UniProt functional annotation for Q5T2W1



	UniProt functional annotation for Q5T2W1

UniProt code: Q5T2W1.

Organism: Homo sapiens (Human).

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

Function: A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with SLC9A3R1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function (By similarity). {ECO:0000250}.

Subunit: Interacts with PDZK1IP1 and ABCC2. Interacts (via PDZ domains 1 and 3) with SCARB1 (C-terminal domain). Forms a heterodimeric complex with SLC9A3R1. Interacts with AKAP2, BCR, CFTR, SLC22A12, SLC22A4, SLC22A5, SLC9A3R2 and SLC17A1. Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain) directly with KLHL17; the interaction is important for integrity of actin cytoskeleton structures in neurons. Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus) (By similarity). Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain) (By similarity). Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain). {ECO:0000250, ECO:0000269|PubMed:10496535, ECO:0000269|PubMed:15494376, ECO:0000269|PubMed:15766278, ECO:0000269|PubMed:16141316, ECO:0000269|PubMed:9461128}.

Subcellular location: Membrane {ECO:0000250|UniProtKB:Q9JJ40}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9JJ40}. Cell membrane {ECO:0000250|UniProtKB:Q9JIL4}. Note=Associated with peripheral membranes. Localizes to the apical compartment of proximal tubular cells and to sinusoidal liver membranes. {ECO:0000250|UniProtKB:Q9JJ40}.

Tissue specificity: Expression is limited to epithelial cells. Expressed in the kidney (brush border of proximal tubule), pancreas, liver, and small intestine. Expressed at a lower level in the adrenal cortex, testis and stomach. Overexpressed in breast, renal and lung carcinomas. {ECO:0000269|PubMed:10496535, ECO:0000269|PubMed:11051556, ECO:0000269|PubMed:9461128}.

Domain: The PDZ 2 and 3 domains seem to be involved in the interaction with SLC26A3. {ECO:0000250}.

Domain: Interaction with the C-terminus of CFTR could be mediated through independent binding of PDZ 1, 3 and 4 domains. {ECO:0000250}.

Domain: The PDZ 1 and 3 domains seem to be involved in the interaction with SLCO1A1. {ECO:0000250}.

Domain: The PDZ 1 domain interacts with BCR.

Domain: The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1. {ECO:0000250}.

Similarity: Belongs to the NHER 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:		A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with SLC9A3R1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function (By similarity). {ECO:0000250}.


Subunit:		Interacts with PDZK1IP1 and ABCC2. Interacts (via PDZ domains 1 and 3) with SCARB1 (C-terminal domain). Forms a heterodimeric complex with SLC9A3R1. Interacts with AKAP2, BCR, CFTR, SLC22A12, SLC22A4, SLC22A5, SLC9A3R2 and SLC17A1. Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain) directly with KLHL17; the interaction is important for integrity of actin cytoskeleton structures in neurons. Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus) (By similarity). Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain) (By similarity). Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain). {ECO:0000250, ECO:0000269\|PubMed:10496535, ECO:0000269\|PubMed:15494376, ECO:0000269\|PubMed:15766278, ECO:0000269\|PubMed:16141316, ECO:0000269\|PubMed:9461128}.
Subcellular location:		Membrane {ECO:0000250\|UniProtKB:Q9JJ40}; Peripheral membrane protein {ECO:0000250\|UniProtKB:Q9JJ40}. Cell membrane {ECO:0000250\|UniProtKB:Q9JIL4}. Note=Associated with peripheral membranes. Localizes to the apical compartment of proximal tubular cells and to sinusoidal liver membranes. {ECO:0000250\|UniProtKB:Q9JJ40}.
Tissue specificity:		Expression is limited to epithelial cells. Expressed in the kidney (brush border of proximal tubule), pancreas, liver, and small intestine. Expressed at a lower level in the adrenal cortex, testis and stomach. Overexpressed in breast, renal and lung carcinomas. {ECO:0000269\|PubMed:10496535, ECO:0000269\|PubMed:11051556, ECO:0000269\|PubMed:9461128}.
Domain:		The PDZ 2 and 3 domains seem to be involved in the interaction with SLC26A3. {ECO:0000250}.
Domain:		Interaction with the C-terminus of CFTR could be mediated through independent binding of PDZ 1, 3 and 4 domains. {ECO:0000250}.
Domain:		The PDZ 1 and 3 domains seem to be involved in the interaction with SLCO1A1. {ECO:0000250}.
Domain:		The PDZ 1 domain interacts with BCR.
Domain:		The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1. {ECO:0000250}.
Similarity:		Belongs to the NHER family. {ECO:0000305}.