Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q92673

- SORL_HUMAN

UniProt

Q92673 - SORL_HUMAN

Protein

Sortilin-related receptor

Gene

SORL1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Likely to be a multifunctional endocytic receptor, that may be implicated in the uptake of lipoproteins and of proteases. Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. Binds the receptor-associated protein (RAP). Could play a role in cell-cell interaction. Involved in APP trafficking to and from the Golgi apparatus. It probably acts as a sorting receptor that protects APP from trafficking to late endosome and from processing into amyloid beta, thereby reducing the burden of amyloidogenic peptide formation. Involved in the regulation of smooth muscle cells migration, probably through PLAUR binding and decreased internalization.2 Publications

    GO - Molecular functioni

    1. ADP-ribosylation factor binding Source: Alzheimers_University_of_Toronto
    2. beta-amyloid binding Source: Alzheimers_University_of_Toronto
    3. low-density lipoprotein particle binding Source: BHF-UCL
    4. protein binding Source: UniProtKB
    5. transmembrane signaling receptor activity Source: ProtInc

    GO - Biological processi

    1. cell death Source: UniProtKB-KW
    2. cell migration Source: Ensembl
    3. cell proliferation Source: Ensembl
    4. cholesterol metabolic process Source: UniProtKB-KW
    5. lipid transport Source: UniProtKB-KW
    6. negative regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: Alzheimers_University_of_Toronto
    7. negative regulation of beta-amyloid formation Source: Alzheimers_University_of_Toronto
    8. negative regulation of MAP kinase activity Source: Alzheimers_University_of_Toronto
    9. negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic process Source: Alzheimers_University_of_Toronto
    10. negative regulation of neurofibrillary tangle assembly Source: Alzheimers_University_of_Toronto
    11. negative regulation of neurogenesis Source: Alzheimers_University_of_Toronto
    12. negative regulation of neuron death Source: Alzheimers_University_of_Toronto
    13. negative regulation of protein binding Source: Alzheimers_University_of_Toronto
    14. negative regulation of protein oligomerization Source: Alzheimers_University_of_Toronto
    15. negative regulation of tau-protein kinase activity Source: Alzheimers_University_of_Toronto
    16. positive regulation of choline O-acetyltransferase activity Source: Alzheimers_University_of_Toronto
    17. positive regulation of early endosome to recycling endosome transport Source: Alzheimers_University_of_Toronto
    18. positive regulation of endocytic recycling Source: Alzheimers_University_of_Toronto
    19. positive regulation of ER to Golgi vesicle-mediated transport Source: Alzheimers_University_of_Toronto
    20. positive regulation of protein catabolic process Source: Alzheimers_University_of_Toronto
    21. positive regulation of protein exit from endoplasmic reticulum Source: Alzheimers_University_of_Toronto
    22. positive regulation of protein localization to early endosome Source: Alzheimers_University_of_Toronto
    23. post-Golgi vesicle-mediated transport Source: Alzheimers_University_of_Toronto
    24. protein maturation Source: Alzheimers_University_of_Toronto
    25. protein retention in Golgi apparatus Source: Alzheimers_University_of_Toronto
    26. protein targeting Source: UniProtKB
    27. protein targeting to Golgi Source: Alzheimers_University_of_Toronto
    28. protein targeting to lysosome Source: Alzheimers_University_of_Toronto
    29. receptor-mediated endocytosis Source: ProtInc
    30. regulation of smooth muscle cell migration Source: UniProtKB
    31. signal transduction Source: GOC

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Cholesterol metabolism, Endocytosis, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sortilin-related receptor
    Alternative name(s):
    Low-density lipoprotein receptor relative with 11 ligand-binding repeats
    Short name:
    LDLR relative with 11 ligand-binding repeats
    Short name:
    LR11
    SorLA-1
    Sorting protein-related receptor containing LDLR class A repeats
    Short name:
    SorLA
    Gene namesi
    Name:SORL1
    Synonyms:C11orf32
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:11185. SORL1.

    Subcellular locationi

    GO - Cellular componenti

    1. early endosome Source: Alzheimers_University_of_Toronto
    2. endoplasmic reticulum Source: Alzheimers_University_of_Toronto
    3. endosome Source: UniProtKB
    4. extracellular space Source: UniProtKB
    5. extracellular vesicular exosome Source: UniProt
    6. Golgi apparatus Source: UniProtKB
    7. Golgi cisterna Source: Alzheimers_University_of_Toronto
    8. integral component of plasma membrane Source: ProtInc
    9. low-density lipoprotein particle Source: UniProtKB-KW
    10. membrane Source: UniProtKB
    11. multivesicular body Source: Ensembl
    12. neuronal cell body Source: Ensembl
    13. nuclear envelope lumen Source: Alzheimers_University_of_Toronto
    14. recycling endosome Source: Alzheimers_University_of_Toronto
    15. trans-Golgi network Source: Alzheimers_University_of_Toronto

    Keywords - Cellular componenti

    Endosome, Golgi apparatus, LDL, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Alzheimer disease (AD) [MIM:104300]: Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.3 Publications
    Note: The gene represented in this entry is involved in disease pathogenesis.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti141 – 1411Y → C in AD; unknown pathological significance. 1 Publication
    VAR_070012
    Natural varianti511 – 5111G → R in AD; unknown pathological significance. 1 Publication
    VAR_070013
    Natural varianti924 – 9241N → S in AD; unknown pathological significance. 1 Publication
    Corresponds to variant rs377498269 [ dbSNP | Ensembl ].
    VAR_070014
    Natural varianti1358 – 13581N → S in AD; unknown pathological significance. 1 Publication
    VAR_070015
    Natural varianti1681 – 16811G → D in AD; unknown pathological significance. 1 Publication
    VAR_070016

    Keywords - Diseasei

    Alzheimer disease, Amyloidosis, Disease mutation, Neurodegeneration

    Organism-specific databases

    MIMi104300. phenotype.
    Orphaneti1020. Early-onset autosomal dominant Alzheimer disease.
    PharmGKBiPA36022.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2828Sequence AnalysisAdd
    BLAST
    Propeptidei29 – 8153Removed in mature form1 PublicationPRO_0000033164Add
    BLAST
    Chaini82 – 22142133Sortilin-related receptorPRO_0000033165Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi99 – 991N-linked (GlcNAc...)1 Publication
    Modified residuei114 – 1141Phosphoserine1 Publication
    Glycosylationi158 – 1581N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi368 – 3681N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi430 – 4301N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi616 – 6161N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi674 – 6741N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi818 – 8181N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi871 – 8711N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1035 – 10351N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1068 – 10681N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1078 ↔ 1090PROSITE-ProRule annotation
    Disulfide bondi1085 ↔ 1103PROSITE-ProRule annotation
    Disulfide bondi1097 ↔ 1112PROSITE-ProRule annotation
    Disulfide bondi1117 ↔ 1131PROSITE-ProRule annotation
    Disulfide bondi1125 ↔ 1144PROSITE-ProRule annotation
    Disulfide bondi1138 ↔ 1153PROSITE-ProRule annotation
    Disulfide bondi1158 ↔ 1170PROSITE-ProRule annotation
    Glycosylationi1164 – 11641N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1165 ↔ 1183PROSITE-ProRule annotation
    Disulfide bondi1177 ↔ 1192PROSITE-ProRule annotation
    Glycosylationi1191 – 11911N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1199 ↔ 1211PROSITE-ProRule annotation
    Disulfide bondi1206 ↔ 1224PROSITE-ProRule annotation
    Disulfide bondi1218 ↔ 1235PROSITE-ProRule annotation
    Disulfide bondi1239 ↔ 1249PROSITE-ProRule annotation
    Disulfide bondi1244 ↔ 1262PROSITE-ProRule annotation
    Glycosylationi1246 – 12461N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1256 ↔ 1271PROSITE-ProRule annotation
    Disulfide bondi1275 ↔ 1289PROSITE-ProRule annotation
    Disulfide bondi1283 ↔ 1302PROSITE-ProRule annotation
    Disulfide bondi1296 ↔ 1315PROSITE-ProRule annotation
    Disulfide bondi1325 ↔ 1337PROSITE-ProRule annotation
    Disulfide bondi1332 ↔ 1350PROSITE-ProRule annotation
    Disulfide bondi1344 ↔ 1359PROSITE-ProRule annotation
    Glycosylationi1367 – 13671N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1368 ↔ 1381PROSITE-ProRule annotation
    Disulfide bondi1376 ↔ 1394PROSITE-ProRule annotation
    Disulfide bondi1388 ↔ 1403PROSITE-ProRule annotation
    Disulfide bondi1419 ↔ 1431PROSITE-ProRule annotation
    Disulfide bondi1426 ↔ 1444PROSITE-ProRule annotation
    Disulfide bondi1438 ↔ 1453PROSITE-ProRule annotation
    Glycosylationi1458 – 14581N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1471 ↔ 1484PROSITE-ProRule annotation
    Disulfide bondi1478 ↔ 1497PROSITE-ProRule annotation
    Disulfide bondi1491 ↔ 1506PROSITE-ProRule annotation
    Disulfide bondi1514 ↔ 1527PROSITE-ProRule annotation
    Disulfide bondi1521 ↔ 1540PROSITE-ProRule annotation
    Disulfide bondi1534 ↔ 1549PROSITE-ProRule annotation
    Glycosylationi1608 – 16081N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1706 – 17061N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1733 – 17331N-linked (GlcNAc...)1 Publication
    Glycosylationi1809 – 18091N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1854 – 18541N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1894 – 18941N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1986 – 19861N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi2010 – 20101N-linked (GlcNAc...)1 Publication
    Glycosylationi2054 – 20541N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi2069 – 20691N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi2076 – 20761N-linked (GlcNAc...)1 Publication
    Glycosylationi2092 – 20921N-linked (GlcNAc...)1 Publication
    Modified residuei2206 – 22061Phosphoserine; by ROCK21 Publication

