LDLR_RAT
ID LDLR_RAT Reviewed; 879 AA.
AC P35952;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Low-density lipoprotein receptor;
DE Short=LDL receptor;
DE Flags: Precursor;
GN Name=Ldlr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RX PubMed=2922268; DOI=10.1093/nar/17.3.1259;
RA Lee L.Y., Mohler W.A., Schafer B.L., Freudenberger J.S., Byrne-Connolly N.,
RA Eager K.B., Mosley S.T., Leighton J.K., Thrift R.N., Davis R.A.,
RA Tanaka R.D.;
RT "Nucleotide sequence of the rat low density lipoprotein receptor cDNA.";
RL Nucleic Acids Res. 17:1259-1260(1989).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-717; THR-724; THR-732;
RP THR-733 AND SER-734, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
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 (By similarity). Interacts (via NPXY motif) with LDLRAP1 (via PID
CC domain). Interacts with ARRB1. Interacts with SNX17. Interacts with the
CC full-length immature form of PCSK9 (via C-terminus) (By similarity).
CC {ECO:0000250|UniProtKB:P01130, ECO:0000250|UniProtKB:P35951}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P01130};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P01131}.
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; X13722; CAA32001.1; -; mRNA.
DR PIR; S03430; QRRTLD.
DR RefSeq; NP_786938.1; NM_175762.2.
DR AlphaFoldDB; P35952; -.
DR SMR; P35952; -.
DR STRING; 10116.ENSRNOP00000013496; -.
DR GlyGen; P35952; 4 sites.
DR iPTMnet; P35952; -.
DR PhosphoSitePlus; P35952; -.
DR jPOST; P35952; -.
DR PaxDb; P35952; -.
DR PRIDE; P35952; -.
DR GeneID; 300438; -.
DR KEGG; rno:300438; -.
DR UCSC; RGD:2998; rat.
DR CTD; 3949; -.
DR RGD; 2998; Ldlr.
DR eggNOG; KOG1215; Eukaryota.
DR InParanoid; P35952; -.
DR OrthoDB; 359795at2759; -.
DR PhylomeDB; P35952; -.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-8964026; Chylomicron clearance.
DR Reactome; R-RNO-8964038; LDL clearance.
DR PRO; PR:P35952; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; ISO:RGD.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
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:1990666; C:PCSK9-LDLR complex; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:RGD.
DR GO; GO:0036477; C:somatodendritic compartment; ISO:RGD.
DR GO; GO:0097443; C:sorting endosome; ISO:RGD.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0071813; F:lipoprotein particle binding; IBA:GO_Central.
DR GO; GO:0030169; F:low-density lipoprotein particle binding; ISO:RGD.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; IDA:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0030229; F:very-low-density lipoprotein particle receptor activity; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0097242; P:amyloid-beta clearance; ISO:RGD.
DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; ISO:RGD.
DR GO; GO:0048844; P:artery morphogenesis; ISO:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; ISO:RGD.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; IEP:RGD.
DR GO; GO:0070508; P:cholesterol import; ISO:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; ISO:RGD.
DR GO; GO:0030301; P:cholesterol transport; ISO:RGD.
DR GO; GO:0006897; P:endocytosis; IMP:RGD.
DR GO; GO:0034384; P:high-density lipoprotein particle clearance; ISO:RGD.
DR GO; GO:0030299; P:intestinal cholesterol absorption; ISO:RGD.
DR GO; GO:0006629; P:lipid metabolic process; ISO:RGD.
DR GO; GO:0042159; P:lipoprotein catabolic process; ISO:RGD.
DR GO; GO:0042157; P:lipoprotein metabolic process; ISO:RGD.
DR GO; GO:0007616; P:long-term memory; ISO:RGD.
DR GO; GO:0034383; P:low-density lipoprotein particle clearance; ISO:RGD.
DR GO; GO:1905907; P:negative regulation of amyloid fibril formation; ISO:RGD.
DR GO; GO:0061889; P:negative regulation of astrocyte activation; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0010989; P:negative regulation of low-density lipoprotein particle clearance; ISO:RGD.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; ISO:RGD.
DR GO; GO:0051248; P:negative regulation of protein metabolic process; ISO:RGD.
DR GO; GO:0001920; P:negative regulation of receptor recycling; ISO:RGD.
DR GO; GO:0006909; P:phagocytosis; ISO:RGD.
DR GO; GO:0015914; P:phospholipid transport; ISO:RGD.
DR GO; GO:0034381; P:plasma lipoprotein particle clearance; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:1905167; P:positive regulation of lysosomal protein catabolic process; ISO:RGD.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISO:RGD.
DR GO; GO:0010898; P:positive regulation of triglyceride catabolic process; IMP:RGD.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISO:RGD.
DR GO; GO:0090118; P:receptor-mediated endocytosis involved in cholesterol transport; ISO:RGD.
DR GO; GO:0090181; P:regulation of cholesterol metabolic process; ISO:RGD.
DR GO; GO:0010899; P:regulation of phosphatidylcholine catabolic process; ISO:RGD.
DR GO; GO:0051246; P:regulation of protein metabolic process; ISO:RGD.
DR GO; GO:0061771; P:response to caloric restriction; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0033762; P:response to glucagon; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
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; 7.
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; Disulfide bond;
KW EGF-like domain; Endocytosis; Endosome; Glycoprotein; Golgi apparatus; LDL;
KW Lipid metabolism; Lipid transport; Lysosome; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Steroid metabolism;
KW Sterol metabolism; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT SIGNAL 1..21
FT /evidence="ECO:0000250|UniProtKB:P01131"
FT CHAIN 22..879
FT /note="Low-density lipoprotein receptor"
FT /id="PRO_0000017314"
FT TOPO_DOM 22..807
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P01131"
FT TRANSMEM 808..829
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 830..879
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DOMAIN 25..65
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 66..106
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 107..145
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 146..186
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 196..234
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 235..273
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 275..314
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 315..354
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 355..394
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 398..439
FT /note="LDL-receptor class B 1"
FT REPEAT 440..485
FT /note="LDL-receptor class B 2"
FT REPEAT 486..528
FT /note="LDL-receptor class B 3"
FT REPEAT 529..572
FT /note="LDL-receptor class B 4"
FT REPEAT 573..615
FT /note="LDL-receptor class B 5"
FT REPEAT 616..658
FT /note="LDL-receptor class B 6"
FT DOMAIN 663..712
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 717..788
FT /note="Clustered O-linked oligosaccharides"
FT REGION 718..797
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 830..879
FT /note="Required for MYLIP-triggered down-regulation of
FT LDLR"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT MOTIF 842..847
FT /note="NPXY motif"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT COMPBIAS 718..733
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 742..759
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 760..792
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 717
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 724
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 732
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 733
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 734
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT CARBOHYD 97
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 657
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 27..39
FT /evidence="ECO:0000250"
FT DISULFID 34..52
FT /evidence="ECO:0000250"
FT DISULFID 46..63
FT /evidence="ECO:0000250"
FT DISULFID 68..82
FT /evidence="ECO:0000250"
FT DISULFID 75..95
FT /evidence="ECO:0000250"
FT DISULFID 89..104
FT /evidence="ECO:0000250"
FT DISULFID 109..121
FT /evidence="ECO:0000250"
FT DISULFID 116..134
FT /evidence="ECO:0000250"
FT DISULFID 128..143
FT /evidence="ECO:0000250"
FT DISULFID 148..160
FT /evidence="ECO:0000250"
FT DISULFID 155..173
FT /evidence="ECO:0000250"
FT DISULFID 167..184
FT /evidence="ECO:0000250"
FT DISULFID 198..210
FT /evidence="ECO:0000250"
FT DISULFID 205..223
FT /evidence="ECO:0000250"
FT DISULFID 217..232
FT /evidence="ECO:0000250"
FT DISULFID 237..249
FT /evidence="ECO:0000250"
FT DISULFID 244..262
FT /evidence="ECO:0000250"
FT DISULFID 256..271
FT /evidence="ECO:0000250"
FT DISULFID 277..290
FT /evidence="ECO:0000250"
FT DISULFID 285..303
FT /evidence="ECO:0000250"
FT DISULFID 297..314
FT /evidence="ECO:0000250"
FT DISULFID 319..330
FT /evidence="ECO:0000250"
FT DISULFID 326..339
FT /evidence="ECO:0000250"
FT DISULFID 341..353
FT /evidence="ECO:0000250"
FT DISULFID 359..369
FT /evidence="ECO:0000250"
FT DISULFID 365..378
FT /evidence="ECO:0000250"
FT DISULFID 380..393
FT /evidence="ECO:0000250"
FT DISULFID 667..681
FT /evidence="ECO:0000250"
FT DISULFID 677..696
FT /evidence="ECO:0000250"
FT DISULFID 698..711
FT /evidence="ECO:0000250"
SQ SEQUENCE 879 AA; 96622 MW; E89F354E3F7C9005 CRC64;
MSTADLMLRW AIALLLAAAG VAAEDSCGKN EFQCRDGKCI VSKWVCDGSR ECPDGSDESP
ETCMSVTCRS GEFSCGGRVS RCIPDSWRCD GRTDCENGSD ELDCSPKTCS LDEFRCQDGK
CISRQFVCDQ DWDCLDGSDE AHCAATTCGP AHFRCNSSSC IPSLWACDGD RDCDDGSDEW
PQNCGAEDTA AEVVSSPCSS LEFHCGSSEC IHRSWVCDGA ADCKDKSDEE NCAVTTCRPD
EFQCADGSCI HGSRQCDREH DCKDMSDELG CINVTQCDGP NKFKCHSGEC ISLDKVCNSA
RDCRDWSDEP IKECKTNECL DNNGGCSHIC KDLKIGYECL CPSGFRLVDG HQCEDIDECQ
EPDTCSQLCV NLEGSFKCEC RAGFHMDPHT RVCKAVGSIG FLLFTNRHEV RKMTLDRSEY
TSLIPNLKNV VALDTEVANN RIYWSDLSQR KIYSAVMDQG TSLSYDAIIS GDLHAPDGLA
VDWIHGNIYW TDSVPGTVSV ADTKGVRRRT LFREKGSRPR AIVVDPVHGF MYWTDWGTPA
KIKKGGLNGV DIYSLVTEDI QWPNGITLDL PSGRLYWVDS KLHSISSIDV NGGGRKTILE
DEKQLAHPFS LAIYEDKVYW TDVLNEAIFS ANRLTGSDVN LVAKNLMSPE DIVLFHNVTQ
PRGVNWCEAT VLPNGGCQYM CLPAPQISAH SPKFTCACPD GMLLAKDMRS CLPEVDTVPT
TQGTSTIGPV VTTSAAVSLK RKEDPSATRH KEDPSATRHN EDPSATSTSR QPGDTPELST
VESVTVSSQV QGDMAGRGDE VQRHGVGFLS IFLPIALVAL LVFGAILLWR NWRLRNINSI
NFDNPVYQKT TEDEIHICRS QDGYTYPSRQ MVSLEDDVA
