F262_HUMAN
ID F262_HUMAN Reviewed; 505 AA.
AC O60825; O60824; Q5VVQ3; Q5VVQ4; Q9H3P1;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 {ECO:0000305};
DE Short=6PF-2-K/Fru-2,6-P2ase 2;
DE Short=PFK/FBPase 2;
DE AltName: Full=6PF-2-K/Fru-2,6-P2ase heart-type isozyme;
DE Includes:
DE RecName: Full=6-phosphofructo-2-kinase;
DE EC=2.7.1.105 {ECO:0000269|PubMed:11069105};
DE Includes:
DE RecName: Full=Fructose-2,6-bisphosphatase;
DE EC=3.1.3.46 {ECO:0000269|PubMed:11069105};
GN Name=PFKFB2 {ECO:0000312|HGNC:HGNC:8873};
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=9652401; DOI=10.1046/j.1432-1327.1998.2540103.x;
RA Heine-Suner D., Diaz-Guillen M.A., Lange A.J., Rodriguez de Cordoba S.;
RT "Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6-
RT bisphosphatase heart isoform gene (PFKFB2).";
RL Eur. J. Biochem. 254:103-110(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Heart;
RX PubMed=11374908; DOI=10.1006/geno.2001.6527;
RA Soejima H., Kawamoto S., Akai J., Miyoshi O., Arai Y., Morohka T.,
RA Matsuo S., Niikawa N., Kimura A., Okubo K., Mukai T.;
RT "Isolation of novel heart-specific genes using the BodyMap database.";
RL Genomics 74:115-120(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Matsutani A.;
RT "Human insulinoma PFK2/F26DPase.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [8]
RP PHOSPHORYLATION AT SER-466, MUTAGENESIS OF SER-466, CATALYTIC ACTIVITY,
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11069105; DOI=10.1016/s0960-9822(00)00742-9;
RA Marsin A.S., Bertrand L., Rider M.H., Deprez J., Beauloye C., Vincent M.F.,
RA Van den Berghe G., Carling D., Hue L.;
RT "Phosphorylation and activation of heart PFK-2 by AMPK has a role in the
RT stimulation of glycolysis during ischaemia.";
RL Curr. Biol. 10:1247-1255(2000).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; THR-468; SER-483 AND
RP SER-493, AND IDENTIFICATION BY 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 [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-483 AND SER-493, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; THR-475 AND SER-493, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
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: Synthesis and degradation of fructose 2,6-bisphosphate.
CC {ECO:0000269|PubMed:11069105}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-fructose 2,6-bisphosphate + H2O = beta-D-fructose 6-
CC phosphate + phosphate; Xref=Rhea:RHEA:17289, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57634, ChEBI:CHEBI:58579; EC=3.1.3.46;
CC Evidence={ECO:0000269|PubMed:11069105};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17290;
CC Evidence={ECO:0000305|PubMed:11069105};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-
CC bisphosphate + H(+); Xref=Rhea:RHEA:15653, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57634, ChEBI:CHEBI:58579,
CC ChEBI:CHEBI:456216; EC=2.7.1.105;
CC Evidence={ECO:0000269|PubMed:11069105};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15654;
CC Evidence={ECO:0000269|PubMed:11069105};
CC -!- ACTIVITY REGULATION: Phosphorylation results in the activation of the
CC kinase activity.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=57 uM for beta-D-fructose 6-phosphate
CC {ECO:0000269|PubMed:11069105};
CC KM=5.1 uM for beta-D-fructose 2,6-bisphosphate
CC {ECO:0000269|PubMed:11069105};
CC KM=46 uM for beta-D-fructose 6-phosphate (in presence of AMPK)
CC {ECO:0000269|PubMed:11069105};
CC KM=29 uM for beta-D-fructose 6-phosphate (in presence of PKB)
CC {ECO:0000269|PubMed:11069105};
CC KM=4.7 uM for beta-D-fructose 2,6-bisphosphate (in presence of AMPK)
CC {ECO:0000269|PubMed:11069105};
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- INTERACTION:
CC O60825; P63104: YWHAZ; NbExp=2; IntAct=EBI-764425, EBI-347088;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60825-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60825-2; Sequence=VSP_004675;
CC -!- TISSUE SPECIFICITY: Heart.
CC -!- PTM: Phosphorylation by AMPK stimulates activity.
CC {ECO:0000269|PubMed:11069105}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the phosphoglycerate
CC mutase family. {ECO:0000305}.
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DR EMBL; AJ005577; CAA06605.1; -; Genomic_DNA.
DR EMBL; AJ005578; CAA06606.1; -; mRNA.
DR EMBL; AB044805; BAB19681.1; -; mRNA.
DR EMBL; AF470623; AAL99386.1; -; mRNA.
DR EMBL; AK292883; BAF85572.1; -; mRNA.
DR EMBL; AL445493; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93508.1; -; Genomic_DNA.
DR EMBL; BC069350; AAH69350.1; -; mRNA.
DR EMBL; BC069385; AAH69385.1; -; mRNA.
DR EMBL; BC069583; AAH69583.1; -; mRNA.
DR EMBL; BC069586; AAH69586.1; -; mRNA.
DR EMBL; BC069600; AAH69600.1; -; mRNA.
DR EMBL; BC075075; AAH75075.1; -; mRNA.
DR EMBL; BC075076; AAH75076.1; -; mRNA.
DR EMBL; BC112103; AAI12104.1; -; mRNA.
DR EMBL; BC112105; AAI12106.1; -; mRNA.
DR CCDS; CCDS31003.1; -. [O60825-2]
DR CCDS; CCDS31004.1; -. [O60825-1]
DR RefSeq; NP_001018063.1; NM_001018053.1. [O60825-2]
DR RefSeq; NP_006203.2; NM_006212.2. [O60825-1]
DR PDB; 5HTK; X-ray; 2.01 A; A/B=1-505.
DR PDBsum; 5HTK; -.
DR AlphaFoldDB; O60825; -.
DR SMR; O60825; -.
DR BioGRID; 111229; 51.
DR ComplexPortal; CPX-1994; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 complex.
DR IntAct; O60825; 28.
DR MINT; O60825; -.
DR STRING; 9606.ENSP00000356047; -.
DR BindingDB; O60825; -.
DR ChEMBL; CHEMBL3421525; -.
DR DEPOD; PFKFB2; -.
DR iPTMnet; O60825; -.
DR PhosphoSitePlus; O60825; -.
DR BioMuta; PFKFB2; -.
DR EPD; O60825; -.
DR jPOST; O60825; -.
DR MassIVE; O60825; -.
DR MaxQB; O60825; -.
DR PaxDb; O60825; -.
DR PeptideAtlas; O60825; -.
DR PRIDE; O60825; -.
DR ProteomicsDB; 49608; -. [O60825-1]
DR ProteomicsDB; 49609; -. [O60825-2]
DR Antibodypedia; 34592; 451 antibodies from 36 providers.
DR DNASU; 5208; -.
DR Ensembl; ENST00000367079.3; ENSP00000356046.2; ENSG00000123836.15. [O60825-2]
DR Ensembl; ENST00000367080.8; ENSP00000356047.3; ENSG00000123836.15. [O60825-1]
DR GeneID; 5208; -.
DR KEGG; hsa:5208; -.
DR MANE-Select; ENST00000367080.8; ENSP00000356047.3; NM_006212.2; NP_006203.2.
DR UCSC; uc001hfg.4; human. [O60825-1]
DR CTD; 5208; -.
DR DisGeNET; 5208; -.
DR GeneCards; PFKFB2; -.
DR HGNC; HGNC:8873; PFKFB2.
DR HPA; ENSG00000123836; Tissue enhanced (retina).
DR MIM; 171835; gene.
DR neXtProt; NX_O60825; -.
DR OpenTargets; ENSG00000123836; -.
DR PharmGKB; PA33212; -.
DR VEuPathDB; HostDB:ENSG00000123836; -.
DR eggNOG; KOG0234; Eukaryota.
DR GeneTree; ENSGT00950000182835; -.
DR HOGENOM; CLU_006383_1_1_1; -.
DR InParanoid; O60825; -.
DR OMA; KIQARYC; -.
DR OrthoDB; 392001at2759; -.
DR PhylomeDB; O60825; -.
DR TreeFam; TF313541; -.
DR BioCyc; MetaCyc:HS04690-MON; -.
DR BRENDA; 2.7.1.105; 2681.
DR BRENDA; 3.1.3.46; 2681.
DR PathwayCommons; O60825; -.
DR Reactome; R-HSA-9634600; Regulation of glycolysis by fructose 2,6-bisphosphate metabolism.
DR SABIO-RK; O60825; -.
DR SignaLink; O60825; -.
DR SIGNOR; O60825; -.
DR BioGRID-ORCS; 5208; 10 hits in 1077 CRISPR screens.
DR ChiTaRS; PFKFB2; human.
DR GeneWiki; PFKFB2; -.
DR GenomeRNAi; 5208; -.
DR Pharos; O60825; Tchem.
DR PRO; PR:O60825; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O60825; protein.
DR Bgee; ENSG00000123836; Expressed in islet of Langerhans and 185 other tissues.
DR ExpressionAtlas; O60825; baseline and differential.
DR Genevisible; O60825; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003873; F:6-phosphofructo-2-kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004331; F:fructose-2,6-bisphosphate 2-phosphatase activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0006003; P:fructose 2,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006000; P:fructose metabolic process; TAS:ProtInc.
DR GO; GO:0006007; P:glucose catabolic process; IEA:Ensembl.
DR GO; GO:0006096; P:glycolytic process; IDA:UniProtKB.
DR GO; GO:0006089; P:lactate metabolic process; IEA:Ensembl.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; IEA:Ensembl.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR CDD; cd07067; HP_PGM_like; 1.
