ID CYSQ_MYCTU Reviewed; 267 AA.
AC P9WKJ1; L0TBL8; O06244; P65163;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 27-MAR-2024, entry version 55.
DE RecName: Full=3'-phosphoadenosine 5'-phosphate phosphatase;
DE Short=PAP phosphatase;
DE EC=3.1.3.7 {ECO:0000269|PubMed:18454554};
DE AltName: Full=3'(2'),5'-bisphosphate nucleotidase;
DE AltName: Full=3'(2'),5-bisphosphonucleoside 3'(2')-phosphohydrolase;
DE AltName: Full=D-fructose-1,6-bisphosphate 1-phosphohydrolase;
DE AltName: Full=DPNPase;
DE AltName: Full=Fructose-1,6-bisphosphatase;
DE Short=FBPase;
DE EC=3.1.3.11 {ECO:0000269|PubMed:16325768, ECO:0000269|PubMed:18454554};
DE AltName: Full=Inositol-1-monophosphatase;
DE Short=I-1-Pase;
DE Short=IMPase;
DE EC=3.1.3.25 {ECO:0000269|PubMed:16325768, ECO:0000269|PubMed:18454554};
DE AltName: Full=Inositol-1-phosphatase;
GN Name=cysQ; OrderedLocusNames=Rv2131c; ORFNames=MTCY270.37;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; 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 FUNCTION AS IMPASE AND FBPASE, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY,
RP COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, MASS
RP SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE, AND MUTAGENESIS OF ASP-40;
RP LEU-71 AND ASP-94.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16325768; DOI=10.1016/j.bbrc.2005.11.088;
RA Gu X., Chen M., Shen H., Jiang X., Huang Y., Wang H.;
RT "Rv2131c gene product: an unconventional enzyme that is both inositol
RT monophosphatase and fructose-1,6-bisphosphatase.";
RL Biochem. Biophys. Res. Commun. 339:897-904(2006).
RN [3]
RP FUNCTION AS PAP PHOSPHATASE, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18454554; DOI=10.1021/bi702453s;
RA Hatzios S.K., Iavarone A.T., Bertozzi C.R.;
RT "Rv2131c from Mycobacterium tuberculosis is a CysQ 3'-phosphoadenosine-5'-
RT phosphatase.";
RL Biochemistry 47:5823-5831(2008).
RN [4]
RP DISRUPTION PHENOTYPE, AND INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20167072; DOI=10.1186/1471-2180-10-50;
RA Movahedzadeh F., Wheeler P.R., Dinadayala P., Av-Gay Y., Parish T.,
RA Daffe M., Stoker N.G.;
RT "Inositol monophosphate phosphatase genes of Mycobacterium tuberculosis.";
RL BMC Microbiol. 10:50-50(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011445;
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: Phosphatase with a broad specificity. Its primary
CC physiological function is to dephosphorylate 3'-phosphoadenosine 5'-
CC phosphate (PAP) and 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Thus,
CC plays a role in mycobacterial sulfur metabolism, since it can serve as
CC a key regulator of the sulfate assimilation pathway by controlling the
CC pools of PAP and PAPS in the cell. To a lesser extent, is also able to
CC hydrolyze inositol 1-phosphate (I-1-P), fructose 1,6-bisphosphate (FBP)
CC (to fructose 6-phosphate (F-6-P)) and AMP in vitro, but this might not
CC be significant in vivo. Glucose-1-phosphate (G-1-P), p-nitrophenyl
CC phosphate (pNPP), and beta-glycerol phosphate (beta-GP) are also good
CC substrates, compared to I-1-P. With much lower efficiency, can also
CC hydrolyze inositol 2-phosphate (I-2-P) and glucose-6-phosphate (G-6-P)
CC in vitro, but not fructose-6-phosphate (F-6-P) and trehalose-6-
CC phosphate (T-6-P). {ECO:0000269|PubMed:16325768,
CC ECO:0000269|PubMed:18454554}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine 3',5'-bisphosphate + H2O = AMP + phosphate;
CC Xref=Rhea:RHEA:10040, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:456215; EC=3.1.3.7;
CC Evidence={ECO:0000269|PubMed:18454554};
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:16325768, ECO:0000269|PubMed:18454554};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a myo-inositol phosphate + H2O = myo-inositol + phosphate;
CC Xref=Rhea:RHEA:24056, ChEBI:CHEBI:15377, ChEBI:CHEBI:17268,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:84139; EC=3.1.3.25;
