SORL_MOUSE
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 03-AUG-2022, entry version 190.
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 GlyGen; O88307; 28 sites, 13 N-linked glycans (12 sites).
DR iPTMnet; O88307; -.
DR PhosphoSitePlus; O88307; -.
DR EPD; O88307; -.
DR MaxQB; O88307; -.
DR PaxDb; O88307; -.
DR PeptideAtlas; O88307; -.
DR PRIDE; O88307; -.
DR ProteomicsDB; 261475; -.
DR Antibodypedia; 32786; 265 antibodies from 38 providers.
DR DNASU; 20660; -.
DR Ensembl; ENSMUST00000060989; ENSMUSP00000058613; ENSMUSG00000049313.
DR GeneID; 20660; -.
DR KEGG; mmu:20660; -.
DR UCSC; uc009pap.1; mouse.
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; 1046610at2759; -.
DR PhylomeDB; O88307; -.
DR TreeFam; TF324918; -.
DR BioGRID-ORCS; 20660; 2 hits in 75 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 272 other tissues.
DR Genevisible; O88307; MM.
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:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
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; IEA:Ensembl.
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: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; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0002024; P:diet induced thermogenesis; IMP:UniProtKB.
DR GO; GO:0038020; P:insulin receptor recycling; IDA:UniProtKB.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:1902960; P:negative regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:1902963; P:negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic process; IMP:Alzheimers_University_of_Toronto.
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:1901215; P:negative regulation of neuron death; IMP:Alzheimers_University_of_Toronto.
DR GO; GO:0032091; P:negative regulation of protein binding; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISS:Alzheimers_University_of_Toronto.
DR GO; GO:1902948; P:negative regulation of tau-protein kinase activity; IMP: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:1902771; P:positive regulation of choline O-acetyltransferase activity; IMP:Alzheimers_University_of_Toronto.
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; 2.120.10.30; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 4.
DR Gene3D; 4.10.400.10; -; 11.
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 Pfam; PF00041; fn3; 3.
DR Pfam; PF00057; Ldl_recept_a; 10.
DR Pfam; PF00058; Ldl_recept_b; 2.
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; SSF49265; 3.
DR SUPFAM; SSF57424; SSF57424; 11.
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.
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
