Y2623_MYCTU
ID Y2623_MYCTU Reviewed; 297 AA.
AC P9WFD7; L0TAF1; O06189; Q7D6V7;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Universal stress protein Rv2623;
DE Short=USP Rv2623;
GN OrderedLocusNames=Rv2623; ORFNames=TB31.7;
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 INDUCTION BY HYPOXIA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11416222; DOI=10.1073/pnas.121172498;
RA Sherman D.R., Voskuil M., Schnappinger D., Liao R., Harrell M.I.,
RA Schoolnik G.K.;
RT "Regulation of the Mycobacterium tuberculosis hypoxic response gene
RT encoding alpha -crystallin.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7534-7539(2001).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INDUCTION BY HYPOXIA.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12057942; DOI=10.1128/jb.184.13.3485-3491.2002;
RA Rosenkrands I., Slayden R.A., Crawford J., Aagaard C., Barry C.E. III,
RA Andersen P.;
RT "Hypoxic response of Mycobacterium tuberculosis studied by metabolic
RT labeling and proteome analysis of cellular and extracellular proteins.";
RL J. Bacteriol. 184:3485-3491(2002).
RN [4]
RP INDUCTION BY NITRIC OXIDE (NO) AND BY HYPOXIA, AND DORMANCY REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12953092; DOI=10.1084/jem.20030205;
RA Voskuil M.I., Schnappinger D., Visconti K.C., Harrell M.I., Dolganov G.M.,
RA Sherman D.R., Schoolnik G.K.;
RT "Inhibition of respiration by nitric oxide induces a Mycobacterium
RT tuberculosis dormancy program.";
RL J. Exp. Med. 198:705-713(2003).
RN [5]
RP INDUCTION BY HOST IMMUNITY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12506197; DOI=10.1073/pnas.0136863100;
RA Shi L., Jung Y.J., Tyagi S., Gennaro M.L., North R.J.;
RT "Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium
RT tuberculosis transcription pattern characteristic of nonreplicating
RT persistence.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:241-246(2003).
RN [6]
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 [7]
RP INDUCTION BY CARBON MONOXIDE (CO).
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007;
RA Shiloh M.U., Manzanillo P., Cox J.S.;
RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during
RT macrophage infection.";
RL Cell Host Microbe 3:323-330(2008).
RN [8]
RP INDUCTION BY CARBON MONOXIDE (CO), AND DORMANCY REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18400743; DOI=10.1074/jbc.m802274200;
RA Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I.,
RA Agarwal A., Steyn A.J.;
RT "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium
RT tuberculosis dormancy regulon.";
RL J. Biol. Chem. 283:18032-18039(2008).
RN [9]
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 [10]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS), SUBUNIT, ADP- AND ATP-BINDING,
RP MUTAGENESIS OF ASP-15 AND GLY-117, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=19478878; DOI=10.1371/journal.ppat.1000460;
RA Drumm J.E., Mi K., Bilder P., Sun M., Lim J., Bielefeldt-Ohmann H.,
RA Basaraba R., So M., Zhu G., Tufariello J.M., Izzo A.A., Orme I.M.,
RA Almo S.C., Leyh T.S., Chan J.;
RT "Mycobacterium tuberculosis universal stress protein Rv2623 regulates
RT bacillary growth by ATP-binding: requirement for establishing chronic
RT persistent infection.";
RL PLoS Pathog. 5:E1000460-E1000460(2009).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (3.22 ANGSTROMS) IN COMPLEX WITH ATP.
RG Mycobacterium tuberculosis structural genomics consortium (TB);
RT "Crystal structure of universal stress protein Rv2623 from mycobacterium
RT tuberculosis.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [12] {ECO:0007744|PDB:3CIS}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH ATP.
RA Drumm J., Mi K., Bilder P., Almo S., Chan J.;
RT "The crystal structure of Rv2623: a novel, tandem-repeat universal stress
RT protein of Mycobacterium tuberculosis.";
RL Submitted (MAR-2008) to the PDB data bank.
CC -!- FUNCTION: May play a role in the establishment of a persistent
CC infection (latency) in the host, as strains without this gene are
CC hypervirulent. Overexpression of the protein retards growth in culture;
CC Glu-15 and Ala-117 mutant proteins which bind less ATP do not show this
CC retardation, suggesting growth may be regulated through an ATP-
CC dependent function.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19478878}.
CC -!- INDUCTION: A member of the dormancy regulon. Induced in response to
CC reduced oxygen tension (hypoxia), low levels of nitric oxide (NO) and
CC carbon monoxide (CO). It is hoped that this regulon will give insight
CC into the latent, or dormant phase of infection. Induced in mouse lungs
CC at the same time that adaptive host immunity induces bacterial growth
CC arrest; induction is dependent on interferon gamma.
CC {ECO:0000269|PubMed:11416222, ECO:0000269|PubMed:12057942,
CC ECO:0000269|PubMed:12506197, ECO:0000269|PubMed:12953092,
CC ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359}.
CC -!- DISRUPTION PHENOTYPE: The deletion strain is hypervirulent compared to
CC the wild-type strain in infection studies with outbred Hartley guinea
CC pigs and with C3H/HeJ mice but not with C57BL/6 mice. No phenotype when
CC grown in culture upon disruption, probably due to functional redundancy
CC among paralogs. {ECO:0000269|PubMed:19478878}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the universal stress protein A family.
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP45421.1; -; Genomic_DNA.
DR PIR; F70572; F70572.
DR RefSeq; NP_217139.1; NC_000962.3.
DR RefSeq; WP_003413592.1; NZ_NVQJ01000075.1.
DR PDB; 2JAX; X-ray; 3.22 A; A=1-297.
DR PDB; 3CIS; X-ray; 2.90 A; A/B/C/D/E/F/G/H=1-297.
DR PDBsum; 2JAX; -.
DR PDBsum; 3CIS; -.
DR AlphaFoldDB; P9WFD7; -.
DR SMR; P9WFD7; -.
DR STRING; 83332.Rv2623; -.
DR PaxDb; P9WFD7; -.
DR DNASU; 887442; -.
DR GeneID; 887442; -.
DR KEGG; mtu:Rv2623; -.
DR TubercuList; Rv2623; -.
DR eggNOG; COG0589; Bacteria.
DR OMA; EMVVTGC; -.
DR PhylomeDB; P9WFD7; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE.
DR GO; GO:0085014; P:dormancy entry of symbiont in host; IDA:MTBBASE.
DR GO; GO:0040008; P:regulation of growth; IDA:MTBBASE.
DR GO; GO:0001666; P:response to hypoxia; IDA:MTBBASE.
DR Gene3D; 3.40.50.620; -; 2.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR006015; Universal_stress_UspA.
DR InterPro; IPR006016; UspA.
DR Pfam; PF00582; Usp; 2.
DR PRINTS; PR01438; UNVRSLSTRESS.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Nucleotide-binding; Reference proteome;
KW Virulence.
FT CHAIN 1..297
FT /note="Universal stress protein Rv2623"
FT /id="PRO_0000392628"
FT BINDING 13
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT BINDING 43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT BINDING 117..123
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT BINDING 127
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT BINDING 131..132
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT BINDING 165
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT BINDING 198
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT BINDING 262..268
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT BINDING 276..278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.11, ECO:0000269|Ref.12,
FT ECO:0007744|PDB:2JAX, ECO:0007744|PDB:3CIS"
FT MUTAGEN 15
FT /note="D->E: Reduces ATP-binding; M.tuberculosis
FT overexpressing this protein grows normally."
FT /evidence="ECO:0000269|PubMed:19478878"
FT MUTAGEN 117
FT /note="G->A: Reduces ATP-binding; M.tuberculosis
FT overexpressing this protein grows normally."
FT /evidence="ECO:0000269|PubMed:19478878"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 18..34
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 58..82
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 91..98
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 111..119
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 170..185
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:2JAX"
FT HELIX 209..224
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 236..243
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 245..253
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 257..264
FT /evidence="ECO:0007829|PDB:3CIS"
FT HELIX 276..284
FT /evidence="ECO:0007829|PDB:3CIS"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:3CIS"
SQ SEQUENCE 297 AA; 31652 MW; A590F7058D1E8695 CRC64;
MSSGNSSLGI IVGIDDSPAA QVAVRWAARD AELRKIPLTL VHAVSPEVAT WLEVPLPPGV
LRWQQDHGRH LIDDALKVVE QASLRAGPPT VHSEIVPAAA VPTLVDMSKD AVLMVVGCLG
SGRWPGRLLG SVSSGLLRHA HCPVVIIHDE DSVMPHPQQA PVLVGVDGSS ASELATAIAF
DEASRRNVDL VALHAWSDVD VSEWPGIDWP ATQSMAEQVL AERLAGWQER YPNVAITRVV
VRDQPARQLV QRSEEAQLVV VGSRGRGGYA GMLVGSVGET VAQLARTPVI VARESLT
