| IED ID | IndEnz0002010143 |
| Enzyme Type ID | protease010143 |
| Protein Name |
Sortilin 100 kDa NT receptor Glycoprotein 95 Gp95 Neurotensin receptor 3 NT3 NTR3 |
| Gene Name | SORT1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MERPWGAADGLSRWPHGLGLLLLLQLLPPSTLSQDRLDAPPPPAAPLPRWSGPIGVSWGLRAAAAGGAFPRGGRWRRSAPGEDEECGRVRDFVAKLANNTHQHVFDDLRGSVSLSWVGDSTGVILVLTTFHVPLVIMTFGQSKLYRSEDYGKNFKDITDLINNTFIRTEFGMAIGPENSGKVVLTAEVSGGSRGGRIFRSSDFAKNFVQTDLPFHPLTQMMYSPQNSDYLLALSTENGLWVSKNFGGKWEEIHKAVCLAKWGSDNTIFFTTYANGSCKADLGALELWRTSDLGKSFKTIGVKIYSFGLGGRFLFASVMADKDTTRRIHVSTDQGDTWSMAQLPSVGQEQFYSILAANDDMVFMHVDEPGDTGFGTIFTSDDRGIVYSKSLDRHLYTTTGGETDFTNVTSLRGVYITSVLSEDNSIQTMITFDQGGRWTHLRKPENSECDATAKNKNECSLHIHASYSISQKLNVPMAPLSEPNAVGIVIAHGSVGDAISVMVPDVYISDDGGYSWTKMLEGPHYYTILDSGGIIVAIEHSSRPINVIKFSTDEGQCWQTYTFTRDPIYFTGLASEPGARSMNISIWGFTESFLTSQWVSYTIDFKDILERNCEEKDYTIWLAHSTDPEDYEDGCILGYKEQFLRLRKSSVCQNGRDYVVTKQPSICLCSLEDFLCDFGYYRPENDSKCVEQPELKGHDLEFCLYGREEHLTTNGYRKIPGDKCQGGVNPVREVKDLKKKCTSNFLSPEKQNSKSNSVPIILAIVGLMLVTVVAGVLIVKKYVCGGRFLVHRYSVLQQHAEANGVDGVDALDTASHTNKSGYHDDSDEDLLE |
| Enzyme Length | 831 |
| Uniprot Accession Number | Q99523 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Lysosomal proteins bind specifically to the receptor in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex (PubMed:16787399). The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi. {ECO:0000269|PubMed:10085125, ECO:0000269|PubMed:11331584, ECO:0000269|PubMed:11390366, ECO:0000269|PubMed:12209882, ECO:0000269|PubMed:12598608, ECO:0000269|PubMed:14657016, ECO:0000269|PubMed:14985763, ECO:0000269|PubMed:15313463, ECO:0000269|PubMed:15930396, ECO:0000269|PubMed:15987945, ECO:0000269|PubMed:16787399, ECO:0000269|PubMed:18817523}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Beta strand (57); Chain (1); Disulfide bond (8); Glycosylation (6); Helix (15); Lipidation (1); Modified residue (3); Motif (2); Mutagenesis (10); Natural variant (1); Propeptide (1); Region (3); Repeat (9); Sequence conflict (1); Signal peptide (1); Topological domain (2); Transmembrane (1); Turn (5) |
| Keywords | 3D-structure;Alternative splicing;Cell membrane;Cleavage on pair of basic residues;Developmental protein;Differentiation;Direct protein sequencing;Disulfide bond;Endocytosis;Endoplasmic reticulum;Endosome;Glycoprotein;Golgi apparatus;Lipoprotein;Lysosome;Membrane;Nucleus;Osteogenesis;Palmitate;Phosphoprotein;Receptor;Reference proteome;Repeat;Signal;Transmembrane;Transmembrane helix;Transport |
| Interact With | Q96K78; P23560-2; Q6PL45-2; Q8TBE1; P26441; Q92520; Q9UJY5; P06280; P28799; P05231; P42702; P30533; P01138; P01138; P04629; Q16288; Q8WY21; Q99523; P02787; P01266; O95183; Q9UBQ0-2; P83714; P11151; Q9JLC4; P06882; P05067-4 |
| Induction | INDUCTION: During osteoblast differentiation. {ECO:0000269|PubMed:12209882}. |
| Subcellular Location | SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane {ECO:0000269|PubMed:16787399, ECO:0000269|PubMed:18817523}; Single-pass type I membrane protein {ECO:0000305}. Endosome membrane {ECO:0000269|PubMed:18817523}; Single-pass type I membrane protein {ECO:0000305}. Endoplasmic reticulum membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Nucleus membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Cell membrane; Single-pass type I membrane protein; Extracellular side. Lysosome membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Note=Localized to membranes of the endoplasmic reticulum, endosomes, Golgi stack, lysosomes and nucleus. A small fraction of the protein is also localized to the plasma membrane. May also be found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes. Localization to the plasma membrane in adipocytes may be enhanced by insulin. |
| Modified Residue | MOD_RES 814; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:23186163"; MOD_RES 819; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21406692"; MOD_RES 825; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" |
| Post Translational Modification | PTM: The N-terminal propeptide is cleaved by furin and possibly other homologous proteases. {ECO:0000269|PubMed:12419319, ECO:0000269|PubMed:9927419}.; PTM: Palmitoylated (PubMed:18817523). Undergoes cysteine S-palmitoylation which promotes the partitioning of the receptor into an endosomal membrane subdomain where it can interact with the retromer cargo-selective complex which mediates its retrograde trafficking to the Golgi apparatus (PubMed:18817523). {ECO:0000269|PubMed:18817523}.; PTM: Phosphorylation at Ser-825 facilitates the interaction with GGA1. {ECO:0000269|PubMed:20015111}. |
| Signal Peptide | SIGNAL 1..33; /evidence=ECO:0000250|UniProtKB:O54861 |
| Structure 3D | X-ray crystallography (12) |
| Cross Reference PDB | 3F6K; 3G2U; 3G2V; 4MSL; 4N7E; 4PO7; 5MRH; 5MRI; 6EHO; 6X3L; 6X48; 6X4H; |
| Mapped Pubmed ID | 10394364; 11604418; 11694590; 11994746; 12360476; 16155256; 17116749; 17220298; 17353931; 18088323; 18191449; 18193043; 18193044; 18603531; 18624930; 18713973; 19060906; 19060910; 19148283; 19198609; 19219422; 19299407; 19487539; 19837406; 19875813; 20031591; 20036257; 20085800; 20159974; 20167577; 20570916; 20584990; 20628624; 20676133; 20679960; 20738937; 20816088; 20971364; 21087763; 21245145; 21261755; 21466885; 21521695; 21730062; 21966426; 22128158; 22256600; 22297619; 22361451; 22418572; 22751103; 22768187; 22884962; 23102784; 23283322; 23318115; 23438231; 23485461; 23535823; 23660633; 23704887; 23895422; 23910371; 24070898; 24128306; 24163244; 24355129; 24355921; 24404198; 24531479; 24674750; 24838608; 24985322; 24986865; 25036637; 25037567; 25042869; 25101658; 25365768; 25542012; 25609649; 25805502; 25854576; 26085104; 26261636; 26297037; 26370502; 26375028; 26464717; 26496610; 26556286; 26566674; 26614389; 26950419; 27085161; 27112212; 27392867; 27612602; 27666481; 27834811; 27838145; 27846466; 27943270; 28279970; 28433812; 28462834; 28768823; 29037860; 29084952; 29107483; 29203673; 29272741; 29275103; 29382723; 29555433; 29972886; 29973585; 30634965; 30770901; 30909233; 31104815; 31608989; 31767632; 32077308; 32125883; 32357547; 32526166; 32712736; 32738972; 32940806; 33153264; 33325631; 33618683; 33634506; 34004257; 34162830; 8374173; 8524399; 8670264; |
| Motif | MOTIF 787..792; /note=Endocytosis signal; /evidence=ECO:0000305; MOTIF 826..830; /note=DXXLL motif involved in the interaction with GGA1; /evidence=ECO:0000269|PubMed:20015111 |
| Gene Encoded By | |
| Mass | 92,068 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |