LDLR_BOVIN
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 03-AUG-2022, entry version 153.
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; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC 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., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA 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., Capra J.D.,
RA Brown M.S.;
RT "Use of antipeptide antibodies to demonstrate external orientation of the
RT NH2-terminus of the low density lipoprotein receptor in the plasma membrane
RT 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 be
CC internalized, the receptor-ligand complexes must first cluster into
CC clathrin-coated pits. {ECO:0000250|UniProtKB:P01130}.
CC -!- SUBUNIT: Interacts (via NPXY motif) with DAB2 (via PID domain); the
CC interaction is impaired by tyrosine phosphorylation of the NPXY motif.
CC Interacts (via NPXY motif) with LDLRAP1 (via PID domain). Interacts
CC with ARRB1. Interacts with SNX17. Interacts with the full-length
CC 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}. Golgi
CC 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 ligand
CC 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 in
CC 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}.
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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 AlphaFoldDB; 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 VEuPathDB; HostDB:ENSBTAG00000012314; -.
DR VGNC; VGNC:55214; LDLR.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000161046; -.
DR InParanoid; P01131; -.
DR OMA; IMNEAIF; -.
DR OrthoDB; 359795at2759; -.
DR TreeFam; TF351700; -.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000012314; Expressed in diaphragm and 104 other tissues.
DR ExpressionAtlas; P01131; baseline and differential.
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:0048844; P:artery morphogenesis; 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:0010989; P:negative regulation of low-density lipoprotein particle clearance; IEA:Ensembl.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; IEA:Ensembl.
DR GO; GO:0001920; P:negative regulation of receptor recycling; 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 Gene3D; 4.10.400.10; -; 6.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
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;
KW Direct protein sequencing; Disulfide bond; EGF-like domain; Endocytosis;
KW Endosome; Glycoprotein; Golgi apparatus; LDL; Lipid metabolism;
KW Lipid transport; Lysosome; Membrane; Receptor; Reference proteome; Repeat;
KW Signal; Steroid metabolism; Sterol metabolism; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:6313699"
FT CHAIN 22..845
FT /note="Low-density lipoprotein receptor"
FT /id="PRO_0000191075"
FT TOPO_DOM 22..774
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:6313699"
FT TRANSMEM 775..795
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 796..845
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DOMAIN 26..64
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 67..105
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 108..144
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 147..185
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 198..234
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 237..273
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 277..316
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 316..355
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 356..388
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 441..487
FT /note="LDL-receptor class B 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 488..530
FT /note="LDL-receptor class B 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 531..574
FT /note="LDL-receptor class B 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 575..619
FT /note="LDL-receptor class B 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 620..660
FT /note="LDL-receptor class B 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REGION 712..753
FT /note="Clustered O-linked oligosaccharides"
FT /evidence="ECO:0000255"
FT REGION 717..765
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 796..845
FT /note="Required for MYLIP-triggered down-regulation of
FT LDLR"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT MOTIF 808..813
FT /note="NPXY motif"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT COMPBIAS 717..764
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 659
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 27..39
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 34..52
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 46..63
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 68..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 75..95
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 89..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 109..121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 116..134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 128..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 148..160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 155..173
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 167..184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 199..211
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 206..224
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 218..233
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 238..250
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 245..263
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 257..272
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 278..291
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 286..304
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 298..315
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 320..331
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 327..340
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 342..354
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 360..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 366..379
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CONFLICT 760
FT /note="I -> V (in Ref. 3; AAA30618)"
FT /evidence="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
