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P35951

- LDLR_MOUSE

UniProt

P35951 - LDLR_MOUSE

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Protein

Low-density lipoprotein receptor

Gene
Ldlr
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. low-density lipoprotein particle binding Source: MGI
  3. low-density lipoprotein receptor activity Source: MGI
  4. protein binding Source: MGI
  5. very-low-density lipoprotein particle receptor activity Source: MGI

GO - Biological processi

  1. cholesterol homeostasis Source: MGI
  2. cholesterol import Source: BHF-UCL
  3. cholesterol metabolic process Source: MGI
  4. cholesterol transport Source: MGI
  5. intestinal cholesterol absorption Source: Ensembl
  6. lipid metabolic process Source: MGI
  7. lipoprotein catabolic process Source: MGI
  8. lipoprotein metabolic process Source: MGI
  9. low-density lipoprotein particle clearance Source: BHF-UCL
  10. phospholipid transport Source: BHF-UCL
  11. positive regulation of triglyceride biosynthetic process Source: BHF-UCL
  12. receptor-mediated endocytosis Source: GOC
  13. regulation of cholesterol homeostasis Source: MGI
  14. regulation of phosphatidylcholine catabolic process Source: BHF-UCL
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

ReactomeiREACT_198569. Retinoid metabolism and transport.
REACT_216017. Chylomicron-mediated lipid transport.
REACT_222614. LDL-mediated lipid 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
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:96765. Ldlr.

Subcellular locationi

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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 790769Extracellular Reviewed predictionAdd
BLAST
Transmembranei791 – 81222Helical; Reviewed predictionAdd
BLAST
Topological domaini813 – 86250Cytoplasmic Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: UniProtKB
  2. coated pit Source: UniProtKB-SubCell
  3. early endosome Source: UniProtKB
  4. endosome Source: MGI
  5. external side of plasma membrane Source: Ensembl
  6. Golgi apparatus Source: UniProtKB
  7. integral component of membrane Source: UniProtKB-KW
  8. late endosome Source: UniProtKB
  9. low-density lipoprotein particle Source: UniProtKB-KW
  10. lysosome Source: UniProtKB
  11. plasma membrane Source: Reactome
  12. receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121 By similarityAdd
BLAST
Chaini22 – 862841Low-density lipoprotein receptorPRO_0000017313Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi34 ↔ 52 By similarity
Disulfide bondi46 ↔ 63 By similarity
Disulfide bondi68 ↔ 82 By similarity
Disulfide bondi75 ↔ 95 By similarity
Disulfide bondi89 ↔ 104 By similarity
Glycosylationi97 – 971N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi109 ↔ 121 By similarity
Disulfide bondi116 ↔ 134 By similarity
Disulfide bondi128 ↔ 143 By similarity
Disulfide bondi148 ↔ 160 By similarity
Disulfide bondi155 ↔ 173 By similarity
Disulfide bondi167 ↔ 184 By similarity
Disulfide bondi198 ↔ 210 By similarity
Disulfide bondi205 ↔ 223 By similarity
Disulfide bondi217 ↔ 232 By similarity
Disulfide bondi237 ↔ 249 By similarity
Disulfide bondi244 ↔ 262 By similarity
Disulfide bondi256 ↔ 271 By similarity
Glycosylationi273 – 2731N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi277 ↔ 290 By similarity
Disulfide bondi285 ↔ 303 By similarity
Disulfide bondi297 ↔ 314 By similarity
Disulfide bondi319 ↔ 330 By similarity
Disulfide bondi326 ↔ 339 By similarity
Disulfide bondi341 ↔ 353 By similarity
Disulfide bondi359 ↔ 369 By similarity
Disulfide bondi365 ↔ 378 By similarity
Disulfide bondi380 ↔ 393 By similarity
Glycosylationi462 – 4621N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi667 ↔ 682 By similarity
Disulfide bondi678 ↔ 697 By similarity
Disulfide bondi699 ↔ 712 By similarity
Modified residuei725 – 7251Phosphothreonine By similarity
Modified residuei733 – 7331Phosphothreonine By similarity
Modified residuei735 – 7351Phosphoserine By similarity

Post-translational modificationi

Ubiquitinated by MYLIP leading to degradation By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP35951.
PRIDEiP35951.

PTM databases

PhosphoSiteiP35951.

Expressioni

Gene expression databases

CleanExiMM_LDLR.
GenevestigatoriP35951.

Interactioni

Subunit structurei

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).2 Publications

Protein-protein interaction databases

BioGridi201133. 2 interactions.
IntActiP35951. 2 interactions.
MINTiMINT-1541606.

Structurei

3D structure databases

ProteinModelPortaliP35951.
SMRiP35951. Positions 22-715.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 6541LDL-receptor class A 1Add
BLAST
Domaini66 – 10641LDL-receptor class A 2Add
BLAST
Domaini107 – 14539LDL-receptor class A 3Add
BLAST
Domaini146 – 18641LDL-receptor class A 4Add
BLAST
Domaini196 – 23439LDL-receptor class A 5Add
BLAST
Domaini235 – 27339LDL-receptor class A 6Add
BLAST
Domaini275 – 31440LDL-receptor class A 7Add
BLAST
Domaini315 – 35440EGF-like 1Add
BLAST
Domaini355 – 39440EGF-like 2; calcium-binding Reviewed predictionAdd
BLAST
Repeati398 – 43942LDL-receptor class B 1Add
BLAST
Repeati440 – 48546LDL-receptor class B 2Add
BLAST
Repeati486 – 52843LDL-receptor class B 3Add
BLAST
Repeati529 – 57244LDL-receptor class B 4Add
BLAST
Repeati573 – 61543LDL-receptor class B 5Add
BLAST
Repeati616 – 65843LDL-receptor class B 6Add
BLAST
Domaini663 – 71351EGF-like 3Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni722 – 77049Clustered O-linked oligosaccharidesAdd
BLAST
Regioni813 – 86250Required for MYLIP-triggered down-regulation of LDLR By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi825 – 8306NPXY motif

Domaini

The NPXY motif mediates the interaction with the clathrin adaptor DAB2 involved in receptor internalization.1 Publication

Sequence similaritiesi

Belongs to the LDLR family.
Contains 3 EGF-like domains.

Keywords - Domaini

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

Phylogenomic databases

eggNOGiNOG255913.
GeneTreeiENSGT00740000114992.
HOGENOMiHOG000115656.
HOVERGENiHBG006250.
InParanoidiP35951.
KOiK12473.
OMAiGQVDCEN.
OrthoDBiEOG7NGQ9P.
TreeFamiTF351700.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
4.10.400.10. 7 hits.
InterProiIPR011042. 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]
PfamiPF07645. EGF_CA. 1 hit.
PF00057. Ldl_recept_a. 7 hits.
PF00058. Ldl_recept_b. 5 hits.
[Graphical view]
PRINTSiPR00261. LDLRECEPTOR.
SMARTiSM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
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

MSTADLMRRW VIALLLAAAG VAAEDSCSRN EFQCRDGKCI ASKWVCDGSP    50
ECPDGSDESP ETCMSVTCQS NQFSCGGRVS RCIPDSWRCD GQVDCENDSD 100
EQGCPPKTCS QDDFRCQDGK CISPQFVCDG DRDCLDGSDE AHCQATTCGP 150
AHFRCNSSIC IPSLWACDGD VDCVDGSDEW PQNCQGRDTA SKGVSSPCSS 200
LEFHCGSSEC IHRSWVCDGE ADCKDKSDEE HCAVATCRPD EFQCADGSCI 250
HGSRQCDREH DCKDMSDELG CVNVTQCDGP NKFKCHSGEC ISLDKVCDSA 300
RDCQDWSDEP IKECKTNECL DNNGGCSHIC KDLKIGSECL CPSGFRLVDL 350
HRCEDIDECQ EPDTCSQLCV NLEGSYKCEC QAGFHMDPHT RVCKAVGSIG 400
YLLFTNRHEV RKMTLDRSEY TSLLPNLKNV VALDTEVTNN RIYWSDLSQK 450
KIYSALMDQA PNLSYDTIIS EDLHAPDGLA VDWIHRNIYW TDSVPGSVSV 500
ADTKGVKRRT LFQEAGSRPR AIVVDPVHGF MYWTDWGTPA KIKKGGLNGV 550
DIHSLVTENI QWPNGITLDL SSGRLYWVDS KLHSISSIDV NGGNRKTILE 600
DENRLAHPFS LAIYEDKVYW TDVINEAIFS ANRLTGSDVN LVAENLLSPE 650
DIVLFHKVTQ PRGVNWCETT ALLPNGGCQY LCLPAPQIGP HSPKFTCACP 700
DGMLLAKDMR SCLTEVDTVL TTQGTSAVRP VVTASATRPP KHSEDLSAPS 750
TPRQPVDTPG LSTVASVTVS HQVQGDMAGR GNEEQPHGMR FLSIFFPIAL 800
VALLVLGAVL LWRNWRLKNI NSINFDNPVY QKTTEDELHI CRSQDGYTYP 850
SRQMVSLEDD VA 862
Length:862
Mass (Da):94,947
Last modified:February 6, 2013 - v2
Checksum:i43E7D6A293BE609C
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti23 – 231A → V in CAA79581. 1 Publication
Sequence conflicti27 – 271C → G in CAA79581. 1 Publication
Sequence conflicti61 – 611E → K in CAA79581. 1 Publication
Sequence conflicti144 – 1441Q → P in CAA79581. 1 Publication
Sequence conflicti156 – 1561N → K in CAA79581. 1 Publication
Sequence conflicti178 – 1781D → H in CAA79581. 1 Publication
Sequence conflicti186 – 1872GR → AE in CAA79581. 1 Publication
Sequence conflicti819 – 8191N → NIT in CAA79581. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UCSCiuc009omi.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS22910.1.
PIRi I48623. QRMSLD.
RefSeqi NP_001239587.1. NM_001252658.1.
NP_001239588.1. NM_001252659.1.
NP_034830.2. NM_010700.3.
UniGenei Mm.3213.

3D structure databases

ProteinModelPortali P35951.
SMRi P35951. Positions 22-715.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 201133. 2 interactions.
IntActi P35951. 2 interactions.
MINTi MINT-1541606.

PTM databases

PhosphoSitei P35951.

Proteomic databases

PaxDbi P35951.
PRIDEi P35951.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000034713 ; ENSMUSP00000034713 ; ENSMUSG00000032193 .
GeneIDi 16835.
KEGGi mmu:16835.
UCSCi uc009omi.2. mouse.

Organism-specific databases

CTDi 3949.
MGIi MGI:96765. Ldlr.

Phylogenomic databases

eggNOGi NOG255913.
GeneTreei ENSGT00740000114992.
HOGENOMi HOG000115656.
HOVERGENi HBG006250.
InParanoidi P35951.
KOi K12473.
OMAi GQVDCEN.
OrthoDBi EOG7NGQ9P.
TreeFami TF351700.

Enzyme and pathway databases

Reactomei REACT_198569. Retinoid metabolism and transport.
REACT_216017. Chylomicron-mediated lipid transport.
REACT_222614. LDL-mediated lipid transport.

Miscellaneous databases

NextBioi 290754.
PROi P35951.
SOURCEi Search...

Gene expression databases

CleanExi MM_LDLR.
Genevestigatori P35951.

Family and domain databases

Gene3Di 2.120.10.30. 1 hit.
4.10.400.10. 7 hits.
InterProi IPR011042. 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 ]
Pfami PF07645. EGF_CA. 1 hit.
PF00057. Ldl_recept_a. 7 hits.
PF00058. Ldl_recept_b. 5 hits.
[Graphical view ]
PRINTSi PR00261. LDLRECEPTOR.
SMARTi SM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00192. LDLa. 7 hits.
SM00135. LY. 5 hits.
[Graphical view ]
SUPFAMi SSF57184. SSF57184. 1 hit.
SSF57424. SSF57424. 6 hits.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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.

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: September 3, 2014
This is version 142 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

External Data

Dasty 3

Similar proteinsi