    Post-translational modificationi

    The propeptide removed in the N-terminus may be cleaved by furin or homologous proteases.

    Keywords - PTMi

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

    Proteomic databases

    MaxQBiQ92673.
    PaxDbiQ92673.
    PRIDEiQ92673.

    PTM databases

    PhosphoSiteiQ92673.

    Expressioni

    Tissue specificityi

    Expressed mainly in brain, where it is most abundant in the cerebellum, cerebral cortex and the occipital pole; low expression in the putamen and the thalamus. Expression is significantly reduced in the frontal cortex of patients suffering from Alzheimer disease. According to PubMed:9157966, found in spinal cord, testis, liver, kidney and pancreas with detectable levels in placenta, lung and heart. According to PubMed:8940146, expressed in the prostate, ovary, thyroid and spleen, but not found in kidney, liver, lung, skeletal muscle, bone marrow and adrenals.1 Publication

    Gene expression databases

    ArrayExpressiQ92673.
    BgeeiQ92673.
    CleanExiHS_SORL1.
    GenevestigatoriQ92673.

    Organism-specific databases

    HPAiCAB011500.
    HPA031321.

    Interactioni

    Subunit structurei

    Interacts with GGA1 and ROCK2. Interacts with PLAUR. Interacts with APP.4 Publications

    Protein-protein interaction databases

    BioGridi112536. 11 interactions.
    IntActiQ92673. 10 interactions.
    MINTiMINT-231252.
    STRINGi9606.ENSP00000260197.

    Structurei

    Secondary structure

    1
    2214
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi1655 – 16606
    Beta strandi1669 – 16746
    Beta strandi1683 – 169210
    Beta strandi1699 – 171012
    Beta strandi1718 – 172912
    Beta strandi1731 – 17344
    Beta strandi1738 – 17414

