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Q99523 (SORT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sortilin
Alternative name(s):
100 kDa NT receptor
Glycoprotein 95
Short name=Gp95
Neurotensin receptor 3
Short name=NT3
Short name=NTR3
Gene names
Name:SORT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length831 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.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.18 Ref.19 Ref.21 Ref.22 Ref.23

Subunit structure

Interacts with LPL and SLC2A4 By similarity. Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP, GM2A, NTS and PSAP. 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. Ref.1 Ref.8 Ref.9 Ref.11 Ref.12 Ref.15 Ref.16 Ref.20 Ref.21 Ref.23 Ref.32 Ref.34

Subcellular location

Membrane; Single-pass type I membrane protein. 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. 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 endoplasmic reticulum, endosomes, Golgi stack, lysosomes and nucleus. A small fraction of the protein is also localized to the plasma membrane. May also be found in SLC2A4/GLUT4 storage vesicles (GSVs) in adipocytes. Localization to the plasma membrane in adipocytes may be enhanced by insulin. Ref.1 Ref.16 Ref.18 Ref.19 Ref.20

Tissue specificity

Expressed in brain and prostate (at protein level). Expressed at high levels in brain, spinal cord, heart, skeletal muscle, thyroid, placenta and testis. Expressed at lower levels in lymphoid organs, kidney, colon and liver. Ref.1 Ref.28

Induction

During osteoblast differentiation. Ref.14

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. Ref.13

The extracellular domain may be shed following protease cleavage in some cell types. Ref.13

Post-translational modification

The N-terminal propeptide is cleaved by furin and possibly other homologous proteases. Ref.8 Ref.13

Polymorphism

Genetic variations in SORT1 influence low density lipoprotein cholesterol (LDL-C) variability and contribute to the low density lipoprotein cholesterol level quantitative trait locus 6 (LDLCQ6) [MIM:613589].

Involvement in disease

A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.

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
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
Receptor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from mutant phenotype PubMed 18258592. Source: BHF-UCL

Golgi to endosome transport

Inferred from direct assay Ref.11. Source: BHF-UCL

endocytosis

Inferred from direct assay Ref.11. Source: BHF-UCL

endosome to lysosome transport

Inferred from direct assay Ref.11. Source: BHF-UCL

endosome transport via multivesicular body sorting pathway

Inferred from direct assay Ref.11. Source: BHF-UCL

extrinsic apoptotic signaling pathway via death domain receptors

Inferred from direct assay Ref.21. Source: BHF-UCL

glucose import

Inferred from mutant phenotype PubMed 15992544. Source: BHF-UCL

multicellular organismal development

Inferred from electronic annotation. Source: UniProtKB-KW

myotube differentiation

Inferred from mutant phenotype PubMed 18258592. Source: BHF-UCL

negative regulation of lipoprotein lipase activity

Inferred from direct assay Ref.10. Source: BHF-UCL

nerve growth factor signaling pathway

Inferred from direct assay Ref.21. Source: GOC

neuropeptide signaling pathway

Inferred from direct assay Ref.7. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Inferred from mutant phenotype Ref.21. Source: BHF-UCL

ossification

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane to endosome transport

Inferred from direct assay Ref.11. Source: BHF-UCL

regulation of gene expression

Inferred from mutant phenotype PubMed 18258592. Source: BHF-UCL

response to insulin

Inferred from mutant phenotype PubMed 15992544. Source: BHF-UCL

vesicle organization

Inferred from direct assay PubMed 15992544. Source: BHF-UCL

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.11. Source: BHF-UCL

Golgi cisterna membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell surface

Inferred from direct assay Ref.10. Source: BHF-UCL

clathrin-coated vesicle

Inferred from direct assay Ref.11. Source: BHF-UCL

coated pit

Inferred from direct assay Ref.11. Source: BHF-UCL

cytoplasmic membrane-bounded vesicle

Inferred from direct assay Ref.7. Source: BHF-UCL

early endosome

Inferred from direct assay Ref.11. Source: BHF-UCL

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 PubMed 15992544. Source: BHF-UCL

lysosomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from direct assay Ref.11. Source: BHF-UCL

plasma membrane

Inferred from direct assay Ref.11. Source: BHF-UCL

trans-Golgi network transport vesicle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionenzyme binding

