ID SORL_MOUSE Reviewed; 2215 AA. AC O88307; O54711; O70581; Q3UHM3; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 27-MAR-2024, entry version 199. DE RecName: Full=Sortilin-related receptor; DE AltName: Full=Gp250; DE AltName: Full=Low-density lipoprotein receptor relative with 11 ligand-binding repeats; DE Short=LDLR relative with 11 ligand-binding repeats; DE Short=LR11 {ECO:0000303|PubMed:9726247}; DE AltName: Full=SorLA-1; DE AltName: Full=Sorting protein-related receptor containing LDLR class A repeats; DE Short=mSorLA {ECO:0000303|PubMed:9510025}; DE Flags: Precursor; GN Name=Sorl1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RC TISSUE=Brain; RX PubMed=9726247; DOI=10.1089/dna.1998.17.647; RA Kanaki T., Bujo H., Hirayama S., Tanaka K., Yamazaki H., Seimiya K., RA Morisaki N., Schneider W.J., Saito Y.; RT "Developmental regulation of LR11 expression in murine brain."; RL DNA Cell Biol. 17:647-657(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 183-2215, TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RC TISSUE=Brain; RX PubMed=9510025; DOI=10.1016/s0925-4773(97)00177-9; RA Hermans-Borgmeyer I., Hampe W., Schinke B., Methner A., Nykjaer A., RA Suesens U., Fenger U., Herbarth B., Schaller H.C.; RT "Unique expression pattern of a novel mosaic receptor in the developing RT cerebral cortex."; RL Mech. Dev. 70:65-76(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1119-1713. RC STRAIN=Swiss Webster; RA Boehmelt G., Antonio L., Iscove N.N.; RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases. RN [5] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11082041; DOI=10.1242/jcs.113.24.4475; RA Hampe W., Riedel I.B., Lintzel J., Bader C.O., Franke I., Schaller H.C.; RT "Ectodomain shedding, translocation and synthesis of SorLA are stimulated RT by its ligand head activator."; RL J. Cell Sci. 113:4475-4485(2000). RN [6] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=14764453; DOI=10.1161/01.res.0000120862.79154.0f; RA Zhu Y., Bujo H., Yamazaki H., Ohwaki K., Jiang M., Hirayama S., Kanaki T., RA Shibasaki M., Takahashi K., Schneider W.J., Saito Y.; RT "LR11, an LDL receptor gene family member, is a novel regulator of smooth RT muscle cell migration."; RL Circ. Res. 94:752-758(2004). RN [7] RP DISRUPTION PHENOTYPE, INTERACTION WITH APP, AND TISSUE SPECIFICITY. RX PubMed=16174740; DOI=10.1073/pnas.0503689102; RA Andersen O.M., Reiche J., Schmidt V., Gotthardt M., Spoelgen R., Behlke J., RA von Arnim C.A., Breiderhoff T., Jansen P., Wu X., Bales K.R., Cappai R., RA Masters C.L., Gliemann J., Mufson E.J., Hyman B.T., Paul S.M., Nykjaer A., RA Willnow T.E.; RT "Neuronal sorting protein-related receptor sorLA/LR11 regulates processing RT of the amyloid precursor protein."; RL Proc. Natl. Acad. Sci. U.S.A. 102:13461-13466(2005). RN [8] RP INTERACTION WITH APP AND BACE1. RX PubMed=16407538; DOI=10.1523/jneurosci.3882-05.2006; RA Spoelgen R., von Arnim C.A., Thomas A.V., Peltan I.D., Koker M., Deng A., RA Irizarry M.C., Andersen O.M., Willnow T.E., Hyman B.T.; RT "Interaction of the cytosolic domains of sorLA/LR11 with the amyloid RT precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme."; RL J. Neurosci. 26:418-428(2006). RN [9] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=17332490; DOI=10.1161/atvbaha.106.137091; RA Ohwaki K., Bujo H., Jiang M., Yamazaki H., Schneider W.J., Saito Y.; RT "A secreted soluble form of LR11, specifically expressed in intimal smooth RT muscle cells, accelerates formation of lipid-laden macrophages."; RL Arterioscler. Thromb. Vasc. Biol. 27:1050-1056(2007). RN [10] RP INDUCTION BY BDNF. RX PubMed=20007471; DOI=10.1523/jneurosci.3960-09.2009; RA Rohe M., Synowitz M., Glass R., Paul S.M., Nykjaer A., Willnow T.E.; RT "Brain-derived neurotrophic factor reduces amyloidogenic processing through RT control of SORLA gene expression."; RL J. Neurosci. 29:15472-15478(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Kidney, Lung, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [12] RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE. RX PubMed=20385770; DOI=10.1128/mcb.01560-09; RA Reiche J., Theilig F., Rafiqi F.H., Carlo A.S., Militz D., Mutig K., RA Todiras M., Christensen E.I., Ellison D.H., Bader M., Nykjaer A., RA Bachmann S., Alessi D., Willnow T.E.; RT "SORLA/SORL1 functionally interacts with SPAK to control renal activation RT of Na(+)-K(+)-Cl(-) cotransporter 2."; RL Mol. Cell. Biol. 30:3027-3037(2010). RN [13] RP FUNCTION. RX PubMed=21994944; DOI=10.1074/jbc.m111.246413; RA Geng Z., Xu F.Y., Huang S.H., Chen Z.Y.; RT "Sorting protein-related receptor SorLA controls regulated secretion of RT glial cell line-derived neurotrophic factor."; RL J. Biol. Chem. 286:41871-41882(2011). RN [14] RP TISSUE SPECIFICITY. RX PubMed=21385844; DOI=10.1242/jcs.072538; RA Klinger S.C., Glerup S., Raarup M.K., Mari M.C., Nyegaard M., Koster G., RA Prabakaran T., Nilsson S.K., Kjaergaard M.M., Bakke O., Nykjaer A., RA Olivecrona G., Petersen C.M., Nielsen M.S.; RT "SorLA regulates the activity of lipoprotein lipase by intracellular RT trafficking."; RL J. Cell Sci. 124:1095-1105(2011). RN [15] RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=23333276; DOI=10.1016/j.celrep.2012.12.011; RA Glerup S., Lume M., Olsen D., Nyengaard J.R., Vaegter C.B., Gustafsen C., RA Christensen E.I., Kjolby M., Hay-Schmidt A., Bender D., Madsen P., RA Saarma M., Nykjaer A., Petersen C.M.; RT "SorLA controls neurotrophic activity by sorting of GDNF and its receptors RT GFRalpha1 and RET."; RL Cell Rep. 3:186-199(2013). RN [16] RP FUNCTION, AND INDUCTION BY HYPOXIA. RX PubMed=23486467; DOI=10.1074/jbc.m112.442491; RA Nishii K., Nakaseko C., Jiang M., Shimizu N., Takeuchi M., Schneider W.J., RA Bujo H.; RT "The soluble form of LR11 protein is a regulator of hypoxia-induced, RT