UniProtKB - Q6PHU5 (SORT_MOUSE)
Protein
Sortilin
Gene
Sort1
Organism
Mus musculus (Mouse)
Status
Functioni
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). 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.7 Publications
GO - Molecular functioni
- enzyme binding Source: MGI
- nerve growth factor binding Source: MGI
- nerve growth factor receptor activity Source: MGI
- neurotensin receptor activity, non-G protein-coupled Source: MGI
GO - Biological processi
- endocytosis Source: MGI
- endosome to lysosome transport Source: MGI
- endosome transport via multivesicular body sorting pathway Source: MGI
- extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
- glucose import Source: BHF-UCL
- Golgi to endosome transport Source: MGI
- G protein-coupled receptor signaling pathway Source: MGI
- multicellular organism development Source: UniProtKB-KW
- myotube differentiation Source: BHF-UCL
- negative regulation of fat cell differentiation Source: MGI
- negative regulation of lipoprotein lipase activity Source: MGI
- neuropeptide signaling pathway Source: MGI
- neurotrophin TRK receptor signaling pathway Source: MGI
- ossification Source: UniProtKB-KW
- plasma membrane to endosome transport Source: MGI
- positive regulation of epithelial cell apoptotic process Source: MGI
- regulation of gene expression Source: MGI
- response to insulin Source: BHF-UCL
- vesicle organization Source: BHF-UCL
Keywordsi
Molecular function | Developmental protein, Receptor |
Biological process | Differentiation, Endocytosis, Osteogenesis, Transport |
Enzyme and pathway databases
Reactomei | R-MMU-432722 Golgi Associated Vesicle Biogenesis |
Names & Taxonomyi
Protein namesi | Recommended name: SortilinAlternative name(s): Neurotensin receptor 3 Short name: NTR3 Short name: mNTR3 |
Gene namesi | Name:Sort1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1338015 Sort1 |
Subcellular locationi
Nucleus
- Nucleus membrane Curated; Single-pass type I membrane protein Curated
Plasma membrane
Golgi apparatus
- Golgi stack membrane Curated; Single-pass type I membrane protein Curated
Lysosome
- Lysosome membrane Curated; Single-pass type I membrane protein Curated
Endoplasmic reticulum
- Endoplasmic reticulum membrane Curated; Single-pass type I membrane protein Curated
Endosome
- Endosome membrane Curated; Single-pass type I membrane protein Curated
Other locations
- Membrane Curated; Single-pass type I membrane protein Curated
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. Interaction with NRADD promotes localization at the cell membrane in neurons; this promotes interaction with NGFR. Also found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes. Localization to the plasma membrane in adipocytes is enhanced by insulin.
Cytosol
- cytosol Source: MGI
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Endosome
- early endosome Source: MGI
- endosome membrane Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: MGI
- Golgi cisterna membrane Source: UniProtKB-SubCell
Lysosome
- lysosomal membrane Source: UniProtKB-SubCell
Nucleus
- nuclear membrane Source: UniProtKB-SubCell
Plasma Membrane
- plasma membrane Source: BHF-UCL
Other locations
- cell surface Source: MGI
- clathrin-coated pit Source: MGI
- clathrin-coated vesicle Source: MGI
- cytoplasmic vesicle Source: MGI
- cytoplasmic vesicle membrane Source: MGI
- dendrite Source: MGI
- integral component of membrane Source: MGI
- intracellular membrane-bounded organelle Source: MGI
- neuronal cell body Source: MGI
- perinuclear region of cytoplasm Source: MGI
- trans-Golgi network transport vesicle Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 74 – 754 | ExtracellularSequence analysisAdd BLAST | 681 | |
Transmembranei | 755 – 775 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 776 – 825 | CytoplasmicSequence analysisAdd BLAST | 50 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 31 | By similarityAdd BLAST | 31 | |
PropeptideiPRO_0000045155 | 32 – 73 | Removed in mature formBy similarityAdd BLAST | 42 | |
ChainiPRO_0000436377 | 74 – 825 | SortilinAdd BLAST | 752 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 84 ↔ 554 | By similarity | ||
Glycosylationi | 96 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 160 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 255 ↔ 275 | By similarity | ||
Glycosylationi | 272 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 404 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 446 ↔ 456 | By similarity | ||
Glycosylationi | 580 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 610 ↔ 649 | By similarity | ||
Disulfide bondi | 632 ↔ 664 | By similarity | ||
Disulfide bondi | 666 ↔ 721 | By similarity | ||
Disulfide bondi | 673 ↔ 686 | By similarity | ||
Glycosylationi | 682 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 700 ↔ 738 | By similarity | ||
Modified residuei | 809 | PhosphoserineBy similarity | 1 | |
Modified residuei | 813 | PhosphoserineBy similarity | 1 | |
Modified residuei | 819 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
The N-terminal propeptide is cleaved by furin and possibly other homologous proteases.By similarity
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
jPOSTi | Q6PHU5 |
PaxDbi | Q6PHU5 |
PeptideAtlasi | Q6PHU5 |
PRIDEi | Q6PHU5 |
PTM databases
iPTMneti | Q6PHU5 |
PhosphoSitePlusi | Q6PHU5 |
SwissPalmi | Q6PHU5 |
Expressioni
Tissue specificityi
Expressed in the brain, particularly the piriform cortex, the cerebral cortex and the hippocampus.1 Publication
Developmental stagei
Expressed in the ectoderm at 7.5 dpc and within the germ cell layers at 8.5 dpc. Expressed within the neural epithelium and the neural tube at 9.5 dpc and subsequently expressed in the nervous system throughout development. Expression in the proliferative zones of the central nervous system declines between 14.5 dpc and 16.5 dpc, while expression remains high in the cerebral cortex and the neural retina. Expressed in the pituitary and the sensory epithelia throughout development.1 Publication
Inductioni
During adipocyte differentiation.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000068747 Expressed in 297 organ(s), highest expression level in epididymal fat pad |
Genevisiblei | Q6PHU5 MM |
Interactioni
Subunit structurei
Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP, NTS and GM2A. Forms a complex with NGFR which binds specifically to the precursor forms of NGFB (proNGFB) and BDNF (proBDNF). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may regulate their anterograde axonal transport and signaling (By similarity). Interacts with LPL (PubMed:10085125). Interacts with PSAP (PubMed:15236332). Interacts with SLC2A4 (PubMed:15992544). Interacts with NRADD and NGFR (PubMed:19407813). Interaction with NRADD protects against degradation in the lysosome. Interacts with CLN5 (By similarity). Interacts with GRN; this interaction mediates endocytosis and lysosome delivrery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system (By similarity).By similarity4 Publications
Binary interactionsi
GO - Molecular functioni
- enzyme binding Source: MGI
- nerve growth factor binding Source: MGI
Protein-protein interaction databases
BioGridi | 203393, 2 interactors |
DIPi | DIP-46095N |
IntActi | Q6PHU5, 11 interactors |
