ISPD_DANRE
ID ISPD_DANRE Reviewed; 462 AA.
AC A0JPF9; E9QIE3; F1R603;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 2.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=D-ribitol-5-phosphate cytidylyltransferase {ECO:0000250|UniProtKB:A4D126};
DE EC=2.7.7.40 {ECO:0000250|UniProtKB:A4D126};
DE AltName: Full=2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein {ECO:0000250|UniProtKB:A4D126};
DE AltName: Full=Isoprenoid synthase domain-containing protein {ECO:0000250|UniProtKB:A4D126};
GN Name=crppa; Synonyms=ispd {ECO:0000250|UniProtKB:A4D126};
GN ORFNames=zgc:154151 {ECO:0000303|Ref.2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22522421; DOI=10.1038/ng.2253;
RA Roscioli T., Kamsteeg E.J., Buysse K., Maystadt I., van Reeuwijk J.,
RA van den Elzen C., van Beusekom E., Riemersma M., Pfundt R., Vissers L.E.,
RA Schraders M., Altunoglu U., Buckley M.F., Brunner H.G., Grisart B.,
RA Zhou H., Veltman J.A., Gilissen C., Mancini G.M., Delree P.,
RA Willemsen M.A., Ramadza D.P., Chitayat D., Bennett C., Sheridan E.,
RA Peeters E.A., Tan-Sindhunata G.M., de Die-Smulders C.E., Devriendt K.,
RA Kayserili H., El-Hashash O.A., Stemple D.L., Lefeber D.J., Lin Y.Y.,
RA van Bokhoven H.;
RT "Mutations in ISPD cause Walker-Warburg syndrome and defective
RT glycosylation of alpha-dystroglycan.";
RL Nat. Genet. 44:581-585(2012).
CC -!- FUNCTION: Cytidylyltransferase required for protein O-linked
CC mannosylation (PubMed:22522421). Catalyzes the formation of CDP-ribitol
CC nucleotide sugar from D-ribitol 5-phosphate (By similarity). CDP-
CC ribitol is a substrate of FKTN during the biosynthesis of the
CC phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-
CC N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate
CC structure present in alpha-dystroglycan (DAG1), which is required for
CC binding laminin G-like domain-containing extracellular proteins with
CC high affinity (By similarity). Shows activity toward other pentose
CC phosphate sugars and mediates formation of CDP-ribulose or CDP-ribose
CC using CTP and ribulose-5-phosphate or ribose-5-phosphate, respectively
CC (By similarity). Not involved in dolichol production (By similarity).
CC {ECO:0000250|UniProtKB:A4D126, ECO:0000269|PubMed:22522421}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CTP + D-ribitol 5-phosphate + H(+) = CDP-L-ribitol +
CC diphosphate; Xref=Rhea:RHEA:12456, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:57608,
CC ChEBI:CHEBI:57695; EC=2.7.7.40;
CC Evidence={ECO:0000250|UniProtKB:A4D126};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CTP + D-ribose 5-phosphate + H(+) = CDP-D-ribose +
CC diphosphate; Xref=Rhea:RHEA:53872, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:78346,
CC ChEBI:CHEBI:137525; Evidence={ECO:0000250|UniProtKB:A4D126};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CTP + D-ribulose 5-phosphate + H(+) = CDP-D-ribulose +
CC diphosphate; Xref=Rhea:RHEA:53612, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:58121,
CC ChEBI:CHEBI:137524; Evidence={ECO:0000250|UniProtKB:A4D126};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:A4D126}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:A4D126}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:A4D126}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A0JPF9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0JPF9-2; Sequence=VSP_044045;
CC Name=3;
CC IsoId=A0JPF9-3; Sequence=VSP_044046;
CC -!- DISRUPTION PHENOTYPE: Hydrocephalus and incomplete brain folding by 48
CC hours post fertilization (h.p.f.), as well as significantly reduced eye
CC size reminiscent of microphthalmia in patients suffering of muscular
CC dystrophy-dystroglycanopathy congenital with brain and eye anomalies in
CC human. {ECO:0000269|PubMed:22522421}.
CC -!- SIMILARITY: Belongs to the IspD/TarI cytidylyltransferase family. IspD
CC subfamily. {ECO:0000305}.
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DR EMBL; BX470068; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP102309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC127405; AAI27406.1; -; mRNA.
DR RefSeq; NP_001071270.1; NM_001077802.1.
