CLTRN
Domain
The cleavage site containing the double Phe-Phe motif acts as negative regulator of shedding by BACE2.
Function
Plays an important role in amino acid transport by acting as binding partner of amino acid transporters SLC6A18 and SLC6A19, regulating their trafficking on the cell surface and their amino acid transporter activity (By similarity). May also play a role in trafficking of amino acid transporters SLC3A1 and SLC7A9 to the renal cortical cell membrane (By similarity). Regulator of SNARE complex function (PubMed:16330323). Stimulator of beta cell replication (PubMed:16330323).
Involvement in disease
An interstitial deletion on chromosome Xp22.2 encompassing CLTRN and a deletion spanning CLTRN exons 1 to 3 have been found in two individuals with a neuropsychiatric disorder characterized by autistic features, anxiety, depression, compulsions, motor tics, and neutral aminoaciduria. Plasma amino acids were normal in both patients.
Post-translational modifications
Glycosylated. Glycosylation is required for plasma membrane localization and for its cleavage by BACE2.
Proteolytically processed in pancreatic beta cells by BACE2 leading to the generation and extracellular release of soluble CLTRN, and a corresponding cell-associated C-terminal fragment which is later cleaved by gamma-secretase. This shedding process inactivates CLTRN (By similarity). Three cleavage sites have been identified for BACE2, two clustered sites after Phe-116 and Leu-118 and a more membrane proximal site at Phe-125; the preferred BACE2 cleavage site seems to be between Phe-125 and Leu-126, Phe-116 and Leu-118 act as alternative sites (PubMed:21907142, PubMed:22628310).
Sequence Similarities
Belongs to the CLTRN family.
Tissue Specificity
Kidney; collecting ducts. Pancreas; beta cells of islets.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Localizes to the brush border membranes of cells in the proximal tubules of kidney (By similarity). Colocalizes with SLC6A19 in the early proximal S1 tubule (By similarity).
Alternative names
TMEM27, UNQ679/PRO1312, CLTRN, Collectrin, Transmembrane protein 27