NGBR_MOUSE
ID NGBR_MOUSE Reviewed; 297 AA.
AC Q99LJ8; Q0P6D7; Q3TIA3; Q3TIR7; Q3U1Z4;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Dehydrodolichyl diphosphate synthase complex subunit Nus1 {ECO:0000305};
DE EC=2.5.1.87 {ECO:0000250|UniProtKB:Q96E22};
DE AltName: Full=Nogo-B receptor {ECO:0000250|UniProtKB:Q96E22};
DE Short=NgBR {ECO:0000250|UniProtKB:Q96E22};
DE AltName: Full=Nuclear undecaprenyl pyrophosphate synthase 1 homolog {ECO:0000305};
GN Name=Nus1 {ECO:0000312|MGI:MGI:1196365}; Synonyms=D10Ertd438e, Ngbr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=BALB/cJ, and C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP TISSUE SPECIFICITY.
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 [4]
RP DISRUPTION PHENOTYPE, AND CONDITIONAL KNOCKOUT IN FIBROBLASTS.
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).
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). Synthesizes long-chain polyprenols,
CC mostly of C95 and C100 chain length. Regulates the glycosylation and
CC stability of nascent NPC2, thereby promoting trafficking of LDL-derived
CC cholesterol. Acts as a specific receptor for the N-terminus of Nogo-B,
CC a neural and cardiovascular regulator. {ECO:0000250|UniProtKB:Q96E22}.
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:0000250|UniProtKB:Q96E22,
CC ECO:0000303|PubMed:25066056};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q96E22};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:Q96E22}.
CC -!- PATHWAY: Lipid metabolism. {ECO:0000250|UniProtKB:Q96E22}.
CC -!- SUBUNIT: Forms an active dehydrodolichyl diphosphate synthase complex
CC with DHDDS. Interacts with NPC2. {ECO:0000250|UniProtKB:Q96E22}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q96E22}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q96E22}. Note=Colocalizes with Nogo-B during
CC VEGF and wound healing angiogenesis. {ECO:0000250|UniProtKB:Q96E22}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, liver, kidney and
CC pancreas. {ECO:0000269|PubMed:16835300}.
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 conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213),
CC while the allylic isopentenyl group is pointed toward the hydrophobic
CC tunnel of the S1 pocket where the product elongation occurs.
CC {ECO:0000250|UniProtKB:Q96E22}.
CC -!- DISRUPTION PHENOTYPE: Leads to early embryonic lethality in vivo and
CC defective cis-prenyltransferase activity and cholesterol levels in
CC isolated fibroblasts. {ECO:0000269|PubMed:25066056}.
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:0000250|UniProtKB:Q96E22}.
CC -!- SIMILARITY: Belongs to the UPP synthase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH18372.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAE33349.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK155620; BAE33349.1; ALT_SEQ; mRNA.
DR EMBL; AK167741; BAE39779.1; -; mRNA.
DR EMBL; AK167939; BAE39943.1; -; mRNA.
DR EMBL; BC003223; AAH03223.1; -; mRNA.
DR EMBL; BC018372; AAH18372.1; ALT_FRAME; mRNA.
DR CCDS; CCDS23841.1; -.
DR RefSeq; NP_084526.1; NM_030250.2.
DR AlphaFoldDB; Q99LJ8; -.
DR SMR; Q99LJ8; -.
DR BioGRID; 206326; 1.
DR IntAct; Q99LJ8; 1.
DR MINT; Q99LJ8; -.
DR STRING; 10090.ENSMUSP00000023830; -.
DR GlyGen; Q99LJ8; 2 sites.
DR PhosphoSitePlus; Q99LJ8; -.
DR SwissPalm; Q99LJ8; -.
DR EPD; Q99LJ8; -.
DR MaxQB; Q99LJ8; -.
DR PaxDb; Q99LJ8; -.
DR PRIDE; Q99LJ8; -.
DR ProteomicsDB; 287419; -.
DR Antibodypedia; 32563; 113 antibodies from 22 providers.
DR Ensembl; ENSMUST00000023830; ENSMUSP00000023830; ENSMUSG00000023068.
DR GeneID; 52014; -.
DR KEGG; mmu:52014; -.
DR UCSC; uc007fbi.2; mouse.
DR CTD; 116150; -.
DR MGI; MGI:1196365; Nus1.
DR VEuPathDB; HostDB:ENSMUSG00000023068; -.
DR eggNOG; KOG2818; Eukaryota.
DR GeneTree; ENSGT00390000003223; -.
DR HOGENOM; CLU_051870_2_1_1; -.
DR InParanoid; Q99LJ8; -.
DR OMA; MPRVYEA; -.
DR OrthoDB; 1448374at2759; -.
DR PhylomeDB; Q99LJ8; -.
DR TreeFam; TF332448; -.
DR BRENDA; 2.5.1.87; 3474.
DR Reactome; R-MMU-446199; Synthesis of Dolichyl-phosphate.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 52014; 22 hits in 74 CRISPR screens.
DR ChiTaRS; Nus1; mouse.
DR PRO; PR:Q99LJ8; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q99LJ8; protein.
DR Bgee; ENSMUSG00000023068; Expressed in adult mammalian kidney and 258 other tissues.
DR Genevisible; Q99LJ8; MM.
DR GO; GO:1904423; C:dehydrodolichyl diphosphate synthase complex; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IMP:MGI.
DR GO; GO:0045547; F:dehydrodolichyl diphosphate synthase activity; ISS:UniProtKB.
DR GO; GO:0004659; F:prenyltransferase activity; IMP:MGI.
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; IMP:MGI.
DR GO; GO:0019408; P:dolichol biosynthetic process; ISO:MGI.
DR GO; GO:0006489; P:dolichyl diphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:MGI.
DR GO; GO:0006486; P:protein glycosylation; IBA:GO_Central.
DR GO; GO:0035268; P:protein mannosylation; IMP:MGI.
DR GO; GO:0032383; P:regulation of intracellular cholesterol transport; IMP:MGI.
DR GO; GO:0055092; P:sterol homeostasis; IMP:MGI.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; ISO:MGI.
DR DisProt; DP01304; -.
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 2: Evidence at transcript level;
KW Angiogenesis; Developmental protein; Differentiation;
KW Endoplasmic reticulum; Glycoprotein; Lipid metabolism; Magnesium; Membrane;
KW Receptor; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..297
FT /note="Dehydrodolichyl diphosphate synthase complex subunit
FT Nus1"
FT /id="PRO_0000273168"
FT TRANSMEM 7..26
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q96E22"
FT TRANSMEM 40..56
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q96E22"
FT TRANSMEM 121..139
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q96E22"
FT REGION 63..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 294..296
FT /note="RXG motif; crucial for prenyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:Q96E22"
FT BINDING 295
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q96E22"
FT BINDING 296
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q96E22"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 275
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 29
FT /note="R -> H (in Ref. 1; BAE39779)"
FT /evidence="ECO:0000305"
FT CONFLICT 91
FT /note="W -> L (in Ref. 1; BAE39943)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="Q -> K (in Ref. 1; BAE39943)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 297 AA; 33485 MW; B1B5C1EFB2336A9E CRC64;
MTGLYELVWR VLHALLCLHL TLTSWLRVRF GTWNWIWRRC CRAASAAVLA PLGFTLRKPR
AVGRNRRHHR HPHGGPGPGP GPAATHPRLR WRADVRSLQK LPVHMGLLVT EEVQEPSFSD
IASLVVWCMA VGISYISVYD HQGIFKRNNS RLMDEILKQQ QELLGQDCSK YSAEFANSND
KDDQDLNCPS AVKVLSPEDG KADIVRAAQD FCQLVAQQQR KPTDLDVDLL GSLLSSHGFP
DPDLVLKFGP VDSTLGFLPW QIRLTEIVSL PSHLNISYED FFSALRQYAA CEQRLGK
