ESPI_MYCTU
ID ESPI_MYCTU Reviewed; 666 AA.
AC P9WJC5; L0TH05; O69740; Q7D4P3;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=ESX-1 secretion-associated protein EspI {ECO:0000305};
GN Name=espI {ECO:0000303|PubMed:19876390}; OrderedLocusNames=Rv3876;
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14557547; DOI=10.1073/pnas.1635213100;
RA Hsu T., Hingley-Wilson S.M., Chen B., Chen M., Dai A.Z., Morin P.M.,
RA Marks C.B., Padiyar J., Goulding C., Gingery M., Eisenberg D.,
RA Russell R.G., Derrick S.C., Collins F.M., Morris S.L., King C.H.,
RA Jacobs W.R. Jr.;
RT "The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss
RT of secreted lytic function required for invasion of lung interstitial
RT tissue.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12420-12425(2003).
RN [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14756778; DOI=10.1046/j.1365-2958.2003.03844.x;
RA Guinn K.M., Hickey M.J., Mathur S.K., Zakel K.L., Grotzke J.E.,
RA Lewinsohn D.M., Smith S., Sherman D.R.;
RT "Individual RD1-region genes are required for export of ESAT-6/CFP-10 and
RT for virulence of Mycobacterium tuberculosis.";
RL Mol. Microbiol. 51:359-370(2004).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=16368961; DOI=10.1128/iai.74.1.88-98.2006;
RA Brodin P., Majlessi L., Marsollier L., de Jonge M.I., Bottai D.,
RA Demangel C., Hinds J., Neyrolles O., Butcher P.D., Leclerc C., Cole S.T.,
RA Brosch R.;
RT "Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on
RT immunogenicity and virulence.";
RL Infect. Immun. 74:88-98(2006).
RN [5]
RP GENE NAME.
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 [6]
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 [7]
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 [8]
RP FUNCTION, ATP-BINDING, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-425.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman, and H37Rv;
RX PubMed=25039394; DOI=10.1111/mmi.12718;
RA Zhang M., Chen J.M., Sala C., Rybniker J., Dhar N., Cole S.T.;
RT "EspI regulates the ESX-1 secretion system in response to ATP levels in
RT Mycobacterium tuberculosis.";
RL Mol. Microbiol. 93:1057-1065(2014).
RN [9]
RP ATP-BINDING, AND MUTAGENESIS OF LYS-425.
RX PubMed=27017992; DOI=10.1016/j.pep.2016.03.009;
RA Chen H., Wang H., Sun T., Tian S., Lin D., Guo C.;
RT "Recombinant preparation and functional studies of EspI ATP binding domain
RT from Mycobacterium tuberculosis.";
RL Protein Expr. Purif. 123:51-59(2016).
CC -!- FUNCTION: Required to repress ESX-1-mediated secretion under low ATP
CC conditions. This function requires the ATP-binding motif.
CC {ECO:0000269|PubMed:25039394, ECO:0000305|PubMed:14557547}.
CC -!- SUBUNIT: Residues 1-81 interact with EsxB while residues 35-186
CC interact with an artificial EsxB-EsxA heterodimer (PubMed:19854905).
CC {ECO:0000269|PubMed:19854905}.
CC -!- DISRUPTION PHENOTYPE: Double espI-eccD1 mutants abolish EsxA and EsxB
CC secretion, but not their expression (PubMed:14557547). One group has
CC shown no growth in the human macrophage-like cell line THP-1, no
CC cytotoxicity, attenutated infection in mice, nearly 100-fold less
CC bacteria in lung and spleen of C57BL/6; Brodin et al., attribute this
CC result to polar effects on the downstream gene (PubMed:14756778,
CC PubMed:16368961). Another group has shown that inactivation does not
CC abolish EsxA (ESAT-6) secretion, EsxA-specific immunogenicity or
CC virulence (PubMed:16368961, PubMed:25039394).
CC {ECO:0000269|PubMed:14557547, ECO:0000269|PubMed:14756778,
CC ECO:0000269|PubMed:16368961, ECO:0000269|PubMed:25039394,
CC ECO:0000305|PubMed:16368961}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL123456; CCP46705.1; -; Genomic_DNA.
DR PIR; B70803; B70803.
DR RefSeq; NP_218393.1; NC_000962.3.
DR RefSeq; WP_003909105.1; NC_018143.2.
DR AlphaFoldDB; P9WJC5; -.
DR SMR; P9WJC5; -.
DR IntAct; P9WJC5; 1.
DR STRING; 83332.Rv3876; -.
DR PaxDb; P9WJC5; -.
DR DNASU; 886206; -.
DR GeneID; 886206; -.
DR KEGG; mtu:Rv3876; -.
DR PATRIC; fig|83332.111.peg.4314; -.
DR TubercuList; Rv3876; -.
DR eggNOG; COG0455; Bacteria.
DR OMA; YGFPQQG; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0051782; P:negative regulation of cell division; IBA:GO_Central.
DR GO; GO:0044315; P:protein secretion by the type VII secretion system; IMP:MTBBASE.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR002586; CobQ/CobB/MinD/ParA_Nub-bd_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01656; CbiA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Nucleotide-binding; Reference proteome.
FT CHAIN 1..666
FT /note="ESX-1 secretion-associated protein EspI"
FT /id="PRO_0000394147"
FT REGION 1..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..50
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 62..218
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..299
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..368
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 424..431
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305|PubMed:25039394"
FT MUTAGEN 425
FT /note="K->Q: Does not block ESX-1-mediated secretion during
FT ATP depletion. Lack of ATP-binding."
FT /evidence="ECO:0000269|PubMed:25039394,
FT ECO:0000269|PubMed:27017992"
SQ SEQUENCE 666 AA; 70645 MW; 752E072FB8B10111 CRC64;
MAADYDKLFR PHEGMEAPDD MAAQPFFDPS ASFPPAPASA NLPKPNGQTP PPTSDDLSER
FVSAPPPPPP PPPPPPPTPM PIAAGEPPSP EPAASKPPTP PMPIAGPEPA PPKPPTPPMP
IAGPEPAPPK PPTPPMPIAG PAPTPTESQL APPRPPTPQT PTGAPQQPES PAPHVPSHGP
HQPRRTAPAP PWAKMPIGEP PPAPSRPSAS PAEPPTRPAP QHSRRARRGH RYRTDTERNV
GKVATGPSIQ ARLRAEEASG AQLAPGTEPS PAPLGQPRSY LAPPTRPAPT EPPPSPSPQR
NSGRRAERRV HPDLAAQHAA AQPDSITAAT TGGRRRKRAA PDLDATQKSL RPAAKGPKVK
KVKPQKPKAT KPPKVVSQRG WRHWVHALTR INLGLSPDEK YELDLHARVR RNPRGSYQIA
VVGLKGGAGK TTLTAALGST LAQVRADRIL ALDADPGAGN LADRVGRQSG ATIADVLAEK
ELSHYNDIRA HTSVNAVNLE VLPAPEYSSA QRALSDADWH FIADPASRFY NLVLADCGAG
FFDPLTRGVL STVSGVVVVA SVSIDGAQQA SVALDWLRNN GYQDLASRAC VVINHIMPGE
PNVAVKDLVR HFEQQVQPGR VVVMPWDRHI AAGTEISLDL LDPIYKRKVL ELAAALSDDF
ERAGRR
