ID G6PI_PIG Reviewed; 558 AA. AC P08059; Q29556; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 168. DE RecName: Full=Glucose-6-phosphate isomerase {ECO:0000303|PubMed:6115414}; DE Short=GPI {ECO:0000303|PubMed:6115414}; DE EC=5.3.1.9 {ECO:0000250|UniProtKB:P06745}; DE AltName: Full=Autocrine motility factor {ECO:0000250|UniProtKB:P06744}; DE Short=AMF {ECO:0000250|UniProtKB:P06744}; DE AltName: Full=Neuroleukin {ECO:0000303|PubMed:3352744}; DE Short=NLK {ECO:0000303|PubMed:3352744}; DE AltName: Full=Phosphoglucose isomerase {ECO:0000303|PubMed:7821788}; DE Short=PGI {ECO:0000303|PubMed:7821788}; DE AltName: Full=Phosphohexose isomerase {ECO:0000303|PubMed:3352744}; DE Short=PHI {ECO:0000303|PubMed:3352744}; GN Name=GPI {ECO:0000303|PubMed:6115414}; OS Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus. OX NCBI_TaxID=9823; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3352744; DOI=10.1038/332454a0; RA Chaput M., Claes V., Portetelle D., Clutdts I., Cravador A., Burny A., RA Gras H., Tartar A.; RT "The neurotrophic factor neuroleukin is 90% homologous with phosphohexose RT isomerase."; RL Nature 332:454-455(1988). RN [2] RP SEQUENCE REVISION. RA Burny A.; RL Submitted (AUG-1988) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7821788; DOI=10.1016/0378-1119(94)90432-4; RA Claes V., Kettmann R., Burny A.; RT "Structure of the gene encoding pig phosphoglucose isomerase."; RL Gene 150:235-241(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-17. RC STRAIN=Belgian Landrace; RX PubMed=2248981; DOI=10.1016/0167-4781(90)90009-q; RA Claes V., Taquet A.N., Kettmann R., Burny A.; RT "Sequence analysis of the pig phosphoglucose isomerase gene promoter RT region."; RL Biochim. Biophys. Acta 1087:339-340(1990). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 238-357. RX PubMed=2889410; DOI=10.1111/j.1365-2052.1987.tb00763.x; RA Davies W., Harbitz I., Hauge J.G.; RT "A partial cDNA clone for porcine glucosephosphate isomerase: isolation, RT characterization and use in detection of restriction fragment length RT polymorphisms."; RL Anim. Genet. 18:233-240(1987). RN [6] RP X-RAY CRYSTALLOGRAPHY (6.0 ANGSTROMS). RX PubMed=4475113; DOI=10.1016/0022-2836(74)90170-3; RA Muirhead H., Shaw P.J.; RT "Three-dimensional structure of pig muscle phosphoglucose isomerase at 6-A RT resolution."; RL J. Mol. Biol. 89:195-203(1974). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), AND PROTEIN SEQUENCE OF 554-558. RX PubMed=6115414; DOI=10.1098/rstb.1981.0068; RA Achari A., Marshall S.E., Muirhead H., Palmieri R.H., Noltmann E.A.; RT "Glucose-6-phosphate isomerase."; RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 293:145-157(1981). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) ALONE AND IN COMPLEX WITH RP 5-PHOSPHOARABINONATE. RX PubMed=12402366; DOI=10.1002/prot.10255; RA Davies C., Muirhead H.; RT "Crystal structure of phosphoglucose isomerase from pig muscle and its RT complex with 5-phosphoarabinonate."; RL Proteins 49:577-579(2002). CC -!- FUNCTION: In the cytoplasm, catalyzes the conversion of glucose-6- CC phosphate to fructose-6-phosphate, the second step in glycolysis, and CC the reverse reaction during gluconeogenesis (By similarity). Besides CC it's role as a glycolytic enzyme, also acts as a secreted cytokine: CC acts as an angiogenic factor (AMF) that stimulates endothelial cell CC motility. Acts as a neurotrophic factor, neuroleukin, for spinal and CC sensory neurons. It is secreted by lectin-stimulated T-cells and CC induces immunoglobulin secretion (By similarity). CC {ECO:0000250|UniProtKB:P06744, ECO:0000250|UniProtKB:P06745}. CC -!- CATALYTIC ACTIVITY: CC Reaction=alpha-D-glucose 6-phosphate = beta-D-fructose 6-phosphate; CC Xref=Rhea:RHEA:11816, ChEBI:CHEBI:57634, ChEBI:CHEBI:58225; CC EC=5.3.1.9; Evidence={ECO:0000250|UniProtKB:P06744}; CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3- CC phosphate and glycerone phosphate from D-glucose: step 2/4. CC {ECO:0000250|UniProtKB:P06744}. CC -!- SUBUNIT: Homodimer in the catalytically active form, monomer in the CC secreted form. {ECO:0000269|PubMed:12402366}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P06744}. CC Secreted {ECO:0000250|UniProtKB:P06744}. CC -!- PTM: Phosphorylation at Ser-185 by CK2 has been shown to decrease CC enzymatic activity and may contribute to secretion by a non-classical CC secretory pathway. {ECO:0000250|UniProtKB:P06744}. CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P06744}. CC -!- SIMILARITY: Belongs to the GPI family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X07382; CAA30295.1; -; mRNA. DR EMBL; Z28396; CAA82246.1; -; Genomic_DNA. DR EMBL; Z28397; CAA82246.1; JOINED; Genomic_DNA. DR EMBL; Z28398; CAA82246.1; JOINED; Genomic_DNA. DR EMBL; Z28399; CAA82246.1; JOINED; Genomic_DNA. DR EMBL; Z28400; CAA82246.1; JOINED; Genomic_DNA. DR EMBL; Z28401; CAA82246.1; JOINED; Genomic_DNA. DR EMBL; Z28402; CAA82246.1; JOINED; Genomic_DNA. DR EMBL; Z28403; CAA82246.1; JOINED; Genomic_DNA. DR EMBL; Z28404; CAA82246.1; JOINED; Genomic_DNA. DR EMBL; X53719; CAA37755.1; -; mRNA. DR EMBL; M54975; AAA31048.1; -; mRNA. DR PIR; I47142; I47142. DR PIR; S00895; NUPG. DR RefSeq; NP_999495.1; NM_214330.1. DR PDB; 1GZD; X-ray; 2.50 A; A=2-558. DR PDB; 1GZV; X-ray; 3.51 A; A=2-558. DR PDBsum; 1GZD; -. DR PDBsum; 1GZV; -. DR AlphaFoldDB; P08059; -. DR SMR; P08059; -. DR STRING; 9823.ENSSSCP00000003094; -. DR PaxDb; 9823-ENSSSCP00000003094; -. DR PeptideAtlas; P08059; -. DR Ensembl; ENSSSCT00000003175.5; ENSSSCP00000003094.3; ENSSSCG00000002873.5. DR Ensembl; ENSSSCT00025047497.1; ENSSSCP00025020351.1; ENSSSCG00025034806.1. DR Ensembl; ENSSSCT00035108133.1; ENSSSCP00035046820.1; ENSSSCG00035079108.1. DR Ensembl; ENSSSCT00040087102.1; ENSSSCP00040038243.1; ENSSSCG00040063535.1. DR Ensembl; ENSSSCT00045030938.1; ENSSSCP00045021461.1; ENSSSCG00045018132.1. DR Ensembl; ENSSSCT00050068357.1; ENSSSCP00050029323.1; ENSSSCG00050050209.1. DR Ensembl; ENSSSCT00055037281.1; ENSSSCP00055029618.1; ENSSSCG00055019026.1. DR Ensembl; ENSSSCT00060052940.1; ENSSSCP00060022543.1; ENSSSCG00060039122.1. DR Ensembl; ENSSSCT00065071617.1; ENSSSCP00065031218.1; ENSSSCG00065052281.1. DR GeneID; 397602; -. DR KEGG; ssc:397602; -. DR CTD; 2821; -. DR VGNC; VGNC:97068; GPI. DR eggNOG; KOG2446; Eukaryota. DR GeneTree; ENSGT00390000000707; -. DR InParanoid; P08059; -. DR OMA; DWYRQLW; -. DR OrthoDB; 1657888at2759; -. DR Reactome; R-SSC-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-SSC-6798695; Neutrophil degranulation. DR Reactome; R-SSC-70171; Glycolysis. DR Reactome; R-SSC-70263; Gluconeogenesis. DR UniPathway; UPA00109; UER00181. DR EvolutionaryTrace; P08059; -. DR Proteomes; UP000008227; Chromosome 6. DR Proteomes; UP000314985; Unplaced. DR Proteomes; UP000694570; Unplaced. DR Proteomes; UP000694571; Unplaced. DR Proteomes; UP000694720; Unplaced. DR Proteomes; UP000694722; Unplaced. DR Proteomes; UP000694723; Unplaced. DR Proteomes; UP000694724; Unplaced. DR Proteomes; UP000694725; Unplaced. DR Proteomes; UP000694726; Unplaced. DR Proteomes; UP000694727; Unplaced. DR Proteomes; UP000694728; Unplaced. DR Bgee; ENSSSCG00000002873; Expressed in semimembranosus muscle and 43 other cell types or tissues. DR ExpressionAtlas; P08059; baseline and differential. DR GO; GO:0060170; C:ciliary membrane; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW. DR GO; GO:0097367; F:carbohydrate derivative binding; IEA:InterPro. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW. DR GO; GO:0004347; F:glucose-6-phosphate isomerase activity; ISS:UniProtKB. DR GO; GO:0048029; F:monosaccharide binding; IBA:GO_Central. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl. DR GO; GO:0034101; P:erythrocyte homeostasis; IEA:Ensembl. DR GO; GO:0006094; P:gluconeogenesis; IBA:GO_Central. DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; ISS:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl. DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IEA:Ensembl. DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IEA:Ensembl. DR CDD; cd05015; SIS_PGI_1; 1. DR CDD; cd05016; SIS_PGI_2; 1. DR Gene3D; 1.10.1390.10; -; 1. DR HAMAP; MF_00473; G6P_isomerase; 1. DR InterPro; IPR001672; G6P_Isomerase. DR InterPro; IPR023096; G6P_Isomerase_C. DR InterPro; IPR018189; Phosphoglucose_isomerase_CS. DR InterPro; IPR046348; SIS_dom_sf. DR InterPro; IPR035476; SIS_PGI_1. DR InterPro; IPR035482; SIS_PGI_2. DR PANTHER; PTHR11469; GLUCOSE-6-PHOSPHATE ISOMERASE; 1. DR PANTHER; PTHR11469:SF1; GLUCOSE-6-PHOSPHATE ISOMERASE; 1. DR Pfam; PF00342; PGI; 1. DR PRINTS; PR00662; G6PISOMERASE. DR SUPFAM; SSF53697; SIS domain; 1. DR PROSITE; PS00765; P_GLUCOSE_ISOMERASE_1; 1. DR PROSITE; PS00174; P_GLUCOSE_ISOMERASE_2; 1. DR PROSITE; PS51463; P_GLUCOSE_ISOMERASE_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytokine; Cytoplasm; Direct protein sequencing; KW Gluconeogenesis; Glycolysis; Hydroxylation; Isomerase; Phosphoprotein; KW Reference proteome; Secreted; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P06744" FT CHAIN 2..558 FT /note="Glucose-6-phosphate isomerase" FT /id="PRO_0000180540" FT ACT_SITE 358 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:P06745" FT ACT_SITE 389 FT /evidence="ECO:0000250|UniProtKB:P06745" FT ACT_SITE 519 FT /evidence="ECO:0000250|UniProtKB:P06745" FT BINDING 159..160 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P06745" FT BINDING 210..215 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P06745" FT BINDING 354 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P06745" FT BINDING 358 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P06745" FT BINDING 389 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P06745" FT BINDING 519 FT /ligand="D-glucose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:61548" FT /evidence="ECO:0000250|UniProtKB:P06745" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P06744" FT MOD_RES 12 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P06744" FT MOD_RES 34 FT /note="N6-(2-hydroxyisobutyryl)lysine" FT /evidence="ECO:0000250|UniProtKB:P06744" FT MOD_RES 107 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06744" FT MOD_RES 109 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P06744" FT MOD_RES 142 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P06744" FT MOD_RES 185 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000250|UniProtKB:P06744" FT MOD_RES 250 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q6P6V0" FT MOD_RES 454 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P06745" FT MOD_RES 454 FT /note="N6-malonyllysine; alternate" FT /evidence="ECO:0000250" FT MOD_RES 454 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P06745" FT MOD_RES 455 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06744" FT CONFLICT 156..157 FT /note="Missing (in Ref. 3; CAA82246)" FT /evidence="ECO:0000305" FT CONFLICT 344 FT /note="Y -> H (in Ref. 5; AAA31048)" FT /evidence="ECO:0000305" FT CONFLICT 347..398 FT /note="RFAAYFQQGDMESNGKYITKSGTRVDHQTGPIVWGEPGTNGQHAFYQLIHQG FT -> ALLPTSSRVTWSPTGSTSPSPAPVWTTRRAPLCGGSQGPMASMPSTSSS (in FT Ref. 3; CAA82246)" FT /evidence="ECO:0000305" FT CONFLICT 481..482 FT /note="KL -> NV (in Ref. 3; CAA82246)" FT /evidence="ECO:0000305" FT CONFLICT 