ID   CRP_HAEIN               Reviewed;         224 AA.
AC   P29281;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-1992, sequence version 1.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=cAMP-activated global transcriptional regulator CRP;
DE   AltName: Full=Catabolite activator protein;
DE            Short=CAP;
DE   AltName: Full=cAMP receptor protein;
DE            Short=CRP;
DE   AltName: Full=cAMP regulatory protein;
GN   Name=crp; Synonyms=cap; OrderedLocusNames=HI_0957;
OS   Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Pasteurellales;
OC   Pasteurellaceae; Haemophilus.
OX   NCBI_TaxID=71421;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PROBABLE AUTOREGULATION, AND
RP   DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX   PubMed=1542653; DOI=10.1073/pnas.89.5.1626;
RA   Chandler M.S.;
RT   "The gene encoding cAMP receptor protein is required for competence
RT   development in Haemophilus influenzae Rd.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:1626-1630(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX   PubMed=7542800; DOI=10.1126/science.7542800;
RA   Fleischmann R.D., Adams M.D., White O., Clayton R.A., Kirkness E.F.,
RA   Kerlavage A.R., Bult C.J., Tomb J.-F., Dougherty B.A., Merrick J.M.,
RA   McKenney K., Sutton G.G., FitzHugh W., Fields C.A., Gocayne J.D.,
RA   Scott J.D., Shirley R., Liu L.-I., Glodek A., Kelley J.M., Weidman J.F.,
RA   Phillips C.A., Spriggs T., Hedblom E., Cotton M.D., Utterback T.R.,
RA   Hanna M.C., Nguyen D.T., Saudek D.M., Brandon R.C., Fine L.D.,
RA   Fritchman J.L., Fuhrmann J.L., Geoghagen N.S.M., Gnehm C.L., McDonald L.A.,
RA   Small K.V., Fraser C.M., Smith H.O., Venter J.C.;
RT   "Whole-genome random sequencing and assembly of Haemophilus influenzae
RT   Rd.";
RL   Science 269:496-512(1995).
RN   [3]
RP   DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX   PubMed=8226661; DOI=10.1128/jb.175.22.7142-7149.1993;
RA   Dorocicz I.R., Williams P.M., Redfield R.J.;
RT   "The Haemophilus influenzae adenylate cyclase gene: cloning, sequence, and
RT   essential role in competence.";
RL   J. Bacteriol. 175:7142-7149(1993).
RN   [4]
RP   FUNCTION, REGULON, AND INDUCTION.
RC   STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX   PubMed=15769466; DOI=10.1016/j.jmb.2005.01.012;
RA   Redfield R.J., Cameron A.D., Qian Q., Hinds J., Ali T.R., Kroll J.S.,
RA   Langford P.R.;
RT   "A novel CRP-dependent regulon controls expression of competence genes in
RT   Haemophilus influenzae.";
RL   J. Mol. Biol. 347:735-747(2005).
RN   [5]
RP   DNA-BINDING.
RC   STRAIN=ATCC 51907 / DSM 11121 / KW20 / Rd;
RX   PubMed=18761017; DOI=10.1016/j.jmb.2008.08.027;
RA   Cameron A.D., Redfield R.J.;
RT   "CRP binding and transcription activation at CRP-S sites.";
RL   J. Mol. Biol. 383:313-323(2008).
CC   -!- FUNCTION: A global transcription regulator required for bacterial
CC       competence. Complexes with cyclic AMP (cAMP) which allosterically
CC       activates DNA binding (to consensus sequence 5'-AAATGTGATCTAGATCACATTT-
CC       3') to regulate transcription at 54 promoters (PubMed:15769466). There
CC       are 2 consensus subclasses; CRP-N (above) and CRP-S (T6 changed to C
CC       and A17 changed to G) which obligatorily also requires Sxy for
CC       expression. CRP-S sites bind DNA but do not activate transcription in
CC       the absence of Sxy. Probably induces a severe bend in DNA. Probably
CC       acts as a negative regulator of its own synthesis as well as for
CC       adenylate cyclase (cyaA), which generates cAMP.
CC       {ECO:0000269|PubMed:1542653, ECO:0000269|PubMed:15769466}.
CC   -!- SUBUNIT: Homodimer, which upon binding cAMP is able to bind DNA
CC       (Probable). Binds RNA polymerase subunit RpoA (By similarity).
CC       {ECO:0000250, ECO:0000305}.
CC   -!- INDUCTION: Constitutively expressed; slightly induced on shifting to
CC       starvation media. {ECO:0000269|PubMed:15769466}.
CC   -!- DOMAIN: The N-terminal domain binds cAMP and is responsible for
CC       homodimerization, while the C-terminal domain binds DNA when cAMP is
CC       bound. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Loss of competence, the ability to bind, take-up
CC       and integrate exogenous DNA. Loss of the ability to ferment ribose or
CC       xylose. {ECO:0000269|PubMed:1542653, ECO:0000269|PubMed:8226661}.
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DR   EMBL; M77207; AAA24952.1; -; Genomic_DNA.
DR   EMBL; L42023; AAC22618.1; -; Genomic_DNA.
DR   PIR; B38225; B38225.
DR   RefSeq; NP_439118.1; NC_000907.1.
DR   AlphaFoldDB; P29281; -.
DR   SMR; P29281; -.
DR   STRING; 71421.HI_0957; -.
DR   EnsemblBacteria; AAC22618; AAC22618; HI_0957.
DR   KEGG; hin:HI_0957; -.
DR   PATRIC; fig|71421.8.peg.999; -.
DR   eggNOG; COG0664; Bacteria.
DR   HOGENOM; CLU_075053_3_5_6; -.
DR   OrthoDB; 61906at2; -.
DR   PhylomeDB; P29281; -.
DR   BioCyc; HINF71421:G1GJ1-998-MONOMER; -.
DR   Proteomes; UP000000579; Chromosome.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR   GO; GO:0030420; P:establishment of competence for transformation; IEA:UniProtKB-KW.
DR   CDD; cd00038; CAP_ED; 1.
DR   CDD; cd00092; HTH_CRP; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR018488; cNMP-bd_CS.
DR   InterPro; IPR000595; cNMP-bd_dom.
DR   InterPro; IPR018490; cNMP-bd_dom_sf.
DR   InterPro; IPR012318; HTH_CRP.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   InterPro; IPR018335; Tscrpt_reg_HTH_Crp-type_CS.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   PANTHER; PTHR24567:SF79; CAMP-ACTIVATED GLOBAL TRANSCRIPTIONAL REGULATOR CRP; 1.
DR   PANTHER; PTHR24567; CRP FAMILY TRANSCRIPTIONAL REGULATORY PROTEIN; 1.
DR   Pfam; PF00027; cNMP_binding; 1.
DR   Pfam; PF13545; HTH_Crp_2; 1.
DR   PRINTS; PR00034; HTHCRP.
DR   SMART; SM00100; cNMP; 1.
DR   SMART; SM00419; HTH_CRP; 1.
DR   SUPFAM; SSF51206; cAMP-binding domain-like; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS00888; CNMP_BINDING_1; 1.
DR   PROSITE; PS00889; CNMP_BINDING_2; 1.
DR   PROSITE; PS50042; CNMP_BINDING_3; 1.
DR   PROSITE; PS00042; HTH_CRP_1; 1.
DR   PROSITE; PS51063; HTH_CRP_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Activator; cAMP; cAMP-binding; Competence; DNA-binding;
KW   Nucleotide-binding; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..224
FT                   /note="cAMP-activated global transcriptional regulator CRP"
FT                   /id="PRO_0000100147"
FT   DOMAIN          152..224
FT                   /note="HTH crp-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00387"
FT   DNA_BIND        194..200
FT                   /note="H-T-H motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00387"
FT   REGION          34..36
FT                   /note="Activating region 2 (AR2); probably contacts the N-
FT                   terminus of RpoA"
FT                   /evidence="ECO:0000250"
FT   REGION          67..73
FT                   /note="Activating region 3 (AR3); probably contacts sigma-
FT                   70 (RpoD)"
FT                   /evidence="ECO:0000250"
FT   REGION          168..177
FT                   /note="Activating region 1 (AR1); probably contacts the C-
FT                   terminus of RpoA"
FT                   /evidence="ECO:0000250"
FT   BINDING         71..77
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         86..88
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         97..98
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         142..143
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         150..151
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         185..195
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   SITE            111
FT                   /note="Activating region 2 (AR2); probably contacts the N-
FT                   terminus of RpoA"
FT                   /evidence="ECO:0000250"
FT   SITE            116
FT                   /note="Activating region 2 (AR2); probably contacts the N-
FT                   terminus of RpoA"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         115
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   224 AA;  25152 MW;  421B7790A48FF50C CRC64;
     MSNELTEIDE VVTSSQEEAT QRDPVLDWFL THCHLHKYPA KSTLIHAGED ATTLYYVIKG
     SVMVSSKDDE GKEMILTYLG AGQFFGEAGL FDEGSKRSAW VKTKTTCEIA EISYKKYRQL
     IQANPEILMF LTAQLARRLQ NTSRQVTNLA FLDVAGRIAQ TLMNLAKQPE AMTHPDGMQI
     KITRQEIGQM VGCSRETVGR IIKMLEDQNL IHAHGKTIVV YGAR
//