PFKAL_HUMAN
ID PFKAL_HUMAN Reviewed; 780 AA.
AC P17858; Q96A64; Q96IH4; Q9BR91;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 6.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=ATP-dependent 6-phosphofructokinase, liver type {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=PFK-L;
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE AltName: Full=6-phosphofructokinase type B;
DE AltName: Full=Phosphofructo-1-kinase isozyme B;
DE Short=PFK-B;
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_03184};
GN Name=PFKL {ECO:0000312|HGNC:HGNC:8876};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT TRP-151.
RC TISSUE=Liver;
RX PubMed=2533063; DOI=10.1089/dna.1989.8.733;
RA Levanon D., Danciger E., Dafni N., Bernstein Y., Elson A., Moens W.,
RA Brandeis M., Groner Y.;
RT "The primary structure of human liver type phosphofructokinase and its
RT comparison with other types of PFK.";
RL DNA 8:733-743(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT ALA-81.
RX PubMed=2139864; DOI=10.1016/0888-7543(90)90517-x;
RA Elson A., Levanon D., Brandeis M., Dafni N., Bernstein Y., Danciger E.,
RA Groner Y.;
RT "The structure of the human liver-type phosphofructokinase gene.";
RL Genomics 7:47-56(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, Lung, and Muscle;
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 [5]
RP PROTEIN SEQUENCE OF 2-10 (ISOFORM 1).
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [6]
RP PROTEIN SEQUENCE OF 2-10; 17-35 AND 185-210, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Prostatic carcinoma;
RA Bienvenut W.V., Gao M., Leug H., Pchelintsev N., Adams P.D.;
RL Submitted (JUL-2009) to UniProtKB.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, GLYCOSYLATION AT
RP SER-529, AND MUTAGENESIS OF THR-527 AND SER-529.
RX PubMed=22923583; DOI=10.1126/science.1222278;
RA Yi W., Clark P.M., Mason D.E., Keenan M.C., Hill C., Goddard W.A. III,
RA Peters E.C., Driggers E.M., Hsieh-Wilson L.C.;
RT "Phosphofructokinase 1 glycosylation regulates cell growth and
RT metabolism.";
RL Science 337:975-980(2012).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to
CC fructose 1,6-bisphosphate by ATP, the first committing step of
CC glycolysis (PubMed:22923583). Negatively regulates the phagocyte
CC oxidative burst in response to bacterial infection by controlling
CC cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen
CC species. Upon macrophage activation, drives the metabolic switch toward
CC glycolysis, thus preventing glucose turnover that produces NADPH via
CC pentose phosphate pathway (By similarity).
CC {ECO:0000250|UniProtKB:P12382, ECO:0000255|HAMAP-Rule:MF_03184,
CC ECO:0000269|PubMed:22923583}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-
CC bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634,
CC ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03184, ECO:0000269|PubMed:22923583};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Allosterically activated by ADP, AMP, or fructose
CC 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.
CC GlcNAcylation by OGT overcomes allosteric regulation.
CC {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000269|PubMed:22923583}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 3/4.
CC {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- SUBUNIT: Homo- and heterotetramers (By similarity). Phosphofructokinase
CC (PFK) enzyme functions as a tetramer composed of different combinations
CC of 3 types of subunits, called PFKM (where M stands for Muscle), PFKL
CC (Liver) and PFKP (Platelet). The composition of the PFK tetramer
CC differs according to the tissue type it is present in. In muscles, it
CC is composed of 4 PFKM subunits (also called M4). In the liver, the
CC predominant form is a tetramer of PFKL subunits (L4). In erythrocytes,
CC both PFKM and PFKL subunits randomly tetramerize to form M4, L4 and
CC other combinations (ML3, M2L2, M3L). The kinetic and regulatory
CC properties of the tetrameric enzyme are dependent on the subunit
CC composition, hence can vary across tissues (Probable).
CC {ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000305}.
CC -!- INTERACTION:
CC P17858; Q969Y2: GTPBP3; NbExp=3; IntAct=EBI-487243, EBI-740290;
CC P17858; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-487243, EBI-10172290;
CC P17858; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-487243, EBI-3958099;
CC P17858; P17858: PFKL; NbExp=3; IntAct=EBI-487243, EBI-487243;
CC P17858; P08237: PFKM; NbExp=6; IntAct=EBI-487243, EBI-514788;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P17858-1; Sequence=Displayed;
CC Name=2; Synonyms=a;
CC IsoId=P17858-2; Sequence=VSP_011854;
CC -!- PTM: GlcNAcylation at Ser-529 by OGT decreases enzyme activity, leading
CC to redirect glucose flux through the oxidative pentose phosphate
CC pathway. Glycosylation is stimulated by both hypoxia and glucose
CC deprivation. {ECO:0000269|PubMed:22923583}.
CC -!- MISCELLANEOUS: In human PFK exists as a system of 3 types of subunits,
CC PFKM (muscle), PFKL (liver) and PFKP (platelet) isoenzymes.
CC -!- MISCELLANEOUS: Glycosylation may play a role in cancer cell
CC proliferation: inhibition of 6-phosphofructokinase activity and
CC subsequent redirection of the glucose flux through the oxidative
CC pentose phosphate pathway confers a selective growth advantage on
CC cancer cells. Moreover GlcNAcylation is observed in multiple cancer
CC cell lines and tissue samples and GlcNAcylation leads to larger
CC xenografts tunors in mice (PubMed:22923583).
CC {ECO:0000305|PubMed:22923583}.
CC -!- SIMILARITY: Belongs to the phosphofructokinase type A (PFKA) family.
CC ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E'
CC sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_03184}.
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DR EMBL; X15573; CAA33597.1; -; mRNA.
DR EMBL; X16911; CAB46744.1; -; Genomic_DNA.
DR EMBL; X16912; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16913; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16914; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16915; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16916; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16917; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16918; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16919; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16920; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16921; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16922; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16923; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16924; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16925; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16926; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16927; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16928; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16929; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; X16930; CAB46744.1; JOINED; Genomic_DNA.
DR EMBL; AP001754; BAA95561.1; -; Genomic_DNA.
DR EMBL; BC006422; AAH06422.1; -; mRNA.
DR EMBL; BC007536; AAH07536.1; -; mRNA.
DR EMBL; BC008964; AAH08964.1; -; mRNA.
DR EMBL; BC009919; AAH09919.1; -; mRNA.
DR CCDS; CCDS33582.1; -. [P17858-1]
DR PIR; A33639; A33639.
DR RefSeq; NP_001002021.2; NM_001002021.2.
DR RefSeq; NP_002617.3; NM_002626.5. [P17858-1]
DR PDB; 7LW1; EM; 2.90 A; A/D/E/F=1-780.
DR PDBsum; 7LW1; -.
DR AlphaFoldDB; P17858; -.
DR SMR; P17858; -.
DR BioGRID; 111232; 135.
DR ComplexPortal; CPX-1998; 6-phosphofructokinase, L4 homotetramer.
DR ComplexPortal; CPX-2000; 6-phosphofructokinase, ML3 heterotetramer.
DR ComplexPortal; CPX-2001; 6-phosphofructokinase, M2L2 heterotetramer.
DR ComplexPortal; CPX-2002; 6-phosphofructokinase, M3L heterotetramer.
DR CORUM; P17858; -.
DR IntAct; P17858; 46.
DR MINT; P17858; -.
DR STRING; 9606.ENSP00000269848; -.
DR ChEMBL; CHEMBL2191; -.
DR GlyConnect; 2022; 1 N-Linked glycan (1 site).
DR GlyGen; P17858; 3 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P17858; -.
DR MetOSite; P17858; -.
DR PhosphoSitePlus; P17858; -.
DR SwissPalm; P17858; -.
DR BioMuta; PFKL; -.
DR DMDM; 134048493; -.
DR CPTAC; CPTAC-425; -.
DR CPTAC; CPTAC-426; -.
DR EPD; P17858; -.
DR jPOST; P17858; -.
DR MassIVE; P17858; -.
DR MaxQB; P17858; -.
DR PaxDb; P17858; -.
DR PeptideAtlas; P17858; -.
DR PRIDE; P17858; -.
DR ProteomicsDB; 53520; -. [P17858-1]
DR ProteomicsDB; 53521; -. [P17858-2]
DR TopDownProteomics; P17858-1; -. [P17858-1]
DR Antibodypedia; 24185; 326 antibodies from 34 providers.
DR DNASU; 5211; -.
DR Ensembl; ENST00000349048.9; ENSP00000269848.6; ENSG00000141959.17. [P17858-1]
DR GeneID; 5211; -.
DR KEGG; hsa:5211; -.
DR MANE-Select; ENST00000349048.9; ENSP00000269848.6; NM_002626.6; NP_002617.3.
DR UCSC; uc002zel.4; human. [P17858-1]
DR CTD; 5211; -.
DR DisGeNET; 5211; -.
DR GeneCards; PFKL; -.
DR HGNC; HGNC:8876; PFKL.
