MMCO_MYCTU
ID MMCO_MYCTU Reviewed; 504 AA.
AC I6WZK7;
DT 27-MAY-2015, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Multicopper oxidase MmcO {ECO:0000305};
DE EC=1.16.3.1 {ECO:0000269|PubMed:23772064};
DE AltName: Full=Mycobacterium multicopper oxidase {ECO:0000303|PubMed:23772064};
DE Flags: Precursor;
GN Name=mmcO {ECO:0000303|PubMed:23772064};
GN OrderedLocusNames=Rv0846c {ECO:0000312|EMBL:CCP43594.1},
GN RVBD_0846c {ECO:0000312|EMBL:AFN48726.1};
GN ORFNames=LH57_04620 {ECO:0000312|EMBL:AIR13579.1},
GN P425_00886 {ECO:0000312|EMBL:KBJ39045.1};
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 25618 / H37Rv;
RG The Broad Institute Genome Sequencing Platform;
RA Galagan J., Kreiswirth B., Dobos K., Fortune S., Fitzgerald M., Young S.K.,
RA Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Berlin A.M., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Gnerre S., Griggs A., Gujja S., Hansen M.,
RA Howarth C., Imamovic A., Larimer J., McCowan C., Murphy C., Pearson M.,
RA Poon T., Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J.,
RA Nusbaum C., Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (NOV-2013) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RG The Broad Institute Genomics Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A.M., Kreiswirth B., Gomez J., Victor T., Desjardins C., Abeel T.,
RA Young S., Zeng Q., Gargeya S., Abouelleil A., Alvarado L., Chapman S.B.,
RA Gainer-Dewar J., Goldberg J., Griggs A., Gujja S., Hansen M., Howarth C.,
RA Imamovic A., Larimer J., Murphy C., Naylor J., Pearson M., Poon T.W.,
RA Priest M., Roberts A., Saif S., Shea T., Sykes S., Wortman J., Nusbaum C.,
RA Birren B.;
RT "The genome sequence of Mycobacterium tuberculosis H37Rv.";
RL Submitted (APR-2014) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [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).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INDUCTION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF CYS-35 AND CYS-486.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23772064; DOI=10.1128/jb.00546-13;
RA Rowland J.L., Niederweis M.;
RT "A multicopper oxidase is required for copper resistance in Mycobacterium
RT tuberculosis.";
RL J. Bacteriol. 195:3724-3733(2013).
RN [7]
RP INDUCTION, DISRUPTION PHENOTYPE, AND OVEREXPRESSION.
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: Required for copper resistance. In vitro, oxidizes organic
CC substrates and Fe(2+). May act in vivo by oxidation of toxic
CC periplasmic Cu(+). {ECO:0000269|PubMed:23772064}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 Fe(2+) + 4 H(+) + O2 = 4 Fe(3+) + 2 H2O;
CC Xref=Rhea:RHEA:11148, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.16.3.1;
CC Evidence={ECO:0000269|PubMed:23772064};
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000250|UniProtKB:Q70KY3};
CC Note=Binds 4 Cu cations per monomer. {ECO:0000250|UniProtKB:Q70KY3};
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000269|PubMed:23772064}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23772064}; Periplasmic side
CC {ECO:0000269|PubMed:23772064}. Periplasm {ECO:0000269|PubMed:23772064}.
CC Note=Could be associated with the membrane through a lipidation site.
CC {ECO:0000269|PubMed:23772064}.
CC -!- INDUCTION: Repressed by RicR (PubMed:24549843). Induced by copper
CC (PubMed:23772064, PubMed:24549843). {ECO:0000269|PubMed:23772064,
CC ECO:0000269|PubMed:24549843}.
CC -!- PTM: Predicted to be exported by the Tat system. The position of the
CC signal peptide cleavage has not been experimentally proven.
CC {ECO:0000255|PROSITE-ProRule:PRU00648}.
CC -!- DISRUPTION PHENOTYPE: Mutant is more sensitive to copper
CC (PubMed:23772064, PubMed:24549843). Deletion does not affect virulence
CC in mice (PubMed:24549843). {ECO:0000269|PubMed:23772064,
CC ECO:0000269|PubMed:24549843}.
CC -!- MISCELLANEOUS: Overexpression results in copper hyperresistance but not
CC hypervirulence. {ECO:0000269|PubMed:24549843}.
CC -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43594.1; -; Genomic_DNA.
DR EMBL; CP003248; AFN48726.1; -; Genomic_DNA.
DR EMBL; JLDD01000008; KBJ39045.1; -; Genomic_DNA.
DR EMBL; CP009480; AIR13579.1; -; Genomic_DNA.
DR RefSeq; NP_215361.1; NC_000962.3.
DR RefSeq; WP_003404392.1; NZ_NVQJ01000040.1.
DR AlphaFoldDB; I6WZK7; -.
DR SMR; I6WZK7; -.
DR STRING; 83332.Rv0846c; -.
DR PaxDb; I6WZK7; -.
DR DNASU; 885207; -.
DR GeneID; 885207; -.
DR KEGG; mtu:Rv0846c; -.
DR KEGG; mtv:RVBD_0846c; -.
DR PATRIC; fig|83332.111.peg.938; -.
DR TubercuList; Rv0846c; -.
DR eggNOG; COG2132; Bacteria.
DR HOGENOM; CLU_009100_6_0_11; -.
DR OMA; WNQMRMS; -.
DR PhylomeDB; I6WZK7; -.
DR BRENDA; 1.16.3.1; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0004322; F:ferroxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR CDD; cd13896; CuRO_3_CopA; 1.
DR Gene3D; 2.60.40.420; -; 3.
DR InterPro; IPR001117; Cu-oxidase.
DR InterPro; IPR011706; Cu-oxidase_C.
DR InterPro; IPR045087; Cu-oxidase_fam.
DR InterPro; IPR011707; Cu-oxidase_N.
DR InterPro; IPR033138; Cu_oxidase_CS.
DR InterPro; IPR002355; Cu_oxidase_Cu_BS.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR034279; CuRO_3_CopA.
DR InterPro; IPR006311; TAT_signal.
DR PANTHER; PTHR11709; PTHR11709; 1.
DR Pfam; PF00394; Cu-oxidase; 1.
DR Pfam; PF07731; Cu-oxidase_2; 1.
DR Pfam; PF07732; Cu-oxidase_3; 1.
DR SUPFAM; SSF49503; SSF49503; 3.
DR PROSITE; PS00079; MULTICOPPER_OXIDASE1; 1.
DR PROSITE; PS00080; MULTICOPPER_OXIDASE2; 1.
DR PROSITE; PS51318; TAT; 1.
PE 1: Evidence at protein level;
KW Cell inner membrane; Cell membrane; Copper; Membrane; Metal-binding;
KW Oxidoreductase; Periplasm; Reference proteome; Signal.
FT SIGNAL 1..44
FT /note="Tat-type signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00648"
FT CHAIN 45..504
FT /note="Multicopper oxidase MmcO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00648"
FT /id="PRO_0000433098"
FT DOMAIN 190..349
FT /note="Plastocyanin-like"
FT /evidence="ECO:0000255"
FT BINDING 120
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 122
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 161
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 163
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 437
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 440
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 442
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 485
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 486
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 487
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT BINDING 491
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q70KY3"
FT MUTAGEN 35
FT /note="C->A: Slight decrease in activity."
FT /evidence="ECO:0000269|PubMed:23772064"
FT MUTAGEN 486
FT /note="C->A: Lack of activity."
FT /evidence="ECO:0000269|PubMed:23772064"
SQ SEQUENCE 504 AA; 53796 MW; 166BC12D4D89E403 CRC64;
MPELATSGNA FDKRRFSRRG FLGAGIASGF ALAACASKPT ASGAAGMTAA IDAAEAARPH
SGRTVTATLT PQPARIDLGG PIVSTLTYGN TIPGPLIRAT VGDEIVVSVT NRLGDPTSVH
WHGIALRNDM DGTEPATANI GPGGDFTYRF SVPDPGTYWA HPHVGLQGDH GLYLPVVVDD
PTEPGHYDAE WIIILDDWTD GIGKSPQQLY GELTDPNKPT MQNTTGMPEG EGVDSNLLGG
DGGDIAYPYY LINGRIPVAA TSFKAKPGQR IRIRIINSAA DTAFRIALAG HSMTVTHTDG
YPVIPTEVDA LLIGMAERYD VMVTAAGGVF PLVALAEGKN ALARALLSTG AGSPPDPQFR
PDELNWRVGT VEMFTAATTA NLGRPEPTHD LPVTLGGTMA KYDWTINGEP YSTTNPLHVR
LGQRPTLMFD NTTMMYHPIH LHGHTFQMIK ADGSPGARKD TVIVLPKQKM RAVLVADNPG
VWVMHCHNNY HQVAGMATRL DYIL
