KEGG   PATHWAY: ko00563
Entry
ko00563                     Pathway                                
Name
Glycosylphosphatidylinositol (GPI)-anchor biosynthesis
Description
Cell surface proteins can be attached to the cell membrane via the glycolipid structure called glycosylphosphatidylinositol (GPI) anchor. Hundreds of GPI-anchored proteins have been identified in many eukaryotes ranging from protozoa and fungi to mammals. All protein-linked GPI anchors share a common core structure, characterized by the substructure Man (a1-4) GlcN (a1-6) myo-inositol-1P-lipid. Biosynthesis of GPI anchors proceeds in three stages: (i) preassembly of a GPI precursor in the ER membrane, (ii) attachment of the GPI to the C-terminus of a newly synthesized protein in the lumen of the ER, and (iii) lipid remodeling and/or carbohydrate side-chain modifications in the ER and the Golgi. Defects of GPI anchor biosynthesis gene result in a genetic disorder, paroxysmal nocturnal hemoglobinuria.
Class
Metabolism; Glycan biosynthesis and metabolism
Pathway map
ko00563  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis
ko00563

Module
M00065  GPI-anchor biosynthesis, core oligosaccharide [PATH:ko00563]
M00983  GPI-anchor remodeling [PATH:ko00563]
Drug
D11694  Fosmanogepix (USAN/INN)
Other DBs
GO: 0006506
Orthology
K00715  B3GALT4; ganglioside galactosyltransferase [EC:2.4.1.62]
K01127  GPLD1; glycosylphosphatidylinositol phospholipase D [EC:3.1.4.50]
K03434  PIGL; N-acetylglucosaminylphosphatidylinositol deacetylase [EC:3.5.1.89]
K03857  PIGA, GPI3; phosphatidylinositol N-acetylglucosaminyltransferase subunit A [EC:2.4.1.198]
K03858  PIGH, GPI15; phosphatidylinositol N-acetylglucosaminyltransferase subunit H
K03859  PIGC, GPI2; phosphatidylinositol N-acetylglucosaminyltransferase subunit C
K03860  PIGQ, GPI1; phosphatidylinositol N-acetylglucosaminyltransferase subunit Q
K03861  PIGP, GPI19, DSCR5; phosphatidylinositol N-acetylglucosaminyltransferase subunit P
K05283  PIGW; glucosaminylphosphatidylinositol acyltransferase [EC:2.3.-.-]
K05284  PIGM; GPI mannosyltransferase 1 subunit M [EC:2.4.1.-]
K05285  PIGN; GPI ethanolamine phosphate transferase 1 [EC:2.7.-.-]
K05286  PIGB; GPI mannosyltransferase 3 [EC:2.4.1.-]
K05287  PIGF; GPI ethanolamine phosphate transferase 2/3 subunit F
K05288  PIGO; GPI ethanolamine phosphate transferase 3 subunit O [EC:2.7.-.-]
K05289  GAA1; GPI-anchor transamidase subunit GAA1
K05290  PIGK; GPI-anchor transamidase subunit K
K05291  PIGS; GPI-anchor transamidase subunit S
K05292  PIGT; GPI-anchor transamidase subunit T
K05293  PIGU; GPI-anchor transamidase subunit U
K05294  PGAP1; GPI inositol-deacylase [EC:3.-.-.-]
K05310  PIGG, GPI7; ethanolamine phosphate transferase 2 subunit G [EC:2.7.-.-]
K07541  PIGX; GPI mannosyltransferase 1 subunit X
K07542  PIGV; GPI mannosyltransferase 2 [EC:2.4.1.-]
K08098  PIGZ, SMP3; GPI mannosyltransferase 4 [EC:2.4.1.-]
K09658  DPM2; dolichol phosphate-mannose biosynthesis regulatory protein
K11001  PIGY; phosphatidylinositol N-acetylglucosaminyltransferase subunit Y
K11002  ERI1; phosphatidylinositol N-acetylglucosaminyltransferase ERI1 subunit
K23362  MPPE1, PGAP5, CDC1; ethanolamine phosphate phosphodiesterase
K23552  PGAP2; post-GPI attachment to proteins factor 2
K23553  PGAP3, PER1; post-GPI attachment to proteins factor 3
K25162  GUP1_2; membrane-bound O-acyltransferase GUP1_2
K26235  PGAP4, TMEM246; post-GPI attachment to proteins factor 4
K27880  PGA1; GPI mannosyltransferase 2 subunit PGA1
K27881  CWH43; protein CWH43
K27886  CLPA; alpha1,3-mannosyltransferase
Compound
C00154  Palmitoyl-CoA
C00249  Hexadecanoic acid
C00346  Ethanolamine phosphate
C00350  Phosphatidylethanolamine
C00412  Stearoyl-CoA
C01194  1-Phosphatidyl-D-myo-inositol
C21932  Cerotoyl-CoA
C22963  C22963
C22964  C22964
C22965  C22965
C22966  C22966
C22967  C22967
C22968  C22968
C22970  C22970
C22971  C22971
C22972  C22972
G00140  
G00141  
G00142  
G00143  
G00144  
G00145  
G00146  
G00148  
G00149  
G00151  
G10610  UDP-N-acetyl-D-glucosamine
G10617  Dolichyl phosphate D-mannose
G12396  6-(alpha-D-glucosaminyl)-1D-myo-inositol
G13044  
G13046  
G13128  
G13150  
G13151  
G13152  
G13350  
G13351  
G13352  
G13353  
G13354  
G13355  
G13356  
G13357  
G13358  
G13359  
Reference
PMID:12655644
  Authors
Eisenhaber B, Maurer-Stroh S, Novatchkova M, Schneider G, Eisenhaber F.
  Title
Enzymes and auxiliary factors for GPI lipid anchor biosynthesis and post-translational transfer to proteins.
  Journal
Bioessays 25:367-85 (2003)
DOI:10.1002/bies.10254
Reference
PMID:11102867
  Authors
Kinoshita T, Inoue N.
  Title
Dissecting and manipulating the pathway for glycosylphos-phatidylinositol-anchor biosynthesis.
  Journal
Curr Opin Chem Biol 4:632-8 (2000)
DOI:10.1016/S1367-5931(00)00151-4
Reference
PMID:8253761
  Authors
Fankhauser C, Homans SW, Thomas-Oates JE, McConville MJ, Desponds C, Conzelmann A, Ferguson MA.
  Title
Structures of glycosylphosphatidylinositol membrane anchors from Saccharomyces cerevisiae.
  Journal
J Biol Chem 268:26365-74 (1993)
Reference
PMID:14517336
  Authors
Murakami Y, Siripanyapinyo U, Hong Y, Kang JY, Ishihara S, Nakakuma H, Maeda Y, Kinoshita T.
  Title
PIG-W is critical for inositol acylation but not for flipping of glycosylphosphatidylinositol-anchor.
  Journal
Mol Biol Cell 14:4285-95 (2003)
DOI:10.1091/mbc.E03-03-0193
Reference
PMID:10329735
  Authors
Benachour A, Sipos G, Flury I, Reggiori F, Canivenc-Gansel E, Vionnet C, Conzelmann A, Benghezal M.
  Title
Deletion of GPI7, a yeast gene required for addition of a side chain to the glycosylphosphatidylinositol (GPI) core structure, affects GPI protein transport, remodeling, and cell wall integrity.
  Journal
J Biol Chem 274:15251-61 (1999)
DOI:10.1074/jbc.274.21.15251
Reference
PMID:14734546
  Authors
Tanaka S, Maeda Y, Tashima Y, Kinoshita T.
  Title
Inositol deacylation of glycosylphosphatidylinositol-anchored proteins is mediated by mammalian PGAP1 and yeast Bst1p.
  Journal
J Biol Chem 279:14256-63 (2004)
DOI:10.1074/jbc.M313755200
Reference
PMID:12802054
  Authors
Hong Y, Ohishi K, Kang JY, Tanaka S, Inoue N, Nishimura J, Maeda Y, Kinoshita T.
  Title
Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins.
  Journal
Mol Biol Cell 14:1780-9 (2003)
DOI:10.1091/mbc.E02-12-0794
Reference
PMID:12807000
  Authors
Tanaka S, Maeda Y, Kinoshita T.
  Title
[Biosynthesis of GPI-anchored proteins]
  Journal
Tanpakushitsu Kakusan Koso 48:990-6 (2003)
Reference
PMID:15623507
  Authors
Kang JY, Hong Y, Ashida H, Shishioh N, Murakami Y, Morita YS, Maeda Y, Kinoshita T.
  Title
PIG-V involved in transferring the second mannose in glycosylphosphatidylinositol.
  Journal
J Biol Chem 280:9489-97 (2005)
DOI:10.1074/jbc.M413867200
Reference
PMID:15635094
  Authors
Ashida H, Hong Y, Murakami Y, Shishioh N, Sugimoto N, Kim YU, Maeda Y, Kinoshita T.
  Title
Mammalian PIG-X and yeast Pbn1p are the essential components of glycosylphosphatidylinositol-mannosyltransferase I.
  Journal
Mol Biol Cell 16:1439-48 (2005)
DOI:10.1091/mbc.E04-09-0802
Reference
PMID:24364251
  Authors
Fujita M
  Title
[Biosynthesis and remodeling of GPI-anchored proteins].
  Journal
Seikagaku 85:985-95 (2013)
Reference
PMID:25509331
  Authors
Kinoshita T
  Title
[Biochemistry of glycosylphosphatidylinositol (GPI) anchored proteins].
  Journal
Seikagaku 86:626-36 (2014)
Reference
PMID:19837036
  Authors
Fujita M, Maeda Y, Ra M, Yamaguchi Y, Taguchi R, Kinoshita T
  Title
GPI glycan remodeling by PGAP5 regulates transport of GPI-anchored proteins from the ER to the Golgi.
  Journal
Cell 139:352-65 (2009)
DOI:10.1016/j.cell.2009.08.040
Reference
PMID:26563290
  Authors
Kinoshita T, Fujita M
  Title
Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling.
  Journal
J Lipid Res 57:6-24 (2016)
DOI:10.1194/jlr.R063313
Reference
PMID:33112703
  Authors
Yang G, Banfield DK.
  Title
Cdc1p is a Golgi-localized glycosylphosphatidylinositol-anchored protein  remodelase.
  Journal
Mol Biol Cell 31:2883-2891 (2020)
DOI:10.1091/mbc.E20-08-0539
Reference
PMID:32156170
  Authors
Kinoshita T.
  Title
Biosynthesis and biology of mammalian GPI-anchored proteins.
  Journal
Open Biol 10:190290 (2020)
DOI:10.1098/rsob.190290
Related
pathway
ko00510  N-Glycan biosynthesis
ko00564  Glycerophospholipid metabolism

DBGET integrated database retrieval system