HRP1_MYCTU
ID HRP1_MYCTU Reviewed; 143 AA.
AC P9WJA3; L0TBT6; O06186; Q7D6V4;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Hypoxic response protein 1;
DE Short=HRP1;
GN Name=hrp1; OrderedLocusNames=Rv2626c;
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); BY HYPOXIA; IN MOUSE MODEL AND DORMANCY
RP 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 STATIONARY PHASE INDUCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=S-02293 Harlingen;
RX PubMed=15528667; DOI=10.1099/mic.0.27284-0;
RA Starck J., Kallenius G., Marklund B.I., Andersson D.I., Akerlund T.;
RT "Comparative proteome analysis of Mycobacterium tuberculosis grown under
RT aerobic and anaerobic conditions.";
RL Microbiology 150:3821-3829(2004).
RN [7]
RP SUBUNIT, AND PRELIMINARY CRYSTALLOGRAPHY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16511097; DOI=10.1107/s1744309105014235;
RA Sharpe M.L., Baker E.N., Lott J.S.;
RT "Crystallization of a protein using dehydration without a precipitant.";
RL Acta Crystallogr. F 61:565-568(2005).
RN [8]
RP BIOTECHNOLOGY.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17145953; DOI=10.1128/iai.01137-06;
RA Roupie V., Romano M., Zhang L., Korf H., Lin M.Y., Franken K.L.,
RA Ottenhoff T.H., Klein M.R., Huygen K.;
RT "Immunogenicity of eight dormancy regulon-encoded proteins of Mycobacterium
RT tuberculosis in DNA-vaccinated and tuberculosis-infected mice.";
RL Infect. Immun. 75:941-949(2007).
RN [9]
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 [10]
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 [11]
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 [12]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-127, SUBUNIT, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF CYS-14; CYS-39 AND CYS-136.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18640126; DOI=10.1016/j.jmb.2008.07.001;
RA Sharpe M.L., Gao C., Kendall S.L., Baker E.N., Lott J.S.;
RT "The structure and unusual protein chemistry of hypoxic response protein 1,
RT a latency antigen and highly expressed member of the DosR regulon in
RT Mycobacterium tuberculosis.";
RL J. Mol. Biol. 383:822-836(2008).
CC -!- FUNCTION: Unlike some other CBS-domain containing proteins does not
CC seem to bind AMP.
CC -!- SUBUNIT: Homodimer. Forms an SDS-resistant dimer that requires Cys-136
CC for SDS-resistance. {ECO:0000269|PubMed:16511097,
CC ECO:0000269|PubMed:18640126}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18640126}. Note=Not
CC seen to be associated with the cell wall.
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. Following a shift from
CC stationary to anaerobic growth this protein is not seen to not be
CC further induced (at protein level). Induced in mouse lungs at the same
CC time that adaptive host immunity induces bacterial growth arrest;
CC 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 -!- BIOTECHNOLOGY: In plasmid DNA-vaccinated mice, subsequent challenge
CC with this protein induces positive levels of antigen-specific IFN-gamma
CC and IL-2, indicating this might be a good vaccine candidate.
CC {ECO:0000269|PubMed:17145953}.
CC -!- MISCELLANEOUS: Has been detected extracellularly but no signal sequence
CC is predicted by bioinformatic programs.
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DR EMBL; AL123456; CCP45424.1; -; Genomic_DNA.
DR PIR; A70573; A70573.
DR RefSeq; NP_217142.1; NC_000962.3.
DR RefSeq; WP_003413598.1; NZ_NVQJ01000075.1.
DR PDB; 1XKF; X-ray; 1.90 A; A/B=1-127.
DR PDB; 1Y5H; X-ray; 1.50 A; A/B=1-127.
DR PDBsum; 1XKF; -.
DR PDBsum; 1Y5H; -.
DR AlphaFoldDB; P9WJA3; -.
DR SMR; P9WJA3; -.
DR STRING; 83332.Rv2626c; -.
DR PaxDb; P9WJA3; -.
DR DNASU; 888576; -.
DR GeneID; 45426630; -.
DR GeneID; 888576; -.
DR KEGG; mtu:Rv2626c; -.
DR TubercuList; Rv2626c; -.
DR eggNOG; COG0517; Bacteria.
DR OMA; YGICELC; -.
DR PhylomeDB; P9WJA3; -.
DR PHI-base; PHI:7581; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; HDA:MTBBASE.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0052553; P:modulation by symbiont of host immune response; IDA:MTBBASE.
DR GO; GO:0052572; P:response to host immune response; IEP:MTBBASE.
DR GO; GO:0001666; P:response to hypoxia; IDA:MTBBASE.
DR Gene3D; 3.10.580.10; -; 1.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR Pfam; PF00571; CBS; 2.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR PROSITE; PS51371; CBS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; CBS domain; Disulfide bond; Metal-binding;
KW Reference proteome; Repeat; Secreted; Zinc.
FT CHAIN 1..143
FT /note="Hypoxic response protein 1"
FT /id="PRO_0000392622"
FT DOMAIN 8..65
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 73..131
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT DISULFID 14..39
FT DISULFID 136
FT /note="Interchain"
FT MUTAGEN 14
FT /note="C->A: Forms less stable dimer."
FT /evidence="ECO:0000269|PubMed:18640126"
FT MUTAGEN 39
FT /note="C->A: Forms less stable dimer."
FT /evidence="ECO:0000269|PubMed:18640126"
FT MUTAGEN 128..143
FT /note="Missing: No longer forms SDS-resistant dimer."
FT MUTAGEN 136
FT /note="C->A: No longer forms SDS-resistant dimer."
FT /evidence="ECO:0000269|PubMed:18640126"
FT HELIX 4..7
FT /evidence="ECO:0007829|PDB:1Y5H"
FT STRAND 8..10
FT /evidence="ECO:0007829|PDB:1Y5H"
FT HELIX 21..31
FT /evidence="ECO:0007829|PDB:1Y5H"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:1Y5H"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:1Y5H"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:1Y5H"
FT HELIX 51..56
FT /evidence="ECO:0007829|PDB:1Y5H"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:1Y5H"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:1Y5H"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:1Y5H"
FT HELIX 87..97
FT /evidence="ECO:0007829|PDB:1Y5H"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:1Y5H"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:1Y5H"
FT HELIX 116..121
FT /evidence="ECO:0007829|PDB:1Y5H"
SQ SEQUENCE 143 AA; 15518 MW; CF65AA9144341038 CRC64;
MTTARDIMNA GVTCVGEHET LTAAAQYMRE HDIGALPICG DDDRLHGMLT DRDIVIKGLA
AGLDPNTATA GELARDSIYY VDANASIQEM LNVMEEHQVR RVPVISEHRL VGIVTEADIA
RHLPEHAIVQ FVKAICSPMA LAS
