Sorl1
entrez
20660
canonical
uniprot
O88307
canonical
ensembl
ENSMUSG00000049313
resolver
ensp
ENSMUSP00000058613
resolver
enst
ENSMUST00000060989
resolver
genesymbol
Sorl1
resolver
uniprot
O54711
resolver
uniprot
O70581
resolver
uniprot
Q3UHM3
resolver
uniprot_entry
SORL_MOUSE
resolver
uniprot_sec
O54711
resolver
uniprot_sec
O70581
resolver
uniprot_sec
Q3UHM3
resolver
amino_acid_sequence
MATRSSRRESRLPFLFALVALLPRGALGGGWTQRLHGGPAPLPQDRGFFVVQGDPRDLRLGTHGDAPGASPAARKPLRTRRSAALQPQPIQVYGQVSLNDSHNQMVVHWAGEKSNVIVALARDSLALARPKSSDVYVSYDYGKSFSKISEKLNFGVGNNSEAVISQFYHSPADNKRYIFVDAYAQYLWITFDFCSTIHGFSIPFRAADLLLHSKASNLLLGFDRSHPNKQLWKSDDFGQTWIMIQEHVKSFSWGIDPYDQPNAIYIERHEPFGFSTVLRSTDFFQSRENQEVILEEVRDFQLRDKYMFATKVVHLPGSQQQSSVQLWVSFGRKPMRAAQFVTKHPINEYYIADAAEDQVFVCVSHSNNSTNLYISEAEGLKFSLSLENVLYYSPGGAGSDTLVRYFANEPFADFHRVEGLQGVYIATLINGSMNEENMRSVITFDKGGTWEFLQAPAFTGYGEKINCELSQGCSLHLAQRLSQLLNLQLRRMPILSKESAPGLIIATGSVGKNLASKTNVYISSSAGARWREALPGPHYYTWGDHGGIIMAIAQGMETNELKYSTNEGETWKTFVFSEKPVFVYGLLTEPGEKSTVFTIFGSNKESVHSWLILQVNATDALGVPCTENDYKLWSPSDERGNECLLGHKTVFKRRTPHATCFNGEDFDRPVVVSNCSCTREDYECDFGFKMSEDLSLEVCVPDPEFSGKPYSPPVPCPVGSSYRRTRGYRKISGDTCSGGDVEARLEGELVPCPLAEENEFILYAMRKSIYRYDLASGATEQLPLSGLRAAVALDFDYERNCLYWSDLALDTIQRLCLNGSTGQEVIINSGLETVEALAFEPLSQLLYWVDAGFKKIEVANPDGDFRLTIVNSSVLDRPRALVLVPQEGVMFWTDWGDLKPGIYRSYMDGSAAYRLVSEDVKWPNGISVDSQWIYWTDAYLDCIERITFSGQQRSVILDSLPHPYAIAVFKNEIYWDDWSQLSIFRASKHSRSQVEILASQLTGLMDMKVFYKGKNAGSNACVPQPCSLLCLPKANNSKSCRCPEGVASSVLPSGDLMCDCPQGYQRKNNTCVKEENTCLRNQYRCSNGNCINSIWWCDFDNDCGDMSDERNCPTTVCDADTQFRCQESGTCIPLSYKCDLEDDCGDNSDESHCEMHQCRSDEFNCSSGMCIRSSWVCDGDNDCRDWSDEANCTAIYHTCEASNFQCHNGHCIPQRWACDGDADCQDGSDEDPVSCEKKCNGFHCPNGTCIPSSKHCDGLRDCPDGSDEQHCEPFCTRFMDFVCKNRQQCLFHSMVCDGIVQCRDGSDEDAAFAGCSQDPEFHKECDEFGFQCQNGVCISLIWKCDGMDDCGDYSDEANCENPTEAPNCSRYFQFHCENGHCIPNRWKCDRENDCGDWSDEKDCGDSHVLPSPTPGPSTCLPNYFHCSSGACVMGTWVCDGYRDCADGSDEEACPSLANSTAASTPTQFGQCDRFEFECHQPKKCIPNWKRCDGHQDCQDGQDEANCPTHSTLTCTSREFKCEDGEACIVLSERCDGFLDCSDESDEKACSDELTVYKVQNLQWTADFSGDVTLTWMRPKKMPSASCVYNVYYRVVGESIWKTLETHSNKTSTVLKVLKPDTTYQVKVQVHCLNKVHNTNDFVTLRTPEGLPDAPRNLQLSLNSEEEGVILGHWAPPVHTHGLIREYIVEYSRSGSKMWASQRAASNSTEIKNLLLNALYTVRVAAVTSRGIGNWSDSKSITTIKGKVIQAPNIHIDSYDENSLSFTLTMDGDIKVNGYVVNLFWSFDAHKQEKKTLSFRGGSALSHRVSNLTAHTSYEISAWAKTDLGDSPLAFEHILTRGSSPPAPSLKAKAINQTAVECIWTGPKNVVYGIFYATSFLDLYRNPKSVTTSLHNKTVIVSKDEQYLFLVRVLIPYQGPSSDYVVVKMIPDSRLPPRHLHAVHIGKTSALIKWESPYDSPDQDLFYAIAVKDLIRKTDRSYKVRSRNSTVEYSLSKLEPGGKYHIIVQLGNMSKDSSIKITTVSLSAPDALKIITENDHVLLFWKSLALKEKQFNETRGYEIHMSDSAVNLTAYLGNTTDNFFKVSNLKMGHNYTFTVQARCLFGSQICGEPAVLLYDELSSGADAAVIQAARSTDVAAVVVPILFLILLSLGVGFAILYTKHRRLQSSFSAFANSHYSSRLGSAIFSSGDDLGEDDEDAPMITGFSDDVPMVIA
uniprot
proteins
function
FUNCTION: Sorting receptor that directs several proteins to their correct location within the cell. Along with AP-1 complex, involved Golgi apparatus - endosome sorting. 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. May also sort newly produced amyloid-beta peptides to lysosomes for catabolism. Does not affect APP trafficking from the endoplasmic reticulum to Golgi compartments (By similarity). 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 (By similarity). Sorting receptor for lipoprotein lipase LPL. Promotes LPL localization to endosomes and later to the lysosomes, leading to degradation of newly synthesized LPL (By similarity). 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 (By similarity). 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 (PubMed:20385770, PubMed:25967121). 