SORL1
entrez
6653
canonical
uniprot
Q92673
canonical
ensembl
ENSG00000137642
resolver
ensp
ENSP00000260197
resolver
enst
ENST00000260197
resolver
genesymbol
SORL1
resolver
genesymbol_syn
C11orf32
resolver
hgnc
HGNC:11185
resolver
uniprot
B2RNX7
resolver
uniprot
Q92856
resolver
uniprot_entry
SORL_HUMAN
resolver
uniprot_sec
B2RNX7
resolver
uniprot_sec
Q92856
resolver
amino_acid_sequence
MATRSSRRESRLPFLFTLVALLPPGALCEVWTQRLHGGSAPLPQDRGFLVVQGDPRELRLWARGDARGASRADEKPLRRKRSAALQPEPIKVYGQVSLNDSHNQMVVHWAGEKSNVIVALARDSLALARPKSSDVYVSYDYGKSFKKISDKLNFGLGNRSEAVIAQFYHSPADNKRYIFADAYAQYLWITFDFCNTLQGFSIPFRAADLLLHSKASNLLLGFDRSHPNKQLWKSDDFGQTWIMIQEHVKSFSWGIDPYDKPNTIYIERHEPSGYSTVFRSTDFFQSRENQEVILEEVRDFQLRDKYMFATKVVHLLGSEQQSSVQLWVSFGRKPMRAAQFVTRHPINEYYIADASEDQVFVCVSHSNNRTNLYISEAEGLKFSLSLENVLYYSPGGAGSDTLVRYFANEPFADFHRVEGLQGVYIATLINGSMNEENMRSVITFDKGGTWEFLQAPAFTGYGEKINCELSQGCSLHLAQRLSQLLNLQLRRMPILSKESAPGLIIATGSVGKNLASKTNVYISSSAGARWREALPGPHYYTWGDHGGIITAIAQGMETNELKYSTNEGETWKTFIFSEKPVFVYGLLTEPGEKSTVFTIFGSNKENVHSWLILQVNATDALGVPCTENDYKLWSPSDERGNECLLGHKTVFKRRTPHATCFNGEDFDRPVVVSNCSCTREDYECDFGFKMSEDLSLEVCVPDPEFSGKSYSPPVPCPVGSTYRRTRGYRKISGDTCSGGDVEARLEGELVPCPLAEENEFILYAVRKSIYRYDLASGATEQLPLTGLRAAVALDFDYEHNCLYWSDLALDVIQRLCLNGSTGQEVIINSGLETVEALAFEPLSQLLYWVDAGFKKIEVANPDGDFRLTIVNSSVLDRPRALVLVPQEGVMFWTDWGDLKPGIYRSNMDGSAAYHLVSEDVKWPNGISVDDQWIYWTDAYLECIERITFSGQQRSVILDNLPHPYAIAVFKNEIYWDDWSQLSIFRASKYSGSQMEILANQLTGLMDMKIFYKGKNTGSNACVPRPCSLLCLPKANNSRSCRCPEDVSSSVLPSGDLMCDCPQGYQLKNNTCVKQENTCLRNQYRCSNGNCINSIWWCDFDNDCGDMSDERNCPTTICDLDTQFRCQESGTCIPLSYKCDLEDDCGDNSDESHCEMHQCRSDEYNCSSGMCIRSSWVCDGDNDCRDWSDEANCTAIYHTCEASNFQCRNGHCIPQRWACDGDTDCQDGSDEDPVNCEKKCNGFRCPNGTCIPSSKHCDGLRDCSDGSDEQHCEPLCTHFMDFVCKNRQQCLFHSMVCDGIIQCRDGSDEDAAFAGCSQDPEFHKVCDEFGFQCQNGVCISLIWKCDGMDDCGDYSDEANCENPTEAPNCSRYFQFRCENGHCIPNRWKCDRENDCGDWSDEKDCGDSHILPFSTPGPSTCLPNYYRCSSGTCVMDTWVCDGYRDCADGSDEEACPLLANVTAASTPTQLGRCDRFEFECHQPKTCIPNWKRCDGHQDCQDGRDEANCPTHSTLTCMSREFQCEDGEACIVLSERCDGFLDCSDESDEKACSDELTVYKVQNLQWTADFSGDVTLTWMRPKKMPSASCVYNVYYRVVGESIWKTLETHSNKTNTVLKVLKPDTTYQVKVQVQCLSKAHNTNDFVTLRTPEGLPDAPRNLQLSLPREAEGVIVGHWAPPIHTHGLIREYIVEYSRSGSKMWASQRAASNFTEIKNLLVNTLYTVRVAAVTSRGIGNWSDSKSITTIKGKVIPPPDIHIDSYGENYLSFTLTMESDIKVNGYVVNLFWAFDTHKQERRTLNFRGSILSHKVGNLTAHTSYEISAWAKTDLGDSPLAFEHVMTRGVRPPAPSLKAKAINQTAVECTWTGPRNVVYGIFYATSFLDLYRNPKSLTTSLHNKTVIVSKDEQYLFLVRVVVPYQGPSSDYVVVKMIPDSRLPPRHLHVVHTGKTSVVIKWESPYDSPDQDLLYAVAVKDLIRKTDRSYKVKSRNSTVEYTLNKLEPGGKYHIIVQLGNMSKDSSIKITTVSLSAPDALKIITENDHVLLFWKSLALKEKHFNESRGYEIHMFDSAMNITAYLGNTTDNFFKISNLKMGHNYTFTVQARCLFGNQICGEPAILLYDELGSGADASATQAARSTDVAAVVVPILFLILLSLGVGFAILYTKHRRLQSSFTAFANSHYSSRLGSAIFSSGDDLGEDDEDAPMITGFSDDVPMVIA
uniprot
proteins
disease_involvement
DISEASE: Alzheimer disease (AD) [MIM:104300]: Alzheimer 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. {ECO:0000269|PubMed:21220680, ECO:0000269|PubMed:22472873, ECO:0000269|PubMed:23565137, ECO:0000269|PubMed:24523320}. Note=The gene represented in this entry may be involved in disease pathogenesis.
uniprot
proteins
