CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002369
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Glucose-6-phosphate isomerase 
Protein Synonyms/Alias
 GPI; Autocrine motility factor; AMF; Neuroleukin; NLK; Phosphoglucose isomerase; PGI; Phosphohexose isomerase; PHI; Sperm antigen 36; SA-36 
Gene Name
 GPI 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
12TRDPQFQKLQQWYREacetylation[1]
12TRDPQFQKLQQWYREubiquitination[2, 3, 4, 5, 6]
34RRLFDANKDRFNHFSubiquitination[5]
73RMLVDLAKSRGVEAAubiquitination[2, 3, 5]
89ERMFNGEKINYTEGRubiquitination[3, 5, 6]
116TPILVDGKDVMPEVNubiquitination[3, 5]
124DVMPEVNKVLDKMKSubiquitination[2, 5]
130NKVLDKMKSFCQRVRubiquitination[5]
142RVRSGDWKGYTGKTIacetylation[1]
142RVRSGDWKGYTGKTIubiquitination[5]
226ITNAETAKEWFLQAAubiquitination[2, 3, 5, 6, 7, 8]
234EWFLQAAKDPSAVAKacetylation[9]
234EWFLQAAKDPSAVAKubiquitination[2, 3, 5, 6, 7, 10]
241KDPSAVAKHFVALSTubiquitination[2, 3, 5, 6, 8]
252ALSTNTTKVKEFGIDubiquitination[2, 3, 5, 7]
362GDMESNGKYITKSGTubiquitination[3, 5, 6]
366SNGKYITKSGTRVDHubiquitination[3]
423IRKGLHHKILLANFLubiquitination[7]
440TEALMRGKSTEEARKubiquitination[3]
454KELQAAGKSPEDLERacetylation[8, 9]
454KELQAAGKSPEDLERmalonylation[11]
454KELQAAGKSPEDLERubiquitination[3, 5, 6, 8]
466LERLLPHKVFEGNRPubiquitination[2, 3, 5, 6, 7, 8]
524LGKQLAKKIEPELDGubiquitination[5]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [10] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [11] The first identification of lysine malonylation substrates and its regulatory enzyme.
 Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y.
 Mol Cell Proteomics. 2011 Dec;10(12):M111.012658. [PMID: 21908771] 
Functional Description
 Besides it's role as a glycolytic enzyme, mammalian GPI can function as a tumor-secreted cytokine and an angiogenic factor (AMF) that stimulates endothelial cell motility. GPI is also a neurotrophic factor (Neuroleukin) for spinal and sensory neurons. 
Sequence Annotation
 ACT_SITE 358 358 Proton donor.
 ACT_SITE 389 389
 ACT_SITE 519 519
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 12 12 N6-acetyllysine.
 MOD_RES 109 109 Phosphothreonine.
 MOD_RES 142 142 N6-acetyllysine.
 MOD_RES 185 185 Phosphoserine; by CK2.
 MOD_RES 454 454 N6-malonyllysine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Angiogenesis; Complete proteome; Cytokine; Cytoplasm; Direct protein sequencing; Disease mutation; Gluconeogenesis; Glycolysis; Growth factor; Hereditary hemolytic anemia; Isomerase; Phosphoprotein; Polymorphism; Reference proteome; Secreted; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 558 AA 
Protein Sequence
MAALTRDPQF QKLQQWYREH RSELNLRRLF DANKDRFNHF SLTLNTNHGH ILVDYSKNLV 60
TEDVMRMLVD LAKSRGVEAA RERMFNGEKI NYTEGRAVLH VALRNRSNTP ILVDGKDVMP 120
EVNKVLDKMK SFCQRVRSGD WKGYTGKTIT DVINIGIGGS DLGPLMVTEA LKPYSSGGPR 180
VWYVSNIDGT HIAKTLAQLN PESSLFIIAS KTFTTQETIT NAETAKEWFL QAAKDPSAVA 240
KHFVALSTNT TKVKEFGIDP QNMFEFWDWV GGRYSLWSAI GLSIALHVGF DNFEQLLSGA 300
HWMDQHFRTT PLEKNAPVLL ALLGIWYINC FGCETHAMLP YDQYLHRFAA YFQQGDMESN 360
GKYITKSGTR VDHQTGPIVW GEPGTNGQHA FYQLIHQGTK MIPCDFLIPV QTQHPIRKGL 420
HHKILLANFL AQTEALMRGK STEEARKELQ AAGKSPEDLE RLLPHKVFEG NRPTNSIVFT 480
KLTPFMLGAL VAMYEHKIFV QGIIWDINSF DQWGVELGKQ LAKKIEPELD GSAQVTSHDA 540
STNGLINFIK QQREARVQ 558 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
 GO:0043005; C:neuron projection; IEA:Compara.
 GO:0005634; C:nucleus; IDA:HPA.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0004347; F:glucose-6-phosphate isomerase activity; TAS:Reactome.
 GO:0016866; F:intramolecular transferase activity; IEA:Compara.
 GO:0048029; F:monosaccharide binding; IEA:Compara.
 GO:0046185; P:aldehyde catabolic process; IEA:Compara.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0006094; P:gluconeogenesis; TAS:Reactome.
 GO:0051156; P:glucose 6-phosphate metabolic process; IEA:Compara.
 GO:0006096; P:glycolysis; TAS:Reactome.
 GO:0007599; P:hemostasis; TAS:ProtInc.
 GO:0006959; P:humoral immune response; TAS:ProtInc.
 GO:0007611; P:learning or memory; IEA:Compara.
 GO:0019242; P:methylglyoxal biosynthetic process; IEA:Compara.
 GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Compara.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:0044281; P:small molecule metabolic process; TAS:Reactome. 
Interpro
 IPR001672; G6P_Isomerase.
 IPR023096; G6P_Isomerase_C.
 IPR018189; Phosphoglucose_isomerase_CS. 
Pfam
 PF00342; PGI 
SMART
  
PROSITE
 PS00765; P_GLUCOSE_ISOMERASE_1
 PS00174; P_GLUCOSE_ISOMERASE_2
 PS51463; P_GLUCOSE_ISOMERASE_3 
PRINTS
 PR00662; G6PISOMERASE.