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Protein

Low-density lipoprotein receptor

Gene

Ldlr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

  • cellular response to fatty acid Source: BHF-UCL
  • 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
  • low-density lipoprotein particle clearance Source: BHF-UCL
  • negative regulation of gene expression Source: BHF-UCL
  • phospholipid transport Source: BHF-UCL
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of triglyceride biosynthetic process Source: BHF-UCL
  • regulation of cholesterol homeostasis Source: MGI
  • regulation of phosphatidylcholine catabolic process Source: BHF-UCL
  • retinoid metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Cholesterol metabolism, Endocytosis, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport

Enzyme and pathway databases

ReactomeiR-MMU-171052. LDL-mediated lipid transport.
R-MMU-174800. Chylomicron-mediated lipid transport.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-MMU-8856828. Clathrin-mediated endocytosis.
R-MMU-975634. Retinoid metabolism and transport.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:96765. Ldlr.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein By similarity
  • Membraneclathrin-coated pit 1 Publication
  • Golgi apparatus By similarity
  • Early endosome By similarity
  • Late endosome By similarity
  • Lysosome By similarity

  • Note: Rapidly endocytosed upon ligand binding.1 Publication

Topology

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

GO - Cellular componenti

Complete GO annotation...

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...)Sequence 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...)Sequence 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...)Sequence 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.
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.
MINTiMINT-1541606.
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
Contains 3 EGF-like domains.PROSITE-ProRule annotation
Contains 7 LDL-receptor class A domains.PROSITE-ProRule annotation
Contains 6 LDL-receptor class B repeats.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410KD0U. Eukaryota.
ENOG410Z5FJ. LUCA.
GeneTreeiENSGT00760000118968.
HOGENOMiHOG000115656.
HOVERGENiHBG006250.
InParanoidiP35951.
KOiK12473.
OMAiKDGSDEW.
OrthoDBiEOG091G01MX.
TreeFamiTF351700.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
4.10.400.10. 7 hits.
InterProiIPR011042. 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_.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
[Graphical view]
PfamiPF07645. EGF_CA. 1 hit.
PF00057. Ldl_recept_a. 7 hits.
PF00058. Ldl_recept_b. 5 hits.
[Graphical view]
PRINTSiPR00261. LDLRECEPTOR.
SMARTiSM00181. EGF. 5 hits.
SM00179. EGF_CA. 2 hits.
SM00192. LDLa. 7 hits.
SM00135. LY. 5 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF57424. SSF57424. 6 hits.
PROSITEiPS00010. 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.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP35951.
SMRiP35951.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201133. 2 interactors.
IntActiP35951. 2 interactors.
MINTiMINT-1541606.
STRINGi10090.ENSMUSP00000034713.

PTM databases

iPTMnetiP35951.
PhosphoSitePlusiP35951.
SwissPalmiP35951.

Proteomic databases

EPDiP35951.
PaxDbiP35951.
PeptideAtlasiP35951.
PRIDEiP35951.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3949.
MGIiMGI:96765. Ldlr.

Phylogenomic databases

eggNOGiENOG410KD0U. Eukaryota.
ENOG410Z5FJ. LUCA.
GeneTreeiENSGT00760000118968.
HOGENOMiHOG000115656.
HOVERGENiHBG006250.
InParanoidiP35951.
KOiK12473.
OMAiKDGSDEW.
OrthoDBiEOG091G01MX.
TreeFamiTF351700.

Enzyme and pathway databases

ReactomeiR-MMU-171052. LDL-mediated lipid transport.
R-MMU-174800. Chylomicron-mediated lipid transport.
R-MMU-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-MMU-8856828. Clathrin-mediated endocytosis.
R-MMU-975634. Retinoid metabolism and transport.

Miscellaneous databases

PROiP35951.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032193.
CleanExiMM_LDLR.
GenevisibleiP35951. MM.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
4.10.400.10. 7 hits.
InterProiIPR011042. 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_.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
[Graphical view]
PfamiPF07645. EGF_CA. 1 hit.
PF00057. Ldl_recept_a. 7 hits.
PF00058. Ldl_recept_b. 5 hits.
[Graphical view]
PRINTSiPR00261. LDLRECEPTOR.
SMARTiSM00181. EGF. 5 hits.
SM00179. EGF_CA. 2 hits.
SM00192. LDLa. 7 hits.
SM00135. LY. 5 hits.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF57424. SSF57424. 6 hits.
PROSITEiPS00010. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLDLR_MOUSE
AccessioniPrimary (citable) accession number: P35951
Secondary accession number(s): Q6GTJ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 6, 2013
Last modified: November 30, 2016
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.