WAG31_MYCTU
ID WAG31_MYCTU Reviewed; 260 AA.
AC P9WMU1; L0TBN0; P0A5N2; P46816;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Cell wall synthesis protein Wag31;
DE AltName: Full=Antigen 84;
GN Name=wag31; Synonyms=ag84; OrderedLocusNames=Rv2145c; ORFNames=MTCY270.23;
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], AND SUBCELLULAR LOCATION.
RX PubMed=7868268; DOI=10.1128/iai.63.3.954-960.1995;
RA Hermans P.W.M., Abebe F., Kuteyi V.I.O., Kolk A.H.J., Thole J.E.R.,
RA Harboe M.;
RT "Molecular and immunological characterization of the highly conserved
RT antigen 84 from Mycobacterium tuberculosis and Mycobacterium leprae.";
RL Infect. Immun. 63:954-960(1995).
RN [2]
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 [3]
RP PHOSPHORYLATION AT THR-73, AND MUTAGENESIS OF THR-73.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15985609; DOI=10.1101/gad.1311105;
RA Kang C.M., Abbott D.W., Park S.T., Dascher C.C., Cantley L.C., Husson R.N.;
RT "The Mycobacterium tuberculosis serine/threonine kinases PknA and PknB:
RT substrate identification and regulation of cell shape.";
RL Genes Dev. 19:1692-1704(2005).
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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18310019; DOI=10.1099/mic.0.2007/014076-0;
RA Kang C.M., Nyayapathy S., Lee J.Y., Suh J.W., Husson R.N.;
RT "Wag31, a homologue of the cell division protein DivIVA, regulates growth,
RT morphology and polar cell wall synthesis in mycobacteria.";
RL Microbiology 154:725-735(2008).
RN [6]
RP FUNCTION, INTERACTION WITH PBPB, SUBUNIT, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF 46-ASN--ASP-48.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19496931; DOI=10.1111/j.1365-2958.2009.06750.x;
RA Mukherjee P., Sureka K., Datta P., Hossain T., Barik S., Das K.P.,
RA Kundu M., Basu J.;
RT "Novel role of Wag31 in protection of mycobacteria under oxidative
RT stress.";
RL Mol. Microbiol. 73:103-119(2009).
RN [7]
RP FUNCTION, SUBUNIT, PHOSPHORYLATION, AND MUTAGENESIS OF THR-73.
RX PubMed=21190553; DOI=10.1186/1471-2180-10-327;
RA Jani C., Eoh H., Lee J.J., Hamasha K., Sahana M.B., Han J.S.,
RA Nyayapathy S., Lee J.Y., Suh J.W., Lee S.H., Rehse S.J., Crick D.C.,
RA Kang C.M.;
RT "Regulation of polar peptidoglycan biosynthesis by Wag31 phosphorylation in
RT mycobacteria.";
RL BMC Microbiol. 10:327-327(2010).
RN [8]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21470298; DOI=10.1111/j.1574-6968.2011.02278.x;
RA Dahl J.L., Lau Bonilla D.;
RT "The wag31 gene of Mycobacterium tuberculosis is positively regulated by
RT the stringent response.";
RL FEMS Microbiol. Lett. 319:153-159(2011).
RN [9]
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 [10]
RP INTERACTION WITH CWSA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23002219; DOI=10.1128/jb.01005-12;
RA Plocinski P., Arora N., Sarva K., Blaszczyk E., Qin H., Das N.,
RA Plocinska R., Ziolkiewicz M., Dziadek J., Kiran M., Gorla P., Cross T.A.,
RA Madiraju M., Rajagopalan M.;
RT "Mycobacterium tuberculosis CwsA interacts with CrgA and Wag31, and the
RT CrgA-CwsA complex is involved in peptidoglycan synthesis and cell shape
RT determination.";
RL J. Bacteriol. 194:6398-6409(2012).
CC -!- FUNCTION: Important for maintaining cell shape and cell wall integrity
CC by localizing peptidoglycan synthesis to the cell poles. Protects PbpB
CC (PBP3, FtsI) from oxidative stress-induced cleavage.
CC {ECO:0000269|PubMed:18310019, ECO:0000269|PubMed:19496931,
CC ECO:0000269|PubMed:21190553}.
CC -!- SUBUNIT: Forms homooligomers. Interacts with PbpB and CwsA.
CC {ECO:0000269|PubMed:19496931, ECO:0000269|PubMed:21190553,
CC ECO:0000269|PubMed:23002219}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18310019,
CC ECO:0000269|PubMed:7868268}. Note=Localizes to the cell poles.