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2DM4NMR-A1651-1745[»]
    3G2SX-ray1.70C/D2202-2214[»]
    3G2TX-ray2.00C/D2202-2214[»]
    ProteinModelPortaliQ92673.
    SMRiQ92673. Positions 95-739, 759-1072, 1077-1550, 1559-1635, 1651-1745, 1931-2018.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ92673.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini82 – 21372056ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini2159 – 221456CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei2138 – 215821HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati136 – 14712BNR 1Add
    BLAST
    Repeati232 – 24312BNR 2Add
    BLAST
    Repeati441 – 45212BNR 3Add
    BLAST
    Repeati521 – 53212BNR 4Add
    BLAST
    Repeati562 – 57312BNR 5Add
    BLAST
    Repeati800 – 84344LDL-receptor class B 1Add
    BLAST
    Repeati844 – 88744LDL-receptor class B 2Add
    BLAST
    Repeati888 – 93245LDL-receptor class B 3Add
    BLAST
    Repeati933 – 97038LDL-receptor class B 4Add
    BLAST
    Repeati971 – 101343LDL-receptor class B 5Add
    BLAST
    Domaini1026 – 107247EGF-likeAdd
    BLAST
    Domaini1076 – 111439LDL-receptor class A 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini1115 – 115541LDL-receptor class A 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini1156 – 119439LDL-receptor class A 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini1198 – 123639LDL-receptor class A 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini1238 – 127235LDL-receptor class A 5PROSITE-ProRule annotationAdd
    BLAST
    Domaini1273 – 131745LDL-receptor class A 6PROSITE-ProRule annotationAdd
    BLAST
    Domaini1323 – 136139LDL-receptor class A 7PROSITE-ProRule annotationAdd
    BLAST
    Domaini1366 – 140540LDL-receptor class A 8PROSITE-ProRule annotationAdd
    BLAST
    Domaini1417 – 145539LDL-receptor class A 9PROSITE-ProRule annotationAdd
    BLAST
    Domaini1469 – 150840LDL-receptor class A 10PROSITE-ProRule annotationAdd
    BLAST
    Domaini1512 – 155140LDL-receptor class A 11PROSITE-ProRule annotationAdd
    BLAST
    Domaini1557 – 164993Fibronectin type-III 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini1653 – 174593Fibronectin type-III 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini1749 – 184496Fibronectin type-III 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini1843 – 192785Fibronectin type-III 4PROSITE-ProRule annotationAdd
    BLAST
    Domaini1934 – 202996Fibronectin type-III 5PROSITE-ProRule annotationAdd
    BLAST
    Domaini2030 – 211889Fibronectin type-III 6PROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi63 – 653Cell attachment siteSequence Analysis
    Motifi2172 – 21776Endocytosis signalSequence Analysis

    Sequence similaritiesi

    Contains 5 BNR repeats.Curated
    Contains 1 EGF-like domain.Curated
    Contains 6 fibronectin type-III domains.PROSITE-ProRule annotation
    Contains 11 LDL-receptor class A domains.PROSITE-ProRule annotation
    Contains 5 LDL-receptor class B repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG281049.
    HOGENOMiHOG000007009.
    HOVERGENiHBG017830.
    InParanoidiQ92673.
    OMAiTNVYISS.
    OrthoDBiEOG7FV3PK.
    PhylomeDBiQ92673.
    TreeFamiTF324918.

    Family and domain databases

    Gene3Di2.120.10.30. 1 hit.
    2.60.40.10. 4 hits.
    4.10.400.10. 10 hits.
    InterProiIPR011042. 6-blade_b-propeller_TolB-like.
    IPR000742. EG-like_dom.
    IPR003961. Fibronectin_type3.
    IPR013783. Ig-like_fold.
    IPR023415. LDLR_class-A_CS.
    IPR000033. LDLR_classB_rpt.
    IPR002172. LDrepeatLR_classA_rpt.
    IPR006581. VPS10.
    [Graphical view]
    PfamiPF00041. fn3. 3 hits.
    PF00057. Ldl_recept_a. 10 hits.
    PF00058. Ldl_recept_b. 2 hits.
    [Graphical view]
    PRINTSiPR00261. LDLRECEPTOR.
    SMARTiSM00181. EGF. 1 hit.
    SM00060. FN3. 6 hits.
    SM00192. LDLa. 11 hits.
    SM00135. LY. 5 hits.
    SM00602. VPS10. 1 hit.
    [Graphical view]
    SUPFAMiSSF49265. SSF49265. 3 hits.
    SSF57424. SSF57424. 11 hits.
    PROSITEiPS01186. EGF_2. 1 hit.
    PS50853. FN3. 4 hits.
    PS01209. LDLRA_1. 10 hits.
    PS50068. LDLRA_2. 11 hits.
    PS51120. LDLRB. 5 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    Q92673-1 [UniParc]FASTAAdd to Basket

