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Q99523

- SORT_HUMAN

UniProt

Q99523 - SORT_HUMAN

Protein

Sortilin

Gene

SORT1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 3 (20 Dec 2005)
      Previous versions | rss
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    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.10 Publications

    GO - Molecular functioni

    1. enzyme binding Source: BHF-UCL
    2. nerve growth factor binding Source: BHF-UCL
    3. nerve growth factor receptor activity Source: BHF-UCL
    4. neurotensin receptor activity, non-G-protein coupled Source: BHF-UCL
    5. protein binding Source: IntAct

    GO - Biological processi

    1. endocytosis Source: BHF-UCL
    2. endosome to lysosome transport Source: BHF-UCL
    3. endosome transport via multivesicular body sorting pathway Source: BHF-UCL
    4. extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
    5. glucose import Source: BHF-UCL
    6. Golgi to endosome transport Source: BHF-UCL
    7. G-protein coupled receptor signaling pathway Source: BHF-UCL
    8. multicellular organismal development Source: UniProtKB-KW
    9. myotube differentiation Source: BHF-UCL
    10. negative regulation of lipoprotein lipase activity Source: BHF-UCL
    11. nerve growth factor signaling pathway Source: GOC
    12. neuropeptide signaling pathway Source: BHF-UCL
    13. neurotrophin TRK receptor signaling pathway Source: BHF-UCL
    14. ossification Source: UniProtKB-KW
    15. plasma membrane to endosome transport Source: BHF-UCL
    16. regulation of gene expression Source: BHF-UCL
    17. response to insulin Source: BHF-UCL
    18. vesicle organization Source: BHF-UCL

    Keywords - Molecular functioni

    Developmental protein, Receptor

    Keywords - Biological processi

    Differentiation, Endocytosis, Osteogenesis, Transport

    Enzyme and pathway databases

    ReactomeiREACT_19400. Golgi Associated Vesicle Biogenesis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sortilin
    Alternative name(s):
    100 kDa NT receptor
    Glycoprotein 95
    Short name:
    Gp95
    Neurotensin receptor 3
    Short name:
    NT3
    Short name:
    NTR3
    Gene namesi
    Name:SORT1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:11186. SORT1.

    Subcellular locationi

    Membrane; Single-pass type I membrane protein. 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. Nucleus membrane Curated; Single-pass type I membrane protein Curated. Cell membrane; Single-pass type I membrane protein; Extracellular side. Lysosome membrane Curated; Single-pass type I membrane protein Curated
    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.

    GO - Cellular componenti

    1. cell surface Source: BHF-UCL
    2. clathrin-coated vesicle Source: BHF-UCL
    3. coated pit Source: BHF-UCL
    4. cytoplasmic membrane-bounded vesicle Source: BHF-UCL
    5. early endosome Source: BHF-UCL
    6. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    7. endosome membrane Source: UniProtKB-SubCell
    8. Golgi apparatus Source: BHF-UCL
    9. Golgi cisterna membrane Source: UniProtKB-SubCell
    10. integral component of membrane Source: BHF-UCL
    11. lysosomal membrane Source: UniProtKB-SubCell
    12. nuclear membrane Source: UniProtKB-SubCell
    13. perinuclear region of cytoplasm Source: BHF-UCL
    14. plasma membrane Source: BHF-UCL
    15. trans-Golgi network transport vesicle Source: Ensembl

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Involvement in diseasei

    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.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi74 – 774RWRR → GWRA: Abrogates propeptide cleavage. 1 Publication
    Mutagenesisi76 – 772RR → GG: Abrogates propeptide cleavage. 1 Publication
    Mutagenesisi792 – 7921Y → A: Reduces endocytosis and Golgi to endosome sorting; when associated with A-795. 2 Publications
    Mutagenesisi795 – 7951L → A: Reduces endocytosis and Golgi to endosome sorting; when associated with A-792. 2 Publications
    Mutagenesisi823 – 8242DD → NN: Reduces interaction with GGA1. 1 Publication
    Mutagenesisi825 – 8251S → A: Reduces interaction with GGA1. 2 Publications
    Mutagenesisi826 – 8283DED → NQN: Abrogates interaction with GGA1 and impairs localization to the Golgi. 1 Publication
    Mutagenesisi829 – 8302LL → AA: Abrogates interaction with GGA1 and impairs localization to the Golgi. 1 Publication
    Mutagenesisi829 – 8302Missing: Abrogates interaction with GGA2. Reduces endocytosis and Golgi to endosome sorting; when associated with A-792 and A-795. 1 Publication

    Organism-specific databases

    MIMi613589. phenotype.
    PharmGKBiPA36023.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3333Sequence AnalysisAdd
    BLAST
    Propeptidei34 – 7744Removed in mature form1 PublicationPRO_0000033162Add
    BLAST
    Chaini78 – 831754SortilinPRO_0000033163Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi86 ↔ 556
    Glycosylationi98 – 981N-linked (GlcNAc...)Curated
    Glycosylationi162 – 1621N-linked (GlcNAc...)2 Publications
    Glycosylationi163 – 1631N-linked (GlcNAc...); atypical1 Publication
    Disulfide bondi257 ↔ 277
    Glycosylationi274 – 2741N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi406 – 4061N-linked (GlcNAc...)1 Publication
    Disulfide bondi448 ↔ 458
    Glycosylationi582 – 5821N-linked (GlcNAc...)1 Publication
    Disulfide bondi612 ↔ 651
    Disulfide bondi634 ↔ 666
    Disulfide bondi668 ↔ 723
    Disulfide bondi675 ↔ 688
    Glycosylationi684 – 6841N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi702 ↔ 740
    Modified residuei819 – 8191Phosphoserine1 Publication
    Modified residuei825 – 8251Phosphoserine2 Publications

    Post-translational modificationi

    The N-terminal propeptide is cleaved by furin and possibly other homologous proteases.2 Publications

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiQ99523.
    PaxDbiQ99523.
    PRIDEiQ99523.

    PTM databases

    PhosphoSiteiQ99523.

    Expressioni

    Tissue specificityi

    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.2 Publications

    Inductioni

    During osteoblast differentiation.1 Publication

    Gene expression databases

    BgeeiQ99523.
    CleanExiHS_SORT1.
    GenevestigatoriQ99523.

    Organism-specific databases

    HPAiCAB011498.
    HPA006889.

    Interactioni

    Subunit structurei

    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.By similarity12 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GGA1Q9UJY52EBI-1057058,EBI-447141
    LPLP111516EBI-1057058,EBI-8794090From a different organism.

    Protein-protein interaction databases

    BioGridi112180. 10 interactions.
    DIPiDIP-41798N.
    IntActiQ99523. 7 interactions.
    MINTiMINT-197682.
    STRINGi9606.ENSP00000256637.

    Structurei

    Secondary structure

    1
    831
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi92 – 976
    Beta strandi100 – 1067
    Beta strandi110 – 1167
    Beta strandi118 – 1214
    Beta strandi124 – 1307
    Beta strandi141 – 1499
    Helixi158 – 1614
    Helixi168 – 1703
    Beta strandi172 – 1743
    Beta strandi182 – 1865
    Beta strandi196 – 2027
    Beta strandi208 – 2114
    Beta strandi216 – 2183
    Beta strandi221 – 2233
    Beta strandi226 – 2349
    Beta strandi239 – 2446
    Beta strandi247 – 26115
    Beta strandi267 – 2715
    Beta strandi273 – 2753
    Turni277 – 2826
    Beta strandi283 – 2919
    Beta strandi297 – 30913
    Beta strandi312 – 3187
    Beta strandi320 – 3234
    Beta strandi325 – 3328
    Beta strandi351 – 3566
    Beta strandi361 – 3666
    Turni368 – 3703
    Beta strandi372 – 3798
    Beta strandi385 – 39511
    Turni397 – 3993
    Beta strandi414 – 4196
    Beta strandi421 – 4233
    Beta strandi425 – 4328
    Beta strandi438 – 4414
    Beta strandi453 – 4564
    Beta strandi459 – 4624
    Helixi465 – 4695
    Beta strandi488 – 49710
    Beta strandi504 – 5107
    Beta strandi516 – 5216
    Beta strandi523 – 5286
    Helixi529 – 5313
    Beta strandi533 – 5386
    Beta strandi546 – 5527
    Beta strandi558 – 5614
    Beta strandi567 – 5737
    Beta strandi581 – 59010
    Beta strandi595 – 6039
    Helixi604 – 6063
    Helixi614 – 6163
    Beta strandi617 – 6215
    Turni630 – 6334
    Beta strandi638 – 6458
    Beta strandi661 – 6655
    Helixi670 – 6723
    Beta strandi673 – 6753
    Beta strandi683 – 6853
    Helixi696 – 7049
    Helixi707 – 7104
    Beta strandi714 – 7174
    Beta strandi724 – 7263
    Beta strandi734 – 7363
    Helixi737 – 7404
    Helixi741 – 7433

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ99523.
    SMRiQ99523. Positions 88-749.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ99523.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini78 – 755678ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini779 – 83153CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei756 – 77823HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati145 – 15612BNR 1Add
    BLAST
    Repeati198 – 20912BNR 2Add
    BLAST
    Repeati240 – 25112BNR 3Add
    BLAST
    Repeati287 – 29812BNR 4Add
    BLAST
    Repeati328 – 33912BNR 5Add
    BLAST
    Repeati377 – 38812BNR 6Add
    BLAST
    Repeati428 – 43912BNR 7Add
    BLAST
    Repeati506 – 51712BNR 8Add
    BLAST
    Repeati548 – 55912BNR 9Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni50 – 6112Intrachain binding of the propeptide and the extracellular domainAdd
    BLAST
    Regioni612 – 756145Interactions with LRPAP1 and NGFBAdd
    BLAST
    Regioni779 – 83153Golgi to endosome transport and interactions with GGA1 and GGA2Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi787 – 7926Endocytosis signalCurated

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

    Sequence similaritiesi

    Contains 9 BNR repeats.Curated

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG281049.
    HOGENOMiHOG000231347.
    HOVERGENiHBG080235.
    InParanoidiQ99523.
    KOiK12388.
    OMAiLTQMMYS.
    OrthoDBiEOG7RBZ7S.
    PhylomeDBiQ99523.
    TreeFamiTF324918.

    Family and domain databases

    Gene3Di2.130.10.10. 1 hit.
    InterProiIPR006581. VPS10.
    IPR015943. WD40/YVTN_repeat-like_dom.
    [Graphical view]
    SMARTiSM00602. VPS10. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q99523-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MERPWGAADG LSRWPHGLGL LLLLQLLPPS TLSQDRLDAP PPPAAPLPRW    50
    SGPIGVSWGL RAAAAGGAFP RGGRWRRSAP GEDEECGRVR DFVAKLANNT 100
    HQHVFDDLRG SVSLSWVGDS TGVILVLTTF HVPLVIMTFG QSKLYRSEDY 150
    GKNFKDITDL INNTFIRTEF GMAIGPENSG KVVLTAEVSG GSRGGRIFRS 200
    SDFAKNFVQT DLPFHPLTQM MYSPQNSDYL LALSTENGLW VSKNFGGKWE 250
    EIHKAVCLAK WGSDNTIFFT TYANGSCKAD LGALELWRTS DLGKSFKTIG 300
    VKIYSFGLGG RFLFASVMAD KDTTRRIHVS TDQGDTWSMA QLPSVGQEQF 350
    YSILAANDDM VFMHVDEPGD TGFGTIFTSD DRGIVYSKSL DRHLYTTTGG 400
    ETDFTNVTSL RGVYITSVLS EDNSIQTMIT FDQGGRWTHL RKPENSECDA 450
    TAKNKNECSL HIHASYSISQ KLNVPMAPLS EPNAVGIVIA HGSVGDAISV 500
    MVPDVYISDD GGYSWTKMLE GPHYYTILDS GGIIVAIEHS SRPINVIKFS 550
    TDEGQCWQTY TFTRDPIYFT GLASEPGARS MNISIWGFTE SFLTSQWVSY 600
    TIDFKDILER NCEEKDYTIW LAHSTDPEDY EDGCILGYKE QFLRLRKSSV 650
    CQNGRDYVVT KQPSICLCSL EDFLCDFGYY RPENDSKCVE QPELKGHDLE 700
    FCLYGREEHL TTNGYRKIPG DKCQGGVNPV REVKDLKKKC TSNFLSPEKQ 750
    NSKSNSVPII LAIVGLMLVT VVAGVLIVKK YVCGGRFLVH RYSVLQQHAE 800
    ANGVDGVDAL DTASHTNKSG YHDDSDEDLL E 831
    Length:831
    Mass (Da):92,068
    Last modified:December 20, 2005 - v3
    Checksum:i91F96A3035A4B43A
    GO
    Isoform 2 (identifier: Q99523-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-136: Missing.
         278-279: KA → T

    Note: No experimental confirmation available.

    Show »
    Length:694
    Mass (Da):77,375
    Checksum:i4F80EC724C360750
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti650 – 6501V → M in CAA66904. (PubMed:9013611)Curated

    Polymorphismi

    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) [MIMi:613589].

