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O54861 (SORT_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sortilin
Alternative name(s):
Glycoprotein 110
Short name=Gp110
Neurotensin receptor 3
Short name=NTR3
Gene names
Name:Sort1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length825 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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). 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. Ref.4

Subunit structure

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). Ref.6

Subcellular location

Membrane; Single-pass type I membrane protein Potential. Endoplasmic reticulum membrane; Single-pass type I membrane protein Potential. Endosome membrane; Single-pass type I membrane protein Potential. Golgi apparatusGolgi stack membrane; Single-pass type I membrane protein Potential. Lysosome membrane; Single-pass type I membrane protein Potential. Nucleus membrane; Single-pass type I membrane protein Potential. Cell membrane; Single-pass type I membrane protein; Extracellular side. Note: Localized to membranes of the endosomes, Golgi stack, lysosomes and nucleus. Interaction with NRADD promotes localization at the cell membrane in neurons; this promotes interaction with NGFR. Localization to the plasma membrane in adipocytes is enhanced by insulin By similarity. Localized to the endoplasmic reticulum and the plasma membrane. Also found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes. Ref.2 Ref.3 Ref.5

Tissue specificity

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. Ref.3 Ref.5

Domain

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.

The extracellular domain may be shed following protease cleavage in some cell types By similarity.

Post-translational modification

The N-terminal propeptide is cleaved by furin and possibly other homologous proteases By similarity.

Sequence similarities

Belongs to the VPS10-related sortilin family. SORT1 subfamily.

Contains 9 BNR repeats.

Ontologies

Keywords
   Biological processDifferentiation
Endocytosis
Osteogenesis
Transport
   Cellular componentCell membrane
Endoplasmic reticulum
Endosome
Golgi apparatus
Lysosome
Membrane
Nucleus
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
Receptor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular protein transport

Non-traceable author statement Ref.2. Source: RGD

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

neuropeptide signaling pathway

Traceable author statement Ref.5. Source: GOC

ossification

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi cisterna membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

dendrite

Inferred from direct assay Ref.5. Source: RGD

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from direct assay Ref.5. Source: RGD

intracellular membrane-bounded organelle

Inferred from direct assay Ref.5Ref.2. Source: RGD

lysosomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuronal cell body

Inferred from direct assay Ref.5. Source: RGD

nuclear membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay Ref.2. Source: RGD

   Molecular_functionG-protein coupled neurotensin receptor activity

Traceable author statement Ref.5. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Propeptide32 – 7544Removed in mature form By similarity
PRO_0000045157
Chain76 – 825750Sortilin
PRO_0000045158

Regions

Topological domain76 – 754679Extracellular Potential
Transmembrane755 – 77521Helical; Potential
Topological domain776 – 82550Cytoplasmic Potential
Repeat143 – 15412BNR 1
Repeat196 – 20712BNR 2
Repeat238 – 24912BNR 3
Repeat285 – 29612BNR 4
Repeat326 – 33712BNR 5
Repeat375 – 38612BNR 6
Repeat426 – 43712BNR 7
Repeat504 – 51512BNR 8
Repeat546 – 55712BNR 9
Region48 – 5912Intrachain binding of the propeptide and the extracellular domain By similarity
Region610 – 754145Interactions with LRPAP1 and NGFB By similarity
Region777 – 82549Golgi to endosome transport and interactions with GGA1 and GGA2 By similarity
Motif785 – 7906Endocytosis signal Potential
Compositional bias38 – 447Poly-Pro

Amino acid modifications

Modified residue8131Phosphoserine By similarity
Modified residue8191Phosphoserine By similarity
Glycosylation961N-linked (GlcNAc...) Potential
Glycosylation1601N-linked (GlcNAc...) Potential
Glycosylation2721N-linked (GlcNAc...) Potential
Glycosylation4041N-linked (GlcNAc...) Potential
Glycosylation5801N-linked (GlcNAc...) Potential
Glycosylation6821N-linked (GlcNAc...) Potential
Disulfide bond84 ↔ 554 By similarity
Disulfide bond255 ↔ 275 By similarity
Disulfide bond446 ↔ 456 By similarity
Disulfide bond610 ↔ 649 By similarity
Disulfide bond632 ↔ 664 By similarity
Disulfide bond666 ↔ 721 By similarity
Disulfide bond673 ↔ 686 By similarity
Disulfide bond700 ↔ 738 By similarity

Experimental info

Sequence conflict911I → V in AAC02932. Ref.2
Sequence conflict276 – 2772KA → T in AAB81864. Ref.3
Sequence conflict4331G → R in AAB81864. Ref.3
Sequence conflict5071D → Y in AAC02932. Ref.2
Sequence conflict6591K → Q AA sequence Ref.3

Sequences

Sequence LengthMass (Da)Tools
O54861 [UniParc].

