ECC1B_MYCTU
ID ECC1B_MYCTU Reviewed; 591 AA.
AC P9WNB1; L0TGZ9; O69736; Q7D4P5;
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=ESX-1 secretion system protein EccCb1 {ECO:0000305};
DE AltName: Full=ESX conserved component Cb1 {ECO:0000303|PubMed:19876390};
DE AltName: Full=Snm2 secretory protein {ECO:0000303|PubMed:14557536};
DE AltName: Full=Type VII secretion system protein EccCb1 {ECO:0000305};
DE Short=T7SS protein EccCb1 {ECO:0000305};
GN Name=eccCb1 {ECO:0000303|PubMed:19876390};
GN Synonyms=snm2 {ECO:0000303|PubMed:14557536}; OrderedLocusNames=Rv3871;
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 FUNCTION, SUBUNIT, INTERACTION WITH ECCCA1 AND ESXB, DOMAIN, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=14557536; DOI=10.1073/pnas.2235593100;
RA Stanley S.A., Raghavan S., Hwang W.W., Cox J.S.;
RT "Acute infection and macrophage subversion by Mycobacterium tuberculosis
RT require a specialized secretion system.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13001-13006(2003).
RN [4]
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 [5]
RP FUNCTION, SUBUNIT, AND 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 [6]
RP FUNCTION, AND INTERACTION WITH ESXB.
RX PubMed=16973880; DOI=10.1126/science.1131167;
RA Champion P.A., Stanley S.A., Champion M.M., Brown E.J., Cox J.S.;
RT "C-terminal signal sequence promotes virulence factor secretion in
RT Mycobacterium tuberculosis.";
RL Science 313:1632-1636(2006).
RN [7]
RP INTERACTION WITH ESPK.
RX PubMed=17676952; DOI=10.1371/journal.ppat.0030105;
RA McLaughlin B., Chon J.S., MacGurn J.A., Carlsson F., Cheng T.L., Cox J.S.,
RA Brown E.J.;
RT "A mycobacterium ESX-1-secreted virulence factor with unique requirements
RT for export.";
RL PLoS Pathog. 3:E105-E105(2007).
RN [8]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [9]
RP NOMENCLATURE, AND SUBUNIT.
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 [10]
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 [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, ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-90 AND LYS-382.
RX PubMed=25865481; DOI=10.1016/j.cell.2015.03.040;
RA Rosenberg O.S., Dovala D., Li X., Connolly L., Bendebury A.,
RA Finer-Moore J., Holton J., Cheng Y., Stroud R.M., Cox J.S.;
RT "Substrates control multimerization and activation of the multi-domain
RT ATPase motor of type VII secretion.";
RL Cell 161:501-512(2015).
RN [13]
RP SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=22233444; DOI=10.1111/j.1365-2958.2011.07958.x;
RA Wirth S.E., Krywy J.A., Aldridge B.B., Fortune S.M., Fernandez-Suarez M.,
RA Gray T.A., Derbyshire K.M.;
RT "Polar assembly and scaffolding proteins of the virulence-associated ESX-1
RT secretory apparatus in mycobacteria.";
RL Mol. Microbiol. 83:654-664(2012).
CC -!- FUNCTION: Part of the ESX-1 specialized secretion system, which
CC delivers several virulence factors to host cells during infection,
CC including the key virulence factors EsxA (ESAT-6) and EsxB (CFP-10)
CC (PubMed:14557547, PubMed:14557536, PubMed:16368961, PubMed:16973880).
CC EccCb1 may link the cytosolic components of the system with the
CC membrane components (PubMed:16973880). {ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:16368961, ECO:0000269|PubMed:16973880,
CC ECO:0000305|PubMed:14557547}.
CC -!- ACTIVITY REGULATION: EsxB binding to the second FtsK domain of EccCb1
CC causes multimerization; a subsequent unknown step relieves the
CC allosteric inhibition of linker 2 on FtsK domain 1 (in EccCa1 subunit),
CC activating the ATPase activity (PubMed:25865481).
CC {ECO:0000305|PubMed:25865481}.
CC -!- SUBUNIT: Part of the ESX-1 / type VII secretion system (T7SS), which is
CC composed of cytosolic and membrane components. The ESX-1 membrane
CC complex is composed of EccB1, EccCa1, EccCb1, EccD1 and EccE1
CC (PubMed:14557536, PubMed:16368961, PubMed:19876390). Interacts with
CC EccCa1, EspK and the C-terminus of EsxB (PubMed:14557536,
CC PubMed:16973880, PubMed:17676952). Residues 1-261 interact with EsxB
CC and an artificial EsxB-EsxA heterodimer (PubMed:19854905).
CC {ECO:0000269|PubMed:14557536, ECO:0000269|PubMed:16368961,
CC ECO:0000269|PubMed:16973880, ECO:0000269|PubMed:17676952,
CC ECO:0000305|PubMed:19876390}.
CC -!- INTERACTION:
CC P9WNB1; P9WNK5: esxB; NbExp=3; IntAct=EBI-6514882, EBI-1253936;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Note=Localizes at or
CC near the cell pole in (on average) 1 discrete spot upon overexpression
CC in M.smegmatis (PubMed:22233444). {ECO:0000269|PubMed:22233444}.
CC -!- DOMAIN: The C-terminus (residues 252-747) interacts with EsxB, the
CC whole protein is required for interaction with EccCa1
CC (PubMed:14557536). {ECO:0000269|PubMed:14557536}.
CC -!- DISRUPTION PHENOTYPE: Disruption abolishes EsxA and EsxB secretion, but
CC not their expression (PubMed:14557547, PubMed:14557536). It results in
CC a lack of antigen specific immunogenicity and leads to attenuated
CC virulence (PubMed:16368961). Mutants exhibit defects in bacterial
CC growth during the acute phase of a mouse infection (PubMed:14557536).
CC No growth in the human macrophage-like cell line THP-1, no cytotoxicity
CC (PubMed:14756778). {ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:14557547, ECO:0000269|PubMed:14756778,
CC ECO:0000269|PubMed:16368961}.
CC -!- MISCELLANEOUS: In ESX-1 cluster, the FtsK/SpoIIIE-like protein is split
CC in two genes. {ECO:0000305}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
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DR EMBL; AL123456; CCP46700.1; -; Genomic_DNA.
DR PIR; E70802; E70802.
DR RefSeq; NP_218388.1; NC_000962.3.
DR RefSeq; WP_003399865.1; NZ_NVQJ01000074.1.
DR PDB; 6J19; X-ray; 1.98 A; A=315-591.
DR PDB; 6JD4; X-ray; 2.10 A; A/B=315-591.
DR PDBsum; 6J19; -.
DR PDBsum; 6JD4; -.
DR AlphaFoldDB; P9WNB1; -.
DR SMR; P9WNB1; -.
DR IntAct; P9WNB1; 1.
DR STRING; 83332.Rv3871; -.
DR PaxDb; P9WNB1; -.
DR DNASU; 886202; -.
DR GeneID; 886202; -.
DR KEGG; mtu:Rv3871; -.
DR TubercuList; Rv3871; -.
DR eggNOG; COG1674; Bacteria.
DR OMA; HRQEVWG; -.
DR PhylomeDB; P9WNB1; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
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 Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR023837; EccCb-like_Actinobacteria.
DR InterPro; IPR002543; FtsK_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01580; FtsK_SpoIIIE; 2.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR TIGRFAMs; TIGR03925; T7SS_EccC_b; 1.
DR PROSITE; PS50901; FTSK; 2.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Nucleotide-binding;
KW Reference proteome; Repeat.
FT CHAIN 1..591
FT /note="ESX-1 secretion system protein EccCb1"
FT /id="PRO_0000393429"
FT DOMAIN 65..259
FT /note="FtsK 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00289"
FT DOMAIN 359..545
FT /note="FtsK 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00289"
FT BINDING 84..91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00289"
FT BINDING 376..383
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00289"
FT MUTAGEN 90
FT /note="K->T: Cells unable to export EsxB."
FT /evidence="ECO:0000269|PubMed:25865481"
FT MUTAGEN 382
FT /note="K->T: Cells unable to export EsxB."
FT /evidence="ECO:0000269|PubMed:25865481"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 344..347
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 349..355
FT /evidence="ECO:0007829|PDB:6J19"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 361..365
FT /evidence="ECO:0007829|PDB:6J19"
FT TURN 366..368
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 372..376
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 382..396
FT /evidence="ECO:0007829|PDB:6J19"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 402..407
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 432..447
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 453..455
FT /evidence="ECO:0007829|PDB:6JD4"
FT HELIX 457..462
FT /evidence="ECO:0007829|PDB:6J19"
FT TURN 463..465
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 470..475
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 478..483
FT /evidence="ECO:0007829|PDB:6J19"
FT TURN 485..487
FT /evidence="ECO:0007829|PDB:6JD4"
FT HELIX 492..494
FT /evidence="ECO:0007829|PDB:6J19"
FT TURN 495..497
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 498..500
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 501..504
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 506..513
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 514..520
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 523..525
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 526..531
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 536..538
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 549..551
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 560..565
FT /evidence="ECO:0007829|PDB:6J19"
FT STRAND 568..573
FT /evidence="ECO:0007829|PDB:6J19"
SQ SEQUENCE 591 AA; 64561 MW; 7CD309E881A9739D CRC64;
MTAEPEVRTL REVVLDQLGT AESRAYKMWL PPLTNPVPLN ELIARDRRQP LRFALGIMDE
PRRHLQDVWG VDVSGAGGNI GIGGAPQTGK STLLQTMVMS AAATHSPRNV QFYCIDLGGG
GLIYLENLPH VGGVANRSEP DKVNRVVAEM QAVMRQRETT FKEHRVGSIG MYRQLRDDPS
QPVASDPYGD VFLIIDGWPG FVGEFPDLEG QVQDLAAQGL AFGVHVIIST PRWTELKSRV
RDYLGTKIEF RLGDVNETQI DRITREIPAN RPGRAVSMEK HHLMIGVPRF DGVHSADNLV
EAITAGVTQI ASQHTEQAPP VRVLPERIHL HELDPNPPGP ESDYRTRWEI PIGLRETDLT
PAHCHMHTNP HLLIFGAAKS GKTTIAHAIA RAICARNSPQ QVRFMLADYR SGLLDAVPDT
HLLGAGAINR NSASLDEAVQ ALAVNLKKRL PPTDLTTAQL RSRSWWSGFD VVLLVDDWHM
IVGAAGGMPP MAPLAPLLPA AADIGLHIIV TCQMSQAYKA TMDKFVGAAF GSGAPTMFLS
GEKQEFPSSE FKVKRRPPGQ AFLVSPDGKE VIQAPYIEPP EEVFAAPPSA G
