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PG30_MYCTU
ID   PG30_MYCTU              Reviewed;        1011 AA.
AC   Q79FL8; I6X1W4; L0T7B2;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   25-MAY-2022, entry version 93.
DE   RecName: Full=PE-PGRS family protein PE_PGRS30 {ECO:0000305};
GN   Name=PE_PGRS30 {ECO:0000312|EMBL:CCP44416.1};
GN   OrderedLocusNames=Rv1651c {ECO:0000312|EMBL:CCP44416.1};
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   SUBCELLULAR LOCATION.
RX   PubMed=21732963; DOI=10.1111/j.1574-6968.2011.02354.x;
RA   Chatrath S., Gupta V.K., Dixit A., Garg L.C.;
RT   "The Rv1651c-encoded PE-PGRS30 protein expressed in Mycobacterium smegmatis
RT   exhibits polar localization and modulates its growth profile.";
RL   FEMS Microbiol. Lett. 322:194-199(2011).
RN   [3]
RP   FUNCTION IN VIRULENCE, DISRUPTION PHENOTYPE, DOMAIN, AND EXPRESSION IN
RP   M.SMEGMATIS.
RC   STRAIN=H37Rv;
RX   PubMed=22050772; DOI=10.1111/j.1462-5822.2011.01721.x;
RA   Iantomasi R., Sali M., Cascioferro A., Palucci I., Zumbo A., Soldini S.,
RA   Rocca S., Greco E., Maulucci G., De Spirito M., Fraziano M., Fadda G.,
RA   Manganelli R., Delogu G.;
RT   "PE_PGRS30 is required for the full virulence of Mycobacterium
RT   tuberculosis.";
RL   Cell. Microbiol. 14:356-367(2012).
RN   [4]
RP   SUBCELLULAR LOCATION, AND DOMAIN.
RX   PubMed=24530527; DOI=10.1016/j.febslet.2014.01.059;
RA   Chatrath S., Gupta V.K., Garg L.C.;
RT   "The PGRS domain is responsible for translocation of PE_PGRS30 to cell
RT   poles while the PE and the C-terminal domains localize it to the cell
RT   wall.";
RL   FEBS Lett. 588:990-994(2014).
RN   [5]
RP   SUBCELLULAR LOCATION, AND DOMAIN.
RX   PubMed=25390359; DOI=10.1371/journal.pone.0112482;
RA   De Maio F., Maulucci G., Minerva M., Anoosheh S., Palucci I., Iantomasi R.,
RA   Palmieri V., Camassa S., Sali M., Sanguinetti M., Bitter W., Manganelli R.,
RA   De Spirito M., Delogu G.;
RT   "Impact of protein domains on PE_PGRS30 polar localization in
RT   Mycobacteria.";
RL   PLoS ONE 9:E112482-E112482(2014).
RN   [6]
RP   FUNCTION, DOMAIN, AND EXPRESSION IN M.SMEGMATIS.
RX   PubMed=27129781; DOI=10.1016/j.micinf.2016.04.004;
RA   Chatrath S., Gupta V.K., Dixit A., Garg L.C.;
RT   "PE_PGRS30 of Mycobacterium tuberculosis mediates suppression of
RT   proinflammatory immune response in macrophages through its PGRS and PE
RT   domains.";
RL   Microbes Infect. 18:536-542(2016).
CC   -!- FUNCTION: Mediates suppression of pro-inflammatory immune response in
CC       macrophages via modulation of host cytokine response (PubMed:27129781).
CC       Required for full virulence. Involved in inhibition of phago-lysosome
CC       fusion (PubMed:22050772). {ECO:0000269|PubMed:22050772,
CC       ECO:0000269|PubMed:27129781}.
CC   -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000269|PubMed:21732963,
CC       ECO:0000269|PubMed:24530527, ECO:0000269|PubMed:25390359}. Cell surface
CC       {ECO:0000269|PubMed:24530527, ECO:0000269|PubMed:25390359}.
CC       Note=Localizes at the cell poles. {ECO:0000269|PubMed:21732963,
CC       ECO:0000269|PubMed:24530527, ECO:0000269|PubMed:25390359}.
CC   -!- DOMAIN: Both the PE domain and the non-PGRS C-terminal domain possess
CC       independent cell wall localization signals. The PGRS domain is
CC       responsible for polar localization of PE_PGRS30 (PubMed:24530527,
CC       PubMed:25390359). PE and PGRS domains are necessary for the cytokine-
CC       modulating function (PubMed:27129781). The non-PGRS C-terminal domain
CC       is not exposed on the surface and is not required for full virulence in
CC       vivo (PubMed:22050772, PubMed:25390359). {ECO:0000269|PubMed:22050772,
CC       ECO:0000269|PubMed:24530527, ECO:0000269|PubMed:25390359,
CC       ECO:0000269|PubMed:27129781}.
CC   -!- DISRUPTION PHENOTYPE: Deletion mutant is attenuated in vivo during
CC       murine tuberculosis, specifically during the chronic steps of
CC       infection. On day 28 post infection, shows a slight reduction of the
CC       bacterial burden. On day 70, shows a strong reduction of the bacterial
CC       burden. Mice infected with the mutant show smaller, non-confluent
CC       tubercules. Mutant shows impaired ability to survive and multiply
CC       within murine macrophages. It is unable to inhibit phago-lysosome
CC       fusion in THP-1 cells. {ECO:0000269|PubMed:22050772}.
CC   -!- MISCELLANEOUS: Infection of human THP-1 macrophages with M.smegmatis
CC       expressing PE_PGRS30 results in reduced production of IL-12, TNF-alpha
CC       and IL-6, as compared to infection with vector control M.smegmatis. No
CC       differential effects are observed on bacterial persistence inside
CC       macrophages or on macrophage mortality upon infection
CC       (PubMed:27129781). However, expression of this gene in M.smegmatis is
CC       sufficient to enhance the ability to persist intracellularly and induce
CC       murine J774 macrophages death (PubMed:22050772). Differential response
CC       of the human and murine macrophages could be due to cell-specific
CC       processes (Probable). {ECO:0000269|PubMed:22050772,
CC       ECO:0000269|PubMed:27129781, ECO:0000305|PubMed:27129781}.
CC   -!- SIMILARITY: Belongs to the mycobacterial PE family. PGRS subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AL123456; CCP44416.1; -; Genomic_DNA.
DR   RefSeq; WP_010886125.1; NZ_KK339370.1.
DR   RefSeq; YP_177826.1; NC_000962.3.
DR   AlphaFoldDB; Q79FL8; -.
DR   STRING; 83332.Rv1651c; -.
DR   PaxDb; Q79FL8; -.
DR   DNASU; 885174; -.
DR   GeneID; 885174; -.
DR   KEGG; mtu:Rv1651c; -.
DR   PATRIC; fig|83332.111.peg.1836; -.
DR   TubercuList; Rv1651c; -.
DR   eggNOG; COG3391; Bacteria.
DR   OMA; IAVGHNS; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   InterPro; IPR000084; PE-PGRS_N.
DR   Pfam; PF00934; PE; 1.
PE   1: Evidence at protein level;
KW   Cell wall; Reference proteome; Secreted; Virulence.
FT   CHAIN           1..1011
FT                   /note="PE-PGRS family protein PE_PGRS30"
FT                   /id="PRO_5004287725"
FT   DOMAIN          1..93
FT                   /note="PE"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:25390359"
FT   REGION          130..696
FT                   /note="PGRS domain"
FT                   /evidence="ECO:0000305|PubMed:25390359"
FT   REGION          595..701
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          697..1011
FT                   /note="C-terminal domain"
FT                   /evidence="ECO:0000305|PubMed:25390359"
SQ   SEQUENCE   1011 AA;  88455 MW;  1F2CBAB67969E066 CRC64;
     MSFLLVEPDL VTAAAANLAG IRSALSEAAA AASTPTTALA SAGADEVSAA VSRLFGAYGQ
     QFQALNARAA TFHAEFVSLL NGGAAAYTGA EAASVSSMQA LLDAVNAPTQ TLLGRPLIGN
     GADGVAGTGS NAGGNGGPGG ILYGNGGNGG AGGNGGAAGL IGNGGAGGAG GAGGAGGAGG
     AGGTGGLLYG NGGAGGNGGS AAAAGGAGGN ALLFGNGGNG GSGASGGAAG HAGTIFGNGG
     NAGAGSGLAG ADGGLFGNGG DGGSSTSKAG GAGGNALFGN GGDGGSSTVA AGGAGGNTLV
     GNGGAGGAGG TSGLTGSGVA GGAGGSVGLW GSGGAGGDGG AATSLLGVGM NAGAGGAGGN
     AGLLYGNGGA GGAGGNGGDT TVPLFDSGVG GAGGAGGNAS LFGNGGTGGV GGKGGTSSDL
     ASATSGAGGA GGAGGVGGLL YGNGGNGGAG GIGGAAINIL ANAGAGGAGG AAGSSFIGNG
     GNGGAGGAGG AAALFSSGVG GAGGSGGTAL LLGSGGAGGN GGTGGANSGS LFASPGGTGG
     AGGHGGAGGL IWGNGGAGGN GGNGGTTADG ALEGGTGGIG GTGGSAIAFG NGGQGGAGGT
     GGDHSGGNGI GGKGGASGNG GNAGQVFGDG GTGGTGGAGG AGSGTKAGGT GSDGGHGGNA
     TLIGNGGDGG AGGAGGAGSP AGAPGNGGTG GTGGVLFGQS GSSGPPGAAA LAFPSLSSSV
     PILGPYEDLI ANTVANLASI GNTWLADPAP FLQQYLANQF GYGQLTLTAL TDATRDFAIG
     LAGIPPSLQS ALQALAAGDV SGAVTDVLGA VVKVFVSGVD ASDLSNILLL GPVGDLFPIL
     SIPGAMSQNF TNVVMTVTDT TIAFSIDTTN LTGVMTFGLP LAMTLNAVGS PITTAIAFAE
     STTAFVSAVQ AGNLQAAAAA LVGAPANVAN GFLNGEARLP LALPTSATGG IPVTVEVPVG
     GILAPLQPFQ ATAVIPVIGP VTVTLEGTPA GGIVPALVNY APTQLAQAIA P
 
 
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