DR RefSeq; XP_005157821.1; XM_005157764.3. [A0JPF9-2]
DR AlphaFoldDB; A0JPF9; -.
DR SMR; A0JPF9; -.
DR STRING; 7955.ENSDARP00000118574; -.
DR PaxDb; A0JPF9; -.
DR PeptideAtlas; A0JPF9; -.
DR Ensembl; ENSDART00000003192; ENSDARP00000025837; ENSDARG00000005034. [A0JPF9-3]
DR Ensembl; ENSDART00000140882; ENSDARP00000118574; ENSDARG00000005034. [A0JPF9-2]
DR GeneID; 798716; -.
DR KEGG; dre:798716; -.
DR CTD; 729920; -.
DR ZFIN; ZDB-GENE-061110-16; crppa.
DR eggNOG; ENOG502QUUE; Eukaryota.
DR GeneTree; ENSGT00390000006412; -.
DR HOGENOM; CLU_033636_0_0_1; -.
DR InParanoid; A0JPF9; -.
DR OMA; LKEWNFI; -.
DR OrthoDB; 1356473at2759; -.
DR TreeFam; TF328415; -.
DR UniPathway; UPA00378; -.
DR PRO; PR:A0JPF9; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 15.
DR Bgee; ENSDARG00000005034; Expressed in testis and 26 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0070567; F:cytidylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0047349; F:D-ribitol-5-phosphate cytidylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0048854; P:brain morphogenesis; IMP:ZFIN.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR GO; GO:0035269; P:protein O-linked mannosylation; IMP:UniProtKB.
DR GO; GO:0060049; P:regulation of protein glycosylation; IMP:ZFIN.
DR CDD; cd02516; CDP-ME_synthetase; 1.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR034683; IspD/TarI.
DR InterPro; IPR040635; ISPD_C.
DR InterPro; IPR018294; ISPD_synthase_CS.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF01128; IspD; 1.
DR Pfam; PF18706; ISPD_C; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS01295; ISPD; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Nucleotidyltransferase;
KW Reference proteome; Transferase.
FT CHAIN 1..462
FT /note="D-ribitol-5-phosphate cytidylyltransferase"
FT /id="PRO_0000343700"
FT SITE 81
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q46893"
FT SITE 88
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q46893"
FT SITE 226
FT /note="Positions substrate for the nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:Q46893"
FT SITE 284
FT /note="Positions substrate for the nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:Q46893"
FT VAR_SEQ 1..40
FT /note="MGTVTIQLSCLRHIRKLCFSCPWEGRRLFKMLLQFHHETQ -> MNTAATNA
FT ELIETKEKMQQERCSSSD (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044045"
FT VAR_SEQ 1..30
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_044046"
FT CONFLICT 50
FT /note="P -> S (in Ref. 2; AAI27406)"
FT /evidence="ECO:0000305"
FT CONFLICT 57
FT /note="A -> G (in Ref. 2; AAI27406)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="V -> I (in Ref. 2; AAI27406)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="L -> S (in Ref. 2; AAI27406)"
FT /evidence="ECO:0000305"
FT CONFLICT 392
FT /note="M -> K (in Ref. 2; AAI27406)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 462 AA; 52064 MW; 1B09E78803C379CE CRC64;
MGTVTIQLSC LRHIRKLCFS CPWEGRRLFK MLLQFHHETQ RPLDPGCLLP QDAERSADQP
GRAVVDFPVA AVLPAGGSGE RMGLTTPKQF CSIFNRPLIS YTIQAFERLP WIVMVVVVVA
KDNHDLMLNI VRKFNHTKVK VVHGGTTRHR SIYNGLQAFS DSTDSSTPKP KVVIIHDAVR
PFVEEDLLLK ITLAAKEQGA SGAIRPLVST VIATTSESYL DHSLERAKYR ASEMPQGFLY
DIIFQAYQRC SEFDLEFGTE CLHLALQYCG TNARLIEGPP TLWKVTYKRD LAAAEAIIKE
TLSVSACIIA EAEEEAVELA KTLQKNLNMM ETDVIPCGKE SNVQYLSKTR NFIHISASAS
SSLWVLEMVK CFEDIDHARL YPVVIVWVQL SMTKQSADSQ ETDEFMALAS EVKQRNVLLY
GIKIDHSKEL EQWQRSLERL GQITLVLIRD RNMALTGQML HV
