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 27-MAR-2024, entry version 212. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8A0E; EM; 2.80 A; A/B/C/D=1-369. DR PDB; 8A0F; X-ray; 1.64 A; A/B=1-369. DR PDB; 8A0G; X-ray; 1.84 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 PDBsum; 8A0E; -. DR PDBsum; 8A0F; -. DR PDBsum; 8A0G; -. DR AlphaFoldDB; P49366; -. DR SMR; P49366; -. DR BioGRID; 108070; 111. 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; 9606-ENSP00000210060; -. DR PeptideAtlas; P49366; -. DR ProteomicsDB; 55996; -. [P49366-1] DR ProteomicsDB; 55997; -. [P49366-2] DR Pumba; P49366; -. DR Antibodypedia; 1964; 350 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 AGR; HGNC:2869; -. 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 OrthoDB; 167433at2759; -. DR PhylomeDB; P49366; -. DR TreeFam; TF300625; -. DR BioCyc; MetaCyc:HS01810-MONOMER; -. 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; 632 hits in 1165 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 97 other cell types or tissues. DR ExpressionAtlas; P49366; baseline and differential. 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; Deoxyhypusine synthase; 1. DR InterPro; IPR002773; Deoxyhypusine_synthase. DR InterPro; IPR036982; Deoxyhypusine_synthase_sf. DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom. DR NCBIfam; TIGR00321; dhys; 1. DR PANTHER; PTHR11703; DEOXYHYPUSINE SYNTHASE; 1. DR PANTHER; PTHR11703:SF0; DEOXYHYPUSINE SYNTHASE; 1. DR Pfam; PF01916; DS; 1. DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 1. DR Genevisible; P49366; HS. 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 //