Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Very low-density lipoprotein receptor

Gene

VLDLR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds VLDL and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Binding to Reelin induces tyrosine phosphorylation of Dab1 and modulation of Tau phosphorylation (By similarity).By similarity

GO - Molecular functioni

  • apolipoprotein binding Source: BHF-UCL
  • calcium-dependent protein binding Source: BHF-UCL
  • calcium ion binding Source: InterPro
  • glycoprotein transporter activity Source: BHF-UCL
  • low-density lipoprotein receptor activity Source: ProtInc
  • reelin receptor activity Source: BHF-UCL
  • very-low-density lipoprotein particle binding Source: BHF-UCL
  • very-low-density lipoprotein particle receptor activity Source: BHF-UCL

GO - Biological processi

  • axon guidance Source: Reactome
  • cholesterol metabolic process Source: UniProtKB-KW
  • dendrite morphogenesis Source: Ensembl
  • glycoprotein transport Source: BHF-UCL
  • lipid transport Source: UniProtKB-KW
  • low-density lipoprotein particle receptor catabolic process Source: Reactome
  • memory Source: ProtInc
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • nervous system development Source: ProtInc
  • positive regulation of dendrite development Source: BHF-UCL
  • positive regulation of protein kinase activity Source: Ensembl
  • receptor-mediated endocytosis Source: BHF-UCL
  • reelin-mediated signaling pathway Source: BHF-UCL
  • signal transduction Source: ProtInc
  • ventral spinal cord development Source: Ensembl
  • very-low-density lipoprotein particle clearance Source: BHF-UCL

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-8866376. Reelin signalling pathway.
R-HSA-8866427. VLDLR internalisation and degradation.
R-HSA-8964046. VLDL clearance.
SIGNORiP98155.

Names & Taxonomyi

Protein namesi
Recommended name:
Very low-density lipoprotein receptor
Short name:
VLDL receptor
Short name:
VLDL-R
Gene namesi
Name:VLDLR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000147852.15.
HGNCiHGNC:12698. VLDLR.

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 domaini28 – 797ExtracellularSequence analysisAdd BLAST770
Transmembranei798 – 819HelicalSequence analysisAdd BLAST22
Topological domaini820 – 873CytoplasmicSequence analysisAdd BLAST54

Keywords - Cellular componenti

Coated pit, Membrane, VLDL

Pathology & Biotechi

Involvement in diseasei

Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 1 (CAMRQ1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA congenital, non-progressive cerebellar ataxia associated with disturbed equilibrium, delayed ambulation, mental retardation, cerebellar hypoplasia and mild cerebral gyral simplification. Additional features include short stature, strabismus, pes planus and, rarely, seizures.
See also OMIM:224050

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi825K → R: Insensitive to MYLIP-triggered degradation; when associated with R-828 and R-839. 1 Publication1
Mutagenesisi828K → R: Insensitive to MYLIP-triggered degradation; when associated with R-825 and R-839. 1 Publication1
Mutagenesisi839K → R: Insensitive to MYLIP-triggered degradation. Insensitive to MYLIP-triggered degradation; when associated with R-825 and R-828. 1 Publication1

Keywords - Diseasei

Mental retardation

Organism-specific databases

DisGeNETi7436.
GeneReviewsiVLDLR.
MalaCardsiVLDLR.
MIMi224050. phenotype.
OpenTargetsiENSG00000147852.
Orphaneti1766. Dysequilibrium syndrome.
PharmGKBiPA37317.

Chemistry databases

DrugBankiDB03017. Lauric Acid.

Polymorphism and mutation databases

BioMutaiVLDLR.
DMDMi1730111.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001734328 – 873Very low-density lipoprotein receptorAdd BLAST846

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 45By similarity
Disulfide bondi40 ↔ 58By similarity
Disulfide bondi52 ↔ 67By similarity
Disulfide bondi72 ↔ 84By similarity
Disulfide bondi79 ↔ 97By similarity
Disulfide bondi91 ↔ 108By similarity
Disulfide bondi113 ↔ 127
Disulfide bondi120 ↔ 140
Disulfide bondi134 ↔ 149
Glycosylationi151N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi154 ↔ 166By similarity
Disulfide bondi161 ↔ 179By similarity
Disulfide bondi173 ↔ 188By similarity
Disulfide bondi193 ↔ 205By similarity
Disulfide bondi200 ↔ 218By similarity
Disulfide bondi212 ↔ 229By similarity
Disulfide bondi239 ↔ 251By similarity
Disulfide bondi246 ↔ 264By similarity
Disulfide bondi258 ↔ 273By similarity
Disulfide bondi278 ↔ 290By similarity
Disulfide bondi285 ↔ 303By similarity
Disulfide bondi297 ↔ 312By similarity
Disulfide bondi318 ↔ 331By similarity
Disulfide bondi326 ↔ 344By similarity
Disulfide bondi338 ↔ 355By similarity
Disulfide bondi360 ↔ 371By similarity
Disulfide bondi367 ↔ 380By similarity
Disulfide bondi382 ↔ 394By similarity
Disulfide bondi400 ↔ 410By similarity
Disulfide bondi406 ↔ 419By similarity
Disulfide bondi421 ↔ 434By similarity
Disulfide bondi706 ↔ 719By similarity
Disulfide bondi715 ↔ 734By similarity
Disulfide bondi736 ↔ 749By similarity
Glycosylationi765N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi781N-linked (GlcNAc...) asparagineSequence analysis1
Cross-linki839Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Ubiquitinated at Lys-839 by MYLIP leading to degradation.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiP98155.
MaxQBiP98155.
PaxDbiP98155.
PeptideAtlasiP98155.
PRIDEiP98155.

PTM databases

iPTMnetiP98155.
PhosphoSitePlusiP98155.

Expressioni

Tissue specificityi

Abundant in heart and skeletal muscle; also ovary and kidney; not in liver.

Gene expression databases

BgeeiENSG00000147852.
CleanExiHS_VLDLR.
ExpressionAtlasiP98155. baseline and differential.
GenevisibleiP98155. HS.

Organism-specific databases

HPAiCAB032462.
HPA051312.

Interactioni

Subunit structurei

Binds to the extracellular matrix protein Reelin. Interacts with VLDLR. Interacts with SNX17 (By similarity). Interacts with DAB1. Receptor for the minor-group human rhinoviruses (HRVs); binds protein VP1 through the second and third LDL-receptor class A domains. Interacts with PCSK9.By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • apolipoprotein binding Source: BHF-UCL
  • calcium-dependent protein binding Source: BHF-UCL
  • very-low-density lipoprotein particle binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi113277. 12 interactors.
DIPiDIP-40925N.
IntActiP98155. 5 interactors.
MINTiMINT-111579.
STRINGi9606.ENSP00000371532.

Structurei

Secondary structure

1873
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni115 – 117Combined sources3
Beta strandi121 – 125Combined sources5
Beta strandi132 – 137Combined sources6
Turni141 – 145Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1V9UX-ray3.605111-151[»]
3DPRX-ray3.50E113-151[»]
ProteinModelPortaliP98155.
SMRiP98155.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP98155.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 69LDL-receptor class A 1Add BLAST39
Domaini70 – 110LDL-receptor class A 2Add BLAST41
Domaini111 – 151LDL-receptor class A 3Add BLAST41
Domaini152 – 190LDL-receptor class A 4Add BLAST39
Domaini191 – 231LDL-receptor class A 5Add BLAST41
Domaini237 – 275LDL-receptor class A 6Add BLAST39
Domaini276 – 314LDL-receptor class A 7Add BLAST39
Domaini316 – 355LDL-receptor class A 8Add BLAST40
Domaini356 – 395EGF-like 1Add BLAST40
Domaini396 – 435EGF-like 2; calcium-bindingAdd BLAST40
Repeati439 – 480LDL-receptor class B 1Add BLAST42
Repeati481 – 524LDL-receptor class B 2Add BLAST44
Repeati525 – 567LDL-receptor class B 3Add BLAST43
Repeati568 – 611LDL-receptor class B 4Add BLAST44
Repeati612 – 654LDL-receptor class B 5Add BLAST43
Repeati655 – 697LDL-receptor class B 6Add BLAST43
Domaini702 – 750EGF-like 3Add BLAST49

