HIGA1_MYCTU
ID HIGA1_MYCTU Reviewed; 149 AA.
AC P9WJA7; L0TB29; P95258; Q7D7P8;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 43.
DE RecName: Full=Antitoxin HigA1 {ECO:0000303|PubMed:24662523};
GN Name=higA1 {ECO:0000303|PubMed:24662523}; Synonyms=higA;
GN OrderedLocusNames=Rv1956;
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 A TOXIN.
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 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 AN ANTITOXIN, AND INDUCTION BY
RP 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 FUNCTION AS A TRANSCRIPTIONAL REPRESSOR, INDUCTION, DNA-BINDING, AND
RP 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 EXPRESSION IN E.COLI, FUNCTION AS AN ANTITOXIN, SUBUNIT, AND REQUIREMENT
RP FOR SECB-LIKE CHAPERONE RV1957.
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 DISCUSSION OF POSSIBLE 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: Antitoxin component of an atypical, type II toxin-antitoxin
CC chaperone (TAC) system. Upon expression in M.smegmatis neutralizes the
CC effect of cognate toxin HigB1. Neutralization of HigB1 toxin in E.coli
CC or M.marinum also requires SecB-like chaperone Rv1957, making this the
CC first toxin-antitoxin chaperone (TAC) system. Antitoxin aggregation and
CC degradation are prevented by the chaperone.
CC {ECO:0000269|PubMed:21536872}.
CC -!- FUNCTION: In M.tuberculosis represses expression of the Rv1954A-higB1-
CC higA1-Rv1957 operon promoter but not that of the higB1-higA1-Rv1957
CC operon. {ECO:0000269|PubMed:20585061}.
CC -!- SUBUNIT: Interacts with SecB-like chaperone Rv1957.
CC {ECO:0000269|PubMed:21536872}.
CC -!- INDUCTION: Induced by hypoxia and probably by the DNA damaging agent
CC mitomycin C. Part of the Rv1954A-higB1-higA1-Rv1957 operon, as well as
CC the higB1 higA1-Rv1957 operon, which is probably the mitomycin-induced
CC operon; 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:20011113,
CC ECO:0000269|PubMed:20585061, ECO:0000269|PubMed:21673191}.
CC -!- DISRUPTION PHENOTYPE: A triple higB1-higA1-Rv1957 disruption mutant has
CC no visible phenotype. A single deletion in this gene cannot be made,
CC suggesting that it has antitoxin activity.
CC {ECO:0000269|PubMed:20585061}.
CC -!- CAUTION: Upon expression in E.coli, Rv1956 has been shown to function
CC as a toxin inhibiting cell growth and colony formation that is
CC neutralized by coexpression with Rv1955 (PubMed:19016878). It is not
CC clear if these conflicting results are due to expression in a
CC heterologous system. The gene names higA and higB have been assigned to
CC both Rv1955 and Rv1956; we have chosen to call Rv1956 higA1 after
CC consulting the authors. {ECO:0000305|PubMed:19016878}.
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DR EMBL; AL123456; CCP44724.1; -; Genomic_DNA.
DR PIR; H70638; H70638.
DR RefSeq; NP_216472.1; NC_000962.3.
DR RefSeq; WP_003409886.1; NZ_NVQJ01000048.1.
DR PDB; 5MTW; X-ray; 1.84 A; E/F/G=104-116.
DR PDBsum; 5MTW; -.
DR AlphaFoldDB; P9WJA7; -.
DR SMR; P9WJA7; -.
DR STRING; 83332.Rv1956; -.
DR PaxDb; P9WJA7; -.
DR GeneID; 45425926; -.
DR GeneID; 885964; -.
DR KEGG; mtu:Rv1956; -.
DR TubercuList; Rv1956; -.
DR eggNOG; COG1396; Bacteria.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0097351; F:toxin sequestering activity; IPI:MTBBASE.
DR GO; GO:0044003; P:modulation by symbiont of host process; IMP:MTBBASE.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0045927; P:positive regulation of growth; IMP:MTBBASE.
DR GO; GO:0001666; P:response to hypoxia; IEP:MTBBASE.
DR CDD; cd00093; HTH_XRE; 1.
DR Gene3D; 1.10.260.40; -; 1.
DR InterPro; IPR001387; Cro/C1-type_HTH.
DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
DR Pfam; PF01381; HTH_3; 1.
DR SMART; SM00530; HTH_XRE; 1.
DR SUPFAM; SSF47413; SSF47413; 1.
DR PROSITE; PS50943; HTH_CROC1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Reference proteome; Repressor;
KW Toxin-antitoxin system; Transcription; Transcription regulation.
FT CHAIN 1..149
FT /note="Antitoxin HigA1"
FT /id="PRO_0000407371"
FT DOMAIN 42..96
FT /note="HTH cro/C1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00257"
FT DNA_BIND 53..72
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00257"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:5MTW"
SQ SEQUENCE 149 AA; 16760 MW; EBCB6124D6BC7158 CRC64;
MSIDFPLGDD LAGYIAEAIA ADPSFKGTLE DAEEARRLVD ALIALRKHCQ LSQVEVAKRM
GVRQPTVSGF EKEPSDPKLS TLQRYARALD ARLRLVLEVP TLREVPTWHR LSSYRGSARD
HQVRVGADKE ILMQTNWARH ISVRQVEVA
