ID   G6PI_RAT                Reviewed;         558 AA.
AC   Q6P6V0;
DT   02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 143.
DE   RecName: Full=Glucose-6-phosphate isomerase {ECO:0000250|UniProtKB:P06745};
DE            Short=GPI {ECO:0000250|UniProtKB:P06745};
DE            EC=5.3.1.9 {ECO:0000269|PubMed:2709006};
DE   AltName: Full=Autocrine motility factor {ECO:0000250|UniProtKB:P06744};
DE            Short=AMF {ECO:0000250|UniProtKB:P06744};
DE   AltName: Full=Neuroleukin {ECO:0000250|UniProtKB:P06745};
DE            Short=NLK {ECO:0000250|UniProtKB:P06745};
DE   AltName: Full=Phosphoglucose isomerase {ECO:0000250|UniProtKB:P06745};
DE            Short=PGI {ECO:0000250|UniProtKB:P06745};
DE   AltName: Full=Phosphohexose isomerase {ECO:0000250|UniProtKB:P06745};
DE            Short=PHI {ECO:0000250|UniProtKB:P06745};
GN   Name=Gpi {ECO:0000312|RGD:2727};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1] {ECO:0000312|EMBL:AAH62005.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Prostate {ECO:0000312|EMBL:AAH62005.1};
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=2709006; DOI=10.1111/j.1471-4159.1989.tb09178.x;
RA   Gaitonde M.K., Murray E., Cunningham V.J.;
RT   "Effect of 6-phosphogluconate on phosphoglucose isomerase in rat brain in
RT   vitro and in vivo.";
RL   J. Neurochem. 52:1348-1352(1989).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX   PubMed=19343716; DOI=10.1002/pmic.200800664;
RA   Maurya D.K., Sundaram C.S., Bhargava P.;
RT   "Proteome profile of the mature rat olfactory bulb.";
RL   Proteomics 9:2593-2599(2009).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-86; THR-250 AND SER-455, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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 (PubMed:2709006). 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:0000269|PubMed:2709006}.
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:0000269|PubMed:2709006};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.593 mM for glucose-6-phosphate {ECO:0000269|PubMed:2709006};
CC         KM=0.095 mM for fructose-6-phosphate {ECO:0000269|PubMed:2709006};
CC         Vmax=2.291 nmol/min/mg enzyme with glucose-6-phosphate as substrate
CC         {ECO:0000269|PubMed:2709006};
CC         Vmax=98 nmol/min/mg enzyme with fructose-6-phosphate as substrate
CC         {ECO:0000269|PubMed:2709006};
CC   -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC       phosphate and glycerone phosphate from D-glucose: step 2/4.
CC       {ECO:0000269|PubMed:2709006}.
CC   -!- SUBUNIT: Homodimer; in the catalytically active form. Monomer in the
CC       secreted form. {ECO:0000250|UniProtKB:P06744}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19343716}. Secreted
CC       {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}.
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DR   EMBL; BC062005; AAH62005.1; -; mRNA.
DR   RefSeq; NP_997475.1; NM_207592.1.
DR   AlphaFoldDB; Q6P6V0; -.
DR   SMR; Q6P6V0; -.
DR   BioGRID; 253982; 2.
DR   IntAct; Q6P6V0; 11.
DR   STRING; 10116.ENSRNOP00000029515; -.
DR   iPTMnet; Q6P6V0; -.
DR   PhosphoSitePlus; Q6P6V0; -.
DR   SwissPalm; Q6P6V0; -.
DR   jPOST; Q6P6V0; -.
DR   PaxDb; 10116-ENSRNOP00000029515; -.
DR   Ensembl; ENSRNOT00000032613.5; ENSRNOP00000029515.3; ENSRNOG00000023150.6.
DR   Ensembl; ENSRNOT00000097410.1; ENSRNOP00000087782.1; ENSRNOG00000023150.6.
DR   Ensembl; ENSRNOT00055057309; ENSRNOP00055047244; ENSRNOG00055033158.
DR   Ensembl; ENSRNOT00060047108; ENSRNOP00060039184; ENSRNOG00060027113.
DR   Ensembl; ENSRNOT00065054503; ENSRNOP00065044842; ENSRNOG00065031609.