urokinase-type plasminogen activator receptor (uPAR)-mediated adhesion of RT immature hematological cells."; RL J. Biol. Chem. 288:11877-11886(2013). RN [17] RP FUNCTION, INTERACTION WITH NTRK2, AND TISSUE SPECIFICITY. RX PubMed=23977241; DOI=10.1371/journal.pone.0072164; RA Rohe M., Hartl D., Fjorback A.N., Klose J., Willnow T.E.; RT "SORLA-mediated trafficking of TrkB enhances the response of neurons to RT BDNF."; RL PLoS ONE 8:E72164-E72164(2013). RN [18] RP FUNCTION, INTERACTION WITH BMPR1A AND BMPR1B, SUBCELLULAR LOCATION, RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INDUCTION BY TEMPERATURE AND RP ENERGY AVAILABILITY. RX PubMed=26584636; DOI=10.1038/ncomms9951; RA Whittle A.J., Jiang M., Peirce V., Relat J., Virtue S., Ebinuma H., RA Fukamachi I., Yamaguchi T., Takahashi M., Murano T., Tatsuno I., RA Takeuchi M., Nakaseko C., Jin W., Jin Z., Campbell M., Schneider W.J., RA Vidal-Puig A., Bujo H.; RT "Soluble LR11/SorLA represses thermogenesis in adipose tissue and RT correlates with BMI in humans."; RL Nat. Commun. 6:8951-8951(2015). RN [19] RP FUNCTION, INTERACTION WITH PPP3CB, TISSUE SPECIFICITY, AND DISRUPTION RP PHENOTYPE. RX PubMed=25967121; DOI=10.1681/asn.2014070728; RA Borschewski A., Himmerkus N., Boldt C., Blankenstein K.I., McCormick J.A., RA Lazelle R., Willnow T.E., Jankowski V., Plain A., Bleich M., Ellison D.H., RA Bachmann S., Mutig K.; RT "Calcineurin and sorting-related receptor with A-type repeats interact to RT regulate the renal Na(+)-K(+)-2Cl(-) cotransporter."; RL J. Am. Soc. Nephrol. 27:107-119(2016). RN [20] RP FUNCTION, INTERACTION WITH INSR, INDUCTION BY INSULIN, DISRUPTION RP PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=27322061; DOI=10.1172/jci84708; RA Schmidt V., Schulz N., Yan X., Schuermann A., Kempa S., Kern M., RA Blueher M., Poy M.N., Olivecrona G., Willnow T.E.; RT "SORLA facilitates insulin receptor signaling in adipocytes and exacerbates RT obesity."; RL J. Clin. Invest. 126:2706-2720(2016). RN [21] RP FUNCTION. RX PubMed=26858303; DOI=10.1128/mcb.00917-15; RA Larsen J.V., Kristensen A.M., Pallesen L.T., Bauer J., Vaegter C.B., RA Nielsen M.S., Madsen P., Petersen C.M.; RT "Cytokine-like factor 1, an essential facilitator of cardiotrophin-like RT cytokine:ciliary neurotrophic factor receptor alpha signaling and sorLA- RT mediated turnover."; RL Mol. Cell. Biol. 36:1272-1286(2016). RN [22] RP FUNCTION, AND INTERACTION WITH IL6 AND IL6R. RX PubMed=28265003; DOI=10.1128/mcb.00641-16; RA Larsen J.V., Petersen C.M.; RT "SorLA in Interleukin-6 Signaling and Turnover."; RL Mol. Cell. Biol. 37:0-0(2017). RN [23] RP TISSUE SPECIFICITY. RX PubMed=30679749; DOI=10.1038/s41598-018-37336-6; RA Madsen P., Isaksen T.J., Siupka P., Toth A.E., Nyegaard M., Gustafsen C., RA Nielsen M.S.; RT "HSPA12A targets the cytoplasmic domain and affects the trafficking of the RT Amyloid Precursor Protein receptor SorLA."; RL Sci. Rep. 9:611-611(2019). CC -!- FUNCTION: Sorting receptor that directs several proteins to their CC correct location within the cell. Along with AP-1 complex, involved CC Golgi apparatus - endosome sorting. Sorting receptor for APP, CC regulating its intracellular trafficking and processing into CC amyloidogenic-beta peptides. Retains APP in the trans-Golgi network, CC hence preventing its transit through late endosomes where amyloid beta CC peptides Abeta40 and Abeta42 are generated. May also sort newly CC produced amyloid-beta peptides to lysosomes for catabolism. Does not CC affect APP trafficking from the endoplasmic reticulum to Golgi CC compartments (By similarity). Sorting receptor for the BDNF receptor CC NTRK2/TRKB that facilitates NTRK2 trafficking between synaptic plasma CC membranes, postsynaptic densities and cell soma, hence positively CC regulates BDNF signaling by controlling the intracellular location of CC its receptor (PubMed:23977241). Sorting receptor for GDNF that promotes CC GDNF regulated, but not constitutive secretion (PubMed:21994944). CC Sorting receptor for the GDNF-GFRA1 complex, directing it from the cell CC surface to endosomes. GDNF is then targeted to lysosomes and degraded, CC while its receptor GFRA1 recycles back to the cell membrane, resulting CC in a GDNF clearance pathway. The SORL1-GFRA1 complex further targets CC RET for endocytosis, but not for degradation, affecting GDNF-induced CC neurotrophic activities (PubMed:23333276). Sorting receptor for CC ERBB2/HER2. Regulates ERBB2 subcellular distribution by promoting its CC recycling after internalization from endosomes back to the plasma CC membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent CC ERBB2 signaling (By similarity). Sorting receptor for lipoprotein CC lipase LPL. Promotes LPL localization to endosomes and later to the CC lysosomes, leading to degradation of newly synthesized LPL (By CC similarity). Potential sorting receptor for APOA5, inducing APOA5 CC internalization to early endosomes, then to late endosomes, wherefrom a CC portion is sent to lysosomes and degradation, another portion is sorted CC to the trans-Golgi network (By similarity). Sorting receptor for the CC insulin receptor INSR. Promotes recycling of internalized INSR via the CC Golgi apparatus back to the cell surface, thereby preventing lysosomal CC INSR catabolism, increasing INSR cell surface expression and CC strengthening insulin signal reception in adipose tissue. Does not CC affect INSR internalization (PubMed:27322061). Plays a role in renal CC ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by CC STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly CC through intracellular sorting of STK39 and PPP3CB (PubMed:20385770, CC PubMed:25967121). Stimulates, via the N-terminal ectodomain, the CC proliferation and migration of smooth muscle cells, possibly by CC increasing cell surface expression of the urokinase receptor CC uPAR/PLAUR. This may promote extracellular matrix proteolysis and hence CC facilitate cell migration (By similarity). By acting on the migration CC of intimal smooth muscle cells, may accelerate intimal thickening CC following vascular injury (PubMed:14764453). Promotes adhesion of CC monocytes (By similarity). Stimulates proliferation and migration of CC monocytes/macrophages. Through its action on intimal smooth muscle CC cells and macrophages, may accelerate intimal thickening and macrophage CC foam cell formation in the process of atherosclerosis CC (PubMed:17332490). Regulates hypoxia-enhanced adhesion of hematopoietic CC stem and progenitor cells to the bone marrow stromal cells via a PLAUR- CC mediated pathway. This function is mediated by the N-terminal CC ectodomain (PubMed:23486467). Metabolic regulator, which functions to CC maintain the adequate balance between lipid storage and oxidation in CC response to changing environmental conditions, such as temperature and CC diet. The N-terminal ectodomain negatively regulates adipose tissue CC energy expenditure, acting through the inhibition the BMP/Smad pathway CC (PubMed:26584636). May regulate signaling by the heterodimeric CC neurotrophic cytokine CLCF1-CRLF1 bound to the CNTFR receptor by CC promoting the endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR CC and lysosomal degradation (PubMed:26858303). May regulate IL6 CC signaling, decreasing cis signaling, possibly by interfering with IL6- CC binding to membrane-bound IL6R, while up-regulating trans signaling via CC soluble IL6R (PubMed:28265003). {ECO:0000250|UniProtKB:Q92673, CC ECO:0000269|PubMed:14764453, ECO:0000269|PubMed:17332490, CC ECO:0000269|PubMed:20385770, ECO:0000269|PubMed:21994944, CC ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:23486467, CC ECO:0000269|PubMed:23977241, ECO:0000269|PubMed:25967121, CC ECO:0000269|PubMed:26584636, ECO:0000269|PubMed:26858303, CC ECO:0000269|PubMed:27322061, ECO:0000269|PubMed:28265003}. CC -!- SUBUNIT: After maturation cleavage, interacts (via N-terminus) with its CC own propeptide; this interaction prevents interaction with other CC ligands, including CRLF1, GDNF, GFRA1, IL6 and IL6R (By similarity). CC Interacts (via N-terminal ectodomain) with APP, forming a 1:1 CC stoichiometric complex, including with isoforms APP695, APP751 and CC APP770; this interaction retains APP in the trans-Golgi network and CC reduces processing into soluble APP-alpha and amyloid-beta peptides CC (PubMed:16174740, PubMed:16407538). Also interacts with APP C-terminal CC fragment C99 and with Abeta40 (By similarity). Interacts with beta- CC secretase BACE1/BACE; this interaction may affect BACE1-binding to APP CC and hence reduce BACE1-dependent APP cleavage (PubMed:16407538). CC Interacts with LRPAP1/RAP (By similarity). Interacts (via C-terminal CC cytosolic domain) with GGA1 and GGA2 (via N-terminal VHS domain) (By CC similarity). Interacts with PACS1 (By similarity). May interact (via CC the N-terminal ectodomain) with the morphogenetic neuropeptide, also CC called head activator or HA; this interaction is impaired in the CC presence of propeptide (By similarity). Interacts with neurotensin/NTS CC (By similarity). Interacts (via the N-terminal ectodomain) with PDGFB CC homodimer (By similarity). Interacts (via N-terminal ectodomain) with CC the uPA receptor PLAUR (By similarity). Interacts with uPA/PLAU and CC PAI1/SERPINE1, either individually or in complex with each other, CC leading to endocytosis (By similarity). Also interacts with CC PAI1/SERPINE1 in complex with tPA/PLAT. Interacts (via C-terminus) with CC AP-1 and AP-2 complexes (By similarity). Interacts with BMPR1A and CC BMPR1B (PubMed:26584636). Interacts with lipoprotein lipase LPL; this CC interaction is optimal in slightly acidic conditions (By similarity). CC Interacts (via N-terminal ectodomain) with GDNF (via propeptide) and CC GDNF receptor alpha-1/GFRA1, either individually or in complex with CC each other (By similarity). The interaction with GDNF occurs mostly CC intracellularly (By similarity). Also interacts with other GDNF CC receptor alpha family members, including GFRA2, GFRA3 and GFRA4 (By CC similarity). Interacts with the insulin receptor INSR; this interaction CC strongly increases the surface exposure of INSR (PubMed:27322061). CC Interacts (via cytosolic C-terminus) with STK39/SPAK (By similarity). CC Interacts (via N-terminal ectodomain) with the heterodimeric complex CC CRLF1-CLC; within this complex, the interaction is mediated CC predominantly by the CRLF1 moiety (By similarity). Interacts with CC CNTFR, as well as with the tripartite signaling complex formed by CC CRLF1, CLC and CNTFR (By similarity). Interacts (via N-terminal CC ectodomain) with IL6; this interaction leads to IL6 internalization and CC lysosomal degradation. Binding of SOLRL1 secreted N-terminal ectodomain CC to IL6 may increase IL6 trans signaling (By similarity). Interacts with CC secreted IL6R; this interaction leads to IL6R internalization CC (PubMed:28265003). Also interacts with transmembrane IL6R; this CC interaction does not affect subcellular location. Interacts with APOE CC (By similarity). Interacts with apolipoprotein E-rich beta-VLDL (By CC similarity). Interacts with APOA5; this interaction leads to APOA5 CC internalization and is abolished by heparin. Interaction with APOA5 CC results in enhanced binding to chylomicrons. Interacts with ROCK2 (By CC similarity). Interacts (via cytosolic C-terminus) with CC PPP3CB/calcineurin A beta (PubMed:25967121). Interacts with NTRK2/TRKB; CC this interaction facilitates NTRK2 trafficking between synaptic plasma CC membranes, postsynaptic densities and cell soma, hence positively CC regulates BDNF signaling (PubMed:23977241). Interacts (via cytosolic C- CC terminus) with HSPA12A in an ADP-dependent manner; this interaction CC affects SORL1 internalization and subcellular localization (By CC similarity). Interacts (via N-terminal ectodomain) with ERBB2/HER2 (By CC similarity). {ECO:0000250|UniProtKB:Q92673, CC ECO:0000250|UniProtKB:Q95209, ECO:0000269|PubMed:16174740, CC ECO:0000269|PubMed:16407538, ECO:0000269|PubMed:23977241, CC ECO:0000269|PubMed:25967121, ECO:0000269|PubMed:26584636, CC ECO:0000269|PubMed:27322061, ECO:0000269|PubMed:28265003}. CC -!