ESPC_MYCTU
ID ESPC_MYCTU Reviewed; 103 AA.
AC P9WJD7; L0TD21; O06268; P65087;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=ESX-1 secretion-associated protein EspC {ECO:0000305};
GN Name=espC; Synonyms=snm9 {ECO:0000303|PubMed:16135231};
GN OrderedLocusNames=Rv3615c; ORFNames=MTCY07H7B.07;
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 35801 / TMC 107 / Erdman;
RX PubMed=16135231; DOI=10.1111/j.1365-2958.2005.04800.x;
RA MacGurn J.A., Raghavan S., Stanley S.A., Cox J.S.;
RT "A non-RD1 gene cluster is required for Snm secretion in Mycobacterium
RT tuberculosis.";
RL Mol. Microbiol. 57:1653-1663(2005).
RN [3]
RP REGULATION BY PHOP/PHOR.
RC STRAIN=H37Rv;
RX PubMed=16573683; DOI=10.1111/j.1365-2958.2006.05102.x;
RA Walters S.B., Dubnau E., Kolesnikova I., Laval F., Daffe M., Smith I.;
RT "The Mycobacterium tuberculosis PhoPR two-component system regulates genes
RT essential for virulence and complex lipid biosynthesis.";
RL Mol. Microbiol. 60:312-330(2006).
RN [4]
RP REGULATION BY ESPR.
RX PubMed=18685700; DOI=10.1038/nature07219;
RA Raghavan S., Manzanillo P., Chan K., Dovey C., Cox J.S.;
RT "Secreted transcription factor controls Mycobacterium tuberculosis
RT virulence.";
RL Nature 454:717-721(2008).
RN [5]
RP FUNCTION, INTERACTION WITH ECCA1 AND ESPF, SUBCELLULAR LOCATION, AND
RP DOMAIN.
RX PubMed=19682254; DOI=10.1111/j.1365-2958.2009.06821.x;
RA DiGiuseppe Champion P.A., Champion M.M., Manzanillo P., Cox J.S.;
RT "ESX-1 secreted virulence factors are recognized by multiple cytosolic AAA
RT ATPases in pathogenic mycobacteria.";
RL Mol. Microbiol. 73:950-962(2009).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 SUBCELLULAR LOCATION, AND BIOTECHNOLOGY.
RX PubMed=21427227; DOI=10.1073/pnas.1015153108;
RA Millington K.A., Fortune S.M., Low J., Garces A., Hingley-Wilson S.M.,
RA Wickremasinghe M., Kon O.M., Lalvani A.;
RT "Rv3615c is a highly immunodominant RD1 (Region of Difference 1)-dependent
RT secreted antigen specific for Mycobacterium tuberculosis infection.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:5730-5735(2011).
RN [8]
RP REGULATION BY ESPR.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22389481; DOI=10.1128/jb.00142-12;
RA Hunt D.M., Sweeney N.P., Mori L., Whalan R.H., Comas I., Norman L.,
RA Cortes T., Arnvig K.B., Davis E.O., Stapleton M.R., Green J., Buxton R.S.;
RT "Long-range transcriptional control of an operon necessary for virulence-
RT critical ESX-1 secretion in Mycobacterium tuberculosis.";
RL J. Bacteriol. 194:2307-2320(2012).
RN [9]
RP REGULATION BY MPRA/MPRB.
RC STRAIN=H37Rv;
RX PubMed=23104803; DOI=10.1128/jb.01067-12;
RA Pang X., Samten B., Cao G., Wang X., Tvinnereim A.R., Chen X.L.,
RA Howard S.T.;
RT "MprAB regulates the espA operon in Mycobacterium tuberculosis and
RT modulates ESX-1 function and host cytokine response.";
RL J. Bacteriol. 195:66-75(2013).
RN [10]
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 [11]
RP TRANSCRIPTIONAL REGULATION.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=25536998; DOI=10.1099/mic.0.000023;
RA Cao G., Howard S.T., Zhang P., Wang X., Chen X.L., Samten B., Pang X.;
RT "EspR, a regulator of the ESX-1 secretion system in Mycobacterium
RT tuberculosis, is directly regulated by the two-component systems MprAB and
RT PhoPR.";
RL Microbiology 161:477-489(2015).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=26048138; DOI=10.1016/j.chom.2015.05.003;
RA Wassermann R., Gulen M.F., Sala C., Perin S.G., Lou Y., Rybniker J.,
RA Schmid-Burgk J.L., Schmidt T., Hornung V., Cole S.T., Ablasser A.;
RT "Mycobacterium tuberculosis differentially activates cGAS- and
RT inflammasome-dependent intracellular immune responses through ESX-1.";
RL Cell Host Microbe 17:799-810(2015).
CC -!- FUNCTION: Required for ESX-1 function. Required for either stability or
CC expression of EspA. {ECO:0000269|PubMed:16135231,
CC ECO:0000269|PubMed:19682254}.
CC -!- SUBUNIT: Interacts with EccA1 and EspF. {ECO:0000269|PubMed:19682254}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:19682254,
CC ECO:0000269|PubMed:21427227}. Note=Secreted via the ESX-1 / type VII
CC secretion system (T7SS). {ECO:0000269|PubMed:19682254,
CC ECO:0000269|PubMed:21427227}.
CC -!- INDUCTION: Transcriptionally activated by EspR (PubMed:18685700,
CC PubMed:22389481, PubMed:25536998). Repressed by the MprB/MprA two-
CC component system, by direct regulation and via EspR (PubMed:23104803,
CC PubMed:25536998). Up-regulated by the PhoP/PhoR two-component system,
CC via EspR (PubMed:16573683, PubMed:25536998).
CC {ECO:0000269|PubMed:16573683, ECO:0000269|PubMed:18685700,
CC ECO:0000269|PubMed:22389481, ECO:0000269|PubMed:23104803,
CC ECO:0000269|PubMed:25536998}.
CC -!- DOMAIN: The C-terminal region is required for secretion by the ESX-1
CC system. {ECO:0000269|PubMed:19682254}.
CC -!- DISRUPTION PHENOTYPE: Mutant exhibits pathogenesis defects, including
CC reduced virulence in mice, attenuated growth in macrophages and an
CC inability to suppress immunostimulatory cytokines such as IL-12
CC (PubMed:16135231). Host (human) cells no longer produce cytokine IP-10
CC (CXCL10) upon infection, but continue to produce IL-1 beta (IL1B)
CC (PubMed:26048138). {ECO:0000269|PubMed:16135231,
CC ECO:0000269|PubMed:26048138}.
CC -!- BIOTECHNOLOGY: Contains multiple, broadly recognized T-cell epitopes
CC and is a major target of cellular immunity in both active and latent
CC tuberculosis infection, indicating this might be a good vaccine
CC candidate (PubMed:21427227). A fusion protein (p846) of 3 well-defined
CC antigens (EspC, EsxH and Rv2660c) induces robust specific T-cell immune
CC response and could be an effective vaccine (PubMed:24280763).
CC {ECO:0000269|PubMed:21427227, ECO:0000269|PubMed:24280763}.
CC -!- SIMILARITY: Belongs to the EspC family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46438.1; -; Genomic_DNA.
DR PIR; H70956; H70956.
DR RefSeq; NP_218132.1; NC_000962.3.
DR RefSeq; WP_003899599.1; NZ_NVQJ01000056.1.
DR AlphaFoldDB; P9WJD7; -.
DR SMR; P9WJD7; -.
DR STRING; 83332.Rv3615c; -.
DR iPTMnet; P9WJD7; -.
DR PaxDb; P9WJD7; -.
DR DNASU; 885770; -.
DR GeneID; 45427601; -.
DR GeneID; 885770; -.
DR KEGG; mtu:Rv3615c; -.
DR TubercuList; Rv3615c; -.
DR eggNOG; ENOG5032HXQ; Bacteria.
DR OMA; KMYESTR; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0042783; P:evasion of host immune response; IMP:MTBBASE.
DR GO; GO:0044315; P:protein secretion by the type VII secretion system; IMP:MTBBASE.
DR InterPro; IPR022536; EspC.
DR Pfam; PF10824; T7SS_ESX_EspC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Reference proteome; Secreted; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..103
FT /note="ESX-1 secretion-associated protein EspC"
FT /id="PRO_0000104138"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
SQ SEQUENCE 103 AA; 10795 MW; 282161E5D41D53EE CRC64;
MTENLTVQPE RLGVLASHHD NAAVDASSGV EAAAGLGESV AITHGPYCSQ FNDTLNVYLT
AHNALGSSLH TAGVDLAKSL RIAAKIYSEA DEAWRKAIDG LFT
