MYMT_MYCTU
ID MYMT_MYCTU Reviewed; 53 AA.
AC P9WK09; P0CI28; Q8VKQ2;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Metallothionein;
DE Short=MT;
DE AltName: Full=Copper-binding metallothionein;
DE Short=Cu(I)-binding metallothionein;
DE AltName: Full=Mycobacterial metallothionein;
DE Flags: Precursor;
GN Name=mymT; OrderedLocusNames=Rv0186A;
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 IDENTIFICATION, FUNCTION AS A COPPER-BINDING PROTEIN, CHARACTERIZATION,
RP MASS SPECTROMETRY, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18724363; DOI=10.1038/nchembio.109;
RA Gold B., Deng H., Bryk R., Vargas D., Eliezer D., Roberts J., Jiang X.,
RA Nathan C.;
RT "Identification of a copper-binding metallothionein in pathogenic
RT mycobacteria.";
RL Nat. Chem. Biol. 4:609-616(2008).
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 INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21166899; DOI=10.1111/j.1365-2958.2010.07431.x;
RA Festa R.A., Jones M.B., Butler-Wu S., Sinsimer D., Gerads R., Bishai W.R.,
RA Peterson S.N., Darwin K.H.;
RT "A novel copper-responsive regulon in Mycobacterium tuberculosis.";
RL Mol. Microbiol. 79:133-148(2011).
RN [5]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=24549843; DOI=10.1128/mbio.00876-13;
RA Shi X., Festa R.A., Ioerger T.R., Butler-Wu S., Sacchettini J.C.,
RA Darwin K.H., Samanovic M.I.;
RT "The copper-responsive RicR regulon contributes to Mycobacterium
RT tuberculosis virulence.";
RL MBio 5:E00876-E00876(2014).
CC -!- FUNCTION: Metallothioneins are small proteins that have a high content
CC of cysteine residues wich allow them to bind heavy metal ions through
CC clusters of thiolate bonds. MymT binds up to seven ions of Cu(+), with
CC a preference for four to six Cu(+) ions, in a solvent-shielded core.
CC MymT protects M.tuberculosis from copper toxicity.
CC {ECO:0000269|PubMed:18724363}.
CC -!- INDUCTION: Up-regulated by copper, cadmium, cobalt, nickel and zinc,
CC but not manganese. Copper and cadmium salts afford the strongest metal-
CC dependent induction at about 1,000-fold. Also highly up-regulated under
CC conditions that are believed to be attained in phagosomes of
CC interferon-gamma-activated macrophages, including production of nitric
CC oxide and reactive oxygen intermediates, mild acid (pH 5.5), and cell
CC wall perturbation (PubMed:18724363). Repressed by RicR
CC (PubMed:21166899). {ECO:0000269|PubMed:18724363,
CC ECO:0000269|PubMed:21166899}.
CC -!- MASS SPECTROMETRY: Mass=4933.4; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:18724363};
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene show hypersensitivity to
CC Cu(+) toxicity but not to divalent heavy metals such as Zn(2+).
CC Deficiency of MymT does not impair M.tuberculosis virulence in mice.
CC {ECO:0000269|PubMed:18724363, ECO:0000269|PubMed:24549843}.
CC -!- MISCELLANEOUS: NO and reactive nitrogen intermediates (RNI) can
CC displace Cu(+) from MymT.
CC -!- SIMILARITY: Belongs to the metallothionein superfamily. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-6 is the initiator. If
CC Met-1 is the initiator, MymT would undergo a first cleavage after Arg-5
CC followed by processing of the N-terminal methionine. {ECO:0000305}.
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DR EMBL; AL123456; CCP42913.1; -; Genomic_DNA.
DR RefSeq; WP_010886068.1; NZ_NVQJ01000001.1.
DR RefSeq; YP_004837046.2; NC_000962.3.
DR AlphaFoldDB; P9WK09; -.
DR STRING; 83332.Rv0186A; -.
DR PaxDb; P9WK09; -.
DR GeneID; 14515880; -.
DR GeneID; 45424157; -.
DR KEGG; mtu:Rv0186A; -.
DR PATRIC; fig|83332.111.peg.214; -.
DR TubercuList; Rv0186A; -.
DR eggNOG; ENOG5031TF4; Bacteria.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005507; F:copper ion binding; IDA:MTBBASE.
DR GO; GO:0008270; F:zinc ion binding; IDA:MTBBASE.
DR GO; GO:0055070; P:copper ion homeostasis; IMP:MTBBASE.
DR GO; GO:0046686; P:response to cadmium ion; IEP:MTBBASE.
DR GO; GO:0032025; P:response to cobalt ion; IEP:MTBBASE.
DR GO; GO:0046688; P:response to copper ion; IDA:MTBBASE.
DR GO; GO:0010045; P:response to nickel cation; IEP:MTBBASE.
DR GO; GO:0010043; P:response to zinc ion; IEP:MTBBASE.
PE 1: Evidence at protein level;
KW Copper; Metal-binding; Metal-thiolate cluster; Reference proteome.
FT PROPEP 1..6
FT /evidence="ECO:0000305"
FT /id="PRO_0000401202"
FT CHAIN 7..53
FT /note="Metallothionein"
FT /id="PRO_0000401203"
FT BINDING 17
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 17
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 19
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 22
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 24
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 24
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000305"
FT BINDING 32
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 32
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000305"
FT BINDING 33
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="4"
FT /evidence="ECO:0000305"
FT BINDING 34
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="1"
FT /evidence="ECO:0000305"
FT BINDING 43
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
FT BINDING 45
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="2"
FT /evidence="ECO:0000305"
FT BINDING 45
FT /ligand="Cu(+)"
FT /ligand_id="ChEBI:CHEBI:49552"
FT /ligand_label="3"
FT /evidence="ECO:0000305"
SQ SEQUENCE 53 AA; 5719 MW; B64C8B485F1668D7 CRC64;
MRVIRMTNYE AGTLLTCSHE GCGCRVRIEV PCHCAGAGDA YRCTCGDELA PVK
