UniProt functional annotation for P35523



	UniProt functional annotation for P35523

UniProt code: P35523.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Voltage-gated chloride channel (PubMed:8112288, PubMed:9122265, PubMed:12456816). Plays an important role in membrane repolarization in skeletal muscle cells after muscle contraction. The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (Probable). The absence of conserved gating glutamate residues is typical for family members that function as channels (Probable). {ECO:0000269|PubMed:12456816, ECO:0000269|PubMed:22521272, ECO:0000269|PubMed:26007199, ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:7951242, ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:9122265, ECO:0000269|PubMed:9736777, ECO:0000305|PubMed:29809153}.

Catalytic activity: Reaction=2 chloride(in) + H(+)(out) = 2 chloride(out) + H(+)(in); Xref=Rhea:RHEA:29567, ChEBI:CHEBI:15378, ChEBI:CHEBI:17996; Evidence={ECO:0000303|PubMed:29809153};

Subunit: Homodimer. {ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:29809153, ECO:0000305|PubMed:8112288}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:12456816, ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:9122265}; Multi-pass membrane protein {ECO:0000269|PubMed:29809153}.

Tissue specificity: Predominantly expressed in skeletal muscles.

Disease: Myotonia congenita, autosomal dominant (MCAD) [MIM:160800]: A non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal dominant form (Thomsen disease) is less common and less severe than the autosomal recessive one (Becker disease). A milder form of autosomal dominant myotonia is characterized by isolated myotonia without muscle weakness, hypotrophy, or hypertrophy (myotonia levior). {ECO:0000269|PubMed:12661046, ECO:0000269|PubMed:26096614, ECO:0000269|PubMed:27653901, ECO:0000269|PubMed:27666773, ECO:0000269|PubMed:7581380, ECO:0000269|PubMed:7981750, ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:8533761, ECO:0000269|PubMed:8845168, ECO:0000269|PubMed:9122265, ECO:0000269|PubMed:9566422, ECO:0000269|PubMed:9736777}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Myotonia congenita, autosomal recessive (MCAR) [MIM:255700]: A non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal recessive form (Becker disease) is more severe than the autosomal dominant one (Thomsen disease). {ECO:0000269|PubMed:10215406, ECO:0000269|PubMed:10644771, ECO:0000269|PubMed:11113225, ECO:0000269|PubMed:12661046, ECO:0000269|PubMed:1379744, ECO:0000269|PubMed:19697366, ECO:0000269|PubMed:22521272, ECO:0000269|PubMed:22641783, ECO:0000269|PubMed:26007199, ECO:0000269|PubMed:26096614, ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:7874130, ECO:0000269|PubMed:7951242, ECO:0000269|PubMed:7981681, ECO:0000269|PubMed:8533761, ECO:0000269|PubMed:8571958, ECO:0000269|PubMed:8845168, ECO:0000269|PubMed:9566422, ECO:0000269|PubMed:9736777}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the chloride channel (TC 2.A.49) family. ClC- 1/CLCN1 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Voltage-gated chloride channel (PubMed:8112288, PubMed:9122265, PubMed:12456816). Plays an important role in membrane repolarization in skeletal muscle cells after muscle contraction. The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (Probable). The absence of conserved gating glutamate residues is typical for family members that function as channels (Probable). {ECO:0000269\|PubMed:12456816, ECO:0000269\|PubMed:22521272, ECO:0000269\|PubMed:26007199, ECO:0000269\|PubMed:26502825, ECO:0000269\|PubMed:26510092, ECO:0000269\|PubMed:7951242, ECO:0000269\|PubMed:8112288, ECO:0000269\|PubMed:9122265, ECO:0000269\|PubMed:9736777, ECO:0000305\|PubMed:29809153}.


Catalytic activity:		Reaction=2 chloride(in) + H(+)(out) = 2 chloride(out) + H(+)(in); Xref=Rhea:RHEA:29567, ChEBI:CHEBI:15378, ChEBI:CHEBI:17996; Evidence={ECO:0000303\|PubMed:29809153};
Subunit:		Homodimer. {ECO:0000269\|PubMed:26502825, ECO:0000269\|PubMed:29809153, ECO:0000305\|PubMed:8112288}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:12456816, ECO:0000269\|PubMed:26502825, ECO:0000269\|PubMed:8112288, ECO:0000269\|PubMed:9122265}; Multi-pass membrane protein {ECO:0000269\|PubMed:29809153}.
Tissue specificity:		Predominantly expressed in skeletal muscles.
Disease:		Myotonia congenita, autosomal dominant (MCAD) [MIM:160800]: A non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal dominant form (Thomsen disease) is less common and less severe than the autosomal recessive one (Becker disease). A milder form of autosomal dominant myotonia is characterized by isolated myotonia without muscle weakness, hypotrophy, or hypertrophy (myotonia levior). {ECO:0000269\|PubMed:12661046, ECO:0000269\|PubMed:26096614, ECO:0000269\|PubMed:27653901, ECO:0000269\|PubMed:27666773, ECO:0000269\|PubMed:7581380, ECO:0000269\|PubMed:7981750, ECO:0000269\|PubMed:8112288, ECO:0000269\|PubMed:8533761, ECO:0000269\|PubMed:8845168, ECO:0000269\|PubMed:9122265, ECO:0000269\|PubMed:9566422, ECO:0000269\|PubMed:9736777}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Myotonia congenita, autosomal recessive (MCAR) [MIM:255700]: A non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal recessive form (Becker disease) is more severe than the autosomal dominant one (Thomsen disease). {ECO:0000269\|PubMed:10215406, ECO:0000269\|PubMed:10644771, ECO:0000269\|PubMed:11113225, ECO:0000269\|PubMed:12661046, ECO:0000269\|PubMed:1379744, ECO:0000269\|PubMed:19697366, ECO:0000269\|PubMed:22521272, ECO:0000269\|PubMed:22641783, ECO:0000269\|PubMed:26007199, ECO:0000269\|PubMed:26096614, ECO:0000269\|PubMed:26502825, ECO:0000269\|PubMed:26510092, ECO:0000269\|PubMed:7874130, ECO:0000269\|PubMed:7951242, ECO:0000269\|PubMed:7981681, ECO:0000269\|PubMed:8533761, ECO:0000269\|PubMed:8571958, ECO:0000269\|PubMed:8845168, ECO:0000269\|PubMed:9566422, ECO:0000269\|PubMed:9736777}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the chloride channel (TC 2.A.49) family. ClC- 1/CLCN1 subfamily. {ECO:0000305}.