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Protein

Low-density lipoprotein receptor

Gene

Ldlr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits.By similarity

GO - Molecular functioni

  • amyloid-beta binding Source: ARUK-UCL
  • calcium ion binding Source: InterPro
  • identical protein binding Source: MGI
  • low-density lipoprotein particle binding Source: MGI
  • low-density lipoprotein particle receptor activity Source: MGI
  • protease binding Source: MGI
  • very-low-density lipoprotein particle receptor activity Source: MGI

GO - Biological processi

  • amyloid-beta clearance Source: ARUK-UCL
  • cellular response to fatty acid Source: BHF-UCL
  • cellular response to low-density lipoprotein particle stimulus Source: MGI
  • cholesterol homeostasis Source: MGI
  • cholesterol import Source: BHF-UCL
  • cholesterol metabolic process Source: MGI
  • cholesterol transport Source: MGI
  • intestinal cholesterol absorption Source: MGI
  • lipid metabolic process Source: MGI
  • lipoprotein catabolic process Source: MGI
  • lipoprotein metabolic process Source: MGI
  • long-term memory Source: ARUK-UCL
  • low-density lipoprotein particle clearance Source: MGI
  • negative regulation of amyloid fibril formation Source: ARUK-UCL
  • negative regulation of astrocyte activation Source: ARUK-UCL
  • negative regulation of gene expression Source: BHF-UCL
  • negative regulation of microglial cell activation Source: ARUK-UCL
  • negative regulation of protein metabolic process Source: ARUK-UCL
  • phospholipid transport Source: BHF-UCL
  • positive regulation of amyloid-beta clearance Source: ARUK-UCL
  • positive regulation of endocytosis Source: ARUK-UCL
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of lipoprotein particle clearance Source: ARUK-UCL
  • positive regulation of lysosomal protein catabolic process Source: ARUK-UCL
  • positive regulation of triglyceride biosynthetic process Source: BHF-UCL
  • receptor-mediated endocytosis Source: ARUK-UCL
  • receptor-mediated endocytosis involved in cholesterol transport Source: MGI
  • regulation of cholesterol homeostasis Source: MGI
  • regulation of cholesterol metabolic process Source: ARUK-UCL
  • regulation of phosphatidylcholine catabolic process Source: BHF-UCL
  • regulation of protein metabolic process Source: ARUK-UCL
  • response to caloric restriction Source: ARUK-UCL

Keywordsi

Molecular functionReceptor
Biological processCholesterol metabolism, Endocytosis, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport

Enzyme and pathway databases

ReactomeiR-MMU-8856825 Cargo recognition for clathrin-mediated endocytosis
R-MMU-8856828 Clathrin-mediated endocytosis
R-MMU-8964026 Chylomicron clearance
R-MMU-8964038 LDL clearance

Names & Taxonomyi

Protein namesi
Recommended name:
Low-density lipoprotein receptor
Short name:
LDL receptor
Gene namesi
Name:Ldlr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:96765 Ldlr

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 790ExtracellularBy similarityAdd BLAST769
Transmembranei791 – 812HelicalSequence analysisAdd BLAST22
Topological domaini813 – 862Cytoplasmic1 PublicationAdd BLAST50

Keywords - Cellular componenti

Cell membrane, Coated pit, Endosome, Golgi apparatus, LDL, Lysosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21By similarityAdd BLAST21
ChainiPRO_000001731322 – 862Low-density lipoprotein receptorAdd BLAST841

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi34 ↔ 52By similarity
Disulfide bondi46 ↔ 63By similarity
Disulfide bondi68 ↔ 82By similarity
Disulfide bondi75 ↔ 95By similarity
Disulfide bondi89 ↔ 104By similarity
Glycosylationi97N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi109 ↔ 121By similarity
Disulfide bondi116 ↔ 134By similarity
Disulfide bondi128 ↔ 143By similarity
Disulfide bondi148 ↔ 160By similarity
Disulfide bondi155 ↔ 173By similarity
Disulfide bondi167 ↔ 184By similarity
Disulfide bondi198 ↔ 210By similarity
Disulfide bondi205 ↔ 223By similarity
Disulfide bondi217 ↔ 232By similarity
Disulfide bondi237 ↔ 249By similarity
Disulfide bondi244 ↔ 262By similarity
Disulfide bondi256 ↔ 271By similarity
Glycosylationi273N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi277 ↔ 290By similarity
Disulfide bondi285 ↔ 303By similarity
Disulfide bondi297 ↔ 314By similarity
Disulfide bondi319 ↔ 330By similarity
Disulfide bondi326 ↔ 339By similarity
Disulfide bondi341 ↔ 353By similarity
Disulfide bondi359 ↔ 369By similarity
Disulfide bondi365 ↔ 378By similarity
Disulfide bondi380 ↔ 393By similarity
Glycosylationi462N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi667 ↔ 682By similarity
Disulfide bondi678 ↔ 697By similarity
Disulfide bondi699 ↔ 712By similarity
Modified residuei725PhosphothreonineBy similarity1
Modified residuei733PhosphothreonineBy similarity1
Modified residuei735PhosphoserineBy similarity1

