Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

cAMP-activated global transcriptional regulator CRP

Gene

crp

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Enzyme 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 keyPosition(s)DescriptionActionsGraphical viewLength
Sitei97Activating region 2 (AR2); probably contacts the N-terminus of RpoA1
Sitei102Activating region 2 (AR2); probably contacts the N-terminus of RpoA1
Binding sitei129cAMP6 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi57 – 63cAMP 16 Publications7
Nucleotide bindingi72 – 74cAMP 16 Publications3
Nucleotide bindingi83 – 84cAMP 16 Publications2
Nucleotide bindingi128 – 129cAMP 16 Publications2
Nucleotide bindingi136 – 137cAMP 26 Publications2
Nucleotide bindingi171 – 181cAMP 26 PublicationsAdd BLAST11
DNA bindingi180 – 186H-T-H motifPROSITE-ProRule annotation7

GO - Molecular functioni

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
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

cAMP, cAMP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciEcoCyc:PD00257.
ECOL316407:JW5702-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-activated global transcriptional regulator CRP
Alternative 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
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10164. crp.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: EcoCyc
Complete GO annotation...

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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20H → A, L or Y: Decreased transcription activation at class II promoters, decreased interaction with RNAP, binds DNA. 1 Publication1
Mutagenesisi22H → A or L: Decreased transcription activation at class II promoters, decreased interaction with RNAP, binds DNA. 1 Publication1
Mutagenesisi53K → N: Increased activation at class II promoters, increased interaction with RNAP. 1 Publication1
Mutagenesisi54 – 56DEE → AAA: 80% reduction in activation of class II promoters; 95% loss when associated with A-59. 1 Publication3
Mutagenesisi59E → A: 45% reduction in activation of class II promoters; 95% loss when associated with AAA-54-56. 2 Publications1
Mutagenesisi59E → G or K: Reduction in activation of class II promoters. 2 Publications1
Mutagenesisi63S → A: Enhanced cAMP-binding, enhanced transcription. 1 Publication1
Mutagenesisi83R → L: Loss of cAMP-binding. 1 Publication1
Mutagenesisi84S → A or K: No modification of cAMP-binding. 1 Publication1
Mutagenesisi97E → A: Increased transcription activation at class II promoters, binds DNA. 1 Publication1
Mutagenesisi102K → E: Disrupts AR2. No activation of class II promoters, decreased interaction with RNAP, binds DNA. 2 Publications1
Mutagenesisi128 – 129TS → 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 Publications2
Mutagenesisi128T → A: No modification of cAMP-binding. 1 Publication1
Mutagenesisi129S → A: Reduced DNA-binding; no modification of cAMP-binding. 2 Publications1
Mutagenesisi139D → L: Some stabilization of an inactive (apo-) form. Decreased affinity for DNA, normal subunit association. 3 Publications1
Mutagenesisi157A → D or P: Decreased transcription activation (6-29%), binds DNA. 2 Publications1
Mutagenesisi159T → A, I, N, S or V: Decreased transcription activation (15-87%) at class I and II promoters, binds DNA. 3 Publications1
Mutagenesisi160H → 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 Publications1
Mutagenesisi163G → A, C, D, R, S or V: Decreased transcription activation (2-62%) at class I and II promoters, binds DNA. 3 Publications1
Mutagenesisi181R → K: Suppresses DNA-binding. 1 Publication1
Mutagenesisi181R → L: Suppresses DNA-binding. 1 Publication1
Mutagenesisi186R → K: No modification of DNA-binding. 1 Publication1
Mutagenesisi186R → L: Marginally reduced DNA-binding. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001001442 – 210cAMP-activated global transcriptional regulator CRPAdd BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei101N6-acetyllysine1 Publication1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP0ACJ8.
PaxDbiP0ACJ8.
PRIDEiP0ACJ8.

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

CollecTFiEXPREG_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 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
nusGP0AFG02EBI-547513,EBI-369628
priCP238622EBI-547513,EBI-1117383
yacLP0A8E53EBI-547513,EBI-554965

Protein-protein interaction databases

DIPiDIP-29232N.
IntActiP0ACJ8. 39 interactors.
MINTiMINT-1249660.
STRINGi511145.b3357.

