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008612; P:peptidyl-lysine modification to hypusine; IMP:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR Gene3D; 1.25.10.10; -; 1.
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 SMART; SM00567; EZ_HEAT; 6.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Direct protein sequencing;
KW Hypusine biosynthesis; Iron; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Repeat.
FT CHAIN 1 302 Deoxyhypusine hydroxylase.
FT /FTId=PRO_0000248575.
FT REPEAT 54 80 HEAT-like PBS-type 1.
FT REPEAT 87 113 HEAT-like PBS-type 2.
FT REPEAT 174 200 HEAT-like PBS-type 3.
FT REPEAT 205 231 HEAT-like PBS-type 4.
FT REPEAT 238 264 HEAT-like PBS-type 5.
FT METAL 56 56 Iron 1.
FT METAL 57 57 Iron 1.
FT METAL 89 89 Iron 1.
FT METAL 90 90 Iron 1.
FT METAL 207 207 Iron 2.
FT METAL 208 208 Iron 2.
FT METAL 240 240 Iron 2.
FT METAL 241 241 Iron 2.
FT MOD_RES 1 1 N-acetylmethionine.
FT MUTAGEN 56 56 H->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 57 57 E->A: Abolishes enzyme activity and
FT impairs iron-binding.
FT MUTAGEN 89 89 H->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 90 90 E->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 207 207 H->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 208 208 E->A: Abolishes enzyme activity and
FT impairs iron-binding.
FT MUTAGEN 240 240 H->A: Abolishes both iron-binding and
FT enzyme activity.
FT MUTAGEN 241 241 E->A: Abolishes both iron-binding and
FT enzyme activity.
SQ SEQUENCE 302 AA; 32904 MW; CDA86E5549B98A2F CRC64;
MVTEQEVDAI GQTLVDPKQP LQARFRALFT LRGLGGPGAI AWISQAFDDD SALLKHELAY
CLGQMQDARA IPMLVDVLQD TRQEPMVRHE AGEALGAIGD PEVLEILKQY SSDPVIEVAE
TCQLAVRRLE WLQQHGGEPA AGPYLSVDPA PPAEERDVGR LREALLDESR PLFERYRAMF
ALRNAGGEEA ALALAEGLHC GSALFRHEVG YVLGQLQHEA AVPQLAAALA RCTENPMVRH
ECAEALGAIA RPACLAALQA HADDPERVVR ESCEVALDMY EHETGRAFQY ADGLEQLRGA
PS
//
MIM
611262
*RECORD*
*FIELD* NO
611262
*FIELD* TI
*611262 DEOXYHYPUSINE HYDROXYLASE; DOHH
;;DEOXYHYPUSINE MONOOXYGENASE;;
DEOXYHYPUSINE DIOXYGENASE;;
read moreHEAT-LIKE REPEAT-CONTAINING PROTEIN 1; HLRC1
*FIELD* TX
DESCRIPTION
Deoxyhypusine hydroxylase (DOHH; EC 1.14.99.29) catalyzes the final step
in the formation of the amino acid hypusine in eukaryotic initiation
factor-5A (EIF5A; see 600187).
CLONING
Posttranslational modification of a single lysine residue to hypusine in
eIF5A requires deoxyhypusine synthase (DHPS; 600944) and deoxyhypusine
hydroxylase. By screening a Saccharomyces cerevisiae GST-ORF library,
Park et al. (2006) identified a novel gene, YJR070C, with deoxyhypusine
hydroxylase activity. By database analysis, they identified a single
homologous DOHH gene in eukaryotes, which are highly conserved from
fungi to humans, but not in eubacteria or archaea. The human DOHH gene,
which they authors designated HLRC1, shares 48% sequence identity with
the yeast protein. DOHH contains 8 heat repeats organized in a
symmetrical dyad connected by a variable region. It contains 2 potential
metal coordination sites (one on each dyad), each composed of 2 strictly
conserved his-glu motifs.
