UniProt functional annotation for P76129



	UniProt functional annotation for P76129

UniProt code: P76129.

Organism: Escherichia coli (strain K12).

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

Function: Heme-based oxygen sensor protein displaying phosphodiesterase (PDE) activity toward c-di-GMP in response to oxygen availability. Involved in the modulation of intracellular c-di-GMP levels, in association with DosC which catalyzes the biosynthesis of c-di-GMP (diguanylate cyclase activity). Cyclic-di-GMP is a second messenger which controls cell surface-associated traits in bacteria. Has very poor PDE activity on cAMP (PubMed:15995192) but is not active with cGMP, bis(p-nitrophenyl) phosphate or p-nitrophenyl phosphate (PubMed:11970957). Via its PDE activity on c-di-GMP, DosP regulates biofilm formation through the repression of transcription of the csgBAC operon, which encodes curli structural subunits. {ECO:0000269|PubMed:11970957, ECO:0000269|PubMed:15995192, ECO:0000269|PubMed:20553324}.

Catalytic activity: Reaction=cyclic di-3',5'-guanylate + H2O = 5'- phosphoguanylyl(3'->5')guanosine + H(+); Xref=Rhea:RHEA:24902, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58754, ChEBI:CHEBI:58805; EC=3.1.4.52; Evidence={ECO:0000269|PubMed:19764732};

Cofactor: Name=heme; Xref=ChEBI:CHEBI:30413;

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;

Activity regulation: Has c-di-GMP PDE activity in both Fe(2+) and Fe(3+)-bound forms; this activity is increased 6-7 fold by binding of O(2) and CO (PubMed:15995192) and NO (PubMed:17535805). Has cAMP PDE activity only when the heme is in the Fe(2+) form. cAMP PDE activity is inhibited by oxidation of the heme iron and by binding of external ligands such as CO and NO. Also strongly inhibited by etazolate hydrochloride, a selective cAMP PDE inhibitor. PDE activity is inhibited in the absence of oxygen. {ECO:0000269|PubMed:15995192, ECO:0000269|PubMed:17535805, ECO:0000269|PubMed:19764732}.

Biophysicochemical properties: Kinetic parameters: KM=36 uM for c-di-GMP; Note=For the EAL domain, residues 532-799. {ECO:0000269|PubMed:15995192};

Subunit: Homodimer (PubMed:19864414); has been previously suggested to be a homotetramer based on size exclusion chromatography (PubMed:11970957). Forms a complex with DosC. {ECO:0000269|PubMed:11970957, ECO:0000269|PubMed:15005609, ECO:0000269|PubMed:19864414}.

Induction: Expressed in the late exponential growth phase and at higher levels in the stationary phase. A member of the dosCP operon. Expression is RpoS dependent and is higher at 28 degrees Celsius than at 37 degrees Celsius. {ECO:0000269|PubMed:19332833, ECO:0000269|PubMed:20553324}.

Domain: The EAL domain (residues 532 to 799) is a cyclic dinucleotide di-GMP (c-di-GMP) PDE hydrolyzing c-di-GMP to 5'pGpG; it has no activity on cAMP. {ECO:0000269|PubMed:15995192}.

Domain: Binding of an external ligand to the heme located in the N- terminal sensory domain displaces the distal heme ligand from Met-87 to the ligand and triggers a conformational change that regulates the activity of the C-terminal catalytic domain.

Domain: The heme-PAS domain (residues 1-139) forms homodimers.

Ptm: The heme distal ligand is coordinated by Met-87 in the active Fe(2+) (ferrous) form, by O(2) in the O(2)-bound form and by H(2)O in the inactive Fe(3+) (ferric) form.

Miscellaneous: Binds O(2) with a dissociation constant of about 74 uM.

Annotations taken from UniProtKB at the EBI.


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



Function:		Heme-based oxygen sensor protein displaying phosphodiesterase (PDE) activity toward c-di-GMP in response to oxygen availability. Involved in the modulation of intracellular c-di-GMP levels, in association with DosC which catalyzes the biosynthesis of c-di-GMP (diguanylate cyclase activity). Cyclic-di-GMP is a second messenger which controls cell surface-associated traits in bacteria. Has very poor PDE activity on cAMP (PubMed:15995192) but is not active with cGMP, bis(p-nitrophenyl) phosphate or p-nitrophenyl phosphate (PubMed:11970957). Via its PDE activity on c-di-GMP, DosP regulates biofilm formation through the repression of transcription of the csgBAC operon, which encodes curli structural subunits. {ECO:0000269\|PubMed:11970957, ECO:0000269\|PubMed:15995192, ECO:0000269\|PubMed:20553324}.


Catalytic activity:		Reaction=cyclic di-3',5'-guanylate + H2O = 5'- phosphoguanylyl(3'->5')guanosine + H(+); Xref=Rhea:RHEA:24902, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58754, ChEBI:CHEBI:58805; EC=3.1.4.52; Evidence={ECO:0000269\|PubMed:19764732};
Cofactor:		Name=heme; Xref=ChEBI:CHEBI:30413;
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Activity regulation:		Has c-di-GMP PDE activity in both Fe(2+) and Fe(3+)-bound forms; this activity is increased 6-7 fold by binding of O(2) and CO (PubMed:15995192) and NO (PubMed:17535805). Has cAMP PDE activity only when the heme is in the Fe(2+) form. cAMP PDE activity is inhibited by oxidation of the heme iron and by binding of external ligands such as CO and NO. Also strongly inhibited by etazolate hydrochloride, a selective cAMP PDE inhibitor. PDE activity is inhibited in the absence of oxygen. {ECO:0000269\|PubMed:15995192, ECO:0000269\|PubMed:17535805, ECO:0000269\|PubMed:19764732}.
Biophysicochemical properties:		Kinetic parameters: KM=36 uM for c-di-GMP; Note=For the EAL domain, residues 532-799. {ECO:0000269\|PubMed:15995192};
Subunit:		Homodimer (PubMed:19864414); has been previously suggested to be a homotetramer based on size exclusion chromatography (PubMed:11970957). Forms a complex with DosC. {ECO:0000269\|PubMed:11970957, ECO:0000269\|PubMed:15005609, ECO:0000269\|PubMed:19864414}.
Induction:		Expressed in the late exponential growth phase and at higher levels in the stationary phase. A member of the dosCP operon. Expression is RpoS dependent and is higher at 28 degrees Celsius than at 37 degrees Celsius. {ECO:0000269\|PubMed:19332833, ECO:0000269\|PubMed:20553324}.
Domain:		The EAL domain (residues 532 to 799) is a cyclic dinucleotide di-GMP (c-di-GMP) PDE hydrolyzing c-di-GMP to 5'pGpG; it has no activity on cAMP. {ECO:0000269\|PubMed:15995192}.
Domain:		Binding of an external ligand to the heme located in the N- terminal sensory domain displaces the distal heme ligand from Met-87 to the ligand and triggers a conformational change that regulates the activity of the C-terminal catalytic domain.
Domain:		The heme-PAS domain (residues 1-139) forms homodimers.
Ptm:		The heme distal ligand is coordinated by Met-87 in the active Fe(2+) (ferrous) form, by O(2) in the O(2)-bound form and by H(2)O in the inactive Fe(3+) (ferric) form.
Miscellaneous:		Binds O(2) with a dissociation constant of about 74 uM.