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UniProtKB/Swiss-Prot entry O54861


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name SORT_RAT
Primary accession number O54861
Secondary accession number O35389
Integrated into Swiss-Prot on December 1, 2000
Sequence was last modified on December 20, 2005 (Sequence version 3)
Annotations were last modified on    December 16, 2008 (Entry version 66)
Name and origin of the protein
Protein name Sortilin [Precursor]
Synonyms Neurotensin receptor 3
NTR3
Glycoprotein 110
Gp110
Gene name
Name: Sort1
From
Rattus norvegicus (Rat) [TaxID: 10116] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Rattus.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Brown Norway;
DOI=10.1038/nature02426; PubMed=15057822 [NCBI, ExPASy, EBI, Israel, Japan]
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., 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.;
"Genome sequence of the Brown Norway rat yields insights into mammalian evolution.";
Nature 428:493-521(2004).
[2]
NUCLEOTIDE SEQUENCE [MRNA] OF 89-825, PROTEIN SEQUENCE OF 78-93, PARTIAL PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
STRAIN=Sprague-Dawley;
TISSUE=Adipocyte;
DOI=10.1074/jbc.273.6.3582; PubMed=9452485 [NCBI, ExPASy, EBI, Israel, Japan]
Morris N.J., Ross S.A., Lane W.S., Moestrup S.K., Petersen C.M., Keller S.R., Lienhard G.E.;
"Sortilin is the major 110-kDa protein in GLUT4 vesicles from adipocytes.";
J. Biol. Chem. 273:3582-3587(1998).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 121-745, PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
STRAIN=Sprague-Dawley;
TISSUE=Skeletal muscle;
DOI=10.1074/jbc.272.39.24145; PubMed=9305862 [NCBI, ExPASy, EBI, Israel, Japan]
Lin B.-Z., Pilch P.F., Kandror K.V.;
"Sortilin is a major protein component of Glut4-containing vesicles.";
J. Biol. Chem. 272:24145-24147(1997).
[4]
FUNCTION.
DOI=10.1074/jbc.C300141200; PubMed=12771154 [NCBI, ExPASy, EBI, Israel, Japan]
Conticello S.G., Kowalsman N.D., Jacobsen C., Yudkovsky G., Sato K., Elazar Z., Petersen C.M., Aronheim A., Fainzilber M.;
"The prodomain of a secreted hydrophobic mini-protein facilitates its export from the endoplasmic reticulum by hitchhiking on sorting receptors.";
J. Biol. Chem. 278:26311-26314(2003).
[5]
SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
DOI=10.1002/cne.10708; PubMed=12746864 [NCBI, ExPASy, EBI, Israel, Japan]
Sarret P., Krzywkowski P., Segal L., Nielsen M.S., Petersen C.M., Mazella J., Stroh T., Beaudet A.;
"Distribution of NTS3 receptor/sortilin mRNA and protein in the rat central nervous system.";
J. Comp. Neurol. 461:483-505(2003).
[6]
INTERACTION WITH BDNF.
DOI=10.1523/JNEUROSCI.1017-05.2005; PubMed=15987945 [NCBI, ExPASy, EBI, Israel, Japan]
Chen Z.-Y., Ieraci A., Teng H., Dall H., Meng C.-X., Herrera D.G., Nykjaer A., Hempstead B.L., Lee F.S.;
"Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway.";
J. Neurosci. 25:6156-6166(2005).
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.
  • SUBUNIT: Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP and GM2A, LPL, PSAP and SLC2A4. Forms a complex with NGFR which binds specifically to the precursor form of NGFB (proNGFB) (By similarity). Interacts with the precursor form of BDNF (proBDNF).
  • 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 apparatus, Golgi 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. Lysosome membrane; Single-pass type I membrane protein (Potential). Note=Localized to membranes of the endosomes, Golgi stack, lysosomes and nucleus. 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.
  • 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.
  • 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).
  • DOMAIN: The extracellular domain may be shed following protease cleavage in some cell types (By similarity).
  • PTM: The N-terminal propeptide is cleaved by furin and possibly other homologous proteases (By similarity).
  • PTM: Contains 8 intrachain disulfide bonds (By similarity).
  • PTM: N-glycosylated (By similarity).
  • SIMILARITY: Contains 9 BNR repeats.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AABR03012291; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
AABR03012896; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
AABR03017724; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
AABR03019134; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
AABR03020083; -; NOT_ANNOTATED_CDS; Genomic_DNA.[EMBL / GenBank / DDBJ]
AF019109; AAC02932.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF023621; AAB81864.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_113955.1; -.
UniGene Rn.11286
3D structure databases
ModBase O54861.
Organism-specific databases
RGD 619999; Sort1.
Gene expression databases
ArrayExpress O54861; -.
GermOnline ENSRNOG00000031814; Rattus norvegicus.
Ontologies
GO
GO:0005789; Cellular component: endoplasmic reticulum membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0010008; Cellular component: endosome membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0016021; Cellular component: integral to membrane (inferred from electronic annotation from InterPro).
GO:0005765; Cellular component: lysosomal membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0031965; Cellular component: nuclear membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0006897; Biological process: endocytosis (inferred from electronic annotation from UniProtKB-KW).
GO:0001503; Biological process: ossification (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR002860; BNR.
IPR006581; VPS10.
Graphical view of domain structure.
Pfam PF02012; BNR; 8.
Pfam graphical view of domain structure.
SMART SM00602; VPS10; 1.
SMART graphical view of domain structure.
Genome annotation databases
Ensembl ENSRNOG00000031814; Rattus norvegicus. [Contig view]
GeneID 83576; -.
Phylogenomic databases
HOVERGEN O54861; -.
Other
NextBio 616085; -.
ProtoNet O54861.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
Cell membrane; Cleavage on pair of basic residues; Developmental protein; Differentiation; Direct protein sequencing; Endocytosis; Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus; Lysosome; Membrane; Nucleus; Osteogenesis; Phosphoprotein; Receptor; Repeat; Signal; Transmembrane; Transport.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    31  31     Potential. 
PROPEP   32    75  44     Removed in mature form (By similarity). PRO_0000045157
CHAIN   76   825  750     Sortilin. PRO_0000045158
TOPO_DOM   76   754  679     Extracellular (Potential). 
TRANSMEM   755   775  21     Potential. 
TOPO_DOM   776   825  50     Cytoplasmic (Potential). 
REPEAT   143   154  12     BNR 1. 
REPEAT   196   207  12     BNR 2. 
REPEAT   238   249  12     BNR 3. 
REPEAT   285   296  12     BNR 4. 
REPEAT   326   337  12     BNR 5. 
REPEAT   375   386  12     BNR 6. 
REPEAT   426   437  12     BNR 7. 
REPEAT   504   515  12     BNR 8. 
REPEAT   546   557  12     BNR 9. 
REGION   48    59  12     Intrachain binding of the propeptide and the extracellular domain (By similarity). 
REGION   610   754  145     Interactions with LRPAP1 and NGFB (By similarity). 
REGION   777   825  49     Golgi to endosome transport and interactions with GGA1 and GGA2 (By similarity). 
MOTIF   785   790  6     Endocytosis signal (Potential). 
COMPBIAS   38    44  7     Poly-Pro. 
MOD_RES   819   819        Phosphoserine (By similarity). 
CARBOHYD   96    96        N-linked (GlcNAc...) (Potential). 
CARBOHYD   160   160        N-linked (GlcNAc...) (Potential). 
CARBOHYD   272   272        N-linked (GlcNAc...) (Potential). 
CARBOHYD   404   404        N-linked (GlcNAc...) (Potential). 
CARBOHYD   580   580        N-linked (GlcNAc...) (Potential). 
CARBOHYD   682   682        N-linked (GlcNAc...) (Potential). 
DISULFID   84   554        By similarity. 
DISULFID   255   275        By similarity. 
DISULFID   446   456        By similarity. 
DISULFID   610   649        By similarity. 
DISULFID   632   664        By similarity. 
DISULFID   666   721        By similarity. 
DISULFID   673   686        By similarity. 
DISULFID   700   738        By similarity. 
CONFLICT   91    91        I -> V (in Ref. 2; AAC02932). 
CONFLICT   276   277        KA -> T (in Ref. 3; AAB81864). 
CONFLICT   433   433        G -> R (in Ref. 3; AAB81864). 
CONFLICT   507   507        D -> Y (in Ref. 2; AAC02932). 
CONFLICT   659   659        K -> Q (in Ref. 3; AA sequence). 
Sequence information
Length: 825 AA [This is the length of the unprocessed precursor] Molecular weight: 91169 Da [This is the MW of the unprocessed precursor] CRC64: 060B43A54993EF06 [This is a checksum on the sequence]
        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 

O54861 in FASTA format

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