ID DHDDS_HUMAN Reviewed; 333 AA. AC Q86SQ9; B7Z4B9; B7ZB20; D3DPK7; D3DPK8; D3DPK9; E9KL43; Q5T0A4; Q8NE90; AC Q9BTG5; Q9BTK3; Q9H905; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 27-MAR-2024, entry version 173. DE RecName: Full=Dehydrodolichyl diphosphate synthase complex subunit DHDDS {ECO:0000305}; DE EC=2.5.1.87 {ECO:0000269|PubMed:25066056, ECO:0000269|PubMed:28842490}; DE AltName: Full=Cis-isoprenyltransferase {ECO:0000303|PubMed:14652022}; DE Short=CIT {ECO:0000303|PubMed:28842490}; DE Short=Cis-IPTase {ECO:0000303|PubMed:14652022}; DE AltName: Full=Cis-prenyltransferase subunit hCIT {ECO:0000303|PubMed:28842490}; DE AltName: Full=Epididymis tissue protein Li 189m; GN Name=DHDDS {ECO:0000303|PubMed:21295283, ECO:0000312|HGNC:HGNC:20603}; GN Synonyms=HDS; 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 1). RC TISSUE=Testis; RX PubMed=12591616; DOI=10.1016/s0167-4781(02)00628-0; RA Endo S., Zhang Y.-W., Takahashi S., Koyama T.; RT "Identification of human dehydrodolichyl diphosphate synthase gene."; RL Biochim. Biophys. Acta 1625:291-295(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-253, AND TISSUE RP SPECIFICITY. RC TISSUE=Epididymis; RX PubMed=20736409; DOI=10.1074/mcp.m110.001719; RA Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., Zhang C., RA Jin S., Liu J., Zhu P., Liu Y.; RT "Systematic mapping and functional analysis of a family of human epididymal RT secretory sperm-located proteins."; RL Mol. Cell. Proteomics 9:2517-2528(2010). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), AND VARIANT RP MET-253. RC TISSUE=Teratocarcinoma, and Thyroid; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP MET-253. RC TISSUE=Lung, Muscle, and Placenta; 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 [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=14652022; DOI=10.1016/j.bbrc.2003.11.065; RA Shridas P., Rush J.S., Waechter C.J.; RT "Identification and characterization of a cDNA encoding a long-chain cis- RT isoprenyltransferase involved in dolichyl monophosphate biosynthesis in the RT ER of brain cells."; RL Biochem. Biophys. Res. Commun. 312:1349-1356(2003). RN [8] RP INTERACTION WITH NUS1. RX PubMed=21572394; DOI=10.1038/emboj.2011.147; RA Harrison K.D., Park E.J., Gao N., Kuo A., Rush J.S., Waechter C.J., RA Lehrman M.A., Sessa W.C.; RT "Nogo-B receptor is necessary for cellular dolichol biosynthesis and RT protein N-glycosylation."; RL EMBO J. 30:2490-2500(2011). RN [9] RP CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, AND PATHWAY. RX PubMed=25066056; DOI=10.1016/j.cmet.2014.06.016; RA Park E.J., Grabinska K.A., Guan Z., Stranecky V., Hartmannova H., RA Hodanova K., Baresova V., Sovova J., Jozsef L., Ondruskova N., RA Hansikova H., Honzik T., Zeman J., Hulkova H., Wen R., Kmoch S., RA Sessa W.C.; RT "Mutation of Nogo-B receptor, a subunit of cis-prenyltransferase, causes a RT congenital disorder of glycosylation."; RL Cell Metab. 20:448-457(2014). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [11] RP COFACTOR, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION, CHARACTERIZATION OF RP VARIANT GLU-42, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND ACTIVITY RP REGULATION. RX PubMed=28842490; DOI=10.1074/jbc.m117.806034; RA Grabinska K.A., Edani B.H., Park E.J., Kraehling J.R., Sessa W.C.; RT "A conserved C-terminal RXG motif in the NgBR subunit of cis- RT prenyltransferase is critical for prenyltransferase activity."; RL J. Biol. Chem. 292:17351-17361(2017). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 1-333 IN COMPLEX WITH NUS1; RP ISOPENTENYL DIPHOSPHATE AND MAGNESIUM, FUNCTION, CATALYTIC ACTIVITY, RP COFACTOR, ACTIVITY REGULATION, DOMAIN, AND MUTAGENESIS OF TRP-12; PHE-15; RP ILE-19; 106-GLU--GLU-109; ARG-306; PHE-313 AND LEU-317. RX PubMed=32817466; DOI=10.1073/pnas.2008381117; RA Edani B.H., Grabinska K.A., Zhang R., Park E.J., Siciliano B., Surmacz L., RA Ha Y., Sessa W.C.; RT "Structural elucidation of the cis-prenyltransferase NgBR/DHDDS complex RT reveals insights in regulation of protein glycosylation."; RL Proc. Natl. Acad. Sci. U.S.A. 117:20794-20802(2020). RN [13] RP VARIANT RP59 GLU-42. RX PubMed=21295283; DOI=10.1016/j.ajhg.2011.01.001; RA Zuchner S., Dallman J., Wen R., Beecham G., Naj A., Farooq A., Kohli M.A., RA Whitehead P.L., Hulme W., Konidari I., Edwards Y.J., Cai G., Peter I., RA Seo D., Buxbaum J.D., Haines J.L., Blanton S., Young J., Alfonso E., RA Vance J.M., Lam B.L., Pericak-Vance M.A.; RT "Whole-exome sequencing links a variant in DHDDS to retinitis pigmentosa."; RL Am. J. Hum. Genet. 88:201-206(2011). RN [14] RP INVOLVEMENT IN DEDSM, AND VARIANTS DEDSM HIS-37 AND GLN-211. RX PubMed=29100083; DOI=10.1016/j.ajhg.2017.09.008; RG Deciphering Developmental Disorders Study; RA Hamdan F.F., Myers C.T., Cossette P., Lemay P., Spiegelman D., RA Laporte A.D., Nassif C., Diallo O., Monlong J., Cadieux-Dion M., RA Dobrzeniecka S., Meloche C., Retterer K., Cho M.T., Rosenfeld J.A., Bi W., RA Massicotte C., Miguet M., Brunga L., Regan B.M., Mo K., Tam C., RA Schneider A., Hollingsworth G., FitzPatrick D.R., Donaldson A., Canham N., RA Blair E., Kerr B., Fry A.E., Thomas R.H., Shelagh J., Hurst J.A., RA Brittain H., Blyth M., Lebel R.R., Gerkes E.H., Davis-Keppen L., Stein Q., RA Chung W.K., Dorison S.J., Benke P.J., Fassi E., Corsten-Janssen N., RA Kamsteeg E.J., Mau-Them F.T., Bruel A.L., Verloes A., Ounap K., RA Wojcik M.H., Albert D.V.F., Venkateswaran S., Ware T., Jones D., Liu Y.C., RA Mohammad S.S., Bizargity P., Bacino C.A., Leuzzi V., Martinelli S., RA Dallapiccola B., Tartaglia M., Blumkin L., Wierenga K.J., Purcarin G., RA O'Byrne J.J., Stockler S., Lehman A., Keren B., Nougues M.C., Mignot C., RA Auvin S., Nava C., Hiatt S.M., Bebin M., Shao Y., Scaglia F., Lalani S.R., RA Frye R.E., Jarjour I.T., Jacques S., Boucher R.M., Riou E., Srour M., RA Carmant L., Lortie A., Major P., Diadori P., Dubeau F., D'Anjou G., RA Bourque G., Berkovic S.F., Sadleir L.G., Campeau P.M., Kibar Z., RA Lafreniere R.G., Girard S.L., Mercimek-Mahmutoglu S., Boelman C., RA Rouleau G.A., Scheffer I.E., Mefford H.C., Andrade D.M., Rossignol E., RA Minassian B.A., Michaud J.L.; RT "High rate of recurrent de novo mutations in developmental and epileptic RT encephalopathies."; RL Am. J. Hum. Genet. 