NGBR_HUMAN
ID NGBR_HUMAN Reviewed; 293 AA.
AC Q96E22; B2RWQ4; O00251;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Dehydrodolichyl diphosphate synthase complex subunit NUS1 {ECO:0000305};
DE EC=2.5.1.87 {ECO:0000269|PubMed:25066056, ECO:0000269|PubMed:28842490};
DE AltName: Full=Cis-prenyltransferase subunit NgBR {ECO:0000303|PubMed:28842490};
DE AltName: Full=Nogo-B receptor {ECO:0000303|PubMed:16835300};
DE Short=NgBR {ECO:0000303|PubMed:16835300, ECO:0000303|PubMed:28842490};
DE AltName: Full=Nuclear undecaprenyl pyrophosphate synthase 1 homolog {ECO:0000305};
GN Name=NUS1 {ECO:0000303|PubMed:28842490, ECO:0000312|HGNC:HGNC:21042};
GN Synonyms=C6orf68, NGBR;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, Muscle, Testis, and Uterus;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 171-293, AND VARIANTS ARG-216 AND LYS-219.
RX PubMed=9294218; DOI=10.1073/pnas.94.19.10373;
RA Still I.H., Vince P., Cowell J.K.;
RT "Direct isolation of human transcribed sequences from yeast artificial
RT chromosomes through the application of RNA fingerprinting.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:10373-10378(1997).
RN [5]
RP FUNCTION, AND LACK OF TRANSFERASE ACTIVITY.
RX PubMed=16835300; DOI=10.1073/pnas.0602427103;
RA Miao R.Q., Gao Y., Harrison K.D., Prendergast J., Acevedo L.M., Yu J.,
RA Hu F., Strittmatter S.M., Sessa W.C.;
RT "Identification of a receptor necessary for Nogo-B stimulated chemotaxis
RT and morphogenesis of endothelial cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10997-11002(2006).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NPC2.
RX PubMed=19723497; DOI=10.1016/j.cmet.2009.07.003;
RA Harrison K.D., Miao R.Q., Fernandez-Hernando C., Suarez Y., Davalos A.,
RA Sessa W.C.;
RT "Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates
RT intracellular cholesterol trafficking.";
RL Cell Metab. 10:208-218(2009).
RN [7]
RP FUNCTION IN DOLICHOL BIOSYNTHESIS, SUBCELLULAR LOCATION, GLYCOSYLATION AT
RP ASN-144 AND ASN-271, AND INTERACTION WITH DHDDS.
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 [8]
RP INVOLVEMENT IN CDG1AA, VARIANT CDG1AA HIS-290, CHARACTERIZATION OF VARIANT
RP CDG1AA HIS-290, 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 [9]
RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP MUTAGENESIS OF HIS-100; GLY-292 AND LYS-293, ACTIVITY REGULATION,
RP CHARACTERIZATION OF VARIANT HIS-290, PATHWAY, AND COFACTOR.
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 [10]
RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 79-293 IN COMPLEX WITH DHDDS AND
RP ISOPENTENYL DIPHOSPHATE, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP DOMAIN, MUTAGENESIS OF GLY-196; LYS-197; ILE-200; LEU-226; LEU-230;
RP GLY-252; PHE-253 AND PRO-255, AND VARIANT CYS-91.
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 [11]
RP INVOLVEMENT IN MRD55.
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 [12]
RP VARIANT 104-VAL--LYS-293 DEL.
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 DHDDS, 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:21572394, PubMed:25066056,
CC PubMed:28842490, PubMed:32817466). Synthesizes long-chain polyprenols,
CC mostly of C95 and C100 chain length (PubMed:32817466). Regulates the
CC glycosylation and stability of nascent NPC2, thereby promoting
CC trafficking of LDL-derived cholesterol. Acts as a specific receptor for
CC the N-terminus of Nogo-B, a neural and cardiovascular regulator
CC (PubMed:16835300). {ECO:0000269|PubMed:16835300,
CC ECO:0000269|PubMed:21572394, ECO:0000269|PubMed:25066056,
CC ECO:0000269|PubMed:28842490, 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};
CC -!- ACTIVITY REGULATION: Activated by phospholipids including cardiolipin,
CC phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and
CC phosphatidylserine. {ECO:0000269|PubMed:28842490,
CC ECO:0000269|PubMed:32817466}.
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 substrates. {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:25066056,
CC ECO:0000269|PubMed:28842490}.
CC -!- SUBUNIT: Forms an active dehydrodolichyl diphosphate synthase complex
CC with DHDDS (NUS1-DHDDS) (PubMed:28842490, PubMed:19723497,
CC PubMed:25066056, PubMed:32817466). Interacts with NPC2
CC (PubMed:21572394). {ECO:0000269|PubMed:19723497,
CC ECO:0000269|PubMed:21572394, ECO:0000269|PubMed:25066056,
CC ECO:0000269|PubMed:28842490}.
CC -!- INTERACTION:
CC Q96E22; Q9H7T3: C10orf95; NbExp=3; IntAct=EBI-6949352, EBI-6949335;
CC Q96E22; Q86SQ9: DHDDS; NbExp=3; IntAct=EBI-6949352, EBI-26942900;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19723497, ECO:0000269|PubMed:21572394}; Multi-pass
CC membrane protein {ECO:0000303|PubMed:21572394}. Note=Colocalizes with
CC Nogo-B during VEGF and wound healing angiogenesis.
CC {ECO:0000269|PubMed:19723497}.
CC -!- DOMAIN: Contains the RXG motif, which is important for substrate
CC binding and prenyltransferase activity. The catalytic site at NUS1-
CC DHDDS interface accomodates both the allylic and the homoallylic IPP
CC substrates to the S1 and S2 pockets respectively. The beta-phosphate
CC groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1
CC and four conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-
CC 213), while the allylic isopentenyl group is pointed toward the
CC hydrophobic tunnel of the S1 pocket where the product elongation
CC occurs. {ECO:0000269|PubMed:32817466}.
CC -!- DISEASE: Congenital disorder of glycosylation 1AA (CDG1AA)
CC [MIM:617082]: A form of congenital disorder of glycosylation, a
CC multisystem disorder caused by a defect in glycoprotein biosynthesis
CC and characterized by under-glycosylated serum glycoproteins. Congenital
CC disorders of glycosylation result in a wide variety of clinical
CC features, such as defects in the nervous system development,
CC psychomotor retardation, dysmorphic features, hypotonia, coagulation
CC disorders, and immunodeficiency. The broad spectrum of features
CC reflects the critical role of N-glycoproteins during embryonic
CC development, differentiation, and maintenance of cell functions. CDG1AA
CC inheritance is autosomal recessive. {ECO:0000269|PubMed:25066056}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 55,
CC with seizures (MRD55) [MIM:617831]: A form of intellectual disability,
CC a disorder characterized by significantly below average general
CC intellectual functioning associated with impairments in adaptive
CC behavior and manifested during the developmental period. MRD55 patients
CC suffer from seizures appearing during the first years of life.
CC {ECO:0000269|PubMed:29100083}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: NUS1 seems to exist in two topological orientations, a
CC minor glycosylated species with its C-terminus oriented towards the
CC lumen regulating NPC2 stability, and a major fraction oriented with its
CC C-terminus directed towards the cytosol where it regulates cis-IPTase
CC activity. {ECO:0000303|PubMed:21572394}.
CC -!- SIMILARITY: Belongs to the UPP synthase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB72234.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; Z98172; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590303; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48201.1; -; Genomic_DNA.
DR EMBL; BC013026; AAH13026.1; -; mRNA.
DR EMBL; BC063794; AAH63794.1; -; mRNA.
DR EMBL; BC066910; AAH66910.1; -; mRNA.
DR EMBL; BC110325; AAI10326.1; -; mRNA.
DR EMBL; BC150654; AAI50655.1; -; mRNA.
DR EMBL; BC150655; AAI50656.1; -; mRNA.
DR EMBL; U82319; AAB72234.1; ALT_FRAME; mRNA.
DR CCDS; CCDS5118.1; -.
DR RefSeq; NP_612468.1; NM_138459.3.
DR PDB; 6W2L; X-ray; 2.31 A; B=80-293.
DR PDB; 6Z1N; X-ray; 2.30 A; B=73-293.
DR PDBsum; 6W2L; -.
DR PDBsum; 6Z1N; -.
DR AlphaFoldDB; Q96E22; -.
DR SMR; Q96E22; -.
DR BioGRID; 125481; 73.
DR ComplexPortal; CPX-6701; Dehydrodolichyl diphosphate synthase complex.
DR CORUM; Q96E22; -.
DR DIP; DIP-61225N; -.
DR IntAct; Q96E22; 24.
DR MINT; Q96E22; -.
DR STRING; 9606.ENSP00000357480; -.
DR GlyGen; Q96E22; 2 sites.
DR iPTMnet; Q96E22; -.
DR PhosphoSitePlus; Q96E22; -.
DR BioMuta; NUS1; -.
DR DMDM; 74762651; -.
DR EPD; Q96E22; -.
DR jPOST; Q96E22; -.
DR MassIVE; Q96E22; -.
DR MaxQB; Q96E22; -.
DR PaxDb; Q96E22; -.
DR PeptideAtlas; Q96E22; -.
DR PRIDE; Q96E22; -.
DR ProteomicsDB; 76366; -.
DR Antibodypedia; 32563; 113 antibodies from 22 providers.
DR DNASU; 116150; -.
DR Ensembl; ENST00000368494.4; ENSP00000357480.3; ENSG00000153989.8.
DR GeneID; 116150; -.
DR KEGG; hsa:116150; -.
DR MANE-Select; ENST00000368494.4; ENSP00000357480.3; NM_138459.5; NP_612468.1.
DR UCSC; uc003pxw.4; human.
DR CTD; 116150; -.
DR DisGeNET; 116150; -.
DR GeneCards; NUS1; -.
DR HGNC; HGNC:21042; NUS1.
DR HPA; ENSG00000153989; Low tissue specificity.
DR MalaCards; NUS1; -.
DR MIM; 610463; gene.
DR MIM; 617082; phenotype.
DR MIM; 617831; phenotype.
DR neXtProt; NX_Q96E22; -.
DR OpenTargets; ENSG00000153989; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA162398248; -.
DR VEuPathDB; HostDB:ENSG00000153989; -.
DR eggNOG; KOG2818; Eukaryota.
DR GeneTree; ENSGT00390000003223; -.
DR HOGENOM; CLU_051870_2_1_1; -.
DR InParanoid; Q96E22; -.
DR OMA; MPRVYEA; -.
DR OrthoDB; 1448374at2759; -.
DR PhylomeDB; Q96E22; -.
DR TreeFam; TF332448; -.
DR BioCyc; MetaCyc:ENSG00000153989-MON; -.
DR BRENDA; 2.5.1.87; 2681.
DR PathwayCommons; Q96E22; -.
DR Reactome; R-HSA-446199; Synthesis of Dolichyl-phosphate.
DR Reactome; R-HSA-4755609; Defective DHDDS causes RP59.
DR SignaLink; Q96E22; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 116150; 760 hits in 1041 CRISPR screens.
DR ChiTaRS; NUS1; human.
DR GenomeRNAi; 116150; -.
DR Pharos; Q96E22; Tbio.
DR PRO; PR:Q96E22; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q96E22; protein.
DR Bgee; ENSG00000153989; Expressed in endometrium and 184 other tissues.
DR Genevisible; Q96E22; HS.
DR GO; GO:1904423; C:dehydrodolichyl diphosphate synthase complex; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
DR GO; GO:0019408; P:dolichol biosynthetic process; IMP:MGI.
DR GO; GO:0006489; P:dolichyl diphosphate biosynthetic process; IDA:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IMP:BHF-UCL.
DR GO; GO:0006486; P:protein glycosylation; IBA:GO_Central.
DR GO; GO:0035268; P:protein mannosylation; IEA:Ensembl.
DR GO; GO:0032383; P:regulation of intracellular cholesterol transport; IGI:MGI.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IMP:BHF-UCL.
DR Gene3D; 3.40.1180.10; -; 1.
DR InterPro; IPR038887; Nus1/NgBR.
DR InterPro; IPR001441; UPP_synth-like.
DR InterPro; IPR036424; UPP_synth-like_sf.
DR PANTHER; PTHR21528; PTHR21528; 1.
DR Pfam; PF01255; Prenyltransf; 1.
DR SUPFAM; SSF64005; SSF64005; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Angiogenesis; Congenital disorder of glycosylation;
KW Developmental protein; Differentiation; Disease variant;
KW Endoplasmic reticulum; Glycoprotein; Intellectual disability;
KW Lipid metabolism; Magnesium; Membrane; Metal-binding; Receptor;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..293
FT /note="Dehydrodolichyl diphosphate synthase complex subunit
FT NUS1"
FT /id="PRO_0000273167"
FT TRANSMEM 1..23
FT /note="Helical; Name=1"
FT /evidence="ECO:0000303|PubMed:21572394"
FT TRANSMEM 35..56
FT /note="Helical; Name=2"
FT /evidence="ECO:0000303|PubMed:21572394"
FT TRANSMEM 117..135
FT /note="Helical; Name=3"
FT /evidence="ECO:0000303|PubMed:21572394"
FT MOTIF 290..292
FT /note="RXG motif; crucial for prenyltransferase activity"
FT /evidence="ECO:0000269|PubMed:32817466,
FT ECO:0000305|PubMed:28842490"
FT BINDING 291
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000269|PubMed:32817466"
FT BINDING 292
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000269|PubMed:32817466"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21572394"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21572394"
FT VARIANT 91
FT /note="G -> C (probable disease-associated variant found in
FT a patient with Parkinson's disease; 40 % reduction in
FT prenyltransferase activity)"
FT /evidence="ECO:0000269|PubMed:32817466"
FT /id="VAR_083900"
FT VARIANT 104..293
FT /note="Missing (probable disease-associated variant found
FT in a patient with progressive myoclonus epilepsy)"
FT /evidence="ECO:0000269|PubMed:33798445"
FT /id="VAR_085036"
FT VARIANT 175
FT /note="N -> Y (in dbSNP:rs28362518)"
FT /id="VAR_030092"
FT VARIANT 179
FT /note="D -> E (in dbSNP:rs28362519)"
FT /id="VAR_030093"
FT VARIANT 210
FT /note="Missing (in dbSNP:rs1052237)"
FT /id="VAR_030094"
FT VARIANT 216
FT /note="K -> R (in dbSNP:rs1052239)"
FT /evidence="ECO:0000269|PubMed:9294218"
FT /id="VAR_030095"
FT VARIANT 219
FT /note="T -> K (in dbSNP:rs1132147)"
FT /evidence="ECO:0000269|PubMed:9294218"
FT /id="VAR_030096"
FT VARIANT 290
FT /note="R -> H (in CDG1AA; loss of function in protein
FT glycosylation; 5-fold reduction in catalytic activity and
FT reduced affinity for FPP and IPP.; dbSNP:rs886037858)"
FT /evidence="ECO:0000269|PubMed:25066056,
FT ECO:0000269|PubMed:28842490"
FT /id="VAR_071210"
FT MUTAGEN 100
FT /note="H->A: 3.5-fold reduction in catalytic activity and
FT no marked change in affinity for FPP and IPP."
FT /evidence="ECO:0000269|PubMed:28842490"
FT MUTAGEN 196
FT /note="G->A: Decreases binding to DHDDS."
FT /evidence="ECO:0000269|PubMed:32817466"
FT MUTAGEN 197
FT /note="K->A: Decreases binding to DHDDS."
FT /evidence="ECO:0000269|PubMed:32817466"
FT MUTAGEN 200
FT /note="I->A: Disrupts NUS1-DHDDS heterodimerization."
FT /evidence="ECO:0000269|PubMed:32817466"
FT MUTAGEN 226
FT /note="L->A: Disrupts NUS1-DHDDS heterodimerization."
FT /evidence="ECO:0000269|PubMed:32817466"
FT MUTAGEN 230
FT /note="L->A: Disrupts NUS1-DHDDS heterodimerization."
FT /evidence="ECO:0000269|PubMed:32817466"
FT MUTAGEN 252
FT /note="G->A: Disrupts NUS1-DHDDS heterodimerization."
FT /evidence="ECO:0000269|PubMed:32817466"
FT MUTAGEN 253
FT /note="F->A: Disrupts NUS1-DHDDS heterodimerization."
FT /evidence="ECO:0000269|PubMed:32817466"
FT MUTAGEN 255
FT /note="P->A: Disrupts NUS1-DHDDS heterodimerization."
FT /evidence="ECO:0000269|PubMed:32817466"
FT MUTAGEN 292
FT /note="G->A: Almost complete loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:28842490"
FT MUTAGEN 293
FT /note="K->KA: Almost complete loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:28842490"
FT MUTAGEN 293
FT /note="Missing: Almost complete loss of catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:28842490"
FT HELIX 80..93
FT /evidence="ECO:0007829|PDB:6Z1N"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 114..127
FT /evidence="ECO:0007829|PDB:6Z1N"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 145..156
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 177..187
FT /evidence="ECO:0007829|PDB:6Z1N"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 197..212
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 223..228
FT /evidence="ECO:0007829|PDB:6Z1N"
FT STRAND 239..246
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:6Z1N"
FT STRAND 262..267
FT /evidence="ECO:0007829|PDB:6Z1N"
FT HELIX 274..285
FT /evidence="ECO:0007829|PDB:6Z1N"
SQ SEQUENCE 293 AA; 33224 MW; E6A0C9D9B39D4BCA CRC64;
MTGLYELVWR VLHALLCLHR TLTSWLRVRF GTWNWIWRRC CRAASAAVLA PLGFTLRKPP
AVGRNRRHHR HPRGGSCLAA AHHRMRWRAD GRSLEKLPVH MGLVITEVEQ EPSFSDIASL
VVWCMAVGIS YISVYDHQGI FKRNNSRLMD EILKQQQELL GLDCSKYSPE FANSNDKDDQ
VLNCHLAVKV LSPEDGKADI VRAAQDFCQL VAQKQKRPTD LDVDTLASLL SSNGCPDPDL
VLKFGPVDST LGFLPWHIRL TEIVSLPSHL NISYEDFFSA LRQYAACEQR LGK
