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ESPD_MYCTU
ID   ESPD_MYCTU              Reviewed;         184 AA.
AC   P9WJD5; L0TEQ0; O06269; Q7D573;
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 EspD {ECO:0000305};
GN   Name=espD; Synonyms=snm10 {ECO:0000303|PubMed:16135231};
GN   OrderedLocusNames=Rv3614c;
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 INTERACTION WITH ECCE1.
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   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   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP   TRP-19; TRP-27; PRO-31; ARG-138 AND TRP-150.
RC   STRAIN=ATCC 35801 / TMC 107 / Erdman, and H37Rv;
RX   PubMed=22155774; DOI=10.1128/jb.06417-11;
RA   Chen J.M., Boy-Roettger S., Dhar N., Sweeney N., Buxton R.S., Pojer F.,
RA   Rosenkrands I., Cole S.T.;
RT   "EspD is critical for the virulence-mediating ESX-1 secretion system in
RT   Mycobacterium tuberculosis.";
RL   J. Bacteriol. 194:884-893(2012).
RN   [7]
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   [8]
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   [9]
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).
CC   -!- FUNCTION: Required for ESX-1 function (PubMed:16135231,
CC       PubMed:22155774). Required for the maintenance of adequate cellular
CC       levels of both EspA and EspC (PubMed:22155774). Facilitates EsxA
CC       secretion (PubMed:22155774). {ECO:0000269|PubMed:16135231,
CC       ECO:0000269|PubMed:22155774}.
CC   -!- SUBUNIT: Interacts with EccE1. {ECO:0000269|PubMed:16135231}.
CC   -!- INTERACTION:
CC       P9WJD5; P9WJB9: espL; NbExp=2; IntAct=EBI-26358082, EBI-25767670;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22155774}.
CC       Note=Export does not exclusively require ESX-1. May require one (or
CC       more) of the other ESX / type VII secretion systems (T7SS).
CC       {ECO:0000269|PubMed:22155774}.
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   -!- DISRUPTION PHENOTYPE: EspD deficiency results in decreased cellular
CC       levels of EspA and EspC, but does not affect their transcription.
CC       {ECO:0000269|PubMed:22155774}.
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DR   EMBL; AL123456; CCP46437.1; -; Genomic_DNA.
DR   PIR; G70956; G70956.
DR   RefSeq; NP_218131.1; NC_000962.3.
DR   RefSeq; WP_003419545.1; NZ_NVQJ01000056.1.
DR   AlphaFoldDB; P9WJD5; -.
DR   SMR; P9WJD5; -.
DR   BioGRID; 4355263; 1.
DR   IntAct; P9WJD5; 1.
DR   MINT; P9WJD5; -.
DR   STRING; 83332.Rv3614c; -.
DR   PaxDb; P9WJD5; -.
DR   DNASU; 885777; -.
DR   GeneID; 45427600; -.
DR   GeneID; 885777; -.
DR   KEGG; mtu:Rv3614c; -.
DR   PATRIC; fig|83332.111.peg.4020; -.
DR   TubercuList; Rv3614c; -.
DR   eggNOG; ENOG5031JYJ; Bacteria.
DR   OMA; DSASEQC; -.
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:0005886; C:plasma membrane; HDA:MTBBASE.
DR   GO; GO:0044315; P:protein secretion by the type VII secretion system; IMP:MTBBASE.
PE   1: Evidence at protein level;
KW   Reference proteome; Secreted; Virulence.
FT   CHAIN           1..184
FT                   /note="ESX-1 secretion-associated protein EspD"
FT                   /id="PRO_0000393904"
FT   REGION          33..56
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         19
FT                   /note="W->R: Absence of EspD secretion."
FT                   /evidence="ECO:0000269|PubMed:22155774"
FT   MUTAGEN         27
FT                   /note="W->R: Absence of EspD secretion."
FT                   /evidence="ECO:0000269|PubMed:22155774"
FT   MUTAGEN         31
FT                   /note="P->A: Decreased EspD secretion and small reduction
FT                   in cellular EspA levels."
FT                   /evidence="ECO:0000269|PubMed:22155774"
FT   MUTAGEN         138
FT                   /note="R->A: Absence of EsxA secretion. Decreases EspD
FT                   stability."
FT                   /evidence="ECO:0000269|PubMed:22155774"
FT   MUTAGEN         150
FT                   /note="W->R: Absence of EspD secretion. Decreases EspA
FT                   levels."
FT                   /evidence="ECO:0000269|PubMed:22155774"
SQ   SEQUENCE   184 AA;  19835 MW;  6326911F65DC5C7A CRC64;
     MDLPGNDFDS NDFDAVDLWG ADGAEGWTAD PIIGVGSAAT PDTGPDLDNA HGQAETDTEQ
     EIALFTVTNP PRTVSVSTLM DGRIDHVELS ARVAWMSESQ LASEILVIAD LARQKAQSAQ
     YAFILDRMSQ QVDADEHRVA LLRKTVGETW GLPSPEEAAA AEAEVFATRY SDDCPAPDDE
     SDPW
 
 
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