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

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14, 211735, 9, 12, 1944157, 1368, 20, 222, 16, 1810, 111endoplasmic reticulum lumencytosolPIGC GPI-RAET1L GPI-VNN1 cleaved GPI-LY6K cleaved GPI-LYPD6B cleaved GPI-CD52 glucosaminyl-PIPIGU cleaved GPI-PSCA PIGX cleaved GPI-NTNG2 DPM2 UDPPIcleaved GPI-NRN1L cleaved GPI-LY6G6C PIGWLCFA(-)dolichyl phosphateGPLD1GPI-CD52 GPI-MDGA1 GPAA1 cleaved GPI-ALPI cleaved GPI-LY6D GPI-XPNPEP2 mannose(a1-2)mannose(a1-6)(ethanolamineP)mannose(a1-4)glucosaminyl-acyl-PIcleaved GPI-VNN2 cleaved GPI-GPIHBP1 GPI-GnTGPI-LYPD2 cleaved GPI-LY6H GPI-LY6G6D cleaved GPI-VNN3 GPI-NRN1 GPI-PLET1 cleaved GPI-LYPD3 (ethanolamineP)mannose(a1-2)(ethanolamineP)mannose(a1-6)(ethanolamineP)mannose(a1-4)glucosaminyl-acyl-PIcleaved GPI-CPM DAGPIGLGPI-THY1 cleaved GPI-LYPD5 GPI-OTOA cleaved GPI-LYPD4 GPI-TEX101 cleaved GPI-CEACAM5 cleaved GPI-RTN4RL2 GPI-MSLN cleaved GPI-XPNPEP2 CoA-SHcleaved GPI-SPRN PIGQ-2 GPI-LSAMP GPI-FOLR2 CH3COO-DPM1 cleaved GPI-PRND UDP-GlcNAccleaved GPI-ART4 PIGP(26-158) PIGK proteins withcleaved GPI-anchorscleaved GPI-PRSS41 dolichyl phosphateGPI-LYPD3 GPI-LY6E PIGF GPI-CNTN3 cleaved GPI-NTNG1 mannose(a1-2)mannose(a1-6)(ethanolamineP)mannose(a1-4)glucosaminyl-acyl-PIcleaved GPI-FCGR3B GPI-LY6G6C GPI-MELTF GPI transamidasecleaved GPI-ALPPL2 PLAUR(306-335)GPI-TECTB GPI-ART3 cleaved GPI-VNN1 GPI-NTM cleaved GPI-LYPD1 PIGVGPI-RTN4RL1 H2OGPI-CNTN5 cleaved GPI-TECTB GPI-LYPD4 DPM3 GDPcleaved GPI-OPCML PLAURGPI-OPCML GPI-GP2 cleaved GPI-IZUMO1R PIGF cleaved GPI-CD109 PEcleaved GPI-NTM PIGNcleaved GPI-CNTN5 cleaved GPI-ART3 cleaved GPI-CNTN3 PIGM glucosaminyl-acyl-PIGPI-NEGR1 GPI-RTN4RL2 PIGBGPI-VNN2 GPI-PSCA cleaved GPI-RTN4RL1 DOLP-Manmannose(a1-4)glucosaminyl-acyl-PIDAGPLAUR(23-335)GPI-SPACA4 cleaved GPI-CNTN4 PIGF:PIGOGPI-CEACAM7 cleaved GPI-GP2 cleaved GPI-LY6G6D PIPGAP1GPI-CD109 PIGY DPM2 PIGA GPI-ALPPL2 GPI-MDGA2(21-956) cleaved GPI-PRSS21 cleaved GPI-OTOA GPImannosyltransferaseIN-acetylglucosaminyl-PIcleaved GPI-THY1 cleaved GPI-LYPD2 GPI-TECTA cleaved GPI-RAET1G GPI-ALPI PIGO cleaved GPI-ULBP2 GPI-NTNG2 cleaved GPI-NRN1 cleaved GPI-SPACA4 cleaved GPI-RAET1L cleaved GPI-TEX101 cleaved GPI-TECTA cleaved GPI-NEGR1 GPI-LY6D cleaved GPI-MELTF GPI-CPM GPI-FCGR3B PIGH GPI-CNTN4 cleaved GPI-LYPD8 GPI-PRND cleaved GPI-LSAMP (ethanolamineP)mannose(a1-4)glucosaminyl-acyl-PIDOLP-ManGPI-LYPD6B GPI-LY6H H2OGPI-BST1 mannose(a1)mannose(a1-2)mannose(a1-6)(ethanolamineP)mannose(a1-4)glucosaminyl-acyl-PIGPI-NRN1L FACoAcleaved GPI-CEACAM7 cleaved GPI-ALPL PIGZcleaved GPI-MSLN GPI-LYPD1 GPI-PRSS21 DOLP-Mancleaved GPI-LY6E PIGG GPI-SPRN cleaved GPI-PLET1 cleaved GPI-MDGA2(21-956) cleaved GPI-MDGA1 PIGF:PIGGcleaved GPI-BST1 GPI-IZUMO1R GPI-ART4 DOLPcleaved GPI-FOLR2 GPI-RAET1G glucosaminyl-acyl-PIGPI-LY6K GPI-LYPD8 DOLP-ManGPI-anchoredproteinsDOLP-ManPEDPM1:DPM2:DPM3GPI-GPIHBP1 H2OGPI-ALPL GDP-ManGPI-NTNG1 PIGS mannose(a1-6)(ethanolamineP)mannose(a1-4)glucosaminyl-acyl-PIGPI-RECK GPI-LYPD5 GPI-ULBP2 GPI-VNN3 N-glycyl-glycosylphosphatidylinositolethanolamine-PLAURGPI-PRSS41 cleaved GPI-RECK PIGT GPI-CEACAM5 9923


