Post-translational modification: synthesis of GPI-anchored proteins (Homo sapiens)

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94111421, 3, 81013, 157, 17, 186, 165, 124cytosolendoplasmic reticulum lumenSMP3Fatty acyl CoA(ethanolamineP) mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PIlong-chain fatty acid(ethanolamineP) mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PIurokinase plasminogen activator receptor precursorurokinase plasminogen activator receptor precursor propeptidedolichyl phosphate D-mannoseDiacylglycerolglucosaminyl-acyl-PIAcetateurokinase plasminogen activator receptorH2Odolichyl phosphate D-mannosemannose (a1) mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PIphosphatidylethanolaminePIG-F:GPI7 complexphosphatidylethanolaminedolichyl phosphatemannose (a1-4) glucosaminyl-acyl-PIN-acetylglucosaminyl-PI(ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PIGPI transamidaseglucosaminyl-PIPost GPI Attachment to Proteins 1GPI mannosyltransferase IPIG-LH2Odolichyl phosphate D-mannoseDiacylglycerolphosphatidylinositolPIG-WGDP-alpha-D-mannosePIG-BPIG-Vurokinase plasminogen activator receptor-acyl-GPImannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PIdolichyl-phosphate mannosyltransferaseuridine 5'-diphosphatemannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PIPIG-Ndolichyl phosphateUDP-N-acetyl-D-glucosaminedolichyl phosphate D-mannosemannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PIGPI-N-acetylglucosaminyltransferaseCoA-SHPIG-F:PIG-O complex


Description

Glycosylphosphatidyl inositol (GPI) acts as a membrane anchor for many cell surface proteins. GPI is synthesized in the endoplasmic reticulum. In humans, a single pathway consisting of eleven reactions appears to be responsible for the synthesis of the major GPI species involved in membrane protein anchoring.

As a nascent protein fated to become GPI-anchored moves into the lumen of the endoplasmic reticulum, it is attacked by a transamidase complex that cleaves it near its carboxy terminus and attaches an acylated GPI moiety. The GPI moiety is deacylated, yielding a protein-GPI conjugate that can be efficiently transported to the Golgi apparatus.</div>

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Ontology Terms

 

Bibliography

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  1. Taron BW, Colussi PA, Wiedman JM, Orlean P, Taron CH.; ''Human Smp3p adds a fourth mannose to yeast and human glycosylphosphatidylinositol precursors in vivo.''; PubMed Europe PMC Scholia
  2. Watanabe R, Kinoshita T, Masaki R, Yamamoto A, Takeda J, Inoue N.; ''PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum.''; PubMed Europe PMC Scholia
  3. Schofield JN, Rademacher TW.; ''Structure and expression of the human glycosylphosphatidylinositol phospholipase D1 (GPLD1) gene.''; PubMed Europe PMC Scholia
  4. Murakami Y, Siripanyaphinyo U, Hong Y, Tashima Y, Maeda Y, Kinoshita T.; ''The initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-Y, a seventh component.''; PubMed Europe PMC Scholia
  5. Takahashi M, Inoue N, Ohishi K, Maeda Y, Nakamura N, Endo Y, Fujita T, Takeda J, Kinoshita T.; ''PIG-B, a membrane protein of the endoplasmic reticulum with a large lumenal domain, is involved in transferring the third mannose of the GPI anchor.''; PubMed Europe PMC Scholia
  6. Kang JY, Hong Y, Ashida H, Shishioh N, Murakami Y, Morita YS, Maeda Y, Kinoshita T.; ''PIG-V involved in transferring the second mannose in glycosylphosphatidylinositol.''; PubMed Europe PMC Scholia
  7. Maeda Y, Tanaka S, Hino J, Kangawa K, Kinoshita T.; ''Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3.''; PubMed Europe PMC Scholia
  8. Watanabe R, Murakami Y, Marmor MD, Inoue N, Maeda Y, Hino J, Kangawa K, Julius M, Kinoshita T.; ''Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2.''; PubMed Europe PMC Scholia
  9. Pottekat A, Menon AK.; ''Subcellular localization and targeting of N-acetylglucosaminyl phosphatidylinositol de-N-acetylase, the second enzyme in the glycosylphosphatidylinositol biosynthetic pathway.''; PubMed Europe PMC Scholia
  10. Murakami Y, Siripanyapinyo U, Hong Y, Kang JY, Ishihara S, Nakakuma H, Maeda Y, Kinoshita T.; ''PIG-W is critical for inositol acylation but not for flipping of glycosylphosphatidylinositol-anchor.''; PubMed Europe PMC Scholia
  11. Davitz MA, Hereld D, Shak S, Krakow J, Englund PT, Nussenzweig V.; ''A glycan-phosphatidylinositol-specific phospholipase D in human serum.''; PubMed Europe PMC Scholia
  12. Fabre AL, Orlean P, Taron CH.; ''Saccharomyces cerevisiae Ybr004c and its human homologue are required for addition of the second mannose during glycosylphosphatidylinositol precursor assembly.''; PubMed Europe PMC Scholia
  13. Shishioh N, Hong Y, Ohishi K, Ashida H, Maeda Y, Kinoshita T.; ''GPI7 is the second partner of PIG-F and involved in modification of glycosylphosphatidylinositol.''; PubMed Europe PMC Scholia
  14. Low MG, Prasad AR.; ''A phospholipase D specific for the phosphatidylinositol anchor of cell-surface proteins is abundant in plasma.''; PubMed Europe PMC Scholia
  15. Hong Y, Ohishi K, Kang JY, Tanaka S, Inoue N, Nishimura J, Maeda Y, Kinoshita T.; ''Human PIG-U and yeast Cdc91p are the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins.''; PubMed Europe PMC Scholia
  16. Ohishi K, Inoue N, Kinoshita T.; ''PIG-S and PIG-T, essential for GPI anchor attachment to proteins, form a complex with GAA1 and GPI8.''; PubMed Europe PMC Scholia
  17. Ashida H, Hong Y, Murakami Y, Shishioh N, Sugimoto N, Kim YU, Maeda Y, Kinoshita T.; ''Mammalian PIG-X and yeast Pbn1p are the essential components of glycosylphosphatidylinositol-mannosyltransferase I.''; PubMed Europe PMC Scholia
  18. Sharma DK, Smith TK, Weller CT, Crossman A, Brimacombe JS, Ferguson MA.; ''Differences between the trypanosomal and human GlcNAc-PI de-N-acetylases of glycosylphosphatidylinositol membrane anchor biosynthesis.''; PubMed Europe PMC Scholia
  19. Kinoshita T, Inoue N.; ''Dissecting and manipulating the pathway for glycosylphos-phatidylinositol-anchor biosynthesis.''; PubMed Europe PMC Scholia
  20. Watanabe R, Inoue N, Westfall B, Taron CH, Orlean P, Takeda J, Kinoshita T.; ''The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPI1.''; PubMed Europe PMC Scholia
  21. Maeda Y, Watanabe R, Harris CL, Hong Y, Ohishi K, Kinoshita K, Kinoshita T.; ''PIG-M transfers the first mannose to glycosylphosphatidylinositol on the lumenal side of the ER.''; PubMed Europe PMC Scholia
  22. Yu J, Nagarajan S, Knez JJ, Udenfriend S, Chen R, Medof ME.; ''The affected gene underlying the class K glycosylphosphatidylinositol (GPI) surface protein defect codes for the GPI transamidase.''; PubMed Europe PMC Scholia
  23. Gaynor EC, Mondésert G, Grimme SJ, Reed SI, Orlean P, Emr SD.; ''MCD4 encodes a conserved endoplasmic reticulum membrane protein essential for glycosylphosphatidylinositol anchor synthesis in yeast.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114905view16:42, 25 January 2021ReactomeTeamReactome version 75
113350view11:42, 2 November 2020ReactomeTeamReactome version 74
112559view15:52, 9 October 2020ReactomeTeamReactome version 73
101472view11:33, 1 November 2018ReactomeTeamreactome version 66
101010view21:13, 31 October 2018ReactomeTeamreactome version 65
100546view19:47, 31 October 2018ReactomeTeamreactome version 64
100094view16:32, 31 October 2018ReactomeTeamreactome version 63
99644view15:03, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99246view12:44, 31 October 2018ReactomeTeamreactome version 62
93983view13:49, 16 August 2017ReactomeTeamreactome version 61
93587view11:28, 9 August 2017ReactomeTeamreactome version 61
88102view09:33, 26 July 2016RyanmillerOntology Term : 'peptide and protein metabolic process' added !
88101view09:31, 26 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
86827view08:17, 12 July 2016MaintBotCHEBI:53058 is a Metabolite in ChEBI (which partially defined structure)
86695view09:24, 11 July 2016ReactomeTeamreactome version 56
83233view10:26, 18 November 2015ReactomeTeamVersion54
81631view13:10, 21 August 2015ReactomeTeamVersion53
80028view09:40, 1 May 2015EgonwRenamed 1,2-Diacylglyceroll to 1,2-Diacylglycerol.
77093view08:39, 17 July 2014ReactomeTeamFixed remaining interactions
76799view12:18, 16 July 2014ReactomeTeamFixed remaining interactions
76122view10:18, 11 June 2014ReactomeTeamRe-fixing comment source
75834view11:40, 10 June 2014ReactomeTeamReactome 48 Update
75194view09:41, 9 May 2014Anwesha
74840view10:06, 30 April 2014ReactomeTeamReactome46
68929view17:33, 8 July 2013MaintBotUpdated to 2013 gpml schema
42103view21:57, 4 March 2011MaintBotAutomatic update
39913view05:56, 21 January 2011MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
(ethanolamineP)

mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI

G00151 (GLYCAN)
(ethanolamineP)

mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI

G00150 (GLYCAN)
(ethanolamineP)

mannose (a1-4) glucosaminyl-acyl-PI

REACT_2468 (Reactome)
Acetate Metabolite15366 (ChEBI)
CoA-SH Metabolite15346 (ChEBI)
Diacylglycerol 18035 (ChEBI)
Fatty acyl CoA C06709 (COMPOUND)
GDP-alpha-D-

mannose

Metabolite15820 (ChEBI)
GPI

mannosyltransferase I

ComplexREACT_2364 (Reactome)
GPI transamidase ComplexREACT_4592 (Reactome)
GPI-N-

acetylglucosaminyltran sferase

ComplexREACT_5237 (Reactome)
H2O Metabolite15377 (ChEBI)
N-

acetylglucosaminyl- PI

G00143 (GLYCAN)
PIG-B ProteinQ92521 (UniProt)
PIG-F:GPI7 complex ComplexREACT_5313 (Reactome)
PIG-F:PIG-O

complex

ComplexREACT_5770 (Reactome)
PIG-L ProteinQ9Y2B2 (UniProt)
PIG-N ProteinO95427 (UniProt)
PIG-V ProteinQ9NUD9 (UniProt)
PIG-W ProteinQ7Z7B1 (UniProt)
Post GPI Attachment

to Proteins 1

ProteinQ75T13 (UniProt)
SMP3 ProteinQ9H9G5 (UniProt)
UDP-N-acetyl-D-

glucosamine

Metabolite16264 (ChEBI)
dolichyl phosphate C00110 (COMPOUND)
dolichyl phosphate

D-mannose

C03862 (COMPOUND)
dolichyl-phosphate

mannosyltransferase

ComplexREACT_3881 (Reactome)
glucosaminyl-PI G00144 (GLYCAN)
glucosaminyl-acyl-PI G00145 (GLYCAN)
long-chain fatty acid 15904 (ChEBI)
mannose (a1)

mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI

REACT_2710 (Reactome)
mannose (a1-2)

mannose (a1-6) (ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI

G00149 (GLYCAN)
mannose (a1-4)

glucosaminyl-acyl-PI

G00146 (GLYCAN)
mannose (a1-6)

(ethanolamineP) mannose (a1-4) glucosaminyl-acyl-PI

G00148 (GLYCAN)
phosphatidylethanola

mine

C00350 (COMPOUND)
phosphatidylinositol C01194 (COMPOUND)
uridine 5'-

diphosphate

Metabolite17659 (ChEBI)
urokinase

plasminogen activator receptor

ProteinQ03405 (UniProt)
urokinase

plasminogen activator receptor precursor

ProteinQ03405 (UniProt)
urokinase

plasminogen activator receptor precursor propeptide

ProteinQ03405 (UniProt)
urokinase

plasminogen activator receptor- acyl-GPI

ProteinQ03405 (UniProt)

Annotated Interactions

No annotated interactions

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