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Protein

Sortilin

Gene

Sort1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

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: Ensembl
  • regulation of gene expression Source: MGI
  • response to insulin Source: BHF-UCL
  • vesicle organization Source: BHF-UCL

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processDifferentiation, Endocytosis, Osteogenesis, Transport

Enzyme and pathway databases

ReactomeiR-MMU-432722 Golgi Associated Vesicle Biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Sortilin
Alternative name(s):
Neurotensin receptor 3
Short name:
NTR3
Short name:
mNTR3
Gene namesi
Name:Sort1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1338015 Sort1

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; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini74 – 754ExtracellularSequence analysisAdd BLAST681
Transmembranei755 – 775HelicalSequence analysisAdd BLAST21
Topological domaini776 – 825CytoplasmicSequence analysisAdd BLAST50

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31By similarityAdd BLAST31
PropeptideiPRO_000004515532 – 73Removed in mature formBy similarityAdd BLAST42
ChainiPRO_000043637774 – 825SortilinAdd BLAST752

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi84 ↔ 554By similarity
Glycosylationi96N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi160N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi255 ↔ 275By similarity
Glycosylationi272N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi404N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi446 ↔ 456By similarity
Glycosylationi580N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi610 ↔ 649By similarity
Disulfide bondi632 ↔ 664By similarity
Disulfide bondi666 ↔ 721By similarity
Disulfide bondi673 ↔ 686By similarity
Glycosylationi682N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi700 ↔ 738By similarity
Modified residuei809PhosphoserineBy similarity1
Modified residuei813PhosphoserineBy similarity1
Modified residuei819PhosphoserineCombined sources1

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, Phosphoprotein

Proteomic databases

PaxDbiQ6PHU5
PeptideAtlasiQ6PHU5
PRIDEiQ6PHU5

PTM databases

iPTMnetiQ6PHU5
PhosphoSitePlusiQ6PHU5
SwissPalmiQ6PHU5

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 E7.5 and within the germ cell layers at E8.5. Expressed within the neural epithelium and the neural tube at E9.5 and subsequently expressed in the nervous system throughout development. Expression in the proliferative zones of the central nervous system declines between E14.5 and E16.5, 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

BgeeiENSMUSG00000068747
CleanExiMM_SORT1
GenevisibleiQ6PHU5 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).By similarity4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203393, 2 interactors
DIPiDIP-46095N
IntActiQ6PHU5, 11 interactors
MINTiQ6PHU5
STRINGi10090.ENSMUSP00000099692

Structurei

Secondary structure

1825
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi92 – 95Combined sources4
Beta strandi98 – 103Combined sources6
Beta strandi108 – 119Combined sources12
Beta strandi121 – 128Combined sources8
Beta strandi132 – 134Combined sources3
Beta strandi139 – 147Combined sources9
Helixi156 – 159Combined sources4
Beta strandi162 – 165Combined sources4
Helixi166 – 168Combined sources3
Beta strandi170 – 172Combined sources3
Turni175 – 177Combined sources3
Beta strandi180 – 184Combined sources5
Beta strandi194 – 200Combined sources7
Beta strandi206 – 209Combined sources4
Beta strandi214 – 216Combined sources3
Beta strandi219 – 221Combined sources3
Beta strandi224 – 232Combined sources9
Beta strandi237 – 242Combined sources6
Beta strandi248 – 259Combined sources12
Helixi261 – 263Combined sources3
Beta strandi265 – 269Combined sources5
Beta strandi271 – 273Combined sources3
Turni275 – 280Combined sources6
Beta strandi281 – 289Combined sources9
Beta strandi295 – 307Combined sources13
Beta strandi310 – 316Combined sources7
Beta strandi318 – 321Combined sources4
Beta strandi323 – 330Combined sources8
Beta strandi349 – 354Combined sources6
Beta strandi359 – 364Combined sources6
Beta strandi366 – 377Combined sources12
Beta strandi384 – 393Combined sources10
Turni395 – 397Combined sources3
Beta strandi412 – 417Combined sources6
Beta strandi423 – 430Combined sources8
Beta strandi436 – 438Combined sources3
Beta strandi457 – 460Combined sources4
Helixi463 – 467Combined sources5
Beta strandi480 – 482Combined sources3
Beta strandi486 – 495Combined sources10
Beta strandi502 – 512Combined sources11
Beta strandi514 – 519Combined sources6
Beta strandi521 – 526Combined sources6
Helixi527 – 529Combined sources3
Beta strandi531 – 536Combined sources6
Beta strandi538 – 540Combined sources3
Beta strandi544 – 550Combined sources7
Beta strandi556 – 559Combined sources4
Beta strandi565 – 571Combined sources7
Beta strandi579 – 588Combined sources10
Beta strandi593 – 601Combined sources9
Turni603 – 605Combined sources3
Helixi612 – 614Combined sources3
Beta strandi615 – 619Combined sources5
Beta strandi623 – 626Combined sources4
Turni628 – 631Combined sources4
Beta strandi636 – 643Combined sources8
Beta strandi659 – 663Combined sources5
Helixi668 – 670Combined sources3
Beta strandi671 – 673Combined sources3
Helixi690 – 692Combined sources3
Beta strandi697 – 701Combined sources5
Beta strandi704 – 715Combined sources12
Beta strandi729 – 737Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5NMRX-ray2.10A32-753[»]
5NMTX-ray2.30A/B32-753[»]
5NNIX-ray3.21A/B31-753[»]
5NNJX-ray4.00A/B/C/D31-753[»]
ProteinModelPortaliQ6PHU5
SMRiQ6PHU5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati143 – 154BNR 1Add BLAST12
Repeati196 – 207BNR 2Add BLAST12
Repeati238 – 249BNR 3Add BLAST12
Repeati285 – 296BNR 4Add BLAST12
Repeati326 – 337BNR 5Add BLAST12
Repeati375 – 386BNR 6Add BLAST12
Repeati426 – 437BNR 7Add BLAST12
Repeati504 – 515BNR 8Add BLAST12
Repeati546 – 557BNR 9Add BLAST12