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni751 – 790Clustered O-linked oligosaccharidesAdd BLAST40

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi832 – 837Endocytosis signalSequence analysis6

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410IPT5. Eukaryota.
ENOG410YQ6J. LUCA.
GeneTreeiENSGT00760000118968.
HOGENOMiHOG000115656.
HOVERGENiHBG006250.
InParanoidiP98155.
KOiK20053.
OMAiHTKCPAS.
OrthoDBiEOG091G01MX.
PhylomeDBiP98155.
TreeFamiTF351700.

Family and domain databases

CDDicd00112. LDLa. 8 hits.
Gene3Di2.120.10.30. 2 hits.
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.
IPR036055. LDL_receptor-like_sf.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
IPR032931. VLDLR.
PANTHERiPTHR43966:SF6. PTHR43966:SF6. 1 hit.
PfamiView protein in Pfam
PF07645. EGF_CA. 1 hit.
PF00057. Ldl_recept_a. 8 hits.
PF00058. Ldl_recept_b. 5 hits.
PRINTSiPR00261. LDLRECEPTOR.
SMARTiView protein in SMART
SM00181. EGF. 6 hits.
SM00179. EGF_CA. 2 hits.
SM00192. LDLa. 8 hits.
SM00135. LY. 5 hits.
SUPFAMiSSF57424. SSF57424. 8 hits.
PROSITEiView protein in PROSITE
PS00010. ASX_HYDROXYL. 2 hits.
PS01186. EGF_2. 3 hits.
PS50026. EGF_3. 2 hits.
PS01187. EGF_CA. 1 hit.
PS01209. LDLRA_1. 8 hits.
PS50068. LDLRA_2. 8 hits.
PS51120. LDLRB. 5 hits.

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P98155-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGTSALWALW LLLALCWAPR ESGATGTGRK AKCEPSQFQC TNGRCITLLW
60 70 80 90 100
KCDGDEDCVD GSDEKNCVKK TCAESDFVCN NGQCVPSRWK CDGDPDCEDG
110 120 130 140 150
SDESPEQCHM RTCRIHEISC GAHSTQCIPV SWRCDGENDC DSGEDEENCG
160 170 180 190 200
NITCSPDEFT CSSGRCISRN FVCNGQDDCS DGSDELDCAP PTCGAHEFQC
210 220 230 240 250
STSSCIPISW VCDDDADCSD QSDESLEQCG RQPVIHTKCP ASEIQCGSGE
260 270 280 290 300
CIHKKWRCDG DPDCKDGSDE VNCPSRTCRP DQFECEDGSC IHGSRQCNGI
310 320 330 340 350
RDCVDGSDEV NCKNVNQCLG PGKFKCRSGE CIDISKVCNQ EQDCRDWSDE
360 370 380 390 400
PLKECHINEC LVNNGGCSHI CKDLVIGYEC DCAAGFELID RKTCGDIDEC
410 420 430 440 450
QNPGICSQIC INLKGGYKCE CSRGYQMDLA TGVCKAVGKE PSLIFTNRRD
460 470 480 490 500
IRKIGLERKE YIQLVEQLRN TVALDADIAA QKLFWADLSQ KAIFSASIDD
510 520 530 540 550
KVGRHVKMID NVYNPAAIAV DWVYKTIYWT DAASKTISVA TLDGTKRKFL
560 570 580 590 600
FNSDLREPAS IAVDPLSGFV YWSDWGEPAK IEKAGMNGFD RRPLVTADIQ
610 620 630 640 650
WPNGITLDLI KSRLYWLDSK LHMLSSVDLN GQDRRIVLKS LEFLAHPLAL
660 670 680 690 700
TIFEDRVYWI DGENEAVYGA NKFTGSELAT LVNNLNDAQD IIVYHELVQP
710 720 730 740 750
SGKNWCEEDM ENGGCEYLCL PAPQINDHSP KYTCSCPSGY NVEENGRDCQ
760 770 780 790 800
STATTVTYSE TKDTNTTEIS ATSGLVPGGI NVTTAVSEVS VPPKGTSAAW
810 820 830 840 850
AILPLLLLVM AAVGGYLMWR NWQHKNMKSM NFDNPVYLKT TEEDLSIDIG
860 870
RHSASVGHTY PAISVVSTDD DLA
Length:873
Mass (Da):96,098
Last modified:October 1, 1996 - v1
Checksum:i8BAC29438A78C2B8
GO
Isoform Short (identifier: P98155-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     751-779: STATTVTYSETKDTNTTEISATSGLVPGG → R

