UniProt functional annotation for Q8K4V4

UniProt code: Q8K4V4.

Organism: Rattus norvegicus (Rat).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.
 
Function: Involved in the retrograde transport from endosome to plasma membrane, a trafficking pathway that promotes the recycling of internalized transmembrane proteins. Following internalization, endocytosed transmembrane proteins are delivered to early endosomes and recycled to the plasma membrane instead of being degraded in lysosomes. SNX27 specifically binds and directs sorting of a subset of transmembrane proteins containing a PDZ-binding motif at the C- terminus: following interaction with target transmembrane proteins, associates with the retromer complex, preventing entry into the lysosomal pathway, and promotes retromer-tubule based plasma membrane recycling. SNX27 also binds with the WASH complex. Interacts with membranes containing phosphatidylinositol-3-phosphate (PtdIns(3P)). May participate in establishment of natural killer cell polarity. Recruits CYTIP to early endosomes. {ECO:0000269|PubMed:17828261, ECO:0000269|PubMed:18690037}.
 
Subunit: Core component of the SNX27-retromer, a multiprotein complex composed of SNX27, the WASH complex and the retromer complex. Interacts (via PDZ domain) with a number of target transmembrane proteins (via PDZ-binding motif): ABCC4, ADRB2, ARHGEF7, GRIA1, GRIA2, GRIN1, GRIN2A GRIN2C, KCNJ6, KCNJ9 and SLC2A1/GLUT1. Interacts (via the FERM-like regions) with the WASH complex. Interacts with SNX1. Interacts with CYTIP. Interacts with DGKZ. Interacts with MCC. {ECO:0000269|PubMed:17828261, ECO:0000269|PubMed:21422294}.
Subcellular location: Early endosome membrane; Peripheral membrane protein. Cytoplasm, cytosol. Note=Localizes to immunological synapse in T-cells. In T-cells, recruited from the cytosol to sorting endosomes by phosphoinositide-3-kinase products (By similarity). {ECO:0000250}.
Tissue specificity: Isoform 1 is predominantly expressed in the testis, whereas isoform 2 is predominant in various brain regions, including, neocortex, paleocortex, striatum, hippocampus, cerebellum and brain stem. Expressed in cells of hematopoietic origin. {ECO:0000269|PubMed:12740601, ECO:0000269|PubMed:17351151, ECO:0000269|PubMed:17828261, ECO:0000269|PubMed:21422294}.
Induction: [Isoform 2]: Up-regulated by methamphetamine and cocaine in the neocortex, but not by pentobarbital nor by D1 antagonist. {ECO:0000269|PubMed:12740601}.
Domain: The PDZ domain mediates binding to a subset of proteins containing a PDZ-binding motif at the C-terminus: the specificity for PDZ-binding motif is provided by the 2 residues located upstream of the canonical PDZ-binding motif (PubMed:17828261, PubMed:21422294). The PDZ domain also mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B). {ECO:0000269|PubMed:17828261, ECO:0000269|PubMed:21422294}.
Domain: The PX domain mediates binding to phosphatidylinositol 3- phosphate (PtdIns(3P)) and localization to early endosome membranes. {ECO:0000269|PubMed:17828261}.

Annotations taken from UniProtKB at the EBI.