550 FT /note="K -> M (in Ref. 3; CAA82246)" FT /evidence="ECO:0000305" FT HELIX 3..6 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 8..20 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 21..23 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 26..32 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 36..39 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 40..45 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 50..54 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 62..74 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 77..86 FT /evidence="ECO:0007829|PDB:1GZD" FT TURN 92..95 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 100..103 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 119..138 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 151..155 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 159..170 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 172..175 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 180..184 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 189..196 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 204..209 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 216..233 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 236..241 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 243..248 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 250..255 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 260..262 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 263..265 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 272..274 FT /evidence="ECO:0007829|PDB:1GZD" FT TURN 276..278 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 279..281 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 282..288 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 290..309 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 312..314 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 316..329 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 335..341 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 343..345 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 348..360 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 386..389 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 392..397 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 398..400 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 404..411 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 416..438 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 442..451 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 456..459 FT /evidence="ECO:0007829|PDB:1GZD" FT TURN 460..462 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 463..466 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 474..481 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 484..505 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 513..515 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 516..528 FT /evidence="ECO:0007829|PDB:1GZD" FT STRAND 530..533 FT /evidence="ECO:0007829|PDB:1GZD" FT HELIX 540..554 FT /evidence="ECO:0007829|PDB:1GZD" SQ SEQUENCE 558 AA; 63126 MW; 84DA1B15CF0C702F CRC64; MAALTQNPQF KKLQTWYHEH RSDLNLRRLF EGDKDRFNHF SLNLNTNHGR ILLDYSKNLV TEAVMQMLVD LAKSRGVEAA RERMFNGEKI NFTEDRAVLH VALRNRSNTP ILVDGKDVMP EVNRVLEKMK SFCKRVRSGE WKGYSGKSIT DVINIGIGGS DLGPLMVTEA LKPYSAEGPR VWFVSNIDGT HIAKTLATLN PESSLFIIAS KTFTTQETIT NAETAKEWFL QSAKDPSAVA KHFVALSTNT TKVKEFGIDP QNMFEFWDWV GGRYSLWSAI GLSIALHVGF DNFEQLLSGA HWMDQHFRTT PLEKNAPVLL ALLGIWYINF FGCETHAMLP YDQYLHRFAA YFQQGDMESN GKYITKSGTR VDHQTGPIVW GEPGTNGQHA FYQLIHQGTK MIPCDFLIPV QTQHPIRKGL HHKILLANFL AQTEALMKGK STEEARKELQ AAGKSPEDFE KLLPHKVFEG NRPTNSIVFT KLTPFILGAL IAMYEHKIFV QGVIWDINSF DQWGVELGKQ LAKKIEPELD GSSPVTSHDS STNGLINFIK QEREARSQ //