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Identification
HMDB Protein ID HMDBP00806
Secondary Accession Numbers
  • 6086
Name Glucose-6-phosphate isomerase
Synonyms
  1. AMF
  2. Autocrine motility factor
  3. GPI
  4. NLK
  5. Neuroleukin
  6. PGI
  7. PHI
  8. Phosphoglucose isomerase
  9. Phosphohexose isomerase
  10. SA-36
  11. Sperm antigen 36
Gene Name GPI
Protein Type Enzyme
Biological Properties
General Function Involved in glucose-6-phosphate isomerase activity
Specific Function 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.
Pathways
  • Amino sugar and nucleotide sugar metabolism
  • Fanconi-bickel syndrome
  • Fructose-1,6-diphosphatase deficiency
  • Gluconeogenesis
  • Glucose-6-phosphate dehydrogenase deficiency
  • Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease
  • Glycogen synthetase deficiency
  • Glycogenosis, Type IA. Von gierke disease
  • Glycogenosis, Type IB
  • Glycogenosis, Type IC
  • Glycogenosis, Type III. Cori disease, Debrancher glycogenosis
  • Glycogenosis, Type IV. Amylopectinosis, Anderson disease
  • Glycogenosis, Type VI. Hers disease
  • Glycogenosis, Type VII. Tarui disease
  • glycolysis
  • Glycolysis
  • Glycolysis / Gluconeogenesis
  • Mucopolysaccharidosis VI. Sly syndrome
  • pentose phosphate pathway
  • Pentose phosphate pathway
  • Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1)
  • Ribose-5-phosphate isomerase deficiency
  • Starch and sucrose metabolism
  • Starch and Sucrose Metabolism
  • Sucrase-isomaltase deficiency
  • Transaldolase deficiency
  • Triosephosphate isomerase
  • Warburg Effect
Reactions
Glucose 6-phosphate → Fructose 6-phosphate details
Glucose 6-phosphate → beta-D-Glucose 6-phosphate details
Glucose 6-phosphate → Beta-D-Fructose 6-phosphate details
beta-D-Glucose 6-phosphate → Beta-D-Fructose 6-phosphate details
GO Classification
Biological Process
small molecule metabolic process
learning or memory
negative regulation of neuron apoptotic process
glycolysis
glucose 6-phosphate metabolic process
hemostasis
methylglyoxal biosynthetic process
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
angiogenesis
gluconeogenesis
aldehyde catabolic process
humoral immune response
Cellular Component
cytosol
plasma membrane
nucleus
extracellular space
Function
catalytic activity
isomerase activity
intramolecular oxidoreductase activity
intramolecular oxidoreductase activity, interconverting aldoses and ketoses
glucose-6-phosphate isomerase activity
Molecular Function
monosaccharide binding
glucose-6-phosphate isomerase activity
intramolecular transferase activity
Process
metabolic process
small molecule metabolic process
alcohol metabolic process
monosaccharide metabolic process
hexose metabolic process
glucose metabolic process
gluconeogenesis
glucose catabolic process
glycolysis
Cellular Location
  1. Cytoplasm
  2. Secreted
Gene Properties
Chromosome Location 19
Locus 19q13.1
SNPs GPI
Gene Sequence
>1677 bp
ATGGCCGCTCTCACCCGGGACCCCCAGTTCCAGAAGCTGCAGCAATGGTACCGCGAGCAC
CGCTCCGAGCTGAACCTGCGCCGCCTCTTCGATGCCAACAAGGACCGCTTCAACCACTTC
AGCTTGACCCTCAACACCAACCATGGGCATATCCTGGTGGATTACTCCAAGAACCTGGTG
ACGGAGGACGTGATGCGGATGCTGGTGGACTTGGCCAAGTCCAGGGGCGTGGAGGCCGCC
CGGGAGCGGATGTTCAATGGTGAGAAGATCAACTACACCGAGGGTCGAGCCGTGCTGCAC
GTGGCTCTGCGGAACCGGTCAAACACACCCATCCTGGTAGACGGCAAGGATGTGATGCCA
GAGGTCAACAAGGTTCTGGACAAGATGAAGTCTTTCTGCCAGCGTGTCCGGAGCGGTGAC
TGGAAGGGGTACACAGGCAAGACCATCACGGACGTCATCAACATTGGCATTGGCGGCTCC
GACCTGGGACCCCTCATGGTGACTGAAGCCCTTAAGCCATACTCTTCAGGAGGTCCCCGC
GTCTGGTATGTCTCCAACATTGATGGAACTCACATTGCCAAAACCCTGGCCCAGCTGAAC
CCCGAGTCCTCCCTGTTCATCATTGCCTCCAAGACCTTTACTACCCAGGAGACCATCACG
AATGCAGAGACGGCGAAGGAGTGGTTTCTCCAGGCGGCCAAGGATCCTTCTGCAGTGGCG
AAGCACTTTGTTGCCCTGTCTACTAACACAACCAAAGTGAAGGAGTTTGGAATTGACCCT
CAAAACATGTTCGAGTTCTGGGATTGGGTGGGAGGACGCTACTCGCTGTGGTCGGCCATC
GGACTCTCCATTGCCCTGCACGTGGGTTTTGACAACTTCGAGCAGCTGCTCTCGGGGGCT
CACTGGATGGACCAGCACTTCCGCACGACGCCCCTGGAGAAGAACGCCCCCGTCCTGCTG
GCCCTGCTGGGTATCTGGTACATCAACTGCTTTGGGTGTGAGACACACGCCATGCTGCCC
TATGACCAGTACCTGCACCGCTTTGCTGCGTACTTCCAGCAGGGCGACATGGAGTCCAAT
GGGAAATACATCACCAAATCTGGAACCCGTGTGGACCACCAGACAGGCCCCATTGTGTGG
GGGGAGCCAGGGACCAATGGCCAGCATGCTTTTTACCAGCTCATCCACCAAGGCACCAAG
ATGATACCCTGTGACTTCCTCATCCCGGTCCAGACCCAGCACCCCATACGGAAGGGTCTG
CATCACAAGATCCTCGTGGCCAACTTCTTGGCCCAGACAGAGGCCGTGATGAGGGGAAAA
TCGACGGAGGAGGCCCGAAAGGAGCTCCAGGCTGCGGGCAAGAGTCCAGAGGACCTTGAG
AGGCTGCTGCCACATAAGGTCTTTGAAGGAAATCGCCCAACCAACTCTATTGTGTTCACC
AAGCTCACACCATTCATGCTTGGAGCCTTGGTCGCCATGTATGAGCACAAGATCTTCGTT
CAGGGCATCATCTGGGACATCAACAGCTTTGACCAGTGGGGAGTGGAGCTGGGAAAGCAG
CTGGCTAAGAAAATAGAGCCTGAGCTTGATGGCAGTGCTCAAGTGACCTCTCACGACGCT
TCTACCAATGGGCTCATCAACTTCATCAAGCAGCAGCGCGAGGCCAGAGTCCAATAA
Protein Properties
Number of Residues 558
Molecular Weight 63146.745
Theoretical pI 8.328
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Glucose-6-phosphate isomerase
MAALTRDPQFQKLQQWYREHRSELNLRRLFDANKDRFNHFSLTLNTNHGHILVDYSKNLV
TEDVMRMLVDLAKSRGVEAARERMFNGEKINYTEGRAVLHVALRNRSNTPILVDGKDVMP
EVNKVLDKMKSFCQRVRSGDWKGYTGKTITDVINIGIGGSDLGPLMVTEALKPYSSGGPR
VWYVSNIDGTHIAKTLAQLNPESSLFIIASKTFTTQETITNAETAKEWFLQAAKDPSAVA
KHFVALSTNTTKVKEFGIDPQNMFEFWDWVGGRYSLWSAIGLSIALHVGFDNFEQLLSGA
HWMDQHFRTTPLEKNAPVLLALLGIWYINCFGCETHAMLPYDQYLHRFAAYFQQGDMESN
GKYITKSGTRVDHQTGPIVWGEPGTNGQHAFYQLIHQGTKMIPCDFLIPVQTQHPIRKGL
HHKILLANFLAQTEALMRGKSTEEARKELQAAGKSPEDLERLLPHKVFEGNRPTNSIVFT
KLTPFMLGALVAMYEHKIFVQGIIWDINSFDQWGVELGKQLAKKIEPELDGSAQVTSHDA
STNGLINFIKQQREARVQ
GenBank ID Protein 6653226
UniProtKB/Swiss-Prot ID P06744
UniProtKB/Swiss-Prot Entry Name G6PI_HUMAN
PDB IDs
GenBank Gene ID AF187554
GeneCard ID GPI
GenAtlas ID GPI
HGNC ID HGNC:4458
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  5. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  6. Yakirevich E, Naot Y: Cloning of a glucose phosphate isomerase/neuroleukin-like sperm antigen involved in sperm agglutination. Biol Reprod. 2000 Apr;62(4):1016-23. [PubMed:10727272 ]
  7. Walker JI, Faik P, Morgan MJ: Characterization of the 5' end of the gene for human glucose phosphate isomerase (GPI). Genomics. 1990 Aug;7(4):638-43. [PubMed:2387591 ]
  8. Faik P, Walker JI, Redmill AA, Morgan MJ: Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences. Nature. 1988 Mar 31;332(6163):455-7. [PubMed:3352745 ]
  9. Haga A, Niinaka Y, Raz A: Phosphohexose isomerase/autocrine motility factor/neuroleukin/maturation factor is a multifunctional phosphoprotein. Biochim Biophys Acta. 2000 Jul 14;1480(1-2):235-44. [PubMed:11004567 ]
  10. Funasaka T, Haga A, Raz A, Nagase H: Tumor autocrine motility factor is an angiogenic factor that stimulates endothelial cell motility. Biochem Biophys Res Commun. 2001 Jul 6;285(1):118-28. [PubMed:11437381 ]
  11. Amraei M, Nabi IR: Species specificity of the cytokine function of phosphoglucose isomerase. FEBS Lett. 2002 Aug 14;525(1-3):151-5. [PubMed:12163179 ]
  12. Yanagawa T, Funasaka T, Tsutsumi S, Raz T, Tanaka N, Raz A: Differential regulation of phosphoglucose isomerase/autocrine motility factor activities by protein kinase CK2 phosphorylation. J Biol Chem. 2005 Mar 18;280(11):10419-26. Epub 2005 Jan 5. [PubMed:15637053 ]
  13. Read J, Pearce J, Li X, Muirhead H, Chirgwin J, Davies C: The crystal structure of human phosphoglucose isomerase at 1.6 A resolution: implications for catalytic mechanism, cytokine activity and haemolytic anaemia. J Mol Biol. 2001 Jun 1;309(2):447-63. [PubMed:11371164 ]
  14. Tanaka N, Haga A, Uemura H, Akiyama H, Funasaka T, Nagase H, Raz A, Nakamura KT: Inhibition mechanism of cytokine activity of human autocrine motility factor examined by crystal structure analyses and site-directed mutagenesis studies. J Mol Biol. 2002 May 10;318(4):985-97. [PubMed:12054796 ]
  15. Davies C, Muirhead H, Chirgwin J: The structure of human phosphoglucose isomerase complexed with a transition-state analogue. Acta Crystallogr D Biol Crystallogr. 2003 Jun;59(Pt 6):1111-3. Epub 2003 May 23. [PubMed:12777791 ]
  16. Cordeiro AT, Godoi PH, Silva CH, Garratt RC, Oliva G, Thiemann OH: Crystal structure of human phosphoglucose isomerase and analysis of the initial catalytic steps. Biochim Biophys Acta. 2003 Feb 21;1645(2):117-22. [PubMed:12573240 ]
  17. Walker JI, Layton DM, Bellingham AJ, Morgan MJ, Faik P: DNA sequence abnormalities in human glucose 6-phosphate isomerase deficiency. Hum Mol Genet. 1993 Mar;2(3):327-9. [PubMed:8499925 ]
  18. Xu W, Beutler E: The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia. J Clin Invest. 1994 Dec;94(6):2326-9. [PubMed:7989588 ]
  19. Baronciani L, Zanella A, Bianchi P, Zappa M, Alfinito F, Iolascon A, Tannoia N, Beutler E, Sirchia G: Study of the molecular defects in glucose phosphate isomerase-deficient patients affected by chronic hemolytic anemia. Blood. 1996 Sep 15;88(6):2306-10. [PubMed:8822952 ]
  20. Kanno H, Fujii H, Hirono A, Ishida Y, Ohga S, Fukumoto Y, Matsuzawa K, Ogawa S, Miwa S: Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia. Blood. 1996 Sep 15;88(6):2321-5. [PubMed:8822954 ]
  21. Beutler E, West C, Britton HA, Harris J, Forman L: Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA). Blood Cells Mol Dis. 1997 Dec;23(3):402-9. [PubMed:9446754 ]
  22. Kugler W, Breme K, Laspe P, Muirhead H, Davies C, Winkler H, Schroter W, Lakomek M: Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency. Hum Genet. 1998 Oct;103(4):450-4. [PubMed:9856489 ]