HIGB1_MYCTU
ID HIGB1_MYCTU Reviewed; 125 AA.
AC P9WJA5; L0T8D1; P95259; Q7D7P9;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Probable endoribonuclease HigB1 {ECO:0000303|PubMed:24662523};
DE EC=3.1.-.-;
DE AltName: Full=Toxin HigB1 {ECO:0000303|PubMed:23927792};
GN Name=higB1 {ECO:0000303|PubMed:24662523}; Synonyms=higB;
GN OrderedLocusNames=Rv1955;
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, AND POSSIBLE FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15718296; DOI=10.1093/nar/gki201;
RA Pandey D.P., Gerdes K.;
RT "Toxin-antitoxin loci are highly abundant in free-living but lost from
RT host-associated prokaryotes.";
RL Nucleic Acids Res. 33:966-976(2005).
RN [3]
RP EXPRESSION IN E.COLI, AND FUNCTION AS AN ANTITOXIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19016878; DOI=10.1111/j.1574-6968.2008.01400.x;
RA Gupta A.;
RT "Killing activity and rescue function of genome-wide toxin-antitoxin loci
RT of Mycobacterium tuberculosis.";
RL FEMS Microbiol. Lett. 290:45-53(2009).
RN [4]
RP START SITE IDENTIFICATION, INDUCTION, AND OPERON STRUCTURE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19118359; DOI=10.1099/mic.0.022889-0;
RA Smollett K.L., Fivian-Hughes A.S., Smith J.E., Chang A., Rao T.,
RA Davis E.O.;
RT "Experimental determination of translational start sites resolves
RT uncertainties in genomic open reading frame predictions - application to
RT Mycobacterium tuberculosis.";
RL Microbiology 155:186-197(2009).
RN [5]
RP EXPRESSION IN M.SMEGMATIS, FUNCTION AS A TOXIN, AND INDUCTION BY HYPOXIA.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=20011113; DOI=10.1371/journal.pgen.1000767;
RA Ramage H.R., Connolly L.E., Cox J.S.;
RT "Comprehensive functional analysis of Mycobacterium tuberculosis toxin-
RT antitoxin systems: implications for pathogenesis, stress responses, and
RT evolution.";
RL PLoS Genet. 5:E1000767-E1000767(2009).
RN [6]
RP PROBABLE FUNCTION AS A TOXIN, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20585061; DOI=10.1128/jb.00454-10;
RA Fivian-Hughes A.S., Davis E.O.;
RT "Analyzing the regulatory role of the HigA antitoxin within Mycobacterium
RT tuberculosis.";
RL J. Bacteriol. 192:4348-4356(2010).
RN [7]
RP INDUCTION IN PERSISTER CELLS.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21673191; DOI=10.1128/mbio.00100-11;
RA Keren I., Minami S., Rubin E., Lewis K.;
RT "Characterization and transcriptome analysis of Mycobacterium tuberculosis
RT persisters.";
RL MBio 2:E00100-E00111(2011).
RN [8]
RP FUNCTION AS A TOXIN, AND EXPRESSION IN E.COLI AND M.MARINUM.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21536872; DOI=10.1073/pnas.1101189108;
RA Bordes P., Cirinesi A.M., Ummels R., Sala A., Sakr S., Bitter W.,
RA Genevaux P.;
RT "SecB-like chaperone controls a toxin-antitoxin stress-responsive system in
RT Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:8438-8443(2011).
RN [9]
RP FUNCTION, AND EXPRESSION IN M.SMEGMATIS AND M.TUBERCULOSIS.
RX PubMed=23927792; DOI=10.1111/mmi.12358;
RA Schuessler D.L., Cortes T., Fivian-Hughes A.S., Lougheed K.E., Harvey E.,
RA Buxton R.S., Davis E.O., Young D.B.;
RT "Induced ectopic expression of HigB toxin in Mycobacterium tuberculosis
RT results in growth inhibition, reduced abundance of a subset of mRNAs and
RT cleavage of tmRNA.";
RL Mol. Microbiol. 90:195-207(2013).
RN [10]
RP DISCUSSION OF FUNCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=24662523; DOI=10.3390/toxins6031002;
RA Sala A., Bordes P., Genevaux P.;
RT "Multiple toxin-antitoxin systems in Mycobacterium tuberculosis.";
RL Toxins 6:1002-1020(2014).
CC -!- FUNCTION: Toxic component of an atypical, type II toxin-antitoxin
CC chaperone (TAC) system. Upon expression in M.smegmatis inhibits colony
CC formation and cell growth (PubMed:20011113, PubMed:23927792). Ectopic
CC expression in wild-type M.tuberculosis has no effect on cell growth;
CC ectopic expression in a triple higB1-higA1-Rv1957 (delta TAC)
CC disruption mutant causes growth arrest, killing a considerable
CC proportion of the cells. Increased ectopic expression leads to
CC decreased levels of IdeR- and Zur-regulated genes as well as cleavage
CC within the mRNA region of tmRNA (transfer-mRNA), strongly suggesting it
CC is an endoribonuclease; also degrades E.coli and M-smegmatis tmRNA
CC (PubMed:23927792). Its toxic effect is neutralized by coexpression with
CC antitoxin HigA. Neutralization of HigB1 toxin in E.coli or M.marinum
CC also requires SecB-like chaperone Rv1957, making this the first toxin-
CC antitoxin chaperone (TAC) system (PubMed:21536872).
CC {ECO:0000269|PubMed:19016878, ECO:0000269|PubMed:20011113,
CC ECO:0000269|PubMed:21536872, ECO:0000269|PubMed:23927792}.
CC -!- INDUCTION: Induced by hypoxia and by DNA damaging agent mitomycin C.
CC Part of the Rv1954A-higB1-higA1-Rv1957 operon, as well as the higB1-
CC higA1-Rv1957 operon, which is probably the mitomycin-induced operon;
CC the former but not latter operon is autorepressed by HigA1
CC (PubMed:20585061). Induced in persister cells in response to D-
CC cycloserine (PubMed:21673191). {ECO:0000269|PubMed:19118359,
CC ECO:0000269|PubMed:20011113, ECO:0000269|PubMed:20585061,
CC ECO:0000269|PubMed:21673191}.
CC -!- DISRUPTION PHENOTYPE: A triple higB1-higA1-Rv1957 disruption mutant has
CC no visible phenotype. {ECO:0000269|PubMed:20585061}.
CC -!- SIMILARITY: Belongs to the mycobacterial HigB family. {ECO:0000305}.
CC -!- CAUTION: Upon expression in E.coli, Rv1955 has been shown to function
CC as an antitoxin against Rv1956 (PubMed:19016878). It is not clear if
CC these conflicting results are due to expression in a heterologous
CC system. The gene names higA and higB have been assigned to both Rv1955
CC and Rv1956; we have chosen to call Rv1955 higB1 after consulting the
CC authors. {ECO:0000305|PubMed:19016878}.
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DR EMBL; AL123456; CCP44723.1; -; Genomic_DNA.
DR PIR; G70638; G70638.
DR RefSeq; NP_216471.2; NC_000962.3.
DR RefSeq; WP_010886136.1; NZ_NVQJ01000048.1.
DR PDB; 7AWK; X-ray; 1.91 A; A=1-125.
DR PDB; 7NBU; EM; 3.11 A; Y=7-125.
DR PDBsum; 7AWK; -.
DR PDBsum; 7NBU; -.
DR AlphaFoldDB; P9WJA5; -.
DR SMR; P9WJA5; -.
DR STRING; 83332.Rv1955; -.
DR PaxDb; P9WJA5; -.
DR DNASU; 885966; -.
DR GeneID; 885966; -.
DR KEGG; mtu:Rv1955; -.
DR PATRIC; fig|83332.12.peg.2183; -.
DR TubercuList; Rv1955; -.
DR eggNOG; COG4679; Bacteria.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0004521; F:endoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0098754; P:detoxification; IMP:MTBBASE.
DR GO; GO:0045926; P:negative regulation of growth; IMP:MTBBASE.
DR GO; GO:0001666; P:response to hypoxia; IEP:MTBBASE.
DR InterPro; IPR009241; HigB-like.
DR Pfam; PF05973; Gp49; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endonuclease; Hydrolase; Nuclease; Reference proteome;
KW Toxin-antitoxin system.
FT CHAIN 1..125
FT /note="Probable endoribonuclease HigB1"
FT /id="PRO_0000407370"
FT HELIX 24..30
FT /evidence="ECO:0007829|PDB:7AWK"
FT HELIX 34..49
FT /evidence="ECO:0007829|PDB:7AWK"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:7AWK"
FT STRAND 57..61
FT /evidence="ECO:0007829|PDB:7AWK"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:7AWK"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:7AWK"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:7AWK"
FT STRAND 86..94
FT /evidence="ECO:0007829|PDB:7AWK"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:7AWK"
FT HELIX 102..119
FT /evidence="ECO:0007829|PDB:7AWK"
SQ SEQUENCE 125 AA; 14430 MW; 1CB206A94F0A92D5 CRC64;
MPPPDPAAMG TWKFFRASVD GRPVFKKEFD KLPDQARAAL IVLMQRYLVG DLAAGSIKPI
RGDILELRWH EANNHFRVLF FRWGQHPVAL TAFYKNQQKT PKTKIETALD RQKIWKRAFG
DTPPI
