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Entry version 198 (31 Jul 2019)
Sequence version 2 (18 May 2010)
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Protein

Sortilin-related receptor

Gene

SORL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sorting receptor that directs several proteins to their correct location within the cell (Probable). Along with AP-1 complex, involved Golgi apparatus - endosome sorting (PubMed:17646382). Sorting receptor for APP, regulating its intracellular trafficking and processing into amyloidogenic-beta peptides. Retains APP in the trans-Golgi network, hence preventing its transit through late endosomes where amyloid beta peptides Abeta40 and Abeta42 are generated (PubMed:16174740, PubMed:16407538, PubMed:17855360, PubMed:24523320). May also sort newly produced amyloid-beta peptides to lysosomes for catabolism (PubMed:24523320). Does not affect APP trafficking from the endoplasmic reticulum to Golgi compartments (PubMed:17855360). Sorting receptor for the BDNF receptor NTRK2/TRKB that facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling by controlling the intracellular location of its receptor (PubMed:23977241). Sorting receptor for GDNF that promotes GDNF regulated, but not constitutive secretion (PubMed:21994944). Sorting receptor for the GDNF-GFRA1 complex, directing it from the cell surface to endosomes. GDNF is then targeted to lysosomes and degraded, while its receptor GFRA1 recycles back to the cell membrane, resulting in a GDNF clearance pathway. The SORL1-GFRA1 complex further targets RET for endocytosis, but not for degradation, affecting GDNF-induced neurotrophic activities (PubMed:23333276). Sorting receptor for ERBB2/HER2. Regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent ERBB2 signaling. In ERBB2-dependent cancer cells, promotes cell proliferation (PubMed:31138794). Sorting receptor for lipoprotein lipase LPL. Promotes LPL localization to endosomes and later to the lysosomes, leading to degradation of newly synthesized LPL (PubMed:21385844). Potential sorting receptor for APOA5, inducing APOA5 internalization to early endosomes, then to late endosomes, wherefrom a portion is sent to lysosomes and degradation, another portion is sorted to the trans-Golgi network (PubMed:18603531). Sorting receptor for the insulin receptor INSR. Promotes recycling of internalized INSR via the Golgi apparatus back to the cell surface, thereby preventing lysosomal INSR catabolism, increasing INSR cell surface expression and strengthening insulin signal reception in adipose tissue. Does not affect INSR internalization (PubMed:27322061). Plays a role in renal ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly through intracellular sorting of STK39 and PPP3CB (By similarity). Stimulates, via the N-terminal ectodomain, the proliferation and migration of smooth muscle cells, possibly by increasing cell surface expression of the urokinase receptor uPAR/PLAUR. This may promote extracellular matrix proteolysis and hence facilitate cell migration (PubMed:14764453). By acting on the migration of intimal smooth muscle cells, may accelerate intimal thickening following vascular injury (PubMed:14764453). Promotes adhesion of monocytes (PubMed:23486467). Stimulates proliferation and migration of monocytes/macrophages (By similarity). Through its action on intimal smooth muscle cells and macrophages, may accelerate intimal thickening and macrophage foam cell formation in the process of atherosclerosis (By similarity). Regulates hypoxia-enhanced adhesion of hematopoietic stem and progenitor cells to the bone marrow stromal cells via a PLAUR-mediated pathway. This function is mediated by the N-terminal ectodomain (PubMed:23486467). Metabolic regulator, which functions to maintain the adequate balance between lipid storage and oxidation in response to changing environmental conditions, such as temperature and diet. The N-terminal ectodomain negatively regulates adipose tissue energy expenditure, acting through the inhibition the BMP/Smad pathway (By similarity). May regulate signaling by the heterodimeric neurotrophic cytokine CLCF1-CRLF1 bound to the CNTFR receptor by promoting the endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR and lysosomal degradation (PubMed:26858303). May regulate IL6 signaling, decreasing cis signaling, possibly by interfering with IL6-binding to membrane-bound IL6R, while up-regulating trans signaling via soluble IL6R (PubMed:28265003).By similarityCurated16 Publications

Miscellaneous

There may be a positive correlation of body mass index with levels of SORL1 transcript and SORLA protein in visceral adipose tissue.1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionReceptor
Biological processEndocytosis, Transport

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-977225 Amyloid fiber formation

SIGNOR Signaling Network Open Resource

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SIGNORi
Q92673

Protein family/group databases

Transport Classification Database

More...
TCDBi
9.B.87.1.17 the selenoprotein p receptor (selp-receptor) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Sortilin-related receptor
Alternative name(s):
Low-density lipoprotein receptor relative with 11 ligand-binding repeats
Short name:
LDLR relative with 11 ligand-binding repeats
Short name:
LR111 Publication
SorLA-11 Publication
Sorting protein-related receptor containing LDLR class A repeats
Short name:
SorLA1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SORL1
Synonyms:C11orf32
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 11

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:11185 SORL1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602005 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q92673

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini82 – 2137LumenalSequence analysisAdd BLAST2056
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei2138 – 2158HelicalSequence analysisAdd BLAST21
Topological domaini2159 – 2214CytoplasmicSequence analysisAdd BLAST56

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionAlzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_070012141Y → C in AD; unknown pathological significance. 1 Publication1
Natural variantiVAR_070013511G → R in AD; unknown pathological significance; loss of interaction with APP amyloid-beta peptides, hence reduced turnover of APP amyloid-beta peptides in cells. 2 Publications1
Natural variantiVAR_070014924N → S in AD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs377498269Ensembl.1
Natural variantiVAR_0700151358N → S in AD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs747306346Ensembl.1
Natural variantiVAR_0700161681G → D in AD; unknown pathological significance. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi78 – 81RRKR → GRKG: Loss of propeptide cleavage. 1 Publication4
Mutagenesisi2163 – 2164RR → AA: Affects the nuclear location of the C-terminal fragment generated by PSEN1. 1 Publication2
Mutagenesisi2172 – 2177FANSHY → AAASHA: No effect on endocytosis. 1 Publication6
Mutagenesisi2190 – 2214Missing : Strong reduction in Golgi apparatus - endosome sorting. Loss of interaction with AP-1 complex. 1 PublicationAdd BLAST25
Mutagenesisi2190 – 2198DDLGEDDED → AALGAAAAA: Loss of interaction with GGA1 and PACS1. No effect on interaction with APP. Affects subcellular location, increasing localization at the cell surface, possibly due to drastically decreased endocytosis. Impaired Golgi apparatus - endosome sorting. Increased amyloidogenic APP processing by beta-secretase, resulting in increased levels of soluble APP-beta and amyloid-beta protein 40 and 42. Loss of APOA5 internalization. 3 Publications9
Mutagenesisi2190 – 2191DD → AA: No effect on the interaction with HSPA12A. 1 Publication2
Mutagenesisi2194 – 2198EDDED → AAAAA: Strong decrease in interaction with HSPA12A. 1 Publication5
Mutagenesisi2201 – 2202MI → AA: No effect on endocytosis. Decreased Golgi apparatus - endosome sorting. 1 Publication2
Mutagenesisi2203 – 2204TG → AA: No effect on the interaction with HSPA12A. 1 Publication2
Mutagenesisi2205 – 2206FS → AA: No effect on the interaction with HSPA12A. 1 Publication2
Mutagenesisi2207 – 2208DD → AA: Strong decrease in interaction with HSPA12A. 1 Publication2
Mutagenesisi2208 – 2211DVPM → AVPA: Loss of interaction with GGA1 and PACS1. No effect on interaction with APP. Affects subcellular location, by causing increased localization to recycling endosomes. Increased APP processing by alpha-secretase, resulting in increased levels of soluble APP-alpha and C83 APP fragments. Decreased APP processing by beta-secretase, resulting in reduced levels of C99 APP fragment. 1 Publication4
Mutagenesisi2209 – 2210VP → AA: No effect on the interaction with HSPA12A. 1 Publication2
Mutagenesisi2211 – 2214Missing : No effect on endocytosis. Affects LPL sorting to endosomes. 2 Publications4

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Disease mutation, Neurodegeneration

Organism-specific databases

DisGeNET

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DisGeNETi
6653

MalaCards human disease database

More...
MalaCardsi
SORL1
MIMi104300 phenotype

NIAGADS Genomics Database

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NIAGADSi
ENSG00000137642

Open Targets

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OpenTargetsi
ENSG00000137642

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
1020 Early-onset autosomal dominant Alzheimer disease
238616 NON RARE IN EUROPE: Alzheimer disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA36022

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
SORL1

Domain mapping of disease mutations (DMDM)

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DMDMi
296452912

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 28Sequence analysisAdd BLAST28
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_000003316429 – 81Removed in mature form1 PublicationAdd BLAST53
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000003316582 – 2214Sortilin-related receptorAdd BLAST2133

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi99N-linked (GlcNAc...) asparagine1 Publication1
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei114PhosphoserineCombined sources1
Glycosylationi158N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi368N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi430N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi616N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi674N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi818N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi871N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1035N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1068N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi1078 ↔ 1090PROSITE-ProRule annotation
Disulfide bondi1085 ↔ 1103PROSITE-ProRule annotation
Disulfide bondi1097 ↔ 1112PROSITE-ProRule annotation
Disulfide bondi1117 ↔ 1131PROSITE-ProRule annotation
Disulfide bondi1125 ↔ 1144PROSITE-ProRule annotation
Disulfide bondi1138 ↔ 1153PROSITE-ProRule annotation
Disulfide bondi1158 ↔ 1170PROSITE-ProRule annotation
Glycosylationi1164N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1165 ↔ 1183PROSITE-ProRule annotation
Disulfide bondi1177 ↔ 1192PROSITE-ProRule annotation
Glycosylationi1191N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1199 ↔ 1211PROSITE-ProRule annotation
Disulfide bondi1206 ↔ 1224PROSITE-ProRule annotation
Disulfide bondi1218 ↔ 1235PROSITE-ProRule annotation
Disulfide bondi1239 ↔ 1249PROSITE-ProRule annotation
Disulfide bondi1244 ↔ 1262PROSITE-ProRule annotation
Glycosylationi1246N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1256 ↔ 1271PROSITE-ProRule annotation
Disulfide bondi1275 ↔ 1289PROSITE-ProRule annotation
Disulfide bondi1283 ↔ 1302PROSITE-ProRule annotation
Disulfide bondi1296 ↔ 1315PROSITE-ProRule annotation
Disulfide bondi1325 ↔ 1337PROSITE-ProRule annotation
Disulfide bondi1332 ↔ 1350PROSITE-ProRule annotation
Disulfide bondi1344 ↔ 1359PROSITE-ProRule annotation
Glycosylationi1367N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1368 ↔ 1381PROSITE-ProRule annotation
Disulfide bondi1376 ↔ 1394PROSITE-ProRule annotation
Disulfide bondi1388 ↔ 1403PROSITE-ProRule annotation
Disulfide bondi1419 ↔ 1431PROSITE-ProRule annotation
Disulfide bondi1426 ↔ 1444PROSITE-ProRule annotation
Disulfide bondi1438 ↔ 1453PROSITE-ProRule annotation
Glycosylationi1458N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1471 ↔ 1484PROSITE-ProRule annotation
Disulfide bondi1478 ↔ 1497PROSITE-ProRule annotation
Disulfide bondi1491 ↔ 1506PROSITE-ProRule annotation
Disulfide bondi1514 ↔ 1527PROSITE-ProRule annotation
Disulfide bondi1521 ↔ 1540PROSITE-ProRule annotation
Disulfide bondi1534 ↔ 1549PROSITE-ProRule annotation
Glycosylationi1608N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1706N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1733N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi1809N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1854N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1894N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1986N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi2010N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi2054N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi2069N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi2076N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi2092N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei2206Phosphoserine; by ROCK21 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Within the Golgi apparatus, the propeptide may be cleaved off by FURIN or a furin-like protease (Probable). After cleavage, the propeptide interacts with the mature protein N-terminus, preventing the association with other ligands (PubMed:11294867). At the cell surface, partially subjected to proteolytic shedding that releases the ectodomain in the extracellular milieu (PubMed:11082041, PubMed:16393139, PubMed:16531402, PubMed:28265003). The shedding may be catalyzed by ADAM17/TACE (PubMed:16393139, PubMed:16531402). Following shedding, PSEN1/presenilin-1 cleaves the remaining transmembrane fragment and catalyzes the release of a C-terminal fragment in the cytosol and of a soluble N-terminal beta fragment in the extracellular milieu. The C-terminal cytosolic fragment localizes to the nucleus (PubMed:16531402).2 Publications5 Publications
Phosphorylation at Ser-2206 facilitates the interaction with GGA1.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q92673

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q92673

MaxQB - The MaxQuant DataBase

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MaxQBi
Q92673

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q92673

PeptideAtlas

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PeptideAtlasi
Q92673

PRoteomics IDEntifications database

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PRIDEi
Q92673

ProteomicsDB human proteome resource

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ProteomicsDBi
75402

PTM databases

GlyConnect protein glycosylation platform

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GlyConnecti
1766

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q92673

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q92673

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Highly expressed in brain (at protein level) (PubMed:9157966, PubMed:16174740, PubMed:21147781). Most abundant in the cerebellum, cerebral cortex and occipital pole; low levels in the putamen and thalamus (PubMed:9157966, PubMed:16174740). Expression is significantly reduced in the frontal cortex of patients suffering from Alzheimer disease (PubMed:16174740). Also expressed in spinal cord, spleen, testis, prostate, ovary, tyroid and lymph nodes (PubMed:9157966, PubMed:8940146).4 Publications

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Up-regulated by morphogenetic neuropeptide, also called head activator or HA (PubMed:11082041). Up-regulated under hypoxic conditions in hematopoietic stem and progenitor cells, a physiological condition encountered by these cells in the endosteum. This up-regulation may be mediated by HIF1A-induced transcription (PubMed:23486467).2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000137642 Expressed in 235 organ(s), highest expression level in blood

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q92673 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q92673 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB011500
HPA031321

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

After maturation cleavage, interacts (via N-terminus) with its own propeptide; this interaction prevents interaction with other ligands, including CRLF1, GDNF, GFRA1, IL6 and IL6R (PubMed:11294867, PubMed:12530537, PubMed:15364913, PubMed:23333276, PubMed:24523320).

Interacts (via N-terminal ectodomain) with APP, forming a 1:1 stoichiometric complex, including with isoforms APP695, APP751 and APP770; this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (PubMed:16174740, PubMed:16407538, PubMed:17855360, PubMed:24523320). Also interact with APP C-terminal fragment C99 and with Abeta40 (PubMed:16407538).

Interacts with beta-secretase BACE1/BACE; this interaction may affect BACE1-binding to APP and hence reduce BACE1-dependent APP cleavage (PubMed:16407538).

Interacts with LRPAP1/RAP (PubMed:8940146, PubMed:11294867, PubMed:12530537, PubMed:15053742, PubMed:14764453, PubMed:15364913, PubMed:26858303).

Interacts (via C-terminal cytosolic domain) with GGA1 and GGA2 (via N-terminal VHS domain) (PubMed:11821067, PubMed:17855360, PubMed:30679749, PubMed:20015111).

Interacts with PACS1 (PubMed:17855360, PubMed:17646382). May interact (via the N-terminal ectodomain) with the morphogenetic neuropeptide, also called head activator or HA; this interaction is impaired in the presence of propeptide (PubMed:11082041, PubMed:11294867, PubMed:12530537).

Interacts with neurotensin/NTS (PubMed:11294867).

Interacts (via the N-terminal ectodomain) with PDGFB homodimer (PubMed:15053742, PubMed:16393139).

Interacts (via N-terminal ectodomain) with the uPA receptor PLAUR; this interaction decreases PLAUR internalization (PubMed:14764453, PubMed:23486467).

Interacts (via N-terminal ectodomain) with uPA/PLAU and PAI1/SERPINE1, either individually or in complex with each other, leading to endocytosis; this interaction is abolished in the presence of LRPAP1 (PubMed:15053742). Also interact with the ternary complex composed of PLAUR-PLAU-PAI1 (PubMed:15053742).

Also interacts with tPA/PLAT either alone or in complex with SERPINE1 (PubMed:15053742).

Interacts (via C-terminus) with AP-1 and AP-2 complexes (PubMed:17646382).

Interacts with BMPR1A and BMPR1B (By similarity).

Interacts with lipoprotein lipase LPL; this interaction is optimal in slightly acidic conditions (PubMed:21385844).

Interacts (via N-terminal ectodomain) with GDNF (via propeptide) and GDNF receptor alpha-1/GFRA1, either individually or in complex with each other (PubMed:15364913, PubMed:21994944, PubMed:23333276). The interaction with GDNF occurs mostly intracellularly (PubMed:21994944).

Also interacts with other GDNF receptor alpha family members, including GFRA2, GFRA3 and GFRA4 (PubMed:23333276).

Interacts with the insulin receptor INSR; this interaction strongly increases the surface exposure of INSR (PubMed:27322061).

Interacts (via cytosolic C-terminus) with STK39/SPAK (PubMed:20385770).

Interacts (via N-terminal ectodomain) with the heterodimeric complex CRLF1-CLC; within this complex, the interaction is mediated predominantly by the CRLF1 moiety (PubMed:26858303).

Interacts with CNTFR, as well as with the tripartite signaling complex formed by CRLF1, CLC and CNTFR (PubMed:26858303).

Interacts (via N-terminal ectodomain) with IL6; this interaction leads to IL6 internalization and lysosomal degradation (PubMed:28265003). Binding of SOLRL1 secreted N-terminal ectodomain to IL6 may increase IL6 trans signaling (PubMed:28265003).

Interacts with secreted IL6R; this interaction leads to IL6R internalization (PubMed:28265003).

Also interacts with transmembrane IL6R; this interaction does not affect IL6R subcellular location (PubMed:28265003).

Interacts with APOE (PubMed:30448281).

Interacts with apolipoprotein E-rich beta-VLDL (By similarity).

Interacts with APOA5; this interaction leads to APOA5 internalization and is abolished by heparin (PubMed:17326667, PubMed:18603531). Interaction with APOA5 results in enhanced binding to chylomicrons (PubMed:17326667).

Interacts with ROCK2 (PubMed:21147781).

Interacts (via cytosolic C-terminus) with PPP3CB/calcineurin A beta (By similarity).

Interacts with NTRK2/TRKB; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling (By similarity).

Interacts (via cytosolic C-terminus) with HSPA12A in an ADP-dependent manner; this interaction affects SORL1 internalization and subcellular localization (PubMed:30679749).

Interacts (via N-terminal ectodomain) with ERBB2/HER2 (PubMed:31138794).

By similarity29 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
112536, 65 interactors

Database of interacting proteins

More...
DIPi
DIP-41229N

Protein interaction database and analysis system

More...
IntActi
Q92673, 15 interactors

Molecular INTeraction database

More...
MINTi
Q92673

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000260197

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

12214
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...
SMRi
Q92673

Database of comparative protein structure models

More...
ModBasei
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
Q92673

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati136 – 147BNR 1Add BLAST12
Repeati232 – 243BNR 2Add BLAST12
Repeati441 – 452BNR 3Add BLAST12
Repeati521 – 532BNR 4Add BLAST12
Repeati562 – 573BNR 5Add BLAST12
Repeati800 – 843LDL-receptor class B 1Add BLAST44
Repeati844 – 887LDL-receptor class B 2Add BLAST44
Repeati888 – 932LDL-receptor class B 3Add BLAST45
Repeati933 – 970LDL-receptor class B 4Add BLAST38
Repeati971 – 1013LDL-receptor class B 5Add BLAST43
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini1026 – 1072EGF-likeAdd BLAST47
Domaini1076 – 1114LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST39
Domaini1115 – 1155LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST41
Domaini1156 – 1194LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST39
Domaini1198 – 1236LDL-receptor class A 4PROSITE-ProRule annotationAdd BLAST39
Domaini1238 – 1272LDL-receptor class A 5PROSITE-ProRule annotationAdd BLAST35
Domaini1273 – 1317LDL-receptor class A 6PROSITE-ProRule annotationAdd BLAST45
Domaini1323 – 1361LDL-receptor class A 7PROSITE-ProRule annotationAdd BLAST39
Domaini1366 – 1405LDL-receptor class A 8PROSITE-ProRule annotationAdd BLAST40
Domaini1417 – 1455LDL-receptor class A 9PROSITE-ProRule annotationAdd BLAST39
Domaini1469 – 1508LDL-receptor class A 10PROSITE-ProRule annotationAdd BLAST40
Domaini1512 – 1551LDL-receptor class A 11PROSITE-ProRule annotationAdd BLAST40
Domaini1557 – 1649Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST93
Domaini1653 – 1745Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST93
Domaini1749 – 1844Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST96
Domaini1843 – 1927Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST85
Domaini1934 – 2029Fibronectin type-III 5PROSITE-ProRule annotationAdd BLAST96
Domaini2030 – 2118Fibronectin type-III 6PROSITE-ProRule annotationAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni2190 – 2214Required for efficient Golgi apparatus - endosome sorting1 PublicationAdd BLAST25
Regioni2201 – 2214Required for interaction with GGA1 and GGA21 PublicationAdd BLAST14

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi63 – 65Cell attachment siteSequence analysis3
Motifi2161 – 2164Potential nuclear localization signal for the C-terminal fragment generated by PSEN11 Publication4
Motifi2172 – 2177Endocytosis signalSequence analysis6
Motifi2208 – 2212DXXLL motif involved in the interaction with GGA11 Publication5

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG1215 Eukaryota
KOG3511 Eukaryota
ENOG410Y3W5 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00950000182727

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000007009

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
Q92673

Identification of Orthologs from Complete Genome Data

More...
OMAi
QLKNNTC

Database of Orthologous Groups

More...
OrthoDBi
1010560at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
Q92673

TreeFam database of animal gene trees

More...
TreeFami
TF324918

Family and domain databases

Conserved Domains Database

More...
CDDi
cd00063 FN3, 5 hits
cd00112 LDLa, 11 hits

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
2.120.10.30, 1 hit
2.130.10.10, 1 hit
2.60.40.10, 3 hits
4.10.400.10, 11 hits

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR013783 Ig-like_fold
IPR036055 LDL_receptor-like_sf
IPR023415 LDLR_class-A_CS
IPR000033 LDLR_classB_rpt
IPR002172 LDrepeatLR_classA_rpt
IPR031777 Sortilin_C
IPR031778 Sortilin_N
IPR006581 VPS10
IPR015943 WD40/YVTN_repeat-like_dom_sf

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00041 fn3, 3 hits
PF00057 Ldl_recept_a, 10 hits
PF00058 Ldl_recept_b, 2 hits
PF15902 Sortilin-Vps10, 1 hit
PF15901 Sortilin_C, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR00261 LDLRECEPTOR

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00060 FN3, 6 hits
SM00192 LDLa, 11 hits
SM00135 LY, 5 hits
SM00602 VPS10, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF49265 SSF49265, 3 hits
SSF57424 SSF57424, 11 hits

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS01186 EGF_2, 1 hit
PS50853 FN3, 4 hits
PS01209 LDLRA_1, 10 hits
PS50068 LDLRA_2, 11 hits
PS51120 LDLRB, 5 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

Q92673-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MATRSSRRES RLPFLFTLVA LLPPGALCEV WTQRLHGGSA PLPQDRGFLV
60 70 80 90 100
VQGDPRELRL WARGDARGAS RADEKPLRRK RSAALQPEPI KVYGQVSLND
110 120 130 140 150
SHNQMVVHWA GEKSNVIVAL ARDSLALARP KSSDVYVSYD YGKSFKKISD
160 170 180 190 200
KLNFGLGNRS EAVIAQFYHS PADNKRYIFA DAYAQYLWIT FDFCNTLQGF
210 220 230 240 250
SIPFRAADLL LHSKASNLLL GFDRSHPNKQ LWKSDDFGQT WIMIQEHVKS
260 270 280 290 300
FSWGIDPYDK PNTIYIERHE PSGYSTVFRS TDFFQSRENQ EVILEEVRDF
310 320 330 340 350
QLRDKYMFAT KVVHLLGSEQ QSSVQLWVSF GRKPMRAAQF VTRHPINEYY
360 370 380 390 400
IADASEDQVF VCVSHSNNRT NLYISEAEGL KFSLSLENVL YYSPGGAGSD
410 420 430 440 450
TLVRYFANEP FADFHRVEGL QGVYIATLIN GSMNEENMRS VITFDKGGTW
460 470 480 490 500
EFLQAPAFTG YGEKINCELS QGCSLHLAQR LSQLLNLQLR RMPILSKESA
510 520 530 540 550
PGLIIATGSV GKNLASKTNV YISSSAGARW REALPGPHYY TWGDHGGIIT
560 570 580 590 600
AIAQGMETNE LKYSTNEGET WKTFIFSEKP VFVYGLLTEP GEKSTVFTIF
610 620 630 640 650
GSNKENVHSW LILQVNATDA LGVPCTENDY KLWSPSDERG NECLLGHKTV
660 670 680 690 700
FKRRTPHATC FNGEDFDRPV VVSNCSCTRE DYECDFGFKM SEDLSLEVCV
710 720 730 740 750
PDPEFSGKSY SPPVPCPVGS TYRRTRGYRK ISGDTCSGGD VEARLEGELV
760 770 780 790 800
PCPLAEENEF ILYAVRKSIY RYDLASGATE QLPLTGLRAA VALDFDYEHN
810 820 830 840 850
CLYWSDLALD VIQRLCLNGS TGQEVIINSG LETVEALAFE PLSQLLYWVD
860 870 880 890 900
AGFKKIEVAN PDGDFRLTIV NSSVLDRPRA LVLVPQEGVM FWTDWGDLKP
910 920 930 940 950
GIYRSNMDGS AAYHLVSEDV KWPNGISVDD QWIYWTDAYL ECIERITFSG
960 970 980 990 1000
QQRSVILDNL PHPYAIAVFK NEIYWDDWSQ LSIFRASKYS GSQMEILANQ
1010 1020 1030 1040 1050
LTGLMDMKIF YKGKNTGSNA CVPRPCSLLC LPKANNSRSC RCPEDVSSSV
1060 1070 1080 1090 1100
LPSGDLMCDC PQGYQLKNNT CVKQENTCLR NQYRCSNGNC INSIWWCDFD
1110 1120 1130 1140 1150
NDCGDMSDER NCPTTICDLD TQFRCQESGT CIPLSYKCDL EDDCGDNSDE
1160 1170 1180 1190 1200
SHCEMHQCRS DEYNCSSGMC IRSSWVCDGD NDCRDWSDEA NCTAIYHTCE
1210 1220 1230 1240 1250
ASNFQCRNGH CIPQRWACDG DTDCQDGSDE DPVNCEKKCN GFRCPNGTCI
1260 1270 1280 1290 1300
PSSKHCDGLR DCSDGSDEQH CEPLCTHFMD FVCKNRQQCL FHSMVCDGII
1310 1320 1330 1340 1350
QCRDGSDEDA AFAGCSQDPE FHKVCDEFGF QCQNGVCISL IWKCDGMDDC
1360 1370 1380 1390 1400
GDYSDEANCE NPTEAPNCSR YFQFRCENGH CIPNRWKCDR ENDCGDWSDE
1410 1420 1430 1440 1450
KDCGDSHILP FSTPGPSTCL PNYYRCSSGT CVMDTWVCDG YRDCADGSDE
1460 1470 1480 1490 1500
EACPLLANVT AASTPTQLGR CDRFEFECHQ PKTCIPNWKR CDGHQDCQDG
1510 1520 1530 1540 1550
RDEANCPTHS TLTCMSREFQ CEDGEACIVL SERCDGFLDC SDESDEKACS
1560 1570 1580 1590 1600
DELTVYKVQN LQWTADFSGD VTLTWMRPKK MPSASCVYNV YYRVVGESIW
1610 1620 1630 1640 1650
KTLETHSNKT NTVLKVLKPD TTYQVKVQVQ CLSKAHNTND FVTLRTPEGL