function
FUNCTION: 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). Sorting receptor that 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). {ECO:0000250|UniProtKB:O88307, ECO:0000269|PubMed:14764453, ECO:0000269|PubMed:16174740, ECO:0000269|PubMed:16407538, ECO:0000269|PubMed:17646382, ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:18603531, ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:23486467, ECO:0000269|PubMed:23977241, ECO:0000269|PubMed:24523320, ECO:0000269|PubMed:26858303, ECO:0000269|PubMed:27322061, ECO:0000269|PubMed:28265003, ECO:0000269|PubMed:31138794, ECO:0000305}.
uniprot
proteins
mass_dalton
248426
uniprot
proteins
mutagenesis
MUTAGEN 78..81; /note="RRKR->GRKG: Loss of propeptide cleavage."; /evidence="ECO:0000269|PubMed:11294867"; MUTAGEN 2163..2164; /note="RR->AA: Affects the nuclear location of the C-terminal fragment generated by PSEN1."; /evidence="ECO:0000269|PubMed:16531402"; MUTAGEN 2172..2177; /note="FANSHY->AAASHA: No effect on endocytosis."; /evidence="ECO:0000269|PubMed:17646382"; MUTAGEN 2190..2214; /note="Missing: Strong reduction in Golgi apparatus - endosome sorting. Loss of interaction with AP-1 complex."; /evidence="ECO:0000269|PubMed:17646382"; MUTAGEN 2190..2198; /note="DDLGEDDED->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."; /evidence="ECO:0000269|PubMed:17646382, ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:18603531"; MUTAGEN 2190..2191; /note="DD->AA: No effect on the interaction with HSPA12A."; /evidence="ECO:0000269|PubMed:30679749"; MUTAGEN 2194..2198; /note="EDDED->AAAAA: Strong decrease in interaction with HSPA12A."; /evidence="ECO:0000269|PubMed:30679749"; MUTAGEN 2201..2202; /note="MI->AA: No effect on endocytosis. Decreased Golgi apparatus - endosome sorting."; /evidence="ECO:0000269|PubMed:17646382"; MUTAGEN 2203..2204; /note="TG->AA: No effect on the interaction with HSPA12A."; /evidence="ECO:0000269|PubMed:30679749"; MUTAGEN 2205..2206; /note="FS->AA: No effect on the interaction with HSPA12A."; /evidence="ECO:0000269|PubMed:30679749"; MUTAGEN 2207..2208; /note="DD->AA: Strong decrease in interaction with HSPA12A."; /evidence="ECO:0000269|PubMed:30679749"; MUTAGEN 2208..2211; /note="DVPM->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."; /evidence="ECO:0000269|PubMed:17855360"; MUTAGEN 2209..2210; /note="VP->AA: No effect on the interaction with HSPA12A."; /evidence="ECO:0000269|PubMed:30679749"; MUTAGEN 2211..2214; /note="Missing: No effect on endocytosis. Affects LPL sorting to endosomes."; /evidence="ECO:0000269|PubMed:17646382, ECO:0000269|PubMed:21385844
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000269|PubMed:11082041, ECO:0000269|PubMed:11294867, ECO:0000269|PubMed:16393139, ECO:0000269|PubMed:16531402, ECO:0000269|PubMed:28265003, ECO:0000305|PubMed:11082041, ECO:0000305|PubMed:11294867}.; PTM: Phosphorylation at Ser-2206 facilitates the interaction with GGA1. {ECO:0000269|PubMed:20015111}.
uniprot
proteins
protein_family
SORL1 subfamily
uniprot
proteins
protein_family
VPS10-related sortilin family
uniprot
proteins
pubmed
11082041
uniprot
proteins
pubmed
11294867
uniprot
proteins
pubmed
11821067
uniprot
proteins
pubmed
12530537
uniprot
proteins
pubmed
14764453
uniprot
proteins
pubmed
15053742
uniprot
proteins
pubmed
15364913
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16174740
uniprot
proteins
pubmed
16393139
uniprot
proteins
pubmed
16407538
uniprot
proteins
pubmed
16531402
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17326667
uniprot
proteins
pubmed
17646382
uniprot
proteins
pubmed
17855360
uniprot
proteins
pubmed
18407551
uniprot
proteins
pubmed
18562096
uniprot
proteins
pubmed
18603531
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
20015111
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20385770
uniprot
proteins
pubmed
21147781
uniprot
proteins
pubmed
21220680
uniprot
proteins
pubmed
21385844
uniprot
proteins
pubmed
21994944
uniprot
proteins
pubmed
22472873
uniprot
proteins
pubmed
23333276
uniprot
proteins
pubmed
23486467
uniprot
proteins
pubmed
23565137
uniprot
proteins
pubmed
23977241
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24523320
uniprot
proteins
pubmed
26584636
uniprot
proteins
pubmed
26858303
uniprot
proteins
pubmed
27322061
uniprot
proteins
pubmed
28265003
uniprot
proteins
pubmed
30448281
uniprot
proteins
pubmed
30679749
uniprot
proteins
pubmed
31138794
uniprot
proteins
pubmed
8940146
uniprot
proteins
pubmed
9157966
uniprot
proteins
sequence_length
2214
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:11294867, ECO:0000269|PubMed:16174740, ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:21994944}; Single-pass type I membrane protein {ECO:0000305}. Golgi apparatus, trans-Golgi network membrane {ECO:0000269|PubMed:17646382, ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:23333276}; Single-pass type I membrane protein {ECO:0000305}. Endosome membrane {ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:23333276}; Single-pass type I membrane protein {ECO:0000305}. Early endosome membrane {ECO:0000269|PubMed:16174740, ECO:0000269|PubMed:17646382, ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:31138794}; Single-pass type I membrane protein {ECO:0000305}. Recycling endosome membrane {ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:31138794}; Single-pass type I membrane protein {ECO:0000305}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:21385844}; Single-pass type I membrane protein {ECO:0000305}. Endosome, multivesicular body membrane {ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:23333276}; Single-pass type I membrane protein {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:11294867, ECO:0000269|PubMed:14764453, ECO:0000269|PubMed:15053742, ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:31138794}; Single-pass type I membrane protein {ECO:0000305}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000269|PubMed:21994944}; Single-pass type I membrane protein {ECO:0000305}. Secreted {ECO:0000269|PubMed:11082041, ECO:0000269|PubMed:14764453, ECO:0000269|PubMed:15053742, ECO:0000269|PubMed:16393139, ECO:0000269|PubMed:16531402}. Note=Mostly intracellular, predominantly in the trans-Golgi network (TGN) and in endosome, as well as in endosome-to-TGN retrograde vesicles; found at low levels on the plasma membrane (PubMed:11294867, PubMed:15053742, PubMed:17855360, PubMed:21385844, PubMed:21994944, PubMed:31138794). At the cell surface, partially subjected to proteolytic shedding that releases the ectodomain (also called soluble SORLA, solLR11 or sLR11) in the extracellular milieu (PubMed:11082041, PubMed:16393139, PubMed:16531402). The shedding may be catalyzed by ADAM17/TACE (PubMed:16393139). 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). At the cell surface, the full-length protein undergoes partial clathrin-dependent endocytosis guided by clathrin adapter protein 2 (AP-2) (PubMed:11294867, PubMed:15053742, PubMed:17646382). {ECO:0000269|PubMed:11082041, ECO:0000269|PubMed:11294867, ECO:0000269|PubMed:15053742, ECO:0000269|PubMed:16393139, ECO:0000269|PubMed:16531402, ECO:0000269|PubMed:17646382, ECO:0000269|PubMed:17855360, ECO:0000269|PubMed:21385844, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:31138794}.
uniprot
proteins
transmembrane_region
TRANSMEM 2138..2158; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins