UniProt functional annotation for Q9H1D0



	UniProt functional annotation for Q9H1D0

UniProt code: Q9H1D0.

Organism: Homo sapiens (Human).

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

Function: Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine (PubMed:11097838, PubMed:11278579, PubMed:11248124 PubMed:15184369, PubMed:23612980, PubMed:29258289). Important for normal Ca(2+) ion homeostasis in the body, including bone and skin (By similarity). The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification (PubMed:15184369). Inactivation includes both a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism; the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating. {ECO:0000250|UniProtKB:Q91WD2, ECO:0000269|PubMed:11097838, ECO:0000269|PubMed:11248124, ECO:0000269|PubMed:11278579, ECO:0000269|PubMed:15184369, ECO:0000269|PubMed:23612980, ECO:0000269|PubMed:29258289, ECO:0000269|PubMed:29861107}.

Subunit: Homotetramer (PubMed:29258289). Probably forms also heterotetramers with TRPV5. Interacts with TRPV5. Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane. Interacts with BSPRY (By similarity). Interacts with TCAF1 and TCAF2 isoform 2 (PubMed:25559186). Interacts with calmodulin (PubMed:11248124). {ECO:0000250|UniProtKB:Q91WD2, ECO:0000269|PubMed:11248124, ECO:0000269|PubMed:25559186, ECO:0000269|PubMed:29258289}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:11097838, ECO:0000269|PubMed:11248124, ECO:0000269|PubMed:11278579, ECO:0000269|PubMed:15184369, ECO:0000269|PubMed:23612980, ECO:0000269|PubMed:29258289, ECO:0000269|PubMed:29861107}; Multi-pass membrane protein {ECO:0000269|PubMed:29258289}.

Tissue specificity: Expressed at high levels in the gastrointestinal tract, including esophagus, stomach, duodenum, jejunum, ileum and colon, and in pancreas, placenta, prostate and salivary gland. Expressed at moderate levels in liver, kidney and testis. Expressed in trophoblasts of placenta villus trees (at protein level)(PubMed:23612980). Expressed in locally advanced prostate cancer, metastatic and androgen-insensitive prostatic lesions but not detected in healthy prostate tissue and benign prostatic hyperplasia. {ECO:0000269|PubMed:11097838, ECO:0000269|PubMed:11278579, ECO:0000269|PubMed:23612980}.

Ptm: Glycosylated. {ECO:0000250|UniProtKB:Q91WD2, ECO:0000269|PubMed:23612980}.

Ptm: Phosphorylation at Tyr-201 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at this site by PTPN1 (By similarity). Phosphorylation by PRKCA at the calmodulin binding site delays channel inactivation (PubMed:11248124). {ECO:0000250|UniProtKB:Q9R186, ECO:0000269|PubMed:11248124}.

Disease: Hyperparathyroidism, transient neonatal (HRPTTN) [MIM:618188]: An autosomal recessive disease characterized by impaired transplacental maternal-fetal transport of calcium, high serum PTH levels and signs of metabolic bone disease in the neonatal period. Skeletal anomalies include generalized osteopenia, narrow chest, short ribs with multiple healing fractures, and bowing or fractures of long bones. Affected individuals experience postnatal respiratory and feeding difficulties. The condition improves within a short time after birth once calcium is provided orally. {ECO:0000269|PubMed:29861107, ECO:0000269|PubMed:30820485}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV6 sub-subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAK50426.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980}; Sequence=AAL40230.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980}; Sequence=AAM00356.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980}; Sequence=AAO38052.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980}; Sequence=BAF84396.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980}; Sequence=CAC20416.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980}; Sequence=CAC20417.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980}; Sequence=CAD32311.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305|PubMed:23612980};

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:		Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine (PubMed:11097838, PubMed:11278579, PubMed:11248124 PubMed:15184369, PubMed:23612980, PubMed:29258289). Important for normal Ca(2+) ion homeostasis in the body, including bone and skin (By similarity). The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification (PubMed:15184369). Inactivation includes both a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism; the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating. {ECO:0000250\|UniProtKB:Q91WD2, ECO:0000269\|PubMed:11097838, ECO:0000269\|PubMed:11248124, ECO:0000269\|PubMed:11278579, ECO:0000269\|PubMed:15184369, ECO:0000269\|PubMed:23612980, ECO:0000269\|PubMed:29258289, ECO:0000269\|PubMed:29861107}.


Subunit:		Homotetramer (PubMed:29258289). Probably forms also heterotetramers with TRPV5. Interacts with TRPV5. Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane. Interacts with BSPRY (By similarity). Interacts with TCAF1 and TCAF2 isoform 2 (PubMed:25559186). Interacts with calmodulin (PubMed:11248124). {ECO:0000250\|UniProtKB:Q91WD2, ECO:0000269\|PubMed:11248124, ECO:0000269\|PubMed:25559186, ECO:0000269\|PubMed:29258289}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:11097838, ECO:0000269\|PubMed:11248124, ECO:0000269\|PubMed:11278579, ECO:0000269\|PubMed:15184369, ECO:0000269\|PubMed:23612980, ECO:0000269\|PubMed:29258289, ECO:0000269\|PubMed:29861107}; Multi-pass membrane protein {ECO:0000269\|PubMed:29258289}.
Tissue specificity:		Expressed at high levels in the gastrointestinal tract, including esophagus, stomach, duodenum, jejunum, ileum and colon, and in pancreas, placenta, prostate and salivary gland. Expressed at moderate levels in liver, kidney and testis. Expressed in trophoblasts of placenta villus trees (at protein level)(PubMed:23612980). Expressed in locally advanced prostate cancer, metastatic and androgen-insensitive prostatic lesions but not detected in healthy prostate tissue and benign prostatic hyperplasia. {ECO:0000269\|PubMed:11097838, ECO:0000269\|PubMed:11278579, ECO:0000269\|PubMed:23612980}.
Ptm:		Glycosylated. {ECO:0000250\|UniProtKB:Q91WD2, ECO:0000269\|PubMed:23612980}.
Ptm:		Phosphorylation at Tyr-201 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at this site by PTPN1 (By similarity). Phosphorylation by PRKCA at the calmodulin binding site delays channel inactivation (PubMed:11248124). {ECO:0000250\|UniProtKB:Q9R186, ECO:0000269\|PubMed:11248124}.
Disease:		Hyperparathyroidism, transient neonatal (HRPTTN) [MIM:618188]: An autosomal recessive disease characterized by impaired transplacental maternal-fetal transport of calcium, high serum PTH levels and signs of metabolic bone disease in the neonatal period. Skeletal anomalies include generalized osteopenia, narrow chest, short ribs with multiple healing fractures, and bowing or fractures of long bones. Affected individuals experience postnatal respiratory and feeding difficulties. The condition improves within a short time after birth once calcium is provided orally. {ECO:0000269\|PubMed:29861107, ECO:0000269\|PubMed:30820485}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV6 sub-subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAK50426.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305\|PubMed:23612980}; Sequence=AAL40230.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305\|PubMed:23612980}; Sequence=AAM00356.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305\|PubMed:23612980}; Sequence=AAO38052.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305\|PubMed:23612980}; Sequence=BAF84396.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305\|PubMed:23612980}; Sequence=CAC20416.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305\|PubMed:23612980}; Sequence=CAC20417.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305\|PubMed:23612980}; Sequence=CAD32311.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.; Evidence={ECO:0000305\|PubMed:23612980};