DR   GeneID; 292804; -.
DR   KEGG; rno:292804; -.
DR   UCSC; RGD:2727; rat.
DR   AGR; RGD:2727; -.
DR   CTD; 2821; -.
DR   RGD; 2727; Gpi.
DR   eggNOG; KOG2446; Eukaryota.
DR   GeneTree; ENSGT00390000000707; -.
DR   HOGENOM; CLU_017947_3_0_1; -.
DR   InParanoid; Q6P6V0; -.
DR   OMA; DWYRQLW; -.
DR   OrthoDB; 1657888at2759; -.
DR   PhylomeDB; Q6P6V0; -.
DR   TreeFam; TF300436; -.
DR   Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   Reactome; R-RNO-70171; Glycolysis.
DR   Reactome; R-RNO-70263; Gluconeogenesis.
DR   SABIO-RK; Q6P6V0; -.
DR   UniPathway; UPA00109; UER00181.
DR   PRO; PR:Q6P6V0; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000023150; Expressed in skeletal muscle tissue and 19 other cell types or tissues.
DR   GO; GO:0060170; C:ciliary membrane; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISO:RGD.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
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; IDA:RGD.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0048029; F:monosaccharide binding; IPI:RGD.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR   GO; GO:0034101; P:erythrocyte homeostasis; ISO:RGD.
DR   GO; GO:0006094; P:gluconeogenesis; ISO:RGD.
DR   GO; GO:0051156; P:glucose 6-phosphate metabolic process; IDA:RGD.
DR   GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR   GO; GO:0006096; P:glycolytic process; ISO:RGD.
DR   GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR   GO; GO:0007611; P:learning or memory; IEP:RGD.
DR   GO; GO:0001707; P:mesoderm formation; ISO:RGD.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR   GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR   GO; GO:0002639; P:positive regulation of immunoglobulin production; ISO:RGD.
DR   GO; GO:0046686; P:response to cadmium ion; IEP:RGD.
DR   GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR   GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR   GO; GO:0035994; P:response to muscle stretch; IEP:RGD.
DR   GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR   GO; GO:0033574; P:response to testosterone; IEP:RGD.
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.
DR   World-2DPAGE; 0004:Q6P6V0; -.
DR   Genevisible; Q6P6V0; RN.
PE   1: Evidence at protein level;
KW   Acetylation; Cytokine; Cytoplasm; Gluconeogenesis; Glycolysis;
KW   Growth factor; Isomerase; Phosphoprotein; Reference proteome; Secreted;
KW   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                   /evidence="ECO:0000250|UniProtKB:P06744"
FT                   /id="PRO_0000349123"
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         86
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         107
FT                   /note="Phosphoserine"
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:0007744|PubMed:22673903"
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:0007744|PubMed:22673903"
SQ   SEQUENCE   558 AA;  62827 MW;  2550ACB874E0302C CRC64;
     MAALTRNPEF QKLLEWHRAN SANLKLRELF EADPERFNHF SLNLNTNHGH ILLDYSKNLV
     NKEVLHMLVD LAKSRGVEAA RDNMFSGLKI NSTEDRAVLH VALRNRSNRS IMMDGKDVMP
     EVNKVLDKMK SFCQRVRSGD WKGYTGKAIT DIINIGIGGS DLGPLMVTEA LKPYSKGGPR
     VWFVSNIDGT HIAKTLANLN PESSLFIIAS KTFTTQETIT NAETAKEWFL QAAKDPSAVA
     KHFVALSTNT DKVKEFGIDP KNMFEFWDWV GGRYSLWSAI GLSIALHVGF DHFEQLLSGA
     HWMDQHFMKT PLDKNAPVLL ALLGIWYINF YGCETHAMLP YDQYMHRFAA YFQQGDMESN
     GKYITKSGAR VDYQTGPIVW GEPGTNGQHA FYQLIHQGTK MIPCDFLIPV QTQHPIRNGL
     HHKILLANFL AQTEALMKGK SPEEARKELQ AAGKSPEELE KLLPHKVFEG NRPTNSIVFT
     KLTPFILGAL IAMYEHKIFV QGIIWDINSF DQWGVELGKQ LAKKIEPELD GSSAVTSHDS
     STNGLIGFIK LQRDTKID
//