MINTi | Q6PHU5 |
STRINGi | 10090.ENSMUSP00000099692 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5NMR | X-ray | 2.10 | A | 32-753 | [»] | |
5NMT | X-ray | 2.30 | A/B | 32-753 | [»] | |
5NNI | X-ray | 3.21 | A/B | 31-753 | [»] | |
5NNJ | X-ray | 4.00 | A/B/C/D | 31-753 | [»] | |
5ZNN | X-ray | 2.45 | A/B | 76-744 | [»] | |
ProteinModelPortali | Q6PHU5 | |||||
SMRi | Q6PHU5 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 143 – 154 | BNR 1Add BLAST | 12 | |
Repeati | 196 – 207 | BNR 2Add BLAST | 12 | |
Repeati | 238 – 249 | BNR 3Add BLAST | 12 | |
Repeati | 285 – 296 | BNR 4Add BLAST | 12 | |
Repeati | 326 – 337 | BNR 5Add BLAST | 12 | |
Repeati | 375 – 386 | BNR 6Add BLAST | 12 | |
Repeati | 426 – 437 | BNR 7Add BLAST | 12 | |
Repeati | 504 – 515 | BNR 8Add BLAST | 12 | |
Repeati | 546 – 557 | BNR 9Add BLAST | 12 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 48 – 59 | Intrachain binding of the propeptide and the extracellular domainBy similarityAdd BLAST | 12 | |
Regioni | 610 – 754 | Interactions with LRPAP1 and NGFBBy similarityAdd BLAST | 145 | |
Regioni | 777 – 825 | Golgi to endosome transport and interactions with GGA1 and GGA2By similarityAdd BLAST | 49 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 785 – 790 | Endocytosis signalSequence analysis | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 38 – 44 | Poly-Pro | 7 |
Domaini
The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding (By similarity).By similarity
The extracellular domain may be shed following protease cleavage in some cell types.By similarity
Sequence similaritiesi
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG410ISX8 Eukaryota ENOG410ZJ6Q LUCA |
GeneTreei | ENSGT00940000153473 |
HOGENOMi | HOG000231347 |
HOVERGENi | HBG080235 |
InParanoidi | Q6PHU5 |
KOi | K12388 |
OMAi | WTKMLEG |
OrthoDBi | 1046610at2759 |
PhylomeDBi | Q6PHU5 |
TreeFami | TF324918 |
Family and domain databases
Gene3Di | 2.130.10.10, 1 hit |
InterProi | View protein in InterPro IPR031777 Sortilin_C IPR031778 Sortilin_N IPR006581 VPS10 IPR015943 WD40/YVTN_repeat-like_dom_sf |
Pfami | View protein in Pfam PF15902 Sortilin-Vps10, 1 hit PF15901 Sortilin_C, 1 hit |
SMARTi | View protein in SMART SM00602 VPS10, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q6PHU5-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MERPRGAADG LLRWPLGLLL LLQLLPPAAV GQDRLDAPPP PAPPLLRWAG
60 70 80 90 100
PVGVSWGLRA AAPGGPVPRA GRWRRGAPAE DQDCGRLPDF IAKLTNNTHQ
110 120 130 140 150
HVFDDLSGSV SLSWVGDSTG VILVLTTFQV PLVIVSFGQS KLYRSEDYGK
160 170 180 190 200
NFKDITNLIN NTFIRTEFGM AIGPENSGKV ILTAEVSGGS RGGRVFRSSD
210 220 230 240 250
FAKNFVQTDL PFHPLTQMMY SPQNSDYLLA LSTENGLWVS KNFGEKWEEI
260 270 280 290 300
HKAVCLAKWG PNNIIFFTTH VNGSCKADLG ALELWRTSDL GKTFKTIGVK
310 320 330 340 350
IYSFGLGGRF LFASVMADKD TTRRIHVSTD QGDTWSMAQL PSVGQEQFYS
360 370 380 390 400
ILAANEDMVF MHVDEPGDTG FGTIFTSDDR GIVYSKSLDR HLYTTTGGET
410 420 430 440 450
DFTNVTSLRG VYITSTLSED NSIQSMITFD QGGRWEHLRK PENSKCDATA
460 470 480 490 500
KNKNECSLHI HASYSISQKL NVPMAPLSEP NAVGIVIAHG SVGDAISVMV
510 520 530 540 550
PDVYISDDGG YSWAKMLEGP HYYTILDSGG IIVAIEHSNR PINVIKFSTD
560 570 580 590 600
EGQCWQSYVF TQEPIYFTGL ASEPGARSMN ISIWGFTESF ITRQWVSYTV
610 620 630 640 650
DFKDILERNC EEDDYTTWLA HSTDPGDYKD GCILGYKEQF LRLRKSSVCQ
660 670 680 690 700
NGRDYVVAKQ PSVCPCSLED FLCDFGYFRP ENASECVEQP ELKGHELEFC
710 720 730 740 750
LYGKEEHLTT NGYRKIPGDK CQGGMNPARE VKDLKKKCTS NFLNPTKQNS
760 770 780 790 800
KSNSVPIILA IVGLMLVTVV AGVLIVKKYV CGGRFLVHRY SVLQQHAEAD
810 820
GVEALDSTSH AKSGYHDDSD EDLLE
