UniProt functional annotation for P69681



	UniProt functional annotation for P69681

UniProt code: P69681.

Organism: Escherichia coli (strain K12).

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

Function: Involved in the uptake of ammonium/ammonia (NH(4)(+)/NH(3)) (PubMed:14668330, PubMed:15876187, PubMed:15563598, PubMed:15361618, PubMed:16910683, PubMed:30211659, PubMed:32662768). Transport is electrogenic (PubMed:30211659, PubMed:32662768). Following sequestration of NH(4)(+) at the periplasmic face, NH(4)(+) is deprotonated and neutral NH(3) is transported into the cytoplasm (PubMed:15876187, PubMed:16910683, PubMed:18362341, PubMed:19278252, PubMed:32662768). Neutral NH(3) and charged H(+) are carried separately across the membrane on a unique two-lane pathway, before recombining to NH(4)(+) inside the cell (PubMed:32662768). In vitro can also transport the larger analogs methylamine and methylammonium (PubMed:11847102, PubMed:14668330, PubMed:12023896, PubMed:15876187, PubMed:17998534, PubMed:18362341). Also acts as a sensor of the extracellular ammonium concentration (PubMed:14668330). {ECO:0000269|PubMed:11847102, ECO:0000269|PubMed:12023896, ECO:0000269|PubMed:14668330, ECO:0000269|PubMed:15361618, ECO:0000269|PubMed:15563598, ECO:0000269|PubMed:15876187, ECO:0000269|PubMed:16910683, ECO:0000269|PubMed:17998534, ECO:0000269|PubMed:18362341, ECO:0000269|PubMed:19278252, ECO:0000269|PubMed:30211659, ECO:0000269|PubMed:32662768}.

Activity regulation: In the presence of high extracellular ammonium concentrations, transport activity is inhibited by interaction with the regulatory protein GlnK (PubMed:11847102, PubMed:14668330, PubMed:16864585). Ammonium transport through AmtB is required for GlnK sequestration (PubMed:14668330). Formation of the GlnK-AmtB complex is influenced by intracellular pools of the effector molecules ATP, ADP, Mg(2+) and 2-oxoglutarate (PubMed:16864585, PubMed:20639578). The rapid drop in the 2-oxoglutarate pool upon ammonium influx and a simultaneous, but transient, change in the ATP/ADP ratio promotes AmtB- GlnK complex formation (PubMed:20639578). The GlnK-AmtB interaction is also controlled by the level of intracellular glutamine and the uridylylation status of GlnK (PubMed:14668330). Inhibited by imidazole and thallium, which likely act by competitive binding to the periplasmic ammonium binding site (PubMed:18362341). Transport activity is independent of the membrane potential and of ATP hydrolysis (PubMed:15876187). {ECO:0000269|PubMed:11847102, ECO:0000269|PubMed:14668330, ECO:0000269|PubMed:15876187, ECO:0000269|PubMed:16864585, ECO:0000269|PubMed:18362341, ECO:0000269|PubMed:20639578}.

Subunit: Homotrimer (PubMed:12023896, PubMed:15563598, PubMed:15361618, PubMed:17040913). In response to elevation of the extracellular ammonium concentration, interacts and forms a complex with GlnK (PubMed:10637624, PubMed:11847102, PubMed:14668330, PubMed:17220269, PubMed:17190799, PubMed:16864585, PubMed:20639578). Interacts with GlnK with a stoichiometry of AmtB(3):GlnK(3) (PubMed:17220269, PubMed:17190799). Sequestration of GlnK is reversible (PubMed:14668330). {ECO:0000269|PubMed:10637624, ECO:0000269|PubMed:11847102, ECO:0000269|PubMed:12023896, ECO:0000269|PubMed:14668330, ECO:0000269|PubMed:15361618, ECO:0000269|PubMed:15563598, ECO:0000269|PubMed:16864585, ECO:0000269|PubMed:17040913, ECO:0000269|PubMed:17190799, ECO:0000269|PubMed:17220269, ECO:0000269|PubMed:20639578}.

Subcellular location: Cell inner membrane {ECO:0000269|PubMed:11847102, ECO:0000269|PubMed:12023896, ECO:0000269|PubMed:15361618, ECO:0000269|PubMed:15563598, ECO:0000269|PubMed:17040913}; Multi-pass membrane protein {ECO:0000269|PubMed:15361618, ECO:0000269|PubMed:15563598, ECO:0000269|PubMed:17040913}.

Domain: The C-terminal cytoplasmic domain plays a significant role in normal function and it might also mediate co-operativity between the three subunits (PubMed:17453422). The C-terminal cytoplasmic domain is also required for interaction with the T-loop of GlnK (PubMed:11847102, PubMed:17190799). {ECO:0000269|PubMed:11847102, ECO:0000269|PubMed:17190799, ECO:0000269|PubMed:17453422}.

Miscellaneous: Specifically binds 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG), which increases protein stability (PubMed:24899312). POPG is an essential cofactor for transport activity and, in the absence of POPG, AmtB cannot complete the full translocation cycle (PubMed:30211659). Can also bind phosphatidylethanolamine and cardiolipin-like molecules, leading to positive allosteric modulation (PubMed:29507234). {ECO:0000269|PubMed:24899312, ECO:0000269|PubMed:29507234, ECO:0000269|PubMed:30211659}.

Similarity: Belongs to the ammonia transporter channel (TC 1.A.11.2) family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


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



Function:		Involved in the uptake of ammonium/ammonia (NH(4)(+)/NH(3)) (PubMed:14668330, PubMed:15876187, PubMed:15563598, PubMed:15361618, PubMed:16910683, PubMed:30211659, PubMed:32662768). Transport is electrogenic (PubMed:30211659, PubMed:32662768). Following sequestration of NH(4)(+) at the periplasmic face, NH(4)(+) is deprotonated and neutral NH(3) is transported into the cytoplasm (PubMed:15876187, PubMed:16910683, PubMed:18362341, PubMed:19278252, PubMed:32662768). Neutral NH(3) and charged H(+) are carried separately across the membrane on a unique two-lane pathway, before recombining to NH(4)(+) inside the cell (PubMed:32662768). In vitro can also transport the larger analogs methylamine and methylammonium (PubMed:11847102, PubMed:14668330, PubMed:12023896, PubMed:15876187, PubMed:17998534, PubMed:18362341). Also acts as a sensor of the extracellular ammonium concentration (PubMed:14668330). {ECO:0000269\|PubMed:11847102, ECO:0000269\|PubMed:12023896, ECO:0000269\|PubMed:14668330, ECO:0000269\|PubMed:15361618, ECO:0000269\|PubMed:15563598, ECO:0000269\|PubMed:15876187, ECO:0000269\|PubMed:16910683, ECO:0000269\|PubMed:17998534, ECO:0000269\|PubMed:18362341, ECO:0000269\|PubMed:19278252, ECO:0000269\|PubMed:30211659, ECO:0000269\|PubMed:32662768}.


Activity regulation:		In the presence of high extracellular ammonium concentrations, transport activity is inhibited by interaction with the regulatory protein GlnK (PubMed:11847102, PubMed:14668330, PubMed:16864585). Ammonium transport through AmtB is required for GlnK sequestration (PubMed:14668330). Formation of the GlnK-AmtB complex is influenced by intracellular pools of the effector molecules ATP, ADP, Mg(2+) and 2-oxoglutarate (PubMed:16864585, PubMed:20639578). The rapid drop in the 2-oxoglutarate pool upon ammonium influx and a simultaneous, but transient, change in the ATP/ADP ratio promotes AmtB- GlnK complex formation (PubMed:20639578). The GlnK-AmtB interaction is also controlled by the level of intracellular glutamine and the uridylylation status of GlnK (PubMed:14668330). Inhibited by imidazole and thallium, which likely act by competitive binding to the periplasmic ammonium binding site (PubMed:18362341). Transport activity is independent of the membrane potential and of ATP hydrolysis (PubMed:15876187). {ECO:0000269\|PubMed:11847102, ECO:0000269\|PubMed:14668330, ECO:0000269\|PubMed:15876187, ECO:0000269\|PubMed:16864585, ECO:0000269\|PubMed:18362341, ECO:0000269\|PubMed:20639578}.
Subunit:		Homotrimer (PubMed:12023896, PubMed:15563598, PubMed:15361618, PubMed:17040913). In response to elevation of the extracellular ammonium concentration, interacts and forms a complex with GlnK (PubMed:10637624, PubMed:11847102, PubMed:14668330, PubMed:17220269, PubMed:17190799, PubMed:16864585, PubMed:20639578). Interacts with GlnK with a stoichiometry of AmtB(3):GlnK(3) (PubMed:17220269, PubMed:17190799). Sequestration of GlnK is reversible (PubMed:14668330). {ECO:0000269\|PubMed:10637624, ECO:0000269\|PubMed:11847102, ECO:0000269\|PubMed:12023896, ECO:0000269\|PubMed:14668330, ECO:0000269\|PubMed:15361618, ECO:0000269\|PubMed:15563598, ECO:0000269\|PubMed:16864585, ECO:0000269\|PubMed:17040913, ECO:0000269\|PubMed:17190799, ECO:0000269\|PubMed:17220269, ECO:0000269\|PubMed:20639578}.
Subcellular location:		Cell inner membrane {ECO:0000269\|PubMed:11847102, ECO:0000269\|PubMed:12023896, ECO:0000269\|PubMed:15361618, ECO:0000269\|PubMed:15563598, ECO:0000269\|PubMed:17040913}; Multi-pass membrane protein {ECO:0000269\|PubMed:15361618, ECO:0000269\|PubMed:15563598, ECO:0000269\|PubMed:17040913}.
Domain:		The C-terminal cytoplasmic domain plays a significant role in normal function and it might also mediate co-operativity between the three subunits (PubMed:17453422). The C-terminal cytoplasmic domain is also required for interaction with the T-loop of GlnK (PubMed:11847102, PubMed:17190799). {ECO:0000269\|PubMed:11847102, ECO:0000269\|PubMed:17190799, ECO:0000269\|PubMed:17453422}.
Miscellaneous:		Specifically binds 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG), which increases protein stability (PubMed:24899312). POPG is an essential cofactor for transport activity and, in the absence of POPG, AmtB cannot complete the full translocation cycle (PubMed:30211659). Can also bind phosphatidylethanolamine and cardiolipin-like molecules, leading to positive allosteric modulation (PubMed:29507234). {ECO:0000269\|PubMed:24899312, ECO:0000269\|PubMed:29507234, ECO:0000269\|PubMed:30211659}.
Similarity:		Belongs to the ammonia transporter channel (TC 1.A.11.2) family. {ECO:0000305}.