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 (By similarity). By acting on the migration of intimal smooth muscle cells, may accelerate intimal thickening following vascular injury (PubMed:14764453). Promotes adhesion of monocytes (By similarity). Stimulates proliferation and migration of monocytes/macrophages. Through its action on intimal smooth muscle cells and macrophages, may accelerate intimal thickening and macrophage foam cell formation in the process of atherosclerosis (PubMed:17332490). 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 (PubMed:26584636). 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:Q92673, ECO:0000269|PubMed:14764453, ECO:0000269|PubMed:17332490, ECO:0000269|PubMed:20385770, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:23486467, ECO:0000269|PubMed:23977241, ECO:0000269|PubMed:25967121, ECO:0000269|PubMed:26584636, ECO:0000269|PubMed:26858303, ECO:0000269|PubMed:27322061, ECO:0000269|PubMed:28265003}.
uniprot
proteins
mass_dalton
247086
uniprot
proteins
post_translational_modification
PTM: Within the Golgi apparatus, the propeptide may be cleaved off by FURIN or a furin-like protease. After cleavage, the propeptide interacts with the mature protein N-terminus, preventing the association with other ligands. At the cell surface, partially subjected to proteolytic shedding that releases the ectodomain in the extracellular milieu. The shedding may be catalyzed by ADAM17/TACE. 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. {ECO:0000250|UniProtKB:Q92673}.; PTM: Phosphorylation at Ser-2207 facilitates the interaction with GGA1. {ECO:0000250|UniProtKB:Q92673}.
uniprot
proteins
protein_family
SORL1 subfamily
uniprot
proteins
protein_family
VPS10-related sortilin family
uniprot
proteins
pubmed
11082041
uniprot
proteins
pubmed
14764453
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16174740
uniprot
proteins
pubmed
16407538
uniprot
proteins
pubmed
17332490
uniprot
proteins
pubmed
20007471
uniprot
proteins
pubmed
20385770
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21385844
uniprot
proteins
pubmed
21994944
uniprot
proteins
pubmed
23333276
uniprot
proteins
pubmed
23486467
uniprot
proteins
pubmed
23977241
uniprot
proteins
pubmed
25967121
uniprot
proteins
pubmed
26584636
uniprot
proteins
pubmed
26858303
uniprot
proteins
pubmed
27322061
uniprot
proteins
pubmed
28265003
uniprot
proteins
pubmed
30679749
uniprot
proteins
pubmed
9510025
uniprot
proteins
pubmed
9726247
uniprot
proteins
sequence_length
2215
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Golgi apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Endosome membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Early endosome membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Recycling endosome membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Endosome, multivesicular body membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Cell membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250|UniProtKB:Q92673}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92673}. Secreted {ECO:0000269|PubMed:11082041, ECO:0000269|PubMed:26584636}. Note=Mostly intracellular, predominantly in the trans-Golgi network (TGN) and in endosome, as well as in endosome-to-TGN recycling compartments; found at low levels on the plasma membrane (By similarity). 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). The shedding may be catalyzed by ADAM17/TACE. 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. At the cell surface, the full-length protein undergoes partial clathrin-dependent endocytosis guided by clathrin adapter protein 2 (AP-2) (By similarity). {ECO:0000250|UniProtKB:Q92673, ECO:0000269|PubMed:11082041}.
uniprot
proteins
transmembrane_region
TRANSMEM 2139..2159; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins