DHYS_HUMAN
ID DHYS_HUMAN Reviewed; 369 AA.
AC P49366; A8K688; M0R1I5; Q13184; Q13276; Q9UDG0;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Deoxyhypusine synthase;
DE Short=DHS;
DE EC=2.5.1.46 {ECO:0000269|PubMed:30661771};
GN Name=DHPS; Synonyms=DS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RX PubMed=7673224; DOI=10.1074/jbc.270.38.22386;
RA Joe Y.A., Wolff E.C., Park M.H.;
RT "Cloning and expression of human deoxyhypusine synthase cDNA. Structure-
RT function studies with the recombinant enzyme and mutant proteins.";
RL J. Biol. Chem. 270:22386-22392(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC TISSUE=Blood;
RX PubMed=8549832; DOI=10.1016/0014-5793(95)01456-x;
RA Bevec D., Kappel B., Jaksche H., Csonga R., Hauber J., Klier H.,
RA Steinkasserer A.;
RT "Molecular characterization of a cDNA encoding functional human
RT deoxyhypusine synthase and chromosomal mapping of the corresponding gene
RT locus.";
RL FEBS Lett. 378:195-198(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RX PubMed=8615810; DOI=10.1042/bj3150429;
RA Yan Y.P., Tao Y., Chen K.Y.;
RT "Molecular cloning and functional expression of human deoxyhypusine
RT synthase cDNA based on expressed sequence tag information.";
RL Biochem. J. 315:429-434(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9666110; DOI=10.1016/s0378-1119(98)00254-6;
RA Mantuano E., Trettel F., Olsen A.S., Lennin G., Frontali M., Jodice C.;
RT "Localization and genomic structure of human deoxyhypusine synthase gene on
RT chromosome 19p13.2-distal 19p13.1.";
RL Gene 215:153-157(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Brain;
RX PubMed=9110174; DOI=10.1101/gr.7.4.353;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Neuroblastoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
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., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Brain, and Lung;
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 [11]
RP PROTEIN SEQUENCE OF 184-189; 192-204; 206-232 AND 278-296 (ISOFORM LONG).
RC TISSUE=Cervix carcinoma;
RX PubMed=7750572; DOI=10.1016/0014-5793(95)00394-o;
RA Klier H., Csonga R., Steinkasserer A., Woehl T., Lottspeich F., Eder J.;
RT "Purification and characterization of human deoxyhypusine synthase from
RT HeLa cells.";
RL FEBS Lett. 364:207-210(1995).
RN [12]
RP MUTAGENESIS OF LYS-287 AND LYS-329, SUBUNIT, AND ACTIVE SITE.
RX PubMed=9405486; DOI=10.1074/jbc.272.51.32679;
RA Joe Y.A., Wolff E.C., Lee Y.B., Park M.H.;
RT "Enzyme-substrate intermediate at a specific lysine residue is required for
RT deoxyhypusine synthesis. The role of Lys329 in human deoxyhypusine
RT synthase.";
RL J. Biol. Chem. 272:32679-32685(1997).
RN [13]
RP MUTAGENESIS OF ASN-106; SER-109; GLU-137; ASP-238; ASP-243; HIS-288;
RP TYR-305; ASP-313; ASP-316; SER-317; GLU-323; TRP-327 AND ASP-342.
RX PubMed=11311149; DOI=10.1042/bj3550841;
RA Lee C.H., Um P.Y., Park M.H.;
RT "Structure-function studies of human deoxyhypusine synthase: identification
RT of amino acid residues critical for the binding of spermidine and NAD.";
RL Biochem. J. 355:841-849(2001).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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., Buerckstuemmer T.,
RA 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 [17]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, VARIANTS NEDSSWI SER-173 AND
RP 305-TYR-ILE-306 DEL, CHARACTERIZATION OF VARIANTS NEDSSWI SER-173 AND
RP 305-TYR-ILE-306 DEL, AND INVOLVEMENT IN NEDSSWI.
RX PubMed=30661771; DOI=10.1016/j.ajhg.2018.12.017;
RA Ganapathi M., Padgett L.R., Yamada K., Devinsky O., Willaert R., Person R.,
RA Au P.B., Tagoe J., McDonald M., Karlowicz D., Wolf B., Lee J., Shen Y.,
RA Okur V., Deng L., LeDuc C.A., Wang J., Hanner A., Mirmira R.G., Park M.H.,
RA Mastracci T.L., Chung W.K.;
RT "Recessive rare variants in deoxyhypusine synthase, an enzyme involved in
RT the synthesis of hypusine, are associated with a neurodevelopmental
RT disorder.";
RL Am. J. Hum. Genet. 104:287-298(2019).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NAD, AND SUBUNIT.
RX PubMed=9493264; DOI=10.1016/s0969-2126(98)00004-5;
RA Liao D.-I., Wolff E.C., Park M.H., Davies D.R.;
RT "Crystal structure of the NAD complex of human deoxyhypusine synthase: an
RT enzyme with a ball-and-chain mechanism for blocking the active site.";
RL Structure 6:23-32(1998).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEXES WITH NAD AND
RP COMPETITIVE INHIBITOR, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBUNIT.
RX PubMed=15100216; DOI=10.1074/jbc.m404095200;
RA Umland T.C., Wolff E.C., Park M.H., Davies D.R.;
RT "A new crystal structure of deoxyhypusine synthase reveals the
RT configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary
RT complex.";
RL J. Biol. Chem. 279:28697-28705(2004).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidative cleavage of spermidine
CC and the subsequent transfer of the butylamine moiety of spermidine to
CC the epsilon-amino group of a critical lysine residue of the eIF-5A
CC precursor protein to form the intermediate deoxyhypusine residue
CC (PubMed:30661771). This is the first step of the post-translational
CC modification of that lysine into an unusual amino acid residue named
CC hypusine. Hypusination is unique to mature eIF-5A factor and is
CC essential for its function. {ECO:0000269|PubMed:30661771}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[eIF5A protein]-L-lysine + spermidine = [eIF5A protein]-
CC deoxyhypusine + propane-1,3-diamine; Xref=Rhea:RHEA:33299, Rhea:RHEA-
CC COMP:10143, Rhea:RHEA-COMP:10144, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57484, ChEBI:CHEBI:57834, ChEBI:CHEBI:82657; EC=2.5.1.46;
CC Evidence={ECO:0000269|PubMed:30661771};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC -!- PATHWAY: Protein modification; eIF5A hypusination.
CC {ECO:0000269|PubMed:30661771}.
CC -!- SUBUNIT: Homotetramer formed by a dimer of dimers.
CC {ECO:0000269|PubMed:15100216, ECO:0000269|PubMed:9405486,
CC ECO:0000269|PubMed:9493264}.
CC -!- INTERACTION:
CC P49366; P49366: DHPS; NbExp=4; IntAct=EBI-741925, EBI-741925;
CC P49366; P63241: EIF5A; NbExp=6; IntAct=EBI-741925, EBI-373150;
CC P49366; Q9GZV4: EIF5A2; NbExp=7; IntAct=EBI-741925, EBI-748028;
CC P49366; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-741925, EBI-739832;
CC P49366; P27361: MAPK3; NbExp=10; IntAct=EBI-741925, EBI-73995;
CC P49366; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-741925, EBI-16439278;
CC P49366; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-741925, EBI-740897;
CC P49366; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-741925, EBI-741158;
CC P49366; Q6ZVK8: NUDT18; NbExp=3; IntAct=EBI-741925, EBI-740486;
CC P49366; P26367: PAX6; NbExp=3; IntAct=EBI-741925, EBI-747278;
CC P49366; Q9HD43: PTPRH; NbExp=3; IntAct=EBI-741925, EBI-1267176;
CC P49366; O00194: RAB27B; NbExp=6; IntAct=EBI-741925, EBI-10179046;
CC P49366; P09455: RBP1; NbExp=3; IntAct=EBI-741925, EBI-2623483;
CC P49366; Q04864: REL; NbExp=3; IntAct=EBI-741925, EBI-307352;
CC P49366; Q04864-2: REL; NbExp=3; IntAct=EBI-741925, EBI-10829018;
CC P49366; P32969: RPL9P9; NbExp=11; IntAct=EBI-741925, EBI-358122;
CC P49366; Q7L8A9: VASH1; NbExp=3; IntAct=EBI-741925, EBI-10256546;
CC P49366; P52744: ZNF138; NbExp=3; IntAct=EBI-741925, EBI-10746567;
CC P49366; P52744-2: ZNF138; NbExp=3; IntAct=EBI-741925, EBI-10213071;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Long;
CC IsoId=P49366-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P49366-2; Sequence=VSP_001351;
CC Name=3;
CC IsoId=P49366-3; Sequence=VSP_047564;
CC -!- DISEASE: Neurodevelopmental disorder with seizures and speech and
CC walking impairment (NEDSSWI) [MIM:618480]: An autosomal recessive
CC disorder characterized by global developmental delay with intellectual
CC disability and poor speech acquisition, and walking difficulties due to
CC hypotonia, hypertonia, spasticity, or poor coordination. Additional
CC features include seizures, mild dysmorphic features, and variable short
CC stature. {ECO:0000269|PubMed:30661771}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform Short]: Inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the deoxyhypusine synthase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AL520040; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L39068; AAA86282.1; -; mRNA.
DR EMBL; U40579; AAA96151.1; -; mRNA.
DR EMBL; U32178; AAB02179.1; -; mRNA.
DR EMBL; U26266; AAB02175.1; -; mRNA.
DR EMBL; AJ001701; CAA04940.1; -; Genomic_DNA.
DR EMBL; AJ001702; CAA04940.1; JOINED; Genomic_DNA.
DR EMBL; AJ001703; CAA04940.1; JOINED; Genomic_DNA.
DR EMBL; AJ001704; CAA04940.1; JOINED; Genomic_DNA.
DR EMBL; U79262; AAB50208.1; -; mRNA.
DR EMBL; AL520040; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK291553; BAF84242.1; -; mRNA.
DR EMBL; AC010422; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84288.1; -; Genomic_DNA.
DR EMBL; BC000333; AAH00333.1; -; mRNA.
DR EMBL; BC014016; AAH14016.1; -; mRNA.
DR CCDS; CCDS12276.1; -. [P49366-1]
DR CCDS; CCDS12277.1; -. [P49366-2]
DR CCDS; CCDS59354.1; -. [P49366-3]
DR PIR; S68692; S68692.
DR RefSeq; NP_001193903.1; NM_001206974.1. [P49366-3]
DR RefSeq; NP_001921.1; NM_001930.3. [P49366-1]
DR RefSeq; NP_037538.1; NM_013406.2. [P49366-2]
DR RefSeq; XP_011526072.1; XM_011527770.1.
DR PDB; 1DHS; X-ray; 2.20 A; A=9-369.
DR PDB; 1RLZ; X-ray; 2.15 A; A=1-369.
DR PDB; 1ROZ; X-ray; 2.21 A; A/B=1-369.
DR PDB; 1RQD; X-ray; 3.00 A; A/B=1-369.
DR PDB; 6P4V; X-ray; 1.65 A; A/B=1-369.
DR PDB; 6PGR; X-ray; 1.95 A; A/B=1-369.
DR PDB; 6WKZ; X-ray; 2.23 A; A/B=1-369.
DR PDB; 6WL6; X-ray; 2.12 A; A/B=1-369.
DR PDB; 6XXH; X-ray; 1.52 A; A/B=1-369.
DR PDB; 6XXI; X-ray; 1.68 A; A/B=1-369.
DR PDB; 6XXJ; X-ray; 1.41 A; A/B=1-369.
DR PDB; 6XXK; X-ray; 1.65 A; A/B=1-369.
DR PDB; 6XXL; X-ray; 1.69 A; A/B=1-369.
DR PDB; 6XXM; X-ray; 1.67 A; A/B=1-369.
DR PDB; 7A6S; X-ray; 1.75 A; A/B=1-369.
DR PDB; 7A6T; X-ray; 1.66 A; A/B=1-369.
DR PDBsum; 1DHS; -.
DR PDBsum; 1RLZ; -.
DR PDBsum; 1ROZ; -.
DR PDBsum; 1RQD; -.
DR PDBsum; 6P4V; -.
DR PDBsum; 6PGR; -.
DR PDBsum; 6WKZ; -.
DR PDBsum; 6WL6; -.
DR PDBsum; 6XXH; -.
DR PDBsum; 6XXI; -.
DR PDBsum; 6XXJ; -.
DR PDBsum; 6XXK; -.
DR PDBsum; 6XXL; -.
DR PDBsum; 6XXM; -.
DR PDBsum; 7A6S; -.
DR PDBsum; 7A6T; -.
DR AlphaFoldDB; P49366; -.
DR SMR; P49366; -.
DR BioGRID; 108070; 101.
DR IntAct; P49366; 38.
DR MINT; P49366; -.
DR STRING; 9606.ENSP00000210060; -.
DR BindingDB; P49366; -.
DR ChEMBL; CHEMBL4415; -.
DR DrugBank; DB03639; 1-Guanidinium-7-Aminoheptane.
DR iPTMnet; P49366; -.
DR MetOSite; P49366; -.
DR PhosphoSitePlus; P49366; -.
DR BioMuta; DHPS; -.
DR DMDM; 1352267; -.
DR EPD; P49366; -.
DR jPOST; P49366; -.
DR MassIVE; P49366; -.
DR MaxQB; P49366; -.
DR PaxDb; P49366; -.
DR PeptideAtlas; P49366; -.
DR PRIDE; P49366; -.
DR ProteomicsDB; 55996; -. [P49366-1]
DR ProteomicsDB; 55997; -. [P49366-2]
DR Antibodypedia; 1964; 321 antibodies from 31 providers.
DR DNASU; 1725; -.
DR Ensembl; ENST00000210060.12; ENSP00000210060.6; ENSG00000095059.17. [P49366-1]
DR Ensembl; ENST00000351660.9; ENSP00000221303.5; ENSG00000095059.17. [P49366-2]
DR Ensembl; ENST00000594424.5; ENSP00000471886.1; ENSG00000095059.17. [P49366-3]
DR GeneID; 1725; -.
DR KEGG; hsa:1725; -.
DR MANE-Select; ENST00000210060.12; ENSP00000210060.6; NM_001930.4; NP_001921.1.
DR UCSC; uc002mug.3; human. [P49366-1]
DR CTD; 1725; -.
DR DisGeNET; 1725; -.
DR GeneCards; DHPS; -.
DR HGNC; HGNC:2869; DHPS.
DR HPA; ENSG00000095059; Low tissue specificity.
DR MalaCards; DHPS; -.
DR MIM; 600944; gene.
DR MIM; 618480; phenotype.
DR neXtProt; NX_P49366; -.
DR OpenTargets; ENSG00000095059; -.
DR PharmGKB; PA27329; -.
DR VEuPathDB; HostDB:ENSG00000095059; -.
DR eggNOG; KOG2924; Eukaryota.
DR GeneTree; ENSGT00390000008063; -.
DR HOGENOM; CLU_039781_0_0_1; -.
DR InParanoid; P49366; -.
DR OMA; FWSYFCQ; -.
DR PhylomeDB; P49366; -.
DR TreeFam; TF300625; -.
DR BioCyc; MetaCyc:HS01810-MON; -.
DR BRENDA; 2.5.1.46; 2681.
DR PathwayCommons; P49366; -.
DR Reactome; R-HSA-204626; Hypusine synthesis from eIF5A-lysine.
DR SABIO-RK; P49366; -.
DR SignaLink; P49366; -.
DR SIGNOR; P49366; -.
DR UniPathway; UPA00354; -.
DR BioGRID-ORCS; 1725; 598 hits in 1085 CRISPR screens.
DR ChiTaRS; DHPS; human.
DR EvolutionaryTrace; P49366; -.
DR GeneWiki; DHPS; -.
DR GenomeRNAi; 1725; -.
DR Pharos; P49366; Tchem.
DR PRO; PR:P49366; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P49366; protein.
DR Bgee; ENSG00000095059; Expressed in right hemisphere of cerebellum and 95 other tissues.
DR ExpressionAtlas; P49366; baseline and differential.
DR Genevisible; P49366; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0034038; F:deoxyhypusine synthase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0008612; P:peptidyl-lysine modification to peptidyl-hypusine; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0046203; P:spermidine catabolic process; IEA:Ensembl.
DR GO; GO:0008216; P:spermidine metabolic process; IDA:UniProtKB.
DR GO; GO:0006412; P:translation; TAS:ProtInc.
DR Gene3D; 3.40.910.10; -; 1.
DR InterPro; IPR002773; Deoxyhypusine_synthase.
DR InterPro; IPR036982; Deoxyhypusine_synthase_sf.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR PANTHER; PTHR11703; PTHR11703; 1.
DR Pfam; PF01916; DS; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR TIGRFAMs; TIGR00321; dhys; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Hypusine biosynthesis; Intellectual disability; NAD;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..369
FT /note="Deoxyhypusine synthase"
FT /id="PRO_0000134469"
FT ACT_SITE 329
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:9405486"
FT BINDING 105..109
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9493264"
FT BINDING 131..133
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9493264"
FT BINDING 136..137
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000305"
FT BINDING 137
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9493264"
FT BINDING 238
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9493264"
FT BINDING 243
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000305"
FT BINDING 283
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9493264"
FT BINDING 288
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000305"
FT BINDING 308..309
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9493264"
FT BINDING 314..316
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000305"
FT BINDING 323..329
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000305"
FT BINDING 342..343
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:9493264"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:20068231"
FT VAR_SEQ 1..68
FT /note="MEGSLEREAPAGALAAVLKHSSTLPPESTQVRGYDFNRGVNYRALLEAFGTT
FT GFQATNFGRAVQQVNA -> MPIIPAFWEAEAGGSREEEFETSLAN (in isoform
FT 3)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_047564"
FT VAR_SEQ 262..308
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8615810"
FT /id="VSP_001351"
FT VARIANT 173
FT /note="N -> S (in NEDSSWI; decreased deoxyhypusine synthase
FT activity; dbSNP:rs758100382)"
FT /evidence="ECO:0000269|PubMed:30661771"
FT /id="VAR_082649"
FT VARIANT 174
FT /note="E -> D (in dbSNP:rs10425108)"
FT /id="VAR_043005"
FT VARIANT 305..306
FT /note="Missing (in NEDSSWI; loss of deoxyhypusine synthase
FT activity)"
FT /evidence="ECO:0000269|PubMed:30661771"
FT /id="VAR_082650"
FT MUTAGEN 106
FT /note="N->A: Strongly reduced NAD and spermidine binding.
FT Reduced activity."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 109
FT /note="S->A: Strongly reduced spermidine binding. Reduced
FT activity."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 137
FT /note="E->A: Strongly reduced NAD binding. Strongly reduced
FT formation of covalent intermediate."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 238
FT /note="D->A: Strongly reduced NAD binding. Strongly reduced
FT formation of covalent intermediate."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 243
FT /note="D->A: Reduces spermidine binding by 98%. Strongly
FT reduced formation of covalent intermediate."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 287
FT /note="K->A: Reduces covalent intermediate formation and
FT deoxyhypusine synthesis by 99.5%. Retains low spermidine
FT cleavage activity."
