ESXH_MYCTU
ID ESXH_MYCTU Reviewed; 96 AA.
AC P9WNK3; L0T606; O53693; P0A568;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=ESAT-6-like protein EsxH {ECO:0000305};
DE AltName: Full=10 kDa antigen CFP7 {ECO:0000305};
DE Short=CFP-7 {ECO:0000305};
DE AltName: Full=Low molecular weight protein antigen 7 {ECO:0000305};
DE AltName: Full=Protein TB10.4 {ECO:0000303|PubMed:10603390};
GN Name=esxH {ECO:0000303|PubMed:15336430, ECO:0000303|PubMed:19876390};
GN Synonyms=cfp7; OrderedLocusNames=Rv0288; ORFNames=MTV035.16;
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 CHARACTERIZATION.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RA Nielsen R.V.;
RL Thesis (1997), Statens Serum Institut / Copenhagen, Denmark.
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 PROTEIN SEQUENCE OF 13-27, AND BIOTECHNOLOGY.
RX PubMed=10603390; DOI=10.1128/iai.68.1.214-220.2000;
RA Skjot R.L., Oettinger T., Rosenkrands I., Ravn P., Brock I., Jacobsen S.,
RA Andersen P.;
RT "Comparative evaluation of low-molecular-mass proteins from Mycobacterium
RT tuberculosis identifies members of the ESAT-6 family as immunodominant T-
RT cell antigens.";
RL Infect. Immun. 68:214-220(2000).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=12228269; DOI=10.1128/iai.70.10.5446-5453.2002;
RA Skjoet R.L., Brock I., Arend S.M., Munk M.E., Theisen M., Ottenhoff T.H.,
RA Andersen P.;
RT "Epitope mapping of the immunodominant antigen TB10.4 and the two
RT homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the
RT esat-6 gene family.";
RL Infect. Immun. 70:5446-5453(2002).
RN [5]
RP INTERACTION WITH ESXG.
RX PubMed=15336430; DOI=10.1111/j.1574-6968.2004.tb09764.x;
RA Lightbody K.L., Renshaw P.S., Collins M.L., Wright R.L., Hunt D.M.,
RA Gordon S.V., Hewinson R.G., Buxton R.S., Williamson R.A., Carr M.D.;
RT "Characterisation of complex formation between members of the Mycobacterium
RT tuberculosis complex CFP-10/ESAT-6 protein family: towards an understanding
RT of the rules governing complex formation and thereby functional
RT flexibility.";
RL FEMS Microbiol. Lett. 238:255-262(2004).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=16714570; DOI=10.1128/iai.02086-05;
RA Hervas-Stubbs S., Majlessi L., Simsova M., Morova J., Rojas M.J., Nouze C.,
RA Brodin P., Sebo P., Leclerc C.;
RT "High frequency of CD4+ T cells specific for the TB10.4 protein correlates
RT with protection against Mycobacterium tuberculosis infection.";
RL Infect. Immun. 74:3396-3407(2006).
RN [7]
RP INTERACTION WITH ESXG.
RX PubMed=18430736; DOI=10.1074/jbc.m800123200;
RA Lightbody K.L., Ilghari D., Waters L.C., Carey G., Bailey M.A.,
RA Williamson R.A., Renshaw P.S., Carr M.D.;
RT "Molecular features governing the stability and specificity of functional
RT complex formation by Mycobacterium tuberculosis CFP-10/ESAT-6 family
RT proteins.";
RL J. Biol. Chem. 283:17681-17690(2008).
RN [8]
RP NOMENCLATURE.
RX PubMed=19876390; DOI=10.1371/journal.ppat.1000507;
RA Bitter W., Houben E.N., Bottai D., Brodin P., Brown E.J., Cox J.S.,
RA Derbyshire K., Fortune S.M., Gao L.Y., Liu J., Gey van Pittius N.C.,
RA Pym A.S., Rubin E.J., Sherman D.R., Cole S.T., Brosch R.;
RT "Systematic genetic nomenclature for type VII secretion systems.";
RL PLoS Pathog. 5:E1000507-E1000507(2009).
