LDLR_RABIT
ID LDLR_RABIT Reviewed; 837 AA.
AC P20063;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 25-MAY-2022, entry version 144.
DE RecName: Full=Low-density lipoprotein receptor;
DE Short=LDL receptor;
DE Flags: Fragment;
GN Name=LDLR;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=3010466; DOI=10.1126/science.3010466;
RA Yamamoto T., Bishop R.W., Brown M.S., Goldstein J.L., Russell D.W.;
RT "Deletion in cysteine-rich region of LDL receptor impedes transport to cell
RT surface in WHHL rabbit.";
RL Science 232:1230-1237(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:3010466};
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; M11501; AAA31383.1; -; mRNA.
DR PIR; A29512; A29512.
DR AlphaFoldDB; P20063; -.
DR SMR; P20063; -.
DR PRIDE; P20063; -.
DR eggNOG; KOG1215; Eukaryota.
DR InParanoid; P20063; -.
DR Proteomes; UP000001811; Unplaced.
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: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:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR CDD; cd00112; LDLa; 7.
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; 5.
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; 1.
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 2: Evidence at transcript 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; Steroid metabolism;
KW Sterol metabolism; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT CHAIN <1..837
FT /note="Low-density lipoprotein receptor"
FT /id="PRO_0000191077"
FT TOPO_DOM <1..765
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P01131"
FT TRANSMEM 766..787
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 788..837
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DOMAIN 12..52
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 53..93
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 94..132
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 133..173
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 182..220
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 221..259
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 261..300
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 301..340
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 341..380
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 384..425
FT /note="LDL-receptor class B 1"
FT REPEAT 426..472
FT /note="LDL-receptor class B 2"
FT REPEAT 473..515
FT /note="LDL-receptor class B 3"
FT REPEAT 516..559
FT /note="LDL-receptor class B 4"
FT REPEAT 560..602
FT /note="LDL-receptor class B 5"
FT REPEAT 603..645
FT /note="LDL-receptor class B 6"
FT DOMAIN 650..699
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 709..731
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 788..837
FT /note="Required for MYLIP-triggered down-regulation of
FT LDLR"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT MOTIF 800..805
FT /note="NPXY motif"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT MOD_RES 720
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35952"
FT MOD_RES 722
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35952"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 644
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 14..26
FT /evidence="ECO:0000250"
FT DISULFID 21..39
FT /evidence="ECO:0000250"
FT DISULFID 33..50
FT /evidence="ECO:0000250"
FT DISULFID 55..69
FT /evidence="ECO:0000250"
FT DISULFID 62..82
FT /evidence="ECO:0000250"
FT DISULFID 76..91
FT /evidence="ECO:0000250"
FT DISULFID 96..108
FT /evidence="ECO:0000250"
FT DISULFID 103..121
FT /evidence="ECO:0000250"
FT DISULFID 115..130
FT /evidence="ECO:0000250"
FT DISULFID 135..147
FT /evidence="ECO:0000250"
FT DISULFID 142..160
FT /evidence="ECO:0000250"
FT DISULFID 154..171
FT /evidence="ECO:0000250"
FT DISULFID 184..196
FT /evidence="ECO:0000250"
FT DISULFID 191..209
FT /evidence="ECO:0000250"
FT DISULFID 203..218
FT /evidence="ECO:0000250"
FT DISULFID 223..235
FT /evidence="ECO:0000250"
FT DISULFID 230..248
FT /evidence="ECO:0000250"
FT DISULFID 242..257
FT /evidence="ECO:0000250"
FT DISULFID 263..276
FT /evidence="ECO:0000250"
FT DISULFID 271..289
FT /evidence="ECO:0000250"
FT DISULFID 283..300
FT /evidence="ECO:0000250"
FT DISULFID 305..316
FT /evidence="ECO:0000250"
FT DISULFID 312..325
FT /evidence="ECO:0000250"
FT DISULFID 327..339
FT /evidence="ECO:0000250"
FT DISULFID 345..355
FT /evidence="ECO:0000250"
FT DISULFID 351..364
FT /evidence="ECO:0000250"
FT DISULFID 366..379
FT /evidence="ECO:0000250"
FT DISULFID 654..668
FT /evidence="ECO:0000250"
FT DISULFID 664..683
FT /evidence="ECO:0000250"
FT DISULFID 685..698
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 837 AA; 91407 MW; ED8D231E234400A9 CRC64;
LLAAAAGAAA GDKCGRNEFQ CRNGKCISYK WVCDGSSECQ DGSDEWEQTC MSLTCKSDDF
SCGGRLNRCI PGHWKCDGQQ DCEDGSDELG CAPKTCSQDE FRCAEGACIS RLFACDGEPD
CPDGSDEASC APSTCGPAHF RCNSSSCVPA LWACDGEPDC DDGSDEWPAR CGARPSPQPG
RGPCSRHEFH CGSGECVHAS WRCDGDADCR DGSDERDCAA ATCRPDEFQC SDGTCIHGSR
QCDQQQDCGD MSDEVGCVNV TLCEGPDKFK CHSGECISLD KVCNSARDCQ DWSDEPIKEC
ATNECMRGNG GCSHTCFDLR IGHECHCPKG YRLVDQRRCE DINECEDPDI CSQLCVNLAG
SYKCECRAGF QLDPHSQACK AVDSIAYLFF TNRHEVRKMT LDRSEYTSLI ANLKNVVALD
AEVASNRIYW SDLSQRKIYS AQIDGAHGFP AYDTVISSDL QAPDGLAVDW IHGHIYWTDS
VLGTVSVADT RGFRRKTLFR QEGSKPRAIV VDPAHGFMYW TDWGVPAKIE KGGLNGVDVY
SLVTEDIQWP NGITLDLSSG RLYWVDSKLH SISSIDVNGG NRKTVLEDEQ RLAHPFSLAI
FEDKVFWTDV INEAIFSANR LTGSDVHLVA ENLLSPEDIV LFHNLTQPRG VNWCEKTALP
NGGCQYLCLP APQINSHSPK FTCACPDGTL LAADMRSCRT EADVILSTQR ASTAARPQLT
GSPAGTTQEP LTEPTLSTLE TATTSQQALH NADGRGSEGT PRSVGALSVV LPIALLGLLC
LGALVLWKNW RLRSVHSINF DNPVYQKTTE DEVHICRSQD GYTYPSRQMV SLEDDVA