- INTERACTION: CC O88307; P12023: App; NbExp=3; IntAct=EBI-7540114, EBI-78814; CC O88307; Q9EQH3: Vps35; NbExp=2; IntAct=EBI-7540114, EBI-775825; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q92673}. Golgi apparatus, trans-Golgi network CC membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:Q92673}. Endosome membrane CC {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q92673}. Early endosome membrane CC {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q92673}. Recycling endosome membrane CC {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q92673}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q92673}. Endosome, multivesicular body membrane CC {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q92673}. Cell membrane CC {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:Q92673}. Cytoplasmic vesicle, secretory vesicle CC membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:Q92673}. Secreted CC {ECO:0000269|PubMed:11082041, ECO:0000269|PubMed:26584636}. Note=Mostly CC intracellular, predominantly in the trans-Golgi network (TGN) and in CC endosome, as well as in endosome-to-TGN recycling compartments; found CC at low levels on the plasma membrane (By similarity). At the cell CC surface, partially subjected to proteolytic shedding that releases the CC ectodomain (also called soluble SORLA, solLR11 or sLR11) in the CC extracellular milieu (PubMed:11082041). The shedding may be catalyzed CC by ADAM17/TACE. Following shedding, PSEN1/presenilin-1 cleaves the CC remaining transmembrane fragment and catalyzes the release of a C- CC terminal fragment in the cytosol and of a soluble N-terminal beta CC fragment in the extracellular milieu. The C-terminal cytosolic fragment CC localizes to the nucleus. At the cell surface, the full-length protein CC undergoes partial clathrin-dependent endocytosis guided by clathrin CC adapter protein 2 (AP-2) (By similarity). CC {ECO:0000250|UniProtKB:Q92673, ECO:0000269|PubMed:11082041}. CC -!- TISSUE SPECIFICITY: Highly expressed in the central nervous system, CC including in the brain and spinal cord, in neurons, as well as in glial CC cells (at protein level) (PubMed:9726247, PubMed:9510025, CC PubMed:11082041, PubMed:16174740, PubMed:21385844, PubMed:23333276, CC PubMed:23977241, PubMed:30679749). In the brain, mainly expressed in CC the cerebellum, hippocampus, dentate gyrus, hypothalamus, and in the CC cerebral cortex (at protein level) (PubMed:9726247, PubMed:9510025, CC PubMed:23333276, PubMed:27322061). Also detected in kidney, heart, lung CC and spleen (PubMed:9726247, PubMed:9510025). In the kidney, expressed CC in epithelial cells in the thick ascending limb of Henle's loop, the CC distal convoluted tubule, the connecting tubule and the cortical CC collecting duct (at protein level) (PubMed:20385770, PubMed:25967121). CC Expressed in skeletal muscle (at protein level) (PubMed:9726247, CC PubMed:9510025, PubMed:27322061). Expressed in adipose tissue, CC including in brown adipose tissue and subcutaneous white adipose tissue CC (PubMed:26584636, PubMed:27322061). Expressed in intimal smooth muscle CC cells (at protein level) (PubMed:14764453). CC {ECO:0000269|PubMed:11082041, ECO:0000269|PubMed:14764453, CC ECO:0000269|PubMed:16174740, ECO:0000269|PubMed:20385770, CC ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:23333276, CC ECO:0000269|PubMed:23977241, ECO:0000269|PubMed:25967121, CC ECO:0000269|PubMed:26584636, ECO:0000269|PubMed:27322061, CC ECO:0000269|PubMed:30679749, ECO:0000269|PubMed:9510025, CC ECO:0000269|PubMed:9726247}. CC -!- DEVELOPMENTAL STAGE: Expression starts at 6.5 dpc (PubMed:9726247, CC PubMed:9510025). At 7.5 dpc, expressed over the entire embryo, with CC highest levels in the amnion. Up to 8.5 dpc, expression further CC increases and becomes more restricted to the foregut and the amnion. At CC 9.5 dpc, expression increases in the somites, as well as the developing CC gut, and is observed over the facial-cranial mesenchyme and the CC branchial arches. At 10.5 dpc, expression in the mesenchyme and the CC somites reaches its maximal intensity. At this stage, highest CC expression level is observed over the ventral part of the neural tube, CC in the marginal zone, and extends throughout the hindbrain. Also CC expressed in motor neurons of the spinal cord. With ongoing CC development, the brain becomes the main site of expression. At 11.5 CC dpc, expressed in the telencephalon, being restricted to the lateral CC aspects of the developing cerebral cortex, with highest levels in the CC outer layer of the neuronal tissue of the developing cerebral cortex. CC Also observed in the myelencephalon and in a thin cell layer in the CC rhombic lip of the metencephalon. At 12.5 dpc, expression begins in the CC mesencephalon and the diencephalon. Up to 14.5 dpc, expression levels CC in the developing cerebral cortex become more even and spread to more CC dorsal and caudal locations. At 14.5 dpc, decreased expression in the CC metencephalon and the myelencephalon. At 16.5 dpc, expressed over the CC entire cortical area, although at a slightly lower intensity. Expressed CC in the hypothalamus. At this stage, expression begins in the peripheral CC nervous system, including in the trigeminal ganglion, the dorsal root CC ganglia, the cochlear-vestibular ganglia and the sympathetic ganglia CC chain, but at lower levels compared to the central nervous system. CC Expressed over the mitral cell layer of the olfactory bulb and between CC the 2 outer walls of the gut. The overall expression levels in the CC cortex decrease until birth. At 18.5 dpc, the outer aspects of the CC cortical plate shows lower expression levels than the subventricular CC zone. At 18.5 dpc, expressed in the retina and the geniculate nucleus CC of the thalamus; this expression increases towards P0. At P0, CC expression levels are higher in the outer aspects of the cortical plate CC than in the subventricular zone (PubMed:9510025). 1 week after birth, CC abundantly expressed in the cerebrum, then levels decrease and become CC nearly undetectable at 4 weeks. Expression increases again and reaches CC moderate levels at 12 weeks. In the cerebellum, expressed at high CC levels during the first 2 weeks. Expression decreases at 4 and 8 weeks, CC and then increases again at 12 weeks (PubMed:9726247). Expressed in CC many organs outside the nervous system during organogenesis, such as CC the primitive gut where expression is detected already at 8.5 dpc. CC Other SORL1-expressing organs include the genital bud, the mesenchymal CC tissue, the developing skeletal muscles, the myocardium, the pituitary, CC the pineal, the thyroid and the Haderian glands, as well as the CC developing serous glands of the nasal cavity, the salivary and the CC submandibular glands, the pancreas, the epithelia of the stomach, the CC tubules of the kidney, the tooth germ, the cochlea, the nasal cavity, CC the trachea, the lung, the bladder and urethra, the intestine and the CC rectum (PubMed:9510025). {ECO:0000269|PubMed:9510025, CC ECO:0000269|PubMed:9726247}. CC -!- INDUCTION: Up-regulated by BDNF in cortical neurons (at protein level) CC (PubMed:20007471). Up-regulated under hypoxic conditions in CC hematopoietic stem and progenitor cells, a physiological conditions CC encountered by these cells in the endosteum (at protein level) CC (PubMed:23486467). In brown and sucutaneous white adipose tissues, CC down-regulated when environmental temperature rises from cold to CC thermoneutrality (PubMed:26584636). Up-regulated in adipose tissue by CC insulin through a post-transcriptional mechanism (PubMed:27322061). CC Expression levels increase in the fed state and decline after fasting CC (PubMed:26584636). {ECO:0000269|PubMed:20007471, CC ECO:0000269|PubMed:23486467, ECO:0000269|PubMed:26584636, CC ECO:0000269|PubMed:27322061}. CC -!- PTM: Within the Golgi apparatus, the propeptide may be cleaved off by CC FURIN or a furin-like protease. After cleavage, the propeptide CC interacts with the mature protein N-terminus, preventing the CC association with other ligands. At the cell surface, partially CC subjected to proteolytic shedding that releases the ectodomain in the CC extracellular milieu. The shedding may be catalyzed by ADAM17/TACE. CC Following shedding, PSEN1/presenilin-1 cleaves the remaining CC transmembrane fragment and catalyzes the release of a C-terminal CC fragment in the cytosol and of a soluble N-terminal beta fragment in CC the extracellular milieu. The C-terminal cytosolic fragment localizes CC to the nucleus. {ECO:0000250|UniProtKB:Q92673}. CC -!- PTM: Phosphorylation at Ser-2207 facilitates the interaction with GGA1. CC {ECO:0000250|UniProtKB:Q92673}. CC -!- DISRUPTION PHENOTYPE: Knockout mice are viable and fertile with no CC overt phenotype (PubMed:16174740). They tend to be lighter than their CC wild-type littermates, with reduced adiposity (PubMed:26584636, CC PubMed:27322061). On a high-fat diet, they show a reduced gain in body CC weight compared with wild-type littermates (PubMed:27322061). Mutant CC animals display improved serum biochemistry profiles compared to wild- CC type, with lower fasting glucose, insulin and triglyceride levels, CC particularly on high fat diet (PubMed:26584636, PubMed:27322061). On a CC high-fat diet, brown adipose tissue from knockout mice shows reduced CC lipid content and subcutaneous white adipose tissue contains smaller, CC less lipid replete adipocytes, with increased thermogenic markers CC (PubMed:26584636). Mutant animals exhibit an increased production of CC soluble APP and enhanced amount of neuron-associated amyloid-beta CC protein 40 and 42 in the brain at 10 months of age (PubMed:16174740). CC Following vascular injury, knockout mice placed on a high-fat diet show CC reduced intimal thickness and decreased infiltration of lipid-laden CC macrophages compared to wild-type littermates (PubMed:17332490). Mutant CC mice display elevated GDNF levels, altered dopaminergic function, CC marked hyperactivity, and reduced anxiety (PubMed:23333276). Knockout CC mice show a weak phenotype in the maintenance of renal ion balance. CC Under basal conditions, they exhibit significant urinary loss of CC potassium and calcium compared to controls. Serum Na(+), Cl(-), and CC K(+) levels are normal, but aldosterone levels are elevated 2-fold. CC Mean arterial blood pressure is decreased despite the CC hyperaldosteronemic phenotype (PubMed:20385770). The lack of major CC renal phenotype in mutant mice may be explained by the fact that CC animals remain responsive to vasopressin endocrine stimulation CC (PubMed:25967121). {ECO:0000269|PubMed:16174740, CC ECO:0000269|PubMed:17332490, ECO:0000269|PubMed:20385770, CC ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:25967121, CC ECO:0000269|PubMed:26584636, ECO:0000269|PubMed:27322061}. CC -!- SIMILARITY: Belongs to the VPS10-related sortilin family. SORL1 CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB015790; BAA31219.1; -; mRNA. DR EMBL; AK147303; BAE27834.1; -; mRNA. DR EMBL; AF031816; AAC16739.1; -; mRNA. DR EMBL; Y12004; CAA72732.1; -; mRNA. DR CCDS; CCDS40594.1; -. DR PIR; T00348; T00348. DR RefSeq; NP_035566.2; NM_011436.3. DR AlphaFoldDB; O88307; -. DR BMRB; O88307; -. DR SMR; O88307; -. DR BioGRID; 203392; 10. DR DIP; DIP-42439N; -. DR IntAct; O88307; 3. DR MINT; O88307; -. DR STRING; 10090.ENSMUSP00000058613; -. DR GlyConnect; 2735; 14 N-Linked glycans (12 sites). DR GlyCosmos; O88307; 28 sites, 13 glycans. DR GlyGen; O88307; 31 sites, 13 N-linked glycans (12 sites), 1 O-linked glycan (3 sites). DR iPTMnet; O88307; -. DR PhosphoSitePlus; O88307; -. DR EPD; O88307; -. DR MaxQB; O88307; -. DR PaxDb; 10090-ENSMUSP00000058613; -. DR PeptideAtlas; O88307; -. DR ProteomicsDB; 261475; -. DR Antibodypedia; 32786; 303 antibodies from 38 providers. DR DNASU; 20660; -. DR Ensembl; ENSMUST00000060989.9; ENSMUSP00000058613.9; ENSMUSG00000049313.9. DR GeneID; 20660; -. DR KEGG; mmu:20660; -. DR UCSC; uc009pap.1; mouse. DR AGR; MGI:1202296; -. DR CTD; 6653; -. DR MGI; MGI:1202296; Sorl1. DR VEuPathDB; HostDB:ENSMUSG00000049313; -. DR eggNOG; KOG1215; Eukaryota. DR eggNOG; KOG3511; Eukaryota. DR GeneTree; ENSGT01030000234563; -. DR HOGENOM; CLU_001389_0_0_1; -. DR InParanoid; O88307; -. DR OMA; LCPDGME; -. DR OrthoDB; 5840at2759; -. DR PhylomeDB; O88307; -. DR TreeFam; TF324918; -. DR BioGRID-ORCS; 20660; 2 hits in 80 CRISPR screens. DR ChiTaRS; Sorl1; mouse. DR PRO; PR:O88307; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; O88307; Protein. DR Bgee; ENSMUSG00000049313; Expressed in facial nucleus and 275 other cell types or tissues. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0005769; C:early endosome; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; ISS:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0031985; C:Golgi cisterna; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005771; C:multivesicular body; ISS:UniProtKB. DR GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0005641; C:nuclear envelope lumen; IDA:Alzheimers_University_of_Toronto. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0097356; C:perinucleolar compartment; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0055037; C:recycling endosome; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005802; C:trans-Golgi network; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0001540; F:amyloid-beta binding; ISO:MGI. DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0030169; F:low-density lipoprotein particle binding; ISO:MGI. DR GO; GO:0042923; F:neuropeptide binding; ISO:MGI. DR GO; GO:0031267; F:small GTPase binding; ISO:MGI. DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISO:MGI. DR GO; GO:1990845; P:adaptive thermogenesis; IMP:UniProtKB. DR GO; GO:0016477; P:cell migration; ISO:MGI. DR GO; GO:0002024; P:diet induced thermogenesis; IMP:UniProtKB. DR GO; GO:0099638; P:endosome to plasma membrane protein transport; IDA:MGI. DR GO; GO:0038020; P:insulin receptor recycling; IDA:UniProtKB. DR GO; GO:1902992; P:negative regulation of amyloid precursor protein catabolic process; IMP:Alzheimers_University_of_Toronto. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:UniProtKB. DR GO; GO:1902997; P:negative regulation of neurofibrillary tangle assembly; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0050768; P:negative regulation of neurogenesis; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0010897; P:negative regulation of triglyceride catabolic process; IMP:UniProtKB. DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:MGI. DR GO; GO:1904179; P:positive regulation of adipose tissue development; IMP:UniProtKB. DR GO; GO:1902955; P:positive regulation of early endosome to recycling endosome transport; ISS:Alzheimers_University_of_Toronto. DR GO; GO:2001137; P:positive regulation of endocytic recycling; ISS:Alzheimers_University_of_Toronto. DR GO; GO:1902953; P:positive regulation of ER to Golgi vesicle-mediated transport; ISS:Alzheimers_University_of_Toronto. DR GO; GO:1900168; P:positive regulation of glial cell-derived neurotrophic factor production; IMP:UniProtKB. DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0070863; P:positive regulation of protein exit from endoplasmic reticulum; ISS:Alzheimers_University_of_Toronto. DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0034067; P:protein localization to Golgi apparatus; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0051604; P:protein maturation; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0045053; P:protein retention in Golgi apparatus; IMP:Alzheimers_University_of_Toronto. DR GO; GO:0006605; P:protein targeting; IDA:UniProtKB. DR GO; GO:0006622; P:protein targeting to lysosome; ISS:Alzheimers_University_of_Toronto. DR GO; GO:0006898; P:receptor-mediated endocytosis; ISO:MGI. DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISO:MGI. DR CDD; cd00063; FN3; 5. DR CDD; cd00112; LDLa; 11. DR Gene3D; 2.10.70.80; -; 1. DR Gene3D; 3.30.60.270; -; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 4. DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 11. DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR036055; LDL_receptor-like_sf. DR InterPro; IPR023415; LDLR_class-A_CS. DR InterPro; IPR000033; LDLR_classB_rpt. DR InterPro; IPR002172; LDrepeatLR_classA_rpt. DR InterPro; IPR031777; Sortilin_C. DR InterPro; IPR031778; Sortilin_N. DR InterPro; IPR006581; VPS10. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR PANTHER; PTHR12106; SORTILIN RELATED; 1. DR PANTHER; PTHR12106:SF20; SORTILIN-RELATED RECEPTOR; 1. DR Pfam; PF00041; fn3; 3. DR Pfam; PF00057; Ldl_recept_a; 10. DR Pfam; PF00058; Ldl_recept_b; 1. DR Pfam; PF15902; Sortilin-Vps10; 1. DR Pfam; PF15901; Sortilin_C; 1. DR PRINTS; PR00261; LDLRECEPTOR. DR SMART; SM00060; FN3; 6. DR SMART; SM00192; LDLa; 11. DR SMART; SM00135; LY; 5. DR SMART; SM00602; VPS10; 1. DR SUPFAM; SSF49265; Fibronectin type III; 3. DR SUPFAM; SSF57424; LDL receptor-like module; 11. DR SUPFAM; SSF110296; Oligoxyloglucan reducing end-specific cellobiohydrolase; 1. DR SUPFAM; SSF63825; YWTD domain; 1. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50853; FN3; 4. DR PROSITE; PS01209; LDLRA_1; 10. DR PROSITE; PS50068; LDLRA_2; 11. DR PROSITE; PS51120; LDLRB; 5. DR Genevisible; O88307; MM. PE 1: Evidence at protein level; KW Cell membrane; Cleavage on pair of basic residues; Cytoplasmic vesicle; KW Developmental protein; Disulfide bond; EGF-like domain; Endocytosis; KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus; Membrane; KW Phosphoprotein; Receptor; Reference proteome; Repeat; Secreted; Signal; KW Transmembrane; Transmembrane helix; Transport. FT SIGNAL 1..28 FT /evidence="ECO:0000255" FT PROPEP 29..81 FT /note="Removed in mature form" FT /evidence="ECO:0000250" FT /id="PRO_0000033166" FT CHAIN 82..2215 FT /note="Sortilin-related receptor" FT /id="PRO_0000033167" FT TOPO_DOM 82..2138 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 2139..2159 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2160..2215 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 136..147 FT /note="BNR 1" FT REPEAT 232..243 FT /note="BNR 2" FT REPEAT 441..452 FT /note="BNR 3" FT REPEAT 521..532 FT /note="BNR 4" FT REPEAT 562..573 FT /note="BNR 5" FT REPEAT 800..843 FT /note="LDL-receptor class B 1" FT REPEAT 844..887 FT /note="LDL-receptor class B 2" FT REPEAT 888..932 FT /note="LDL-receptor class B 3" FT REPEAT 933..972 FT /note="LDL-receptor class B 4" FT REPEAT 973..1013 FT /note="LDL-receptor class B 5" FT DOMAIN 1026..1072 FT /note="EGF-like" FT DOMAIN 1076..1114 FT /note="LDL-receptor class A 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1115..1155 FT /note="LDL-receptor class A 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1156..1194 FT /note="LDL-receptor class A 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1198..1236 FT /note="LDL-receptor class A 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1238..1272 FT /note="LDL-receptor class A 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1273..1317 FT /note="LDL-receptor class A 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1323..1361 FT /note="LDL-receptor class A 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1366..1405 FT /note="LDL-receptor class A 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1417..1455 FT /note="LDL-receptor class A 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1469..1508 FT /note="LDL-receptor class A 10" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1512..1551 FT /note="LDL-receptor class A 11" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DOMAIN 1557..1649 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1653..1745 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1747..1846 FT /note="Fibronectin type-III 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1844..1928 FT /note="Fibronectin type-III 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 1935..2030 FT /note="Fibronectin type-III 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 2031..2119 FT /note="Fibronectin type-III 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT REGION 59..84 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2191..2215 FT /note="Required for efficient Golgi apparatus - endosome FT sorting" FT /evidence="ECO:0000250|UniProtKB:Q92673" FT REGION 2202..2215 FT /note="Required for interaction with GGA1 and GGA2" FT /evidence="ECO:0000250|UniProtKB:Q92673" FT MOTIF 2162..2165 FT /note="Potential nuclear localization signal for the C- FT terminal fragment generated by PSEN1" FT /evidence="ECO:0000250|UniProtKB:Q92673" FT MOTIF 2173..2178 FT /note="Endocytosis signal" FT /evidence="ECO:0000255" FT MOTIF 2209..2213 FT /note="DXXLL motif involved in the interaction with GGA1" FT /evidence="ECO:0000250|UniProtKB:Q92673" FT MOD_RES 114 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q92673" FT MOD_RES 2207 FT /note="Phosphoserine; by ROCK2" FT /evidence="ECO:0000250|UniProtKB:Q92673" FT CARBOHYD 99 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 158 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 367 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 368 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 430 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 616 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 674 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 818 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 871 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1035 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1068 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1164 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1191 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1246 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1367 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1458 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1608 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1706 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1733 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1810 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1855 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1895 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1987 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2011 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2055 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2070 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2077 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 2093 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 