UniProtKB - P0ACJ8 (CRP_ECOLI)
Protein
cAMP-activated global transcriptional regulator CRP
Gene
crp
Organism
Escherichia coli (strain K12)
Status
Functioni
A global transcription regulator. Complexes with cyclic AMP (cAMP) which allosterically activates DNA binding (to consensus sequence 5'-AAATGTGATCTAGATCACATTT-3') to directly regulate the transcription of about 300 genes in about 200 operons and indirectly regulate the expression of about half the genome. There are 3 classes of CRP promoters; class I promoters have a single CRP-binding site upstream of the RNA polymerase (RNAP)-binding site, whereas in class II promoters the single CRP- and RNAP-binding site overlap, CRP making multiple contacts with RNAP. Class III promoters require multiple activator molecules, including at least one CRP dimer. It can act as an activator, repressor, coactivator or corepressor. Induces a severe bend in DNA (about 87 degrees), bringing upstream promoter elements into contact with RNAP. Acts as a negative regulator of its own synthesis as well as for adenylate cyclase (cyaA), which generates cAMP. High levels of active CRP are detrimental to growth (PubMed:16260780). Plays a major role in carbon catabolite repression (CCR). CCR involves cAMP, adenylate cyclase (cyaA), CRP and the EIIA-Glc component of the PTS (crr). In the presence of glucose EIIA-Glc is dephosphorylated, and does not activate adenylate cyclase, leading to reduced cAMP and thus decreased CRP activity. Also plays a role in many other processes (see PubMed:22573269).10 Publications
Miscellaneous
Binds 2 cAMP; cAMP 1 is in the anti conformation, while cAMP 2 is in the syn conformation.1 Publication
Activity regulationi
In the apo-form the DNA-binding helices form a rigid body in which their DNA recognitions helices are buried. cAMP binding causes a coil-to helix transition, stabilizing the active DNA binding conformation by reorienting and elongating these helices, which precludes a return to the inactive state.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 97 | Activating region 2 (AR2); probably contacts the N-terminus of RpoA | 1 | |
Sitei | 102 | Activating region 2 (AR2); probably contacts the N-terminus of RpoA | 1 | |
Binding sitei | 129 | cAMP6 Publications | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 57 – 63 | cAMP 16 Publications | 7 | |
Nucleotide bindingi | 72 – 74 | cAMP 16 Publications | 3 | |
Nucleotide bindingi | 83 – 84 | cAMP 16 Publications | 2 | |
Nucleotide bindingi | 128 – 129 | cAMP 16 Publications | 2 | |
Nucleotide bindingi | 136 – 137 | cAMP 26 Publications | 2 | |
Nucleotide bindingi | 171 – 181 | cAMP 26 PublicationsAdd BLAST | 11 | |
DNA bindingi | 180 – 186 | H-T-H motifPROSITE-ProRule annotation | 7 |
GO - Molecular functioni
- cAMP binding Source: UniProtKB-KW
- DNA binding, bending Source: UniProtKB
- DNA-binding transcription factor activity Source: GO_Central
- identical protein binding Source: IntAct
- minor groove of adenine-thymine-rich DNA binding Source: UniProtKB
- sequence-specific DNA binding Source: CollecTF
GO - Biological processi
- carbon catabolite repression of transcription Source: EcoCyc
- negative regulation of transcription, DNA-templated Source: EcoliWiki
- positive regulation of transcription, DNA-templated Source: EcoliWiki
- transcription, DNA-templated Source: EcoCyc
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Transcription, Transcription regulation |
Ligand | cAMP, cAMP-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | EcoCyc:PD00257 |
Names & Taxonomyi
Protein namesi | Recommended name: cAMP-activated global transcriptional regulator CRPAlternative name(s): Catabolite activator protein Short name: CAP Catabolite gene activator cAMP receptor protein Short name: CRP cAMP regulatory protein |
Gene namesi | Name:crp Synonyms:cap, csm Ordered Locus Names:b3357, JW5702 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
GO - Cellular componenti
- cytosol Source: EcoCyc
- protein-DNA complex Source: CollecTF
Pathology & Biotechi
Disruption phenotypei
Not essential (on rich medium), greatly increased levels of cAMP. Eliminates the NaCl sensitivity of an rnlA deletion mutant.3 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 20 | H → A, L or Y: Decreased transcription activation at class II promoters, decreased interaction with RNAP, binds DNA. 1 Publication | 1 | |
Mutagenesisi | 22 | H → A or L: Decreased transcription activation at class II promoters, decreased interaction with RNAP, binds DNA. 1 Publication | 1 | |
Mutagenesisi | 53 | K → N: Increased activation at class II promoters, increased interaction with RNAP. 1 Publication | 1 | |
Mutagenesisi | 54 – 56 | DEE → AAA: 80% reduction in activation of class II promoters; 95% loss when associated with A-59. 1 Publication | 3 | |
Mutagenesisi | 59 | E → A: 45% reduction in activation of class II promoters; 95% loss when associated with AAA-54-56. 2 Publications | 1 | |
Mutagenesisi | 59 | E → G or K: Reduction in activation of class II promoters. 2 Publications | 1 | |
Mutagenesisi | 63 | S → A: Enhanced cAMP-binding, enhanced transcription. 1 Publication | 1 | |
Mutagenesisi | 83 | R → L: Loss of cAMP-binding. 1 Publication | 1 | |
Mutagenesisi | 84 | S → A or K: No modification of cAMP-binding. 1 Publication | 1 | |
Mutagenesisi | 97 | E → A: Increased transcription activation at class II promoters, binds DNA. 1 Publication | 1 | |
Mutagenesisi | 102 | K → E: Disrupts AR2. No activation of class II promoters, decreased interaction with RNAP, binds DNA. 2 Publications | 1 | |
Mutagenesisi | 128 – 129 | TS → LI: Constitutively active at class I and II promoters in the absence of cAMP, binds DNA almost as well in the absence as in the presence of cAMP. Binds cAMP normally. 2 Publications | 2 | |
Mutagenesisi | 128 | T → A: No modification of cAMP-binding. 1 Publication | 1 | |
Mutagenesisi | 129 | S → A: Reduced DNA-binding; no modification of cAMP-binding. 2 Publications | 1 | |
Mutagenesisi | 139 | D → L: Some stabilization of an inactive (apo-) form. Decreased affinity for DNA, normal subunit association. 3 Publications | 1 | |
Mutagenesisi | 157 | A → D or P: Decreased transcription activation (6-29%), binds DNA. 2 Publications | 1 | |
Mutagenesisi | 159 | T → A, I, N, S or V: Decreased transcription activation (15-87%) at class I and II promoters, binds DNA. 3 Publications | 1 | |
Mutagenesisi | 160 | H → A, K, L, N, P, Q, R or Y: Disrupts AR1. Decreased transcription activation (3-45%) at class I and II promoters, binds DNA. 4 Publications | 1 | |
Mutagenesisi | 163 | G → A, C, D, R, S or V: Decreased transcription activation (2-62%) at class I and II promoters, binds DNA. 3 Publications | 1 | |
Mutagenesisi | 181 | R → K: Suppresses DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 181 | R → L: Suppresses DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 186 | R → K: No modification of DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 186 | R → L: Marginally reduced DNA-binding. 1 Publication | 1 |
Chemistry databases
DrugBanki | DB02527, Cyclic adenosine monophosphate |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000100144 | 2 – 210 | cAMP-activated global transcriptional regulator CRPAdd BLAST | 209 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 101 | N6-acetyllysine1 Publication | 1 |
Keywords - PTMi
AcetylationProteomic databases
jPOSTi | P0ACJ8 |
PaxDbi | P0ACJ8 |
PRIDEi | P0ACJ8 |
PTM databases
iPTMneti | P0ACJ8 |
Expressioni
Inductioni
Constitutively expressed, levels decrease in stationary phase; more strongly induced in an rnlA deletion mutant, levels remain high even in stationary phase (at protein level). Both positively (PubMed:1328816) and negatively autoregulated (PubMed:6297782).3 Publications
Gene expression databases
CollecTFi | EXPREG_00000850 |
Interactioni
Subunit structurei
Homodimer, which upon binding cAMP is able to bind DNA. AR1 of the upstream subunit binds to the C-terminus of RNAP subunit RpoA, AR2 of the downstream subunit binds to the N-terminus of RpoA while AR3 binds to sigma-70 (RpoD).
14 PublicationsBinary interactionsi
Hide detailsP0ACJ8
With | #Exp. | IntAct |
---|---|---|
itself | 5 | EBI-547513,EBI-547513 |
nusG [P0AFG0] | 2 | EBI-547513,EBI-369628 |
priC [P23862] | 2 | EBI-547513,EBI-1117383 |
rplL [P0A7K2] | 2 | EBI-547513,EBI-543702 |
yacL [P0A8E5] | 4 | EBI-547513,EBI-554965 |
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 4262928, 15 interactors 852178, 31 interactors |
DIPi | DIP-29232N |
IntActi | P0ACJ8, 42 interactors |
MINTi | P0ACJ8 |
STRINGi | 511145.b3357 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P0ACJ8 |
SMRi | P0ACJ8 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P0ACJ8 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 138 – 210 | HTH crp-typePROSITE-ProRule annotationAdd BLAST | 73 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 20 – 22 | Activating region 2 (AR2); probably contacts the N-terminus of RpoA | 3 | |
Regioni | 53 – 59 | Activating region 3 (AR3); probably contacts sigma-70 (RpoD) | 7 | |
Regioni | 154 – 163 | Activating region 1 (AR1); probably contacts the C-terminus of RpoA | 10 |
Domaini
The N-terminal domain binds cAMP and is responsible for homodimerization, while the C-terminal domain binds DNA when cAMP is bound.2 Publications
Phylogenomic databases
eggNOGi | COG0664, Bacteria |
HOGENOMi | CLU_075053_3_5_6 |
InParanoidi | P0ACJ8 |
PhylomeDBi | P0ACJ8 |
Family and domain databases
CDDi | cd00038, CAP_ED, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 2.60.120.10, 1 hit |
InterProi | View protein in InterPro IPR018490, cNMP-bd-like IPR018488, cNMP-bd_CS IPR000595, cNMP-bd_dom IPR012318, HTH_CRP IPR014710, RmlC-like_jellyroll IPR018335, Tscrpt_reg_HTH_Crp-type_CS IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
Pfami | View protein in Pfam PF00027, cNMP_binding, 1 hit PF13545, HTH_Crp_2, 1 hit |
PRINTSi | PR00034, HTHCRP |
SMARTi | View protein in SMART SM00100, cNMP, 1 hit SM00419, HTH_CRP, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF51206, SSF51206, 1 hit |
PROSITEi | View protein in PROSITE PS00888, CNMP_BINDING_1, 1 hit PS00889, CNMP_BINDING_2, 1 hit PS50042, CNMP_BINDING_3, 1 hit PS00042, HTH_CRP_1, 1 hit PS51063, HTH_CRP_2, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P0ACJ8-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MVLGKPQTDP TLEWFLSHCH IHKYPSKSTL IHQGEKAETL YYIVKGSVAV
60 70 80 90 100
LIKDEEGKEM ILSYLNQGDF IGELGLFEEG QERSAWVRAK TACEVAEISY
110 120 130 140 150
KKFRQLIQVN PDILMRLSAQ MARRLQVTSE KVGNLAFLDV TGRIAQTLLN
160 170 180 190 200
LAKQPDAMTH PDGMQIKITR QEIGQIVGCS RETVGRILKM LEDQNLISAH
210
GKTIVVYGTR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 29 | T → K in BAE77933 (PubMed:16738553).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J01598 Genomic DNA Translation: AAA23601.1 U18997 Genomic DNA Translation: AAA58154.1 U00096 Genomic DNA Translation: AAC76382.1 AP009048 Genomic DNA Translation: BAE77933.1 |
PIRi | A93416, QRECC |
RefSeqi | NP_417816.1, NC_000913.3 WP_000242755.1, NZ_STEB01000004.1 |
Genome annotation databases
EnsemblBacteriai | AAC76382; AAC76382; b3357 BAE77933; BAE77933; BAE77933 |
GeneIDi | 52075081 947867 |
KEGGi | ecj:JW5702 eco:b3357 |
PATRICi | fig|1411691.4.peg.3373 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J01598 Genomic DNA Translation: AAA23601.1 U18997 Genomic DNA Translation: AAA58154.1 U00096 Genomic DNA Translation: AAC76382.1 AP009048 Genomic DNA Translation: BAE77933.1 |
PIRi | A93416, QRECC |
RefSeqi | NP_417816.1, NC_000913.3 WP_000242755.1, NZ_STEB01000004.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1CGP | X-ray | 3.00 | A/B | 2-206 | [»] | |
1G6N | X-ray | 2.10 | A/B | 1-210 | [»] | |
1HW5 | X-ray | 1.82 | A/B | 1-210 | [»] | |
1I5Z | X-ray | 1.90 | A/B | 2-210 | [»] | |
1I6X | X-ray | 2.20 | A/B | 2-210 | [»] | |
1J59 | X-ray | 2.50 | A/B | 2-210 | [»] | |
1LB2 | X-ray | 3.10 | A | 2-210 | [»] | |
1O3Q | X-ray | 3.00 | A | 9-208 | [»] | |
1O3R | X-ray | 3.00 | A | 9-208 | [»] | |
1O3S | X-ray | 3.00 | A | 9-208 | [»] | |
1O3T | X-ray | 2.80 | A/B | 9-208 | [»] | |
1RUN | X-ray | 2.70 | A/B | 2-210 | [»] | |
1RUO | X-ray | 2.70 | A/B | 2-210 | [»] | |
1ZRC | X-ray | 2.80 | A/B | 2-210 | [»] | |
1ZRD | X-ray | 2.80 | A/B | 2-210 | [»] | |
1ZRE | X-ray | 2.80 | A/B | 2-210 | [»] | |
1ZRF | X-ray | 2.10 | A/B | 2-210 | [»] | |
2CGP | X-ray | 2.20 | A | 1-210 | [»] | |
2GAP | model | - | A/B | 2-209 | [»] | |
2GZW | X-ray | 2.21 | A/B/C/D | 2-210 | [»] | |
2WC2 | NMR | - | A/B | 2-210 | [»] | |
3FWE | X-ray | 2.30 | A/B | 1-210 | [»] | |
3HIF | X-ray | 3.59 | A/B/C/D/E/F | 1-210 | [»] | |
3IYD | electron microscopy | - | G/H | 2-210 | [»] | |
3KCC | X-ray | 1.66 | A/B | 1-210 | [»] | |
3N4M | X-ray | 2.99 | A | 2-210 | [»] | |
3QOP | X-ray | 1.96 | A/B | 1-210 | [»] | |
3RDI | X-ray | 2.95 | A/B | 1-210 | [»] | |
3ROU | X-ray | 2.10 | A/B | 1-210 | [»] | |
3RPQ | X-ray | 2.61 | A/B | 1-210 | [»] | |
3RYP | X-ray | 1.60 | A/B | 1-210 | [»] | |
3RYR | X-ray | 2.70 | A/B | 1-210 | [»] | |
4BH9 | NMR | - | A | 2-210 | [»] | |
4BHP | NMR | - | A | 2-210 | [»] | |
4FT8 | X-ray | 1.97 | A/B | 2-210 | [»] | |
4HZF | X-ray | 1.48 | A/B | 1-210 | [»] | |
4I01 | X-ray | 2.30 | A/B | 1-210 | [»] | |
4I02 | X-ray | 1.75 | A/B/C/D/E/F | 1-210 | [»] | |
4I09 | X-ray | 2.05 | A/B | 1-210 | [»] | |
4I0A | X-ray | 2.20 | A/B | 1-210 | [»] | |
4I0B | X-ray | 1.50 | A/B | 1-210 | [»] | |
4R8H | X-ray | 1.46 | A/B | 1-210 | [»] | |
5CIZ | X-ray | 5.01 | A | 2-210 | [»] | |
BMRBi | P0ACJ8 | |||||
SMRi | P0ACJ8 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4262928, 15 interactors 852178, 31 interactors |
DIPi | DIP-29232N |
IntActi | P0ACJ8, 42 interactors |
MINTi | P0ACJ8 |
STRINGi | 511145.b3357 |
Chemistry databases
DrugBanki | DB02527, Cyclic adenosine monophosphate |
PTM databases
iPTMneti | P0ACJ8 |
Proteomic databases
jPOSTi | P0ACJ8 |
PaxDbi | P0ACJ8 |
PRIDEi | P0ACJ8 |
Genome annotation databases
EnsemblBacteriai | AAC76382; AAC76382; b3357 BAE77933; BAE77933; BAE77933 |
GeneIDi | 52075081 947867 |
KEGGi | ecj:JW5702 eco:b3357 |
PATRICi | fig|1411691.4.peg.3373 |
Organism-specific databases
EchoBASEi | EB0162 |
Phylogenomic databases
eggNOGi | COG0664, Bacteria |
HOGENOMi | CLU_075053_3_5_6 |
InParanoidi | P0ACJ8 |
PhylomeDBi | P0ACJ8 |
Enzyme and pathway databases
BioCyci | EcoCyc:PD00257 |
Miscellaneous databases
EvolutionaryTracei | P0ACJ8 |
PROi | PR:P0ACJ8 |
Gene expression databases
CollecTFi | EXPREG_00000850 |
Family and domain databases
CDDi | cd00038, CAP_ED, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 2.60.120.10, 1 hit |
InterProi | View protein in InterPro IPR018490, cNMP-bd-like IPR018488, cNMP-bd_CS IPR000595, cNMP-bd_dom IPR012318, HTH_CRP IPR014710, RmlC-like_jellyroll IPR018335, Tscrpt_reg_HTH_Crp-type_CS IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
Pfami | View protein in Pfam PF00027, cNMP_binding, 1 hit PF13545, HTH_Crp_2, 1 hit |
PRINTSi | PR00034, HTHCRP |
SMARTi | View protein in SMART SM00100, cNMP, 1 hit SM00419, HTH_CRP, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF51206, SSF51206, 1 hit |
PROSITEi | View protein in PROSITE PS00888, CNMP_BINDING_1, 1 hit PS00889, CNMP_BINDING_2, 1 hit PS50042, CNMP_BINDING_3, 1 hit PS00042, HTH_CRP_1, 1 hit PS51063, HTH_CRP_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CRP_ECOLI | |
Accessioni | P0ACJ8Primary (citable) accession number: P0ACJ8 Secondary accession number(s): P03020, Q2M723 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | July 21, 1986 | |
Last modified: | December 2, 2020 | |
This is version 135 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references