    « Hide

    MATRSSRRES RLPFLFTLVA LLPPGALCEV WTQRLHGGSA PLPQDRGFLV     50
    VQGDPRELRL WARGDARGAS RADEKPLRRK RSAALQPEPI KVYGQVSLND 100
    SHNQMVVHWA GEKSNVIVAL ARDSLALARP KSSDVYVSYD YGKSFKKISD 150
    KLNFGLGNRS EAVIAQFYHS PADNKRYIFA DAYAQYLWIT FDFCNTLQGF 200
    SIPFRAADLL LHSKASNLLL GFDRSHPNKQ LWKSDDFGQT WIMIQEHVKS 250
    FSWGIDPYDK PNTIYIERHE PSGYSTVFRS TDFFQSRENQ EVILEEVRDF 300
    QLRDKYMFAT KVVHLLGSEQ QSSVQLWVSF GRKPMRAAQF VTRHPINEYY 350
    IADASEDQVF VCVSHSNNRT NLYISEAEGL KFSLSLENVL YYSPGGAGSD 400
    TLVRYFANEP FADFHRVEGL QGVYIATLIN GSMNEENMRS VITFDKGGTW 450
    EFLQAPAFTG YGEKINCELS QGCSLHLAQR LSQLLNLQLR RMPILSKESA 500
    PGLIIATGSV GKNLASKTNV YISSSAGARW REALPGPHYY TWGDHGGIIT 550
    AIAQGMETNE LKYSTNEGET WKTFIFSEKP VFVYGLLTEP GEKSTVFTIF 600
    GSNKENVHSW LILQVNATDA LGVPCTENDY KLWSPSDERG NECLLGHKTV 650
    FKRRTPHATC FNGEDFDRPV VVSNCSCTRE DYECDFGFKM SEDLSLEVCV 700
    PDPEFSGKSY SPPVPCPVGS TYRRTRGYRK ISGDTCSGGD VEARLEGELV 750
    PCPLAEENEF ILYAVRKSIY RYDLASGATE QLPLTGLRAA VALDFDYEHN 800
    CLYWSDLALD VIQRLCLNGS TGQEVIINSG LETVEALAFE PLSQLLYWVD 850
    AGFKKIEVAN PDGDFRLTIV NSSVLDRPRA LVLVPQEGVM FWTDWGDLKP 900
    GIYRSNMDGS AAYHLVSEDV KWPNGISVDD QWIYWTDAYL ECIERITFSG 950
    QQRSVILDNL PHPYAIAVFK NEIYWDDWSQ LSIFRASKYS GSQMEILANQ 1000
    LTGLMDMKIF YKGKNTGSNA CVPRPCSLLC LPKANNSRSC RCPEDVSSSV 1050
    LPSGDLMCDC PQGYQLKNNT CVKQENTCLR NQYRCSNGNC INSIWWCDFD 1100
    NDCGDMSDER NCPTTICDLD TQFRCQESGT CIPLSYKCDL EDDCGDNSDE 1150
    SHCEMHQCRS DEYNCSSGMC IRSSWVCDGD NDCRDWSDEA NCTAIYHTCE 1200
    ASNFQCRNGH CIPQRWACDG DTDCQDGSDE DPVNCEKKCN GFRCPNGTCI 1250
    PSSKHCDGLR DCSDGSDEQH CEPLCTHFMD FVCKNRQQCL FHSMVCDGII 1300
    QCRDGSDEDA AFAGCSQDPE FHKVCDEFGF QCQNGVCISL IWKCDGMDDC 1350
    GDYSDEANCE NPTEAPNCSR YFQFRCENGH CIPNRWKCDR ENDCGDWSDE 1400
    KDCGDSHILP FSTPGPSTCL PNYYRCSSGT CVMDTWVCDG YRDCADGSDE 1450
    EACPLLANVT AASTPTQLGR CDRFEFECHQ PKTCIPNWKR CDGHQDCQDG 1500
    RDEANCPTHS TLTCMSREFQ CEDGEACIVL SERCDGFLDC SDESDEKACS 1550
    DELTVYKVQN LQWTADFSGD VTLTWMRPKK MPSASCVYNV YYRVVGESIW 1600
    KTLETHSNKT NTVLKVLKPD TTYQVKVQVQ CLSKAHNTND FVTLRTPEGL 1650
    PDAPRNLQLS LPREAEGVIV GHWAPPIHTH GLIREYIVEY SRSGSKMWAS 1700
    QRAASNFTEI KNLLVNTLYT VRVAAVTSRG IGNWSDSKSI TTIKGKVIPP 1750
    PDIHIDSYGE NYLSFTLTME SDIKVNGYVV NLFWAFDTHK QERRTLNFRG 1800
    SILSHKVGNL TAHTSYEISA WAKTDLGDSP LAFEHVMTRG VRPPAPSLKA 1850
    KAINQTAVEC TWTGPRNVVY GIFYATSFLD LYRNPKSLTT SLHNKTVIVS 1900
    KDEQYLFLVR VVVPYQGPSS DYVVVKMIPD SRLPPRHLHV VHTGKTSVVI 1950
    KWESPYDSPD QDLLYAVAVK DLIRKTDRSY KVKSRNSTVE YTLNKLEPGG 2000
    KYHIIVQLGN MSKDSSIKIT TVSLSAPDAL KIITENDHVL LFWKSLALKE 2050
    KHFNESRGYE IHMFDSAMNI TAYLGNTTDN FFKISNLKMG HNYTFTVQAR 2100
    CLFGNQICGE PAILLYDELG SGADASATQA ARSTDVAAVV VPILFLILLS 2150
    LGVGFAILYT KHRRLQSSFT AFANSHYSSR LGSAIFSSGD DLGEDDEDAP 2200
    MITGFSDDVP MVIA 2214
    Length:2,214
    Mass (Da):248,426
    Last modified:May 18, 2010 - v2
    Checksum:i4C215BB33E65C0B2
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti120 – 1201L → S in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036371
    Natural varianti141 – 1411Y → C in AD; unknown pathological significance. 1 Publication
    VAR_070012
    Natural varianti511 – 5111G → R in AD; unknown pathological significance. 1 Publication
    VAR_070013
    Natural varianti528 – 5281A → T.1 Publication
    Corresponds to variant rs2298813 [ dbSNP | Ensembl ].
    VAR_020360
    Natural varianti924 – 9241N → S in AD; unknown pathological significance. 1 Publication
    Corresponds to variant rs377498269 [ dbSNP | Ensembl ].
    VAR_070014
    Natural varianti1074 – 10741Q → E.4 Publications
    Corresponds to variant rs1699107 [ dbSNP | Ensembl ].
    VAR_034508
    Natural varianti1358 – 13581N → S in AD; unknown pathological significance. 1 Publication
    VAR_070015
    Natural varianti1581 – 15811M → L in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036372
    Natural varianti1681 – 16811G → D in AD; unknown pathological significance. 1 Publication
    VAR_070016
    Natural varianti1967 – 19671V → I.4 Publications
    Corresponds to variant rs1792120 [ dbSNP | Ensembl ].
    VAR_034509
    Natural varianti1972 – 19721L → V in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_036373

