N-Glycan biosynthesis - Homo sapiens (human)
N-glycans or asparagine-linked glycans are major constituents of glycoproteins in eukaryotes. N-glycans are covalently attached to asparagine with the consensus sequence of Asn-X-Ser/Thr by an N-glycosidic bond, GlcNAc b1- Asn. Biosynthesis of N-glycans begins on the cytoplasmic face of the ER membrane with the transferase reaction of UDP-GlcNAc and the lipid-like precursor P-Dol (dolichol phosphate) to generate GlcNAc a1- PP-Dol. After sequential addition of monosaccharides by ALG glycosyltransferases [MD:
], the N-glycan precursor is attached by the OST (oligosaccharyltransferase) complex to the polypeptide chain that is being synthesized and translocated through the ER membrane. The protein-bound N-glycan precursor is subsequently trimmed, extended, and modified in the ER and Golgi by a complex series of reactions catalyzed by membrane-bound glycosidases and glycosyltransferases. N-glycans thus synthesized are classified into three types: high-mannose type, complex type, and hybrid type. Defects in N-glycan biosynthesis lead to a variety of human diseases known as congenital disorders of glycosylation [DS:
Metabolism; Glycan biosynthesis and metabolism
Pathway map Ortholog table
N00653 N-Glycan precursor biosynthesis, ALG7 to ALG11
N00667 N-Glycan precursor biosynthesis, Glc-6P to Man-P-Dol
N00675 N-Glycan precursor biosynthesis, farnesy-PP to P-Dol
N00680 N-Glycan precursor biosynthesis, ALG3 to ALG9
N00681 N-Glycan precursor biosynthesis, ALG6 to OST
N00682 N-Glycan precursor biosynthesis, P-Dol to Glc-P-Dol
Homo sapiens (human) [GN:
1798 DPAGT1; dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 [KO: K01001] [EC: 18.104.22.168]
8813 DPM1; dolichyl-phosphate mannosyltransferase subunit 1, catalytic [KO: K00721] [EC: 22.214.171.124]
8818 DPM2; dolichyl-phosphate mannosyltransferase subunit 2, regulatory [KO: K09658]
54344 DPM3; dolichyl-phosphate mannosyltransferase subunit 3, regulatory [KO: K09659]
3703 STT3A; STT3 oligosaccharyltransferase complex catalytic subunit A [KO: K07151] [EC: 126.96.36.199]
1603 DAD1; defender against cell death 1 [KO: K12668]
1650 DDOST; dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit [KO: K12670]
7991 TUSC3; tumor suppressor candidate 3 [KO: K19478]
58505 OSTC; oligosaccharyltransferase complex non-catalytic subunit [KO: K26501]
746 TMEM258; transmembrane protein 258 [KO: K26502]
4245 MGAT1; alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase [KO: K00726] [EC: 188.8.131.52]
4247 MGAT2; alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase [KO: K00736] [EC: 184.108.40.206]
6480 ST6GAL1; ST6 beta-galactoside alpha-2,6-sialyltransferase 1 [KO: K00778] [EC: 220.127.116.11]
84620 ST6GAL2; ST6 beta-galactoside alpha-2,6-sialyltransferase 2 [KO: K00779] [EC: 18.104.22.168]
4248 MGAT3; beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase [KO: K00737] [EC: 22.214.171.124]
11320 MGAT4A; alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase A [KO: K00738] [EC: 126.96.36.199]
11282 MGAT4B; alpha-1,3-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase B [KO: K00738] [EC: 188.8.131.52]
4249 MGAT5; alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase [KO: K00744] [EC: 184.108.40.206]
146664 MGAT5B; alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B [KO: K09661] [EC:2.4.1.-]
C01246 Dolichyl beta-D-glucosyl phosphate
C03862 Dolichyl phosphate D-mannose
The role of the lipid matrix in the biosynthesis of dolichyl-linked oligosaccharides.
Oriol R, Martinez-Duncker I, Chantret I, Mollicone R, Codogno P.
Common origin and evolution of glycosyltransferases using Dol-P-monosaccharides as donor substrate.
Thiel C, Schwarz M, Peng J, Grzmil M, Hasilik M, Braulke T, Kohlschutter A, von Figura K, Lehle L, Korner C.
A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis.
Cipollo JF, Trimble RB, Chi JH, Yan Q, Dean N.
The yeast ALG11 gene specifies addition of the terminal alpha 1,2-Man to the Man5GlcNAc2-PP-dolichol N-glycosylation intermediate formed on the cytosolic side of the endoplasmic reticulum.
Frank CG, Aebi M.
ALG9 mannosyltransferase is involved in two different steps of lipid-linked oligosaccharide biosynthesis.
O'Reilly MK, Zhang G, Imperiali B.
In vitro evidence for the dual function of Alg2 and Alg11: essential mannosyltransferases in N-linked glycoprotein biosynthesis.
hsa00051 Fructose and mannose metabolism
hsa00513 Various types of N-glycan biosynthesis
hsa00515 Mannose type O-glycan biosynthesis
hsa00520 Amino sugar and nucleotide sugar metabolism
hsa00533 Glycosaminoglycan biosynthesis - keratan sulfate
hsa00563 Glycosylphosphatidylinositol (GPI)-anchor biosynthesis
hsa00900 Terpenoid backbone biosynthesis