UniProt functional annotation for P63235



	UniProt functional annotation for P63235

UniProt code: P63235.

Organism: Escherichia coli (strain K12).

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

Function: Involved in glutaminase-dependent acid resistance (PubMed:8682809, PubMed:30498489). Exchanges extracellular glutamate (Glu) for intracellular gamma-aminobutyric acid (GABA) under acidic conditions (PubMed:22407317, PubMed:23589309). The protonation states of substrates are crucial for transport. Selectively transports Glu with no net charge and GABA with a positive charge (PubMed:23589309). Also efficiently transports glutamine and, to a smaller extent, methionine and leucine (PubMed:22407317). When the extracellular pH drops below 2.5, can import L-glutamine and export either glutamate or GABA (PubMed:30498489). The ability to survive the extremely acidic conditions of the stomach is essential for successful colonization of the host by commensal and pathogenic bacteria (PubMed:8682809, PubMed:30498489). {ECO:0000269|PubMed:22407317, ECO:0000269|PubMed:23589309, ECO:0000269|PubMed:30498489, ECO:0000269|PubMed:8682809, ECO:0000305|PubMed:30498489, ECO:0000305|PubMed:8682809}.

Catalytic activity: Reaction=4-aminobutanoate(in) + L-glutamate(out) = 4- aminobutanoate(out) + L-glutamate(in); Xref=Rhea:RHEA:28919, ChEBI:CHEBI:29985, ChEBI:CHEBI:59888; Evidence={ECO:0000269|PubMed:22407317, ECO:0000269|PubMed:23589309};

Activity regulation: Shows pH-dependent activity (PubMed:22407317, PubMed:23589309). The Glu/GABA transport activity is robust at pH 4.5 and rapidly decreases with increasing pH, with no detectable activity at pH 6.5 or above (PubMed:22407317, PubMed:23589309). The Glu analog L-trans-pyrrolidine-2,4-dicarboxylic acid (L-PDC) blocks the uptake of glutamate by selective inhibition (PubMed:12855178). {ECO:0000269|PubMed:12855178, ECO:0000269|PubMed:22407317, ECO:0000269|PubMed:23589309}.

Biophysicochemical properties: Kinetic parameters: KM=146.6 uM for L-glutamate (at pH 5) {ECO:0000269|PubMed:22407317}; KM=85.3 uM for L-glutamate (at pH 5.5) {ECO:0000269|PubMed:22407317}; KM=92 uM for L-glutamate (at pH 6) {ECO:0000269|PubMed:22407317}; KM=203.3 uM for L-glutamine (at pH 5.5) {ECO:0000269|PubMed:22407317}; KM=202.4 uM for GABA (at pH 5.5) {ECO:0000269|PubMed:22407317}; Vmax=666 nmol/min/mg enzyme with L-glutamate as substrate (at pH 5) {ECO:0000269|PubMed:22407317}; Vmax=112 nmol/min/mg enzyme with L-glutamate as substrate (at pH 5.5) {ECO:0000269|PubMed:22407317}; Vmax=14.8 nmol/min/mg enzyme with L-glutamate as substrate (at pH 6) {ECO:0000269|PubMed:22407317}; Vmax=280 nmol/min/mg enzyme with L-glutamine as substrate (at pH 5.5) {ECO:0000269|PubMed:22407317}; Vmax=88.4 nmol/min/mg enzyme with GABA as substrate (at pH 5.5) {ECO:0000269|PubMed:22407317}; pH dependence: Inactive at pH 6.5 or above. {ECO:0000269|PubMed:22407317};

Subunit: Monomer. {ECO:0000269|PubMed:22407317}.

Subcellular location: Cell inner membrane {ECO:0000269|PubMed:15919996, ECO:0000269|PubMed:22407317}; Multi-pass membrane protein {ECO:0000269|PubMed:22407317}.

Induction: By acidic conditions. Expression is regulated by a complex system involving RpoS, cAMP, CRP, EvgAS, H-NS, GadE, GadW and GadX. The level of involvement for each regulator varies depending upon the growth phase and the medium. {ECO:0000269|PubMed:10383761, ECO:0000269|PubMed:11976288, ECO:0000269|PubMed:12399493, ECO:0000269|PubMed:12694615, ECO:0000269|PubMed:12867478, ECO:0000269|PubMed:12940989}.

Domain: Contains a unique C-terminal C-plug that plays an important role in substrate transport. The C-plug forms a folded domain and completely blocks the path to the putative substrate-binding site. Under neutral or basic pH, the C-plug probably remains closed and prevents substrate transport (PubMed:22407317, PubMed:23589309). At acidic pH, the C-plug may be displaced, allowing influx of Glu and efflux of GABA (PubMed:23589309). {ECO:0000269|PubMed:22407317, ECO:0000269|PubMed:23589309}.

Disruption phenotype: Mutant shows a 10-fold decrease in resistance with glutamate. {ECO:0000269|PubMed:8682809}.

Similarity: Belongs to the amino acid-polyamine-organocation (APC) superfamily. Glutamate:GABA antiporter (GGA) (TC 2.A.3.7) 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 glutaminase-dependent acid resistance (PubMed:8682809, PubMed:30498489). Exchanges extracellular glutamate (Glu) for intracellular gamma-aminobutyric acid (GABA) under acidic conditions (PubMed:22407317, PubMed:23589309). The protonation states of substrates are crucial for transport. Selectively transports Glu with no net charge and GABA with a positive charge (PubMed:23589309). Also efficiently transports glutamine and, to a smaller extent, methionine and leucine (PubMed:22407317). When the extracellular pH drops below 2.5, can import L-glutamine and export either glutamate or GABA (PubMed:30498489). The ability to survive the extremely acidic conditions of the stomach is essential for successful colonization of the host by commensal and pathogenic bacteria (PubMed:8682809, PubMed:30498489). {ECO:0000269\|PubMed:22407317, ECO:0000269\|PubMed:23589309, ECO:0000269\|PubMed:30498489, ECO:0000269\|PubMed:8682809, ECO:0000305\|PubMed:30498489, ECO:0000305\|PubMed:8682809}.


Catalytic activity:		Reaction=4-aminobutanoate(in) + L-glutamate(out) = 4- aminobutanoate(out) + L-glutamate(in); Xref=Rhea:RHEA:28919, ChEBI:CHEBI:29985, ChEBI:CHEBI:59888; Evidence={ECO:0000269\|PubMed:22407317, ECO:0000269\|PubMed:23589309};
Activity regulation:		Shows pH-dependent activity (PubMed:22407317, PubMed:23589309). The Glu/GABA transport activity is robust at pH 4.5 and rapidly decreases with increasing pH, with no detectable activity at pH 6.5 or above (PubMed:22407317, PubMed:23589309). The Glu analog L-trans-pyrrolidine-2,4-dicarboxylic acid (L-PDC) blocks the uptake of glutamate by selective inhibition (PubMed:12855178). {ECO:0000269\|PubMed:12855178, ECO:0000269\|PubMed:22407317, ECO:0000269\|PubMed:23589309}.
Biophysicochemical properties:		Kinetic parameters: KM=146.6 uM for L-glutamate (at pH 5) {ECO:0000269\|PubMed:22407317}; KM=85.3 uM for L-glutamate (at pH 5.5) {ECO:0000269\|PubMed:22407317}; KM=92 uM for L-glutamate (at pH 6) {ECO:0000269\|PubMed:22407317}; KM=203.3 uM for L-glutamine (at pH 5.5) {ECO:0000269\|PubMed:22407317}; KM=202.4 uM for GABA (at pH 5.5) {ECO:0000269\|PubMed:22407317}; Vmax=666 nmol/min/mg enzyme with L-glutamate as substrate (at pH 5) {ECO:0000269\|PubMed:22407317}; Vmax=112 nmol/min/mg enzyme with L-glutamate as substrate (at pH 5.5) {ECO:0000269\|PubMed:22407317}; Vmax=14.8 nmol/min/mg enzyme with L-glutamate as substrate (at pH 6) {ECO:0000269\|PubMed:22407317}; Vmax=280 nmol/min/mg enzyme with L-glutamine as substrate (at pH 5.5) {ECO:0000269\|PubMed:22407317}; Vmax=88.4 nmol/min/mg enzyme with GABA as substrate (at pH 5.5) {ECO:0000269\|PubMed:22407317}; pH dependence: Inactive at pH 6.5 or above. {ECO:0000269\|PubMed:22407317};
Subunit:		Monomer. {ECO:0000269\|PubMed:22407317}.
Subcellular location:		Cell inner membrane {ECO:0000269\|PubMed:15919996, ECO:0000269\|PubMed:22407317}; Multi-pass membrane protein {ECO:0000269\|PubMed:22407317}.
Induction:		By acidic conditions. Expression is regulated by a complex system involving RpoS, cAMP, CRP, EvgAS, H-NS, GadE, GadW and GadX. The level of involvement for each regulator varies depending upon the growth phase and the medium. {ECO:0000269\|PubMed:10383761, ECO:0000269\|PubMed:11976288, ECO:0000269\|PubMed:12399493, ECO:0000269\|PubMed:12694615, ECO:0000269\|PubMed:12867478, ECO:0000269\|PubMed:12940989}.
Domain:		Contains a unique C-terminal C-plug that plays an important role in substrate transport. The C-plug forms a folded domain and completely blocks the path to the putative substrate-binding site. Under neutral or basic pH, the C-plug probably remains closed and prevents substrate transport (PubMed:22407317, PubMed:23589309). At acidic pH, the C-plug may be displaced, allowing influx of Glu and efflux of GABA (PubMed:23589309). {ECO:0000269\|PubMed:22407317, ECO:0000269\|PubMed:23589309}.
Disruption phenotype:		Mutant shows a 10-fold decrease in resistance with glutamate. {ECO:0000269\|PubMed:8682809}.
Similarity:		Belongs to the amino acid-polyamine-organocation (APC) superfamily. Glutamate:GABA antiporter (GGA) (TC 2.A.3.7) family. {ECO:0000305}.