SORL_RAT
ID SORL_RAT Reviewed; 2215 AA.
AC P0DSP1;
DT 31-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Sortilin-related receptor;
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;
DE AltName: Full=Sorting protein-related receptor containing LDLR class A repeats;
DE Short=SorLA;
DE Flags: Precursor;
GN Name=Sorl1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY.
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 TISSUE SPECIFICITY.
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 [5]
RP FUNCTION, AND INTERACTION WITH GDNF.
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 [6]
RP FUNCTION, AND INTERACTION WITH GFRA1.
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 [7]
RP FUNCTION, AND INTERACTION WITH PPP3CB.
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).
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. Sorting receptor for the BDNF receptor NTRK2/TRKB that
CC facilitates NTRK2 trafficking between synaptic plasma membranes,
CC postsynaptic densities and cell soma, hence positively regulates BDNF
CC signaling by controlling the intracellular location of its receptor (By
CC similarity). Sorting receptor for GDNF that promotes GDNF regulated,
CC but not constitutive secretion (PubMed:21994944). Sorting receptor for
CC the GDNF-GFRA1 complex, directing it from the cell surface to
CC endosomes. GDNF is then targeted to lysosomes and degraded, while its
CC receptor GFRA1 recycles back to the cell membrane, resulting in a GDNF
CC clearance pathway. The SORL1-GFRA1 complex further targets RET for
CC 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. Potential
CC sorting receptor for APOA5, inducing APOA5 internalization to early
CC endosomes, then to late endosomes, wherefrom a portion is sent to
CC lysosomes and degradation, another portion is sorted to the trans-Golgi
CC network. Sorting receptor for the insulin receptor INSR. Promotes
CC recycling of internalized INSR via the Golgi apparatus back to the cell
CC surface, thereby preventing lysosomal INSR catabolism, increasing INSR
CC cell surface expression and strengthening insulin signal reception in
CC adipose tissue. Does not affect INSR internalization (By similarity).
CC Plays a role in renal ion homeostasis, controlling the phospho-
CC regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin
CC A beta phosphatase, possibly through intracellular sorting of STK39 and
CC PPP3CB (PubMed:25967121). Stimulates, via the N-terminal ectodomain,
CC the 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 acting on the migration of intimal smooth
CC muscle cells, may accelerate intimal thickening following vascular
CC injury (By similarity). Stimulates proliferation and migration
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 (By similarity).
CC Regulates hypoxia-enhanced adhesion of hematopoietic stem and
CC progenitor cells to the bone marrow stromal cells via a PLAUR-mediated
CC pathway. This function is mediated by the N-terminal ectodomain (By
CC similarity). Metabolic regulator, which functions to maintain the
CC adequate balance between lipid storage and oxidation in response to
CC changing environmental conditions, such as temperature and diet. The N-
CC terminal ectodomain negatively regulates adipose tissue energy
CC expenditure, acting through the inhibition the BMP/Smad pathway (By
CC similarity). May regulate signaling by the heterodimeric neurotrophic
CC cytokine CLCF1-CRLF1 bound to the CNTFR receptor by promoting the
CC endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR and lysosomal
CC degradation. Might regulate IL6 signaling, decreasing cis signaling,
CC while up-regulating trans signaling (By similarity).
CC {ECO:0000250|UniProtKB:O88307, ECO:0000250|UniProtKB:Q92673,
CC ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276,
CC ECO:0000269|PubMed:25967121}.
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. Interacts (via N-
CC terminal ectodomain) with APP, forming a 1:1 stoichiometric complex,
CC including with isoforms APP695, APP751 and APP770. Also interacts with
CC APP C-terminal fragment C99 and with Abeta40. Interacts with beta-
CC secretase BACE1/BACE; this interaction may affect BACE1-binding to APP
CC and hence reduce BACE1-dependent APP cleavage. Interacts with
CC LRPAP1/RAP. Interacts (via C-terminal cytosolic domain) with GGA1 and
CC GGA2 (via N-terminal VHS domain). Interacts with PACS1. May interact
CC (via the N-terminal ectodomain) with the morphogenetic neuropeptide,
CC also called head activator or HA; this interaction is impaired in the
CC presence of propeptide. Interacts with neurotensin/NTS. Interacts (via
CC the N-terminal ectodomain) with PDGFB homodimer. Interacts (via N-
CC terminal ectodomain) with the uPA receptor PLAUR. Interacts with
CC uPA/PLAU and PAI1/SERPINE1, either individually or in complex with each
CC other, leading to endocytosis. Also interacts with PAI1/SERPINE1 in
CC complex with tPA/PLAT. Interacts (via C-terminus) with AP-1 and AP-2
CC complexes (By similarity). Interacts with BMPR1A and BMPR1B (By
CC similarity). Interacts with lipoprotein lipase LPL; this interaction is
CC optimal in slightly acidic conditions (By similarity). Interacts (via
CC N-terminal ectodomain) with GDNF (via propeptide) and GDNF receptor
CC alpha-1/GFRA1, either individually or in complex with each other
CC (PubMed:21994944, PubMed:23333276). Also interacts with other GDNF
CC receptor alpha family members, including GFRA2, GFRA3 and GFRA4.
