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 24-JAN-2024, entry version 113. 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}; 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; 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; 9606-ENSP00000385478; -. DR PeptideAtlas; A4D126; -. DR ProteomicsDB; 602; -. [A4D126-1] DR ProteomicsDB; 603; -. [A4D126-2] DR Pumba; A4D126; -. DR Antibodypedia; 43951; 109 antibodies from 16 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 AGR; HGNC:37276; -. DR CTD; 729920; -. DR DisGeNET; 729920; -. DR GeneCards; CRPPA; -. DR HGNC; HGNC:37276; CRPPA. DR HPA; ENSG00000214960; Tissue enhanced (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; 588; Muscle-eye-brain disease. 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; 5405361at2759; -. DR PhylomeDB; A4D126; -. DR TreeFam; TF328415; -. DR BioCyc; MetaCyc:MONOMER66-43822; -. DR BRENDA; 2.7.7.40; 2681. DR PathwayCommons; A4D126; -. DR SignaLink; A4D126; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 729920; 6 hits in 300 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 112 other cell types or 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 InterPro; IPR034683; IspD/TarI. DR InterPro; IPR040635; ISPD_C. DR InterPro; IPR018294; ISPD_synthase_CS. DR InterPro; IPR029044; Nucleotide-diphossugar_trans. DR PANTHER; PTHR43015; D-RIBITOL-5-PHOSPHATE CYTIDYLYLTRANSFERASE; 1. DR PANTHER; PTHR43015:SF1; D-RIBITOL-5-PHOSPHATE CYTIDYLYLTRANSFERASE; 1. DR Pfam; PF01128; IspD; 1. DR Pfam; PF18706; ISPD_C; 1. DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 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 //