1078..1090 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1085..1103 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1097..1112 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1117..1131 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1125..1144 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1138..1153 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1158..1170 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1165..1183 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1177..1192 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1199..1211 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1206..1224 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1218..1235 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1239..1249 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1244..1262 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1256..1271 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1275..1289 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1283..1302 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1296..1315 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1325..1337 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1332..1350 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1344..1359 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1368..1381 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1376..1394 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1388..1403 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1419..1431 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1426..1444 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1438..1453 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1471..1484 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1478..1497 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1491..1506 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1514..1527 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1521..1540 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT DISULFID 1534..1549 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124" FT CONFLICT 706 FT /note="S -> F (in Ref. 3; AAC16739)" FT /evidence="ECO:0000305" FT CONFLICT 768 FT /note="S -> F (in Ref. 3; AAC16739)" FT /evidence="ECO:0000305" FT CONFLICT 785 FT /note="S -> W (in Ref. 1; BAA31219)" FT /evidence="ECO:0000305" FT CONFLICT 796 FT /note="D -> G (in Ref. 3; AAC16739)" FT /evidence="ECO:0000305" FT CONFLICT 953 FT /note="R -> G (in Ref. 1; BAA31219)" FT /evidence="ECO:0000305" FT CONFLICT 1268..1269 FT /note="EQ -> DE (in Ref. 1; BAA31219)" FT /evidence="ECO:0000305" FT CONFLICT 1425 FT /note="H -> A (in Ref. 1; BAA31219)" FT /evidence="ECO:0000305" FT CONFLICT 1425 FT /note="H -> R (in Ref. 3; AAC16739 and 4; CAA72732)" FT /evidence="ECO:0000305" FT CONFLICT 1468 FT /note="F -> L (in Ref. 1; BAA31219, 3; AAC16739 and 4; FT CAA72732)" FT /evidence="ECO:0000305" FT CONFLICT 1663 FT /note="S -> R (in Ref. 1; BAA31219, 3; AAC16739 and 4; FT CAA72732)" FT /evidence="ECO:0000305" FT CONFLICT 1709..1713 FT /note="EIKNL -> KKKKK (in Ref. 4; CAA72732)" FT /evidence="ECO:0000305" FT CONFLICT 1807 FT /note="R -> K (in Ref. 1; BAA31219 and 3; AAC16739)" FT /evidence="ECO:0000305" FT CONFLICT 2130 FT /note="Q -> H (in Ref. 1; BAA31219)" FT /evidence="ECO:0000305" SQ SEQUENCE 2215 AA; 247086 MW; 5D7F53806EFE2CB0 CRC64; MATRSSRRES RLPFLFALVA LLPRGALGGG WTQRLHGGPA PLPQDRGFFV VQGDPRDLRL GTHGDAPGAS PAARKPLRTR RSAALQPQPI QVYGQVSLND SHNQMVVHWA GEKSNVIVAL ARDSLALARP KSSDVYVSYD YGKSFSKISE KLNFGVGNNS EAVISQFYHS PADNKRYIFV DAYAQYLWIT FDFCSTIHGF SIPFRAADLL LHSKASNLLL GFDRSHPNKQ LWKSDDFGQT WIMIQEHVKS FSWGIDPYDQ PNAIYIERHE PFGFSTVLRS TDFFQSRENQ EVILEEVRDF QLRDKYMFAT KVVHLPGSQQ QSSVQLWVSF GRKPMRAAQF VTKHPINEYY IADAAEDQVF VCVSHSNNST NLYISEAEGL KFSLSLENVL YYSPGGAGSD TLVRYFANEP FADFHRVEGL QGVYIATLIN GSMNEENMRS VITFDKGGTW EFLQAPAFTG YGEKINCELS QGCSLHLAQR LSQLLNLQLR RMPILSKESA PGLIIATGSV GKNLASKTNV YISSSAGARW REALPGPHYY TWGDHGGIIM AIAQGMETNE LKYSTNEGET WKTFVFSEKP VFVYGLLTEP GEKSTVFTIF GSNKESVHSW LILQVNATDA LGVPCTENDY KLWSPSDERG NECLLGHKTV FKRRTPHATC FNGEDFDRPV VVSNCSCTRE DYECDFGFKM SEDLSLEVCV PDPEFSGKPY SPPVPCPVGS SYRRTRGYRK ISGDTCSGGD VEARLEGELV PCPLAEENEF ILYAMRKSIY RYDLASGATE QLPLSGLRAA VALDFDYERN CLYWSDLALD TIQRLCLNGS TGQEVIINSG LETVEALAFE PLSQLLYWVD AGFKKIEVAN PDGDFRLTIV NSSVLDRPRA LVLVPQEGVM FWTDWGDLKP GIYRSYMDGS AAYRLVSEDV KWPNGISVDS QWIYWTDAYL DCIERITFSG QQRSVILDSL PHPYAIAVFK NEIYWDDWSQ LSIFRASKHS RSQVEILASQ LTGLMDMKVF YKGKNAGSNA CVPQPCSLLC LPKANNSKSC RCPEGVASSV LPSGDLMCDC PQGYQRKNNT CVKEENTCLR NQYRCSNGNC INSIWWCDFD NDCGDMSDER NCPTTVCDAD TQFRCQESGT CIPLSYKCDL EDDCGDNSDE SHCEMHQCRS DEFNCSSGMC IRSSWVCDGD NDCRDWSDEA NCTAIYHTCE ASNFQCHNGH CIPQRWACDG DADCQDGSDE DPVSCEKKCN GFHCPNGTCI PSSKHCDGLR DCPDGSDEQH CEPFCTRFMD FVCKNRQQCL FHSMVCDGIV QCRDGSDEDA AFAGCSQDPE FHKECDEFGF QCQNGVCISL IWKCDGMDDC GDYSDEANCE NPTEAPNCSR YFQFHCENGH CIPNRWKCDR ENDCGDWSDE KDCGDSHVLP SPTPGPSTCL PNYFHCSSGA CVMGTWVCDG YRDCADGSDE EACPSLANST AASTPTQFGQ CDRFEFECHQ PKKCIPNWKR CDGHQDCQDG QDEANCPTHS TLTCTSREFK CEDGEACIVL SERCDGFLDC SDESDEKACS DELTVYKVQN LQWTADFSGD VTLTWMRPKK MPSASCVYNV YYRVVGESIW KTLETHSNKT STVLKVLKPD TTYQVKVQVH CLNKVHNTND FVTLRTPEGL PDAPRNLQLS LNSEEEGVIL GHWAPPVHTH GLIREYIVEY SRSGSKMWAS QRAASNSTEI KNLLLNALYT VRVAAVTSRG IGNWSDSKSI TTIKGKVIQA PNIHIDSYDE NSLSFTLTMD GDIKVNGYVV NLFWSFDAHK QEKKTLSFRG GSALSHRVSN LTAHTSYEIS AWAKTDLGDS PLAFEHILTR GSSPPAPSLK AKAINQTAVE CIWTGPKNVV YGIFYATSFL DLYRNPKSVT TSLHNKTVIV SKDEQYLFLV RVLIPYQGPS SDYVVVKMIP DSRLPPRHLH AVHIGKTSAL IKWESPYDSP DQDLFYAIAV KDLIRKTDRS YKVRSRNSTV EYSLSKLEPG GKYHIIVQLG NMSKDSSIKI TTVSLSAPDA LKIITENDHV LLFWKSLALK EKQFNETRGY EIHMSDSAVN LTAYLGNTTD NFFKVSNLKM GHNYTFTVQA RCLFGSQICG EPAVLLYDEL SSGADAAVIQ AARSTDVAAV VVPILFLILL SLGVGFAILY TKHRRLQSSF SAFANSHYSS RLGSAIFSSG DDLGEDDEDA PMITGFSDDV PMVIA //