CC Evidence={ECO:0000269|PubMed:16325768, ECO:0000269|PubMed:18454554};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16325768, ECO:0000269|PubMed:18454554};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:16325768, ECO:0000269|PubMed:18454554};
CC Note=Mg(2+). Mn(2+) can substitute for Mg(2+) for PAP phosphatase and
CC IMPase activities, but is less efficient (50%-60% of the activity
CC observed with Mg(2+)). {ECO:0000269|PubMed:16325768,
CC ECO:0000269|PubMed:18454554};
CC -!- ACTIVITY REGULATION: PAP phosphatase and IMPase activities are
CC inhibited by Li(+). To a lesser extent, PAP hydrolysis is also
CC inhibited by Na(+) and K(+), with IC50 values of 150 and 250 mM,
CC respectively, so much higher than IC50 with Li(+) (0.5 mM). Exhibits
CC about 50% residual IMPase activity at 5 mM Li(+) and about 10% at 30 mM
CC Li(+). Na(+) and K(+) have no significant effect on IMPase activity
CC between 0 and 200 mM. {ECO:0000269|PubMed:16325768,
CC ECO:0000269|PubMed:18454554}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.1 uM for 3'-phosphoadenosine 5'-phosphate (at pH 9.0 and 30
CC degrees Celsius) {ECO:0000269|PubMed:16325768,
CC ECO:0000269|PubMed:18454554};
CC KM=0.22 mM for inositol-1-phosphate (at pH 9.3 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:16325768, ECO:0000269|PubMed:18454554};
CC KM=0.45 mM for fructose 1,6-bisphosphate (at pH 9.3 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:16325768, ECO:0000269|PubMed:18454554};
CC Vmax=6.9 umol/min/mg enzyme for IMPase activity (at pH 9.3 and 37
CC degrees Celsius) {ECO:0000269|PubMed:16325768,
CC ECO:0000269|PubMed:18454554};
CC Note=The second-order rate constant for PAP was determined to be over
CC 3 orders of magnitude greater than those determined for IMP and FBP.;
CC pH dependence:
CC Optimum pH is 8.5-9.5 for PAP phosphatase activity, 9.3 for IMPase
CC activity, and about 10 for FBPase activity. IMPase activity shows a
CC dramatic decrease at low pH. In contrast, IMPase activity is highly
CC stable at alkaline pH, with more than 60% activity remaining at pH
CC 12. {ECO:0000269|PubMed:16325768, ECO:0000269|PubMed:18454554};
CC Temperature dependence:
CC Optimum temperature is 62 degrees Celsius for IMPase activity. After
CC preincubation at 70 degrees Celsius for 2 minutes and then being
CC assayed at 37 degrees Celsius, more than 95% activities of IMPase and
CC FBPase are lost. {ECO:0000269|PubMed:16325768,
CC ECO:0000269|PubMed:18454554};
CC -!- PATHWAY: Sulfur metabolism; sulfate assimilation.
CC {ECO:0000269|PubMed:18454554}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16325768}.
CC -!- INDUCTION: When comparing gene expression levels of the four IMPase
CC family genes in exponential cultures of M.tuberculosis, the level of
CC cysQ is the highest, almost equal to sigA; impA and impC are expressed
CC at approximately 40% of this level, while suhB is lowest, at 12% of the
CC cysQ level. {ECO:0000269|PubMed:20167072}.
CC -!- MASS SPECTROMETRY: Mass=30584; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:16325768};
CC -!- MASS SPECTROMETRY: Mass=30578; Mass_error=1; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:18454554};
CC -!- DISRUPTION PHENOTYPE: Strains lacking this gene show normal growth, do
CC not require exogenous inositol for growth, and show no differences in
CC levels of phosphatidylinosotol mannosides (PIMs), lipomannan (LM),
CC lipoarabinomannan (LAM) or mycothiol (in the absence of exogenous
CC inositol). {ECO:0000269|PubMed:20167072}.
CC -!- SIMILARITY: Belongs to the inositol monophosphatase superfamily.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP44906.1; -; Genomic_DNA.
DR PIR; G70576; G70576.
DR RefSeq; NP_216647.1; NC_000962.3.
DR RefSeq; WP_003411096.1; NZ_NVQJ01000044.1.
DR PDB; 5DJF; X-ray; 1.70 A; A=2-267.
DR PDB; 5DJG; X-ray; 1.95 A; A=2-267.
DR PDB; 5DJH; X-ray; 1.45 A; A=2-267.
DR PDB; 5DJI; X-ray; 1.66 A; A=2-267.
DR PDB; 5DJJ; X-ray; 1.50 A; A=2-267.
DR PDB; 5DJK; X-ray; 1.80 A; A=2-267.
DR PDBsum; 5DJF; -.
DR PDBsum; 5DJG; -.
DR PDBsum; 5DJH; -.
DR PDBsum; 5DJI; -.
DR PDBsum; 5DJJ; -.
DR PDBsum; 5DJK; -.
DR AlphaFoldDB; P9WKJ1; -.
DR SMR; P9WKJ1; -.
DR STRING; 83332.Rv2131c; -.
DR PaxDb; 83332-Rv2131c; -.
DR DNASU; 888142; -.
DR GeneID; 45426106; -.
DR GeneID; 888142; -.
DR KEGG; mtu:Rv2131c; -.
DR PATRIC; fig|83332.111.peg.2375; -.
DR TubercuList; Rv2131c; -.
DR eggNOG; COG1218; Bacteria.
DR InParanoid; P9WKJ1; -.
DR OrthoDB; 9772456at2; -.
DR PhylomeDB; P9WKJ1; -.
DR BRENDA; 3.1.3.7; 3445.
DR Reactome; R-MTU-936635; Sulfate assimilation.
DR UniPathway; UPA00097; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008441; F:3'(2'),5'-bisphosphate nucleotidase activity; IDA:MTBBASE.
DR GO; GO:0050897; F:cobalt ion binding; IDA:MTBBASE.
DR GO; GO:0042132; F:fructose 1,6-bisphosphate 1-phosphatase activity; IDA:MTBBASE.
DR GO; GO:0008934; F:inositol monophosphate 1-phosphatase activity; IDA:MTBBASE.
DR GO; GO:0052832; F:inositol monophosphate 3-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0052833; F:inositol monophosphate 4-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0050427; P:3'-phosphoadenosine 5'-phosphosulfate metabolic process; IDA:MTBBASE.
DR GO; GO:0000103; P:sulfate assimilation; IBA:GO_Central.
DR CDD; cd01638; CysQ; 1.
DR Gene3D; 3.40.190.80; -; 1.
DR Gene3D; 3.30.540.10; Fructose-1,6-Bisphosphatase, subunit A, domain 1; 1.
DR InterPro; IPR020583; Inositol_monoP_metal-BS.
DR InterPro; IPR000760; Inositol_monophosphatase-like.
DR PANTHER; PTHR43028; 3'(2'),5'-BISPHOSPHATE NUCLEOTIDASE 1; 1.
DR PANTHER; PTHR43028:SF5; 3'(2'),5'-BISPHOSPHATE NUCLEOTIDASE 1; 1.
DR Pfam; PF00459; Inositol_P; 1.
DR SUPFAM; SSF56655; Carbohydrate phosphatase; 1.
DR PROSITE; PS00629; IMP_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Magnesium; Metal-binding; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000305|PubMed:16325768,
FT ECO:0000305|PubMed:18454554"
FT CHAIN 2..267
FT /note="3'-phosphoadenosine 5'-phosphate phosphatase"
FT /id="PRO_0000142551"
FT BINDING 73
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 73
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 93..96
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 93
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 212
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 212
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MUTAGEN 40
FT /note="D->N: Less than 2% of wild-type IMPase and FBPase
FT activities."
FT /evidence="ECO:0000269|PubMed:16325768"
FT MUTAGEN 71
FT /note="L->A: No effect on IMPase and FBPase activities.
FT Much less sensitive to inhibition by Li(+)."
FT /evidence="ECO:0000269|PubMed:16325768"
FT MUTAGEN 94
FT /note="D->N: Less than 3% of wild-type IMPase and FBPase
FT activities."
FT /evidence="ECO:0000269|PubMed:16325768"
FT HELIX 15..37
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:5DJH"
FT HELIX 42..64
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:5DJH"
FT HELIX 80..83
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 85..94
FT /evidence="ECO:0007829|PDB:5DJH"
FT HELIX 96..99
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 108..115
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:5DJF"
FT STRAND 123..131
FT /evidence="ECO:0007829|PDB:5DJH"
FT TURN 132..136
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:5DJH"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 155..165
FT /evidence="ECO:0007829|PDB:5DJH"
FT HELIX 169..173
FT /evidence="ECO:0007829|PDB:5DJH"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:5DJH"
FT HELIX 187..195
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:5DJH"
FT HELIX 210..222
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:5DJH"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:5DJF"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:5DJH"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:5DJH"
FT HELIX 255..264
FT /evidence="ECO:0007829|PDB:5DJH"
SQ SEQUENCE 267 AA; 28447 MW; AFF7347E34129AF6 CRC64;
MVSPAAPDLT DDLTDAELAA DLAADAGKLL LQVRAEIGFD QPWTLGEAGD RQANSLLLRR
LQAERPGDAV LSEEAHDDLA RLKSDRVWII DPLDGTREFS TPGRDDWAVH IALWRRSSNG
QPEITDAAVA LPARGNVVYR TDTVTSGAAP AGVPGTLRIA VSATRPPAVL HRIRQTLAIQ
PVSIGSAGAK AMAVIDGYVD AYLHAGGQWE WDSAAPAGVM LAAGMHASRL DGSPLRYNQL
DPYLPDLLMC RAEVAPILLG AIADAWR
//