DR HPA; ENSG00000141959; Low tissue specificity.
DR MIM; 171860; gene.
DR neXtProt; NX_P17858; -.
DR OpenTargets; ENSG00000141959; -.
DR PharmGKB; PA33215; -.
DR VEuPathDB; HostDB:ENSG00000141959; -.
DR eggNOG; KOG2440; Eukaryota.
DR GeneTree; ENSGT00940000159292; -.
DR HOGENOM; CLU_011053_0_0_1; -.
DR InParanoid; P17858; -.
DR OMA; WFNLRPM; -.
DR OrthoDB; 172878at2759; -.
DR PhylomeDB; P17858; -.
DR TreeFam; TF300411; -.
DR BioCyc; MetaCyc:HS06881-MON; -.
DR BRENDA; 2.7.1.11; 2681.
DR PathwayCommons; P17858; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-70171; Glycolysis.
DR SABIO-RK; P17858; -.
DR SignaLink; P17858; -.
DR SIGNOR; P17858; -.
DR UniPathway; UPA00109; UER00182.
DR BioGRID-ORCS; 5211; 16 hits in 1076 CRISPR screens.
DR ChiTaRS; PFKL; human.
DR GeneWiki; PFKL; -.
DR GenomeRNAi; 5211; -.
DR Pharos; P17858; Tbio.
DR PRO; PR:P17858; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P17858; protein.
DR Bgee; ENSG00000141959; Expressed in mucosa of transverse colon and 195 other tissues.
DR ExpressionAtlas; P17858; baseline and differential.
DR Genevisible; P17858; HS.
DR GO; GO:0005945; C:6-phosphofructokinase complex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; HDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IDA:UniProtKB.
DR GO; GO:0016208; F:AMP binding; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0070061; F:fructose binding; IDA:BHF-UCL.
DR GO; GO:0070095; F:fructose-6-phosphate binding; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019900; F:kinase binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048029; F:monosaccharide binding; IBA:GO_Central.
DR GO; GO:0061621; P:canonical glycolysis; IBA:GO_Central.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006096; P:glycolytic process; IDA:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IDA:UniProtKB.
DR CDD; cd00764; Eukaryotic_PFK; 1.
DR Gene3D; 3.40.50.460; -; 2.
DR HAMAP; MF_03184; Phosphofructokinase_I_E; 1.
DR InterPro; IPR009161; 6-Pfructokinase_euk.
DR InterPro; IPR022953; ATP_PFK.
DR InterPro; IPR041914; PFK_vert-type.
DR InterPro; IPR015912; Phosphofructokinase_CS.
DR InterPro; IPR000023; Phosphofructokinase_dom.
DR InterPro; IPR035966; PKF_sf.
DR Pfam; PF00365; PFK; 2.
DR PIRSF; PIRSF000533; ATP_PFK_euk; 1.
DR PRINTS; PR00476; PHFRCTKINASE.
DR SUPFAM; SSF53784; SSF53784; 2.
DR TIGRFAMs; TIGR02478; 6PF1K_euk; 1.
DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing;
KW ATP-binding; Cytoplasm; Direct protein sequencing; Glycolysis;
KW Glycoprotein; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..780
FT /note="ATP-dependent 6-phosphofructokinase, liver type"
FT /id="PRO_0000112021"
FT REGION 2..390
FT /note="N-terminal catalytic PFK domain 1"
FT REGION 391..400
FT /note="Interdomain linker"
FT REGION 401..780
FT /note="C-terminal regulatory PFK domain 2"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 25
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 88..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 118..121
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 119
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 164..166
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 201
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 208..210
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 264
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 292
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 298..301
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 470
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 527..531
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 565
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 572..574
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 628
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 654
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 660..663
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 734
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.6, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47857"
FT MOD_RES 640
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P12382"
FT MOD_RES 775
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CARBOHYD 529
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:22923583"
FT VAR_SEQ 1..28
FT /note="MAAVDLEKLRASGAGKAIGVLTSGGDAQ -> MCNQGRGRESSRGGLHVQGS
FT CRGLSRSPQQETGFAKAPAGTDCFFHCSPGSRGQGDRKEEVTSEPGGTSIMSRLG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011854"
FT VARIANT 81
FT /note="G -> A"
FT /evidence="ECO:0000269|PubMed:2139864"
FT /id="VAR_006070"
FT VARIANT 151
FT /note="R -> W (in dbSNP:rs755851304)"
FT /evidence="ECO:0000269|PubMed:2533063"
FT /id="VAR_006071"
FT VARIANT 237
FT /note="D -> V (in dbSNP:rs1057037)"
FT /id="VAR_030872"
FT MUTAGEN 527
FT /note="T->A: Does not affect GlcNAcylation."
FT /evidence="ECO:0000269|PubMed:22923583"
FT MUTAGEN 529
FT /note="S->A: Prevents GlcNAcylation and enhance enzyme
FT activity."
FT /evidence="ECO:0000269|PubMed:22923583"
FT CONFLICT 27
FT /note="A -> R (in Ref. 1; CAA33597 and 2; CAB46744)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="S -> T (in Ref. 2; CAB46744)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="C -> S (in Ref. 1; CAA33597 and 2; CAB46744)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="Y -> N (in Ref. 2; CAB46744)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="E -> EAPPE (in Ref. 2; CAB46744)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="K -> R (in Ref. 2; CAB46744)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="A -> T (in Ref. 1; CAA33597 and 2; CAB46744)"
FT /evidence="ECO:0000305"
FT CONFLICT 648
FT /note="K -> N (in Ref. 4; AAH08964/AAH09919)"
FT /evidence="ECO:0000305"
FT CONFLICT 717
FT /note="V -> A (in Ref. 4; AAH08964/AAH09919)"
FT /evidence="ECO:0000305"
FT STRAND 16..22
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 30..43
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 56..60
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:7LW1"
FT TURN 70..75
FT /evidence="ECO:0007829|PDB:7LW1"
FT TURN 90..93
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 95..108
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 132..141
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 147..152
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 178..199
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 202..207
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 214..223
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 239..252
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 276..287
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 291..295
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 298..301
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 307..326
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 334..339
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 342..347
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 348..363
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 367..374
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 376..390
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 401..409
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 414..427
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 431..435
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 438..443
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 453..455
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 473..476
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 477..487
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 491..497
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 498..508
FT /evidence="ECO:0007829|PDB:7LW1"
FT TURN 509..513
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 515..517
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 519..526
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 541..561
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 562..571
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 578..587
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 590..593
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 601..614
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 621..627
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 636..646
FT /evidence="ECO:0007829|PDB:7LW1"
FT TURN 647..650
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 652..657
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 660..663
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 669..691
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 695..698
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 704..706
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 707..712
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 714..721
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 724..728
FT /evidence="ECO:0007829|PDB:7LW1"
FT TURN 731..734
FT /evidence="ECO:0007829|PDB:7LW1"
FT STRAND 735..738
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 740..743
FT /evidence="ECO:0007829|PDB:7LW1"
FT HELIX 744..751
FT /evidence="ECO:0007829|PDB:7LW1"
SQ SEQUENCE 780 AA; 85018 MW; 0D686CE074E9626D CRC64;
MAAVDLEKLR ASGAGKAIGV LTSGGDAQGM NAAVRAVTRM GIYVGAKVFL IYEGYEGLVE
GGENIKQANW LSVSNIIQLG GTIIGSARCK AFTTREGRRA AAYNLVQHGI TNLCVIGGDG
SLTGANIFRS EWGSLLEELV AEGKISETTA RTYSHLNIAG LVGSIDNDFC GTDMTIGTDS
ALHRIMEVID AITTTAQSHQ RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE
NFMCERLGET RSRGSRLNII IIAEGAIDRN GKPISSSYVK DLVVQRLGFD TRVTVLGHVQ
RGGTPSAFDR ILSSKMGMEA VMALLEATPD TPACVVTLSG NQSVRLPLME CVQMTKEVQK
AMDDKRFDEA TQLRGGSFEN NWNIYKLLAH QKPPKEKSNF SLAILNVGAP AAGMNAAVRS
AVRTGISHGH TVYVVHDGFE GLAKGQVQEV GWHDVAGWLG RGGSMLGTKR TLPKGQLESI
VENIRIYGIH ALLVVGGFEA YEGVLQLVEA RGRYEELCIV MCVIPATISN NVPGTDFSLG
SDTAVNAAME SCDRIKQSAS GTKRRVFIVE TMGGYCGYLA TVTGIAVGAD AAYVFEDPFN
IHDLKVNVEH MTEKMKTDIQ RGLVLRNEKC HDYYTTEFLY NLYSSEGKGV FDCRTNVLGH
LQQGGAPTPF DRNYGTKLGV KAMLWLSEKL REVYRKGRVF ANAPDSACVI GLKKKAVAFS
PVTELKKDTD FEHRMPREQW WLSLRLMLKM LAQYRISMAA YVSGELEHVT RRTLSMDKGF