Last modified December 20, 2005. Version 3.
Checksum: 060B43A54993EF06

FASTA82591,169
        10         20         30         40         50         60 
MERPRGAADG LLRWPLGLLL LLQLLPPAAV GQDRLDAPPP PAPPLLRWAG PVGVSWGLRA 

        70         80         90        100        110        120 
AAPGGPVPRA GRWRRGAPAE DQDCGRLPDF IAKLTNNTHQ HVFDDLSGSV SLSWVGDSTG 

       130        140        150        160        170        180 
VILVLTTFQV PLVIVSFGQS KLYRSEDYGK NFKDITNLIN NTFIRTEFGM AIGPENSGKV 

       190        200        210        220        230        240 
ILTAEVSGGS RGGRVFRSSD FAKNFVQTDL PFHPLTQMMY SPQNSDYLLA LSTENGLWVS 

       250        260        270        280        290        300 
KNFGEKWEEI HKAVCLAKWG PNNIIFFTTH VNGSCKADLG ALELWRTSDL GKTFKTIGVK 

       310        320        330        340        350        360 
IYSFGLGGRF LFASVMADKD TTRRIHVSTD QGDTWSMAQL PSVGQEQFYS ILAANDDMVF 

       370        380        390        400        410        420 
MHVDEPGDTG FGTIFTSDDR GIVYSKSLDR HLYTTTGGET DFTNVTSLRG VYITSTLSED 

       430        440        450        460        470        480 
NSIQSMITFD QGGRWEHLQK PENSKCDATA KNKNECSLHI HASYSISQKL NVPMAPLSEP 

       490        500        510        520        530        540 
NAVGIVIAHG SVGDAISVMV PDVYISDDGG YSWAKMLEGP HYYTILDSGG IIVAIEHSNR 

       550        560        570        580        590        600 
PINVIKFSTD EGQCWQSYVF SQEPVYFTGL ASEPGARSMN ISIWGFTESF LTRQWVSYTI 

       610        620        630        640        650        660 
DFKDILERNC EENDYTTWLA HSTDPGDYKD GCILGYKEQF LRLRKSSVCQ NGRDYVVAKQ 

       670        680        690        700        710        720 
PSICPCSLED FLCDFGYFRP ENASECVEQP ELKGHELEFC LYGKEEHLTT NGYRKIPGDR 

       730        740        750        760        770        780 
CQGGMNPARE VKDLKKKCTS NFLNPKKQNS KSSSVPIILA IVGLMLVTVV AGVLIVKKYV 

       790        800        810        820 
CGGRFLVHRY SVLQQHAEAD GVEALDTASH AKSGYHDDSD EDLLE 

« Hide

References

« Hide 'large scale' references
[1]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[2]"Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipocytes."
Morris N.J., Ross S.A., Lane W.S., Moestrup S.K., Petersen C.M., Keller S.R., Lienhard G.E.
J. Biol. Chem. 273:3582-3587(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 89-825, PROTEIN SEQUENCE OF 78-93, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION.
Strain: Sprague-Dawley.
Tissue: Adipocyte.
[3]"Sortilin is a major protein component of Glut4-containing vesicles."
Lin B.-Z., Pilch P.F., Kandror K.V.
J. Biol. Chem. 272:24145-24147(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 121-745, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Skeletal muscle.
[4]"The prodomain of a secreted hydrophobic mini-protein facilitates its export from the endoplasmic reticulum by hitchhiking on sorting receptors."
Conticello S.G., Kowalsman N.D., Jacobsen C., Yudkovsky G., Sato K., Elazar Z., Petersen C.M., Aronheim A., Fainzilber M.
J. Biol. Chem. 278:26311-26314(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Distribution of NTS3 receptor/sortilin mRNA and protein in the rat central nervous system."
Sarret P., Krzywkowski P., Segal L., Nielsen M.S., Petersen C.M., Mazella J., Stroh T., Beaudet A.
J. Comp. Neurol. 461:483-505(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway."
Chen Z.-Y., Ieraci A., Teng H., Dall H., Meng C.-X., Herrera D.G., Nykjaer A., Hempstead B.L., Lee F.S.
J. Neurosci. 25:6156-6166(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BDNF.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_113955.1. NM_031767.1.
UniGeneRn.11286.

3D structure databases

ProteinModelPortalO54861.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO54861. 3 interactions.
MINTMINT-4583532.

Proteomic databases

PaxDbO54861.
PRIDEO54861.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID83576.
KEGGrno:83576.
UCSCRGD:619999. rat.

Organism-specific databases

CTD6272.
RGD619999. Sort1.

Phylogenomic databases

eggNOGNOG281049.
HOGENOMHOG000231347.
HOVERGENHBG080235.
KOK12388.

Gene expression databases

GenevestigatorO54861.

Family and domain databases

InterProIPR006581. VPS10.
[Graphical view]
SMARTSM00602. VPS10. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio616085.
PROO54861.

Entry information

Entry nameSORT_RAT
AccessionPrimary (citable) accession number: O54861
Secondary accession number(s): O35389
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 20, 2005
Last modified: April 16, 2014
This is version 114 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families