CC Interacts with the insulin receptor INSR; this interaction strongly
CC increases the surface exposure of INSR. Interacts (via cytosolic C-
CC terminus) with STK39/SPAK. Interacts (via N-terminal ectodomain) with
CC the heterodimeric complex CRLF1-CLC; within this complex, the
CC interaction is mediated predominantly by the CRLF1 moiety. Interacts
CC with CNTFR, as well as with the tripartite signaling complex formed by
CC CRLF1, CLC and CNTFR. Interacts (via N-terminal ectodomain) with IL6;
CC this interaction leads to IL6 internalization and lysosomal
CC degradation. Binding of SOLRL1 secreted N-terminal ectodomain to IL6
CC may increase IL6 trans signaling. Interacts with secreted IL6R; this
CC interaction leads to IL6R internalization. Also interacts with
CC transmembrane IL6R; this interaction does not seem to affect
CC subcellular location. Interacts with APOE (By similarity). Interacts
CC with apolipoprotein E-rich beta-VLDL (By similarity). Interacts with
CC APOA5; this interaction leads to APOA5 internalization and is abolished
CC by heparin. Interaction with APOA5 results in enhanced binding to
CC chylomicrons. Interacts with ROCK2 (By similarity). Interacts (via
CC cytosolic C-terminus) with PPP3CB/calcineurin A beta (PubMed:25967121).
CC Interacts with NTRK2/TRKB (By similarity). 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:O88307,
CC ECO:0000250|UniProtKB:Q92673, ECO:0000250|UniProtKB:Q95209,
CC ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276,
CC ECO:0000269|PubMed:25967121}.
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:0000250|UniProtKB:Q92673}. Note=Mostly intracellular,
CC predominantly in the trans-Golgi network (TGN) and in endosome, as well
CC as in endosome-to-TGN recycling compartments; found at low levels on
CC the plasma membrane. At the cell surface, partially subjected to
CC proteolytic shedding that releases the ectodomain (also called soluble
CC SORLA, solLR11 or sLR11) in the extracellular milieu. The shedding may
CC be catalyzed by ADAM17/TACE. Following shedding, PSEN1/presenilin-1
CC cleaves the remaining transmembrane fragment and catalyzes the release
CC of a C-terminal fragment in the cytosol and of a soluble N-terminal
CC beta fragment in the extracellular milieu. The C-terminal cytosolic
CC fragment localizes to the nucleus. At the cell surface, the full-length
CC protein undergoes partial clathrin-dependent endocytosis guided by the
CC clathrin adapter protein 2 (AP-2). {ECO:0000250|UniProtKB:Q92673}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the cerebral cortex, the
CC pyramidal cells of the CA region of the hippocampus, the granular cells
CC of the dentate gyrus, the Purkinje cell layer of the cerebellum and the
CC piriform cortex. Lower levels were detected over the mitral cell layer
CC of the olfactory bulb, the nuclei of the amygdala, the nucleus
CC reticularis of the thalamus and several hypothalamic nuclei. In the
CC brainstem weak expression in the pontine nuclei. In the central nervous
CC system, expression is restricted to neurons (PubMed:9510025). Expressed
CC in intimal smooth muscle cell after vascular injury (PubMed:17332490).
CC {ECO:0000269|PubMed:17332490, ECO:0000269|PubMed:9510025}.
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 -!- SIMILARITY: Belongs to the VPS10-related sortilin family. SORL1
CC subfamily. {ECO:0000305}.
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DR EMBL; AABR07070055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07070056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473975; EDL95248.1; -; Genomic_DNA.
DR RefSeq; NP_445971.1; NM_053519.1.
DR AlphaFoldDB; P0DSP1; -.
DR SMR; P0DSP1; -.
DR STRING; 10116.ENSRNOP00000056722; -.
DR GlyGen; P0DSP1; 27 sites.
