URE1_MYCTU
ID URE1_MYCTU Reviewed; 577 AA.
AC P9WFF1; L0T9F6; P0A660; P50042;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Urease subunit alpha {ECO:0000255|HAMAP-Rule:MF_01953};
DE EC=3.5.1.5 {ECO:0000255|HAMAP-Rule:MF_01953};
DE AltName: Full=Urea amidohydrolase subunit alpha {ECO:0000255|HAMAP-Rule:MF_01953};
GN Name=ureC {ECO:0000255|HAMAP-Rule:MF_01953}; OrderedLocusNames=Rv1850;
GN ORFNames=MTCY359.23c;
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 [GENOMIC DNA], PROTEIN SEQUENCE OF 2-28, CATALYTIC
RP ACTIVITY, COFACTOR, INTERACTION WITH UREA AND UREB, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=7559354; DOI=10.1128/jb.177.19.5644-5652.1995;
RA Clemens D.L., Lee B.-Y., Horwitz M.A.;
RT "Purification, characterization, and genetic analysis of Mycobacterium
RT tuberculosis urease, a potentially critical determinant of host-pathogen
RT interaction.";
RL J. Bacteriol. 177:5644-5652(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=7568014; DOI=10.1073/pnas.92.19.8768;
RA Reyrat J.-M., Berthet F.-X., Gicquel B.;
RT "The urease locus of Mycobacterium tuberculosis and its utilization for the
RT demonstration of allelic exchange in Mycobacterium bovis bacillus Calmette-
RT Guerin.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:8768-8772(1995).
RN [3]
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 [4]
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 [5]
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).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + H2O + urea = CO2 + 2 NH4(+); Xref=Rhea:RHEA:20557,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16199,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:28938; EC=3.5.1.5;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01953,
CC ECO:0000269|PubMed:7559354};
CC -!- COFACTOR:
CC Name=Ni cation; Xref=ChEBI:CHEBI:25516;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01953,
CC ECO:0000269|PubMed:7559354};
CC Note=Binds 2 nickel ions per subunit. {ECO:0000255|HAMAP-Rule:MF_01953,
CC ECO:0000269|PubMed:7559354};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3 mM for urea {ECO:0000269|PubMed:7559354};
CC Vmax=0.05 mmol/min/mg enzyme {ECO:0000269|PubMed:7559354};
CC pH dependence:
CC Optimum pH is 7.2. {ECO:0000269|PubMed:7559354};
CC -!- PATHWAY: Nitrogen metabolism; urea degradation; CO(2) and NH(3) from
CC urea (urease route): step 1/1. {ECO:0000255|HAMAP-Rule:MF_01953}.
CC -!- SUBUNIT: Heterotrimer of UreA (gamma), UreB (beta) and UreC (alpha)
CC subunits. Three heterotrimers associate to form the active enzyme.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01953}.
CC -!- PTM: Carboxylation allows a single lysine to coordinate two nickel
CC ions. {ECO:0000255|HAMAP-Rule:MF_01953}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Urease alpha subunit family. {ECO:0000255|HAMAP-Rule:MF_01953}.
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DR EMBL; U33011; AAC43475.1; -; Genomic_DNA.
DR EMBL; L41141; AAC37007.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44616.1; -; Genomic_DNA.
DR PIR; B70665; B70665.
DR RefSeq; NP_216366.1; NC_000962.3.
DR RefSeq; WP_003899049.1; NZ_NVQJ01000013.1.
DR AlphaFoldDB; P9WFF1; -.
DR SMR; P9WFF1; -.
DR STRING; 83332.Rv1850; -.
DR MEROPS; M38.982; -.
DR PaxDb; P9WFF1; -.
DR DNASU; 885359; -.
DR GeneID; 885359; -.
DR KEGG; mtu:Rv1850; -.
DR TubercuList; Rv1850; -.
DR eggNOG; COG0804; Bacteria.
DR OMA; GFDSHIH; -.
