Hmdb loader
Identification
HMDB Protein ID HMDBP14173
Secondary Accession Numbers None
Name D-ribitol-5-phosphate cytidylyltransferase
Synonyms
  1. 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein
  2. Isoprenoid synthase domain-containing protein
  3. hISPD
Gene Name CRPPA
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Cytidylyltransferase required for protein O-linked mannosylation (PubMed:22522420, PubMed:27130732, PubMed:27601598, PubMed:26687144, PubMed:22522421, PubMed:26923585). Catalyzes the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate (PubMed:27130732, PubMed:26687144, PubMed:26923585). CDP-ribitol is a substrate of FKTN during the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:27130732, PubMed:26687144, PubMed:26923585). Shows activity toward other pentose phosphate sugars and mediates formation of CDP-ribulose or CDP-ribose using CTP and ribulose-5-phosphate or ribose-5-phosphate, respectively (PubMed:26687144). Not Involved in dolichol production (PubMed:26687144).
Pathways
  • Mannose type O-glycan biosynthesis
  • Pentose and glucuronate interconversions
  • protein glycosylation
Reactions Not Available
GO Classification
Biological Process
isoprenoid biosynthetic process
protein O-linked mannosylation
axon guidance
Cellular Component
cytosol
Molecular Function
cytidylyltransferase activity
D-ribitol-5-phosphate cytidylyltransferase activity
protein homodimerization activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 451
Molecular Weight 49872.16
Theoretical pI 6.25
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID A4D126
UniProtKB/Swiss-Prot Entry Name ISPD_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10. [PubMed:12690205 ]
  2. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed:12853948 ]
  3. Roscioli T, Kamsteeg EJ, Buysse K, Maystadt I, van Reeuwijk J, van den Elzen C, van Beusekom E, Riemersma M, Pfundt R, Vissers LE, Schraders M, Altunoglu U, Buckley MF, Brunner HG, Grisart B, Zhou H, Veltman JA, Gilissen C, Mancini GM, Delree P, Willemsen MA, Ramadza DP, Chitayat D, Bennett C, Sheridan E, Peeters EA, Tan-Sindhunata GM, de Die-Smulders CE, Devriendt K, Kayserili H, El-Hashash OA, Stemple DL, Lefeber DJ, Lin YY, van Bokhoven H: Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan. Nat Genet. 2012 May;44(5):581-5. doi: 10.1038/ng.2253. [PubMed:22522421 ]
  4. Willer T, Lee H, Lommel M, Yoshida-Moriguchi T, de Bernabe DB, Venzke D, Cirak S, Schachter H, Vajsar J, Voit T, Muntoni F, Loder AS, Dobyns WB, Winder TL, Strahl S, Mathews KD, Nelson SF, Moore SA, Campbell KP: ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome. Nat Genet. 2012 May;44(5):575-80. doi: 10.1038/ng.2252. [PubMed:22522420 ]
  5. Kanagawa M, Kobayashi K, Tajiri M, Manya H, Kuga A, Yamaguchi Y, Akasaka-Manya K, Furukawa JI, Mizuno M, Kawakami H, Shinohara Y, Wada Y, Endo T, Toda T: Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy. Cell Rep. 2016 Mar 8;14(9):2209-2223. doi: 10.1016/j.celrep.2016.02.017. Epub 2016 Feb 25. [PubMed:26923585 ]
  6. Praissman JL, Willer T, Sheikh MO, Toi A, Chitayat D, Lin YY, Lee H, Stalnaker SH, Wang S, Prabhakar PK, Nelson SF, Stemple DL, Moore SA, Moremen KW, Campbell KP, Wells L: The functional O-mannose glycan on alpha-dystroglycan contains a phospho-ribitol primed for matriglycan addition. Elife. 2016 Apr 29;5. doi: 10.7554/eLife.14473. [PubMed:27130732 ]
  7. Yagi H, Kuo CW, Obayashi T, Ninagawa S, Khoo KH, Kato K: Direct Mapping of Additional Modifications on Phosphorylated O-glycans of alpha-Dystroglycan by Mass Spectrometry Analysis in Conjunction with Knocking Out of Causative Genes for Dystroglycanopathy. Mol Cell Proteomics. 2016 Nov;15(11):3424-3434. doi: 10.1074/mcp.M116.062729. Epub 2016 Sep 6. [PubMed:27601598 ]
  8. Riemersma M, Froese DS, van Tol W, Engelke UF, Kopec J, van Scherpenzeel M, Ashikov A, Krojer T, von Delft F, Tessari M, Buczkowska A, Swiezewska E, Jae LT, Brummelkamp TR, Manya H, Endo T, van Bokhoven H, Yue WW, Lefeber DJ: Human ISPD Is a Cytidyltransferase Required for Dystroglycan O-Mannosylation. Chem Biol. 2015 Dec 17;22(12):1643-52. doi: 10.1016/j.chembiol.2015.10.014. Epub 2015 Dec 10. [PubMed:26687144 ]
  9. Vuillaumier-Barrot S, Bouchet-Seraphin C, Chelbi M, Devisme L, Quentin S, Gazal S, Laquerriere A, Fallet-Bianco C, Loget P, Odent S, Carles D, Bazin A, Aziza J, Clemenson A, Guimiot F, Bonniere M, Monnot S, Bole-Feysot C, Bernard JP, Loeuillet L, Gonzales M, Socha K, Grandchamp B, Attie-Bitach T, Encha-Razavi F, Seta N: Identification of mutations in TMEM5 and ISPD as a cause of severe cobblestone lissencephaly. Am J Hum Genet. 2012 Dec 7;91(6):1135-43. doi: 10.1016/j.ajhg.2012.10.009. [PubMed:23217329 ]
  10. Cirak S, Foley AR, Herrmann R, Willer T, Yau S, Stevens E, Torelli S, Brodd L, Kamynina A, Vondracek P, Roper H, Longman C, Korinthenberg R, Marrosu G, Nurnberg P, Michele DE, Plagnol V, Hurles M, Moore SA, Sewry CA, Campbell KP, Voit T, Muntoni F: ISPD gene mutations are a common cause of congenital and limb-girdle muscular dystrophies. Brain. 2013 Jan;136(Pt 1):269-81. doi: 10.1093/brain/aws312. Epub 2013 Jan 3. [PubMed:23288328 ]
  11. Czeschik JC, Hehr U, Hartmann B, Ludecke HJ, Rosenbaum T, Schweiger B, Wieczorek D: 160 kb deletion in ISPD unmasking a recessive mutation in a patient with Walker-Warburg syndrome. Eur J Med Genet. 2013 Dec;56(12):689-94. doi: 10.1016/j.ejmg.2013.09.014. Epub 2013 Oct 10. [PubMed:24120487 ]
  12. Tasca G, Moro F, Aiello C, Cassandrini D, Fiorillo C, Bertini E, Bruno C, Santorelli FM, Ricci E: Limb-girdle muscular dystrophy with alpha-dystroglycan deficiency and mutations in the ISPD gene. Neurology. 2013 Mar 5;80(10):963-5. doi: 10.1212/WNL.0b013e3182840cbc. Epub 2013 Feb 6. [PubMed:23390185 ]
  13. Fattahi Z, Kalhor Z, Fadaee M, Vazehan R, Parsimehr E, Abolhassani A, Beheshtian M, Zamani G, Nafissi S, Nilipour Y, Akbari MR, Kahrizi K, Kariminejad A, Najmabadi H: Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population. Clin Genet. 2017 Mar;91(3):386-402. doi: 10.1111/cge.12810. Epub 2016 Jul 21. [PubMed:27234031 ]