ECCA1_MYCTU
ID ECCA1_MYCTU Reviewed; 573 AA.
AC P9WPH9; L0TFH7; O69733;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=ESX-1 secretion system protein EccA1 {ECO:0000305};
DE AltName: Full=ESX conserved component A1 {ECO:0000303|PubMed:19876390};
DE AltName: Full=Type VII secretion system protein EccA1 {ECO:0000305};
DE Short=T7SS protein EccA1 {ECO:0000305};
GN Name=eccA1 {ECO:0000303|PubMed:19876390}; OrderedLocusNames=Rv3868;
GN ORFNames=MTV027.03;
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 PROTEIN SEQUENCE OF 2-6, FUNCTION, ATPASE ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, DOMAIN, AND MUTAGENESIS OF PRO-336; THR-338; LYS-340
RP AND ARG-429.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18974091; DOI=10.1074/jbc.m807144200;
RA Luthra A., Mahmood A., Arora A., Ramachandran R.;
RT "Characterization of Rv3868, an essential hypothetical protein of the ESX-1
RT secretion system in Mycobacterium tuberculosis.";
RL J. Biol. Chem. 283:36532-36541(2008).
RN [3]
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 [4]
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 [5]
RP INTERACTION WITH PPE68.
RX PubMed=17433643; DOI=10.1016/j.micres.2006.11.016;
RA Teutschbein J., Schumann G., Mollmann U., Grabley S., Cole S.T., Munder T.;
RT "A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of
RT Mycobacterium tuberculosis.";
RL Microbiol. Res. 164:253-259(2009).
RN [6]
RP INTERACTION WITH ESPC AND ESPF.
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 [7]
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 [8]
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 [9] {ECO:0007744|PDB:4F3V}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-280.
RC STRAIN=H37Rv;
RX PubMed=23818233; DOI=10.1002/prot.24351;
RA Wagner J.M., Evans T.J., Korotkov K.V.;
RT "Crystal structure of the N-terminal domain of EccA ATPase from the ESX-1
RT secretion system of Mycobacterium tuberculosis.";
RL Proteins 82:159-163(2014).
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:18974091, PubMed:16368961). EccA1 exhibits ATPase activity and
CC may provide energy for the export of ESX-1 substrates
CC (PubMed:18974091). {ECO:0000269|PubMed:16368961,
CC ECO:0000269|PubMed:18974091}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.8 uM for ATP {ECO:0000269|PubMed:18974091};
CC Vmax=0.139 pmol/min/ug enzyme {ECO:0000269|PubMed:18974091};
CC -!- SUBUNIT: Part of the ESX-1 / type VII secretion system (T7SS), which is
CC composed of cytosolic and membrane components (PubMed:16368961,
CC PubMed:19876390). Homohexamer (PubMed:18974091). Interacts with Ppe68,
CC EspF and the C-terminus of EspC (PubMed:17433643, PubMed:19682254).
CC {ECO:0000269|PubMed:16368961, ECO:0000269|PubMed:17433643,
CC ECO:0000269|PubMed:18974091, ECO:0000269|PubMed:19682254,
CC ECO:0000305|PubMed:19876390}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DOMAIN: The N-terminal region is compact and probably functions to
CC regulate the ATPase activity and the oligomerization. The C-terminal
CC region contains the ATPase activity and the oligomerization domain.
CC {ECO:0000269|PubMed:18974091}.
CC -!- DISRUPTION PHENOTYPE: Disruption abolishes EsxA and EsxB secretion, but
CC not their expression. It results in a lack of antigen specific
CC immunogenicity and leads to attenuated virulence.
CC {ECO:0000269|PubMed:16368961}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the CbxX/CfxQ family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46697.1; -; Genomic_DNA.
DR PIR; B70802; B70802.
DR RefSeq; NP_218385.1; NC_000962.3.
DR RefSeq; WP_003399850.1; NZ_NVQJ01000074.1.
DR PDB; 4F3V; X-ray; 2.00 A; A/B=1-280.
DR PDBsum; 4F3V; -.
DR AlphaFoldDB; P9WPH9; -.
DR SMR; P9WPH9; -.
DR STRING; 83332.Rv3868; -.
DR PaxDb; P9WPH9; -.
DR PRIDE; P9WPH9; -.
DR DNASU; 886199; -.
DR GeneID; 886199; -.
DR KEGG; mtu:Rv3868; -.
DR TubercuList; Rv3868; -.
DR eggNOG; COG0464; Bacteria.
DR OMA; VEAGEQN; -.
DR PhylomeDB; P9WPH9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:MTBBASE.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR041627; AAA_lid_6.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR000641; CbxX/CfxQ.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR023835; T7SS_EccA.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF17866; AAA_lid_6; 1.
DR PRINTS; PR00819; CBXCFQXSUPER.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR03922; T7SS_EccA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cytoplasm; Direct protein sequencing;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..573
FT /note="ESX-1 secretion system protein EccA1"
FT /id="PRO_0000063049"
FT BINDING 334..341
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MUTAGEN 336
FT /note="P->A: Does not distord the binding site
FT architecture. No change in catalytic efficiency and Vmax."
FT /evidence="ECO:0000269|PubMed:18974091"
FT MUTAGEN 338
FT /note="T->A: Decrease in substrate-binding and in catalytic
FT efficiency."
FT /evidence="ECO:0000269|PubMed:18974091"
FT MUTAGEN 340
FT /note="K->A: Does not affect substrate-binding, but
FT decreases the catalytic efficiency and the Vmax."
FT /evidence="ECO:0000269|PubMed:18974091"
FT MUTAGEN 429
FT /note="R->A: Large increase in the Km and strong decrease
FT in catalytic efficiency. Loses the ability to self-
FT associate in the presence of ATP and the cooperativity is
FT nearly abolished."
FT /evidence="ECO:0000269|PubMed:18974091"
FT HELIX 1..15
FT /evidence="ECO:0007829|PDB:4F3V"
FT TURN 16..18
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 20..33
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 52..60
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 67..70
FT /evidence="ECO:0007829|PDB:4F3V"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 76..79
FT /evidence="ECO:0007829|PDB:4F3V"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:4F3V"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:4F3V"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 99..113
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 116..123
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 132..145
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 149..156
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 165..181
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 185..196
FT /evidence="ECO:0007829|PDB:4F3V"
FT TURN 199..204
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 205..219
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 222..235
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 239..246
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 257..261
FT /evidence="ECO:0007829|PDB:4F3V"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:4F3V"
FT HELIX 269..271
FT /evidence="ECO:0007829|PDB:4F3V"
SQ SEQUENCE 573 AA; 62426 MW; 58D4751E2D9F19EA CRC64;
MTDRLASLFE SAVSMLPMSE ARSLDLFTEI TNYDESACDA WIGRIRCGDT DRVTLFRAWY
SRRNFGQLSG SVQISMSTLN ARIAIGGLYG DITYPVTSPL AITMGFAACE AAQGNYADAM
EALEAAPVAG SEHLVAWMKA VVYGAAERWT DVIDQVKSAG KWPDKFLAGA AGVAHGVAAA
NLALFTEAER RLTEANDSPA GEACARAIAW YLAMARRSQG NESAAVALLE WLQTTHPEPK
VAAALKDPSY RLKTTTAEQI ASRADPWDPG SVVTDNSGRE RLLAEAQAEL DRQIGLTRVK
NQIERYRAAT LMARVRAAKG MKVAQPSKHM IFTGPPGTGK TTIARVVANI LAGLGVIAEP
KLVETSRKDF VAEYEGQSAV KTAKTIDQAL GGVLFIDEAY ALVQERDGRT DPFGQEALDT
LLARMENDRD RLVVIIAGYS SDIDRLLETN EGLRSRFATR IEFDTYSPEE LLEIANVIAA
ADDSALTAEA AENFLQAAKQ LEQRMLRGRR ALDVAGNGRY ARQLVEASEQ CRDMRLAQVL
DIDTLDEDRL REINGSDMAE AIAAVHAHLN MRE