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y08110 mRNA. Translation: CAA69325.1.
    U60975 mRNA. Translation: AAC50891.2.
    AP000664 Genomic DNA. No translation available.
    AP000977 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW67525.1.
    BC137171 mRNA. Translation: AAI37172.1.
    CCDSiCCDS8436.1.
    RefSeqiNP_003096.1. NM_003105.5.
    UniGeneiHs.368592.

    Genome annotation databases

    EnsembliENST00000260197; ENSP00000260197; ENSG00000137642.
    GeneIDi6653.
    KEGGihsa:6653.
    UCSCiuc001pxx.3. human.

    Polymorphism databases

    DMDMi296452912.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y08110 mRNA. Translation: CAA69325.1 .
    U60975 mRNA. Translation: AAC50891.2 .
    AP000664 Genomic DNA. No translation available.
    AP000977 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW67525.1 .
    BC137171 mRNA. Translation: AAI37172.1 .
    CCDSi CCDS8436.1.
    RefSeqi NP_003096.1. NM_003105.5.
    UniGenei Hs.368592.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2DM4 NMR - A 1651-1745 [» ]
    3G2S X-ray 1.70 C/D 2202-2214 [» ]
    3G2T X-ray 2.00 C/D 2202-2214 [» ]
    ProteinModelPortali Q92673.
    SMRi Q92673. Positions 95-739, 759-1072, 1077-1550, 1559-1635, 1651-1745, 1931-2018.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112536. 11 interactions.
    IntActi Q92673. 10 interactions.
    MINTi MINT-231252.
    STRINGi 9606.ENSP00000260197.

    PTM databases

    PhosphoSitei Q92673.

    Polymorphism databases

    DMDMi 296452912.

    Proteomic databases

    MaxQBi Q92673.
    PaxDbi Q92673.
    PRIDEi Q92673.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000260197 ; ENSP00000260197 ; ENSG00000137642 .
    GeneIDi 6653.
    KEGGi hsa:6653.
    UCSCi uc001pxx.3. human.

    Organism-specific databases

    CTDi 6653.
    GeneCardsi GC11P121356.
    HGNCi HGNC:11185. SORL1.
    HPAi CAB011500.
    HPA031321.
    MIMi 104300. phenotype.
    602005. gene.
    neXtProti NX_Q92673.
    Orphaneti 1020. Early-onset autosomal dominant Alzheimer disease.
    PharmGKBi PA36022.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG281049.
    HOGENOMi HOG000007009.
    HOVERGENi HBG017830.
    InParanoidi Q92673.
    OMAi TNVYISS.
    OrthoDBi EOG7FV3PK.
    PhylomeDBi Q92673.
    TreeFami TF324918.

    Miscellaneous databases

    ChiTaRSi SORL1. human.
    EvolutionaryTracei Q92673.
    GenomeRNAii 6653.
    NextBioi 25935.
    PROi Q92673.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q92673.
    Bgeei Q92673.
    CleanExi HS_SORL1.
    Genevestigatori Q92673.

    Family and domain databases

    Gene3Di 2.120.10.30. 1 hit.
    2.60.40.10. 4 hits.
    4.10.400.10. 10 hits.
    InterProi IPR011042. 6-blade_b-propeller_TolB-like.
    IPR000742. EG-like_dom.
    IPR003961. Fibronectin_type3.
    IPR013783. Ig-like_fold.
    IPR023415. LDLR_class-A_CS.
    IPR000033. LDLR_classB_rpt.
    IPR002172. LDrepeatLR_classA_rpt.
    IPR006581. VPS10.
    [Graphical view ]
    Pfami PF00041. fn3. 3 hits.
    PF00057. Ldl_recept_a. 10 hits.
    PF00058. Ldl_recept_b. 2 hits.
    [Graphical view ]
    PRINTSi PR00261. LDLRECEPTOR.
    SMARTi SM00181. EGF. 1 hit.
    SM00060. FN3. 6 hits.
    SM00192. LDLa. 11 hits.
    SM00135. LY. 5 hits.
    SM00602. VPS10. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49265. SSF49265. 3 hits.
    SSF57424. SSF57424. 11 hits.
    PROSITEi PS01186. EGF_2. 1 hit.
    PS50853. FN3. 4 hits.
    PS01209. LDLRA_1. 10 hits.
    PS50068. LDLRA_2. 11 hits.
    PS51120. LDLRB. 5 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel mosaic protein containing LDL receptor elements is highly conserved in humans and chickens."
      Morwald S., Yamazaki H., Bujo H., Kusunoki J., Kanaki T., Seimiya K., Morisaki N., Nimpf J., Schneider W.J., Saito Y.
      Arterioscler. Thromb. Vasc. Biol. 17:996-1002(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLU-1074 AND ILE-1967.
      Tissue: Brain.
    2. "Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein."
      Jacobsen L., Madsen P., Moestrup S.K., Lund A.H., Tommerup N., Nykjaer A., Sottrup-Jensen L., Gliemann J., Petersen C.M.
      J. Biol. Chem. 271:31379-31383(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF N-TERMINUS, PARTIAL PROTEIN SEQUENCE, VARIANTS GLU-1074 AND ILE-1967.
      Tissue: Brain and T-cell.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS GLU-1074 AND ILE-1967.
    5. "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], VARIANTS GLU-1074 AND ILE-1967.
      Tissue: Brain.
    6. "LR11, an LDL receptor gene family member, is a novel regulator of smooth muscle cell migration."
      Zhu Y., Bujo H., Yamazaki H., Ohwaki K., Jiang M., Hirayama S., Kanaki T., Shibasaki M., Takahashi K., Schneider W.J., Saito Y.
      Circ. Res. 94:752-758(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PLAUR.
    7. Cited for: FUNCTION IN APP TRAFFICKING, SUBCELLULAR LOCATION, INTERACTION WITH APP, TISSUE SPECIFICITY.
    8. "No association of SORL1 SNPs with Alzheimer's disease."
      Minster R.L., DeKosky S.T., Kamboh M.I.
      Neurosci. Lett. 440:190-192(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: LACK OF ASSOCIATION WITH SUSCEPTIBILITY TO LATE-ONSET ALZHEIMER DISEASE.
    9. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-99; ASN-1733; ASN-2010; ASN-2076 AND ASN-2092.
      Tissue: Liver.
    10. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    11. Cited for: INVOLVEMENT IN AD.
    12. "Rho kinase II phosphorylation of the lipoprotein receptor LR11/SORLA alters amyloid-beta production."
      Herskowitz J.H., Seyfried N.T., Gearing M., Kahn R.A., Peng J., Levey A.I., Lah J.J.
      J. Biol. Chem. 286:6117-6127(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-2206, INTERACTION WITH ROCK2.
    13. "SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and Caucasians."
      Alzheimer Disease Genetics Consortium
      Miyashita A., Koike A., Jun G., Wang L.S., Takahashi S., Matsubara E., Kawarabayashi T., Shoji M., Tomita N., Arai H., Asada T., Harigaya Y., Ikeda M., Amari M., Hanyu H., Higuchi S., Ikeuchi T., Nishizawa M.
      , Suga M., Kawase Y., Akatsu H., Kosaka K., Yamamoto T., Imagawa M., Hamaguchi T., Yamada M., Moriaha T., Takeda M., Takao T., Nakata K., Fujisawa Y., Sasaki K., Watanabe K., Nakashima K., Urakami K., Ooya T., Takahashi M., Yuzuriha T., Serikawa K., Yoshimoto S., Nakagawa R., Kim J.W., Ki C.S., Won H.H., Na D.L., Seo S.W., Mook-Jung I., St George-Hyslop P., Mayeux R., Haines J.L., Pericak-Vance M.A., Yoshida M., Nishida N., Tokunaga K., Yamamoto K., Tsuji S., Kanazawa I., Ihara Y., Schellenberg G.D., Farrer L.A., Kuwano R.
      PLoS ONE 8:E58618-E58618(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN AD.
    14. "Solution structure of the second FN3 domain of human SORLA/LR11."
      RIKEN structural genomics initiative (RSGI)
      Submitted (OCT-2006) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 1651-1745.
    15. Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 2202-2214 IN COMPLEX WITH GGA1, INTERACTION WITH GGA1.
    16. Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-120; LEU-1581 AND VAL-1972.
    17. "SORL1 is genetically associated with increased risk for late-onset Alzheimer disease in the Belgian population."
      Bettens K., Brouwers N., Engelborghs S., De Deyn P.P., Van Broeckhoven C., Sleegers K.
      Hum. Mutat. 29:769-770(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: POSSIBLE ASSOCIATION WITH SUSCEPTIBILITY TO LATE-ONSET ALZHEIMER DISEASE, VARIANT THR-528.
    18. Cited for: VARIANTS AD CYS-141; ARG-511; SER-924; SER-1358 AND ASP-1681.

    Entry informationi

    Entry nameiSORL_HUMAN
    AccessioniPrimary (citable) accession number: Q92673
    Secondary accession number(s): B2RNX7, Q92856
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 18, 2010
    Last modified: October 1, 2014
    This is version 150 of the entry and version 2 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 11
      Human chromosome 11: 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