KEGG   PATHWAY: hsa00515Help
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
BRITE hierarchy
Pathway map
hsa00515  Mannose type O-glycan biosynthesis
hsa00515

Ortholog table
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
N00628  LARGE1 deficiency in mannose type O-glycan biosynthesis
N00629  B4GAT1 deficiency in mannose type O-glycan biosynthesis
N00630  TMEM5 deficiency in mannose type O-glycan biosynthesis
N00631  FKRP deficiency in mannose type O-glycan biosynthesis
N00632  FKTN deficiency in mannose type O-glycan biosynthesis
N00633  POMK deficiency in mannose type O-glycan biosynthesis
N00634  ISPD deficiency in mannose type O-glycan biosynthesis
N00635  B3GALNT2 deficiency in mannose type O-glycan biosynthesis
N00636  POMGNT2 deficiency in mannose type O-glycan biosynthesis
N00637  POMT1 deficiency in mannose type O-glycan biosynthesis
N00638  POMT2 deficiency in mannose type O-glycan biosynthesis
N00639  POMGNT1 deficiency in mannose type O-glycan biosynthesis
N00698  Mannose type O-glycan biosynthesis, Rib-ol-5P to CDP-Rib-ol
N00699  Mannose type O-glycan biosynthesis, FKTN to LARGE
Disease
H00120  Muscular dystrophy-dystroglycanopathy type A
H00593  Limb-girdle muscular dystrophy
H01957  Fukuyama congenital muscular dystrophy
H01959  Muscular dystrophy-dystroglycanopathy type C
H01960  Muscular dystrophy-dystroglycanopathy type B
H01961  Congenital muscular dystrophy type 1C
H01962  Congenital muscular dystrophy type 1D
H02307  Muscular dystrophy-dystroglycanopathy
Other DBs
GO: 0006493
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.- 2.4.1.38 2.4.1.90 2.4.1.22]
8704  B4GALT2; beta-1,4-galactosyltransferase 2 [KO:K07967] [EC:2.4.1.- 2.4.1.38 2.4.1.90 2.4.1.22]
8703  B4GALT3; beta-1,4-galactosyltransferase 3 [KO:K07968] [EC:2.4.1.- 2.4.1.38 2.4.1.90]
6487  ST3GAL3; ST3 beta-galactoside alpha-2,3-sialyltransferase 3 [KO:K00781] [EC:2.4.99.6]
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:2.4.1.- 2.4.2.-]
120071  LARGE2; LARGE xylosyl- and glucuronyltransferase 2 [KO:K09668] [EC:2.4.1.- 2.4.2.-]
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
  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
  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
  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
  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
KO pathway
ko00515   

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