Post-translational modificationi

N- and O-glycosylated.By similarity
Ubiquitinated by MYLIP leading to degradation.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP35951
PaxDbiP35951
PeptideAtlasiP35951
PRIDEiP35951

PTM databases

iPTMnetiP35951
PhosphoSitePlusiP35951
SwissPalmiP35951

Expressioni

Gene expression databases

BgeeiENSMUSG00000032193
CleanExiMM_LDLR
ExpressionAtlasiP35951 baseline and differential
GenevisibleiP35951 MM

Interactioni

Subunit structurei

Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (PubMed:11247302). Interacts (via NPXY motif) with LDLRAP1 (via PID domain) (By similarity). Interacts with ARRB1 (By similarity). Interacts with SNX17 (PubMed:12169628). Interacts with the full-length immature form of PCSK9 (via C-terminus) (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201133, 2 interactors
IntActiP35951, 2 interactors
MINTiP35951
STRINGi10090.ENSMUSP00000034713

Structurei

3D structure databases

ProteinModelPortaliP35951
SMRiP35951
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 65LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST41
Domaini66 – 106LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST41
Domaini107 – 145LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST39
Domaini146 – 186LDL-receptor class A 4PROSITE-ProRule annotationAdd BLAST41
Domaini196 – 234LDL-receptor class A 5PROSITE-ProRule annotationAdd BLAST39
Domaini235 – 273LDL-receptor class A 6PROSITE-ProRule annotationAdd BLAST39
Domaini275 – 314LDL-receptor class A 7PROSITE-ProRule annotationAdd BLAST40
Domaini315 – 354EGF-like 1PROSITE-ProRule annotationAdd BLAST40
Domaini355 – 394EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST40
Repeati398 – 439LDL-receptor class B 1Add BLAST42
Repeati440 – 485LDL-receptor class B 2Add BLAST46
Repeati486 – 528LDL-receptor class B 3Add BLAST43
Repeati529 – 572LDL-receptor class B 4Add BLAST44
Repeati573 – 615LDL-receptor class B 5Add BLAST43
Repeati616 – 658LDL-receptor class B 6Add BLAST43
Domaini663 – 713EGF-like 3PROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni722 – 770Clustered O-linked oligosaccharidesAdd BLAST49
Regioni813 – 862Required for MYLIP-triggered down-regulation of LDLRBy similarityAdd BLAST50

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi825 – 830NPXY motifBy similarity6

Domaini

The NPXY motif mediates the interaction with the clathrin adapter DAB2 and with LDLRAP1 which are involved in receptor internalization. A few residues outside the motif also play a role in the interaction.1 Publication

Sequence similaritiesi

Belongs to the LDLR family.Curated

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410KD0U Eukaryota
ENOG410Z5FJ LUCA
GeneTreeiENSGT00760000118968
HOGENOMiHOG000115656
HOVERGENiHBG006250
InParanoidiP35951
KOiK12473
OMAiINVTLCE
OrthoDBiEOG091G01MX
TreeFamiTF351700

Family and domain databases

CDDicd00112 LDLa, 7 hits
Gene3Di2.120.10.30, 1 hit
InterProiView protein in InterPro
IPR011042 6-blade_b-propeller_TolB-like
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR009030 Growth_fac_rcpt_cys_sf
IPR036055 LDL_receptor-like_sf
IPR023415 LDLR_class-A_CS
IPR000033 LDLR_classB_rpt
IPR002172 LDrepeatLR_classA_rpt
PfamiView protein in Pfam
PF07645 EGF_CA, 1 hit
PF00057 Ldl_recept_a, 7 hits
PF00058 Ldl_recept_b, 5 hits
PRINTSiPR00261 LDLRECEPTOR
SMARTiView protein in SMART
SM00181 EGF, 5 hits
SM00179 EGF_CA, 2 hits
SM00192 LDLa, 7 hits
SM00135 LY, 5 hits
SUPFAMiSSF57184 SSF57184, 1 hit
SSF57424 SSF57424, 6 hits
PROSITEiView protein in PROSITE
PS00010 ASX_HYDROXYL, 1 hit
PS01186 EGF_2, 2 hits
PS50026 EGF_3, 2 hits
PS01187 EGF_CA, 1 hit
PS01209 LDLRA_1, 7 hits
PS50068 LDLRA_2, 7 hits
PS51120 LDLRB, 5 hits

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P35951-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTADLMRRW VIALLLAAAG VAAEDSCSRN EFQCRDGKCI ASKWVCDGSP
60 70 80 90 100
ECPDGSDESP ETCMSVTCQS NQFSCGGRVS RCIPDSWRCD GQVDCENDSD
110 120 130 140 150
EQGCPPKTCS QDDFRCQDGK CISPQFVCDG DRDCLDGSDE AHCQATTCGP
160 170 180 190 200
AHFRCNSSIC IPSLWACDGD VDCVDGSDEW PQNCQGRDTA SKGVSSPCSS
210 220 230 240 250
LEFHCGSSEC IHRSWVCDGE ADCKDKSDEE HCAVATCRPD EFQCADGSCI
260 270 280 290 300
HGSRQCDREH DCKDMSDELG CVNVTQCDGP NKFKCHSGEC ISLDKVCDSA
310 320 330 340 350
RDCQDWSDEP IKECKTNECL DNNGGCSHIC KDLKIGSECL CPSGFRLVDL
360 370 380 390 400
HRCEDIDECQ EPDTCSQLCV NLEGSYKCEC QAGFHMDPHT RVCKAVGSIG
410 420 430 440 450
YLLFTNRHEV RKMTLDRSEY TSLLPNLKNV VALDTEVTNN RIYWSDLSQK
460 470 480 490 500
KIYSALMDQA PNLSYDTIIS EDLHAPDGLA VDWIHRNIYW TDSVPGSVSV
510 520 530 540 550
ADTKGVKRRT LFQEAGSRPR AIVVDPVHGF MYWTDWGTPA KIKKGGLNGV
560 570 580 590 600
DIHSLVTENI QWPNGITLDL SSGRLYWVDS KLHSISSIDV NGGNRKTILE
610 620 630 640 650
DENRLAHPFS LAIYEDKVYW TDVINEAIFS ANRLTGSDVN LVAENLLSPE
660 670 680 690 700
DIVLFHKVTQ PRGVNWCETT ALLPNGGCQY LCLPAPQIGP HSPKFTCACP
710 720 730 740 750
DGMLLAKDMR SCLTEVDTVL TTQGTSAVRP VVTASATRPP KHSEDLSAPS
760 770 780 790 800
TPRQPVDTPG LSTVASVTVS HQVQGDMAGR GNEEQPHGMR FLSIFFPIAL
810 820 830 840 850
VALLVLGAVL LWRNWRLKNI NSINFDNPVY QKTTEDELHI CRSQDGYTYP
860
SRQMVSLEDD VA
Length:862
Mass (Da):94,947
Last modified:February 6, 2013 - v2
Checksum:i43E7D6A293BE609C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti23A → V in CAA79581 (PubMed:8466528).Curated1
Sequence conflicti27C → G in CAA79581 (PubMed:8466528).Curated1
Sequence conflicti61E → K in CAA79581 (PubMed:8466528).Curated1
Sequence conflicti144Q → P in CAA79581 (PubMed:8466528).Curated1
Sequence conflicti156N → K in CAA79581 (PubMed:8466528).Curated1
Sequence conflicti178D → H in CAA79581 (PubMed:8466528).Curated1
Sequence conflicti186 – 187GR → AE in CAA79581 (PubMed:8466528).Curated2
Sequence conflicti819N → NIT in CAA79581 (PubMed:8466528).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z19521 mRNA Translation: CAA79581.1
X64414 mRNA Translation: CAA45759.1
AC161371 Genomic DNA No translation available.
CH466522 Genomic DNA Translation: EDL25212.1
BC053041 mRNA Translation: AAH53041.1
CCDSiCCDS22910.1
PIRiI48623 QRMSLD
RefSeqiNP_001239587.1, NM_001252658.1
NP_001239588.1, NM_001252659.1
NP_034830.2, NM_010700.3
UniGeneiMm.3213

Genome annotation databases

EnsembliENSMUST00000034713; ENSMUSP00000034713; ENSMUSG00000032193
GeneIDi16835
KEGGimmu:16835
UCSCiuc009omh.2 mouse

Similar proteinsi

Entry informationi

Entry nameiLDLR_MOUSE
AccessioniPrimary (citable) accession number: P35951
Secondary accession number(s): Q6GTJ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 6, 2013
Last modified: April 25, 2018
This is version 178 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health