RN [9]
RP SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19854905; DOI=10.1128/jb.01032-09;
RA Callahan B., Nguyen K., Collins A., Valdes K., Caplow M., Crossman D.K.,
RA Steyn A.J., Eisele L., Derbyshire K.M.;
RT "Conservation of structure and protein-protein interactions mediated by the
RT secreted mycobacterial proteins EsxA, EsxB, and EspA.";
RL J. Bacteriol. 192:326-335(2010).
RN [10]
RP SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20085764; DOI=10.1016/j.febslet.2009.12.057;
RA Poulsen C., Holton S., Geerlof A., Wilmanns M., Song Y.H.;
RT "Stoichiometric protein complex formation and over-expression using the
RT prokaryotic native operon structure.";
RL FEBS Lett. 584:669-674(2010).
RN [11]
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 [12]
RP FUNCTION IN VIRULENCE, SUBCELLULAR LOCATION, INTERACTION WITH ESXG AND HOST
RP HGS/HRS, AND MUTAGENESIS OF HIS-14; HIS-70; HIS-76 AND GLU-77.
RC STRAIN=H37Rv;
RX PubMed=24204276; DOI=10.1371/journal.ppat.1003734;
RA Mehra A., Zahra A., Thompson V., Sirisaengtaksin N., Wells A., Porto M.,
RA Koester S., Penberthy K., Kubota Y., Dricot A., Rogan D., Vidal M.,
RA Hill D.E., Bean A.J., Philips J.A.;
RT "Mycobacterium tuberculosis type VII secreted effector EsxH targets host
RT ESCRT to impair trafficking.";
RL PLoS Pathog. 9:E1003734-E1003734(2013).
RN [13]
RP BIOTECHNOLOGY.
RX PubMed=24280763; DOI=10.4161/hv.27121;
RA Kong H., Dong C., Xiong S.;
RT "A novel vaccine p846 encoding Rv3615c, Mtb10.4, and Rv2660c elicits robust
RT immune response and alleviates lung injury induced by Mycobacterium
RT infection.";
RL Hum. Vaccin. Immunother. 10:378-390(2014).
RN [14]
RP STRUCTURE BY NMR, INTERACTION WITH ESXG, ZINC-BINDING, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21730061; DOI=10.1074/jbc.m111.248732;
RA Ilghari D., Lightbody K.L., Veverka V., Waters L.C., Muskett F.W.,
RA Renshaw P.S., Carr M.D.;
RT "Solution structure of the Mycobacterium tuberculosis EsxG.EsxH complex:
RT functional implications and comparisons with other M. tuberculosis Esx
RT family complexes.";
RL J. Biol. Chem. 286:29993-30002(2011).
CC -!- FUNCTION: EsxH, in complex with EsxG, disrupts ESCRT function and
CC impairs host phagosome maturation, thereby promoting intracellular
CC bacterial growth. The complex acts by interacting, via EsxH, with the
CC host hepatocyte growth factor-regulated tyrosine kinase substrate
CC (HGS/HRS), a component of the ESCRT machinery.
CC {ECO:0000269|PubMed:24204276}.
CC -!- SUBUNIT: Forms a tight 1:1 complex with EsxG (PubMed:15336430,
CC PubMed:18430736, PubMed:19854905, PubMed:20085764, PubMed:21730061,
CC PubMed:24204276). When it is complexed to EsxG, interacts directly with
CC host HGS/HRS (PubMed:24204276). {ECO:0000269|PubMed:15336430,
CC ECO:0000269|PubMed:18430736, ECO:0000269|PubMed:19854905,
CC ECO:0000269|PubMed:20085764, ECO:0000269|PubMed:21730061,
CC ECO:0000269|PubMed:24204276}.
CC -!- INTERACTION:
CC P9WNK3; O53692: esxG; NbExp=4; IntAct=EBI-6409599, EBI-6409586;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24204276}.
CC Note=Secreted via the ESX-3 / type VII secretion system (T7SS).
CC {ECO:0000305|PubMed:21730061, ECO:0000305|PubMed:24204276}.
CC -!- BIOTECHNOLOGY: Contains a number of strongly recognized T-cell epitopes
CC distributed throughout the protein sequence and induces high level of
CC IFN-gamma, indicating this might be a good vaccine candidate
CC (PubMed:10603390, PubMed:12228269, PubMed:16714570). A fusion protein
CC (p846) of 3 well-defined antigens (EspC, EsxH and Rv2660c) induces
CC robust specific T-cell immune response and could be an effective
CC vaccine (PubMed:24280763). {ECO:0000269|PubMed:10603390,
CC ECO:0000269|PubMed:12228269, ECO:0000269|PubMed:16714570,
CC ECO:0000269|PubMed:24280763}.
CC -!- MISCELLANEOUS: To improve expression in E.coli the proteins were cloned
CC as a single protein in the order esxH-esxG with a cleavable thrombin
CC tag (PubMed:19854905). {ECO:0000269|PubMed:19854905}.
CC -!- SIMILARITY: Belongs to the WXG100 family. ESAT-6 subfamily.
CC {ECO:0000305|PubMed:19876390}.
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DR EMBL; AJ002067; CAA05168.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP43018.1; -; Genomic_DNA.
DR PIR; F70836; F70836.
DR RefSeq; NP_214802.1; NC_000962.3.
DR RefSeq; WP_003401514.1; NZ_NVQJ01000026.1.
DR PDB; 2KG7; NMR; -; B=1-96.
DR PDB; 6J29; X-ray; 1.60 A; C=3-11.
DR PDBsum; 2KG7; -.
DR PDBsum; 6J29; -.
DR AlphaFoldDB; P9WNK3; -.
DR BMRB; P9WNK3; -.
DR SMR; P9WNK3; -.
DR IntAct; P9WNK3; 1.
DR MINT; P9WNK3; -.
DR STRING; 83332.Rv0288; -.
DR PaxDb; P9WNK3; -.
DR DNASU; 886603; -.
DR GeneID; 45424262; -.
DR GeneID; 886603; -.
DR KEGG; mtu:Rv0288; -.
DR TubercuList; Rv0288; -.
DR eggNOG; COG4842; Bacteria.
DR OMA; HEANTMS; -.
DR PhylomeDB; P9WNK3; -.
DR Reactome; R-HSA-9635644; Inhibition of membrane repair.
DR Reactome; R-HSA-9636383; Prevention of phagosomal-lysosomal fusion.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0097013; C:phagocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR DisProt; DP00799; -.
DR InterPro; IPR036689; ESAT-6-like_sf.
DR InterPro; IPR010310; T7SS_ESAT-6-like.
DR Pfam; PF06013; WXG100; 1.
DR SUPFAM; SSF140453; SSF140453; 1.
DR TIGRFAMs; TIGR03930; WXG100_ESAT6; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Metal-binding; Reference proteome;
KW Secreted; Virulence; Zinc.
FT CHAIN 1..96
FT /note="ESAT-6-like protein EsxH"
FT /id="PRO_0000167798"
FT BINDING 14
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:21730061"
FT BINDING 70
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:21730061"
FT BINDING 76
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:21730061"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:21730061"
FT MUTAGEN 14
FT /note="H->A: No change in activity."
FT /evidence="ECO:0000269|PubMed:24204276"
FT MUTAGEN 70
FT /note="H->R: No change in activity."
FT /evidence="ECO:0000269|PubMed:24204276"
FT MUTAGEN 76
FT /note="H->A: Still interacts with EsxG, but impairs
FT interaction with host HGS/HRS; when associated with A-77."
FT /evidence="ECO:0000269|PubMed:24204276"
FT MUTAGEN 77
FT /note="E->A: Still interacts with EsxG, but impairs
FT interaction with host HGS/HRS; when associated with A-76."
FT /evidence="ECO:0000269|PubMed:24204276"
FT TURN 3..5
FT /evidence="ECO:0007829|PDB:2KG7"
FT STRAND 10..13
FT /evidence="ECO:0007829|PDB:2KG7"
FT HELIX 18..38
FT /evidence="ECO:0007829|PDB:2KG7"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:2KG7"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:2KG7"
FT HELIX 51..70
FT /evidence="ECO:0007829|PDB:2KG7"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:2KG7"
FT HELIX 75..81
FT /evidence="ECO:0007829|PDB:2KG7"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:2KG7"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:2KG7"
SQ SEQUENCE 96 AA; 10391 MW; EC47BE7E10690437 CRC64;
MSQIMYNYPA MLGHAGDMAG YAGTLQSLGA EIAVEQAALQ SAWQGDTGIT YQAWQAQWNQ
AMEDLVRAYH AMSSTHEANT MAMMARDTAE AAKWGG