CC -!- INDUCTION: Positively regulated by the stringent response.
CC {ECO:0000269|PubMed:21470298}.
CC -!- PTM: Phosphorylated by PknA. Phosphorylation enhances polar
CC localization, which in turn heightens polar peptidoglycan biosynthesis.
CC {ECO:0000269|PubMed:15985609, ECO:0000269|PubMed:21190553}.
CC -!- DISRUPTION PHENOTYPE: Proteolysis of PbpB (PBP3, FtsI) upon oxidative
CC stress in depletion experiments; degradation is prevented by
CC overexpression of Wag31 but not the 46-Asn--Asp-48 deletion.
CC {ECO:0000269|PubMed:19496931}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the DivIVA family. {ECO:0000305}.
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DR EMBL; X77129; CAA54385.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44921.1; -; Genomic_DNA.
DR PIR; E70578; E70578.
DR RefSeq; NP_216661.1; NC_000962.3.
DR RefSeq; WP_003411131.1; NZ_NVQJ01000044.1.
DR PDB; 6LFA; X-ray; 2.30 A; A/B=2-60.
DR PDBsum; 6LFA; -.
DR AlphaFoldDB; P9WMU1; -.
DR SASBDB; P9WMU1; -.
DR SMR; P9WMU1; -.
DR IntAct; P9WMU1; 3.
DR STRING; 83332.Rv2145c; -.
DR iPTMnet; P9WMU1; -.
DR PaxDb; P9WMU1; -.
DR DNASU; 888224; -.
DR GeneID; 888224; -.
DR KEGG; mtu:Rv2145c; -.
DR TubercuList; Rv2145c; -.
DR eggNOG; COG3599; Bacteria.
DR OMA; VNKRFQP; -.
DR PhylomeDB; P9WMU1; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0060187; C:cell pole; IDA:MTBBASE.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0009273; P:peptidoglycan-based cell wall biogenesis; IMP:MTBBASE.
DR GO; GO:0050821; P:protein stabilization; IDA:MTBBASE.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0040009; P:regulation of growth rate; IMP:UniProtKB.
DR InterPro; IPR019933; DivIVA_domain.
DR InterPro; IPR007793; DivIVA_fam.
DR PANTHER; PTHR35794; PTHR35794; 2.
DR Pfam; PF05103; DivIVA; 1.
DR TIGRFAMs; TIGR03544; DivI1A_domain; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Cell shape; Coiled coil;
KW Cytoplasm; Phosphoprotein; Reference proteome; Stress response.
FT CHAIN 1..260
FT /note="Cell wall synthesis protein Wag31"
FT /id="PRO_0000064492"
FT REGION 233..260
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 31..64
FT /evidence="ECO:0000255"
FT COILED 161..196
FT /evidence="ECO:0000255"
FT MOD_RES 73
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:15985609"
FT MUTAGEN 46..48
FT /note="Missing: No interaction with PbpB (PBP3, FtsI).
FT Slower growth, increased sensitivity to H(2)O(2) and to
FT antibiotics ofloxacin and isoniazid, increased degradation
FT of PbpB. Decreased survival in human macrophage line THP-
FT 1."
FT /evidence="ECO:0000269|PubMed:19496931"
FT MUTAGEN 73
FT /note="T->A,S: Strong decrease in phosphorylation of
FT Wag31."
FT /evidence="ECO:0000269|PubMed:15985609,
FT ECO:0000269|PubMed:21190553"
FT MUTAGEN 73
FT /note="T->E: Increases homooligomerization."
FT /evidence="ECO:0000269|PubMed:15985609,
FT ECO:0000269|PubMed:21190553"
FT HELIX 5..10
FT /evidence="ECO:0007829|PDB:6LFA"
FT HELIX 25..59
FT /evidence="ECO:0007829|PDB:6LFA"
SQ SEQUENCE 260 AA; 28277 MW; D36113355149CEDC CRC64;
MPLTPADVHN VAFSKPPIGK RGYNEDEVDA FLDLVENELT RLIEENSDLR QRINELDQEL
AAGGGAGVTP QATQAIPAYE PEPGKPAPAA VSAGMNEEQA LKAARVLSLA QDTADRLTNT
AKAESDKMLA DARANAEQIL GEARHTADAT VAEARQRADA MLADAQSRSE AQLRQAQEKA
DALQADAERK HSEIMGTINQ QRAVLEGRLE QLRTFEREYR TRLKTYLESQ LEELGQRGSA
APVDSNADAG GFDQFNRGKN
