ISPD_HUMAN
ID ISPD_HUMAN Reviewed; 451 AA.
AC A4D126; A8MU35; H9KVB2;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=D-ribitol-5-phosphate cytidylyltransferase {ECO:0000305};
DE EC=2.7.7.40 {ECO:0000269|PubMed:26687144, ECO:0000269|PubMed:26923585, ECO:0000269|PubMed:27130732};
DE AltName: Full=2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein;
DE AltName: Full=Isoprenoid synthase domain-containing protein {ECO:0000312|HGNC:HGNC:37276};
DE Short=hISPD {ECO:0000303|PubMed:26687144};
GN Name=CRPPA {ECO:0000312|HGNC:HGNC:37276};
GN Synonyms=ISPD {ECO:0000312|HGNC:HGNC:37276};
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=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [3]
RP FUNCTION, VARIANT MDDGA7 ILE-93 DEL, AND TISSUE SPECIFICITY.
RX PubMed=22522420; DOI=10.1038/ng.2252;
RA Willer T., Lee H., Lommel M., Yoshida-Moriguchi T., de Bernabe D.B.,
RA Venzke D., Cirak S., Schachter H., Vajsar J., Voit T., Muntoni F.,
RA Loder A.S., Dobyns W.B., Winder T.L., Strahl S., Mathews K.D., Nelson S.F.,
RA Moore S.A., Campbell K.P.;
RT "ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and
RT cause Walker-Warburg syndrome.";
RL Nat. Genet. 44:575-580(2012).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26923585; DOI=10.1016/j.celrep.2016.02.017;
RA Kanagawa M., Kobayashi K., Tajiri M., Manya H., Kuga A., Yamaguchi Y.,
RA Akasaka-Manya K., Furukawa J.I., Mizuno M., Kawakami H., Shinohara Y.,
RA Wada Y., Endo T., Toda T.;
RT "Identification of a Post-translational Modification with Ribitol-Phosphate
RT and Its Defect in Muscular Dystrophy.";
RL Cell Rep. 14:2209-2223(2016).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=27130732; DOI=10.7554/elife.14473;
RA Praissman J.L., Willer T., Sheikh M.O., Toi A., Chitayat D., Lin Y.Y.,
RA Lee H., Stalnaker S.H., Wang S., Prabhakar P.K., Nelson S.F., Stemple D.L.,
RA Moore S.A., Moremen K.W., Campbell K.P., Wells L.;
RT "The functional O-mannose glycan on alpha-dystroglycan contains a phospho-
RT ribitol primed for matriglycan addition.";
RL Elife 5:0-0(2016).
RN [6]
RP FUNCTION.
RX PubMed=27601598; DOI=10.1074/mcp.m116.062729;
RA Yagi H., Kuo C.W., Obayashi T., Ninagawa S., Khoo K.H., Kato K.;
RT "Direct mapping of additional modifications on phosphorylated O-glycans of
RT alpha-dystroglycan by mass spectrometry analysis in conjunction with
RT knocking out of causative genes for dystroglycanopathy.";
RL Mol. Cell. Proteomics 15:3424-3434(2016).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS) OF 43-451, FUNCTION, CATALYTIC
RP ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=26687144; DOI=10.1016/j.chembiol.2015.10.014;
RA Riemersma M., Froese D.S., van Tol W., Engelke U.F., Kopec J.,
RA van Scherpenzeel M., Ashikov A., Krojer T., von Delft F., Tessari M.,
RA Buczkowska A., Swiezewska E., Jae L.T., Brummelkamp T.R., Manya H.,
RA Endo T., van Bokhoven H., Yue W.W., Lefeber D.J.;
RT "Human ISPD is a cytidyltransferase required for dystroglycan O-
RT mannosylation.";
RL Chem. Biol. 22:1643-1652(2015).
RN [8]
RP VARIANTS MDDGA7 ASN-156; ARG-213; HIS-226 AND ILE-238.
RX PubMed=23217329; DOI=10.1016/j.ajhg.2012.10.009;
RA Vuillaumier-Barrot S., Bouchet-Seraphin C., Chelbi M., Devisme L.,
RA Quentin S., Gazal S., Laquerriere A., Fallet-Bianco C., Loget P., Odent S.,
RA Carles D., Bazin A., Aziza J., Clemenson A., Guimiot F., Bonniere M.,
RA Monnot S., Bole-Feysot C., Bernard J.P., Loeuillet L., Gonzales M.,
RA Socha K., Grandchamp B., Attie-Bitach T., Encha-Razavi F., Seta N.;
RT "Identification of mutations in TMEM5 and ISPD as a cause of severe
RT cobblestone lissencephaly.";
RL Am. J. Hum. Genet. 91:1135-1143(2012).
RN [9]
RP VARIANTS MDDGA7 PRO-122; HIS-126 AND ASP-216, AND FUNCTION.
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).
RN [10]
RP VARIANTS MDDGC7 THR-53; LEU-149; 215-GLN--ALA-451 DEL; CYS-226; VAL-372 DEL
RP AND 395-ARG--ALA-451 DEL, AND VARIANT MDDGA7 HIS-126.
RX PubMed=23288328; DOI=10.1093/brain/aws312;
RG UK10K Consortium;
RA Cirak S., Foley A.R., Herrmann R., Willer T., Yau S., Stevens E.,
RA Torelli S., Brodd L., Kamynina A., Vondracek P., Roper H., Longman C.,
RA Korinthenberg R., Marrosu G., Nuernberg P., Michele D.E., Plagnol V.,
RA Hurles M., Moore S.A., Sewry C.A., Campbell K.P., Voit T., Muntoni F.;
RT "ISPD gene mutations are a common cause of congenital and limb-girdle
RT muscular dystrophies.";
RL Brain 136:269-281(2013).
RN [11]
RP VARIANT MDDGA7 HIS-205.
RX PubMed=24120487; DOI=10.1016/j.ejmg.2013.09.014;
RA Czeschik J.C., Hehr U., Hartmann B., Luedecke H.J., Rosenbaum T.,
RA Schweiger B., Wieczorek D.;
RT "160 kb deletion in ISPD unmasking a recessive mutation in a patient with
RT Walker-Warburg syndrome.";
RL Eur. J. Med. Genet. 56:689-694(2013).
RN [12]
RP VARIANTS MDDGC7 ALA-54 AND VAL-372 DEL, INVOLVEMENT IN MDDGC7, AND
RP CHARACTERIZATION OF VARIANTS MDDGC7 ALA-54 AND VAL-372 DEL.
RX PubMed=23390185; DOI=10.1212/wnl.0b013e3182840cbc;
RA Tasca G., Moro F., Aiello C., Cassandrini D., Fiorillo C., Bertini E.,
RA Bruno C., Santorelli F.M., Ricci E.;
RT "Limb-girdle muscular dystrophy with alpha-dystroglycan deficiency and
RT mutations in the ISPD gene.";
RL Neurology 80:963-965(2013).
RN [13]
RP VARIANT MDDGC7 VAL-372 DEL.
RX PubMed=27234031; DOI=10.1111/cge.12810;
RA Fattahi Z., Kalhor Z., Fadaee M., Vazehan R., Parsimehr E., Abolhassani A.,
RA Beheshtian M., Zamani G., Nafissi S., Nilipour Y., Akbari M.R., Kahrizi K.,
RA Kariminejad A., Najmabadi H.;
RT "Improved diagnostic yield of neuromuscular disorders applying clinical
RT exome sequencing in patients arising from a consanguineous population.";
RL Clin. Genet. 91:386-402(2017).
CC -!- FUNCTION: Cytidylyltransferase required for protein O-linked
CC mannosylation (PubMed:22522420, PubMed:27130732, PubMed:27601598,
CC PubMed:26687144, PubMed:22522421, PubMed:26923585). Catalyzes the
CC formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate
CC (PubMed:27130732, PubMed:26687144, PubMed:26923585). CDP-ribitol is a
CC substrate of FKTN during the biosynthesis of the phosphorylated O-
CC mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-
CC 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 (PubMed:27130732, PubMed:26687144, PubMed:26923585).
CC Shows activity toward other pentose phosphate sugars and mediates
CC formation of CDP-ribulose or CDP-ribose using CTP and ribulose-5-
CC phosphate or ribose-5-phosphate, respectively (PubMed:26687144). Not
CC Involved in dolichol production (PubMed:26687144).
CC {ECO:0000269|PubMed:22522420, ECO:0000269|PubMed:22522421,
CC ECO:0000269|PubMed:26687144, ECO:0000269|PubMed:26923585,
CC ECO:0000269|PubMed:27130732, ECO:0000269|PubMed:27601598}.
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:0000269|PubMed:26687144, ECO:0000269|PubMed:26923585,
CC ECO:0000269|PubMed:27130732};
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:0000269|PubMed:26687144,
CC ECO:0000269|PubMed:27130732};
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:0000269|PubMed:26687144};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:26687144, ECO:0000269|PubMed:26923585,
CC ECO:0000269|PubMed:27130732}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:26687144}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:26687144}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A4D126-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A4D126-2; Sequence=VSP_044044;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with high expression in
CC brain. {ECO:0000269|PubMed:22522420}.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain
CC and eye anomalies A7 (MDDGA7) [MIM:614643]: An autosomal recessive
CC disorder characterized by congenital muscular dystrophy associated with
CC cobblestone lissencephaly and other brain anomalies, eye malformations,
CC profound intellectual disability, and death usually in the first years
CC of life. Included diseases are the more severe Walker-Warburg syndrome
CC and the slightly less severe muscle-eye-brain disease.
CC {ECO:0000269|PubMed:22522420, ECO:0000269|PubMed:22522421,
CC ECO:0000269|PubMed:23217329, ECO:0000269|PubMed:23288328,
CC ECO:0000269|PubMed:24120487}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C7 (MDDGC7)
CC [MIM:616052]: A form of muscular dystrophy resulting from defective
CC glycosylation of alpha-dystroglycan, and characterized by a limb-girdle
CC phenotype with muscular weakness apparent after ambulation is achieved.
CC MDDGC7 individuals do not show epilepsy, intellectual disability,
CC structural eye/brain abnormalities, or white matter changes.
CC {ECO:0000269|PubMed:23288328, ECO:0000269|PubMed:23390185,
CC ECO:0000269|PubMed:27234031}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the IspD/TarI cytidylyltransferase family. IspD
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAL24288.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AC004741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073629; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079155; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236948; EAL24288.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471073; EAW93668.1; -; Genomic_DNA.
DR RefSeq; NP_001094887.1; NM_001101417.3. [A4D126-2]
DR RefSeq; NP_001094896.1; NM_001101426.3. [A4D126-1]
DR PDB; 4CVH; X-ray; 2.39 A; A=43-451.
DR PDBsum; 4CVH; -.
DR AlphaFoldDB; A4D126; -.
DR SMR; A4D126; -.
DR BioGRID; 610311; 1.
DR IntAct; A4D126; 2.
DR STRING; 9606.ENSP00000385478; -.
DR iPTMnet; A4D126; -.
DR PhosphoSitePlus; A4D126; -.
DR BioMuta; ISPD; -.
DR MassIVE; A4D126; -.
DR PaxDb; A4D126; -.
DR PeptideAtlas; A4D126; -.
DR PRIDE; A4D126; -.
DR ProteomicsDB; 602; -. [A4D126-1]
DR ProteomicsDB; 603; -. [A4D126-2]
DR Antibodypedia; 43951; 103 antibodies from 15 providers.
DR DNASU; 729920; -.
DR Ensembl; ENST00000399310.3; ENSP00000382249.3; ENSG00000214960.11. [A4D126-2]
DR Ensembl; ENST00000407010.7; ENSP00000385478.2; ENSG00000214960.11. [A4D126-1]
DR GeneID; 729920; -.
DR KEGG; hsa:729920; -.
DR MANE-Select; ENST00000407010.7; ENSP00000385478.2; NM_001101426.4; NP_001094896.1.
