UniProt functional annotation for P0ACJ8



	UniProt functional annotation for P0ACJ8

UniProt codes: P0ACJ8, P03020.

Organism: Escherichia coli (strain K12).

Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.

Function: 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). {ECO:0000269|PubMed:10860739, ECO:0000269|PubMed:10860740, ECO:0000269|PubMed:15520470, ECO:0000269|PubMed:16260780, ECO:0000269|PubMed:16301522, ECO:0000269|PubMed:1646077, ECO:0000269|PubMed:2982847, ECO:0000269|PubMed:7966284, ECO:0000269|PubMed:8392187, ECO:0000269|PubMed:8978616}.

Activity regulation: 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. {ECO:0000269|PubMed:19359484, ECO:0000269|PubMed:19805344}.

Subunit: 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). {ECO:0000269|PubMed:11124031, ECO:0000269|PubMed:12202833, ECO:0000269|PubMed:1646077, ECO:0000269|PubMed:1653449, ECO:0000269|PubMed:19359484, ECO:0000269|PubMed:19805344, ECO:0000269|PubMed:19903881, ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:2839152, ECO:0000269|PubMed:6286624, ECO:0000269|PubMed:8757802, ECO:0000269|PubMed:8978616, ECO:0000269|PubMed:9096308, ECO:0000269|Ref.41}.

Induction: 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). {ECO:0000269|PubMed:1328816, ECO:0000269|PubMed:19019153, ECO:0000269|PubMed:6297782}.

Domain: The N-terminal domain binds cAMP and is responsible for homodimerization, while the C-terminal domain binds DNA when cAMP is bound. {ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:6286624}.

Disruption phenotype: Not essential (on rich medium), greatly increased levels of cAMP. Eliminates the NaCl sensitivity of an rnlA deletion mutant. {ECO:0000269|PubMed:15520470, ECO:0000269|PubMed:164435, ECO:0000269|PubMed:19019153}.

Miscellaneous: Binds 2 cAMP; cAMP 1 is in the anti conformation, while cAMP 2 is in the syn conformation. {ECO:0000305|PubMed:9096308}.

Annotations taken from UniProtKB at the EBI.


Organism:		Escherichia coli (strain K12).
Taxonomy:		Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.



Function:		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). {ECO:0000269\|PubMed:10860739, ECO:0000269\|PubMed:10860740, ECO:0000269\|PubMed:15520470, ECO:0000269\|PubMed:16260780, ECO:0000269\|PubMed:16301522, ECO:0000269\|PubMed:1646077, ECO:0000269\|PubMed:2982847, ECO:0000269\|PubMed:7966284, ECO:0000269\|PubMed:8392187, ECO:0000269\|PubMed:8978616}.


Activity regulation:		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. {ECO:0000269\|PubMed:19359484, ECO:0000269\|PubMed:19805344}.
Subunit:		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). {ECO:0000269\|PubMed:11124031, ECO:0000269\|PubMed:12202833, ECO:0000269\|PubMed:1646077, ECO:0000269\|PubMed:1653449, ECO:0000269\|PubMed:19359484, ECO:0000269\|PubMed:19805344, ECO:0000269\|PubMed:19903881, ECO:0000269\|PubMed:2828639, ECO:0000269\|PubMed:2839152, ECO:0000269\|PubMed:6286624, ECO:0000269\|PubMed:8757802, ECO:0000269\|PubMed:8978616, ECO:0000269\|PubMed:9096308, ECO:0000269\|Ref.41}.
Induction:		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). {ECO:0000269\|PubMed:1328816, ECO:0000269\|PubMed:19019153, ECO:0000269\|PubMed:6297782}.
Domain:		The N-terminal domain binds cAMP and is responsible for homodimerization, while the C-terminal domain binds DNA when cAMP is bound. {ECO:0000269\|PubMed:2828639, ECO:0000269\|PubMed:6286624}.
Disruption phenotype:		Not essential (on rich medium), greatly increased levels of cAMP. Eliminates the NaCl sensitivity of an rnlA deletion mutant. {ECO:0000269\|PubMed:15520470, ECO:0000269\|PubMed:164435, ECO:0000269\|PubMed:19019153}.
Miscellaneous:		Binds 2 cAMP; cAMP 1 is in the anti conformation, while cAMP 2 is in the syn conformation. {ECO:0000305\|PubMed:9096308}.