TLYA_MYCTU
ID TLYA_MYCTU Reviewed; 268 AA.
AC P9WJ63; L0TA51; O07264; Q50760; Q79FL7; Q7D847;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA;
DE EC=2.1.1.226 {ECO:0000269|PubMed:16857584};
DE EC=2.1.1.227 {ECO:0000269|PubMed:16857584};
DE AltName: Full=16S rRNA (cytidine1409-2'-O)-methyltransferase;
DE AltName: Full=23S rRNA (cytidine1920-2'-O)-methyltransferase;
DE AltName: Full=Hemolysin TlyA;
GN Name=tlyA; OrderedLocusNames=Rv1694;
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 FUNCTION IN HEMOLYSIS.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9611795; DOI=10.1099/00221287-144-5-1205;
RA Wren B.W., Stabler R.A., Das S.S., Butcher P.D., Mangan J.A., Clarke J.D.,
RA Casali N., Parish T., Stoker N.G.;
RT "Characterization of a haemolysin from Mycobacterium tuberculosis with
RT homology to a virulence factor of Serpulina hyodysenteriae.";
RL Microbiology 144:1205-1211(1998).
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 DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15673735; DOI=10.1128/aac.49.2.571-577.2005;
RA Maus C.E., Plikaytis B.B., Shinnick T.M.;
RT "Mutation of tlyA confers capreomycin resistance in Mycobacterium
RT tuberculosis.";
RL Antimicrob. Agents Chemother. 49:571-577(2005).
RN [4]
RP FUNCTION AS A METHYLTRANSFERASE, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16857584; DOI=10.1016/j.molcel.2006.05.044;
RA Johansen S.K., Maus C.E., Plikaytis B.B., Douthwaite S.;
RT "Capreomycin binds across the ribosomal subunit interface using tlyA-
RT encoded 2'-O-methylations in 16S and 23S rRNAs.";
RL Mol. Cell 23:173-182(2006).
RN [5]
RP FUNCTION AS A METHYLTRANSFERASE AND IN HEMOLYSIS, SUBUNIT, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20854656; DOI=10.1186/1471-2091-11-35;
RA Rahman A., Srivastava S.S., Sneh A., Ahmed N., Krishnasastry M.V.;
RT "Molecular characterization of tlyA gene product, Rv1694 of Mycobacterium
RT tuberculosis: a non-conventional hemolysin and a ribosomal RNA methyl
RT transferase.";
RL BMC Biochem. 11:35-35(2010).
RN [6]
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 [7]
RP 3D-STRUCTURE MODELING, AND FUNCTION.
RX PubMed=21443791; DOI=10.1186/1472-6807-11-16;
RA Arenas N.E., Salazar L.M., Soto C.Y., Vizcaino C., Patarroyo M.E.,
RA Patarroyo M.A., Gomez A.;
RT "Molecular modeling and in silico characterization of Mycobacterium
RT tuberculosis TlyA: possible misannotation of this tubercle bacilli-
RT hemolysin.";
RL BMC Struct. Biol. 11:16-16(2011).
RN [8]
RP SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=26347855; DOI=10.3389/fcimb.2015.00060;
RA Kumar S., Mittal E., Deore S., Kumar A., Rahman A., Krishnasastry M.V.;
RT "Mycobacterial tlyA gene product is localized to the cell-wall without
RT signal sequence.";
RL Front. Cell. Infect. Microbiol. 5:60-60(2015).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=25847237; DOI=10.1074/jbc.m115.653600;
RA Rahman M.A., Sobia P., Dwivedi V.P., Bhawsar A., Singh D.K., Sharma P.,
RA Moodley P., Van Kaer L., Bishai W.R., Das G.;
RT "Mycobacterium tuberculosis TlyA protein negatively regulates T helper (Th)
RT 1 and Th17 differentiation and promotes tuberculosis pathogenesis.";
RL J. Biol. Chem. 290:14407-14417(2015).
CC -!- FUNCTION: Acts as a host evasion factor, that significantly contributes
CC to the pathogenesis of M.tuberculosis by modulating adaptive immune
CC responses by inhibiting host-protective Th1 and Th17 cytokine responses
CC as well as autophagy (PubMed:25847237). Catalyzes the 2'-O-methylation
CC at nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA
CC (PubMed:16857584, PubMed:20854656). Is likely involved in ribosomal
CC biogenesis (PubMed:21443791). Also exhibits hemolytic activity in
CC vitro, by binding with and oligomerizing into host cell membranes
CC (PubMed:20854656, PubMed:9611795). {ECO:0000269|PubMed:16857584,
CC ECO:0000269|PubMed:20854656, ECO:0000269|PubMed:21443791,
CC ECO:0000269|PubMed:25847237, ECO:0000269|PubMed:9611795}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(1409) in 16S rRNA + S-adenosyl-L-methionine = 2'-O-
CC methylcytidine(1409) in 16S rRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:43204, Rhea:RHEA-COMP:10405, Rhea:RHEA-COMP:10406,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74495, ChEBI:CHEBI:82748; EC=2.1.1.227;
CC Evidence={ECO:0000269|PubMed:16857584};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(1920) in 23S rRNA + S-adenosyl-L-methionine = 2'-O-
CC methylcytidine(1920) in 23S rRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:43200, Rhea:RHEA-COMP:10403, Rhea:RHEA-COMP:10404,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74495, ChEBI:CHEBI:82748; EC=2.1.1.226;
CC Evidence={ECO:0000269|PubMed:16857584};
CC -!- SUBUNIT: Can form oligomers on macrophage phagosomal membranes.
CC {ECO:0000269|PubMed:20854656}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20854656}.
CC Secreted, cell wall {ECO:0000269|PubMed:26347855}. Host cell membrane
CC {ECO:0000269|PubMed:20854656}. Note=Can bind to target membranes such
CC as macrophage phagosomal membranes (PubMed:20854656). In native and
CC recombinant hosts (M.smegmatis and E.coli), M.tuberculosis TlyA can
CC reach the bacterial surface in functional form and colocalizes with the
CC HBHA protein which is known to be part of cell-wall (PubMed:26347855).
CC TlyA does not seem to depend on either Tat or Sec pathways for
CC translocation to cell-wall (PubMed:26347855). Appears to be capable of
CC reaching the extra-cellular milieu using a vesicle mediated transport
CC (PubMed:26347855). {ECO:0000269|PubMed:20854656,
CC ECO:0000269|PubMed:26347855}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene induce increased IL-12
CC and reduced IL-1beta and IL-10 cytokine responses, which sharply
CC contrasts with the immune responses induced by wild-type M.tuberculosis
CC (PubMed:25847237). They are also more susceptible to autophagy in
CC macrophages (PubMed:25847237). Consequently, animals infected with the
CC TlyA-deficient mutant M.tuberculosis organisms exhibit increased host-
CC protective immune responses, reduced bacillary load, and increased
CC survival compared with animals infected with wild-type M.tuberculosis
CC (PubMed:25847237). Disruption of this gene leads to capreomycin
CC resistance (PubMed:15673735). {ECO:0000269|PubMed:15673735,
CC ECO:0000269|PubMed:25847237}.
CC -!- SIMILARITY: Belongs to the TlyA family. {ECO:0000305}.
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DR EMBL; X98295; CAA66941.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44459.1; -; Genomic_DNA.
DR PIR; E70502; E70502.
DR RefSeq; NP_216210.1; NC_000962.3.
DR RefSeq; WP_003408382.1; NZ_NVQJ01000010.1.
DR PDB; 5KS2; X-ray; 2.18 A; A=60-268.
DR PDB; 5KYG; X-ray; 1.90 A; A=60-268.
DR PDBsum; 5KS2; -.
DR PDBsum; 5KYG; -.
DR AlphaFoldDB; P9WJ63; -.
DR SMR; P9WJ63; -.
DR STRING; 83332.Rv1694; -.
DR DrugBank; DB00314; Capreomycin.
DR DrugBank; DB06827; Viomycin.
DR PaxDb; P9WJ63; -.
DR DNASU; 885396; -.
DR GeneID; 45425663; -.
DR GeneID; 885396; -.
DR KEGG; mtu:Rv1694; -.
DR TubercuList; Rv1694; -.
DR eggNOG; COG1189; Bacteria.
DR OMA; VLMVKPQ; -.
DR PhylomeDB; P9WJ63; -.
DR BioCyc; MetaCyc:G185E-5885-MON; -.
DR BRENDA; 2.1.1.226; 3445.
DR BRENDA; 2.1.1.227; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008649; F:rRNA methyltransferase activity; IDA:MTBBASE.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0019836; P:hemolysis by symbiont of host erythrocytes; IDA:MTBBASE.
DR GO; GO:0044179; P:hemolysis in another organism; IEA:UniProtKB-KW.
DR GO; GO:0031167; P:rRNA methylation; IDA:MTBBASE.
DR CDD; cd00165; S4; 1.
DR Gene3D; 3.10.290.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR004538; Haemolysin_A/TlyA.
DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR002942; S4_RNA-bd.
DR InterPro; IPR036986; S4_RNA-bd_sf.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PANTHER; PTHR32319:SF0; PTHR32319:SF0; 1.
DR Pfam; PF01728; FtsJ; 1.
DR Pfam; PF01479; S4; 1.
DR PIRSF; PIRSF005578; TlyA; 1.
DR SMART; SM00363; S4; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR TIGRFAMs; TIGR00478; tly; 1.
DR PROSITE; PS50889; S4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell wall; Cytolysis; Cytoplasm; Hemolysis;
KW Host cell membrane; Host membrane; Membrane; Methyltransferase;
KW Reference proteome; Ribosome biogenesis; RNA-binding; rRNA processing;
KW S-adenosyl-L-methionine; Secreted; Toxin; Transferase; Virulence.
FT CHAIN 1..268
FT /note="16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA"
FT /id="PRO_0000415501"
FT DOMAIN 5..67
FT /note="S4 RNA-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00182"
FT HELIX 66..77
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:5KS2"
FT HELIX 95..102
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 160..170
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 171..181
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:5KYG"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 194..196
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 201..217
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:5KYG"
FT STRAND 239..246
FT /evidence="ECO:0007829|PDB:5KYG"
FT HELIX 253..266
FT /evidence="ECO:0007829|PDB:5KYG"
SQ SEQUENCE 268 AA; 28074 MW; B62AB8400CCC71CE CRC64;
MARRARVDAE LVRRGLARSR QQAAELIGAG KVRIDGLPAV KPATAVSDTT ALTVVTDSER
AWVSRGAHKL VGALEAFAIA VAGRRCLDAG ASTGGFTEVL LDRGAAHVVA ADVGYGQLAW
SLRNDPRVVV LERTNARGLT PEAIGGRVDL VVADLSFISL ATVLPALVGC ASRDADIVPL
VKPQFEVGKG QVGPGGVVHD PQLRARSVLA VARRAQELGW HSVGVKASPL PGPSGNVEYF
LWLRTQTDRA LSAKGLEDAV HRAISEGP
