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HAMAP rule MF_01128

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General rule information [?]

Accession MF_01128
Dates 22-APR-2003 (Created)
19-NOV-2022 (Last updated, Version 37)
Name CLC_ClcA
Template P37019 (CLCA_ECOLI)

Propagated annotation [?]

Identifier, protein and gene names [?]

Protein name
RecName: Full=H(+)/Cl(-) exchange transporter ClcA;
case <OC:Enterobacterales>
Gene name
clcA, eriC
Gene name
end case

Comments [?]

Function Proton-coupled chloride transporter. Functions as antiport system and exchanges two chloride ions for 1 proton. Probably acts as an electrical shunt for an outwardly-directed proton pump that is linked to amino acid decarboxylation, as part of the extreme acid resistance (XAR) response.
Catalytic activity RHEA:29567: 2 chloride(in) + H(+)(out) = 2 chloride(out) + H(+)(in)
Subunit Homodimer.
case not defined <Property:Membrane> or <Property:Membrane=1>
Subcellular location Cell membrane; Multi-pass membrane protein.
else case <Property:Membrane=2>
Subcellular location Cell inner membrane; Multi-pass membrane protein.
end case
Similarity Belongs to the chloride channel (TC 2.A.49) family. ClcA subfamily.

Keywords [?]

case defined <Property:Membrane> and <Property:Membrane=2>
end case

Gene Ontology [?]

GO:0015297; Molecular function: antiporter activity.
GO:0006821; Biological process: chloride transport.
GO:0005886; Cellular component: plasma membrane.

Cross-references [?]

Pfam PF00654; Voltage_CLC; 1;

Computed features [?]

case not defined <Property:Membrane> or <Property:Membrane=1>
General Transmembrane; -; 11; trigger=yes;
end case

Features [?]

case defined <Property:Membrane> and <Property:Membrane=2>
From: CLCA_ECOLI (P37019)
Key     From     To       Description   Tag   Condition   FTGroup
TOPO_DOM     Nter     32       Cytoplasmic        
TRANSMEM     33     69       Helical        
TOPO_DOM     70     76       Periplasmic        
TRANSMEM     77     100       Helical        
INTRAMEM     109     116       Helical        
TOPO_DOM     117     123       Cytoplasmic        
TRANSMEM     124     141       Helical        
TRANSMEM     148     166       Helical        
TOPO_DOM     167     176       Cytoplasmic        
INTRAMEM     177     189       Helical        
INTRAMEM     193     201       Helical        
TOPO_DOM     202     214       Cytoplasmic        
TRANSMEM     215     232       Helical        
TOPO_DOM     233     252       Periplasmic        
TRANSMEM     253     281       Helical        
TOPO_DOM     282     287       Cytoplasmic        
TRANSMEM     288     309       Helical        
TOPO_DOM     310     329       Periplasmic        
TRANSMEM     330     349       Helical        
TRANSMEM     355     376       Helical        
TOPO_DOM     377     386       Periplasmic        
INTRAMEM     387     401       Helical        
INTRAMEM     402     404       Note=Loop between two helices        
INTRAMEM     405     416       Helical        
INTRAMEM     417     421       Note=Loop between two helices        
TRANSMEM     422     438       Helical        
TOPO_DOM     439     Cter       Cytoplasmic        
MOTIF     106     110       Selectivity filter part_1        
MOTIF     146     150       Selectivity filter part_2        
MOTIF     355     359       Selectivity filter part_3        
end case
BINDING     107     107       /ligand="chloride" /ligand_id="ChEBI:CHEBI:17996     S  
BINDING     356     356       /ligand="chloride" /ligand_id="ChEBI:CHEBI:17996     I  
BINDING     357     357       /ligand="chloride" /ligand_id="ChEBI:CHEBI:17996     F  
BINDING     445     445       /ligand="chloride" /ligand_id="ChEBI:CHEBI:17996     Y  
SITE     148     148       Mediates proton transfer from the outer aqueous phase to the interior of the protein; involved in linking H(+) and Cl(-) transport     E  
SITE     203     203       Mediates proton transfer from the protein to the inner aqueous phase     E  

Additional information [?]

Size range 467-478 amino acids
Related rules None
Fusion None
Comments ClcA from E.coli was originally characterized as a voltage-gated chloride channel. It has now become clear that it is, in fact, a transporter. E.coli has at least one paralog, ClcB, and maybe YfeO, for which there is no electrophysiological characterization - they may or may not be transporters too. This family of proteins with high similarity to ClcA have, therefore, been considered as transporters as well. Further characterization is needed to distinguish ion channels from transporters, as it seems that the structural boundary separating channels and transporters is not as clear-cut as generally thought.