Structurei

Secondary structure

1210
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 6Combined sources3
Helixi10 – 16Combined sources7
Beta strandi19 – 24Combined sources6
Beta strandi25 – 27Combined sources3
Beta strandi29 – 31Combined sources3
Beta strandi33 – 36Combined sources4
Beta strandi39 – 45Combined sources7
Beta strandi47 – 53Combined sources7
Beta strandi55 – 57Combined sources3
Beta strandi59 – 66Combined sources8
Beta strandi70 – 72Combined sources3
Helixi74 – 77Combined sources4
Beta strandi78 – 80Combined sources3
Beta strandi85 – 91Combined sources7
Beta strandi93 – 99Combined sources7
Helixi100 – 109Combined sources10
Helixi112 – 137Combined sources26
Helixi140 – 152Combined sources13
Beta strandi154 – 156Combined sources3
Beta strandi158 – 160Combined sources3
Beta strandi163 – 167Combined sources5
Helixi170 – 177Combined sources8
Helixi181 – 193Combined sources13
Beta strandi196 – 200Combined sources5
Beta strandi203 – 207Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CGPX-ray3.00A/B2-206[»]
1G6NX-ray2.10A/B1-210[»]
1HW5X-ray1.82A/B1-210[»]
1I5ZX-ray1.90A/B2-210[»]
1I6XX-ray2.20A/B2-210[»]
1J59X-ray2.50A/B2-210[»]
1LB2X-ray3.10A2-210[»]
1O3QX-ray3.00A9-208[»]
1O3RX-ray3.00A9-208[»]
1O3SX-ray3.00A9-208[»]
1O3TX-ray2.80A/B9-208[»]
1RUNX-ray2.70A/B2-210[»]
1RUOX-ray2.70A/B2-210[»]
1ZRCX-ray2.80A/B2-210[»]
1ZRDX-ray2.80A/B2-210[»]
1ZREX-ray2.80A/B2-210[»]
1ZRFX-ray2.10A/B2-210[»]
2CGPX-ray2.20A1-210[»]
2GAPmodel-A/B2-209[»]
2GZWX-ray2.21A/B/C/D2-210[»]
2WC2NMR-A/B2-210[»]
3FWEX-ray2.30A/B1-210[»]
3HIFX-ray3.59A/B/C/D/E/F1-210[»]
3IYDelectron microscopy-G/H2-210[»]
3KCCX-ray1.66A/B1-210[»]
3N4MX-ray2.99A2-210[»]
3QOPX-ray1.96A/B1-210[»]
3RDIX-ray2.95A/B1-210[»]
3ROUX-ray2.10A/B1-210[»]
3RPQX-ray2.61A/B1-210[»]
3RYPX-ray1.60A/B1-210[»]
3RYRX-ray2.70A/B1-210[»]
4BH9NMR-A2-210[»]
4BHPNMR-A2-210[»]
4FT8X-ray1.97A/B2-210[»]
4HZFX-ray1.48A/B1-210[»]
4I01X-ray2.30A/B1-210[»]
4I02X-ray1.75A/B/C/D/E/F1-210[»]
4I09X-ray2.05A/B1-210[»]
4I0AX-ray2.20A/B1-210[»]
4I0BX-ray1.50A/B1-210[»]
4R8HX-ray1.46A/B1-210[»]
5CIZX-ray5.01A2-210[»]
ProteinModelPortaliP0ACJ8.
SMRiP0ACJ8.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0ACJ8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini138 – 210HTH crp-typePROSITE-ProRule annotationAdd BLAST73

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni20 – 22Activating region 2 (AR2); probably contacts the N-terminus of RpoA3
Regioni53 – 59Activating region 3 (AR3); probably contacts sigma-70 (RpoD)7
Regioni154 – 163Activating region 1 (AR1); probably contacts the C-terminus of RpoA10

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

Sequence similaritiesi

Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation
Contains 1 HTH crp-type DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0664. LUCA.
HOGENOMiHOG000250565.
InParanoidiP0ACJ8.
KOiK10914.
OMAiKTMVVYG.
PhylomeDBiP0ACJ8.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.120.10. 1 hit.
InterProiIPR018490. 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.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00325. Crp. 1 hit.
[Graphical view]
PRINTSiPR00034. HTHCRP.
SMARTiSM00100. cNMP. 1 hit.
SM00419. HTH_CRP. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF51206. SSF51206. 1 hit.
PROSITEiPS00888. 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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P0ACJ8-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:210
Mass (Da):23,640
Last modified:July 21, 1986 - v1
Checksum:iDCBC24FA46C61B3D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti29T → K in BAE77933 (PubMed:16738553).Curated1

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.
PIRiA93416. QRECC.
RefSeqiNP_417816.1. NC_000913.3.
WP_000242755.1. NZ_CP014272.1.