101:664-685(2017). RN [15] RP VARIANTS ASN-95; GLN-205 AND GLN-211. RX PubMed=33798445; DOI=10.1016/j.ajhg.2021.03.013; RA Courage C., Oliver K.L., Park E.J., Cameron J.M., Grabinska K.A., Muona M., RA Canafoglia L., Gambardella A., Said E., Afawi Z., Baykan B., Brandt C., RA di Bonaventura C., Chew H.B., Criscuolo C., Dibbens L.M., Castellotti B., RA Riguzzi P., Labate A., Filla A., Giallonardo A.T., Berecki G., RA Jackson C.B., Joensuu T., Damiano J.A., Kivity S., Korczyn A., Palotie A., RA Striano P., Uccellini D., Giuliano L., Andermann E., Scheffer I.E., RA Michelucci R., Bahlo M., Franceschetti S., Sessa W.C., Berkovic S.F., RA Lehesjoki A.E.; RT "Progressive myoclonus epilepsies-Residual unsolved cases have marked RT genetic heterogeneity including dolichol-dependent protein glycosylation RT pathway genes."; RL Am. J. Hum. Genet. 108:722-738(2021). CC -!- FUNCTION: With NUS1, forms the dehydrodolichyl diphosphate synthase CC (DDS) complex, an essential component of the dolichol monophosphate CC (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic CC activity, i.e. condensation of multiple copies of isopentenyl CC pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce CC dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol CC phosphate which is utilized as a sugar carrier in protein glycosylation CC in the endoplasmic reticulum (ER) (PubMed:25066056, PubMed:28842490, CC PubMed:32817466). Synthesizes long-chain polyprenols, mostly of C95 and CC C100 chain length (PubMed:32817466). Regulates the glycosylation and CC stability of nascent NPC2, thereby promoting trafficking of LDL-derived CC cholesterol (PubMed:21572394). {ECO:0000269|PubMed:21572394, CC ECO:0000269|PubMed:25066056, ECO:0000269|PubMed:28842490, CC ECO:0000269|PubMed:32817466}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,6E)-farnesyl diphosphate + n isopentenyl diphosphate = di- CC trans,poly-cis-polyprenyl diphosphate + n diphosphate; CC Xref=Rhea:RHEA:53008, Rhea:RHEA-COMP:13431, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:128769, ChEBI:CHEBI:136960, ChEBI:CHEBI:175763; CC EC=2.5.1.87; Evidence={ECO:0000269|PubMed:25066056, CC ECO:0000269|PubMed:28842490, ECO:0000269|PubMed:32817466}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:28842490, ECO:0000269|PubMed:32817466}; CC Note=Binds 1 magnesium ion per subunit. {ECO:0000269|PubMed:32817466}; CC -!- ACTIVITY REGULATION: Activated by phospholipids including cardiolipin, CC phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and CC phosphatidylserine. {ECO:0000269|PubMed:28842490}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=11.1 uM for isopentenyl diphosphate {ECO:0000269|PubMed:28842490}; CC KM=0.68 uM for (2E,6E)-farnesyl diphosphate CC {ECO:0000269|PubMed:28842490}; CC Note=Values were measured with the heterodimer. kcat is 0.58 sec(-1) CC with (2E,6E)-farnesyl diphosphate and isopentenyl diphosphate as CC substrate. {ECO:0000269|PubMed:28842490}; CC pH dependence: CC Optimum pH is 8-9. Active from pH 5.5 to 9.3. CC {ECO:0000269|PubMed:28842490}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:25066056}. CC -!- PATHWAY: Lipid metabolism. {ECO:0000269|PubMed:28842490}. CC -!- SUBUNIT: Forms an active dehydrodolichyl diphosphate synthase complex CC with NUS1 (PubMed:25066056, PubMed:28842490, PubMed:32817466). CC Interacts with NPC2 (PubMed:21572394). {ECO:0000269|PubMed:21572394, CC ECO:0000269|PubMed:25066056, ECO:0000269|PubMed:28842490}. CC -!- INTERACTION: CC Q86SQ9; Q96E22: NUS1; NbExp=3; IntAct=EBI-26942900, EBI-6949352; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:14652022}; Peripheral membrane protein CC {ECO:0000269|PubMed:14652022}. Note=colocalizes with calnexin. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q86SQ9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86SQ9-2; Sequence=VSP_010031; CC Name=3; CC IsoId=Q86SQ9-3; Sequence=VSP_010030; CC Name=4; CC IsoId=Q86SQ9-4; Sequence=VSP_045007; CC -!- TISSUE SPECIFICITY: Expressed at high levels in testis and kidney. CC Expressed in epididymis (at protein level). Slightly expressed in CC heart, spleen and thymus. {ECO:0000269|PubMed:20736409}. CC -!- DOMAIN: The catalytic site at NUS1-DHDDS interface accomodates both the CC allylic and the homoallylic IPP substrates to the S1 and S2 pockets CC respectively. The beta-phosphate groups of IPP substrates form hydrogen CC bonds with the RXG motif of NUS1 and four conserved residues of DHDDS CC (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl CC group is pointed toward the hydrophobic tunnel of the S1 pocket where CC the product elongation occurs. {ECO:0000269|PubMed:32817466}. CC -!- DISEASE: Retinitis pigmentosa 59 (RP59) [MIM:613861]: A retinal CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis CC pigmentosa is characterized by retinal pigment deposits visible on CC fundus examination and primary loss of rod photoreceptor cells followed CC by secondary loss of cone photoreceptors. Patients typically have night CC vision blindness and loss of midperipheral visual field. As their CC condition progresses, they lose their far peripheral visual field and CC eventually central vision as well. {ECO:0000269|PubMed:21295283}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Developmental delay and seizures with or without movement CC abnormalities (DEDSM) [MIM:617836]: An autosomal dominant CC neurodevelopmental disorder characterized by global developmental CC delay, variable intellectual disability, and early-onset seizures with CC a myoclonic component. Most patients have delayed motor development and CC show abnormal movements, including ataxia, dystonia, and tremor. CC {ECO:0000269|PubMed:29100083}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: May be due to exon skipping. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the UPP synthase family. {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; AB090852; BAC57588.1; -; mRNA. DR EMBL; GU727641; ADU87642.1; -; mRNA. DR EMBL; AK023164; BAB14439.1; -; mRNA. DR EMBL; AK297134; BAH12505.1; -; mRNA. DR EMBL; AK316485; BAH14856.1; -; mRNA. DR EMBL; AL513365; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07806.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07808.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07809.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07810.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07811.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07812.1; -; Genomic_DNA. DR EMBL; BC003643; AAH03643.1; -; mRNA. DR EMBL; BC004117; AAH04117.1; -; mRNA. DR EMBL; BC034152; AAH34152.1; -; mRNA. DR CCDS; CCDS281.1; -. [Q86SQ9-2] DR CCDS; CCDS282.1; -. [Q86SQ9-1] DR CCDS; CCDS57983.1; -. [Q86SQ9-4] DR CCDS; CCDS57984.1; -. [Q86SQ9-3] DR RefSeq; NP_001230493.1; NM_001243564.1. [Q86SQ9-4] DR RefSeq; NP_001230494.1; NM_001243565.1. [Q86SQ9-3] DR RefSeq; NP_079163.2; NM_024887.3. [Q86SQ9-2] DR RefSeq; NP_995583.1; NM_205861.2. [Q86SQ9-1] DR RefSeq; XP_006710975.1; XM_006710912.2. DR RefSeq; XP_006710976.1; XM_006710913.2. DR RefSeq; XP_006710977.1; XM_006710914.2. DR RefSeq; XP_011540485.1; XM_011542183.2. DR RefSeq; XP_011540486.1; XM_011542184.2. DR RefSeq; XP_011540488.1; XM_011542186.2. DR RefSeq; XP_016857868.1; XM_017002379.1. DR RefSeq; XP_016857869.1; XM_017002380.1. DR PDB; 6W2L; X-ray; 2.31 A; A=2-330. DR PDB; 6Z1N; X-ray; 2.30 A; A=1-333. DR PDB; 7PAX; X-ray; 2.00 A; A=1-333. DR PDB; 7PAY; X-ray; 2.40 A; A=1-333. DR PDB; 7PB0; X-ray; 2.30 A; A=1-333. DR PDB; 7PB1; X-ray; 2.59 A; A=1-333. DR PDBsum; 6W2L; -. DR PDBsum; 6Z1N; -. DR PDBsum; 7PAX; -. DR PDBsum; 7PAY; -. DR PDBsum; 7PB0; -. DR PDBsum; 7PB1; -. DR AlphaFoldDB; Q86SQ9; -. DR SASBDB; Q86SQ9; -. DR SMR; Q86SQ9; -. DR BioGRID; 123018; 14. DR ComplexPortal; CPX-6701; Dehydrodolichyl diphosphate synthase complex. DR CORUM; Q86SQ9; -. DR IntAct; Q86SQ9; 2. DR STRING; 9606.ENSP00000353104; -. DR iPTMnet; Q86SQ9; -. DR PhosphoSitePlus; Q86SQ9; -. DR BioMuta; DHDDS; -. DR DMDM; 116241329; -. DR EPD; Q86SQ9; -. DR jPOST; Q86SQ9; -. DR MassIVE; Q86SQ9; -. DR MaxQB; Q86SQ9; -. DR PaxDb; 9606-ENSP00000353104; -. DR PeptideAtlas; Q86SQ9; -. DR ProteomicsDB; 6588; -. DR ProteomicsDB; 69620; -. [Q86SQ9-1] DR ProteomicsDB; 69621; -. [Q86SQ9-2] DR ProteomicsDB; 69622; -. [Q86SQ9-3] DR Pumba; Q86SQ9; -. DR Antibodypedia; 16091; 120 antibodies from 22 providers. DR CPTC; Q86SQ9; 4 antibodies. DR DNASU; 79947; -. DR Ensembl; ENST00000236342.12; ENSP00000236342.7; ENSG00000117682.18. [Q86SQ9-1] DR Ensembl; ENST00000360009.6; ENSP00000353104.2; ENSG00000117682.18. [Q86SQ9-2] DR Ensembl; ENST00000525682.6; ENSP00000434984.1; ENSG00000117682.18. [Q86SQ9-4] DR Ensembl; ENST00000526219.5; ENSP00000434219.1; ENSG00000117682.18. [Q86SQ9-3] DR Ensembl; ENST00000528557.6; ENSP00000515248.1; ENSG00000117682.18. [Q86SQ9-1] DR GeneID; 79947; -. DR KEGG; hsa:79947; -. DR MANE-Select; ENST00000236342.12; ENSP00000236342.7; NM_205861.3; NP_995583.1. DR UCSC; uc001bmk.4; human. [Q86SQ9-1] DR AGR; HGNC:20603; -. DR CTD; 79947; -. DR DisGeNET; 79947; -. DR GeneCards; DHDDS; -. DR GeneReviews; DHDDS; -. DR HGNC; HGNC:20603; DHDDS. DR HPA; ENSG00000117682; Low tissue specificity. DR MalaCards; DHDDS; -. DR MIM; 608172; gene. DR MIM; 613861; phenotype. DR MIM; 617836; phenotype. DR neXtProt; NX_Q86SQ9; -. DR OpenTargets; ENSG00000117682; -. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR Orphanet; 791; Retinitis pigmentosa. DR PharmGKB; PA134867119; -. DR VEuPathDB; HostDB:ENSG00000117682; -. DR eggNOG; KOG1602; Eukaryota. DR GeneTree; ENSGT00390000007879; -. DR InParanoid; Q86SQ9; -. DR OMA; FDRRDLW; -. DR OrthoDB; 521455at2759; -. DR PhylomeDB; Q86SQ9; -. DR TreeFam; TF323753; -. DR BioCyc; MetaCyc:HS04165-MONOMER; -. DR BRENDA; 2.5.1.87; 2681. DR PathwayCommons; Q86SQ9; -. DR Reactome; R-HSA-446199; Synthesis of Dolichyl-phosphate. DR Reactome; R-HSA-4755609; Defective DHDDS causes RP59. DR SABIO-RK; Q86SQ9; -. DR SignaLink; Q86SQ9; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 79947; 841 hits in 1171 CRISPR screens. DR ChiTaRS; DHDDS; human. DR GeneWiki; Dehydrodolichyl_diphosphate_synthase; -. DR GeneWiki; DHDDS; -. DR GenomeRNAi; 79947; -. DR Pharos; Q86SQ9; Tbio. DR PRO; PR:Q86SQ9; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q86SQ9; Protein. DR Bgee; ENSG00000117682; Expressed in sperm and 181 other cell types or tissues. DR ExpressionAtlas; Q86SQ9; baseline and differential. DR GO; GO:1904423; C:dehydrodolichyl diphosphate synthase complex; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0045547; F:dehydrodolichyl diphosphate synthase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006489; P:dolichyl diphosphate biosynthetic process; IDA:UniProtKB. DR GO; GO:0016094; P:polyprenol biosynthetic process; IBA:GO_Central. DR CDD; cd00475; Cis_IPPS; 1. DR Gene3D; 3.40.1180.10; Decaprenyl diphosphate synthase-like; 1. DR HAMAP; MF_01139; ISPT; 1. DR InterPro; IPR001441; UPP_synth-like. DR InterPro; IPR018520; UPP_synth-like_CS. DR InterPro; IPR036424; UPP_synth-like_sf. DR NCBIfam; TIGR00055; uppS; 1. DR PANTHER; PTHR10291:SF43; DEHYDRODOLICHYL DIPHOSPHATE SYNTHASE COMPLEX SUBUNIT DHDDS; 1. DR PANTHER; PTHR10291; DEHYDRODOLICHYL DIPHOSPHATE SYNTHASE FAMILY MEMBER; 1. DR Pfam; PF01255; Prenyltransf; 1. DR SUPFAM; SSF64005; Undecaprenyl diphosphate synthase; 1. DR PROSITE; PS01066; UPP_SYNTHASE; 1. DR Genevisible; Q86SQ9; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; Endoplasmic reticulum; KW Epilepsy; Intellectual disability; Lipid metabolism; Magnesium; Membrane; KW Metal-binding; Reference proteome; Retinitis pigmentosa; Transferase. FT CHAIN 1..333 FT /note="Dehydrodolichyl diphosphate synthase complex subunit FT DHDDS" FT /id="PRO_0000123749" FT BINDING 34 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:32817466" FT BINDING 38 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000269|PubMed:32817466" FT BINDING 85 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000269|PubMed:32817466" FT BINDING 205 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000269|PubMed:32817466" FT BINDING 211 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000269|PubMed:32817466" FT BINDING 213 FT /ligand="isopentenyl diphosphate" FT /ligand_id="ChEBI:CHEBI:128769" FT /evidence="ECO:0000269|PubMed:32817466" FT VAR_SEQ 109..147 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_010030" FT VAR_SEQ 147..181 FT /note="KCFLNVCFAYTSRHEISNAVREMAWGVEQGLLDPS -> N (in isoform FT 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045007" FT VAR_SEQ 255 FT /note="Q -> QQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_010031" FT VARIANT 37 FT /note="R -> H (in DEDSM; uncertain significance; FT dbSNP:rs1553121073)" FT /evidence="ECO:0000269|PubMed:29100083" FT /id="VAR_080708" FT VARIANT 42 FT /note="K -> E (in RP59; 5-fold reduction in catalytic FT activity and reduced affinity for FPP but not for IPP.; FT dbSNP:rs147394623)" FT /evidence="ECO:0000269|PubMed:21295283, FT ECO:0000269|PubMed:28842490" FT /id="VAR_065356" FT VARIANT 95 FT /note="D -> N (found in a patient with progressive FT myoclonus epilepsy; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33798445" FT /id="VAR_085034" FT VARIANT 205 FT /note="R -> Q (found in a patient with progressive FT myoclonus epilepsy; uncertain significance; FT dbSNP:rs1557447255)" FT /evidence="ECO:0000269|PubMed:33798445" FT /id="VAR_085035" FT VARIANT 211 FT /note="R -> Q (in DEDSM; uncertain significance; FT dbSNP:rs1553122926)" FT /evidence="ECO:0000269|PubMed:29100083, FT ECO:0000269|PubMed:33798445" FT /id="VAR_080709" FT VARIANT 253 FT /note="V -> M (in dbSNP:rs3816539)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:20736409" FT /id="VAR_028088" FT MUTAGEN 12 FT /note="W->A: Markedly decreases FT phosphatidylinositol-mediated activation of FT cis-prenyltransferase activity resulting in products with FT longer chain length; when associated with A-15 and A-19." FT /evidence="ECO:0000269|PubMed:32817466" FT MUTAGEN 15 FT /note="F->A: Markedly decreases FT phosphatidylinositol-mediated activation of FT cis-prenyltransferase activity resulting in products with FT longer chain length; when associated with A-12 and A-19." FT /evidence="ECO:0000269|PubMed:32817466" FT MUTAGEN 19 FT /note="I->A: Markedly decreases FT phosphatidylinositol-mediated activation of FT cis-prenyltransferase activity resulting in products with FT longer chain length; when associated with A-12 and A-15." FT /evidence="ECO:0000269|PubMed:32817466" FT MUTAGEN 106..109 FT /note="Missing: Affects chain elongation resulting in FT shorter products." FT /evidence="ECO:0000269|PubMed:32817466" FT MUTAGEN 306 FT /note="R->A: Delays cell growth; when associated with A-313 FT and A-317." FT /evidence="ECO:0000269|PubMed:32817466" FT MUTAGEN 313 FT /note="F->A: Delays cell growth; when associated with A-306 FT and A-317." FT /evidence="ECO:0000269|PubMed:32817466" FT MUTAGEN 317 FT /note="L->A: Delays cell growth; when associated with A-306 FT and A-313." FT /evidence="ECO:0000269|PubMed:32817466" FT CONFLICT 151 FT /note="N -> Y (in Ref. 3; BAB14439)" FT /evidence="ECO:0000305" FT CONFLICT 277 FT /note="V -> E (in Ref. 6; AAH34152)" FT /evidence="ECO:0000305" FT TURN 2..4 FT /evidence="ECO:0007829|PDB:6Z1N" FT HELIX 11..20 FT /evidence="ECO:0007829|PDB:7PAX" FT STRAND 27..32 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 36..42 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 47..67 FT /evidence="ECO:0007829|PDB:7PAX" FT STRAND 72..79 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 80..84 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 87..106 FT /evidence="ECO:0007829|PDB:7PAX" FT TURN 107..109 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 110..113 FT /evidence="ECO:0007829|PDB:7PAX" FT STRAND 116..122 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 129..142 FT /evidence="ECO:0007829|PDB:7PAX" FT STRAND 147..156 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 158..174 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 180..182 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 185..189 FT /evidence="ECO:0007829|PDB:7PAX" FT TURN 193..196 FT /evidence="ECO:0007829|PDB:7PAX" FT STRAND 201..206 FT /evidence="ECO:0007829|PDB:7PAX" FT STRAND 214..216 FT /evidence="ECO:0007829|PDB:6Z1N" FT TURN 217..222 FT /evidence="ECO:0007829|PDB:7PAX" FT STRAND 223..228 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 232..234 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 237..282 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 283..285 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 294..322 FT /evidence="ECO:0007829|PDB:7PAX" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:7PAY" SQ SEQUENCE 333 AA; 38657 MW; 12EF3A15437A2583 CRC64; MSWIKEGELS LWERFCANII KAGPMPKHIA FIMDGNRRYA KKCQVERQEG HSQGFNKLAE TLRWCLNLGI LEVTVYAFSI ENFKRSKSEV DGLMDLARQK FSRLMEEKEK LQKHGVCIRV LGDLHLLPLD LQELIAQAVQ ATKNYNKCFL NVCFAYTSRH EISNAVREMA WGVEQGLLDP SDISESLLDK CLYTNRSPHP DILIRTSGEV RLSDFLLWQT SHSCLVFQPV LWPEYTFWNL FEAILQFQMN HSVLQKARDM YAEERKRQQL ERDQATVTEQ LLREGLQASG DAQLRRTRLH KLSARREERV QGFLQALELK RADWLARLGT ASA //