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni48 – 59Intrachain binding of the propeptide and the extracellular domainBy similarityAdd BLAST12
Regioni610 – 754Interactions with LRPAP1 and NGFBBy similarityAdd BLAST145
Regioni777 – 825Golgi to endosome transport and interactions with GGA1 and GGA2By similarityAdd BLAST49

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi785 – 790Endocytosis signalSequence analysis6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi38 – 44Poly-Pro7

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 helix

Phylogenomic databases

eggNOGiENOG410ISX8 Eukaryota
ENOG410ZJ6Q LUCA
GeneTreeiENSGT00510000046443
HOGENOMiHOG000231347
HOVERGENiHBG080235
InParanoidiQ6PHU5
KOiK12388
OMAiWTKMLEG
OrthoDBiEOG091G0ETU
PhylomeDBiQ6PHU5
TreeFamiTF324918

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR031777 Sortilin_C
IPR031778 Sortilin_N
IPR006581 VPS10
IPR015943 WD40/YVTN_repeat-like_dom_sf
PfamiView protein in Pfam
PF15902 Sortilin-Vps10, 1 hit
PF15901 Sortilin_C, 1 hit
SMARTiView protein in SMART
SM00602 VPS10, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 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.

« Hide

        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
Length:825
Mass (Da):91,200
Last modified:July 5, 2004 - v1
Checksum:i9A7A73C6FE1C8201
GO
Isoform 2 (identifier: Q6PHU5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     748-748: Q → QDSRPQGHSLSQNPAPPPLGYTENTHFLSPTQKQ

Note: No experimental confirmation available.
Show »
Length:858
Mass (Da):94,813
Checksum:iB4AC632F993E8E14
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti315V → E in AAF22639 (PubMed:11322955).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016650748Q → QDSRPQGHSLSQNPAPPPLG YTENTHFLSPTQKQ in isoform 2. 1 Publication1

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
CCDSiCCDS17756.1 [Q6PHU5-1]
CCDS80003.1 [Q6PHU5-2]
RefSeqiNP_001258528.1, NM_001271599.1 [Q6PHU5-2]
NP_064356.2, NM_019972.3 [Q6PHU5-1]
UniGeneiMm.157119

Genome annotation databases

EnsembliENSMUST00000102632; ENSMUSP00000099692; ENSMUSG00000068747 [Q6PHU5-1]
ENSMUST00000135636; ENSMUSP00000123564; ENSMUSG00000068747 [Q6PHU5-2]
GeneIDi20661
KEGGimmu:20661
UCSCiuc008qyr.2 mouse [Q6PHU5-1]
uc008qys.2 mouse [Q6PHU5-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSORT_MOUSE
AccessioniPrimary (citable) accession number: Q6PHU5
Secondary accession number(s): A2AEE8
, Q3UHE2, Q8K043, Q9QXW6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: July 5, 2004
Last modified: March 28, 2018
This is version 134 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
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