By computer modeling, Park et al. (2006) found that the predicted
structure of DOHH is different than that of the Fe(II)- and
2-oxoacid-dependent dioxygenases. CD spectroscopy of purified
recombinant wildtype DOHH indicated an alpha-helix-rich protein (Kim et
al., 2006), and site-directed mutagenesis showed that the alpha-helical
structure of DOHH does not depend on the conserved his-glu motifs or
metal binding.
GENE FUNCTION
Park et al. (2006) demonstrated that purified recombinant yeast and
human DOHH effectively catalyzed hydroxylation of the deoxyhypusine
residue in the eIF5A intermediate. Overexpression of DHPS and DOHH along
with eIF5A was necessary for overproduction of fully modified eIF5A,
indicating that DHPS and DOHH are the rate-limiting factors in this
process. An S. cerevisiae DOHH knockout strain produced only
deoxyhypusine but no hypusine, indicating that a single gene is
responsible for DOHH activity in this organism.
Kim et al. (2006) determined that iron is the major metal in DOHH, with
2 moles of iron per mole of protein. In contrast to the wildtype
holoenzyme, to which iron is bound, the DOHH apoenzyme, which lacks
iron, showed a marked reduction in DOHH activity. Addition of ferrous
ions restored activity. Substitution of alanine for any of the his or
glu residues in the his-glu motifs resulted in complete lack of DOHH
activity. Kim et al. (2006) showed that 6 of these mutants (H56A, H89A,
E90A, H207A, H240A, and E241A) had markedly reduced iron content, and
suggested that lack of iron binding affected activity. Kim et al. (2006)
separated the DOHH holoenzyme and apoenzyme by native gel
electrophoresis and found that the iron-bound holoenzyme migrated in a
focused, fast-moving band that had DOHH activity, whereas the iron-free
apoenzyme migrated more slowly in a diffuse fashion and lacked DOHH
activity. Kim et al. (2006) suggested that iron binding induces the DOHH
apoenzyme to undergo a conformational change to a more compact form.
They showed that while DOHH binds both Fe(II) and Fe(III) ions, only
Fe(II) ions induced activity. No other metal ions increased activity.
Kim et al. (2006) concluded that Fe(II) is the active-site bound metal
critical for DOHH catalysis and that the strictly conserved his-glu
motifs are essential for iron binding and catalysis. They also suggested
a binuclear iron-mediated reaction mechanism.
*FIELD* RF
1. Kim, Y. S.; Kang, K. R.; Wolff, E. C.; Bell, J. K.; McPhie, P.;
Park, M. H.: Deoxyhypusine hydroxylase is an Fe(II)-dependent, heat-repeat
enzyme: identification of amino acid residues critical for Fe(II)
binding and catalysis. J. Biol. Chem. 281: 13217-13225, 2006. Note:
Erratum: J. Biol. Chem. 282: 10840 only, 2007.
2. Park, J.-H.; Aravind, L.; Wolff, E. C.; Kaevel, J.; Kim, Y. S.;
Park, M. H.: Molecular cloning, expression, and structural prediction
of deoxyhypusine hydroxylase: a HEAT-repeat-containing metalloenzyme. Proc.
Nat. Acad. Sci. 103: 51-56, 2006.
*FIELD* CD
Jennifer L. Goldstein: 7/26/2007
*FIELD* ED
terry: 04/01/2013
terry: 3/28/2013
terry: 11/3/2010
carol: 7/27/2007
carol: 7/26/2007
*RECORD*
*FIELD* NO
611262
*FIELD* TI
*611262 DEOXYHYPUSINE HYDROXYLASE; DOHH
;;DEOXYHYPUSINE MONOOXYGENASE;;
DEOXYHYPUSINE DIOXYGENASE;;
read moreHEAT-LIKE REPEAT-CONTAINING PROTEIN 1; HLRC1
*FIELD* TX
DESCRIPTION
Deoxyhypusine hydroxylase (DOHH; EC 1.14.99.29) catalyzes the final step
in the formation of the amino acid hypusine in eukaryotic initiation
factor-5A (EIF5A; see 600187).