DR Ensembl; ENSRNOT00000095508; ENSRNOP00000089955; ENSRNOG00000064634.
DR GeneID; 300652; -.
DR KEGG; rno:300652; -.
DR CTD; 6653; -.
DR RGD; 619914; Sorl1.
DR GeneTree; ENSGT01030000234563; -.
DR PRO; PR:P0DSP1; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Proteomes; UP000234681; Chromosome 8.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0031985; C:Golgi cisterna; ISO:RGD.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005771; C:multivesicular body; IDA:RGD.
DR GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005641; C:nuclear envelope lumen; ISO:RGD.
DR GO; GO:0097356; C:perinucleolar compartment; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0055037; C:recycling endosome; ISO:RGD.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; ISO:RGD.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:RGD.
DR GO; GO:0030169; F:low-density lipoprotein particle binding; ISO:RGD.
DR GO; GO:0042923; F:neuropeptide binding; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISO:RGD.
DR GO; GO:1990845; P:adaptive thermogenesis; ISO:RGD.
DR GO; GO:0016477; P:cell migration; IMP:RGD.
DR GO; GO:0008283; P:cell population proliferation; IEP:RGD.
DR GO; GO:0002024; P:diet induced thermogenesis; ISO:RGD.
DR GO; GO:0038020; P:insulin receptor recycling; ISO:RGD.
DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISO:RGD.
DR GO; GO:1902960; P:negative regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:1902963; P:negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:1902997; P:negative regulation of neurofibrillary tangle assembly; ISO:RGD.
DR GO; GO:0050768; P:negative regulation of neurogenesis; ISO:RGD.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:1902948; P:negative regulation of tau-protein kinase activity; ISO:RGD.
DR GO; GO:0010897; P:negative regulation of triglyceride catabolic process; ISO:RGD.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISO:RGD.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; ISO:RGD.
DR GO; GO:1902771; P:positive regulation of choline O-acetyltransferase activity; ISO:RGD.
DR GO; GO:1902955; P:positive regulation of early endosome to recycling endosome transport; ISO:RGD.
DR GO; GO:2001137; P:positive regulation of endocytic recycling; ISO:RGD.
DR GO; GO:1902953; P:positive regulation of ER to Golgi vesicle-mediated transport; ISO:RGD.
DR GO; GO:1900168; P:positive regulation of glial cell-derived neurotrophic factor production; ISO:RGD.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0070863; P:positive regulation of protein exit from endoplasmic reticulum; ISO:RGD.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISO:RGD.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; ISO:RGD.
DR GO; GO:0034067; P:protein localization to Golgi apparatus; ISO:RGD.
DR GO; GO:0051604; P:protein maturation; ISO:RGD.
DR GO; GO:0045053; P:protein retention in Golgi apparatus; ISO:RGD.
DR GO; GO:0006605; P:protein targeting; ISO:RGD.
DR GO; GO:0006622; P:protein targeting to lysosome; ISO:RGD.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISO:RGD.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISO:RGD.
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; 4.
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|UniProtKB:Q92673"
FT /id="PRO_0000447670"
FT CHAIN 82..2215
FT /note="Sortilin-related receptor"
FT /evidence="ECO:0000255"
FT /id="PRO_0000447671"
FT TOPO_DOM 29..2138
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 2139..2159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2160..2215
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 844..887
FT /note="LDL-receptor class B 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 888..930
FT /note="LDL-receptor class B 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 931..972
FT /note="LDL-receptor class B 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 1026..1072
FT /note="EGF-like"
FT DOMAIN 1077..1113
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1116..1154
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1157..1193
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 1234..1272
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1274..1316
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1324..1360
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1367..1404
FT /note="LDL-receptor class A 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1418..1454
FT /note="LDL-receptor class A 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1470..1507
FT /note="LDL-receptor class A 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1513..1550
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..1843
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 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 63..65
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
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"
FT /evidence="ECO:0000250|UniProtKB:Q92673"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q92673"
FT CARBOHYD 158
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:0000250|UniProtKB:Q92673"
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:0000250|UniProtKB:Q92673"
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:0000250|UniProtKB:Q92673"
FT CARBOHYD 2093
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q92673"
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 1235..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"
SQ SEQUENCE 2215 AA; 247316 MW; 4D9A196919A5C406 CRC64;
MATRSSRRES RLPFLFTLVA LLPPGALGGG WTQRLHGGGA PLPQDRGFFV VQGDPHELRL
GTHGDAWGAS PAARKPLRTR RSAALQPQPI QVYGQVSLND SHNQMVVHWA GEKSNVIVAL
ARDSLALTRP KSSDVYVSYD YGKSFNKISE KLNFGVGNSS EAVISQFYHS PADNKRYIFV
DAYARYLWIT FDFGSTIHGF SIPFRAADLL LHSKASNLLL GFDSSHPNKQ LWKSDDFGQT
WIMIQEHVKS FSWGIDPYDQ PNTIYIERHE PFGFSTVFRS TDFFQSRENQ EVILEEVRDF
QLRDKYLFAT KVVHLPGSQQ QSSVQLWVSF GRKPMRAAQF VTKHPINEYY IADASEDQVF
VCVSHSNNST NLYISEAEGL KFSLSLENVL YYSPGGAGSD TLVRYFANEP FADFHRVEGL
QGVYIATLIN GSMSEENMRS 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 SEDISLEVCV PDPEFSGKPY SPPVPCPVGS
SYRRTRGYRK ISGDTCSGGD VEARLEGELV PCPLAEENEF ILYAMRKSIY RYDLASGATE
QLPLSGLRAA VALDFDYEHN CLYWSDLALD TIQRLCLNGS TGQEVIINSG LETVEALAFE
PLSQLLYWVD AGFKKIEVAN PDGDFRLTIV NSSVLDRPRA LVLVPQEGVM FWTDWGDLKP
GIYRSNMDGS AAYRLVSEDV KWPNGISVDG HWIYWTDAYL DCIERITFSG QQRSVILDNL
PHPYAIAVFK NEIYWDDWSQ LSIFRASKYS RSQVETLASQ LTGLMDMKIF YKGKNAGSNA
CIPQPCSLLC LPKANNSKSC RCPEGVASSV LPSGYLMCDC PQGYERKNNT CVKEENTCLR
NQYHCSNGNC INSIWWCDFD NDCGDMSDER NCPTTICDAD TQFRCQESGT CIPLSYKCDL
EDDCGDNSDE SHCEMHQCRS DEFNCSSGMC IRSSWVCDGD NDCRDWSDEA NCTAIYHTCE
ASNFQCHNGH CIPQRWACDG DADCQDGSDE DPISCEKKCN GFHCPNGTCI PSSKHCDGLR
DCPDGSDEQH CEPFCTRFMD FVCKNRQQCL FHSMVCDGII QCRDGSDEDA TFAGCSQDPE
FHKECDEFGF QCQNGVCISL IWKCDGMDDC GDYSDEANCE NPTEAPNCSR YFQFHCENGR
CIPNRWKCDR ENDCGDWSDE KDCGDSHIFP SPTPGPSTCL PNYFRCSSGA CVMGTWVCDG
YRDCADGSDE EACPSLANST AASTPTQLGQ CDRFEFECRQ PKKCIPNWKR CDGHQDCQDG
QDEANCPTHS TLTCMSREFK CEDGEACIVL SERCDGFLDC SDESDEKACS DELTVYKVQN
LQWIADFSGD VTLTWTRPKK MPSASCVYNV YYRVVGESIW KTLETHSNKT STVLKVLKPD
TTYQVKVQVH CLSKVHNTND FVTLRTPEGL PDAPRNLQLS LNSEEEGVIL GHWAPPVHTH
GLIREYIVEY SRSGSKMWAS QRAASNSTEI KNLLLNALYT VRVAAVTSRG IGNWSDSKSI
TTTKGKVIQA PNIHIDSYDE NSLSFTLTMD GDIKVNGYVV NLFWSFDAHK QEKKTLNFRG
GSSLSHKVSN LTAHTSYEVS AWAKTDLGDS PLAFEHILTR GISPPAPSLK AKAINQTAVE
CIWTGPKNVV YGIFYATSFL DLYRNPKSLT TSLHNKTVIV SKDEQYLFLV RVLIPYQGPS
SDYVVVKMIP DSRLPPRHLH AVQIGKTSAV IKWESPYDSP DQDLFYAIAV KDLIRKTDRS
YKVRSRNSTV EYSLSKLEPG GKYHIIVQLG NMSKDSSIKI TTVSLSAPDA LKIITENDHV
LLFWKSLALK EKQFNETRGY EIHMFDSAVN LTAYLGNTTD NFFKVSNLKM GHNYTFTVQA
RCLFGSQICG EPAVLLYDEL SSGGDATVVQ TARSTDVAAV VVPILFLILL SLGVGFAVLY
TKHRRLQSSF TAFANSHYSS RLGSAIFSSG DDLGEDDEDA PMITGFSDDV PMVIA
