CRPL_MYCTU
ID CRPL_MYCTU Reviewed; 224 AA.
AC P9WMH3; F2GFB8; L0TDH2; O69644; Q7D534;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=CRP-like cAMP-activated global transcriptional regulator {ECO:0000303|PubMed:16267303};
DE AltName: Full=cAMP receptor protein {ECO:0000303|PubMed:16267303};
DE Short=CRP {ECO:0000303|PubMed:16267303};
DE AltName: Full=cAMP regulatory protein {ECO:0000303|PubMed:16267303};
GN Name=crp {ECO:0000303|PubMed:16267303}; OrderedLocusNames=Rv3676;
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 DNA-BINDING, DNA-BENDING, AND PROBABLE CAMP-BINDING.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16267303; DOI=10.1128/jb.187.22.7795-7804.2005;
RA Bai G., McCue L.A., McDonough K.A.;
RT "Characterization of Mycobacterium tuberculosis Rv3676 (CRPMt), a cyclic
RT AMP receptor protein-like DNA binding protein.";
RL J. Bacteriol. 187:7795-7804(2005).
RN [3]
RP FUNCTION AS A TRANSCRIPTION REGULATOR, DNA-BINDING, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15882420; DOI=10.1111/j.1365-2958.2005.04609.x;
RA Rickman L., Scott C., Hunt D.M., Hutchinson T., Menendez M.C., Whalan R.,
RA Hinds J., Colston M.J., Green J., Buxton R.S.;
RT "A member of the cAMP receptor protein family of transcription regulators
RT in Mycobacterium tuberculosis is required for virulence in mice and
RT controls transcription of the rpfA gene coding for a resuscitation
RT promoting factor.";
RL Mol. Microbiol. 56:1274-1286(2005).
RN [4]
RP FUNCTION, SUBUNIT, DNA-BINDING, AND CAMP-BINDING.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20028978; DOI=10.1074/jbc.m109.047720;
RA Stapleton M., Haq I., Hunt D.M., Arnvig K.B., Artymiuk P.J., Buxton R.S.,
RA Green J.;
RT "Mycobacterium tuberculosis cAMP receptor protein (Rv3676) differs from the
RT Escherichia coli paradigm in its cAMP binding and DNA binding properties
RT and transcription activation properties.";
RL J. Biol. Chem. 285:7016-7027(2010).
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 X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF APO-CRP (OFF-STATE), AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19193643; DOI=10.1074/jbc.c800215200;
RA Gallagher D.T., Smith N., Kim S.K., Robinson H., Reddy P.T.;
RT "Profound asymmetry in the structure of the cAMP-free cAMP receptor protein
RT (CRP) from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 284:8228-8232(2009).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH CAMP (ON-STATE) AND
RP IN COMPLEX WITH A CAMP ANALOG, SUBUNIT, AND CAMP-BINDING.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19740754; DOI=10.1074/jbc.m109.041343;
RA Reddy M.C., Palaninathan S.K., Bruning J.B., Thurman C., Smith D.,
RA Sacchettini J.C.;
RT "Structural insights into the mechanism of the allosteric transitions of
RT Mycobacterium tuberculosis cAMP receptor protein.";
RL J. Biol. Chem. 284:36581-36591(2009).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS).
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20338852; DOI=10.1016/j.bpj.2009.10.016;
RA Kumar P., Joshi D.C., Akif M., Akhter Y., Hasnain S.E., Mande S.C.;
RT "Mapping conformational transitions in cyclic AMP receptor protein: crystal
RT structure and normal-mode analysis of Mycobacterium tuberculosis apo-cAMP
RT receptor protein.";
RL Biophys. J. 98:305-314(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH CAMP AND DNA.
RA Akhter Y., Pogenberg V., Hasnain S.E., Wilmanns M.;
RT "Crystal structure of cAMP receptor protein from Mycobacterium tuberculosis
RT in complex with DNA and cAMP.";
RL Submitted (MAY-2010) to the PDB data bank.
RN [10]
RP STRUCTURE BY NMR.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22074452; DOI=10.1021/ja206967d;
RA Godoy-Ruiz R., Krejcirikova A., Gallagher D.T., Tugarinov V.;
RT "Solution NMR evidence for symmetry in functionally or crystallographically
RT asymmetric homodimers.";
RL J. Am. Chem. Soc. 133:19578-19581(2011).
CC -!- FUNCTION: Global transcriptional regulator that complexes with cAMP and
CC binds to specific DNA promoter sites, causing DNA-bending, to regulate
CC transcription. cAMP improves binding to specific DNA sequences,
CC probably by altering protein conformation. The CRP regulon is predicted
CC to contain about 115 genes. Some genes are activated by CRP (rpfA,
CC whiB1) while others are repressed (fadD10). There are 2 CRP-binding
CC sites in the promoter of whiB1, at low concentrations of CRP with or
CC without cAMP transcription of whiB1 is enhanced via site CRP1, then
CC repressed as site CRP2 is filled. {ECO:0000269|PubMed:15882420,
CC ECO:0000269|PubMed:20028978}.
CC -!- SUBUNIT: Homodimer; in the absence of cAMP the DNA-binding domains are
CC asymmetric in one structure; upon cAMP binding the dimer becomes
CC symmetric, preparing it to bind DNA. {ECO:0000269|PubMed:19193643,
CC ECO:0000269|PubMed:19740754, ECO:0000269|PubMed:20028978,
CC ECO:0000269|Ref.9}.
CC -!- DISRUPTION PHENOTYPE: Grows more slowly in aerobic liquid culture and
CC on plates, severely impaired growth in unactivated mouse bone marrow-
CC derived macrophages and in infected mice.
CC {ECO:0000269|PubMed:15882420}.
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DR EMBL; AL123456; CCP46499.1; -; Genomic_DNA.
DR PIR; E70790; E70790.
DR RefSeq; NP_218193.1; NC_000962.3.
DR RefSeq; WP_003419728.1; NZ_NVQJ01000028.1.
DR PDB; 3D0S; X-ray; 2.00 A; A/B=1-224.
DR PDB; 3H3U; X-ray; 2.90 A; A/B=1-224.
DR PDB; 3I54; X-ray; 2.20 A; A/B/C/D=1-224.
DR PDB; 3I59; X-ray; 2.29 A; A/B=1-224.
DR PDB; 3MZH; X-ray; 2.90 A; A/B=1-224.
DR PDB; 4A2U; X-ray; 2.63 A; A/B/C/D/E/F/G/H=1-224.
DR PDBsum; 3D0S; -.
DR PDBsum; 3H3U; -.
DR PDBsum; 3I54; -.
DR PDBsum; 3I59; -.
DR PDBsum; 3MZH; -.
DR PDBsum; 4A2U; -.
DR AlphaFoldDB; P9WMH3; -.
DR SMR; P9WMH3; -.
DR STRING; 83332.Rv3676; -.
DR PaxDb; P9WMH3; -.
DR GeneID; 885502; -.
DR KEGG; mtu:Rv3676; -.
DR TubercuList; Rv3676; -.
DR eggNOG; COG0664; Bacteria.
DR OMA; VLCRDFG; -.
DR PhylomeDB; P9WMH3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0030552; F:cAMP binding; IDA:MTBBASE.
DR GO; GO:0003677; F:DNA binding; IDA:MTBBASE.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MTBBASE.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MTBBASE.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MTBBASE.
DR CDD; cd00038; CAP_ED; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR012318; HTH_CRP.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF13545; HTH_Crp_2; 1.
DR SMART; SM00100; cNMP; 1.
DR SMART; SM00419; HTH_CRP; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS51063; HTH_CRP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; cAMP; cAMP-binding; DNA-binding;
KW Nucleotide-binding; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Virulence.
FT CHAIN 1..224
FT /note="CRP-like cAMP-activated global transcriptional
FT regulator"
FT /id="PRO_0000420402"
FT DOMAIN 144..217
FT /note="HTH crp-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00387"
FT DNA_BIND 177..196
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00387"
FT BINDING 64..70
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P0ACJ8"
FT BINDING 79..82
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.9"
FT BINDING 89..90
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.9"
FT BINDING 134..135
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.9"
FT BINDING 142..143
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P0ACJ8"
FT BINDING 178..188
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P0ACJ8"
FT HELIX 2..5
FT /evidence="ECO:0007829|PDB:3D0S"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:3I54"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:3MZH"
FT HELIX 20..23
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3H3U"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 55..60
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:3D0S"
FT HELIX 81..84
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:3D0S"
FT HELIX 106..111
FT /evidence="ECO:0007829|PDB:3D0S"
FT HELIX 117..143
FT /evidence="ECO:0007829|PDB:3D0S"
FT HELIX 146..161
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 162..165
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 168..172
FT /evidence="ECO:0007829|PDB:3D0S"
FT HELIX 177..184
FT /evidence="ECO:0007829|PDB:3D0S"
FT HELIX 188..200
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:3D0S"
FT STRAND 210..214
FT /evidence="ECO:0007829|PDB:3D0S"
FT HELIX 216..223
FT /evidence="ECO:0007829|PDB:3D0S"
SQ SEQUENCE 224 AA; 24791 MW; BAB89A61B64839E3 CRC64;
MDEILARAGI FQGVEPSAIA ALTKQLQPVD FPRGHTVFAE GEPGDRLYII ISGKVKIGRR
APDGRENLLT IMGPSDMFGE LSIFDPGPRT SSATTITEVR AVSMDRDALR SWIADRPEIS
EQLLRVLARR LRRTNNNLAD LIFTDVPGRV AKQLLQLAQR FGTQEGGALR VTHDLTQEEI
AQLVGASRET VNKALADFAH RGWIRLEGKS VLISDSERLA RRAR
