ENTRY       hsa00515                    Pathway
NAME        Mannose type O-glycan biosynthesis - Homo sapiens (human)
DESCRIPTION Biosynthesis of mammalian O-mannosyl glycans is initiated by the transfer of mannose from mannose-P-Dol to serine or threonine residue, followed by extensions with N-acetylglucosamine (GlcNAc) and galactose (Gal) to generate core M1, M2 and M3 glycans. Core M1 and M2 glycans can then be further attached by fucose residues, sialic acid terminals and sulfatded glucuroinc acid terminals. Core M3 glycan is involved in the synthesis of alpha-dystroglycan, a heavily glycosylated protein found in muscle and brain tissues. Core M3 glycan contains a tandem repeat of ribitol 5-phosphate (Rbo5P) and -alpha3-GlcA-beta3-Xyl- repeating structures. Defects of genes encoding core glycans and modified core M3 glycans are associated with various congenital diseases, such as muscular dystrophies caused by reduced O-mannosylation of alpha-dystroglycan in skeletal muscles [DS:H00120].
CLASS       Metabolism; Glycan biosynthesis and metabolism
PATHWAY_MAP hsa00515  Mannose type O-glycan biosynthesis
MODULE      hsa_M00872  O-glycan biosynthesis, mannose type (core M3) [PATH:hsa00515]
NETWORK     nt06013  O-Glycan biosynthesis
  ELEMENT   N00627  Mannose type O-glycan biosynthesis, POMT to POMK
            N00698  Mannose type O-glycan biosynthesis, Rib-ol-5P to CDP-Rib-ol
            N00699  Mannose type O-glycan biosynthesis, FKTN to LARGE
DBLINKS     GO: 0035269
ORGANISM    Homo sapiens (human) [GN:hsa]
GENE        10585  POMT1; protein O-mannosyltransferase 1 [KO:K00728] [EC:2.4.1.109]
            29954  POMT2; protein O-mannosyltransferase 2 [KO:K00728] [EC:2.4.1.109]
            55624  POMGNT1; protein O-linked mannose N-acetylglucosaminyltransferase 1 (beta 1,2-) [KO:K09666] [EC:2.4.1.-]
            2683  B4GALT1; beta-1,4-galactosyltransferase 1 [KO:K07966] [EC:2.4.1.22 2.4.1.90 2.4.1.38 2.4.1.-]
            8704  B4GALT2; beta-1,4-galactosyltransferase 2 [KO:K07967] [EC:2.4.1.22 2.4.1.90 2.4.1.38 2.4.1.-]
            8703  B4GALT3; beta-1,4-galactosyltransferase 3 [KO:K07968] [EC:2.4.1.90 2.4.1.38 2.4.1.-]
            6487  ST3GAL3; ST3 beta-galactoside alpha-2,3-sialyltransferase 3 [KO:K00781] [EC:2.4.3.6]
            27087  B3GAT1; beta-1,3-glucuronyltransferase 1 [KO:K00735] [EC:2.4.1.135]
            135152  B3GAT2; beta-1,3-glucuronyltransferase 2 [KO:K10157] [EC:2.4.1.135]
            9486  CHST10; carbohydrate sulfotransferase 10 [KO:K09674] [EC:2.8.2.-]
            10690  FUT9; fucosyltransferase 9 [KO:K03663] [EC:2.4.1.152]
            2526  FUT4; fucosyltransferase 4 [KO:K07632] [EC:2.4.1.-]
            146664  MGAT5B; alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B [KO:K09661] [EC:2.4.1.-]
            84892  POMGNT2; protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-) [KO:K18207] [EC:2.4.1.312]
            148789  B3GALNT2; beta-1,3-N-acetylgalactosaminyltransferase 2 [KO:K09654] [EC:2.4.1.313]
            84197  POMK; protein O-mannose kinase [KO:K17547] [EC:2.7.1.183]
            729920  CRPPA; CDP-L-ribitol pyrophosphorylase A [KO:K21031] [EC:2.7.7.40]
            2218  FKTN; fukutin [KO:K19872] [EC:2.7.8.-]
            79147  FKRP; fukutin related protein [KO:K19873] [EC:2.7.8.-]
            10329  RXYLT1; ribitol xylosyltransferase 1 [KO:K21052] [EC:2.4.2.61]
            11041  B4GAT1; beta-1,4-glucuronyltransferase 1 [KO:K21032] [EC:2.4.1.-]
            9215  LARGE1; LARGE xylosyl- and glucuronyltransferase 1 [KO:K09668] [EC:2.4.2.- 2.4.1.-]
            120071  LARGE2; LARGE xylosyl- and glucuronyltransferase 2 [KO:K09668] [EC:2.4.2.- 2.4.1.-]
COMPOUND    C00063  CTP
            C00789  CDP-ribitol
            C01068  D-Ribitol 5-phosphate
            C02189  [Protein]-L-serine
            G10617  Dolichyl phosphate D-mannose
            G13026
            G13027
            G13028
            G13082
            G13083
            G13084  O-Mannose core M1
            G13085
            G13086  O-Mannose core M2
            G13087
            G13088
            G13089
            G13090
            G13091  O-mannose core M3
            G13092  Phospho-core M3
            G13093
            G13094
            G13095
            G13096
            G13097
            G13098
            G13099
            G13100
REFERENCE   PMID:24786756
  AUTHORS   Praissman JL, Wells L
  TITLE     Mammalian O-mannosylation pathway: glycan structures, enzymes, and protein substrates.
  JOURNAL   Biochemistry 53:3066-78 (2014)
            DOI:10.1021/bi500153y
REFERENCE   PMID:21945038
  AUTHORS   Stalnaker SH, Stuart R, Wells L
  TITLE     Mammalian O-mannosylation: unsolved questions of structure/function.
  JOURNAL   Curr Opin Struct Biol 21:603-9 (2011)
            DOI:10.1016/j.sbi.2011.09.001
REFERENCE   PMID:26923585
  AUTHORS   Kanagawa M, Kobayashi K, Tajiri M, Manya H, Kuga A, Yamaguchi Y, Akasaka-Manya K, Furukawa J, Mizuno M, Kawakami H, Shinohara Y, Wada Y, Endo T, Toda T
  TITLE     Identification of a Post-translational Modification with Ribitol-Phosphate and Its Defect in Muscular Dystrophy.
  JOURNAL   Cell Rep 14:2209-23 (2016)
            DOI:10.1016/j.celrep.2016.02.017
REFERENCE   PMID:27733679
  AUTHORS   Manya H, Yamaguchi Y, Kanagawa M, Kobayashi K, Tajiri M, Akasaka-Manya K, Kawakami H, Mizuno M, Wada Y, Toda T, Endo T
  TITLE     The Muscular Dystrophy Gene TMEM5 Encodes a Ribitol beta1,4-Xylosyltransferase Required for the Functional Glycosylation of Dystroglycan.
  JOURNAL   J Biol Chem 291:24618-24627 (2016)
            DOI:10.1074/jbc.M116.751917
REL_PATHWAY hsa00510  N-Glycan biosynthesis
KO_PATHWAY  ko00515
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