module: dmel_protein_o_glycosylation title: Protein O-glycosylation in Drosophila melanogaster label: Protein O-glycosylation module_type: BIOLOGICAL_PROCESS description: >- O-glycosylation attaches sugars to the hydroxyl groups of serine, threonine or hydroxylysine. Flies use several independent O-glycosylation pathways, each started by a dedicated transferase. Mucin-type O-GalNAc glycans are initiated by a family of polypeptide GalNAc transferases (Pgant) and extended by core 1 galactosyltransferase (C1GalTA) and glucuronyltransferase. EGF repeats of Notch and other receptors carry O-fucose added by Ofut1 and elongated by the GlcNAc transferase Fringe, and O-glucose added by Rumi and extended with xylose by Shams and Xxylt. Thrombospondin repeats are O-fucosylated by Ofut2. O-mannose glycans are added in the ER by the Rotated abdomen-Twisted (POMT1-POMT2) complex and, on cadherins, by the TMTC transferases. Nuclear and cytosolic proteins are modified by single O-GlcNAc residues by Super sex combs (OGT) and the modification is removed by O-GlcNAcase, while EGF repeats receive extracellular O-GlcNAc from Eogt. Collagen hydroxylysines are galactosylated after hydroxylation by Plod. summary: >- Independent pathways that initiate and extend O-GalNAc, O-fucose, O-glucose, O-mannose, O-GlcNAc and hydroxylysine-linked galactose glycans on proteins. concepts: - {id: GO:0006493, label: protein O-linked glycosylation} parts: - id: o_galnac label: Mucin-type O-GalNAc glycosylation role: O-GalNAc initiation and core 1 extension module_type: METABOLIC_PATHWAY parts: - id: galnac_initiation label: Polypeptide GalNAc transferases role: transfer of GalNAc to serine or threonine module_type: REACTION genes: [Pgant1, Pgant2, Pgant3, Pgant35A, Pgant4, Pgant5, Pgant6, Pgant7, Pgant8, Pgant9] function: {id: GO:0004653, label: polypeptide N-acetylgalactosaminyltransferase activity} processes: - {id: GO:0016266, label: protein O-linked glycosylation via N-acetylgalactosamine} - id: core1_galactosylation label: Core 1 galactosylation role: galactose addition to make the T antigen module_type: REACTION genes: [C1GalTA] function: {id: GO:0016263, label: "N-acetylgalactosaminide beta-1,3-galactosyltransferase activity"} - id: core1_glucuronylation label: Glucuronylation of core 1 role: glucuronic acid addition to core 1 module_type: REACTION genes: [GlcAT-P] connections: - source: galnac_initiation target: core1_galactosylation connection_type: PRECEDES description: GalNAc-Ser/Thr is the acceptor of core 1 galactosyltransferase. - source: core1_galactosylation target: core1_glucuronylation connection_type: PRECEDES description: Core 1 glycans can be capped with glucuronic acid. - id: o_fucose label: O-fucosylation role: O-fucose addition to EGF and TSR repeats and its extension module_type: METABOLIC_PATHWAY parts: - id: egf_o_fucosylation label: EGF-repeat O-fucosylation role: O-fucose addition to EGF repeats module_type: REACTION genes: [Ofut1] function: {id: GO:0046922, label: peptide-O-fucosyltransferase activity} processes: - {id: GO:0036066, label: protein O-linked glycosylation via fucose} - id: fringe_elongation label: Fringe elongation of O-fucose role: GlcNAc addition to O-fucose module_type: REACTION genes: [fng] function: {id: GO:0033829, label: O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity} - id: tsr_o_fucosylation label: TSR O-fucosylation role: O-fucose addition to thrombospondin type 1 repeats module_type: REACTION genes: [Ofut2] function: {id: GO:0046922, label: peptide-O-fucosyltransferase activity} processes: - {id: GO:0036066, label: protein O-linked glycosylation via fucose} connections: - source: egf_o_fucosylation target: fringe_elongation connection_type: PRECEDES description: Fringe extends O-fucose on EGF repeats with GlcNAc. - id: o_glucose label: O-glucosylation role: O-glucose addition to EGF repeats and its xylosylation module_type: METABOLIC_PATHWAY parts: - id: egf_o_glucosylation label: EGF-repeat O-glucosylation role: O-glucose addition to EGF repeats module_type: REACTION genes: [rumi] function: {id: GO:0140561, label: EGF-domain serine glucosyltransferase activity} processes: - {id: GO:0180059, label: protein O-linked glycosylation via glucose} - id: first_xylosylation label: First xylose addition role: xylose addition to O-glucose module_type: REACTION genes: [shams] function: {id: GO:0140563, label: "UDP-D-xylose:beta-D-glucoside alpha-1,3-D-xylosyltransferase activity"} - id: second_xylosylation label: Second xylose addition role: xylose addition to xylosyl-glucose module_type: REACTION genes: [Xxylt] function: {id: GO:0140560, label: "xylosyl alpha-1,3-xylosyltransferase activity"} connections: - source: egf_o_glucosylation target: first_xylosylation connection_type: PRECEDES description: Shams adds xylose to O-glucose. - source: first_xylosylation target: second_xylosylation connection_type: PRECEDES description: Xxylt adds a second xylose to make the trisaccharide. - id: o_mannose label: O-mannosylation role: O-mannose addition in the ER module_type: BIOLOGICAL_PROCESS variant_sets: - id: o_mannosyltransferases label: O-mannosyltransferase classes selection: ONE_OR_MORE variants: - id: pomt_complex label: Rotated abdomen-Twisted POMT complex module_type: PROTEIN_COMPLEX complex: true group: POMT1-2C complex_term: {id: GO:0031502, label: dolichyl-phosphate-mannose-protein mannosyltransferase complex} function: {id: GO:0004169, label: dolichyl-phosphate-mannose-protein mannosyltransferase activity} processes: - {id: GO:0035269, label: protein O-linked glycosylation via mannose} - id: tmtc_transferases label: TMTC O-mannosyltransferases module_type: REACTION genes: [Tmtc1, Tmtc2, Tmtc3, Tmtc4] processes: - {id: GO:0035269, label: protein O-linked glycosylation via mannose} - id: o_glcnac label: O-GlcNAc modification role: addition and removal of O-GlcNAc module_type: BIOLOGICAL_PROCESS parts: - id: intracellular_o_glcnac_transfer label: Intracellular O-GlcNAc transfer role: O-GlcNAc addition to nuclear and cytosolic proteins module_type: REACTION genes: [sxc] function: {id: GO:0097363, label: protein O-acetylglucosaminyltransferase activity} - id: o_glcnac_removal label: O-GlcNAc removal role: removal of O-GlcNAc module_type: REACTION genes: [Oga] function: {id: GO:0102571, label: "[protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine/L-threonine O-N-acetyl-alpha-D-glucosaminase activity"} - id: egf_o_glcnac_transfer label: Extracellular EGF-domain O-GlcNAc transfer role: O-GlcNAc addition to EGF repeats in the ER module_type: REACTION genes: [Eogt] function: {id: GO:0097363, label: protein O-acetylglucosaminyltransferase activity} connections: - source: intracellular_o_glcnac_transfer target: o_glcnac_removal connection_type: PRECEDES description: O-GlcNAc added by OGT is removed by O-GlcNAcase in a reversible cycle. - id: hydroxylysine_galactosylation label: Hydroxylysine O-galactosylation role: galactosylation of collagen hydroxylysine module_type: METABOLIC_PATHWAY parts: - id: lysine_hydroxylation label: Lysine hydroxylation role: hydroxylation of collagen lysines module_type: REACTION genes: [Plod] function: {id: GO:0008475, label: procollagen-lysine 5-dioxygenase activity} - id: hydroxylysine_galactosyl_transfer label: Galactose transfer to hydroxylysine role: galactose addition to hydroxylysine module_type: REACTION genes: [CG31915] function: {id: GO:0050211, label: procollagen galactosyltransferase activity} processes: - {id: GO:0180062, label: protein O-linked glycosylation via galactose} connections: - source: lysine_hydroxylation target: hydroxylysine_galactosyl_transfer connection_type: PRECEDES description: Hydroxylysine is the acceptor for galactose. notes: >- Boundary. FlyBase's protein O-glycosylation group also contains the chondroitin sulfate and heparan sulfate proteoglycan biosynthesis subgroups (GACSB, GAHSB), which are xylose-initiated O-glycans; they are modelled in the separate module dmel_glycosaminoglycan_biosynthesis and are excluded here. The POMT1-POMT2 complex group is realized as the POMT variant of the O-mannosylation part. The O-GalNAc, O-fucose, O-glucose and hydroxylysine branches are shown with their elongation steps in order; the different O-glycan classes are independent of one another. No molecular function is given to GlcAT-P in this branch (its glucuronyltransferase specificity on core 1 has been shown in vitro but the GO term for that acceptor is not established for this reaction) or to the TMTC transferases, whose O-mannosyltransferase activity in flies is inferred from their human orthologs. Plod is listed by FlyBase under O-galactosylation because lysine hydroxylation precedes galactose transfer; Plod itself is a hydroxylase. The intracellular O-GlcNAc cycle is a regulatory modification of nucleocytoplasmic proteins, distinct from the secretory-pathway glycans.