G6PI_RABIT
ID G6PI_RABIT Reviewed; 558 AA.
AC Q9N1E2; Q9N184;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Glucose-6-phosphate isomerase {ECO:0000250|UniProtKB:P06744};
DE Short=GPI {ECO:0000250|UniProtKB:P06744};
DE EC=5.3.1.9 {ECO:0000250|UniProtKB:P06745};
DE AltName: Full=Autocrine motility factor {ECO:0000303|PubMed:10669800};
DE Short=AMF {ECO:0000303|PubMed:10669800};
DE AltName: Full=Neuroleukin {ECO:0000303|PubMed:10669800};
DE Short=NLK {ECO:0000303|PubMed:10669800};
DE AltName: Full=Phosphoglucose isomerase {ECO:0000303|PubMed:10653639};
DE Short=PGI {ECO:0000303|PubMed:10653639};
DE AltName: Full=Phosphohexose isomerase {ECO:0000250|UniProtKB:P06744};
DE Short=PHI {ECO:0000250|UniProtKB:P06744};
GN Name=GPI {ECO:0000250|UniProtKB:P06744};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Fast-twitch skeletal muscle;
RX PubMed=10669800; DOI=10.1016/s0167-4838(99)00258-7;
RA Li X., Chirgwin J.M.;
RT "Rabbit phosphoglucose isomerase/neuroleukin/autocrine motility factor:
RT cloning via interspecies identity.";
RL Biochim. Biophys. Acta 1476:363-367(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RC STRAIN=New Zealand white; TISSUE=Muscle;
RX PubMed=10653639; DOI=10.1021/bi991604m;
RA Jeffery C.J., Bahnson B.J., Chien W., Ringe D., Petsko G.A.;
RT "Crystal structure of rabbit phosphoglucose isomerase, a glycolytic enzyme
RT that moonlights as neuroleukin, autocrine motility factor, and
RT differentiation mediator.";
RL Biochemistry 39:955-964(2000).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH
RP 5-PHOSPHO-D-ARABINONATE, AND ACTIVE SITE.
RX PubMed=11327814; DOI=10.1021/bi0018483;
RA Jeffery C.J., Hardre R., Salmon L.;
RT "Crystal structure of rabbit phosphoglucose isomerase complexed with 5-
RT phospho-D-arabinonate identifies the role of Glu357 in catalysis.";
RL Biochemistry 40:1560-1566(2001).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH F6P, AND ACTIVE SITE.
RX PubMed=11425306; DOI=10.1021/bi002916o;
RA Lee J.H., Chang K.Z., Patel V., Jeffery C.J.;
RT "Crystal structure of rabbit phosphoglucose isomerase complexed with its
RT substrate D-fructose 6-phosphate.";
RL Biochemistry 40:7799-7805(2001).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), AND SUBUNIT.
RX PubMed=12368100; DOI=10.1016/s0022-2836(02)00892-6;
RA Arsenieva D., Jeffery C.J.;
RT "Conformational changes in phosphoglucose isomerase induced by ligand
RT binding.";
RL J. Mol. Biol. 323:77-84(2002).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH
RP 5-PHOSPHO-D-ARABINONOHYDROXAMIC ACID.
RX PubMed=11983887; DOI=10.1073/pnas.052131799;
RA Arsenieva D., Hardre R., Salmon L., Jeffery C.J.;
RT "The crystal structure of rabbit phosphoglucose isomerase complexed with 5-
RT phospho-D-arabinonohydroxamic acid.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:5872-5877(2002).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
RX PubMed=12595702; DOI=10.1107/s0907444902023387;
RA Davies C., Muirhead H.;
RT "Structure of native phosphoglucose isomerase from rabbit: conformational
RT changes associated with catalytic function.";
RL Acta Crystallogr. D 59:453-465(2003).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH
RP D-SORBITOL-6-PHOSPHATE.
RX PubMed=15689508; DOI=10.1110/ps.041070205;
RA Lee J.H., Jeffery C.J.;
RT "The crystal structure of rabbit phosphoglucose isomerase complexed with D-
RT sorbitol-6-phosphate, an analog of the open chain form of D-glucose-6-
RT phosphate.";
RL Protein Sci. 14:727-734(2005).
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:11327814,
CC ECO:0000269|PubMed:11425306, ECO:0000269|PubMed:11983887,
CC ECO:0000269|PubMed:12368100, ECO:0000269|PubMed:15689508}.
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}.
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DR EMBL; AF199601; AAF13713.2; -; mRNA.
DR EMBL; AF222069; AAF35988.1; -; mRNA.
DR RefSeq; NP_001075538.1; NM_001082069.2.
DR PDB; 1DQR; X-ray; 2.50 A; A/B=2-558.
DR PDB; 1G98; X-ray; 1.90 A; A/B=1-558.
DR PDB; 1HM5; X-ray; 1.80 A; A/B=1-558.
DR PDB; 1HOX; X-ray; 2.10 A; A/B=1-558.
DR PDB; 1KOJ; X-ray; 1.90 A; A/B=2-558.
DR PDB; 1N8T; X-ray; 2.50 A; A/B=2-558.
