UniProt functional annotation for P19634



	UniProt functional annotation for P19634

UniProt code: P19634.

Organism: Homo sapiens (Human).

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

Function: Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. {ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:8901634}.

Biophysicochemical properties: pH dependence: Fully active at acidic pHs, the antiporter is virtually turned off at neutral pH.;

Subunit: Oligomer (By similarity). Interacts with CALM1 in a calcium- dependent manner (PubMed:12809501, PubMed:30287853). Interacts with TESC (PubMed:11696366, PubMed:30287853, PubMed:12809501). Interacts (via the juxtamembrane region of the cytoplasmic C-terminal domain) with CHP1; the interaction occurs at the plasma membrane in a calcium- dependent manner (PubMed:8967452, PubMed:8901634, PubMed:11350981, PubMed:15035633, PubMed:17050540). Interacts with CHP2; the interaction occurs in a calcium-dependent manner (PubMed:12226101, PubMed:16710297, PubMed:21392185). {ECO:0000250|UniProtKB:P26431, ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:11696366, ECO:0000269|PubMed:12226101, ECO:0000269|PubMed:12809501, ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:16710297, ECO:0000269|PubMed:17050540, ECO:0000269|PubMed:21392185, ECO:0000269|PubMed:30287853, ECO:0000269|PubMed:8901634, ECO:0000269|PubMed:8967452}.

Subcellular location: Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Cell membrane; Multi-pass membrane protein. Note=Colocalizes with CHP1 at the reticulum endoplasmic (By similarity). Colocalizes with CHP1 and CHP2 at the plasma membrane. {ECO:0000250}.

Tissue specificity: Kidney and intestine.

Ptm: O-glycosylated. {ECO:0000269|PubMed:8068684}.

Ptm: Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1 (By similarity). {ECO:0000250}.

Disease: Lichtenstein-Knorr syndrome (LIKNS) [MIM:616291]: An autosomal recessive neurologic disorder characterized by progressive cerebellar ataxia and severe progressive sensorineural hearing loss. {ECO:0000269|PubMed:25205112, ECO:0000269|PubMed:30237576}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: Inhibited by amiloride and 5-amino-substituted derivatives and activated in a cooperative fashion by intracellular H(+). In quiescent cells upon growth factor stimulation, the apparent affinity for internal H(+) is increased, resulting in a persistent rise in cytoplasmic pH.

Similarity: Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. {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:		Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. {ECO:0000269\|PubMed:11350981, ECO:0000269\|PubMed:15035633, ECO:0000269\|PubMed:8901634}.


Biophysicochemical properties:		pH dependence: Fully active at acidic pHs, the antiporter is virtually turned off at neutral pH.;
Subunit:		Oligomer (By similarity). Interacts with CALM1 in a calcium- dependent manner (PubMed:12809501, PubMed:30287853). Interacts with TESC (PubMed:11696366, PubMed:30287853, PubMed:12809501). Interacts (via the juxtamembrane region of the cytoplasmic C-terminal domain) with CHP1; the interaction occurs at the plasma membrane in a calcium- dependent manner (PubMed:8967452, PubMed:8901634, PubMed:11350981, PubMed:15035633, PubMed:17050540). Interacts with CHP2; the interaction occurs in a calcium-dependent manner (PubMed:12226101, PubMed:16710297, PubMed:21392185). {ECO:0000250\|UniProtKB:P26431, ECO:0000269\|PubMed:11350981, ECO:0000269\|PubMed:11696366, ECO:0000269\|PubMed:12226101, ECO:0000269\|PubMed:12809501, ECO:0000269\|PubMed:15035633, ECO:0000269\|PubMed:16710297, ECO:0000269\|PubMed:17050540, ECO:0000269\|PubMed:21392185, ECO:0000269\|PubMed:30287853, ECO:0000269\|PubMed:8901634, ECO:0000269\|PubMed:8967452}.
Subcellular location:		Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Cell membrane; Multi-pass membrane protein. Note=Colocalizes with CHP1 at the reticulum endoplasmic (By similarity). Colocalizes with CHP1 and CHP2 at the plasma membrane. {ECO:0000250}.
Tissue specificity:		Kidney and intestine.
Ptm:		O-glycosylated. {ECO:0000269\|PubMed:8068684}.
Ptm:		Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1 (By similarity). {ECO:0000250}.
Disease:		Lichtenstein-Knorr syndrome (LIKNS) [MIM:616291]: An autosomal recessive neurologic disorder characterized by progressive cerebellar ataxia and severe progressive sensorineural hearing loss. {ECO:0000269\|PubMed:25205112, ECO:0000269\|PubMed:30237576}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		Inhibited by amiloride and 5-amino-substituted derivatives and activated in a cooperative fashion by intracellular H(+). In quiescent cells upon growth factor stimulation, the apparent affinity for internal H(+) is increased, resulting in a persistent rise in cytoplasmic pH.
Similarity:		Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. {ECO:0000305}.