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P35951 (LDLR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Low-density lipoprotein receptor

Short name=LDL receptor
Gene names
Name:Ldlr
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length862 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Interacts with LDLRAP1, ARRB1, SNX17. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts with the full length immature form of PCSK9 (via C-terminus). Ref.6 Ref.7

Subcellular location

Cell membrane; Single-pass type I membrane protein. Endomembrane system; Single-pass type I membrane protein. Membraneclathrin-coated pit; Single-pass type I membrane protein By similarity. Golgi apparatus By similarity. Early endosome By similarity. Late endosome By similarity. Cell surface By similarity. Lysosome By similarity. Note: Found distributed from the plasma membrane to intracellular compartments. Localizes to the Golgi apparatus, early and late endosomes/lysosomes and cell surface in the presence of PCSK9 By similarity.

Domain

The NPXY motif mediates the interaction with the clathrin adaptor DAB2 involved in receptor internalization. Ref.6

Post-translational modification

Ubiquitinated by MYLIP leading to degradation By similarity.

Sequence similarities

Belongs to the LDLR family.

Contains 3 EGF-like domains.

Contains 7 LDL-receptor class A domains.

Contains 6 LDL-receptor class B repeats.

Ontologies

Keywords
   Biological processCholesterol metabolism
Endocytosis
Lipid metabolism
Lipid transport
Steroid metabolism
Sterol metabolism
Transport
   Cellular componentCell membrane
Coated pit
Endosome
Golgi apparatus
LDL
Lysosome
Membrane
   DomainEGF-like domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol homeostasis

Inferred from mutant phenotype PubMed 12746448PubMed 9788969. Source: MGI

cholesterol import

Inferred from mutant phenotype PubMed 18175806. Source: BHF-UCL

cholesterol metabolic process

Inferred from mutant phenotype PubMed 17071966. Source: MGI

cholesterol transport

Inferred from mutant phenotype PubMed 17148552. Source: MGI

intestinal cholesterol absorption

Inferred from electronic annotation. Source: Ensembl

lipid metabolic process

Inferred from genetic interaction PubMed 11120757. Source: MGI

lipoprotein catabolic process

Inferred from direct assay PubMed 15741654. Source: MGI

lipoprotein metabolic process

Inferred from genetic interaction PubMed 11120757PubMed 13130124. Source: MGI

low-density lipoprotein particle clearance

Inferred from mutant phenotype PubMed 18175806. Source: BHF-UCL

phospholipid transport

Inferred from mutant phenotype PubMed 18175806. Source: BHF-UCL

positive regulation of triglyceride biosynthetic process

Inferred from mutant phenotype PubMed 18175806. Source: BHF-UCL

receptor-mediated endocytosis

Inferred from direct assay PubMed 12072432PubMed 16166565. Source: GOC

regulation of cholesterol homeostasis

Inferred from mutant phenotype PubMed 23580231. Source: MGI

regulation of phosphatidylcholine catabolic process

Inferred from mutant phenotype PubMed 18175806. Source: BHF-UCL

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

cell surface

Inferred from sequence or structural similarity. Source: UniProtKB

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

early endosome

Inferred from sequence or structural similarity. Source: UniProtKB

endosome

Inferred from direct assay PubMed 12746448. Source: MGI

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

late endosome

Inferred from sequence or structural similarity. Source: UniProtKB

low-density lipoprotein particle

Inferred from electronic annotation. Source: UniProtKB-KW

lysosome

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

receptor complex

Inferred from sequence orthology PubMed 23382219. Source: MGI

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

low-density lipoprotein particle binding

Inferred from direct assay PubMed 15741654PubMed 7848292. Source: MGI

low-density lipoprotein receptor activity

Inferred from direct assay PubMed 12072432. Source: MGI

protein binding

Inferred from physical interaction PubMed 12746448. Source: MGI

very-low-density lipoprotein particle receptor activity

Inferred from direct assay PubMed 16166565. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 By similarity
Chain22 – 862841Low-density lipoprotein receptor
PRO_0000017313

Regions

Topological domain22 – 790769Extracellular Potential
Transmembrane791 – 81222Helical; Potential
Topological domain813 – 86250Cytoplasmic Potential
Domain25 – 6541LDL-receptor class A 1
Domain66 – 10641LDL-receptor class A 2
Domain107 – 14539LDL-receptor class A 3
Domain146 – 18641LDL-receptor class A 4
Domain196 – 23439LDL-receptor class A 5
Domain235 – 27339LDL-receptor class A 6
Domain275 – 31440LDL-receptor class A 7
Domain315 – 35440EGF-like 1
Domain355 – 39440EGF-like 2; calcium-binding Potential
Repeat398 – 43942LDL-receptor class B 1
Repeat440 – 48546LDL-receptor class B 2
Repeat486 – 52843LDL-receptor class B 3
Repeat529 – 57244LDL-receptor class B 4
Repeat573 – 61543LDL-receptor class B 5
Repeat616 – 65843LDL-receptor class B 6
Domain663 – 71351EGF-like 3
Region722 – 77049Clustered O-linked oligosaccharides
Region813 – 86250Required for MYLIP-triggered down-regulation of LDLR By similarity
Motif825 – 8306NPXY motif

Amino acid modifications

Modified residue7251Phosphothreonine By similarity
Modified residue7331Phosphothreonine By similarity
Modified residue7351Phosphoserine By similarity
Glycosylation971N-linked (GlcNAc...) Potential
Glycosylation2731N-linked (GlcNAc...) Potential
Glycosylation4621N-linked (GlcNAc...) Potential
Disulfide bond34 ↔ 52 By similarity
Disulfide bond46 ↔ 63 By similarity
Disulfide bond68 ↔ 82 By similarity
Disulfide bond75 ↔ 95 By similarity
Disulfide bond89 ↔ 104 By similarity
Disulfide bond109 ↔ 121 By similarity
Disulfide bond116 ↔ 134 By similarity
Disulfide bond128 ↔ 143 By similarity
Disulfide bond148 ↔ 160 By similarity
Disulfide bond155 ↔ 173 By similarity
Disulfide bond167 ↔ 184 By similarity
Disulfide bond198 ↔ 210 By similarity
Disulfide bond205 ↔ 223 By similarity
Disulfide bond217 ↔ 232 By similarity
Disulfide bond237 ↔ 249 By similarity
Disulfide bond244 ↔ 262 By similarity
Disulfide bond256 ↔ 271 By similarity
Disulfide bond277 ↔ 290 By similarity
Disulfide bond285 ↔ 303 By similarity
Disulfide bond297 ↔ 314 By similarity
Disulfide bond319 ↔ 330 By similarity
Disulfide bond326 ↔ 339 By similarity
Disulfide bond341 ↔ 353 By similarity
Disulfide bond359 ↔ 369 By similarity
Disulfide bond365 ↔ 378 By similarity
Disulfide bond380 ↔ 393 By similarity
Disulfide bond667 ↔ 682 By similarity
Disulfide bond678 ↔ 697 By similarity
Disulfide bond699 ↔ 712 By similarity

Experimental info

Sequence conflict231A → V in CAA79581. Ref.1
Sequence conflict271C → G in CAA79581. Ref.1
Sequence conflict611E → K in CAA79581. Ref.1
Sequence conflict1441Q → P in CAA79581. Ref.1
Sequence conflict1561N → K in CAA79581. Ref.1
Sequence conflict1781D → H in CAA79581. Ref.1
Sequence conflict186 – 1872GR → AE in CAA79581. Ref.1
Sequence conflict8191N → NIT in CAA79581. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P35951 [UniParc].

Last modified February 6, 2013. Version 2.
Checksum: 43E7D6A293BE609C

FASTA86294,947
        10         20         30         40         50         60 
MSTADLMRRW VIALLLAAAG VAAEDSCSRN EFQCRDGKCI ASKWVCDGSP ECPDGSDESP 

        70         80         90        100        110        120 
ETCMSVTCQS NQFSCGGRVS RCIPDSWRCD GQVDCENDSD EQGCPPKTCS QDDFRCQDGK 

       130        140        150        160        170        180 
CISPQFVCDG DRDCLDGSDE AHCQATTCGP AHFRCNSSIC IPSLWACDGD VDCVDGSDEW 

       190        200        210        220        230        240 
PQNCQGRDTA SKGVSSPCSS LEFHCGSSEC IHRSWVCDGE ADCKDKSDEE HCAVATCRPD 

       250        260        270        280        290        300 
EFQCADGSCI HGSRQCDREH DCKDMSDELG CVNVTQCDGP NKFKCHSGEC ISLDKVCDSA 

       310        320        330        340        350        360 
RDCQDWSDEP IKECKTNECL DNNGGCSHIC KDLKIGSECL CPSGFRLVDL HRCEDIDECQ 

       370        380        390        400        410        420 
EPDTCSQLCV NLEGSYKCEC QAGFHMDPHT RVCKAVGSIG YLLFTNRHEV RKMTLDRSEY 

       430        440        450        460        470        480 
TSLLPNLKNV VALDTEVTNN RIYWSDLSQK KIYSALMDQA PNLSYDTIIS EDLHAPDGLA 

       490        500        510        520        530        540 
VDWIHRNIYW TDSVPGSVSV ADTKGVKRRT LFQEAGSRPR AIVVDPVHGF MYWTDWGTPA 

       550        560        570        580        590        600 
KIKKGGLNGV DIHSLVTENI QWPNGITLDL SSGRLYWVDS KLHSISSIDV NGGNRKTILE 

       610        620        630        640        650        660 
DENRLAHPFS LAIYEDKVYW TDVINEAIFS ANRLTGSDVN LVAENLLSPE DIVLFHKVTQ 

       670        680        690        700        710        720 
PRGVNWCETT ALLPNGGCQY LCLPAPQIGP HSPKFTCACP DGMLLAKDMR SCLTEVDTVL 

       730        740        750        760        770        780 
TTQGTSAVRP VVTASATRPP KHSEDLSAPS TPRQPVDTPG LSTVASVTVS HQVQGDMAGR 

       790        800        810        820        830        840 
GNEEQPHGMR FLSIFFPIAL VALLVLGAVL LWRNWRLKNI NSINFDNPVY QKTTEDELHI 

       850        860 
CRSQDGYTYP SRQMVSLEDD VA 

« Hide

References

« Hide 'large scale' references
[1]"The mouse low density lipoprotein receptor gene: cDNA sequence and exon-intron structure."
Hoffer M.J.V., van Eck M.M., Petrij F., van der Zee A., de Wit E., Meijer D., Grosveld G., Havekes L.M., Hofker M.H., Frants R.R.
Biochem. Biophys. Res. Commun. 191:880-886(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
Tissue: Liver.
[2]"Molecular cloning and nucleotide sequence of cDNA encoding a functional murine low-density-lipoprotein receptor."
Polvino W.J., Dichek D.A., Mason J., Anderson W.F.
Somat. Cell Mol. Genet. 18:443-450(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[5]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2."
Morris S.M., Cooper J.A.
Traffic 2:111-123(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2, DOMAIN.
[7]"The PX-domain protein SNX17 interacts with members of the LDL receptor family and modulates endocytosis of the LDL receptor."
Stockinger W., Sailler B., Strasser V., Recheis B., Fasching D., Kahr L., Schneider W.J., Nimpf J.
EMBO J. 21:4259-4267(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SNX17.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS22910.1.
PIRQRMSLD. I48623.
RefSeqNP_001239587.1. NM_001252658.1.
NP_001239588.1. NM_001252659.1.
NP_034830.2. NM_010700.3.
UniGeneMm.3213.

3D structure databases

ProteinModelPortalP35951.
SMRP35951. Positions 22-715.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201133. 2 interactions.
IntActP35951. 2 interactions.
MINTMINT-1541606.

PTM databases

PhosphoSiteP35951.

Proteomic databases

PaxDbP35951.
PRIDEP35951.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034713; ENSMUSP00000034713; ENSMUSG00000032193.
GeneID16835.
KEGGmmu:16835.
UCSCuc009omi.2. mouse.

Organism-specific databases

CTD3949.
MGIMGI:96765. Ldlr.

Phylogenomic databases

eggNOGNOG255913.
GeneTreeENSGT00740000114992.
HOGENOMHOG000115656.
HOVERGENHBG006250.
InParanoidP35951.
KOK12473.
OMAGQVDCEN.
OrthoDBEOG7NGQ9P.
TreeFamTF351700.

Enzyme and pathway databases

ReactomeREACT_188257. Signal Transduction.
REACT_189085. Disease.

Gene expression databases

CleanExMM_LDLR.
GenevestigatorP35951.

Family and domain databases

Gene3D2.120.10.30. 1 hit.
4.10.400.10. 7 hits.
InterProIPR011042. 6-blade_b-propeller_TolB-like.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR009030. Growth_fac_rcpt_N_dom.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
[Graphical view]
PfamPF07645. EGF_CA. 1 hit.
PF00057. Ldl_recept_a. 7 hits.
PF00058. Ldl_recept_b. 5 hits.
[Graphical view]
PRINTSPR00261. LDLRECEPTOR.
SMARTSM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00192. LDLa. 7 hits.
SM00135. LY. 5 hits.
[Graphical view]
SUPFAMSSF57184. SSF57184. 1 hit.
SSF57424. SSF57424. 6 hits.
PROSITEPS00010. 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]
ProtoNetSearch...

Other

NextBio290754.
PROP35951.
SOURCESearch...

Entry information

Entry nameLDLR_MOUSE
AccessionPrimary (citable) accession number: P35951
Secondary accession number(s): Q6GTJ9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 6, 2013
Last modified: July 9, 2014
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot