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O54861

- SORT_RAT

UniProt

O54861 - SORT_RAT

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Protein

Sortilin

Gene

Sort1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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

  1. G-protein coupled neurotensin receptor activity Source: RGD

GO - Biological processi

  1. cell differentiation Source: UniProtKB-KW
  2. endocytosis Source: UniProtKB-KW
  3. intracellular protein transport Source: RGD
  4. multicellular organismal development Source: UniProtKB-KW
  5. neuropeptide signaling pathway Source: GOC
  6. ossification Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Differentiation, Endocytosis, Osteogenesis, Transport

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
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi619999. Sort1.

Subcellular locationi

Membrane Curated; Single-pass type I membrane protein Curated. Endoplasmic reticulum membrane Curated; Single-pass type I membrane protein Curated. Endosome membrane Curated; Single-pass type I membrane protein Curated. Golgi apparatusGolgi stack membrane Curated; Single-pass type I membrane protein Curated. Lysosome membrane Curated; Single-pass type I membrane protein Curated. Nucleus membrane Curated; Single-pass type I membrane protein Curated. 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.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini76 – 754679ExtracellularSequence AnalysisAdd
BLAST
Transmembranei755 – 77521HelicalSequence AnalysisAdd
BLAST
Topological domaini776 – 82550CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. dendrite Source: RGD
  2. endoplasmic reticulum Source: UniProtKB-KW
  3. endosome Source: UniProtKB-KW
  4. Golgi apparatus Source: UniProtKB-KW
  5. integral component of membrane Source: RGD
  6. intracellular membrane-bounded organelle Source: RGD
  7. lysosome Source: UniProtKB-KW
  8. neuronal cell body Source: RGD
  9. nucleus Source: UniProtKB-KW
  10. plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131Sequence AnalysisAdd
BLAST
Propeptidei32 – 7544Removed in mature formBy similarityPRO_0000045157Add
BLAST
Chaini76 – 825750SortilinPRO_0000045158Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi84 ↔ 554By similarity
Glycosylationi96 – 961N-linked (GlcNAc...)Sequence Analysis
Glycosylationi160 – 1601N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi255 ↔ 275By similarity
Glycosylationi272 – 2721N-linked (GlcNAc...)Sequence Analysis
Glycosylationi404 – 4041N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi446 ↔ 456By similarity
Glycosylationi580 – 5801N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi610 ↔ 649By similarity
Disulfide bondi632 ↔ 664By similarity
Disulfide bondi666 ↔ 721By similarity
Disulfide bondi673 ↔ 686By similarity
Glycosylationi682 – 6821N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi700 ↔ 738By similarity
Modified residuei813 – 8131PhosphoserineBy similarity
Modified residuei819 – 8191PhosphoserineBy similarity

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.

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

GenevestigatoriO54861.

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).By similarity1 Publication

Protein-protein interaction databases

IntActiO54861. 3 interactions.
MINTiMINT-4583532.

Structurei

3D structure databases

ProteinModelPortaliO54861.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati143 – 15412BNR 1Add
BLAST
Repeati196 – 20712BNR 2Add
BLAST
Repeati238 – 24912BNR 3Add
BLAST
Repeati285 – 29612BNR 4Add
BLAST
Repeati326 – 33712BNR 5Add
BLAST
Repeati375 – 38612BNR 6Add
BLAST
Repeati426 – 43712BNR 7Add
BLAST
Repeati504 – 51512BNR 8Add
BLAST
Repeati546 – 55712BNR 9Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni48 – 5912Intrachain binding of the propeptide and the extracellular domainBy similarityAdd
BLAST
Regioni610 – 754145Interactions with LRPAP1 and NGFBBy similarityAdd
BLAST
Regioni777 – 82549Golgi to endosome transport and interactions with GGA1 and GGA2By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi785 – 7906Endocytosis signalSequence Analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi38 – 447Poly-Pro

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

eggNOGiNOG281049.
HOGENOMiHOG000231347.
HOVERGENiHBG080235.
InParanoidiO54861.
KOiK12388.

Family and domain databases

InterProiIPR006581. VPS10.
[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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti91 – 911I → V in AAC02932. (PubMed:9452485)Curated
Sequence conflicti276 – 2772KA → T in AAB81864. (PubMed:9305862)Curated
Sequence conflicti433 – 4331G → R in AAB81864. (PubMed:9305862)Curated
Sequence conflicti507 – 5071D → Y in AAC02932. (PubMed:9452485)Curated
Sequence conflicti659 – 6591K → Q AA sequence (PubMed:9305862)Curated

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

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 .
RefSeqi NP_113955.1. NM_031767.1.
UniGenei Rn.11286.

3D structure databases

ProteinModelPortali O54861.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi O54861. 3 interactions.
MINTi MINT-4583532.

Proteomic databases

PaxDbi O54861.
PRIDEi O54861.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 83576.
KEGGi rno:83576.
UCSCi RGD:619999. rat.

Organism-specific databases

CTDi 6272.
RGDi 619999. Sort1.

Phylogenomic databases

eggNOGi NOG281049.
HOGENOMi HOG000231347.
HOVERGENi HBG080235.
InParanoidi O54861.
KOi K12388.

Miscellaneous databases

NextBioi 616085.
PROi O54861.

Gene expression databases

Genevestigatori O54861.

Family and domain databases

InterProi IPR006581. VPS10.
[Graphical view ]
SMARTi SM00602. VPS10. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

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: October 29, 2014
This is version 116 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

External Data

Dasty 3