LDLR_PIG
ID LDLR_PIG Reviewed; 811 AA.
AC Q28832; O62817; O77619; Q9TV95;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 2.
DT 25-MAY-2022, entry version 142.
DE RecName: Full=Low-density lipoprotein receptor;
DE Short=LDL receptor;
DE Flags: Fragment;
GN Name=LDLR;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC17444.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-801, AND VARIANT FH CYS-84.
RC TISSUE=Liver {ECO:0000312|EMBL:AAC17444.1};
RX PubMed=9556295;
RX DOI=10.1002/(sici)1096-8628(19980413)76:5<379::aid-ajmg3>3.0.co;2-i;
RA Hasler-Rapacz J., Ellegren H., Fridolfsson A.-K., Kirkpatrick B., Kirk S.,
RA Andersson L., Rapacz J.;
RT "Identification of a mutation in the low density lipoprotein receptor gene
RT associated with recessive familial hypercholesterolemia in swine.";
RL Am. J. Med. Genet. 76:379-386(1998).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAD13300.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-801, AND VARIANT FH CYS-84.
RC TISSUE=Skin fibroblast {ECO:0000269|PubMed:10064736};
RX PubMed=10064736;
RA Grunwald K.A.A., Schueler K., Uelmen P.J., Lipton B.A., Kaiser M.,
RA Buhman K., Attie A.D.;
RT "Identification of a novel Arg-->Cys mutation in the LDL receptor that
RT contributes to spontaneous hypercholesterolemia in pigs.";
RL J. Lipid Res. 40:475-485(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 765-811.
RC TISSUE=Corpus luteum;
RX PubMed=8344216; DOI=10.1210/endo.133.2.8344216;
RA Garmey J.C., Day R.N., Day K.H., Veldhuis J.D.;
RT "Mechanisms of regulation of ovarian sterol metabolism by insulin-like
RT growth factor type II: in vitro studies with swine granulosa cells.";
RL Endocrinology 133:800-808(1993).
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: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 -!- DISEASE: Note=Defects in LDLR are the cause of familial
CC hypercholesterolemia (FH). {ECO:0000269|PubMed:10064736,
CC ECO:0000269|PubMed:9556295}.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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DR EMBL; AF065990; AAC17444.1; -; mRNA.
DR EMBL; AF067952; AAC39254.1; -; mRNA.
DR EMBL; AF118147; AAD13300.1; -; mRNA.
DR EMBL; S64272; AAB27716.1; -; mRNA.
DR RefSeq; NP_001193283.1; NM_001206354.2.
DR AlphaFoldDB; Q28832; -.
DR SMR; Q28832; -.
DR STRING; 9823.ENSSSCP00000030589; -.
DR PaxDb; Q28832; -.
DR PRIDE; Q28832; -.
DR GeneID; 396801; -.
DR KEGG; ssc:396801; -.
DR CTD; 3949; -.
DR eggNOG; KOG1215; Eukaryota.
DR HOGENOM; CLU_3177973_0_0_1; -.
DR InParanoid; Q28832; -.
DR OrthoDB; 359795at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR Genevisible; Q28832; SS.
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:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0071813; F:lipoprotein particle binding; IBA:GO_Central.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; IBA:GO_Central.
DR GO; GO:0042632; P:cholesterol homeostasis; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IBA:GO_Central.
DR GO; GO:0090118; P:receptor-mediated endocytosis involved in cholesterol transport; IBA:GO_Central.
DR GO; GO:0045056; P:transcytosis; IMP:AgBase.
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; 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; Disease variant;
KW Disulfide bond; EGF-like domain; Endocytosis; Endosome; Glycoprotein;
KW Golgi apparatus; LDL; Lipid metabolism; Lipid transport; Lipoprotein;
KW Lysosome; Membrane; Receptor; Reference proteome; Repeat;
KW Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation.
FT CHAIN <1..811
FT /note="Low-density lipoprotein receptor"
FT /id="PRO_0000191076"
FT TOPO_DOM <1..743
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P01131"
FT TRANSMEM 744..764
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 765..811
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DOMAIN <1..33
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 36..74
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 77..113
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 116..154
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 167..203
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 206..242
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 246..285
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 285..324
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 325..357
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 368..409
FT /note="LDL-receptor class B 1"
FT /evidence="ECO:0000255"
FT REPEAT 410..456
FT /note="LDL-receptor class B 2"
FT REPEAT 457..499
FT /note="LDL-receptor class B 3"
FT REPEAT 500..543
FT /note="LDL-receptor class B 4"
FT REPEAT 544..587
FT /note="LDL-receptor class B 5"
FT /evidence="ECO:0000255"
FT REPEAT 588..629
FT /note="LDL-receptor class B 6"
FT REGION 686..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 692..722
FT /note="Clustered O-linked oligosaccharides"
FT REGION 765..811
FT /note="Required for MYLIP-triggered down-regulation of
FT LDLR"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT MOTIF 777..782
FT /note="NPXY motif"
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 243
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 628
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 699
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 3..21
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 15..32
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 37..51
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 44..64
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 58..73
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 78..90
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 85..103
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 97..112
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 117..129
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 124..142
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 136..153
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 168..180
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 175..193
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 187..202
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 207..219
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 214..232
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 226..241
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 247..260
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 255..273
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 267..284
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 289..300
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 296..309
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 311..323
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 329..339
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 335..348
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 350..363
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 638..652
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 648..667
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT DISULFID 669..682
FT /evidence="ECO:0000250|UniProtKB:P01130"
FT VARIANT 84
FT /note="R -> C (in FH; recessive)"
FT /evidence="ECO:0000269|PubMed:10064736,
FT ECO:0000269|PubMed:9556295"
FT CONFLICT 235
FT /note="M -> L (in Ref. 2; AAD13300)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="A -> V (in Ref. 2; AAD13300)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="D -> N (in Ref. 2; AAD13300)"
FT /evidence="ECO:0000305"
FT CONFLICT 594
FT /note="I -> V (in Ref. 2; AAD13300)"
FT /evidence="ECO:0000305"
FT NON_TER 1
SQ SEQUENCE 811 AA; 89920 MW; 6FE24DF0EA307904 CRC64;
FQCQDGKCIS YKWICDGNTE CKDGSDESLE TCMSVTCKIG DFSCGGRVNR CIPESWRCDG
QQDCENGSDE EGCSPKTCSQ DEFRCQDGKC IAPKFVCDSD RDCLDGSDEA SCPTPTCGPA
SFQCNSSTCI PELWACDGDP DCEDGSDEWP QHCRSHSSSL PERSNNPCSA LEFHCHSGEC
IHSSWRCDGD TDCKDKSDEE NCDVATCRPD EFQCSDGTCI HGSRQCDREY DCKDMSDEQG
CVNATLCEGP NKFKCQSGEC ISLDKVCNSV RDCRDWSDEP LKECGTNECL DNKGGCSHIC
NDLKIGYECL CPEGFQLVDK HRCEDIDECQ DPDACSQICV NLEGSYKCQC EEGFQLEPLT
KACKAIGTIA YLFFTNRHEV RKMTLDRSEY TSLIPNLKNV VALDTEVASN RIYWSDLSQR
KIYSTQIDRA PSFSSYDTII GEDLQAPDGL AVDWIHSNIY WTDSILGTVS VADTKGVKRK
TLFQEKGSKP RAIVVDPVHG FMYWTDWGTP AKIKKGGLNG VDVYSLVTED IQWPNGITLD
LSGGRLYWVD SKLHSISSID VNGGNRKTVL EDKTKLAHPF SLAIFEDKVF WTDIINEAIF
SANRLTGSDI HLMAENLLSP EDIVLFHNLT QPRGVNWCER TALQNGGCQY LCLPAPQINP
RSPKFTCACP DGMLLAKDMR SCLTETEPAG TTQGPSMVNS TAVGPKHTAS SELTTAESVT
MSQHALGDVA GRGVTEKPQS VGALYIVLPI ALLILLFFGT FLLWKNWRLK SINSINFDNP
VYQKTTEDEV HICRSQDGYT YPSRQMVSLE D