DR PDB; 1XTB; X-ray; 2.00 A; A/B=1-558.
DR PDBsum; 1DQR; -.
DR PDBsum; 1G98; -.
DR PDBsum; 1HM5; -.
DR PDBsum; 1HOX; -.
DR PDBsum; 1KOJ; -.
DR PDBsum; 1N8T; -.
DR PDBsum; 1XTB; -.
DR AlphaFoldDB; Q9N1E2; -.
DR SMR; Q9N1E2; -.
DR STRING; 9986.ENSOCUP00000001250; -.
DR BindingDB; Q9N1E2; -.
DR ChEMBL; CHEMBL1770045; -.
DR GeneID; 100008744; -.
DR KEGG; ocu:100008744; -.
DR CTD; 2821; -.
DR eggNOG; KOG2446; Eukaryota.
DR InParanoid; Q9N1E2; -.
DR OrthoDB; 446616at2759; -.
DR BRENDA; 5.3.1.9; 1749.
DR SABIO-RK; Q9N1E2; -.
DR UniPathway; UPA00109; UER00181.
DR EvolutionaryTrace; Q9N1E2; -.
DR PRO; PR:Q9N1E2; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0006094; P:gluconeogenesis; IEA:UniProtKB-KW.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; ISS:UniProtKB.
DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway.
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; PTHR11469; 1.
DR Pfam; PF00342; PGI; 1.
DR PRINTS; PR00662; G6PISOMERASE.
DR SUPFAM; SSF53697; SSF53697; 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; Gluconeogenesis;
KW Glycolysis; Hydroxylation; Isomerase; Phosphoprotein; Reference proteome;
KW 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_0000180541"
FT ACT_SITE 358
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:11327814,
FT ECO:0000269|PubMed:11425306"
FT ACT_SITE 389
FT /evidence="ECO:0000269|PubMed:11327814,
FT ECO:0000269|PubMed:11425306"
FT ACT_SITE 519
FT /evidence="ECO:0000269|PubMed:11327814,
FT ECO:0000269|PubMed:11425306"
FT BINDING 159..160
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000269|PubMed:11425306,
FT ECO:0007744|PDB:1HOX"
FT BINDING 210..215
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000269|PubMed:11425306,
FT ECO:0007744|PDB:1HOX"
FT BINDING 354
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000269|PubMed:11425306,
FT ECO:0007744|PDB:1HOX"
FT BINDING 358
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000269|PubMed:11425306,
FT ECO:0007744|PDB:1HOX"
FT BINDING 389
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /evidence="ECO:0000269|PubMed:11425306,
FT ECO:0007744|PDB:1HOX"
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 223
FT /note="E -> K (in Ref. 2; AAF35988)"
FT /evidence="ECO:0000305"
FT HELIX 3..6
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 8..20
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 21..23
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 26..31
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:1DQR"
FT HELIX 62..74
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 77..85
FT /evidence="ECO:0007829|PDB:1HM5"
FT TURN 92..95
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 100..103
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 112..118
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 119..138
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 162..170
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 189..196
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 204..209
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 216..233
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 239..242
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 250..256
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:1G98"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:1HM5"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:1XTB"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 282..288
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 290..309
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 316..329
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 335..341
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 348..360
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:1HM5"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 392..397
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:1KOJ"
FT STRAND 404..411
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 417..419
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 420..438
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 442..451
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 456..462
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 463..466
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 474..481
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 484..504
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 516..529
FT /evidence="ECO:0007829|PDB:1HM5"
FT STRAND 530..533
FT /evidence="ECO:0007829|PDB:1HM5"
FT HELIX 540..552
FT /evidence="ECO:0007829|PDB:1HM5"
SQ SEQUENCE 558 AA; 62747 MW; BB4E3AB31BBD55E4 CRC64;
MAALTRNPQF QKLQQWHREH GSELNLRHLF DTDKERFNHF SLTLNTNHGH ILLDYSKNLV
TEEVMHMLLD LAKSRGVEAA RESMFNGEKI NSTEDRAVLH VALRNRSNTP IVVDGKDVMP
EVNKVLDKMK AFCQRVRSGD WKGYTGKTIT DVINIGIGGS DLGPLMVTEA LKPYSSGGPR
VWFVSNIDGT HIAKTLACLN PESSLFIIAS KTFTTQETIT NAETAKDWFL LSAKDPSTVA
KHFVALSTNT AKVKEFGIDP QNMFEFWDWV GGRYSLWSAI GLSIALHVGF DNFEQLLSGA
HWMDQHFRTT PLEKNAPVLL AMLGIWYINC FGCETQAVLP YDQYLHRFAA YFQQGDMESN
GKYITKSGAR VDHQTGPIVW GEPGTNGQHA FYQLIHQGTK MIPCDFLIPV QTQHPIRKGL
HHKILLANFL AQTEALMKGK STEEARKELQ AAGKSPEDLM KLLPHKVFEG NRPTNSIVFT
KLTPFILGAL IAMYEHKIFV QGVVWDINSF DQWGVELGKQ LAKKIEPELD GSSPVTSHDS
STNGLINFIK QQREAKIQ