Show »
Length:845
Mass (Da):93,383
Checksum:i588311D7C6B2C1FD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9L → V in AAA53684 (PubMed:8128315).Curated1
Sequence conflicti13L → V in AAA61344 (PubMed:8020981).Curated1
Sequence conflicti424G → A in AAA53684 (PubMed:8128315).Curated1
Sequence conflicti678L → H in AAA53684 (PubMed:8128315).Curated1
Sequence conflicti766T → S in AAA61344 (PubMed:8020981).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01186559V → I2 PublicationsCorresponds to variant dbSNP:rs6149Ensembl.1
Natural variantiVAR_025063262P → H1 PublicationCorresponds to variant dbSNP:rs34761707Ensembl.1
Natural variantiVAR_011866379E → K1 PublicationCorresponds to variant dbSNP:rs6146Ensembl.1
Natural variantiVAR_025064464L → I1 PublicationCorresponds to variant dbSNP:rs34753566Ensembl.1
Natural variantiVAR_025065561I → V1 PublicationCorresponds to variant dbSNP:rs35724190Ensembl.1
Natural variantiVAR_025066613R → H1 PublicationCorresponds to variant dbSNP:rs35948251Ensembl.1
Natural variantiVAR_025067791V → I1 PublicationCorresponds to variant dbSNP:rs35334949Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004304751 – 779STATT…LVPGG → R in isoform Short. CuratedAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L20470 mRNA. Translation: AAA53684.1.
S73849 mRNA. Translation: AAB31735.1.
D16532 Genomic DNA. Translation: BAA03969.1.
D16493 mRNA. Translation: BAA03945.1.
D16494 mRNA. Translation: BAA03946.1.
L22431 mRNA. Translation: AAA61344.1.
DQ067198 Genomic DNA. Translation: AAY46157.1.
AL450467 Genomic DNA. No translation available.
CH471071 Genomic DNA. Translation: EAW58805.1.
CH471071 Genomic DNA. Translation: EAW58806.1.
BC136562 mRNA. Translation: AAI36563.1.
CCDSiCCDS34979.1. [P98155-2]
CCDS6446.1. [P98155-1]
PIRiA49729.
RefSeqiNP_001018066.1. NM_001018056.2. [P98155-2]
NP_003374.3. NM_003383.4. [P98155-1]
UniGeneiHs.370422.

Genome annotation databases

EnsembliENST00000382099; ENSP00000371531; ENSG00000147852. [P98155-2]
ENST00000382100; ENSP00000371532; ENSG00000147852. [P98155-1]
GeneIDi7436.
KEGGihsa:7436.
UCSCiuc003zhk.2. human. [P98155-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiVLDLR_HUMAN
AccessioniPrimary (citable) accession number: P98155
Secondary accession number(s): B2RMZ7, D3DRH6, Q5VVF6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 22, 2017
This is version 185 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references