SUGPH_MYCTU
ID SUGPH_MYCTU Reviewed; 203 AA.
AC Q6MWZ7; I6YFI9;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Acid phosphatase {ECO:0000303|PubMed:16672613};
DE EC=3.1.3.2 {ECO:0000269|PubMed:16672613};
DE AltName: Full=Broad-specificity phosphatase {ECO:0000303|PubMed:16672613};
DE AltName: Full=Fructose-1,6-bisphosphatase {ECO:0000303|PubMed:26258286};
DE Short=FBPase {ECO:0000303|PubMed:26258286};
DE EC=3.1.3.11 {ECO:0000269|PubMed:26258286};
GN Name=gpm2 {ECO:0000303|PubMed:26258286, ECO:0000312|EMBL:CCP46030.1};
GN OrderedLocusNames=Rv3214 {ECO:0000312|EMBL:CCP46030.1},
GN LH57_17570 {ECO:0000312|EMBL:AIR16007.1};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RA Hazbon M.H., Riojas M.A., Damon A.M., Alalade R.O., Cantwell B.J.,
RA Monaco A., King S., Sohrabi A.;
RT "Phylogenetic analysis of Mycobacterial species using whole genome
RT sequences.";
RL Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [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).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION AS A FBPASE, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, DISRUPTION
RP PHENOTYPE, AND PATHWAY.
RC STRAIN=H37Rv;
RX PubMed=26258286; DOI=10.1038/ncomms8912;
RA Ganapathy U., Marrero J., Calhoun S., Eoh H., de Carvalho L.P., Rhee K.,
RA Ehrt S.;
RT "Two enzymes with redundant fructose bisphosphatase activity sustain
RT gluconeogenesis and virulence in Mycobacterium tuberculosis.";
RL Nat. Commun. 6:7912-7912(2015).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS), FUNCTION AS A BROAD-SPECTRUM
RP PHOSPHATASE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP SPECIFICITY, AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=16672613; DOI=10.1128/jb.188.10.3589-3599.2006;
RA Watkins H.A., Baker E.N.;
RT "Structural and functional analysis of Rv3214 from Mycobacterium
RT tuberculosis, a protein with conflicting functional annotations, leads to
RT its characterization as a phosphatase.";
RL J. Bacteriol. 188:3589-3599(2006).
CC -!- FUNCTION: Phosphatase with a broad specificity. Can dephosphorylate a
CC variety of substrates including phosphorylated sugars like fructose-6-
CC phosphate (F6P) (PubMed:16672613). Is able to function in vivo as a
CC fructose-1,6-bisphosphatase (FBPase) and to maintain gluconeogenesis
CC when the classical FBPase GlpX is absent (PubMed:26258286). Shows
CC negligible phosphoglycerate mutase activity (PubMed:16672613). Has no
CC phosphatase activity against 3-phosphoglycerate, 2,3-
CC bisphosphoglycerate, or hydrophobic substrates such as alpha-napthyl
CC phosphate (PubMed:16672613). {ECO:0000269|PubMed:16672613,
CC ECO:0000269|PubMed:26258286}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a phosphate monoester + H2O = an alcohol + phosphate;
CC Xref=Rhea:RHEA:15017, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:67140; EC=3.1.3.2;
CC Evidence={ECO:0000269|PubMed:16672613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-fructose 1,6-bisphosphate + H2O = beta-D-fructose 6-
CC phosphate + phosphate; Xref=Rhea:RHEA:11064, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:32966, ChEBI:CHEBI:43474, ChEBI:CHEBI:57634; EC=3.1.3.11;
CC Evidence={ECO:0000269|PubMed:26258286};
CC -!- ACTIVITY REGULATION: In contrast to classical FBPases, is resistant to
CC inhibition by lithium. {ECO:0000269|PubMed:26258286}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.04 mM for p-nitrophenyl phosphate (at pH 5.5 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:16672613};
CC KM=101.1 uM for 3-phosphoglycerate {ECO:0000269|PubMed:16672613};
CC Note=kcat is 0.00071 sec(-1) for phosphoglycerate mutase activity
CC (PubMed:16672613). The enzyme's FBPase activity does not follow
CC Michaelis-Menten kinetics but follows allosteric sigmoidal kinetics
CC that show lower affinity for FBP compared with GlpX, but the enzyme's
CC higher turnover number makes it a robust FBPase at high FBP
CC concentrations (PubMed:26258286). {ECO:0000269|PubMed:16672613,
CC ECO:0000269|PubMed:26258286};
CC pH dependence:
CC Optimum pH is 5.4 for phosphatase activity using pNPP as the
CC substrate. {ECO:0000269|PubMed:16672613};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC {ECO:0000305|PubMed:26258286}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16672613}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking both glpX and gpm2 grow as well as
CC wild-type on glucose, but are unable to grow on any of the
CC gluconeogenic carbon sources tested (glycerol, acetate and butyrate);
CC the growth defect on gluconeogenic carbon sources is fully complemented
CC by restoring expression of either GlpX or Gpm2. This double mutant
CC lacks detectable FBPase activity and accumulates FBP. It is also
CC severely attenuated in a mouse model of infection, as it fails to
CC replicate in mouse lungs during the first 10 days of infection and
CC begins to die thereafter. {ECO:0000269|PubMed:26258286}.
CC -!- MISCELLANEOUS: Gluconeogenesis is critical to M.tuberculosis ability to
CC establish infection and is necessary for its survival in the host.
CC {ECO:0000269|PubMed:26258286}.
CC -!- SIMILARITY: Belongs to the phosphoglycerate mutase family.
CC {ECO:0000305}.
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DR EMBL; CP009480; AIR16007.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46030.1; -; Genomic_DNA.
DR RefSeq; WP_003416878.1; NZ_NVQJ01000003.1.
DR RefSeq; YP_177944.1; NC_000962.3.
DR PDB; 2A6P; X-ray; 2.20 A; A/B=1-203.
DR PDBsum; 2A6P; -.
DR AlphaFoldDB; Q6MWZ7; -.
DR SMR; Q6MWZ7; -.
DR STRING; 83332.Rv3214; -.
DR PaxDb; Q6MWZ7; -.
DR DNASU; 888830; -.
DR GeneID; 45427207; -.
DR GeneID; 888830; -.
DR KEGG; mtu:Rv3214; -.
DR PATRIC; fig|83332.111.peg.3589; -.
DR TubercuList; Rv3214; -.
DR eggNOG; COG0406; Bacteria.
DR HOGENOM; CLU_033323_13_1_11; -.
DR InParanoid; Q6MWZ7; -.
DR OMA; VCGFEHG; -.
DR PhylomeDB; Q6MWZ7; -.
DR UniPathway; UPA00138; -.
DR EvolutionaryTrace; Q6MWZ7; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003993; F:acid phosphatase activity; IDA:MTBBASE.
DR GO; GO:0042132; F:fructose 1,6-bisphosphate 1-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0016791; F:phosphatase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:MTBBASE.
DR GO; GO:0006094; P:gluconeogenesis; IEA:UniProtKB-UniPathway.
DR CDD; cd07067; HP_PGM_like; 1.
DR Gene3D; 3.40.50.1240; -; 1.
DR InterPro; IPR013078; His_Pase_superF_clade-1.
DR InterPro; IPR029033; His_PPase_superfam.
DR Pfam; PF00300; His_Phos_1; 1.
DR SMART; SM00855; PGAM; 1.
DR SUPFAM; SSF53254; SSF53254; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carbohydrate metabolism; Gluconeogenesis; Hydrolase;
KW Reference proteome.
FT CHAIN 1..203
FT /note="Acid phosphatase"
FT /id="PRO_0000437244"
FT ACT_SITE 13
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P36136,
FT ECO:0000305|PubMed:16672613"
FT ACT_SITE 85
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P36136"
FT SITE 147
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P36136"
SQ SEQUENCE 203 AA; 21949 MW; 25293CE08DD88D55 CRC64;
MGVRNHRLLL LRHGETAWST LGRHTGGTEV ELTDTGRTQA ELAGQLLGEL ELDDPIVICS
PRRRTLDTAK LAGLTVNEVT GLLAEWDYGS YEGLTTPQIR ESEPDWLVWT HGCPAGESVA
QVNDRADSAV ALALEHMSSR DVLFVSHGHF SRAVITRWVQ LPLAEGSRFA MPTASIGICG
FEHGVRQLAV LGLTGHPQPI AAG