Inferred from physical interaction Ref.10. Source: BHF-UCL

nerve growth factor binding

Inferred from physical interaction Ref.21. Source: BHF-UCL

nerve growth factor receptor activity

Inferred from direct assay Ref.21. Source: BHF-UCL

neurotensin receptor activity, non-G-protein coupled

Inferred from direct assay Ref.7. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.10Ref.12PubMed 20676133. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GGA1Q9UJY52EBI-1057058,EBI-447141
LPLP111516EBI-1057058,EBI-8794090From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99523-1)

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.
Isoform 2 (identifier: Q99523-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-136: Missing.
     278-279: KA → T
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Potential
Propeptide34 – 7744Removed in mature form
PRO_0000033162
Chain78 – 831754Sortilin
PRO_0000033163

Regions

Topological domain78 – 755678Extracellular Potential
Transmembrane756 – 77823Helical; Potential
Topological domain779 – 83153Cytoplasmic Potential
Repeat145 – 15612BNR 1
Repeat198 – 20912BNR 2
Repeat240 – 25112BNR 3
Repeat287 – 29812BNR 4
Repeat328 – 33912BNR 5
Repeat377 – 38812BNR 6
Repeat428 – 43912BNR 7
Repeat506 – 51712BNR 8
Repeat548 – 55912BNR 9
Region50 – 6112Intrachain binding of the propeptide and the extracellular domain
Region612 – 756145Interactions with LRPAP1 and NGFB
Region779 – 83153Golgi to endosome transport and interactions with GGA1 and GGA2
Motif787 – 7926Endocytosis signal Probable

Amino acid modifications

Modified residue8191Phosphoserine Ref.33
Modified residue8251Phosphoserine Ref.25 Ref.33
Glycosylation981N-linked (GlcNAc...) Probable
Glycosylation1621N-linked (GlcNAc...) Ref.24 Ref.27
Glycosylation1631N-linked (GlcNAc...); atypical Ref.27
Glycosylation2741N-linked (GlcNAc...) Potential
Glycosylation4061N-linked (GlcNAc...) Ref.34
Glycosylation5821N-linked (GlcNAc...) Ref.34
Glycosylation6841N-linked (GlcNAc...) Potential
Disulfide bond86 ↔ 556 Ref.20 Ref.34
Disulfide bond257 ↔ 277 Ref.20 Ref.34
Disulfide bond448 ↔ 458 Ref.20 Ref.34
Disulfide bond612 ↔ 651 Ref.20 Ref.34
Disulfide bond634 ↔ 666 Ref.20 Ref.34
Disulfide bond668 ↔ 723 Ref.20 Ref.34
Disulfide bond675 ↔ 688 Ref.20 Ref.34
Disulfide bond702 ↔ 740 Ref.20 Ref.34

Natural variations

Alternative sequence1 – 136136Missing in isoform 2.
VSP_046239
Alternative sequence278 – 2792KA → T in isoform 2.
VSP_046240
Natural variant3581D → Y.
Corresponds to variant rs2228605 [ dbSNP | Ensembl ].
VAR_053681

Experimental info

Mutagenesis74 – 774RWRR → GWRA: Abrogates propeptide cleavage. Ref.8
Mutagenesis76 – 772RR → GG: Abrogates propeptide cleavage.
Mutagenesis7921Y → A: Reduces endocytosis and Golgi to endosome sorting; when associated with A-795. Ref.11
Mutagenesis7951L → A: Reduces endocytosis and Golgi to endosome sorting; when associated with A-792. Ref.11
Mutagenesis823 – 8242DD → NN: Reduces interaction with GGA1.
Mutagenesis8251S → A: Reduces interaction with GGA1. Ref.12
Mutagenesis826 – 8283DED → NQN: Abrogates interaction with GGA1 and impairs localization to the Golgi. Ref.12
Mutagenesis829 – 8302LL → AA: Abrogates interaction with GGA1 and impairs localization to the Golgi.
Mutagenesis829 – 8302Missing: Abrogates interaction with GGA2. Reduces endocytosis and Golgi to endosome sorting; when associated with A-792 and A-795.
Sequence conflict6501V → M in CAA66904. Ref.1

Secondary structure

............................................................................................................................ 831
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 20, 2005. Version 3.
Checksum: 91F96A3035A4B43A

FASTA83192,068
        10         20         30         40         50         60 
MERPWGAADG LSRWPHGLGL LLLLQLLPPS TLSQDRLDAP PPPAAPLPRW SGPIGVSWGL 

        70         80         90        100        110        120 
RAAAAGGAFP RGGRWRRSAP GEDEECGRVR DFVAKLANNT HQHVFDDLRG SVSLSWVGDS 

       130        140        150        160        170        180 
TGVILVLTTF HVPLVIMTFG QSKLYRSEDY GKNFKDITDL INNTFIRTEF GMAIGPENSG 

       190        200        210        220        230        240 
KVVLTAEVSG GSRGGRIFRS SDFAKNFVQT DLPFHPLTQM MYSPQNSDYL LALSTENGLW 

       250        260        270        280        290        300 
VSKNFGGKWE EIHKAVCLAK WGSDNTIFFT TYANGSCKAD LGALELWRTS DLGKSFKTIG 

       310        320        330        340        350        360 
VKIYSFGLGG RFLFASVMAD KDTTRRIHVS TDQGDTWSMA QLPSVGQEQF YSILAANDDM 

       370        380        390        400        410        420 
VFMHVDEPGD TGFGTIFTSD DRGIVYSKSL DRHLYTTTGG ETDFTNVTSL RGVYITSVLS 

       430        440        450        460        470        480 
EDNSIQTMIT FDQGGRWTHL RKPENSECDA TAKNKNECSL HIHASYSISQ KLNVPMAPLS 

       490        500        510        520        530        540 
EPNAVGIVIA HGSVGDAISV MVPDVYISDD GGYSWTKMLE GPHYYTILDS GGIIVAIEHS 

       550        560        570        580        590        600 
SRPINVIKFS TDEGQCWQTY TFTRDPIYFT GLASEPGARS MNISIWGFTE SFLTSQWVSY 

       610        620        630        640        650        660 
TIDFKDILER NCEEKDYTIW LAHSTDPEDY EDGCILGYKE QFLRLRKSSV CQNGRDYVVT 

       670        680        690        700        710        720 
KQPSICLCSL EDFLCDFGYY RPENDSKCVE QPELKGHDLE FCLYGREEHL TTNGYRKIPG 

       730        740        750        760        770        780 
DKCQGGVNPV REVKDLKKKC TSNFLSPEKQ NSKSNSVPII LAIVGLMLVT VVAGVLIVKK 

       790        800        810        820        830 
YVCGGRFLVH RYSVLQQHAE ANGVDGVDAL DTASHTNKSG YHDDSDEDLL E 

« Hide

Isoform 2 [UniParc].

Checksum: 4F80EC724C360750
Show »

FASTA69477,375

References

« Hide 'large scale' references
[1]"Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography."
Petersen C.M., Nielsen M.S., Nykjaer A., Jacobsen L., Tommerup N., Rasmussen H.H., Roeigaard H., Gliemann J., Madsen P., Moestrup S.K.
J. Biol. Chem. 272:3599-3605(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, INTERACTION WITH LRPAP1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION.
Tissue: T-cell.
[2]Madsen P.
Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Mammary gland.
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Muscle.
[7]"The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor."
Mazella J., Zsurger N., Navarro V., Chabry J., Kaghad M., Caput D., Ferrara P., Vita M., Gully D., Maffrand J.-P., Vincent J.-P.
J. Biol. Chem. 273:26273-26276(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 78-100, IDENTIFICATION AS A NEUROTENSIN RECEPTOR.
Tissue: Brain.
[8]"Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding."
Petersen C.M., Nielsen M.S., Jacobsen C., Tauris J., Jacobsen L., Gliemann J., Moestrup S.K., Madsen P.
EMBO J. 18:595-604(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, INTERACTION WITH LRPAP1, MUTAGENESIS OF 74-ARG--ARG-77 AND 76-ARG-ARG-77, CLEAVAGE BY FURIN, GLYCOSYLATION.
[9]"The carboxy-terminal domain of the receptor-associated protein binds to the Vps10p domain of sortilin."
Tauris J., Ellgaard L., Jacobsen C., Nielsen M.S., Madsen P., Thoegersen H.C., Gliemann J., Petersen C.M., Moestrup S.K.
FEBS Lett. 429:27-30(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRPAP1.
[10]"Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase."
Nielsen M.S., Jacobsen C., Olivecrona G., Gliemann J., Petersen C.M.
J. Biol. Chem. 274:8832-8836(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein."
Nielsen M.S., Madsen P., Christensen E.I., Nykjaer A., Gliemann J., Kasper D., Pohlmann R., Petersen C.M.
EMBO J. 20:2180-2190(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GGA2, MUTAGENESIS OF TYR-792; LEU-795 AND 829-LEU-LEU-830.
[12]"Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains."
Takatsu H., Katoh Y., Shiba Y., Nakayama K.
J. Biol. Chem. 276:28541-28545(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GGA1 AND GGA2, MUTAGENESIS OF 823-ASP-ASP-824; SER-825; 826-ASP--ASP-828 AND 829-LEU-LEU-830.
[13]"Shedding of the luminal domain of the neurotensin receptor-3/sortilin in the HT29 cell line."
Navarro V., Vincent J.-P., Mazella J.
Biochem. Biophys. Res. Commun. 298:760-764(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF THE EXTRACELLULAR DOMAIN.
[14]"Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization."
Maeda S., Nobukuni T., Shimo-Onoda K., Hayashi K., Yone K., Komiya S., Inoue I.
J. Cell. Physiol. 193:73-79(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[15]"Structural basis for recognition of acidic-cluster dileucine sequence by GGA1."
Shiba T., Takatsu H., Nogi T., Matsugaki N., Kawasaki M., Igarashi N., Suzuki M., Kato R., Earnest T., Nakayama K., Wakatsuki S.
Nature 415:937-941(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GGA1.
[16]"The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin."
Lefrancois S., Zeng J., Hassan A.J., Canuel M., Morales C.R.
EMBO J. 22:6430-6437(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GM2A AND PSAP, SUBCELLULAR LOCATION.
[17]Erratum
Lefrancois S., Zeng J., Hassan A.J., Canuel M., Morales C.R.
EMBO J. 23:1680-1680(2004)
[18]"Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia."
Martin S., Vincent J.-P., Mazella J.
J. Neurosci. 23:1198-1205(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[19]"Internalization and trafficking of neurotensin via NTS3 receptors in HT29 cells."
Morinville A., Martin S., Lavallee M., Vincent J.-P., Beaudet A., Mazella J.
Int. J. Biochem. Cell Biol. 36:2153-2168(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[20]"Functional organization of the sortilin Vps10p domain."
Westergaard U.B., Soerensen E.S., Hermey G., Nielsen M.S., Nykjaer A., Kirkegaard K., Jacobsen C., Gliemann J., Madsen P., Petersen C.M.
J. Biol. Chem. 279:50221-50229(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRPAP1 AND NGFB, SUBCELLULAR LOCATION, DISULFIDE BONDS, IDENTIFICATION BY MASS SPECTROMETRY.
[21]"Sortilin is essential for proNGF-induced neuronal cell death."
Nykjaer A., Lee R., Teng K.K., Jansen P., Madsen P., Nielsen M.S., Jacobsen C., Kliemannel M., Schwarz E., Willnow T.E., Hempstead B.L., Petersen C.M.
Nature 427:843-848(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NGFB AND NGFR.
[22]"ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin."
Teng H.K., Teng K.K., Lee R., Wright S., Tevar S., Almeida R.D., Kermani P., Torkin R., Chen Z.-Y., Lee F.S., Kraemer R.T., Nykjaer A., Hempstead B.L.
J. Neurosci. 25:5455-5463(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[23]"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: FUNCTION, INTERACTION WITH BDNF.
[24]"Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
Lewandrowski U., Moebius J., Walter U., Sickmann A.
Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-162.
Tissue: Platelet.
[25]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-825, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[26]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-162 AND ASN-163.
Tissue: Leukemic T-cell.
[28]"Altered expression of neurotensin receptors is associated with the differentiation state of prostate cancer."
Swift S.L., Burns J.E., Maitland N.J.
Cancer Res. 70:347-356(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[29]"Biological, clinical and population relevance of 95 loci for blood lipids."
Teslovich T.M., Musunuru K., Smith A.V., Edmondson A.C., Stylianou I.M., Koseki M., Pirruccello J.P., Ripatti S., Chasman D.I., Willer C.J., Johansen C.T., Fouchier S.W., Isaacs A., Peloso G.M., Barbalic M., Ricketts S.L., Bis J.C., Aulchenko Y.S. expand/collapse author list , Thorleifsson G., Feitosa M.F., Chambers J., Orho-Melander M., Melander O., Johnson T., Li X., Guo X., Li M., Shin Cho Y., Jin Go M., Jin Kim Y., Lee J.Y., Park T., Kim K., Sim X., Twee-Hee Ong R., Croteau-Chonka D.C., Lange L.A., Smith J.D., Song K., Hua Zhao J., Yuan X., Luan J., Lamina C., Ziegler A., Zhang W., Zee R.Y., Wright A.F., Witteman J.C., Wilson J.F., Willemsen G., Wichmann H.E., Whitfield J.B., Waterworth D.M., Wareham N.J., Waeber G., Vollenweider P., Voight B.F., Vitart V., Uitterlinden A.G., Uda M., Tuomilehto J., Thompson J.R., Tanaka T., Surakka I., Stringham H.M., Spector T.D., Soranzo N., Smit J.H., Sinisalo J., Silander K., Sijbrands E.J., Scuteri A., Scott J., Schlessinger D., Sanna S., Salomaa V., Saharinen J., Sabatti C., Ruokonen A., Rudan I., Rose L.M., Roberts R., Rieder M., Psaty B.M., Pramstaller P.P., Pichler I., Perola M., Penninx B.W., Pedersen N.L., Pattaro C., Parker A.N., Pare G., Oostra B.A., O'Donnell C.J., Nieminen M.S., Nickerson D.A., Montgomery G.W., Meitinger T., McPherson R., McCarthy M.I., McArdle W., Masson D., Martin N.G., Marroni F., Mangino M., Magnusson P.K., Lucas G., Luben R., Loos R.J., Lokki M.L., Lettre G., Langenberg C., Launer L.J., Lakatta E.G., Laaksonen R., Kyvik K.O., Kronenberg F., Konig I.R., Khaw K.T., Kaprio J., Kaplan L.M., Johansson A., Jarvelin M.R., Janssens A.C., Ingelsson E., Igl W., Kees Hovingh G., Hottenga J.J., Hofman A., Hicks A.A., Hengstenberg C., Heid I.M., Hayward C., Havulinna A.S., Hastie N.D., Harris T.B., Haritunians T., Hall A.S., Gyllensten U., Guiducci C., Groop L.C., Gonzalez E., Gieger C., Freimer N.B., Ferrucci L., Erdmann J., Elliott P., Ejebe K.G., Doring A., Dominiczak A.F., Demissie S., Deloukas P., de Geus E.J., de Faire U., Crawford G., Collins F.S., Chen Y.D., Caulfield M.J., Campbell H., Burtt N.P., Bonnycastle L.L., Boomsma D.I., Boekholdt S.M., Bergman R.N., Barroso I., Bandinelli S., Ballantyne C.M., Assimes T.L., Quertermous T., Altshuler D., Seielstad M., Wong T.Y., Tai E.S., Feranil A.B., Kuzawa C.W., Adair L.S., Taylor H.A. Jr., Borecki I.B., Gabriel S.B., Wilson J.G., Holm H., Thorsteinsdottir U., Gudnason V., Krauss R.M., Mohlke K.L., Ordovas J.M., Munroe P.B., Kooner J.S., Tall A.R., Hegele R.A., Kastelein J.J., Schadt E.E., Rotter J.I., Boerwinkle E., Strachan D.P., Mooser V., Stefansson K., Reilly M.P., Samani N.J., Schunkert H., Cupples L.A., Sandhu M.S., Ridker P.M., Rader D.J., van Duijn C.M., Peltonen L., Abecasis G.R., Boehnke M., Kathiresan S.
Nature 466:707-713(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN LDLCQ6.
[30]"From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus."
Musunuru K., Strong A., Frank-Kamenetsky M., Lee N.E., Ahfeldt T., Sachs K.V., Li X., Li H., Kuperwasser N., Ruda V.M., Pirruccello J.P., Muchmore B., Prokunina-Olsson L., Hall J.L., Schadt E.E., Morales C.R., Lund-Katz S., Phillips M.C. expand/collapse author list , Wong J., Cantley W., Racie T., Ejebe K.G., Orho-Melander M., Melander O., Koteliansky V., Fitzgerald K., Krauss R.M., Cowan C.A., Kathiresan S., Rader D.J.
Nature 466:714-719(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO MYOCARDIAL INFARCTION.
[31]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[32]"Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling."
Vaegter C.B., Jansen P., Fjorback A.W., Glerup S., Skeldal S., Kjolby M., Richner M., Erdmann B., Nyengaard J.R., Tessarollo L., Lewin G.R., Willnow T.E., Chao M.V., Nykjaer A.
Nat. Neurosci. 14:54-61(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NTRK1.
[33]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-819 AND SER-825, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]"Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain."
Quistgaard E.M., Madsen P., Groftehauge M.K., Nissen P., Petersen C.M., Thirup S.S.
Nat. Struct. Mol. Biol. 16:96-98(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 78-756 IN COMPLEX WITH NTS, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-406 AND ASN-582.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X98248 mRNA. Translation: CAA66904.2.
FJ525881 Genomic DNA. Translation: ACN81319.1.
AK301548 mRNA. Translation: BAG63045.1.
AL390252 Genomic DNA. Translation: CAI13180.1.
BC023542 mRNA. Translation: AAH23542.1.
CCDSCCDS55618.1. [Q99523-2]
CCDS798.1. [Q99523-1]
RefSeqNP_001192157.1. NM_001205228.1. [Q99523-2]
NP_002950.3. NM_002959.5. [Q99523-1]
UniGeneHs.485195.
Hs.703487.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3F6KX-ray2.00A78-756[»]
3G2UX-ray2.30C/D819-831[»]
3G2VX-ray2.10C/D819-831[»]
4MSLX-ray2.70A78-756[»]
4N7EX-ray2.70A78-756[»]
ProteinModelPortalQ99523.
SMRQ99523. Positions 88-749.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112180. 10 interactions.
DIPDIP-41798N.
IntActQ99523. 6 interactions.
MINTMINT-197682.
STRING9606.ENSP00000256637.

Chemistry

BindingDBQ99523.
ChEMBLCHEMBL3091.

PTM databases

PhosphoSiteQ99523.

Polymorphism databases

DMDM84028263.

Proteomic databases

MaxQBQ99523.
PaxDbQ99523.
PRIDEQ99523.

Protocols and materials databases

DNASU6272.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256637; ENSP00000256637; ENSG00000134243. [Q99523-1]
ENST00000538502; ENSP00000438597; ENSG00000134243. [Q99523-2]
GeneID6272.
KEGGhsa:6272.
UCSCuc001dxm.2. human. [Q99523-1]
uc010ovi.2. human.

Organism-specific databases

CTD6272.
GeneCardsGC01M109852.
HGNCHGNC:11186. SORT1.
HPACAB011498.
HPA006889.
MIM602458. gene.
613589. phenotype.
neXtProtNX_Q99523.
PharmGKBPA36023.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG281049.
HOGENOMHOG000231347.
HOVERGENHBG080235.
InParanoidQ99523.
KOK12388.
OMALTQMMYS.
OrthoDBEOG7RBZ7S.
PhylomeDBQ99523.
TreeFamTF324918.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.

Gene expression databases

BgeeQ99523.
CleanExHS_SORT1.
GenevestigatorQ99523.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
InterProIPR006581. VPS10.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
SMARTSM00602. VPS10. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSORT1. human.
EvolutionaryTraceQ99523.
GeneWikiSortilin_1.
GenomeRNAi6272.
NextBio24343.
PROQ99523.
SOURCESearch...

Entry information

Entry nameSORT_HUMAN
AccessionPrimary (citable) accession number: Q99523
Secondary accession number(s): B4DWI3, C0JYZ0, Q8IZ49
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 20, 2005
Last modified: July 9, 2014
This is version 141 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM