DHDDS_MOUSE
ID DHDDS_MOUSE Reviewed; 333 AA.
AC Q99KU1; A3KGL4; Q3UF13; Q8BZ16; Q8BZK8;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Dehydrodolichyl diphosphate synthase complex subunit Dhdds {ECO:0000305};
DE EC=2.5.1.87 {ECO:0000250|UniProtKB:Q86SQ9};
DE AltName: Full=Cis-isoprenyltransferase {ECO:0000250|UniProtKB:Q86SQ9};
DE Short=CIT {ECO:0000250|UniProtKB:Q86SQ9};
DE Short=Cis-IPTase {ECO:0000250|UniProtKB:Q86SQ9};
GN Name=Dhdds {ECO:0000312|MGI:MGI:1914672};
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Diencephalon, Hippocampus, Olfactory bulb, Sympathetic ganglion, and
RC Vagina;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC 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).
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). 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. {ECO:0000250|UniProtKB:Q86SQ9}.
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:Q86SQ9};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q86SQ9};
CC Note=Binds 1 magnesium ion per subunit. {ECO:0000250|UniProtKB:Q86SQ9};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:Q86SQ9}.
CC -!- PATHWAY: Lipid metabolism. {ECO:0000250|UniProtKB:Q86SQ9}.
CC -!- SUBUNIT: Forms an active dehydrodolichyl diphosphate synthase complex
CC with NUS1. Interacts with NPC2. {ECO:0000250|UniProtKB:Q86SQ9}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q86SQ9}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q86SQ9}. Note=colocalizes with calnexin.
CC {ECO:0000250|UniProtKB:Q86SQ9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99KU1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99KU1-2; Sequence=VSP_010032;
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:0000250|UniProtKB:Q86SQ9}.
CC -!- SIMILARITY: Belongs to the UPP synthase family. {ECO:0000305}.
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DR EMBL; AK034277; BAC28657.1; -; mRNA.
DR EMBL; AK036929; BAC29643.1; -; mRNA.
DR EMBL; AK049991; BAC34020.1; -; mRNA.
DR EMBL; AK135087; BAE22416.1; -; mRNA.
DR EMBL; AK149138; BAE28748.1; -; mRNA.
DR EMBL; AK171207; BAE42313.1; -; mRNA.
DR EMBL; AL670680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL837508; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004011; AAH04011.1; -; mRNA.
DR CCDS; CCDS18760.1; -. [Q99KU1-1]
DR CCDS; CCDS89839.1; -. [Q99KU1-2]
DR RefSeq; NP_080420.2; NM_026144.4. [Q99KU1-1]
DR AlphaFoldDB; Q99KU1; -.
DR SMR; Q99KU1; -.
DR STRING; 10090.ENSMUSP00000012262; -.
DR iPTMnet; Q99KU1; -.
DR PhosphoSitePlus; Q99KU1; -.
DR EPD; Q99KU1; -.
DR MaxQB; Q99KU1; -.
DR PaxDb; Q99KU1; -.
DR PRIDE; Q99KU1; -.
DR ProteomicsDB; 279862; -. [Q99KU1-1]
DR ProteomicsDB; 279863; -. [Q99KU1-2]
DR Antibodypedia; 16091; 112 antibodies from 22 providers.
DR DNASU; 67422; -.
DR Ensembl; ENSMUST00000012262; ENSMUSP00000012262; ENSMUSG00000012117. [Q99KU1-1]
DR Ensembl; ENSMUST00000105887; ENSMUSP00000101511; ENSMUSG00000012117. [Q99KU1-2]
DR Ensembl; ENSMUST00000144668; ENSMUSP00000116098; ENSMUSG00000012117. [Q99KU1-1]
DR GeneID; 67422; -.
DR KEGG; mmu:67422; -.
DR UCSC; uc008vds.1; mouse. [Q99KU1-1]
DR UCSC; uc008vdv.1; mouse. [Q99KU1-2]
DR CTD; 79947; -.
DR MGI; MGI:1914672; Dhdds.
DR VEuPathDB; HostDB:ENSMUSG00000012117; -.
DR eggNOG; KOG1602; Eukaryota.
DR GeneTree; ENSGT00390000007879; -.
DR InParanoid; Q99KU1; -.
DR OMA; PRTEGHK; -.
DR OrthoDB; 1362420at2759; -.
DR PhylomeDB; Q99KU1; -.
DR TreeFam; TF323753; -.
DR Reactome; R-MMU-446199; Synthesis of Dolichyl-phosphate.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 67422; 24 hits in 75 CRISPR screens.
DR ChiTaRS; Dhdds; mouse.
DR PRO; PR:Q99KU1; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q99KU1; protein.
DR Bgee; ENSMUSG00000012117; Expressed in saccule of membranous labyrinth and 256 other tissues.
DR ExpressionAtlas; Q99KU1; baseline and differential.
DR Genevisible; Q99KU1; MM.
DR GO; GO:1904423; C:dehydrodolichyl diphosphate synthase complex; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045547; F:dehydrodolichyl diphosphate synthase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002094; F:polyprenyltransferase activity; ISO:MGI.
DR GO; GO:0006489; P:dolichyl diphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0016094; P:polyprenol biosynthetic process; IBA:GO_Central.
DR CDD; cd00475; Cis_IPPS; 1.
DR Gene3D; 3.40.1180.10; -; 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 PANTHER; PTHR10291; PTHR10291; 1.
DR Pfam; PF01255; Prenyltransf; 1.
DR SUPFAM; SSF64005; SSF64005; 1.
DR TIGRFAMs; TIGR00055; uppS; 1.
DR PROSITE; PS01066; UPP_SYNTHASE; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Endoplasmic reticulum; Lipid metabolism; Magnesium;
KW Membrane; Metal-binding; Reference proteome; Transferase.
FT CHAIN 1..333
FT /note="Dehydrodolichyl diphosphate synthase complex subunit
FT Dhdds"
FT /id="PRO_0000123750"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q86SQ9"
FT BINDING 38
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q86SQ9"
FT BINDING 85
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q86SQ9"
FT BINDING 205
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q86SQ9"
FT BINDING 211
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q86SQ9"
FT BINDING 213
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q86SQ9"
FT VAR_SEQ 255
FT /note="Q -> QQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_010032"
FT CONFLICT 30
FT /note="A -> L (in Ref. 1; BAC29643)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 333 AA; 38509 MW; 53992F5E92D3F2C9 CRC64;
MSWIKEGELS LWERFCANII KAGPVPKHIA FIMDGNRRYA KKCQVERQEG HTQGFNKLAE
TLRWCLNLGI LEVTVYAFSI ENFKRSKSEV DGLLDLARQK FSCLMEEQEK LQKHGVCIRV
LGDLHLLPLD LQEKIAHAIQ ATKNYNKCFL NVCFAYTSRH EIANAVREMA WGVEQGLLEP
SDVSESLLDK CLYSNHSPHP DILIRTSGEV RLSDFLLWQT SHSCLVFQPV LWPEYTFWNL
CEAILQFQRN HGALQKARDM YAEERKRRQL ERDQAAVTEQ LLREGLQASG DAQLRRTRLH
KLSTKREERV QGFLKALELK RANWLALWGT ASA