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti358 – 3581D → Y.
    Corresponds to variant rs2228605 [ dbSNP | Ensembl ].
    VAR_053681

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 136136Missing in isoform 2. 1 PublicationVSP_046239Add
    BLAST
    Alternative sequencei278 – 2792KA → T in isoform 2. 1 PublicationVSP_046240

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS55618.1. [Q99523-2]
    CCDS798.1. [Q99523-1]
    RefSeqiNP_001192157.1. NM_001205228.1. [Q99523-2]
    NP_002950.3. NM_002959.5. [Q99523-1]
    UniGeneiHs.485195.
    Hs.703487.

    Genome annotation databases

    EnsembliENST00000256637; ENSP00000256637; ENSG00000134243. [Q99523-1]
    ENST00000538502; ENSP00000438597; ENSG00000134243. [Q99523-2]
    GeneIDi6272.
    KEGGihsa:6272.
    UCSCiuc001dxm.2. human. [Q99523-1]
    uc010ovi.2. human.

    Polymorphism databases

    DMDMi84028263.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS55618.1. [Q99523-2 ]
    CCDS798.1. [Q99523-1 ]
    RefSeqi NP_001192157.1. NM_001205228.1. [Q99523-2 ]
    NP_002950.3. NM_002959.5. [Q99523-1 ]
    UniGenei Hs.485195.
    Hs.703487.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3F6K X-ray 2.00 A 78-756 [» ]
    3G2U X-ray 2.30 C/D 819-831 [» ]
    3G2V X-ray 2.10 C/D 819-831 [» ]
    4MSL X-ray 2.70 A 78-756 [» ]
    4N7E X-ray 2.70 A 78-756 [» ]
    ProteinModelPortali Q99523.
    SMRi Q99523. Positions 88-749.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112180. 10 interactions.
    DIPi DIP-41798N.
    IntActi Q99523. 7 interactions.
    MINTi MINT-197682.
    STRINGi 9606.ENSP00000256637.

    Chemistry

    BindingDBi Q99523.
    ChEMBLi CHEMBL3091.

    PTM databases

    PhosphoSitei Q99523.

    Polymorphism databases

    DMDMi 84028263.

    Proteomic databases

    MaxQBi Q99523.
    PaxDbi Q99523.
    PRIDEi Q99523.

    Protocols and materials databases

    DNASUi 6272.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000256637 ; ENSP00000256637 ; ENSG00000134243 . [Q99523-1 ]
    ENST00000538502 ; ENSP00000438597 ; ENSG00000134243 . [Q99523-2 ]
    GeneIDi 6272.
    KEGGi hsa:6272.
    UCSCi uc001dxm.2. human. [Q99523-1 ]
    uc010ovi.2. human.

    Organism-specific databases

    CTDi 6272.
    GeneCardsi GC01M109852.
    HGNCi HGNC:11186. SORT1.
    HPAi CAB011498.
    HPA006889.
    MIMi 602458. gene.
    613589. phenotype.
    neXtProti NX_Q99523.
    PharmGKBi PA36023.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG281049.
    HOGENOMi HOG000231347.
    HOVERGENi HBG080235.
    InParanoidi Q99523.
    KOi K12388.
    OMAi LTQMMYS.
    OrthoDBi EOG7RBZ7S.
    PhylomeDBi Q99523.
    TreeFami TF324918.

    Enzyme and pathway databases

    Reactomei REACT_19400. Golgi Associated Vesicle Biogenesis.

    Miscellaneous databases

    ChiTaRSi SORT1. human.
    EvolutionaryTracei Q99523.
    GeneWikii Sortilin_1.
    GenomeRNAii 6272.
    NextBioi 24343.
    PROi Q99523.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q99523.
    CleanExi HS_SORT1.
    Genevestigatori Q99523.

    Family and domain databases

    Gene3Di 2.130.10.10. 1 hit.
    InterProi IPR006581. VPS10.
    IPR015943. WD40/YVTN_repeat-like_dom.
    [Graphical view ]
    SMARTi SM00602. VPS10. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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.
      , 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. Cited for: INTERACTION WITH LRPAP1 AND NGFB, SUBCELLULAR LOCATION, DISULFIDE BONDS, IDENTIFICATION BY MASS SPECTROMETRY.
    21. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-825, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Platelet.
    26. 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.
      , 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. Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO MYOCARDIAL INFARCTION.
    31. 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.

    Entry informationi

    Entry nameiSORT_HUMAN
    AccessioniPrimary (citable) accession number: Q99523
    Secondary accession number(s): B4DWI3, C0JYZ0, Q8IZ49
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: December 20, 2005
    Last modified: October 1, 2014
    This is version 143 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3