SORL1

Disease related genes, Plasma proteins, Potential drug targets, Transporters

Membrane, Secreted (different isoforms)

Cell type enhanced (Microglial cells, Cone photoreceptor cells, Excitatory neurons)

Immune cell enhanced (neutrophil)

Cell line enhanced (CAPAN-2, Daudi, OE19, RT4, U-698)

After maturation cleavage, interacts (via N-terminus) with its own propeptide; this interaction prevents interaction with other ligands, including CRLF1, GDNF, GFRA1, IL6 and IL6R (PubMed:11294867, PubMed:12530537, PubMed:15364913, PubMed:23333276, PubMed:24523320). Interacts (via N-terminal ectodomain) with APP, forming a 1:1 stoichiometric complex, including with isoforms APP695, APP751 and APP770; this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (PubMed:16174740, PubMed:16407538, PubMed:17855360, PubMed:24523320). Also interacts with APP C-terminal fragment C99 and with Abeta40 (PubMed:16407538). Interacts with beta-secretase BACE1/BACE; this interaction may affect BACE1-binding to APP and hence reduce BACE1-dependent APP cleavage (PubMed:16407538). Interacts with LRPAP1/RAP (PubMed:8940146, PubMed:11294867, PubMed:12530537, PubMed:15053742, PubMed:14764453, PubMed:15364913, PubMed:26858303). Interacts (via C-terminal cytosolic domain) with GGA1 and GGA2 (via N-terminal VHS domain) (PubMed:11821067, PubMed:17855360, PubMed:30679749, PubMed:20015111). Interacts with PACS1 (PubMed:17855360, PubMed:17646382). May interact (via the N-terminal ectodomain) with the morphogenetic neuropeptide, also called head activator or HA; this interaction is impaired in the presence of propeptide (PubMed:11082041, PubMed:11294867, PubMed:12530537). Interacts with neurotensin/NTS (PubMed:11294867). Interacts (via the N-terminal ectodomain) with PDGFB homodimer (PubMed:15053742, PubMed:16393139). Interacts (via N-terminal ectodomain) with the uPA receptor PLAUR; this interaction decreases PLAUR internalization (PubMed:14764453, PubMed:23486467). Interacts (via N-terminal ectodomain) with uPA/PLAU and PAI1/SERPINE1, either individually or in complex with each other, leading to endocytosis; this interaction is abolished in the presence of LRPAP1 (PubMed:15053742). Also interacts with the ternary complex composed of PLAUR-PLAU-PAI1 (PubMed:15053742). Also interacts with tPA/PLAT either alone or in complex with SERPINE1 (PubMed:15053742). Interacts (via C-terminus) with AP-1 and AP-2 complexes (PubMed:17646382). Interacts with BMPR1A and BMPR1B (By similarity). Interacts with lipoprotein lipase LPL; this interaction is optimal in slightly acidic conditions (PubMed:21385844). Interacts (via N-terminal ectodomain) with GDNF (via propeptide) and GDNF receptor alpha-1/GFRA1, either individually or in complex with each other (PubMed:15364913, PubMed:21994944, PubMed:23333276). The interaction with GDNF occurs mostly intracellularly (PubMed:21994944). Also interacts with other GDNF receptor alpha family members, including GFRA2, GFRA3 and GFRA4 (PubMed:23333276). Interacts with the insulin receptor INSR; this interaction strongly increases the surface exposure of INSR (PubMed:27322061). Interacts (via cytosolic C-terminus) with STK39/SPAK (PubMed:20385770). Interacts (via N-terminal ectodomain) with the heterodimeric complex CRLF1-CLC; within this complex, the interaction is mediated predominantly by the CRLF1 moiety (PubMed:26858303). Interacts with CNTFR, as well as with the tripartite signaling complex formed by CRLF1, CLC and CNTFR (PubMed:26858303). Interacts (via N-terminal ectodomain) with IL6; this interaction leads to IL6 internalization and lysosomal degradation (PubMed:28265003). Binding of SOLRL1 secreted N-terminal ectodomain to IL6 may increase IL6 trans signaling (PubMed:28265003). Interacts with secreted IL6R; this interaction leads to IL6R internalization (PubMed:28265003). Also interacts with transmembrane IL6R; this interaction does not affect IL6R subcellular location (PubMed:28265003). Interacts with APOE (PubMed:30448281). Interacts with apolipoprotein E-rich beta-VLDL (By similarity). Interacts with APOA5; this interaction leads to APOA5 internalization and is abolished by heparin (PubMed:17326667, PubMed:18603531). Interaction with APOA5 results in enhanced binding to chylomicrons (PubMed:17326667). Interacts with ROCK2 (PubMed:21147781). Interacts (via cytosolic C-terminus) with PPP3CB/calcineurin A beta (By similarity). Interacts with NTRK2/TRKB; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling (By similarity). Interacts (via cytosolic C-terminus) with HSPA12A in an ADP-dependent manner; this interaction affects SORL1 internalization and subcellular localization (PubMed:30679749). Interacts (via N-terminal ectodomain) with ERBB2/HER2 (PubMed:31138794).

Receptor