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 315 | V → E in AAF22639 (PubMed:11322955).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016650 | 748 | Q → QDSRPQGHSLSQNPAPPPLG YTENTHFLSPTQKQ in isoform 2. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF175279 mRNA Translation: AAF22639.1 AK147442 mRNA Translation: BAE27915.1 AL671899 Genomic DNA No translation available. BC034129 mRNA Translation: AAH34129.1 BC056343 mRNA Translation: AAH56343.1 |
CCDSi | CCDS17756.1 [Q6PHU5-1] CCDS80003.1 [Q6PHU5-2] |
RefSeqi | NP_001258528.1, NM_001271599.1 [Q6PHU5-2] NP_064356.2, NM_019972.3 [Q6PHU5-1] |
UniGenei | Mm.157119 |
Genome annotation databases
Ensembli | ENSMUST00000102632; ENSMUSP00000099692; ENSMUSG00000068747 [Q6PHU5-1] ENSMUST00000135636; ENSMUSP00000123564; ENSMUSG00000068747 [Q6PHU5-2] |
GeneIDi | 20661 |
KEGGi | mmu:20661 |
UCSCi | uc008qyr.2 mouse [Q6PHU5-1] uc008qys.2 mouse [Q6PHU5-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF175279 mRNA Translation: AAF22639.1 AK147442 mRNA Translation: BAE27915.1 AL671899 Genomic DNA No translation available. BC034129 mRNA Translation: AAH34129.1 BC056343 mRNA Translation: AAH56343.1 |
CCDSi | CCDS17756.1 [Q6PHU5-1] CCDS80003.1 [Q6PHU5-2] |
RefSeqi | NP_001258528.1, NM_001271599.1 [Q6PHU5-2] NP_064356.2, NM_019972.3 [Q6PHU5-1] |
UniGenei | Mm.157119 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5NMR | X-ray | 2.10 | A | 32-753 | [»] | |
5NMT | X-ray | 2.30 | A/B | 32-753 | [»] | |
5NNI | X-ray | 3.21 | A/B | 31-753 | [»] | |
5NNJ | X-ray | 4.00 | A/B/C/D | 31-753 | [»] | |
5ZNN | X-ray | 2.45 | A/B | 76-744 | [»] | |
ProteinModelPortali | Q6PHU5 | |||||
SMRi | Q6PHU5 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 203393, 2 interactors |
DIPi | DIP-46095N |
IntActi | Q6PHU5, 11 interactors |
MINTi | Q6PHU5 |
STRINGi | 10090.ENSMUSP00000099692 |
PTM databases
iPTMneti | Q6PHU5 |
PhosphoSitePlusi | Q6PHU5 |
SwissPalmi | Q6PHU5 |
Proteomic databases
jPOSTi | Q6PHU5 |
PaxDbi | Q6PHU5 |
PeptideAtlasi | Q6PHU5 |
PRIDEi | Q6PHU5 |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENSMUST00000102632; ENSMUSP00000099692; ENSMUSG00000068747 [Q6PHU5-1] ENSMUST00000135636; ENSMUSP00000123564; ENSMUSG00000068747 [Q6PHU5-2] |
GeneIDi | 20661 |
KEGGi | mmu:20661 |
UCSCi | uc008qyr.2 mouse [Q6PHU5-1] uc008qys.2 mouse [Q6PHU5-2] |
Organism-specific databases
CTDi | 6272 |
MGIi | MGI:1338015 Sort1 |
Phylogenomic databases
eggNOGi | ENOG410ISX8 Eukaryota ENOG410ZJ6Q LUCA |
GeneTreei | ENSGT00940000153473 |
HOGENOMi | HOG000231347 |
HOVERGENi | HBG080235 |
InParanoidi | Q6PHU5 |
KOi | K12388 |
OMAi | WTKMLEG |
OrthoDBi | 1046610at2759 |
PhylomeDBi | Q6PHU5 |
TreeFami | TF324918 |
Enzyme and pathway databases
Reactomei | R-MMU-432722 Golgi Associated Vesicle Biogenesis |
Miscellaneous databases
ChiTaRSi | Sort1 mouse |
PROi | PR:Q6PHU5 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000068747 Expressed in 297 organ(s), highest expression level in epididymal fat pad |
Genevisiblei | Q6PHU5 MM |
Family and domain databases
Gene3Di | 2.130.10.10, 1 hit |
InterProi | View protein in InterPro IPR031777 Sortilin_C IPR031778 Sortilin_N IPR006581 VPS10 IPR015943 WD40/YVTN_repeat-like_dom_sf |
Pfami | View protein in Pfam PF15902 Sortilin-Vps10, 1 hit PF15901 Sortilin_C, 1 hit |
SMARTi | View protein in SMART SM00602 VPS10, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | SORT_MOUSE | |
Accessioni | Q6PHU5Primary (citable) accession number: Q6PHU5 Secondary accession number(s): A2AEE8 Q9QXW6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 20, 2005 |
Last sequence update: | July 5, 2004 | |
Last modified: | February 13, 2019 | |
This is version 141 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot