ID LDLR_CRIGR Reviewed; 862 AA.
AC P35950; G3H6A6;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 2.
DT 27-MAR-2024, entry version 148.
DE RecName: Full=Low-density lipoprotein receptor;
DE Short=LDL receptor;
DE Flags: Precursor;
GN Name=LDLR; Synonyms=LDLA; ORFNames=I79_005860;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-843.
RC TISSUE=Ovary;
RX PubMed=1527478;
RA Bishop R.W.;
RT "Structure of the hamster low density lipoprotein receptor gene.";
RL J. Lipid Res. 33:549-557(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 568-615.
RX PubMed=3785227; DOI=10.1128/mcb.6.9.3268-3277.1986;
RA Sege R.D., Kozarsky K.F., Krieger M.;
RT "Characterization of a family of gamma-ray-induced CHO mutants demonstrates
RT that the ldlA locus is diploid and encodes the low-density lipoprotein
RT receptor.";
RL Mol. Cell. Biol. 6:3268-3277(1986).
CC -!- FUNCTION: Binds low density lipoprotein /LDL, the major cholesterol-
CC carrying lipoprotein of plasma, and transports it into cells by
CC endocytosis. In order to be internalized, the receptor-ligand complexes
CC must first cluster into clathrin-coated pits. Forms a ternary complex
CC with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL
CC internalization. {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 Interacts with PGRMC1 and TMEM97; the interaction increases LDL
CC internalization (By similarity). {ECO:0000250|UniProtKB:P01130,
CC 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; JH000173; EGV96177.1; -; Genomic_DNA.
DR EMBL; M94387; AAA51449.1; -; Genomic_DNA.
DR EMBL; M13877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A48908; QRHYLD.
DR RefSeq; NP_001233752.1; NM_001246823.1.
DR AlphaFoldDB; P35950; -.
DR SMR; P35950; -.
DR STRING; 10029.P35950; -.
DR GlyCosmos; P35950; 3 sites, No reported glycans.
DR PaxDb; 10029-NP_001233752-1; -.
DR GeneID; 100689399; -.
DR KEGG; cge:100689399; -.
DR CTD; 3949; -.
DR eggNOG; KOG1215; Eukaryota.
DR InParanoid; P35950; -.
DR OrthoDB; 3918101at2759; -.
DR Proteomes; UP000001075; Unassembled WGS sequence.
DR Proteomes; UP000694386; Unplaced.
DR Proteomes; UP001108280; Chromosome 4.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
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:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; IEA:UniProt.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR CDD; cd00054; EGF_CA; 1.
DR CDD; cd00112; LDLa; 6.
DR Gene3D; 4.10.1220.10; EGF-type module; 1.
DR Gene3D; 2.10.25.10; Laminin; 3.
DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 6.
DR Gene3D; 2.120.10.30; TolB, C-terminal domain; 1.
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 PANTHER; PTHR24270:SF21; LOW-DENSITY LIPOPROTEIN RECEPTOR; 1.
DR PANTHER; PTHR24270; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF14670; FXa_inhibition; 1.
DR Pfam; PF00057; Ldl_recept_a; 7.
DR Pfam; PF00058; Ldl_recept_b; 5.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 5.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00192; LDLa; 7.
DR SMART; SM00135; LY; 5.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF57424; LDL receptor-like module; 7.
DR SUPFAM; SSF63825; YWTD domain; 1.
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 3: Inferred from homology;
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..862
FT /note="Low-density lipoprotein receptor"
FT /id="PRO_0000017311"
FT TOPO_DOM 22..782
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P01131"
FT TRANSMEM 783..804
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 805..862
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 721..765
FT /note="Clustered O-linked oligosaccharides"
FT REGION 729..760
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 805..862
FT /note="Required for MYLIP-triggered down-regulation of
FT LDLR"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT MOTIF 817..822
FT /note="NPXY motif"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT MOD_RES 724
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35952"
FT MOD_RES 732
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35952"
FT CARBOHYD 97
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"
FT CONFLICT 158..159
FT /note="SA -> WP (in Ref. 2; AAA51449)"
FT /evidence="ECO:0000305"
FT CONFLICT 710
FT /note="S -> T (in Ref. 2; AAA51449)"
FT /evidence="ECO:0000305"
FT CONFLICT 738
FT /note="L -> C (in Ref. 2; AAA51449)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 862 AA; 95236 MW; 7B0DD369C4E33402 CRC64;
MSTADLRLRW AIALLLAAAG AAAEDTCDRN EFRCRDGKCI ASKWVCDGSP ECPDGSDESS
ETCMSVTCQS KEFSCGGRVS RCIPNSWRCD GQTDCENGSD EQGCAPKTCS QDEFRCQDGK
CISQKFVCDQ DQDCVDGSDE AHCQAATCGP AHFRCNSSAC IPSLWACDGD DDCEDGSDEW
PQNCGGRDTA AAWSSSPCSS LEFHCGSSEC IHRSWVCDGS ADCKDKSDEE HCVTATCRPD
EFQCADGTCI HGSRQCDREY DCKDMSDELG CINVTQCDGP NKFKCHSGEC IALDKVCDSM
RDCRDWSDEP IKDCRTNECL DNNGGCSHVC KDLKIGYECL CPNGFQLVDQ HRCEDIDECQ
EPDTCDQLCV NLEGSYKCEC RAGFHMDPHT RVCKAVGSVA YLLFTNRHEV RKMTLDRSEY
TSLIPNLKNV VALDTEVANN RIYWSDLSQG KIYSALMDQA PTLSYDTIIS GDLQAPDGLA
VDWIHGNIYW TDSVPGSVSV ADTKGIRRRT LFQEKGSRPR DIVVDPVHGF MYWTDWGTPA
KIKKGGLNGV DIYSLVTEDI QWPNGITLDI PSGRLYWVDS KLHSISSIDV NGGNRKTILE
DEKQLAHPFS LAIYEDKVFW TDVINEAIFS ANRLTGSDVN LVAENLLSPE DIVLFHNITQ
PRGVNWCERT ALPNGGCQYL CLPAPQINPH SPKFTCACPD GMLLAKDMRS CLTEVAPVLT
TQGTSTIRPE ITAGAEGLPK HKEDQSASST SRQPALSTVE SVTMSHQVQG DRRNEERPQG
VGVLSITLPI ALVILLVFGA ILLWRNWRLR NINSINFDNP VYQKTTEDEL HICRSQDGYS
YPSVSMPFCG REEAASKLKD RS
//
