ID   UPPS_GIAIC              Reviewed;         265 AA.
AC   A8B1Z2;
DT   07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 1.
DT   25-MAY-2022, entry version 76.
DE   RecName: Full=Di-trans,poly-cis-undecaprenyl-diphosphate synthase {ECO:0000305|PubMed:20308470};
DE            EC=2.5.1.31 {ECO:0000269|PubMed:20308470, ECO:0000269|PubMed:28842490};
DE   AltName: Full=Cis-prenyltransferase {ECO:0000303|PubMed:20308470};
GN   Name=UPPS {ECO:0000303|PubMed:20308470};
GN   ORFNames=GL50803_15256 {ECO:0000303|PubMed:17901334};
OS   Giardia intestinalis (strain ATCC 50803 / WB clone C6) (Giardia lamblia).
OC   Eukaryota; Metamonada; Diplomonadida; Hexamitidae; Giardiinae; Giardia.
OX   NCBI_TaxID=184922;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 50803 / WB clone C6;
RX   PubMed=17901334; DOI=10.1126/science.1143837;
RA   Morrison H.G., McArthur A.G., Gillin F.D., Aley S.B., Adam R.D.,
RA   Olsen G.J., Best A.A., Cande W.Z., Chen F., Cipriano M.J., Davids B.J.,
RA   Dawson S.C., Elmendorf H.G., Hehl A.B., Holder M.E., Huse S.M., Kim U.U.,
RA   Lasek-Nesselquist E., Manning G., Nigam A., Nixon J.E.J., Palm D.,
RA   Passamaneck N.E., Prabhu A., Reich C.I., Reiner D.S., Samuelson J.,
RA   Svard S.G., Sogin M.L.;
RT   "Genomic minimalism in the early diverging intestinal parasite Giardia
RT   lamblia.";
RL   Science 317:1921-1926(2007).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=20308470; DOI=10.1093/glycob/cwq036;
RA   Grabinska K.A., Cui J., Chatterjee A., Guan Z., Raetz C.R., Robbins P.W.,
RA   Samuelson J.;
RT   "Molecular characterization of the cis-prenyltransferase of Giardia
RT   lamblia.";
RL   Glycobiology 20:824-832(2010).
RN   [3]
RP   FUNCTION.
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   [4]
RP   CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF ARG-236 AND GLY-238, AND
RP   PATHWAY.
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).
CC   -!- FUNCTION: Cis-prenyl transferase involved in the synthesis of dolichol,
CC       a long-chain polyprenol that is utilized as a sugar carrier in protein
CC       glycosylation in the endoplasmic reticulum (ER). Catalyzes the
CC       sequential condensation of isopentenyl pyrophosphate (IPP) with
CC       farnesyl pyrophosphate (FPP) to produce a polyprenyl pyrophosphate
CC       which contains 11 (major) and 12 (minor) isoprene units.
CC       {ECO:0000269|PubMed:20308470, ECO:0000269|PubMed:25066056,
CC       ECO:0000269|PubMed:28842490}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E,6E)-farnesyl diphosphate + 8 isopentenyl diphosphate = di-
CC         trans,octa-cis-undecaprenyl diphosphate + 8 diphosphate;
CC         Xref=Rhea:RHEA:27551, ChEBI:CHEBI:33019, ChEBI:CHEBI:58405,
CC         ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.31;
CC         Evidence={ECO:0000269|PubMed:20308470, ECO:0000269|PubMed:28842490};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P60472};
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC       {ECO:0000305|PubMed:20308470}.
CC   -!- PATHWAY: Lipid metabolism. {ECO:0000269|PubMed:20308470,
CC       ECO:0000269|PubMed:28842490}.
CC   -!- MISCELLANEOUS: The synthetic pathway for dolichol synthesis is
CC       conserved in Giardia lamblia, even if some of the important enzymes are
CC       different from those of higher eukaryotes or remain unidentified.
CC       {ECO:0000269|PubMed:20308470}.
CC   -!- SIMILARITY: Belongs to the UPP synthase family.
CC       {ECO:0000255|RuleBase:RU003962}.
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; AACB02000001; EDO82194.1; -; Genomic_DNA.
DR   RefSeq; XP_001709868.1; XM_001709816.1.
DR   AlphaFoldDB; A8B1Z2; -.
DR   SMR; A8B1Z2; -.
DR   STRING; 5741.EDO82194; -.
DR   EnsemblProtists; EDO82194; EDO82194; GL50803_15256.
DR   GeneID; 5702774; -.
DR   KEGG; gla:GL50803_0015256; -.
DR   VEuPathDB; GiardiaDB:GL50803_15256; -.
DR   HOGENOM; CLU_038505_1_1_1; -.
DR   InParanoid; A8B1Z2; -.
DR   OMA; PRTEGHK; -.
DR   OrthoDB; 1362420at2759; -.
DR   UniPathway; UPA00378; -.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0045547; F:dehydrodolichyl diphosphate synthase activity; IDA:UniProtKB.
DR   GO; GO:0008834; F:di-trans,poly-cis-decaprenylcistransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0002094; F:polyprenyltransferase activity; IBA:GO_Central.
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; -; 1.
DR   HAMAP; MF_01139; ISPT; 1.
DR   InterPro; IPR001441; UPP_synth-like.
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.
PE   1: Evidence at protein level;
KW   Lipid metabolism; Magnesium; Transferase.
FT   CHAIN           1..265
FT                   /note="Di-trans,poly-cis-undecaprenyl-diphosphate synthase"
FT                   /id="PRO_0000431404"
FT   MOTIF           236..238
FT                   /note="RXG motif; crucial for prenyltransferase activity"
FT                   /evidence="ECO:0000305|PubMed:28842490"
FT   MUTAGEN         236
FT                   /note="R->H: 5-fold decrease in catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:28842490"
FT   MUTAGEN         238
FT                   /note="G->A: Loss of catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:28842490"
SQ   SEQUENCE   265 AA;  29968 MW;  31B975D2D0EFA758 CRC64;
     MIPMHVAVIM DGNGRWARKQ LQERTFGHEQ GVSVLESIVD ECINCGIRFL TVYAFSTENW
     SRPPTEVSFL FELLSAAIQR VRTTYRERNV KVQFCGERTT QIPETVIAAM NCIEQDTAAC
     TGLILSVCFN YGGHTEIAQA CRSVLADCLE GDAVENIKTR LQMPIEQFIQ QIDTHLYANL
     PPVDLLIRTG CEKRLSNFLP WHLAYAEIIF SDLLWPEFSV RAFKDCLDEF ASRTRRFGGV
     QLSPMTGVYS DTHPHSSTNA LSNHD