N型糖鎖合成経路（２）
Alpha-1,3/1,6-mannosyltransferase ALG2
EC=2.4.1.132
EC=2.4.1.257
Alternative name(s):
Asparagine-linked glycosylation protein 2 homolog
GDP-Man:Man(1)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase
GDP-Man:Man(1)GlcNAc(2)-PP-dolichol mannosyltransferase
GDP-Man:Man(2)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase
Function
Mannosylates Man2GlcNAc(2)-dolichol diphosphate and Man1GlcNAc(2)-dolichol diphosphate to form Man3GlcNAc(2)-dolichol diphosphate. Ref.6
Catalytic activity
GDP-D-mannose + D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol = GDP + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-GlcNAc-diphosphodolichol.
GDP-D-mannose + D-Man-alpha-(1->3)-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol = GDP + D-Man-alpha-(1->3)-(D-Man-alpha-(1->6))-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol.
Pathway
Protein modification; protein glycosylation.
Subcellular location
Membrane; Single-pass membrane protein Potential.
Involvement in disease
Congenital disorder of glycosylation 1I (CDG1I) [MIM:607906]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Note: The disease is caused by mutations affecting the gene represented in this entry.
GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
EC=2.4.1.131
Alternative name(s):
Asparagine-linked glycosylation protein 11 homolog
Glycolipid 2-alpha-mannosyltransferase
Function
Mannosyltransferase involved in the last steps of the synthesis of Man5GlcNAc(2)-PP-dolichol core oligosaccharide on the cytoplasmic face of the endoplasmic reticulum. Catalyzes the addition of the 4th and 5th mannose residues to the dolichol-linked oligosaccharide chain. Ref.4
Catalytic activity
2 GDP-alpha-D-mannose + D-Man-alpha-(1->3)-(D-Man-alpha-(1->6))-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol = 2 GDP + D-Man-alpha-(1->2)-D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-(D-Man-alpha-(1->6))-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol. Ref.4
Subcellular location
Endoplasmic reticulum. Endoplasmic reticulum membrane; Multi-pass membrane protein Probable Ref.4.
Involvement in disease
Congenital disorder of glycosylation 1P (CDG1P) [MIM:613661]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.5
Sequence similarities
Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.
Dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase
EC=2.4.1.258
Alternative name(s):
Asparagine-linked glycosylation protein 3 homolog
Dol-P-Man-dependent alpha(1-3)-mannosyltransferase
Dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase
Dolichyl-phosphate-mannose--glycolipid alpha-mannosyltransferase
Not56-like protein
Function
Adds the first Dol-P-Man derived mannose in an alpha-1,3 linkage to Man5GlcNAc2-PP-Dol. Ref.5
Catalytic activity
Dolichyl beta-D-mannosyl phosphate + D-Man-alpha-(1->2)-D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-(D-Man-alpha-(1->6))-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol = D-Man-alpha-(1->2)-D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-(D-Man-alpha-(1->3)-D-Man-alpha-(1->6))-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol + dolichyl phosphate.
Pathway
Protein modification; protein glycosylation.
Subcellular location
Endoplasmic reticulum membrane; Multi-pass membrane protein Probable.
Involvement in disease
Congenital disorder of glycosylation 1D (CDG1D) [MIM:601110]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.10
Sequence similarities
Belongs to the glycosyltransferase 58 family.
Alpha-1,2-mannosyltransferase ALG9
EC=2.4.1.259
EC=2.4.1.261
Alternative name(s):
Asparagine-linked glycosylation protein 9 homolog
Disrupted in bipolar disorder protein 1
Dol-P-Man:Man(6)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
Dol-P-Man:Man(8)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase
Function
Catalyzes the transfer of mannose from Dol-P-Man to lipid-linked oligosaccharides. Ref.6 Ref.7
Catalytic activity
Dolichyl beta-D-mannosyl phosphate + D-Man-alpha-(1->2)-D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-(D-Man-alpha-(1->3)-D-Man-alpha-(1->6))-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol = D-Man-alpha-(1->2)-D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-(D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-D-Man-alpha-(1->6))-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol + dolichyl phosphate.
Dolichyl beta-D-mannosyl phosphate + D-Man-alpha-(1->2)-D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-(D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-(D-Man-alpha-(1->6))-D-Man-alpha-(1->6))-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol = D-Man-alpha-(1->2)-D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-[D-Man-alpha-(1->2)-D-Man-alpha-(1->3)-(D-Man-alpha-(1->2)-D-Man-alpha-(1->6))-D-Man-alpha-(1->6)]-D-Man-beta-(1->4)-D-GlcNAc-beta-(1->4)-D-GlcNAc-diphosphodolichol + dolichyl phosphate.
Pathway
Protein modification; protein glycosylation.
Subcellular location
Endoplasmic reticulum membrane; Multi-pass membrane protein Probable.
Tissue specificity
Ubiquitously expressed; with highest levels in heart, liver and pancreas. Ref.1
Involvement in disease
A chromosomal aberration involving ALG9 is found in a family with bipolar affective disorder. Translocation t(9;11)(p24;q23). However, common variations in ALG9 do not play a major role in predisposition to bipolar affective disorder.
Congenital disorder of glycosylation 1L (CDG1L) [MIM:608776]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7
Sequence similarities
Belongs to the glycosyltransferase 22 family.