FT /evidence="ECO:0000269|PubMed:9405486"
FT MUTAGEN 288
FT /note="H->A: Reduces spermidine binding by 98%. Strongly
FT reduced NAD binding. Strongly reduced formation of covalent
FT intermediate."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 305
FT /note="Y->A: Strongly reduced NAD binding. No effect on
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 313
FT /note="D->A: Strongly reduced NAD binding."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 316
FT /note="D->A: Reduces spermidine binding by 98%. Loss of
FT covalent intermediate formation and deoxyhypusine
FT synthesis."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 317
FT /note="S->A: Strongly reduced NAD binding. No effect on
FT enzyme activity."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 323
FT /note="E->A: Reduces spermidine binding by 98%. Strongly
FT reduced formation of covalent intermediate."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 327
FT /note="W->A: Reduces spermidine binding by 98%. Loss of
FT covalent intermediate formation and deoxyhypusine
FT synthesis."
FT /evidence="ECO:0000269|PubMed:11311149"
FT MUTAGEN 329
FT /note="K->A,R: Loss of covalent intermediate formation and
FT deoxyhypusine synthesis."
FT /evidence="ECO:0000269|PubMed:9405486"
FT MUTAGEN 342
FT /note="D->A: Strongly reduced NAD binding. Strongly reduced
FT activity."
FT /evidence="ECO:0000269|PubMed:11311149"
FT CONFLICT 11
FT /note="A -> R (in Ref. 3; AAB02175/AAB02179)"
FT /evidence="ECO:0000305"
FT CONFLICT 13..14
FT /note="AL -> R (in Ref. 3; AAB02175/AAB02179)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="A -> G (in Ref. 3; AAB02175/AAB02179)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="T -> I (in Ref. 3; AAB02175/AAB02179)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="V -> A (in Ref. 3; AAB02175/AAB02179)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="V -> A (in Ref. 3; AAB02175/AAB02179)"
FT /evidence="ECO:0000305"
FT CONFLICT 228
FT /note="H -> K (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 296..297
FT /note="MR -> SG (in Ref. 3; AAB02179)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="E -> EE (in Ref. 3; AAB02179)"
FT /evidence="ECO:0000305"
FT HELIX 11..17
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 42..47
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 54..73
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 81..88
FT /evidence="ECO:0007829|PDB:6XXJ"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 105..109
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:6XXJ"
FT STRAND 126..130
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 132..140
FT /evidence="ECO:0007829|PDB:6XXJ"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 155..160
FT /evidence="ECO:0007829|PDB:6XXJ"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:6XXJ"
FT STRAND 169..172
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 173..196
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 203..214
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 220..226
FT /evidence="ECO:0007829|PDB:6XXJ"
FT TURN 234..237
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 240..251
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 260..271
FT /evidence="ECO:0007829|PDB:6XXJ"
FT STRAND 274..282
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 284..295
FT /evidence="ECO:0007829|PDB:6XXJ"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:6XXJ"
FT STRAND 300..307
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:6XXJ"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 321..327
FT /evidence="ECO:0007829|PDB:6XXJ"
FT STRAND 337..341
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 343..353
FT /evidence="ECO:0007829|PDB:6XXJ"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:6XXJ"
FT TURN 359..362
FT /evidence="ECO:0007829|PDB:6XXJ"
SQ SEQUENCE 369 AA; 40971 MW; 5314FED620AC9EE7 CRC64;
MEGSLEREAP AGALAAVLKH SSTLPPESTQ VRGYDFNRGV NYRALLEAFG TTGFQATNFG
RAVQQVNAMI EKKLEPLSQD EDQHADLTQS RRPLTSCTIF LGYTSNLISS GIRETIRYLV
QHNMVDVLVT TAGGVEEDLI KCLAPTYLGE FSLRGKELRE NGINRIGNLL VPNENYCKFE
DWLMPILDQM VMEQNTEGVK WTPSKMIARL GKEINNPESV YYWAQKNHIP VFSPALTDGS
LGDMIFFHSY KNPGLVLDIV EDLRLINTQA IFAKCTGMII LGGGVVKHHI ANANLMRNGA
DYAVYINTAQ EFDGSDSGAR PDEAVSWGKI RVDAQPVKVY ADASLVFPLL VAETFAQKMD
AFMHEKNED