DR PhylomeDB; P9WFF1; -.
DR UniPathway; UPA00258; UER00370.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016151; F:nickel cation binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009039; F:urease activity; IEA:UniProtKB-UniRule.
DR GO; GO:0043419; P:urea catabolic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00375; Urease_alpha; 1.
DR Gene3D; 2.30.40.10; -; 1.
DR HAMAP; MF_01953; Urease_alpha; 1.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR011059; Metal-dep_hydrolase_composite.
DR InterPro; IPR032466; Metal_Hydrolase.
DR InterPro; IPR011612; Urease_alpha_N_dom.
DR InterPro; IPR017950; Urease_AS.
DR InterPro; IPR005848; Urease_asu.
DR InterPro; IPR017951; Urease_asu_c.
DR InterPro; IPR029754; Urease_Ni-bd.
DR Pfam; PF01979; Amidohydro_1; 1.
DR Pfam; PF00449; Urease_alpha; 1.
DR PRINTS; PR01752; UREASE.
DR SUPFAM; SSF51338; SSF51338; 2.
DR SUPFAM; SSF51556; SSF51556; 1.
DR TIGRFAMs; TIGR01792; urease_alph; 1.
DR PROSITE; PS01120; UREASE_1; 1.
DR PROSITE; PS00145; UREASE_2; 1.
DR PROSITE; PS51368; UREASE_3; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Metal-binding; Nickel;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:7559354"
FT CHAIN 2..577
FT /note="Urease subunit alpha"
FT /id="PRO_0000067549"
FT DOMAIN 136..577
FT /note="Urease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT ACT_SITE 327
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT BINDING 141
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT BINDING 143
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT BINDING 224
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_label="1"
FT /note="via carbamate group"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT BINDING 224
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_label="2"
FT /note="via carbamate group"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT BINDING 253
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_label="2"
FT BINDING 279
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT BINDING 367
FT /ligand="Ni(2+)"
FT /ligand_id="ChEBI:CHEBI:49786"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT MOD_RES 224
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01953"
FT CONFLICT 62
FT /note="G -> A (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
FT CONFLICT 67
FT /note="A -> T (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="A -> T (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
FT CONFLICT 96..97
FT /note="GR -> AP (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="A -> T (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="A -> T (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
FT CONFLICT 174
FT /note="A -> T (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="G -> D (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
FT CONFLICT 448
FT /note="A -> V (in Ref. 2; AAC37007)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 577 AA; 60825 MW; 010FB33C3FDFED12 CRC64;
MARLSRERYA QLYGPTTGDR IRLADTNLLV EVTEDRCGGP GLAGDEAVFG GGKVLRESMG
QGRASRADGA PDTVITGAVI IDYWGIIKAD IGIRDGRIVG IGKAGNPDIM TGVHRDLVVG
PSTEIISGNR RIVTAGTVDC HVHLICPQII VEALAAGTTT IIGGGTGPAE GTKATTVTPG
EWHLARMLES LDGWPVNFAL LGKGNTVNPD ALWEQLRGGA SGFKLHEDWG STPAAIDTCL
AVADVAGVQV ALHSDTLNET GFVEDTIGAI AGRSIHAYHT EGAGGGHAPD IITVAAQPNV
LPSSTNPTRP HTVNTLDEHL DMLMVCHHLN PRIPEDLAFA ESRIRPSTIA AEDVLHDMGA
ISMIGSDSQA MGRVGEVVLR TWQTAHVMKA RRGALEGDPS GSQAADNNRV RRYIAKYTIC
PAIAHGMDHL IGSVEVGKLA DLVLWEPAFF GVRPHVVLKG GAIAWAAMGD ANASIPTPQP
VLPRPMFGAA AATAAATSVH FVAPQSIDAR LADRLAVNRG LAPVADVRAV GKTDLPLNDA
LPSIEVDPDT FTVRIDGQVW QPQPAAELPM TQRYFLF