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. View original pathway at:Reactome.</div>

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 163125
Reactome-version 
Reactome version: 66

Quality Tags

Ontology Terms

 

Bibliography

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  1. 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
  2. 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
  3. 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
  4. Kinoshita T, Inoue N.; ''Dissecting and manipulating the pathway for glycosylphos-phatidylinositol-anchor biosynthesis.''; PubMed Europe PMC
  5. 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
  6. Gaynor EC, Mond├ęsert 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
  7. 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
  8. Low MG, Prasad AR.; ''A phospholipase D specific for the phosphatidylinositol anchor of cell-surface proteins is abundant in plasma.''; PubMed Europe PMC
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. Davitz MA, Hereld D, Shak S, Krakow J, Englund PT, Nussenzweig V.; ''A glycan-phosphatidylinositol-specific phospholipase D in human serum.''; PubMed Europe PMC
  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
  22. Schofield JN, Rademacher TW.; ''Structure and expression of the human glycosylphosphatidylinositol phospholipase D1 (GPLD1) gene.''; PubMed Europe PMC
  23. 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

History

View all...
CompareRevisionActionTimeUserComment
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

View all...
NameTypeDatabase referenceComment
(ethanolamineP)

mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
MetaboliteCHEBI:77364 (ChEBI)
(ethanolamineP)

mannose (a1-4)

glucosaminyl-acyl-PI
R-ALL-8855663 (Reactome)
CH3COO-MetaboliteCHEBI:15366 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
DAGMetaboliteCHEBI:17815 (ChEBI)
DOLP-ManMetaboliteCHEBI:15809 (ChEBI)
DOLPMetaboliteCHEBI:16214 (ChEBI)
DPM1 ProteinO60762 (Uniprot-TrEMBL)
DPM1:DPM2:DPM3ComplexR-HSA-162692 (Reactome)
DPM2 ProteinO94777 (Uniprot-TrEMBL)
DPM3 ProteinQ9P2X0 (Uniprot-TrEMBL)
FACoAMetaboliteCHEBI:37554 (ChEBI)
GDP-ManMetaboliteCHEBI:15820 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GPAA1 ProteinO43292 (Uniprot-TrEMBL)
GPI

mannosyltransferase

I
ComplexR-HSA-162829 (Reactome)
GPI transamidaseComplexR-HSA-162690 (Reactome)
GPI-ALPI ProteinP09923 (Uniprot-TrEMBL)
GPI-ALPL ProteinP05186 (Uniprot-TrEMBL)
GPI-ALPPL2 ProteinP10696 (Uniprot-TrEMBL)
GPI-ART3 ProteinQ13508 (Uniprot-TrEMBL)
GPI-ART4 ProteinQ93070 (Uniprot-TrEMBL)
GPI-BST1 ProteinQ10588 (Uniprot-TrEMBL)
GPI-CD109 ProteinQ6YHK3 (Uniprot-TrEMBL)
GPI-CD52 ProteinP31358 (Uniprot-TrEMBL)
GPI-CEACAM5 ProteinP06731 (Uniprot-TrEMBL)
GPI-CEACAM7 ProteinQ14002 (Uniprot-TrEMBL)
GPI-CNTN3 ProteinQ9P232 (Uniprot-TrEMBL)
GPI-CNTN4 ProteinQ8IWV2 (Uniprot-TrEMBL)
GPI-CNTN5 ProteinO94779 (Uniprot-TrEMBL)
GPI-CPM ProteinP14384 (Uniprot-TrEMBL)
GPI-FCGR3B ProteinO75015 (Uniprot-TrEMBL)
GPI-FOLR2 ProteinP14207 (Uniprot-TrEMBL)
GPI-GP2 ProteinP55259 (Uniprot-TrEMBL)
GPI-GPIHBP1 ProteinQ8IV16 (Uniprot-TrEMBL)
GPI-GnTComplexR-HSA-162850 (Reactome)
GPI-IZUMO1R ProteinA6ND01 (Uniprot-TrEMBL)
GPI-LSAMP ProteinQ13449 (Uniprot-TrEMBL)
GPI-LY6D ProteinQ14210 (Uniprot-TrEMBL)
GPI-LY6E ProteinQ16553 (Uniprot-TrEMBL)
GPI-LY6G6C ProteinO95867 (Uniprot-TrEMBL)
GPI-LY6G6D ProteinO95868 (Uniprot-TrEMBL)
GPI-LY6H ProteinO94772 (Uniprot-TrEMBL)
GPI-LY6K ProteinQ17RY6 (Uniprot-TrEMBL)
GPI-LYPD1 ProteinQ8N2G4 (Uniprot-TrEMBL)
GPI-LYPD2 ProteinQ6UXB3 (Uniprot-TrEMBL)
GPI-LYPD3 ProteinO95274 (Uniprot-TrEMBL)
GPI-LYPD4 ProteinQ6UWN0 (Uniprot-TrEMBL)
GPI-LYPD5 ProteinQ6UWN5 (Uniprot-TrEMBL)
GPI-LYPD6B ProteinQ8NI32 (Uniprot-TrEMBL)
GPI-LYPD8 ProteinQ6UX82 (Uniprot-TrEMBL)
GPI-MDGA1 ProteinQ8NFP4 (Uniprot-TrEMBL)
GPI-MDGA2(21-956) ProteinQ7Z553 (Uniprot-TrEMBL)
GPI-MELTF ProteinP08582 (Uniprot-TrEMBL)
GPI-MSLN ProteinQ13421 (Uniprot-TrEMBL)
GPI-NEGR1 ProteinQ7Z3B1 (Uniprot-TrEMBL)
GPI-NRN1 ProteinQ9NPD7 (Uniprot-TrEMBL)
GPI-NRN1L ProteinQ496H8 (Uniprot-TrEMBL)
GPI-NTM ProteinQ9P121 (Uniprot-TrEMBL)
GPI-NTNG1 ProteinQ9Y2I2 (Uniprot-TrEMBL)
GPI-NTNG2 ProteinQ96CW9 (Uniprot-TrEMBL)
GPI-OPCML ProteinQ14982 (Uniprot-TrEMBL)
GPI-OTOA ProteinQ7RTW8 (Uniprot-TrEMBL)
GPI-PLET1 ProteinQ6UQ28 (Uniprot-TrEMBL)
GPI-PRND ProteinQ9UKY0 (Uniprot-TrEMBL)
GPI-PRSS21 ProteinQ9Y6M0 (Uniprot-TrEMBL)
GPI-PRSS41 ProteinQ7RTY9 (Uniprot-TrEMBL)
GPI-PSCA ProteinO43653 (Uniprot-TrEMBL)
GPI-RAET1G ProteinQ6H3X3 (Uniprot-TrEMBL)
GPI-RAET1L ProteinQ5VY80 (Uniprot-TrEMBL)
GPI-RECK ProteinO95980 (Uniprot-TrEMBL)
GPI-RTN4RL1 ProteinQ86UN2 (Uniprot-TrEMBL)
GPI-RTN4RL2 ProteinQ86UN3 (Uniprot-TrEMBL)
GPI-SPACA4 ProteinQ8TDM5 (Uniprot-TrEMBL)
GPI-SPRN ProteinQ5BIV9 (Uniprot-TrEMBL)
GPI-TECTA ProteinO75443 (Uniprot-TrEMBL)
GPI-TECTB ProteinQ96PL2 (Uniprot-TrEMBL)
GPI-TEX101 ProteinQ9BY14 (Uniprot-TrEMBL)
GPI-THY1 ProteinP04216 (Uniprot-TrEMBL)
GPI-ULBP2 ProteinQ9BZM5 (Uniprot-TrEMBL)
GPI-VNN1 ProteinO95497 (Uniprot-TrEMBL)
GPI-VNN2 ProteinO95498 (Uniprot-TrEMBL)
GPI-VNN3 ProteinQ9NY84 (Uniprot-TrEMBL)
GPI-XPNPEP2 ProteinO43895 (Uniprot-TrEMBL)
GPI-anchored proteinsComplexR-HSA-8940978 (Reactome)
GPLD1ProteinP80108 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
LCFA(-)MetaboliteCHEBI:57560 (ChEBI)
N-acetylglucosaminyl-PIMetaboliteCHEBI:15935 (ChEBI)
N-glycyl-glycosylphosphatidylinositolethanolamine-PLAURProteinQ03405 (Uniprot-TrEMBL)
PEMetaboliteCHEBI:16038 (ChEBI)
PGAP1ProteinQ75T13 (Uniprot-TrEMBL)
PIMetaboliteCHEBI:16749 (ChEBI)
PIGA ProteinP37287 (Uniprot-TrEMBL)
PIGBProteinQ92521 (Uniprot-TrEMBL)
PIGC ProteinQ92535 (Uniprot-TrEMBL)
PIGF ProteinQ07326 (Uniprot-TrEMBL)
PIGF:PIGGComplexR-HSA-162728 (Reactome)
PIGF:PIGOComplexR-HSA-162885 (Reactome)
PIGG ProteinQ5H8A4 (Uniprot-TrEMBL)
PIGH ProteinQ14442 (Uniprot-TrEMBL)
PIGK ProteinQ92643 (Uniprot-TrEMBL)
PIGLProteinQ9Y2B2 (Uniprot-TrEMBL)
PIGM ProteinQ9H3S5 (Uniprot-TrEMBL)
PIGNProteinO95427 (Uniprot-TrEMBL)
PIGO ProteinQ8TEQ8 (Uniprot-TrEMBL)
PIGP(26-158) ProteinP57054 (Uniprot-TrEMBL)
PIGQ-2 ProteinQ9BRB3-2 (Uniprot-TrEMBL)
PIGS ProteinQ96S52 (Uniprot-TrEMBL)
PIGT ProteinQ969N2 (Uniprot-TrEMBL)
PIGU ProteinQ9H490 (Uniprot-TrEMBL)
PIGVProteinQ9NUD9 (Uniprot-TrEMBL)
PIGWProteinQ7Z7B1 (Uniprot-TrEMBL)
PIGX ProteinQ8TBF5 (Uniprot-TrEMBL)
PIGY ProteinQ3MUY2 (Uniprot-TrEMBL)
PIGZProteinQ86VD9 (Uniprot-TrEMBL)
PLAUR(23-335)ProteinQ03405 (Uniprot-TrEMBL)
PLAUR(306-335)ProteinQ03405 (Uniprot-TrEMBL)
PLAURProteinQ03405 (Uniprot-TrEMBL)
UDP-GlcNAcMetaboliteCHEBI:16264 (ChEBI)
UDPMetaboliteCHEBI:17659 (ChEBI)
cleaved GPI-ALPI ProteinP09923 (Uniprot-TrEMBL)
cleaved GPI-ALPL ProteinP05186 (Uniprot-TrEMBL)
cleaved GPI-ALPPL2 ProteinP10696 (Uniprot-TrEMBL)
cleaved GPI-ART3 ProteinQ13508 (Uniprot-TrEMBL)
cleaved GPI-ART4 ProteinQ93070 (Uniprot-TrEMBL)
cleaved GPI-BST1 ProteinQ10588 (Uniprot-TrEMBL)
cleaved GPI-CD109 ProteinQ6YHK3 (Uniprot-TrEMBL)
cleaved GPI-CD52 ProteinP31358 (Uniprot-TrEMBL)
cleaved GPI-CEACAM5 ProteinP06731 (Uniprot-TrEMBL)
cleaved GPI-CEACAM7 ProteinQ14002 (Uniprot-TrEMBL)
cleaved GPI-CNTN3 ProteinQ9P232 (Uniprot-TrEMBL)
cleaved GPI-CNTN4 ProteinQ8IWV2 (Uniprot-TrEMBL)
cleaved GPI-CNTN5 ProteinO94779 (Uniprot-TrEMBL)
cleaved GPI-CPM ProteinP14384 (Uniprot-TrEMBL)
cleaved GPI-FCGR3B ProteinO75015 (Uniprot-TrEMBL)
cleaved GPI-FOLR2 ProteinP14207 (Uniprot-TrEMBL)
cleaved GPI-GP2 ProteinP55259 (Uniprot-TrEMBL)
cleaved GPI-GPIHBP1 ProteinQ8IV16 (Uniprot-TrEMBL)
cleaved GPI-IZUMO1R ProteinA6ND01 (Uniprot-TrEMBL)
cleaved GPI-LSAMP ProteinQ13449 (Uniprot-TrEMBL)
cleaved GPI-LY6D ProteinQ14210 (Uniprot-TrEMBL)
cleaved GPI-LY6E ProteinQ16553 (Uniprot-TrEMBL)
cleaved GPI-LY6G6C ProteinO95867 (Uniprot-TrEMBL)
cleaved GPI-LY6G6D ProteinO95868 (Uniprot-TrEMBL)
cleaved GPI-LY6H ProteinO94772 (Uniprot-TrEMBL)
cleaved GPI-LY6K ProteinQ17RY6 (Uniprot-TrEMBL)
cleaved GPI-LYPD1 ProteinQ8N2G4 (Uniprot-TrEMBL)
cleaved GPI-LYPD2 ProteinQ6UXB3 (Uniprot-TrEMBL)
cleaved GPI-LYPD3 ProteinO95274 (Uniprot-TrEMBL)
cleaved GPI-LYPD4 ProteinQ6UWN0 (Uniprot-TrEMBL)
cleaved GPI-LYPD5 ProteinQ6UWN5 (Uniprot-TrEMBL)
cleaved GPI-LYPD6B ProteinQ8NI32 (Uniprot-TrEMBL)
cleaved GPI-LYPD8 ProteinQ6UX82 (Uniprot-TrEMBL)
cleaved GPI-MDGA1 ProteinQ8NFP4 (Uniprot-TrEMBL)
cleaved GPI-MDGA2(21-956) ProteinQ7Z553 (Uniprot-TrEMBL)
cleaved GPI-MELTF ProteinP08582 (Uniprot-TrEMBL)
cleaved GPI-MSLN ProteinQ13421 (Uniprot-TrEMBL)
cleaved GPI-NEGR1 ProteinQ7Z3B1 (Uniprot-TrEMBL)
cleaved GPI-NRN1 ProteinQ9NPD7 (Uniprot-TrEMBL)
cleaved GPI-NRN1L ProteinQ496H8 (Uniprot-TrEMBL)
cleaved GPI-NTM ProteinQ9P121 (Uniprot-TrEMBL)
cleaved GPI-NTNG1 ProteinQ9Y2I2 (Uniprot-TrEMBL)
cleaved GPI-NTNG2 ProteinQ96CW9 (Uniprot-TrEMBL)
cleaved GPI-OPCML ProteinQ14982 (Uniprot-TrEMBL)
cleaved GPI-OTOA ProteinQ7RTW8 (Uniprot-TrEMBL)
cleaved GPI-PLET1 ProteinQ6UQ28 (Uniprot-TrEMBL)
cleaved GPI-PRND ProteinQ9UKY0 (Uniprot-TrEMBL)
cleaved GPI-PRSS21 ProteinQ9Y6M0 (Uniprot-TrEMBL)
cleaved GPI-PRSS41 ProteinQ7RTY9 (Uniprot-TrEMBL)
cleaved GPI-PSCA ProteinO43653 (Uniprot-TrEMBL)
cleaved GPI-RAET1G ProteinQ6H3X3 (Uniprot-TrEMBL)
cleaved GPI-RAET1L ProteinQ5VY80 (Uniprot-TrEMBL)
cleaved GPI-RECK ProteinO95980 (Uniprot-TrEMBL)
cleaved GPI-RTN4RL1 ProteinQ86UN2 (Uniprot-TrEMBL)
cleaved GPI-RTN4RL2 ProteinQ86UN3 (Uniprot-TrEMBL)
cleaved GPI-SPACA4 ProteinQ8TDM5 (Uniprot-TrEMBL)
cleaved GPI-SPRN ProteinQ5BIV9 (Uniprot-TrEMBL)
cleaved GPI-TECTA ProteinO75443 (Uniprot-TrEMBL)
cleaved GPI-TECTB ProteinQ96PL2 (Uniprot-TrEMBL)
cleaved GPI-TEX101 ProteinQ9BY14 (Uniprot-TrEMBL)
cleaved GPI-THY1 ProteinP04216 (Uniprot-TrEMBL)
cleaved GPI-ULBP2 ProteinQ9BZM5 (Uniprot-TrEMBL)
cleaved GPI-VNN1 ProteinO95497 (Uniprot-TrEMBL)
cleaved GPI-VNN2 ProteinO95498 (Uniprot-TrEMBL)
cleaved GPI-VNN3 ProteinQ9NY84 (Uniprot-TrEMBL)
cleaved GPI-XPNPEP2 ProteinO43895 (Uniprot-TrEMBL)
dolichyl phosphateMetaboliteCHEBI:16214 (ChEBI)
glucosaminyl-PIMetaboliteCHEBI:24275 (ChEBI)
glucosaminyl-acyl-PIMetaboliteCHEBI:52572 (ChEBI)
mannose

(a1) mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
R-ALL-8855664 (Reactome)
mannose

(a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
MetaboliteCHEBI:53059 (ChEBI)
mannose

(a1-4)

glucosaminyl-acyl-PI
MetaboliteCHEBI:53056 (ChEBI)
mannose

(a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
MetaboliteCHEBI:53058 (ChEBI)
proteins with cleaved GPI-anchorsComplexR-HSA-8941069 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
(ethanolamineP)

mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
ArrowR-HSA-162742 (Reactome)
(ethanolamineP)

mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
ArrowR-HSA-163069 (Reactome)
(ethanolamineP)

mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
R-HSA-162742 (Reactome)
(ethanolamineP)

mannose (a1-2) (ethanolamineP) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
R-HSA-162836 (Reactome)
(ethanolamineP)

mannose (a1-4)

glucosaminyl-acyl-PI
ArrowR-HSA-162798 (Reactome)
(ethanolamineP)

mannose (a1-4)

glucosaminyl-acyl-PI
R-HSA-162873 (Reactome)
CH3COO-ArrowR-HSA-162857 (Reactome)
CoA-SHArrowR-HSA-162683 (Reactome)
DAGArrowR-HSA-162798 (Reactome)
DAGArrowR-HSA-163069 (Reactome)
DOLP-ManArrowR-HSA-162715 (Reactome)
DOLP-ManArrowR-HSA-162721 (Reactome)
DOLP-ManR-HSA-162715 (Reactome)
DOLP-ManR-HSA-162797 (Reactome)
DOLP-ManR-HSA-162821 (Reactome)
DOLP-ManR-HSA-162830 (Reactome)
DOLP-ManR-HSA-162873 (Reactome)
DOLPR-HSA-162721 (Reactome)
DPM1:DPM2:DPM3mim-catalysisR-HSA-162721 (Reactome)
FACoAR-HSA-162683 (Reactome)
GDP-ManR-HSA-162721 (Reactome)
GDPArrowR-HSA-162721 (Reactome)
GPI

mannosyltransferase

I
mim-catalysisR-HSA-162830 (Reactome)
GPI transamidasemim-catalysisR-HSA-162836 (Reactome)
GPI-GnTmim-catalysisR-HSA-162730 (Reactome)
GPI-anchored proteinsR-HSA-8940388 (Reactome)
GPLD1mim-catalysisR-HSA-8940388 (Reactome)
H2OR-HSA-162729 (Reactome)
H2OR-HSA-162857 (Reactome)
H2OR-HSA-8940388 (Reactome)
LCFA(-)ArrowR-HSA-162729 (Reactome)
N-acetylglucosaminyl-PIArrowR-HSA-162730 (Reactome)
N-acetylglucosaminyl-PIR-HSA-162857 (Reactome)
N-glycyl-glycosylphosphatidylinositolethanolamine-PLAURArrowR-HSA-162836 (Reactome)
N-glycyl-glycosylphosphatidylinositolethanolamine-PLAURR-HSA-162729 (Reactome)
PER-HSA-162798 (Reactome)
PER-HSA-163069 (Reactome)
PGAP1mim-catalysisR-HSA-162729 (Reactome)
PIArrowR-HSA-8940388 (Reactome)
PIGBmim-catalysisR-HSA-162821 (Reactome)
PIGF:PIGGmim-catalysisR-HSA-162742 (Reactome)
PIGF:PIGOmim-catalysisR-HSA-163069 (Reactome)
PIGLmim-catalysisR-HSA-162857 (Reactome)
PIGNmim-catalysisR-HSA-162798 (Reactome)
PIGVmim-catalysisR-HSA-162873 (Reactome)
PIGWmim-catalysisR-HSA-162683 (Reactome)
PIGZmim-catalysisR-HSA-162797 (Reactome)
PIR-HSA-162730 (Reactome)
PLAUR(23-335)R-HSA-162836 (Reactome)
PLAUR(306-335)ArrowR-HSA-162836 (Reactome)
PLAURArrowR-HSA-162729 (Reactome)
R-HSA-162683 (Reactome) In the fourth step of GPI synthesis, an acyl group (typically palmitate) is transferred from acyl CoA to glucosaminyl-PI. Mutagenesis and cloning studies suggest that a single protein, PIG-W, catalyzes this reaction (Murakami et al. 2003).
R-HSA-162715 (Reactome) Dolichyl phosphate D-mannose (DOLPman) is flipped in the endoplasmic reticulum membrane so that its mannose moiety is oriented inwards, towards the endoplasmic reticulum lumen, where it is accessible to transferases catalyzing the synthesis of glycolipids and glycoproteins (Kinoshita & Inoue 2000).
R-HSA-162721 (Reactome) Cytosolic GDP-mannose reacts with dolichyl phosphate in the endoplasmic reticulum membrane to form dolichyl phosphate D-mannose (DOLPman). The reaction is catalysed by dolichyl-phosphate mannosyltransferase, a heterotrimeric protein embedded in the endoplasmic reticulum membrane. The first subunit of the heterotrimer (DPM1) appears to be the actual catalyst, and the other two subunits appear to stabilise it (Maeda et al. 2000).
R-HSA-162729 (Reactome) The fatty acid group added to inositol in the fourth step of GPI biosynthsis is removed from GPI-conjugated uPAR. This hydrolysis event occurs in the endoplasmic reticulum and appears to be associated with efficient transport of the conjugated protein from the endoplasmic reticulum to the Golgi apparatus (Tanaka et al. 2004).
R-HSA-162730 (Reactome) The first step of GPI synthesis is the transfer of N-acetylglucosamine from cytosolic UDP-N-acetylglucosamine to phosphatidyl inositol (PI) in the endoplasmic reticulum membrane. The reaction is catalyzed by a multimeric enzyme, also localized to the endoplasmic reticulum membrane, seven components of which have been identified to date by mutagenesis studies in cultured cells and by co-precipitation and reconstitution studies in vitro (Murakami et al. 2005; Watanabe et al. 1996, 1998, 2000).
R-HSA-162742 (Reactome) Most human GPI anchors have ethanolamine phosphate groups attached to their first and third mannose residues, but GPI anchors with ethanolamine phosphates attached to all three mannose residues have also been identified. Addition of the third ethanolamine phosphate can be catalyzed by a complex of PIG-F and a newly described human protein, GPI7. The donor of the ethanolamine phosphate for this reaction is unknown (Shishioh et al. 2005).
R-HSA-162797 (Reactome) Most human GPI anchors are thought to contain three mannose residues, while most yeast GPI anchors contain four. Recently, a human homologue of the yeast enzyme responsible for addition of the fourth mannose residue to GPI molecules was identified and shown to mediate synthesis of human GPI molecules with four mannose residues. While the mannose donor and the nature of the bond linking the third and fourth mannose residues have not been established directly in studies with the human enzyme, these features are known for yeast and the normal human gene restores GPI synthesis in mutant yeast. This observation, tegether with the sequence similarities between human PIGZ and and Saccharomyces cerevisiae smp3,supports the inference that the human enzyme uses dolichol-P-mannose as a donor. The functional distinction between GPI anchors with three and four mannose residues is unknown, although the latter appear to be abundant in many human tissues (Taron et al. 2004).
R-HSA-162798 (Reactome) In the sixth step of GPI synthesis, a phosphoethanolamine group is transferred from phosphatidylethanolamine onto the first mannose of the GPI precursor. The human protein that catalyzes this reaction was first identified because it could complement a yeast mutant strain defective for GPI synthesis (Gaynor et al. 1999); its specific function in phosphoethanolamine transfer is inferred from functional studies of the homologous mouse protein (Hong et al. 1999). The reaction is annotated here with phosphatidylethanolamine as the donor of the phosphoethanolamine group on the basis of studies in yeast (Imhof et al. 2000).
R-HSA-162821 (Reactome) In the eighth reaction of GPI synthesis, a third mannose residue is added, catalyzed by PIG-B (Takahashi et al. 1996).
R-HSA-162830 (Reactome) In the fifth step of GPI synthesis, a mannose residue is added to glucosaminyl-acyl-PI. The reaction takes place at the lumenal surface of the endoplasmic reticulum membrane. It is catalyzed by a complex of at least two components, PIG-M and PIG-X (Maeda et al. 2001; Ashida et al. 2005).
R-HSA-162836 (Reactome) In the endoplasmic reticulum, the precursor form of urokinase plasminogen activator receptor is transamidated at residue 305, replacing the 30 carboxyterminal residues of the protein with an acylated glucosylphosphatidylinositol (acyl-GPI) moiety. The released carboxyterminal propeptide has no known function. The reaction is catalyzed by GPI transamidase, a complex of at least five proteins associated with the lumenal surface of the endoplasmic reticulum membrane (Yu et al. 1997; Ohishi et al. 2001; Hong et al. 2003).
R-HSA-162840 (Reactome) GPI moieties are synthesized anchored to dolichol phosphate in the membrane of the endoplasmic reticulum. The first two steps of the synthetic pathway, leading to the production of glucosaminyl-PI, occur on the cytosolic face of the membrane, while addition of an acyl group (step 4) and all subsequent steps occur on the lumenal face (Murakami et al. 2003). No mutant cell lines defective in the reorientation step have been identified, and the mechanism by which it occurs is unknown.
R-HSA-162857 (Reactome) In the second step of GPI synthesis, N-acetylglucosaminyl-PI is hydrolyzed to yield glucosaminyl-PI and acetate. The phosphatidylinositol (PI) derivatives involved in this reaction are located in the endoplasmic reticulum membrane, as is the PIG-L enzyme that catalyzes it (Sharma et al. 1999; Pottekat and Menon 2004).
R-HSA-162873 (Reactome) In the seventh reaction of GPI synthesis, a second mannose residue is added to the glycolipid on the lumenal face of the endoplasmic reticulum membrane. PIG-V was identified as the catylyst, or a component of the catalyst, of this reaction, on the basis of its ability to correct the metabolic defects of yeast and mammalian mutant cells arrested at this stage of the GPI synthetic process (Fabre et al. 2005; Kang et al. 2005).
R-HSA-163069 (Reactome) The final step in the main pathway for the synthesis of GPI moieties in human cells is the addition of an ethanolamine phosphate to the third mannose residue of the glycolipid, donated by phosphatidylethanolamine. This reaction has been experimentally characterized in the mouse, where studies with mutated cell lines defective in GPI biosynthesis have established the role of two proteins, PIG-F and PIG-O, in this reaction (Hong et al. 2000). While a human PIG-F protein has been identified and shown to be involved in this event (Inoue et al. 1993), the human event has not been fully characterized and is therefore annotated here as inferred from studies of the mouse event.
R-HSA-8940388 (Reactome) Some proteins function at the cell's surface, attached to the plasma membrane via GPI (glycosylphosphatidylinositol) anchors and include enzymes, receptors, cell adhesion molecules and antigens. These GPI-anchored proteins participate in many important cellular functions including immune recognition, complement regulation and intracellular signaling. Phosphatidylinositol-glycan-specific phospholipase D (GPLD1) (Schofield et al. 2000) is a secreted protein that specifically cleaves GPI-anchored proteins by cleaving the linkage between the phosphate and inositol in GPI (Davitz et al. 1987, Low & Prasad 1988). In addition, it also localises to the ER where it can cleave GPI anchor intermediates transiting to the plasma membrane (not shown here). GPLD1 may play a role in the regulation of GPI-anchored proteins on (intra)cellular membranes.
UDP-GlcNAcR-HSA-162730 (Reactome)
UDPArrowR-HSA-162730 (Reactome)
dolichyl phosphateArrowR-HSA-162821 (Reactome)
dolichyl phosphateArrowR-HSA-162830 (Reactome)
dolichyl phosphateArrowR-HSA-162873 (Reactome)
glucosaminyl-PIArrowR-HSA-162857 (Reactome)
glucosaminyl-PIR-HSA-162683 (Reactome)
glucosaminyl-acyl-PIArrowR-HSA-162683 (Reactome)
glucosaminyl-acyl-PIArrowR-HSA-162840 (Reactome)
glucosaminyl-acyl-PIR-HSA-162830 (Reactome)
glucosaminyl-acyl-PIR-HSA-162840 (Reactome)
mannose

(a1) mannose (a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
ArrowR-HSA-162797 (Reactome)
mannose

(a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
ArrowR-HSA-162821 (Reactome)
mannose

(a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
R-HSA-162797 (Reactome)
mannose

(a1-2) mannose (a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
R-HSA-163069 (Reactome)
mannose

(a1-4)

glucosaminyl-acyl-PI
ArrowR-HSA-162830 (Reactome)
mannose

(a1-4)

glucosaminyl-acyl-PI
R-HSA-162798 (Reactome)
mannose

(a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
ArrowR-HSA-162873 (Reactome)
mannose

(a1-6) (ethanolamineP) mannose (a1-4)

glucosaminyl-acyl-PI
R-HSA-162821 (Reactome)
proteins with cleaved GPI-anchorsArrowR-HSA-8940388 (Reactome)

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