ID PFKB_MYCTU Reviewed; 339 AA. AC P9WID3; L0T8F1; O86352; Q7D7L4; DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2014, sequence version 1. DT 12-AUG-2020, entry version 36. DE RecName: Full=Putative ATP-dependent 6-phosphofructokinase isozyme 2; DE Short=ATP-PFK 2; DE Short=Phosphofructokinase 2; DE EC=2.7.1.11; DE AltName: Full=Phosphohexokinase 2; GN Name=pfkB; OrderedLocusNames=Rv2029c; OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv). OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; OC Mycobacterium; Mycobacterium tuberculosis complex. OX NCBI_TaxID=83332; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=9634230; DOI=10.1038/31159; RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K., RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., RA Barrell B.G.; RT "Deciphering the biology of Mycobacterium tuberculosis from the complete RT genome sequence."; RL Nature 393:537-544(1998). RN [2] RP INDUCTION BY HYPOXIA. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=11416222; DOI=10.1073/pnas.121172498; RA Sherman D.R., Voskuil M., Schnappinger D., Liao R., Harrell M.I., RA Schoolnik G.K.; RT "Regulation of the Mycobacterium tuberculosis hypoxic response gene RT encoding alpha -crystallin."; RL Proc. Natl. Acad. Sci. U.S.A. 98:7534-7539(2001). RN [3] RP INDUCTION BY NITRIC OXIDE (NO) AND BY HYPOXIA, AND DORMANCY REGULON. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=12953092; DOI=10.1084/jem.20030205; RA Voskuil M.I., Schnappinger D., Visconti K.C., Harrell M.I., Dolganov G.M., RA Sherman D.R., Schoolnik G.K.; RT "Inhibition of respiration by nitric oxide induces a Mycobacterium RT tuberculosis dormancy program."; RL J. Exp. Med. 198:705-713(2003). RN [4] RP BIOTECHNOLOGY. RX PubMed=16931093; DOI=10.1016/j.micinf.2006.03.018; RA Leyten E.M., Lin M.Y., Franken K.L., Friggen A.H., Prins C., RA van Meijgaarden K.E., Voskuil M.I., Weldingh K., Andersen P., RA Schoolnik G.K., Arend S.M., Ottenhoff T.H., Klein M.R.; RT "Human T-cell responses to 25 novel antigens encoded by genes of the RT dormancy regulon of Mycobacterium tuberculosis."; RL Microbes Infect. 8:2052-2060(2006). RN [5] RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS]. RX PubMed=19099550; DOI=10.1186/1752-0509-2-109; RA Raman K., Yeturu K., Chandra N.; RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis RT through an interactome, reactome and genome-scale structural analysis."; RL BMC Syst. Biol. 2:109-109(2008). RN [6] RP INDUCTION BY CARBON MONOXIDE (CO). RC STRAIN=ATCC 35801 / TMC 107 / Erdman; RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007; RA Shiloh M.U., Manzanillo P., Cox J.S.; RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during RT macrophage infection."; RL Cell Host Microbe 3:323-330(2008). RN [7] RP INDUCTION BY CARBON MONOXIDE (CO), AND DORMANCY REGULON. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=18400743; DOI=10.1074/jbc.m802274200; RA Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I., RA Agarwal A., Steyn A.J.; RT "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium RT tuberculosis dormancy regulon."; RL J. Biol. Chem. 283:18032-18039(2008). RN [8] RP PUPYLATION AT LYS-283, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=20066036; DOI=10.1371/journal.pone.0008589; RA Festa R.A., McAllister F., Pearce M.J., Mintseris J., Burns K.E., RA Gygi S.P., Darwin K.H.; RT "Prokayrotic ubiquitin-like protein (Pup) proteome of Mycobacterium RT tuberculosis."; RL PLoS ONE 5:E8589-E8589(2010). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=21969609; DOI=10.1074/mcp.m111.011627; RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K., RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R., RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M., RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.; RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution RT mass spectrometry."; RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011). 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. {ECO:0000250}. 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; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Allosterically inhibited by ATP. {ECO:0000250}. CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3- CC phosphate and glycerone phosphate from D-glucose: step 3/4. CC -!- SUBUNIT: Homodimer. {ECO:0000250}. CC -!- INDUCTION: A member of the dormancy regulon. Induced in response to CC reduced oxygen tension (hypoxia), low levels of nitric oxide (NO) and CC carbon monoxide (CO). It is hoped that this regulon will give insight CC into the latent, or dormant phase of infection. CC {ECO:0000269|PubMed:11416222, ECO:0000269|PubMed:12953092, CC ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359}. CC -!- BIOTECHNOLOGY: Has strong T-cell and IFN-gamma inducing capacity in CC human tuberculin skin test positive patients, indicating this might be CC a good vaccine candidate. {ECO:0000269|PubMed:16931093}. CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target. CC -!- SIMILARITY: Belongs to the carbohydrate kinase PfkB family. CC {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; AL123456; CCP44802.1; -; Genomic_DNA. DR PIR; D70942; D70942. DR RefSeq; NP_216545.1; NC_000962.3. DR RefSeq; WP_003899139.1; NZ_NVQJ01000046.1. DR SMR; P9WID3; -. DR STRING; 83332.Rv2029c; -. DR iPTMnet; P9WID3; -. DR PaxDb; P9WID3; -. DR EnsemblBacteria; CCP44802; CCP44802; Rv2029c. DR GeneID; 23491790; -. DR GeneID; 887491; -. DR KEGG; mtu:Rv2029c; -. DR KEGG; mtv:RVBD_2029c; -. DR TubercuList; Rv2029c; -. DR eggNOG; COG1105; Bacteria. DR KO; K16370; -. DR OMA; GHVNMAH; -. DR PhylomeDB; P9WID3; -. DR BioCyc; MTBH37RV:G185E-6232-MONOMER; -. DR UniPathway; UPA00109; UER00182. DR Proteomes; UP000001584; Chromosome. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0003872; F:6-phosphofructokinase activity; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008443; F:phosphofructokinase activity; IBA:GO_Central. DR CDD; cd01164; FruK_PfkB_like; 1. DR Gene3D; 3.40.1190.20; -; 1. DR InterPro; IPR002173; Carboh/pur_kinase_PfkB_CS. DR InterPro; IPR011611; PfkB_dom. DR InterPro; IPR029056; Ribokinase-like. DR InterPro; IPR017583; Tagatose/fructose_Pkinase. DR Pfam; PF00294; PfkB; 1. DR PIRSF; PIRSF000535; 1PFK/6PFK/LacC; 1. DR SUPFAM; SSF53613; SSF53613; 1. DR TIGRFAMs; TIGR03168; 1-PFK; 1. DR PROSITE; PS00583; PFKB_KINASES_1; 1. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Glycolysis; Isopeptide bond; Kinase; Magnesium; KW Metal-binding; Nucleotide-binding; Potassium; Reference proteome; KW Transferase; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000244|PubMed:21969609" FT CHAIN 2..339 FT /note="Putative ATP-dependent 6-phosphofructokinase isozyme FT 2" FT /id="PRO_0000392912" FT NP_BIND 194..196 FT /note="ATP" FT /evidence="ECO:0000250" FT NP_BIND 233..238 FT /note="ATP" FT /evidence="ECO:0000250" FT REGION 22..24 FT /note="Substrate binding" FT /evidence="ECO:0000250" FT REGION 37..39 FT /note="Substrate binding" FT /evidence="ECO:0000250" FT REGION 49..53 FT /note="Substrate binding" FT /evidence="ECO:0000250" FT REGION 100..102 FT /note="Substrate binding" FT /evidence="ECO:0000250" FT REGION 196..198 FT /note="Allosteric inhibitor ATP binding" FT /evidence="ECO:0000250" FT ACT_SITE 265 FT /evidence="ECO:0000250" FT METAL 199 FT /note="Magnesium; catalytic" FT /evidence="ECO:0000250" FT METAL 259 FT /note="Potassium; via carbonyl oxygen" FT /evidence="ECO:0000250" FT METAL 261 FT /note="Potassium; via carbonyl oxygen" FT /evidence="ECO:0000250" FT METAL 295 FT /note="Potassium; via carbonyl oxygen" FT /evidence="ECO:0000250" FT METAL 298 FT /note="Potassium; via carbonyl oxygen" FT /evidence="ECO:0000250" FT METAL 300 FT /note="Potassium; via carbonyl oxygen" FT /evidence="ECO:0000250" FT METAL 302 FT /note="Potassium; via carbonyl oxygen" FT /evidence="ECO:0000250" FT BINDING 37 FT /note="Allosteric inhibitor ATP; shared with dimeric FT partner" FT /evidence="ECO:0000250" FT BINDING 37 FT /note="ATP; shared with dimeric partner" FT /evidence="ECO:0000250" FT BINDING 150 FT /note="Substrate" FT /evidence="ECO:0000250" FT BINDING 265 FT /note="Substrate" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0000244|PubMed:21969609" FT CROSSLNK 283 FT /note="Isoglutamyl lysine isopeptide (Lys-Gln) (interchain FT with Q-Cter in protein Pup)" FT /evidence="ECO:0000269|PubMed:20066036" SQ SEQUENCE 339 AA; 35401 MW; D773E363FF73DADD CRC64; MTEPAAWDEG KPRIITLTMN PALDITTSVD VVRPTEKMRC GAPRYDPGGG GINVARIVHV LGGCSTALFP AGGSTGSLLM ALLGDAGVPF RVIPIAASTR ESFTVNESRT AKQYRFVLPG PSLTVAEQEQ CLDELRGAAA SAAFVVASGS LPPGVAADYY QRVADICRRS STPLILDTSG GGLQHISSGV FLLKASVREL RECVGSELLT EPEQLAAAHE LIDRGRAEVV VVSLGSQGAL LATRHASHRF SSIPMTAVSG VGAGDAMVAA ITVGLSRGWS LIKSVRLGNA AGAAMLLTPG TAACNRDDVE RFFELAAEPT EVGQDQYVWH PIVNPEASP //