CLONING
Posttranslational modification of a single lysine residue to hypusine in
eIF5A requires deoxyhypusine synthase (DHPS; 600944) and deoxyhypusine
hydroxylase. By screening a Saccharomyces cerevisiae GST-ORF library,
Park et al. (2006) identified a novel gene, YJR070C, with deoxyhypusine
hydroxylase activity. By database analysis, they identified a single
homologous DOHH gene in eukaryotes, which are highly conserved from
fungi to humans, but not in eubacteria or archaea. The human DOHH gene,
which they authors designated HLRC1, shares 48% sequence identity with
the yeast protein. DOHH contains 8 heat repeats organized in a
symmetrical dyad connected by a variable region. It contains 2 potential
metal coordination sites (one on each dyad), each composed of 2 strictly
conserved his-glu motifs.
By computer modeling, Park et al. (2006) found that the predicted
structure of DOHH is different than that of the Fe(II)- and
2-oxoacid-dependent dioxygenases. CD spectroscopy of purified
recombinant wildtype DOHH indicated an alpha-helix-rich protein (Kim et
al., 2006), and site-directed mutagenesis showed that the alpha-helical
structure of DOHH does not depend on the conserved his-glu motifs or
metal binding.
GENE FUNCTION
Park et al. (2006) demonstrated that purified recombinant yeast and
human DOHH effectively catalyzed hydroxylation of the deoxyhypusine
residue in the eIF5A intermediate. Overexpression of DHPS and DOHH along
with eIF5A was necessary for overproduction of fully modified eIF5A,
indicating that DHPS and DOHH are the rate-limiting factors in this
process. An S. cerevisiae DOHH knockout strain produced only
deoxyhypusine but no hypusine, indicating that a single gene is
responsible for DOHH activity in this organism.
Kim et al. (2006) determined that iron is the major metal in DOHH, with
2 moles of iron per mole of protein. In contrast to the wildtype
holoenzyme, to which iron is bound, the DOHH apoenzyme, which lacks
iron, showed a marked reduction in DOHH activity. Addition of ferrous
ions restored activity. Substitution of alanine for any of the his or
glu residues in the his-glu motifs resulted in complete lack of DOHH
activity. Kim et al. (2006) showed that 6 of these mutants (H56A, H89A,
E90A, H207A, H240A, and E241A) had markedly reduced iron content, and
suggested that lack of iron binding affected activity. Kim et al. (2006)
separated the DOHH holoenzyme and apoenzyme by native gel
electrophoresis and found that the iron-bound holoenzyme migrated in a
focused, fast-moving band that had DOHH activity, whereas the iron-free
apoenzyme migrated more slowly in a diffuse fashion and lacked DOHH
activity. Kim et al. (2006) suggested that iron binding induces the DOHH
apoenzyme to undergo a conformational change to a more compact form.
They showed that while DOHH binds both Fe(II) and Fe(III) ions, only
Fe(II) ions induced activity. No other metal ions increased activity.
Kim et al. (2006) concluded that Fe(II) is the active-site bound metal
critical for DOHH catalysis and that the strictly conserved his-glu
motifs are essential for iron binding and catalysis. They also suggested
a binuclear iron-mediated reaction mechanism.
*FIELD* RF
1. Kim, Y. S.; Kang, K. R.; Wolff, E. C.; Bell, J. K.; McPhie, P.;
Park, M. H.: Deoxyhypusine hydroxylase is an Fe(II)-dependent, heat-repeat
enzyme: identification of amino acid residues critical for Fe(II)
binding and catalysis. J. Biol. Chem. 281: 13217-13225, 2006. Note:
Erratum: J. Biol. Chem. 282: 10840 only, 2007.
2. Park, J.-H.; Aravind, L.; Wolff, E. C.; Kaevel, J.; Kim, Y. S.;
Park, M. H.: Molecular cloning, expression, and structural prediction
of deoxyhypusine hydroxylase: a HEAT-repeat-containing metalloenzyme. Proc.
Nat. Acad. Sci. 103: 51-56, 2006.
*FIELD* CD
Jennifer L. Goldstein: 7/26/2007
*FIELD* ED
terry: 04/01/2013
terry: 3/28/2013
terry: 11/3/2010
carol: 7/27/2007
carol: 7/26/2007