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Database: UniProt
Entry: P01131
LinkDB: P01131
Original site: P01131 
ID   LDLR_BOVIN              Reviewed;         845 AA.
AC   P01131; F1MZ58;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   30-NOV-2016, sequence version 2.
DT   16-JAN-2019, entry version 138.
DE   RecName: Full=Low-density lipoprotein receptor;
DE            Short=LDL receptor;
DE   Flags: Precursor;
GN   Name=LDLR;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC   Pecora; Bovidae; Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Hereford;
RX   PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA   Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C.,
RA   Puiu D., Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S.,
RA   Marcais G., Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT   "A whole-genome assembly of the domestic cow, Bos taurus.";
RL   Genome Biol. 10:R42.01-R42.10(2009).
RN   [2]
RP   PROTEIN SEQUENCE OF 22-37, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX   PubMed=6313699; DOI=10.1083/jcb.97.5.1635;
RA   Schneider W.J., Slaughter C.J., Goldstein J.L., Anderson R.G.,
RA   Capra J.D., Brown M.S.;
RT   "Use of antipeptide antibodies to demonstrate external orientation of
RT   the NH2-terminus of the low density lipoprotein receptor in the plasma
RT   membrane of fibroblasts.";
RL   J. Cell Biol. 97:1635-1640(1983).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 582-845.
RX   PubMed=6327078; DOI=10.1016/0092-8674(84)90388-X;
RA   Russell D.W., Schneider W.J., Yamamoto T., Luskey K.L., Brown M.S.,
RA   Goldstein J.L.;
RT   "Domain map of the LDL receptor: sequence homology with the epidermal
RT   growth factor precursor.";
RL   Cell 37:577-585(1984).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 644-679.
RX   PubMed=6143315; DOI=10.1073/pnas.80.24.7501;
RA   Russell D.W., Yamamoto T., Schneider W.J., Slaughter C.J., Brown M.S.,
RA   Goldstein J.L.;
RT   "cDNA cloning of the bovine low density lipoprotein receptor: feedback
RT   regulation of a receptor mRNA.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:7501-7505(1983).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 644-679.
RX   PubMed=3755212; DOI=10.1016/0076-6879(86)28113-6;
RA   Russell D.W., Yamamoto T.;
RT   "Molecular cloning of bovine LDL receptor cDNAs.";
RL   Methods Enzymol. 128:895-909(1986).
CC   -!- FUNCTION: Binds LDL, the major cholesterol-carrying lipoprotein of
CC       plasma, and transports it into cells by endocytosis. In order to
CC       be internalized, the receptor-ligand complexes must first cluster
CC       into clathrin-coated pits. {ECO:0000250|UniProtKB:P01130}.
CC   -!- SUBUNIT: Interacts (via NPXY motif) with DAB2 (via PID domain);
CC       the interaction is impaired by tyrosine phosphorylation of the
CC       NPXY motif. Interacts (via NPXY motif) with LDLRAP1 (via PID
CC       domain). Interacts with ARRB1. Interacts with SNX17. Interacts
CC       with the full-length immature form of PCSK9 (via C-terminus).
CC       {ECO:0000250|UniProtKB:P01130}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:6313699};
CC       Single-pass type I membrane protein {ECO:0000269|PubMed:6313699}.
CC       Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:P01130}.
CC       Golgi apparatus {ECO:0000250|UniProtKB:P01130}. Early endosome
CC       {ECO:0000250|UniProtKB:P01130}. Late endosome
CC       {ECO:0000250|UniProtKB:P01130}. Lysosome
CC       {ECO:0000250|UniProtKB:P01130}. Note=Rapidly endocytosed upon
CC       ligand binding. {ECO:0000250|UniProtKB:P01130}.
CC   -!- DOMAIN: The NPXY motif mediates the interaction with the clathrin
CC       adapter DAB2 and with LDLRAP1 which are involved in receptor
CC       internalization. A few residues outside the motif also play a role
CC       in the interaction. {ECO:0000250|UniProtKB:P01130}.
CC   -!- PTM: N- and O-glycosylated. {ECO:0000250|UniProtKB:P01130}.
CC   -!- PTM: Ubiquitinated by MYLIP leading to degradation.
CC       {ECO:0000250|UniProtKB:P01130}.
CC   -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
DR   EMBL; DAAA02019482; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; K01830; AAA30618.1; -; mRNA.
DR   EMBL; K01429; AAA30620.1; -; mRNA.
DR   EMBL; M29843; AAA30619.1; -; mRNA.
DR   PIR; A01384; QRBOLD.
DR   RefSeq; NP_001160002.1; NM_001166530.1.
DR   UniGene; Bt.3562; -.
DR   ProteinModelPortal; P01131; -.
DR   SMR; P01131; -.
DR   STRING; 9913.ENSBTAP00000016342; -.
DR   PaxDb; P01131; -.
DR   PRIDE; P01131; -.
DR   Ensembl; ENSBTAT00000016342; ENSBTAP00000016342; ENSBTAG00000012314.
DR   GeneID; 281276; -.
DR   KEGG; bta:281276; -.
DR   CTD; 3949; -.
DR   VGNC; VGNC:55214; LDLR.
DR   eggNOG; ENOG410KD0U; Eukaryota.
DR   eggNOG; ENOG410Z5FJ; LUCA.
DR   GeneTree; ENSGT00940000161046; -.
DR   HOGENOM; HOG000115656; -.
DR   HOVERGEN; HBG006250; -.
DR   InParanoid; P01131; -.
DR   KO; K12473; -.
DR   OMA; INVTLCE; -.
DR   OrthoDB; 359795at2759; -.
DR   TreeFam; TF351700; -.
DR   Reactome; R-BTA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-BTA-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-BTA-8964026; Chylomicron clearance.
DR   Reactome; R-BTA-8964038; LDL clearance.
DR   Proteomes; UP000009136; Chromosome 7.
DR   Bgee; ENSBTAG00000012314; Expressed in 10 organ(s), highest expression level in colon.
DR   GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR   GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR   GO; GO:0005901; C:caveola; IDA:AgBase.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR   GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR   GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR   GO; GO:0034362; C:low-density lipoprotein particle; IEA:UniProtKB-KW.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0005771; C:multivesicular body; IDA:AgBase.
DR   GO; GO:1990666; C:PCSK9-LDLR complex; IEA:Ensembl.
DR   GO; GO:0043235; C:receptor complex; IEA:Ensembl.
DR   GO; GO:0036477; C:somatodendritic compartment; IEA:Ensembl.
DR   GO; GO:0097443; C:sorting endosome; IEA:Ensembl.
DR   GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0030169; F:low-density lipoprotein particle binding; IEA:Ensembl.
DR   GO; GO:0005041; F:low-density lipoprotein particle receptor activity; IEA:Ensembl.
DR   GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR   GO; GO:0030229; F:very-low-density lipoprotein particle receptor activity; IEA:Ensembl.
DR   GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; IEA:Ensembl.
DR   GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR   GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IEA:Ensembl.
DR   GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
DR   GO; GO:0070508; P:cholesterol import; IEA:Ensembl.
DR   GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0034384; P:high-density lipoprotein particle clearance; IEA:Ensembl.
DR   GO; GO:0030299; P:intestinal cholesterol absorption; IEA:Ensembl.
DR   GO; GO:0042159; P:lipoprotein catabolic process; IEA:Ensembl.
DR   GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR   GO; GO:0034383; P:low-density lipoprotein particle clearance; IEA:Ensembl.
DR   GO; GO:1905907; P:negative regulation of amyloid fibril formation; IEA:Ensembl.
DR   GO; GO:0061889; P:negative regulation of astrocyte activation; IEA:Ensembl.
DR   GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR   GO; GO:1903979; P:negative regulation of microglial cell activation; IEA:Ensembl.
DR   GO; GO:0006909; P:phagocytosis; IEA:Ensembl.
DR   GO; GO:0015914; P:phospholipid transport; IEA:Ensembl.
DR   GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR   GO; GO:1905167; P:positive regulation of lysosomal protein catabolic process; IEA:Ensembl.
DR   GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; IEA:Ensembl.
DR   GO; GO:0090118; P:receptor-mediated endocytosis involved in cholesterol transport; IEA:Ensembl.
DR   GO; GO:0090181; P:regulation of cholesterol metabolic process; IEA:Ensembl.
DR   GO; GO:0010899; P:regulation of phosphatidylcholine catabolic process; IEA:Ensembl.
DR   GO; GO:0061771; P:response to caloric restriction; IEA:Ensembl.
DR   CDD; cd00112; LDLa; 6.
DR   Gene3D; 2.120.10.30; -; 1.
DR   InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR   InterPro; IPR018097; EGF_Ca-bd_CS.
DR   InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR036055; LDL_receptor-like_sf.
DR   InterPro; IPR023415; LDLR_class-A_CS.
DR   InterPro; IPR000033; LDLR_classB_rpt.
DR   InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR   Pfam; PF07645; EGF_CA; 1.
DR   Pfam; PF00057; Ldl_recept_a; 7.
DR   Pfam; PF00058; Ldl_recept_b; 5.
DR   PRINTS; PR00261; LDLRECEPTOR.
DR   SMART; SM00181; EGF; 4.
DR   SMART; SM00179; EGF_CA; 2.
DR   SMART; SM00192; LDLa; 7.
DR   SMART; SM00135; LY; 5.
DR   SUPFAM; SSF57184; SSF57184; 1.
DR   SUPFAM; SSF57424; SSF57424; 6.
DR   PROSITE; PS00010; ASX_HYDROXYL; 2.
DR   PROSITE; PS01186; EGF_2; 2.
DR   PROSITE; PS50026; EGF_3; 2.
DR   PROSITE; PS01187; EGF_CA; 1.
DR   PROSITE; PS01209; LDLRA_1; 7.
DR   PROSITE; PS50068; LDLRA_2; 7.
DR   PROSITE; PS51120; LDLRB; 5.
PE   1: Evidence at protein level;
KW   Cell membrane; Cholesterol metabolism; Coated pit; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; EGF-like domain;
KW   Endocytosis; Endosome; Glycoprotein; Golgi apparatus; LDL;
KW   Lipid metabolism; Lipid transport; Lysosome; Membrane; Receptor;
KW   Reference proteome; Repeat; Signal; Steroid metabolism;
KW   Sterol metabolism; Transmembrane; Transmembrane helix; Transport;
KW   Ubl conjugation.
FT   SIGNAL        1     21       {ECO:0000269|PubMed:6313699}.
FT   CHAIN        22    845       Low-density lipoprotein receptor.
FT                                /FTId=PRO_0000191075.
FT   TOPO_DOM     22    774       Extracellular.
FT                                {ECO:0000269|PubMed:6313699}.
FT   TRANSMEM    775    795       Helical. {ECO:0000255}.
FT   TOPO_DOM    796    845       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P01130}.
FT   DOMAIN       26     64       LDL-receptor class A 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN       67    105       LDL-receptor class A 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      108    144       LDL-receptor class A 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      147    185       LDL-receptor class A 4.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      198    234       LDL-receptor class A 5.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      237    273       LDL-receptor class A 6.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      277    316       LDL-receptor class A 7.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      316    355       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      356    388       EGF-like 2; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   REPEAT      441    487       LDL-receptor class B 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      488    530       LDL-receptor class B 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      531    574       LDL-receptor class B 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      575    619       LDL-receptor class B 4.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      620    660       LDL-receptor class B 5.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REGION      712    753       Clustered O-linked oligosaccharides.
FT                                {ECO:0000255}.
FT   REGION      796    845       Required for MYLIP-triggered down-
FT                                regulation of LDLR.
FT                                {ECO:0000250|UniProtKB:P01130}.
FT   MOTIF       808    813       NPXY motif.
FT                                {ECO:0000250|UniProtKB:P01130}.
FT   CARBOHYD    659    659       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     27     39       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     34     52       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     46     63       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     68     82       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     75     95       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     89    104       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    109    121       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    116    134       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    128    143       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    148    160       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    155    173       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    167    184       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    199    211       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    206    224       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    218    233       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    238    250       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    245    263       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    257    272       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    278    291       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    286    304       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    298    315       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    320    331       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    327    340       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    342    354       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    360    370       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    366    379       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   CONFLICT    760    760       I -> V (in Ref. 3; AAA30618).
FT                                {ECO:0000305}.
SQ   SEQUENCE   845 AA;  92869 MW;  5EB7D1F939DEBF10 CRC64;
     MRLAGWGLRW AIALLIAVGE AAVEDNCGRN EFQCQDGKCI SYKWVCDGTA ECQDGSDESQ
     ETCKSVTCKM GDFSCGGRVN RCISGSWRCD GQVDCENGSD EEGCSPKTCS QDEFRCNDGK
     CIAPKFVCDL DLDCLDGSDE ASCPMPTCGP ANFQCNSSMC IPQLWACDGD PDCDDGSDEW
     PKHCGTPHPS GPLQDNNPCS ALEFHCGSGE CIHSSWHCDH DPDCKDKSDE ENCAVATCRP
     DEFQCSDGTC IHGSRQCDRE PDCKDLSDEL GCVNVTLCEG PNKFKCQSGE CISLDKVCNS
     VRDCRDWSDE PLKDCGTNEC LDNKGGCSHI CNDLKIGYEC LCPEGFQLVG KHRCEDIDEC
     QNPDTCSQLC VNLEGSYKCE CEEGFRLEPL TKACKAVGTI AYLFFTNRHE VRKMTLDRSE
     YTSLIPNLKN VVALDTEVAS NRIYWSDLSQ RKIYSAQIDG APGFSSYDTV IGEDLQAPDG
     LAVDWIHSNI YWTDSILGTV SVADTKGVKR KTLFQEEGSK PRAIVVDPVH GFMYWTDWGA
     PAEIKKGGLN GVDVYSLVTE DIQWPNGITL DLSGGRLYWV DSKLHSISSI DVNGGNRKTV
     LEDKKKLAHP FSLAIFEDKV FWTDVINEAI FSANRLTGSD ISLMAENLLS PEDIVLFHNL
     TQPRGVNWCE RTALRNGGCQ YLCLPAPQIN PRSPKFTCAC PDGMLLAKDM RSCLTESESA
     VTTRGPSTVS STAVGPKRTA SPELTTAESV TMSQQGQGDI ASQADTERPG SVGALYIVLP
     IALLILLAFG TFLLWKNWRL KSINSINFDN PVYQKTTEDE VHICRSQDGY TYPSRQMVSL
     EDDVA
//
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