ECCD1_MYCTU
ID ECCD1_MYCTU Reviewed; 511 AA.
AC P9WNQ7; L0TGV6; O69741; Q7D4P2;
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 system protein EccD1 {ECO:0000305};
DE AltName: Full=ESX conserved component D1 {ECO:0000303|PubMed:19876390};
DE AltName: Full=Snm4 secretory protein {ECO:0000303|PubMed:14557536};
DE AltName: Full=Type VII secretion system protein EccD1 {ECO:0000305};
DE Short=T7SS protein EccD1 {ECO:0000305};
GN Name=eccD1 {ECO:0000303|PubMed:19876390};
GN Synonyms=snm4 {ECO:0000303|PubMed:14557536}; OrderedLocusNames=Rv3877;
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, AND DISRUPTION 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 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 [5]
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 [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-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 DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=26048137; DOI=10.1016/j.chom.2015.05.005;
RA Collins A.C., Cai H., Li T., Franco L.H., Li X.D., Nair V.R., Scharn C.R.,
RA Stamm C.E., Levine B., Chen Z.J., Shiloh M.U.;
RT "Cyclic GMP-AMP synthase is an innate immune DNA sensor for Mycobacterium
RT tuberculosis.";
RL Cell Host Microbe 17:820-828(2015).
RN [8] {ECO:0007744|PDB:4KV2, ECO:0007744|PDB:4KV3}
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 21-109, AND SUBUNIT.
RC STRAIN=H37Rv;
RX PubMed=26922638; DOI=10.1186/s12900-016-0056-6;
RA Wagner J.M., Chan S., Evans T.J., Kahng S., Kim J., Arbing M.A.,
RA Eisenberg D., Korotkov K.V.;
RT "Structures of EccB1 and EccD1 from the core complex of the mycobacterial
RT ESX-1 type VII secretion system.";
RL BMC Struct. Biol. 16:5-5(2016).
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 {ECO:0000269|PubMed:14557536, ECO:0000269|PubMed:16368961,
CC ECO:0000305|PubMed:14557547}.
CC -!- SUBUNIT: Possibly a homodimer (PubMed:26922638). Part of the ESX-1 /
CC type VII secretion system (T7SS), which is composed of cytosolic and
CC membrane components. The ESX-1 membrane complex is composed of EccB1,
CC EccCa1, EccCb1, EccD1 and EccE1. {ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:16368961, ECO:0000305|PubMed:19876390,
CC ECO:0000305|PubMed:26922638}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Double espI-eccD1 mutants abolish EsxA and EsxB
CC secretion, but not their expression (PubMed:14557547). Disruption
CC abolishes EsxA and EsxB secretion, but not their expression
CC (PubMed:14557536). Results in a lack of antigen specific immunogenicity
CC and leads to attenuated virulence (PubMed:16368961). Mutants exhibit
CC defects in bacterial growth during the acute phase of C57BL/6 mouse
CC infection, but survive for 140 days despite a wild-type bacterial load
CC in the lungs at 100 days post-infection, suggesting the pathway is
CC required for virulence (PubMed:14557536). Nearly wild-type levels of
CC IL-12 p40 (IL12B) and TNF-alpha are produced by infected murine
CC macrophages, while the nitric oxide response is about 50% reduced
CC (PubMed:14557536). Mouse macrophages do not induce cGAMP production,
CC and thus do not sense bacterial DNA correctly to induce the innate
CC immune response (PubMed:26048137). {ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:14557547, ECO:0000269|PubMed:16368961,
CC ECO:0000269|PubMed:26048137}.
CC -!- MISCELLANEOUS: The structure in 4KV3 was determined for a fusion
CC protein with E.coli maltose-binding protein.
CC {ECO:0000269|PubMed:26922638}.
CC -!- SIMILARITY: Belongs to the EccD/Snm4 family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46706.1; -; Genomic_DNA.
DR PIR; C70803; C70803.
DR RefSeq; NP_218394.1; NC_000962.3.
DR RefSeq; WP_003399976.1; NZ_NVQJ01000086.1.
DR PDB; 4KV2; X-ray; 1.88 A; A/B=21-109.
DR PDB; 4KV3; X-ray; 2.20 A; A/B=21-109.
DR PDBsum; 4KV2; -.
DR PDBsum; 4KV3; -.
DR AlphaFoldDB; P9WNQ7; -.
DR SMR; P9WNQ7; -.
DR STRING; 83332.Rv3877; -.
DR iPTMnet; P9WNQ7; -.
DR PaxDb; P9WNQ7; -.
DR DNASU; 886207; -.
DR GeneID; 886207; -.
DR KEGG; mtu:Rv3877; -.
DR TubercuList; Rv3877; -.
DR eggNOG; ENOG5031ZTA; Bacteria.
DR OMA; WCAWALM; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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 InterPro; IPR006707; T7SS_EccD.
DR InterPro; IPR024962; YukD-like.
DR Pfam; PF08817; YukD; 1.
DR PIRSF; PIRSF017804; Secretion_EccD1; 1.
DR TIGRFAMs; TIGR03920; T7SS_EccD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell inner membrane; Cell membrane; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..511
FT /note="ESX-1 secretion system protein EccD1"
FT /id="PRO_0000393233"
FT TOPO_DOM 2..143
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:26922638"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 165..170
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 171..191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 192..202
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 203..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 224..227
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 228..248
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 249..257
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 258..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..285
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 286..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 307..367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 368..388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 410..420
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 421..441
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 442..444
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 445..465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 466..482
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..511
FT /note="Periplasmic"
FT /evidence="ECO:0000305"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:21969609"
SQ SEQUENCE 511 AA; 53999 MW; 32B7C158E6E7C6FF CRC64;
MSAPAVAAGP TAAGATAARP ATTRVTILTG RRMTDLVLPA AVPMETYIDD TVAVLSEVLE
DTPADVLGGF DFTAQGVWAF ARPGSPPLKL DQSLDDAGVV DGSLLTLVSV SRTERYRPLV
EDVIDAIAVL DESPEFDRTA LNRFVGAAIP LLTAPVIGMA MRAWWETGRS LWWPLAIGIL
GIAVLVGSFV ANRFYQSGHL AECLLVTTYL LIATAAALAV PLPRGVNSLG APQVAGAATA
VLFLTLMTRG GPRKRHELAS FAVITAIAVI AAAAAFGYGY QDWVPAGGIA FGLFIVTNAA
KLTVAVARIA LPPIPVPGET VDNEELLDPV ATPEATSEET PTWQAIIASV PASAVRLTER
SKLAKQLLIG YVTSGTLILA AGAIAVVVRG HFFVHSLVVA GLITTVCGFR SRLYAERWCA
WALLAATVAI PTGLTAKLII WYPHYAWLLL SVYLTVALVA LVVVGSMAHV RRVSPVVKRT
LELIDGAMIA AIIPMLLWIT GVYDTVRNIR F