DR UCSC; uc010ktx.2; human. [A4D126-1]
DR CTD; 729920; -.
DR DisGeNET; 729920; -.
DR GeneCards; CRPPA; -.
DR HGNC; HGNC:37276; CRPPA.
DR HPA; ENSG00000214960; Tissue enriched (choroid).
DR MalaCards; CRPPA; -.
DR MIM; 614631; gene.
DR MIM; 614643; phenotype.
DR MIM; 616052; phenotype.
DR neXtProt; NX_A4D126; -.
DR OpenTargets; ENSG00000214960; -.
DR Orphanet; 370980; Congenital muscular dystrophy without intellectual disability.
DR Orphanet; 352479; ISPD-related limb-girdle muscular dystrophy R20.
DR Orphanet; 899; Walker-Warburg syndrome.
DR PharmGKB; PA165618128; -.
DR VEuPathDB; HostDB:ENSG00000214960; -.
DR eggNOG; ENOG502QUUE; Eukaryota.
DR GeneTree; ENSGT00390000006412; -.
DR HOGENOM; CLU_033636_0_0_1; -.
DR InParanoid; A4D126; -.
DR OMA; LKEWNFI; -.
DR OrthoDB; 1356473at2759; -.
DR PhylomeDB; A4D126; -.
DR TreeFam; TF328415; -.
DR BioCyc; MetaCyc:MON66-43822; -.
DR BRENDA; 2.7.7.40; 2681.
DR PathwayCommons; A4D126; -.
DR SignaLink; A4D126; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 729920; 5 hits in 244 CRISPR screens.
DR ChiTaRS; ISPD; human.
DR GenomeRNAi; 729920; -.
DR Pharos; A4D126; Tbio.
DR PRO; PR:A4D126; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; A4D126; protein.
DR Bgee; ENSG00000214960; Expressed in corpus callosum and 111 other tissues.
DR ExpressionAtlas; A4D126; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070567; F:cytidylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0047349; F:D-ribitol-5-phosphate cytidylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR GO; GO:0035269; P:protein O-linked mannosylation; IMP:UniProtKB.
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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Congenital muscular dystrophy;
KW Cytoplasm; Disease variant; Dystroglycanopathy;
KW Limb-girdle muscular dystrophy; Lissencephaly; Nucleotidyltransferase;
KW Reference proteome; Transferase.
FT CHAIN 1..451
FT /note="D-ribitol-5-phosphate cytidylyltransferase"
FT /id="PRO_0000343697"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 59
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q46893"
FT SITE 66
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q46893"
FT SITE 205
FT /note="Positions substrate for the nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:Q46893"
FT SITE 263
FT /note="Positions substrate for the nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:Q46893"
FT VAR_SEQ 179..228
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_044044"
FT VARIANT 53
FT /note="A -> T (in MDDGC7)"
FT /evidence="ECO:0000269|PubMed:23288328"
FT /id="VAR_078970"
FT VARIANT 54
FT /note="G -> A (in MDDGC7; decreased alpha-dystroglycan
FT glycosylation; dbSNP:rs587777797)"
FT /evidence="ECO:0000269|PubMed:23390185"
FT /id="VAR_071955"
FT VARIANT 93
FT /note="Missing (in MDDGA7; dbSNP:rs397515398)"
FT /evidence="ECO:0000269|PubMed:22522420"
FT /id="VAR_069740"
FT VARIANT 122
FT /note="A -> P (in MDDGA7; dbSNP:rs387907162)"
FT /evidence="ECO:0000269|PubMed:22522421"
FT /id="VAR_068101"
FT VARIANT 126
FT /note="R -> H (in MDDGA7; also found in a patient with an
FT atypical phenotype presenting with limb-girdle muscular
FT dystrophy, ocular features and cerebellar involvement;
FT dbSNP:rs752817129)"
FT /evidence="ECO:0000269|PubMed:22522421,
FT ECO:0000269|PubMed:23288328"
FT /id="VAR_068102"
FT VARIANT 149
FT /note="P -> L (in MDDGC7; atypical form presenting with
FT congenital muscular dystrophy; dbSNP:rs369219851)"
FT /evidence="ECO:0000269|PubMed:23288328"
FT /id="VAR_078948"
FT VARIANT 156
FT /note="D -> N (in MDDGA7; dbSNP:rs397514547)"
FT /evidence="ECO:0000269|PubMed:23217329"
FT /id="VAR_069741"
FT VARIANT 205
FT /note="R -> H (in MDDGA7; dbSNP:rs566179705)"
FT /evidence="ECO:0000269|PubMed:24120487"
FT /id="VAR_078949"
FT VARIANT 213
FT /note="M -> R (in MDDGA7; dbSNP:rs397515408)"
FT /evidence="ECO:0000269|PubMed:23217329"
FT /id="VAR_069742"
FT VARIANT 215..451
FT /note="Missing (in MDDGC7; atypical form presenting with
FT congenital muscular dystrophy)"
FT /evidence="ECO:0000269|PubMed:23288328"
FT /id="VAR_078950"
FT VARIANT 216
FT /note="A -> D (in MDDGA7; dbSNP:rs387907160)"
FT /evidence="ECO:0000269|PubMed:22522421"
FT /id="VAR_068103"
FT VARIANT 226
FT /note="Y -> C (in MDDGC7; atypical form with learning
FT difficulties; dbSNP:rs1289931198)"
FT /evidence="ECO:0000269|PubMed:23288328"
FT /id="VAR_078951"
FT VARIANT 226
FT /note="Y -> H (in MDDGA7; dbSNP:rs1282788711)"
FT /evidence="ECO:0000269|PubMed:23217329"
FT /id="VAR_069743"
FT VARIANT 238
FT /note="T -> I (in MDDGA7; dbSNP:rs397515409)"
FT /evidence="ECO:0000269|PubMed:23217329"
FT /id="VAR_069744"
FT VARIANT 372
FT /note="Missing (in MDDGC7; decreased alpha-dystroglycan
FT glycosylation; dbSNP:rs587777798)"
FT /evidence="ECO:0000269|PubMed:23288328,
FT ECO:0000269|PubMed:23390185, ECO:0000269|PubMed:27234031"
FT /id="VAR_071956"
FT VARIANT 395..451
FT /note="Missing (in MDDGC7)"
FT /evidence="ECO:0000269|PubMed:23288328"
FT /id="VAR_078952"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 76..85
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 102..112
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 126..137
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 164..177
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 178..185
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 209..218
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 231..236
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 240..248
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 267..280
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 293..309
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 314..319
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 337..344
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 349..360
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 369..377
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 385..391
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 394..402
FT /evidence="ECO:0007829|PDB:4CVH"
FT TURN 403..405
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 406..414
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 419..439
FT /evidence="ECO:0007829|PDB:4CVH"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:4CVH"
FT STRAND 448..450
FT /evidence="ECO:0007829|PDB:4CVH"
SQ SEQUENCE 451 AA; 49873 MW; 988B9D1CFE98935C CRC64;
MEAGPPGSAR PAEPGPCLSG QRGADHTASA SLQSVAGTEP GRHPQAVAAV LPAGGCGERM
GVPTPKQFCP ILERPLISYT LQALERVCWI KDIVVAVTGE NMEVMKSIIQ KYQHKRISLV
EAGVTRHRSI FNGLKALAED QINSKLSKPE VVIIHDAVRP FVEEGVLLKV VTAAKEHGAA
GAIRPLVSTV VSPSADGCLD YSLERARHRA SEMPQAFLFD VIYEAYQQCS DYDLEFGTEC
LQLALKYCCT KAKLVEGSPD LWKVTYKRDL YAAESIIKER ISQEICVVMD TEEDNKHVGH
LLEEVLKSEL NHVKVTSEAL GHAGRHLQQI ILDQCYNFVC VNVTTSDFQE TQKLLSMLEE
SSLCILYPVV VVSVHFLDFK LVPPSQKMEN LMQIREFAKE VKERNILLYG LLISYPQDDQ
KLQESLRQGA IIIASLIKER NSGLIGQLLI A