OPRA_MYCTU
ID OPRA_MYCTU Reviewed; 158 AA.
AC O33361; F2GND1; I6XVH4; L0T6Q7;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Osmosensory protein A {ECO:0000303|PubMed:24309377};
DE AltName: Full=Putative SigF antagonist {ECO:0000305|PubMed:24309377};
DE AltName: Full=Putative anti-anti-sigma factor Rv0516c {ECO:0000305|PubMed:17411339};
GN Name=OprA {ECO:0000303|PubMed:24309377};
GN OrderedLocusNames=Rv0516c {ECO:0000312|EMBL:CCP43253.1};
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 PHOSPHORYLATION AT THR-2, INTERACTION WITH RV2638, AND MUTAGENESIS OF
RP THR-2.
RX PubMed=17411339; DOI=10.1371/journal.ppat.0030049;
RA Greenstein A.E., MacGurn J.A., Baer C.E., Falick A.M., Cox J.S., Alber T.;
RT "M. tuberculosis Ser/Thr protein kinase D phosphorylates an anti-anti-sigma
RT factor homolog.";
RL PLoS Pathog. 3:E49-E49(2007).
RN [3]
RP INDUCTION.
RX PubMed=17485404; DOI=10.2741/2417;
RA Dhandayuthapani S.;
RT "Stress response of genes encoding putative stress signaling molecules of
RT Mycobacterium tuberculosis.";
RL Front. Biosci. 12:4676-4681(2007).
RN [4]
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 [5]
RP FUNCTION, ACTIVITY REGULATION, INDUCTION, PHOSPHORYLATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF THR-2.
RX PubMed=24309377; DOI=10.1073/pnas.1321205110;
RA Hatzios S.K., Baer C.E., Rustad T.R., Siegrist M.S., Pang J.M., Ortega C.,
RA Alber T., Grundner C., Sherman D.R., Bertozzi C.R.;
RT "Osmosensory signaling in Mycobacterium tuberculosis mediated by a
RT eukaryotic-like Ser/Thr protein kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E5069-E5077(2013).
CC -!- FUNCTION: Part of a signaling pathway that enables adaptation to
CC osmotic stress through cell wall remodeling and virulence factor
CC production (PubMed:24309377). Unphosphorylated OprA forms a complex
CC with the anti-anti-sigma-factor paralog Rv2638 that dissociates on OprA
CC phosphorylation by PknD (PubMed:17411339). Phosphorylation of OprA may
CC stimulate the release of SigF from an inhibitory complex and enable the
CC transcription of osmotically regulated genes, such as oprA and the ESX-
CC 1-associated virulence factor espA (PubMed:24309377).
CC {ECO:0000269|PubMed:17411339, ECO:0000269|PubMed:24309377}.
CC -!- ACTIVITY REGULATION: Regulated by PknD under osmotic stress.
CC {ECO:0000269|PubMed:24309377}.
CC -!- SUBUNIT: Interacts with Rv2638. Phosphorylation abolishes binding to
CC Rv2638. {ECO:0000269|PubMed:17411339}.
CC -!- INDUCTION: Highly up-regulated by osmotic stress (PubMed:24309377,
CC PubMed:17485404). Also induced during oxidative and starvation stresses
CC (PubMed:17485404). {ECO:0000269|PubMed:17485404,
CC ECO:0000269|PubMed:24309377}.
CC -!- PTM: Phosphorylated on Thr-2 by the serine/threonine-protein kinase
CC PknD (PubMed:17411339, PubMed:24309377). Also phosphorylated to a
CC lesser extent by PknB and PknE (PubMed:17411339). Dephosphorylated by
CC PstP (PubMed:17411339). {ECO:0000269|PubMed:17411339,
CC ECO:0000269|PubMed:24309377}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the gene enhances resistance to
CC osmotic stress, increases resistance to several peptidoglycan
CC biosynthesis inhibitors, decreases peptidoglycan thickness, enhances
CC antibiotic resistance and activates genes in the SigF regulon.
CC {ECO:0000269|PubMed:24309377}.
CC -!- SIMILARITY: Belongs to the anti-sigma-factor antagonist family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP43253.1; -; Genomic_DNA.
DR RefSeq; NP_215030.1; NC_000962.3.
DR RefSeq; WP_003402807.1; NZ_NVQJ01000068.1.
DR AlphaFoldDB; O33361; -.
DR SMR; O33361; -.
DR IntAct; O33361; 2.
DR STRING; 83332.Rv0516c; -.
DR PaxDb; O33361; -.
DR PRIDE; O33361; -.
DR GeneID; 45424480; -.
DR GeneID; 887324; -.
DR KEGG; mtu:Rv0516c; -.
DR PATRIC; fig|83332.111.peg.568; -.
DR TubercuList; Rv0516c; -.
DR eggNOG; COG1366; Bacteria.
DR OMA; TETRHDN; -.
DR Proteomes; UP000001584; Chromosome.
DR Gene3D; 3.30.750.24; -; 1.
DR InterPro; IPR002645; STAS_dom.
DR InterPro; IPR036513; STAS_dom_sf.
DR Pfam; PF01740; STAS; 1.
DR SUPFAM; SSF52091; SSF52091; 1.
DR PROSITE; PS50801; STAS; 1.
PE 1: Evidence at protein level;
KW Phosphoprotein; Reference proteome; Stress response.
FT CHAIN 1..158
FT /note="Osmosensory protein A"
FT /id="PRO_0000451030"
FT DOMAIN 28..139
FT /note="STAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00198"
FT MOD_RES 2
FT /note="Phosphothreonine; by PknD"
FT /evidence="ECO:0000269|PubMed:17411339"
FT MUTAGEN 2
FT /note="T->A: Lack of phosphorylation by PknD. Reduced oprA
FT induction in response to osmotic stress."
FT /evidence="ECO:0000269|PubMed:17411339,
FT ECO:0000269|PubMed:24309377"
SQ SEQUENCE 158 AA; 16987 MW; 9AD77DACE3093650 CRC64;
MTTTIPTSKS ACSVTTRPGN AAVDYGGAQI RAYLHHLATV VTIRGEIDAA NVEQISEHVR
RFSLGTNPMV LDLSELSHFS GAGISLLCIL DEDCRAAGVQ WALVASPAVV EQLGGRCDQG
EHESMFPMAR SVHKALHDLA DAIDRRRQLV LPLISRSA