Genome annotation databases

EnsemblBacteriaiAAC76382; AAC76382; b3357.
BAE77933; BAE77933; BAE77933.
GeneIDi947867.
KEGGiecj:JW5702.
eco:b3357.
PATRICi32122148. VBIEscCol129921_3451.

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.
PIRiA93416. QRECC.
RefSeqiNP_417816.1. NC_000913.3.
WP_000242755.1. NZ_CP014272.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CGPX-ray3.00A/B2-206[»]
1G6NX-ray2.10A/B1-210[»]
1HW5X-ray1.82A/B1-210[»]
1I5ZX-ray1.90A/B2-210[»]
1I6XX-ray2.20A/B2-210[»]
1J59X-ray2.50A/B2-210[»]
1LB2X-ray3.10A2-210[»]
1O3QX-ray3.00A9-208[»]
1O3RX-ray3.00A9-208[»]
1O3SX-ray3.00A9-208[»]
1O3TX-ray2.80A/B9-208[»]
1RUNX-ray2.70A/B2-210[»]
1RUOX-ray2.70A/B2-210[»]
1ZRCX-ray2.80A/B2-210[»]
1ZRDX-ray2.80A/B2-210[»]
1ZREX-ray2.80A/B2-210[»]
1ZRFX-ray2.10A/B2-210[»]
2CGPX-ray2.20A1-210[»]
2GAPmodel-A/B2-209[»]
2GZWX-ray2.21A/B/C/D2-210[»]
2WC2NMR-A/B2-210[»]
3FWEX-ray2.30A/B1-210[»]
3HIFX-ray3.59A/B/C/D/E/F1-210[»]
3IYDelectron microscopy-G/H2-210[»]
3KCCX-ray1.66A/B1-210[»]
3N4MX-ray2.99A2-210[»]
3QOPX-ray1.96A/B1-210[»]
3RDIX-ray2.95A/B1-210[»]
3ROUX-ray2.10A/B1-210[»]
3RPQX-ray2.61A/B1-210[»]
3RYPX-ray1.60A/B1-210[»]
3RYRX-ray2.70A/B1-210[»]
4BH9NMR-A2-210[»]
4BHPNMR-A2-210[»]
4FT8X-ray1.97A/B2-210[»]
4HZFX-ray1.48A/B1-210[»]
4I01X-ray2.30A/B1-210[»]
4I02X-ray1.75A/B/C/D/E/F1-210[»]
4I09X-ray2.05A/B1-210[»]
4I0AX-ray2.20A/B1-210[»]
4I0BX-ray1.50A/B1-210[»]
4R8HX-ray1.46A/B1-210[»]
5CIZX-ray5.01A2-210[»]
ProteinModelPortaliP0ACJ8.
SMRiP0ACJ8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-29232N.
IntActiP0ACJ8. 39 interactors.
MINTiMINT-1249660.
STRINGi511145.b3357.

Proteomic databases

EPDiP0ACJ8.
PaxDbiP0ACJ8.
PRIDEiP0ACJ8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC76382; AAC76382; b3357.
BAE77933; BAE77933; BAE77933.
GeneIDi947867.
KEGGiecj:JW5702.
eco:b3357.
PATRICi32122148. VBIEscCol129921_3451.

Organism-specific databases

EchoBASEiEB0162.
EcoGeneiEG10164. crp.

Phylogenomic databases

eggNOGiCOG0664. LUCA.
HOGENOMiHOG000250565.
InParanoidiP0ACJ8.
KOiK10914.
OMAiKTMVVYG.
PhylomeDBiP0ACJ8.

Enzyme and pathway databases

BioCyciEcoCyc:PD00257.
ECOL316407:JW5702-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP0ACJ8.
PROiP0ACJ8.

Gene expression databases

CollecTFiEXPREG_00000850.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.120.10. 1 hit.
InterProiIPR018490. 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.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00325. Crp. 1 hit.
[Graphical view]
PRINTSiPR00034. HTHCRP.
SMARTiSM00100. cNMP. 1 hit.
SM00419. HTH_CRP. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF51206. SSF51206. 1 hit.
PROSITEiPS00888. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCRP_ECOLI
AccessioniPrimary (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: November 2, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Binds 2 cAMP; cAMP 1 is in the anti conformation, while cAMP 2 is in the syn conformation.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.