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Protein

Sortilin

Gene

Sort1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Differentiation, Endocytosis, Osteogenesis, Transport

Enzyme and pathway databases

ReactomeiR-RNO-432722. Golgi Associated Vesicle Biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Sortilin
Alternative name(s):
Glycoprotein 110
Short name:
Gp110
Neurotensin receptor 3
Short name:
NTR3
Gene namesi
Name:Sort1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi619999. Sort1.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • cell surface Source: Ensembl
  • clathrin-coated pit Source: Ensembl
  • cytosol Source: GOC
  • dendrite Source: RGD
  • early endosome Source: Ensembl
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • endosome membrane Source: UniProtKB-SubCell
  • Golgi cisterna membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: RGD
  • intracellular membrane-bounded organelle Source: RGD
  • lysosomal membrane Source: UniProtKB-SubCell
  • neuronal cell body Source: RGD
  • nuclear membrane Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: RGD
  • trans-Golgi network transport vesicle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 311 PublicationAdd BLAST31
PropeptideiPRO_000043637832 – 73Removed in mature form1 PublicationAdd BLAST42
ChainiPRO_000004515874 – 825SortilinAdd BLAST752

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi84 ↔ 554By similarity
Glycosylationi96N-linked (GlcNAc...)Sequence analysis1
Glycosylationi160N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi255 ↔ 275By similarity
Glycosylationi272N-linked (GlcNAc...)Sequence analysis1
Glycosylationi404N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi446 ↔ 456By similarity
Glycosylationi580N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi610 ↔ 649By similarity
Disulfide bondi632 ↔ 664By similarity
Disulfide bondi666 ↔ 721By similarity
Disulfide bondi673 ↔ 686By similarity
Glycosylationi682N-linked (GlcNAc...)Sequence 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

PaxDbiO54861.
PRIDEiO54861.

PTM databases

iPTMnetiO54861.
PhosphoSitePlusiO54861.
SwissPalmiO54861.
UniCarbKBiO54861.

Expressioni

Tissue specificityi

Highly expressed in fat, brain, and lung. Expressed in neuronal bodies and dendrites of the piriform cortex and hippocampus. Also expressed in the islands of Calleja, medial and lateral septal nuclei, amygdaloid nuclei, thalamic nuclei, the supraoptic nucleus, the substantia nigra, the Purkinje layer of the cerebellar cortex and the cranial motor nerve nuclei of the brainstem.2 Publications

Gene expression databases

ExpressionAtlasiO54861. baseline and differential.
GenevisibleiO54861. RN.

Interactioni

Subunit structurei

Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP and GM2A, LPL, NTS, PSAP and SLC2A4. Forms a complex with NGFR which binds specifically to the precursor form of NGFB (proNGFB). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may regulate their anterograde axonal transport and signaling. Interacts with NRADD and NGFR. Interaction with NRADD protects against degradation in the lysosome (By similarity). Interacts with the precursor form of BDNF (proBDNF) (PubMed:15987945). Interacts with CLN5 (By similarity).By similarity1 Publication

Protein-protein interaction databases

IntActiO54861. 3 interactors.
MINTiMINT-4583532.
STRINGi10116.ENSRNOP00000051102.

Structurei

3D structure databases

ProteinModelPortaliO54861.
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

Contains 9 BNR repeats.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ISX8. Eukaryota.
ENOG410ZJ6Q. LUCA.
GeneTreeiENSGT00510000046443.
HOGENOMiHOG000231347.
HOVERGENiHBG080235.
InParanoidiO54861.
KOiK12388.
OMAiCDSTAKN.
OrthoDBiEOG091G0ETU.

Family and domain databases

InterProiIPR031777. Sortilin_C.
IPR031778. Sortilin_N.
IPR006581. VPS10.
[Graphical view]
PfamiPF15902. Sortilin-Vps10. 1 hit.
PF15901. Sortilin_C. 1 hit.
[Graphical view]
SMARTiSM00602. VPS10. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

O54861-1 [UniParc]FASTAAdd to basket

« 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
ILAANDDMVF MHVDEPGDTG FGTIFTSDDR GIVYSKSLDR HLYTTTGGET
410 420 430 440 450
DFTNVTSLRG VYITSTLSED NSIQSMITFD QGGRWEHLQK 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 SQEPVYFTGL ASEPGARSMN ISIWGFTESF LTRQWVSYTI
610 620 630 640 650
DFKDILERNC EENDYTTWLA HSTDPGDYKD GCILGYKEQF LRLRKSSVCQ
660 670 680 690 700
NGRDYVVAKQ PSICPCSLED FLCDFGYFRP ENASECVEQP ELKGHELEFC
710 720 730 740 750
LYGKEEHLTT NGYRKIPGDR CQGGMNPARE VKDLKKKCTS NFLNPKKQNS
760 770 780 790 800
KSSSVPIILA IVGLMLVTVV AGVLIVKKYV CGGRFLVHRY SVLQQHAEAD
810 820
GVEALDTASH AKSGYHDDSD EDLLE
Length:825
Mass (Da):91,169
Last modified:December 20, 2005 - v3
Checksum:i060B43A54993EF06
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti91I → V in AAC02932 (PubMed:9452485).Curated1
Sequence conflicti276 – 277KA → T in AAB81864 (PubMed:9305862).Curated2
Sequence conflicti433G → R in AAB81864 (PubMed:9305862).Curated1
Sequence conflicti507D → Y in AAC02932 (PubMed:9452485).Curated1
Sequence conflicti659K → Q AA sequence (PubMed:9305862).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03012291 Genomic DNA. No translation available.
AABR03012896 Genomic DNA. No translation available.
AABR03017724 Genomic DNA. No translation available.
AABR03019134 Genomic DNA. No translation available.
AABR03020083 Genomic DNA. No translation available.
AF019109 mRNA. Translation: AAC02932.1.
AF023621 mRNA. Translation: AAB81864.1.
RefSeqiNP_113955.1. NM_031767.1.
UniGeneiRn.11286.

Genome annotation databases

EnsembliENSRNOT00000049127; ENSRNOP00000051102; ENSRNOG00000031814.
GeneIDi83576.
KEGGirno:83576.
UCSCiRGD:619999. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03012291 Genomic DNA. No translation available.
AABR03012896 Genomic DNA. No translation available.
AABR03017724 Genomic DNA. No translation available.
AABR03019134 Genomic DNA. No translation available.
AABR03020083 Genomic DNA. No translation available.
AF019109 mRNA. Translation: AAC02932.1.
AF023621 mRNA. Translation: AAB81864.1.
RefSeqiNP_113955.1. NM_031767.1.
UniGeneiRn.11286.

3D structure databases

ProteinModelPortaliO54861.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO54861. 3 interactors.
MINTiMINT-4583532.
STRINGi10116.ENSRNOP00000051102.

PTM databases

iPTMnetiO54861.
PhosphoSitePlusiO54861.
SwissPalmiO54861.
UniCarbKBiO54861.

Proteomic databases

PaxDbiO54861.
PRIDEiO54861.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000049127; ENSRNOP00000051102; ENSRNOG00000031814.
GeneIDi83576.
KEGGirno:83576.
UCSCiRGD:619999. rat.

Organism-specific databases

CTDi6272.
RGDi619999. Sort1.

Phylogenomic databases

eggNOGiENOG410ISX8. Eukaryota.
ENOG410ZJ6Q. LUCA.
GeneTreeiENSGT00510000046443.
HOGENOMiHOG000231347.
HOVERGENiHBG080235.
InParanoidiO54861.
KOiK12388.
OMAiCDSTAKN.
OrthoDBiEOG091G0ETU.

Enzyme and pathway databases

ReactomeiR-RNO-432722. Golgi Associated Vesicle Biogenesis.

Miscellaneous databases

PROiO54861.

Gene expression databases

ExpressionAtlasiO54861. baseline and differential.
GenevisibleiO54861. RN.

Family and domain databases

InterProiIPR031777. Sortilin_C.
IPR031778. Sortilin_N.
IPR006581. VPS10.
[Graphical view]
PfamiPF15902. Sortilin-Vps10. 1 hit.
PF15901. Sortilin_C. 1 hit.
[Graphical view]
SMARTiSM00602. VPS10. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSORT_RAT
AccessioniPrimary (citable) accession number: O54861
Secondary accession number(s): O35389
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 20, 2005
Last modified: November 2, 2016
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.