1660 1670 1680 1690 1700
PDAPRNLQLS LPREAEGVIV GHWAPPIHTH GLIREYIVEY SRSGSKMWAS
1710 1720 1730 1740 1750
QRAASNFTEI KNLLVNTLYT VRVAAVTSRG IGNWSDSKSI TTIKGKVIPP
1760 1770 1780 1790 1800
PDIHIDSYGE NYLSFTLTME SDIKVNGYVV NLFWAFDTHK QERRTLNFRG
1810 1820 1830 1840 1850
SILSHKVGNL TAHTSYEISA WAKTDLGDSP LAFEHVMTRG VRPPAPSLKA
1860 1870 1880 1890 1900
KAINQTAVEC TWTGPRNVVY GIFYATSFLD LYRNPKSLTT SLHNKTVIVS
1910 1920 1930 1940 1950
KDEQYLFLVR VVVPYQGPSS DYVVVKMIPD SRLPPRHLHV VHTGKTSVVI
1960 1970 1980 1990 2000
KWESPYDSPD QDLLYAVAVK DLIRKTDRSY KVKSRNSTVE YTLNKLEPGG
2010 2020 2030 2040 2050
KYHIIVQLGN MSKDSSIKIT TVSLSAPDAL KIITENDHVL LFWKSLALKE
2060 2070 2080 2090 2100
KHFNESRGYE IHMFDSAMNI TAYLGNTTDN FFKISNLKMG HNYTFTVQAR
2110 2120 2130 2140 2150
CLFGNQICGE PAILLYDELG SGADASATQA ARSTDVAAVV VPILFLILLS
2160 2170 2180 2190 2200
LGVGFAILYT KHRRLQSSFT AFANSHYSSR LGSAIFSSGD DLGEDDEDAP
2210
MITGFSDDVP MVIA
Length:2,214
Mass (Da):248,426
Last modified:May 18, 2010 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i4C215BB33E65C0B2
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PPB3E9PPB3_HUMAN
Sortilin-related receptor
SORL1
1,158Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E9PP43E9PP43_HUMAN
Sortilin-related receptor
SORL1
1,124Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E9PS32E9PS32_HUMAN
Sortilin-related receptor
SORL1
1,060Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E9PKB0E9PKB0_HUMAN
Sortilin-related receptor
SORL1
829Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036371120L → S in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_070012141Y → C in AD; unknown pathological significance. 1 Publication1
Natural variantiVAR_070013511G → R in AD; unknown pathological significance; loss of interaction with APP amyloid-beta peptides, hence reduced turnover of APP amyloid-beta peptides in cells. 2 Publications1
Natural variantiVAR_020360528A → T1 PublicationCorresponds to variant dbSNP:rs2298813Ensembl.1
Natural variantiVAR_070014924N → S in AD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs377498269Ensembl.1
Natural variantiVAR_0345081074Q → E4 PublicationsCorresponds to variant dbSNP:rs1699107Ensembl.1
Natural variantiVAR_0700151358N → S in AD; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs747306346Ensembl.1
Natural variantiVAR_0363721581M → L in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_0700161681G → D in AD; unknown pathological significance. 1 Publication1
Natural variantiVAR_0345091967V → I4 PublicationsCorresponds to variant dbSNP:rs1792120Ensembl.1
Natural variantiVAR_0363731972L → V in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs766895956Ensembl.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
Y08110 mRNA Translation: CAA69325.1
U60975 mRNA Translation: AAC50891.2
AP000664 Genomic DNA No translation available.
AP000977 Genomic DNA No translation available.
CH471065 Genomic DNA Translation: EAW67525.1
BC137171 mRNA Translation: AAI37172.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS8436.1

NCBI Reference Sequences

More...
RefSeqi
NP_003096.1, NM_003105.5

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000260197; ENSP00000260197; ENSG00000137642

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
6653

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:6653

UCSC genome browser

More...
UCSCi
uc001pxx.4 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08110 mRNA Translation: CAA69325.1
U60975 mRNA Translation: AAC50891.2
AP000664 Genomic DNA No translation available.
AP000977 Genomic DNA No translation available.
CH471065 Genomic DNA Translation: EAW67525.1
BC137171 mRNA Translation: AAI37172.1
CCDSiCCDS8436.1
RefSeqiNP_003096.1, NM_003105.5

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DM4NMR-A1651-1745[»]
3G2SX-ray1.70C/D2202-2214[»]
3G2TX-ray2.00C/D2202-2214[»]
3WSXX-ray2.35A29-753[»]
3WSYX-ray3.11A86-753[»]
C42-56[»]
3WSZX-ray3.20A86-753[»]
SMRiQ92673
ModBaseiSearch...

Protein-protein interaction databases

BioGridi112536, 65 interactors
DIPiDIP-41229N
IntActiQ92673, 15 interactors
MINTiQ92673
STRINGi9606.ENSP00000260197

Protein family/group databases

TCDBi9.B.87.1.17 the selenoprotein p receptor (selp-receptor) family

PTM databases

GlyConnecti1766
iPTMnetiQ92673
PhosphoSitePlusiQ92673

Polymorphism and mutation databases

BioMutaiSORL1
DMDMi296452912

Proteomic databases

EPDiQ92673
jPOSTiQ92673
MaxQBiQ92673
PaxDbiQ92673
PeptideAtlasiQ92673
PRIDEiQ92673
ProteomicsDBi75402

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260197; ENSP00000260197; ENSG00000137642
GeneIDi6653
KEGGihsa:6653
UCSCiuc001pxx.4 human

Organism-specific databases

Comparative Toxicogenomics Database

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CTDi
6653
DisGeNETi6653

GeneCards: human genes, protein and diseases

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GeneCardsi
SORL1
HGNCiHGNC:11185 SORL1
HPAiCAB011500
HPA031321
MalaCardsiSORL1
MIMi104300 phenotype
602005 gene
neXtProtiNX_Q92673
NIAGADSiENSG00000137642
OpenTargetsiENSG00000137642
Orphaneti1020 Early-onset autosomal dominant Alzheimer disease
238616 NON RARE IN EUROPE: Alzheimer disease
PharmGKBiPA36022

GenAtlas: human gene database

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GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1215 Eukaryota
KOG3511 Eukaryota
ENOG410Y3W5 LUCA
GeneTreeiENSGT00950000182727
HOGENOMiHOG000007009
InParanoidiQ92673
OMAiQLKNNTC
OrthoDBi1010560at2759
PhylomeDBiQ92673
TreeFamiTF324918

Enzyme and pathway databases

ReactomeiR-HSA-977225 Amyloid fiber formation
SIGNORiQ92673

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

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ChiTaRSi
SORL1 human
EvolutionaryTraceiQ92673

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
6653

Protein Ontology

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PROi
PR:Q92673

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSG00000137642 Expressed in 235 organ(s), highest expression level in blood
ExpressionAtlasiQ92673 baseline and differential
GenevisibleiQ92673 HS

Family and domain databases

CDDicd00063 FN3, 5 hits
cd00112 LDLa, 11 hits
Gene3Di2.120.10.30, 1 hit
2.130.10.10, 1 hit
2.60.40.10, 3 hits
4.10.400.10, 11 hits
InterProiView protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR013783 Ig-like_fold
IPR036055 LDL_receptor-like_sf
IPR023415 LDLR_class-A_CS
IPR000033 LDLR_classB_rpt
IPR002172 LDrepeatLR_classA_rpt
IPR031777 Sortilin_C
IPR031778 Sortilin_N
IPR006581 VPS10
IPR015943 WD40/YVTN_repeat-like_dom_sf
PfamiView protein in Pfam
PF00041 fn3, 3 hits
PF00057 Ldl_recept_a, 10 hits
PF00058 Ldl_recept_b, 2 hits
PF15902 Sortilin-Vps10, 1 hit
PF15901 Sortilin_C, 1 hit
PRINTSiPR00261 LDLRECEPTOR
SMARTiView protein in SMART
SM00060 FN3, 6 hits
SM00192 LDLa, 11 hits
SM00135 LY, 5 hits
SM00602 VPS10, 1 hit
SUPFAMiSSF49265 SSF49265, 3 hits
SSF57424 SSF57424, 11 hits
PROSITEiView protein in PROSITE
PS01186 EGF_2, 1 hit
PS50853 FN3, 4 hits
PS01209 LDLRA_1, 10 hits
PS50068 LDLRA_2, 11 hits
PS51120 LDLRB, 5 hits

ProtoNet; Automatic hierarchical classification of proteins

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ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSORL_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q92673
Secondary accession number(s): B2RNX7, Q92856
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 18, 2010
Last modified: July 31, 2019
This is version 198 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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