DR Gene3D; 3.40.50.1240; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003094; 6Pfruct_kin.
DR InterPro; IPR013079; 6Phosfructo_kin.
DR InterPro; IPR013078; His_Pase_superF_clade-1.
DR InterPro; IPR029033; His_PPase_superfam.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001345; PG/BPGM_mutase_AS.
DR PANTHER; PTHR10606; PTHR10606; 1.
DR Pfam; PF01591; 6PF2K; 1.
DR Pfam; PF00300; His_Phos_1; 1.
DR PRINTS; PR00991; 6PFRUCTKNASE.
DR SMART; SM00855; PGAM; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF53254; SSF53254; 1.
DR PROSITE; PS00175; PG_MUTASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Hydrolase;
KW Kinase; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..505
FT /note="6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
FT 2"
FT /id="PRO_0000179964"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..248
FT /note="6-phosphofructo-2-kinase"
FT REGION 249..505
FT /note="Fructose-2,6-bisphosphatase"
FT REGION 445..505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 445..481
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 128
FT /evidence="ECO:0000255"
FT ACT_SITE 158
FT /evidence="ECO:0000255"
FT ACT_SITE 257
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT ACT_SITE 326
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 45..53
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 78
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 102
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 130
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 136
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 167..172
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 172
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 193
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 197
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 256
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 263
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 269
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 337
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 348..351
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 351
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 355
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 366
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 392..396
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 392
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT BINDING 396
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /evidence="ECO:0000250|UniProtKB:P07953"
FT BINDING 428
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 256
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 263
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT SITE 391
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q16875"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 29
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250"
FT MOD_RES 466
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:11069105,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 468
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 475
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 493
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 451..505
FT /note="NNFPKNQTPVRMRRNSFTPLSSSNTIRRPRNYSVGSRPLKPLSPLRAQDMQE
FT GAD -> AAETTLAVRRRPSAASLMLPC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11374908,
FT ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_004675"
FT MUTAGEN 466
FT /note="S->E: Constitutively active mutant that cannot be
FT phosphorylated and further activated by AMPK."
FT /evidence="ECO:0000269|PubMed:11069105"
FT CONFLICT 28
FT /note="Missing (in Ref. 1; CAA06605)"
FT /evidence="ECO:0000305"
FT CONFLICT 303..304
FT /note="QL -> HV (in Ref. 1; CAA06606)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="R -> L (in Ref. 1; CAA06606)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="R -> H (in Ref. 1; CAA06606)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="G -> D (in Ref. 1; CAA06606)"
FT /evidence="ECO:0000305"
FT CONFLICT 427
FT /note="A -> T (in Ref. 1; CAA06606)"
FT /evidence="ECO:0000305"
FT STRAND 39..44
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 51..64
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 74..82
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 96..119
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 123..129
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 134..147
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 150..157
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 161..174
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 186..200
FT /evidence="ECO:0007829|PDB:5HTK"
FT TURN 206..212
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:5HTK"
FT TURN 220..223
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 233..242
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 261..265
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 276..292
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 298..301
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 305..312
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 337..343
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 345..353
FT /evidence="ECO:0007829|PDB:5HTK"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 366..382
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 384..390
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 392..402
FT /evidence="ECO:0007829|PDB:5HTK"
FT TURN 407..409
FT /evidence="ECO:0007829|PDB:5HTK"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 419..426
FT /evidence="ECO:0007829|PDB:5HTK"
FT STRAND 429..436
FT /evidence="ECO:0007829|PDB:5HTK"
SQ SEQUENCE 505 AA; 58477 MW; 5CD6A933A7EBF604 CRC64;
MSGASSSEQN NNSYETKTPN LRMSEKKCSW ASYMTNSPTL IVMIGLPARG KTYVSKKLTR
YLNWIGVPTK VFNLGVYRRE AVKSYKSYDF FRHDNEEAMK IRKQCALVAL EDVKAYLTEE
NGQIAVFDAT NTTRERRDMI LNFAEQNSFK VFFVESVCDD PDVIAANILE VKVSSPDYPE
RNRENVMEDF LKRIECYKVT YRPLDPDNYD KDLSFIKVIN VGQRFLVNRV QDYIQSKIVY
YLMNIHVQPR TIYLCRHGES EFNLLGKIGG DSGLSVRGKQ FAQALRKFLE EQEITDLKVW
TSQLKRTIQT AESLGVPYEQ WKILNEIDAG VCEEMTYAEI EKRYPEEFAL RDQEKYLYRY
PGGESYQDLV QRLEPVIMEL ERQGNVLVIS HQAVMRCLLA YFLDKGADEL PYLRCPLHTI
FKLTPVAYGC KVETIKLNVE AVNTHRDKPT NNFPKNQTPV RMRRNSFTPL SSSNTIRRPR
NYSVGSRPLK PLSPLRAQDM QEGAD
