VLDLR

Protein identityUniProt · HPA

UniProt accession

P98155

Gene

VLDLR

Ensembl

ENSG00000147852

Chromosome

9

Canonical length

873 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Vesicles,Cytokinetic bridge,Centriolar satellite

Quaternary structure

Homooligomer

OverviewNCBI Gene

The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. This gene encodes a lipoprotein receptor that is a member of the LDLR family and plays important roles in VLDL-triglyceride metabolism and the reelin signaling pathway. Mutations in this gene cause VLDLR-associated cerebellar hypoplasia. Alternative splicing generates multiple transcript variants encoding distinct isoforms for this gene. [provided by RefSeq, Aug 2009]

Canonical amino-acid sequenceUniProt

873 residues, UniProt reviewed canonical sequence.

>P98155|VLDLR
     1  MGTSALWALW LLLALCWAPR ESGATGTGRK AKCEPSQFQC TNGRCITLLW KCDGDEDCVD
    61  GSDEKNCVKK TCAESDFVCN NGQCVPSRWK CDGDPDCEDG SDESPEQCHM RTCRIHEISC
   121  GAHSTQCIPV SWRCDGENDC DSGEDEENCG NITCSPDEFT CSSGRCISRN FVCNGQDDCS
   181  DGSDELDCAP PTCGAHEFQC STSSCIPISW VCDDDADCSD QSDESLEQCG RQPVIHTKCP
   241  ASEIQCGSGE CIHKKWRCDG DPDCKDGSDE VNCPSRTCRP DQFECEDGSC IHGSRQCNGI
   301  RDCVDGSDEV NCKNVNQCLG PGKFKCRSGE CIDISKVCNQ EQDCRDWSDE PLKECHINEC
   361  LVNNGGCSHI CKDLVIGYEC DCAAGFELID RKTCGDIDEC QNPGICSQIC INLKGGYKCE
   421  CSRGYQMDLA TGVCKAVGKE PSLIFTNRRD IRKIGLERKE YIQLVEQLRN TVALDADIAA
   481  QKLFWADLSQ KAIFSASIDD KVGRHVKMID NVYNPAAIAV DWVYKTIYWT DAASKTISVA
   541  TLDGTKRKFL FNSDLREPAS IAVDPLSGFV YWSDWGEPAK IEKAGMNGFD RRPLVTADIQ
   601  WPNGITLDLI KSRLYWLDSK LHMLSSVDLN GQDRRIVLKS LEFLAHPLAL TIFEDRVYWI
   661  DGENEAVYGA NKFTGSELAT LVNNLNDAQD IIVYHELVQP SGKNWCEEDM ENGGCEYLCL
   721  PAPQINDHSP KYTCSCPSGY NVEENGRDCQ STATTVTYSE TKDTNTTEIS ATSGLVPGGI
   781  NVTTAVSEVS VPPKGTSAAW AILPLLLLVM AAVGGYLMWR NWQHKNMKSM NFDNPVYLKT
   841  TEEDLSIDIG RHSASVGHTY PAISVVSTDD DLA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against VLDLR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about VLDLR.

Disease | AllUniProt

Conditions VLDLR is implicated in, by any mechanism.

• Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 1 (CAMRQ1) MIM:224050

Disease | GeneticClinVar

63 pathogenic / likely-pathogenic of 861 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1
• Cerebellar hypoplasia
• Abnormality of the nervous system
• Dysequilibrium syndrome
• Inborn genetic diseases

ReferencesPubMed · IEDB

Publications for VLDLR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.72

gnomAD pLI

0

gnomAD missense Z

-1.12

DepMap mean gene effect

0.1

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cholesterol metabolic process
• dendrite morphogenesis
• glycoprotein transport
• lipid transport
• memory
• nervous system development
• positive regulation of dendrite development
• receptor-mediated endocytosis
• reelin-mediated signaling pathway
• regulation of synapse assembly
• signal transduction
• ventral spinal cord development
• very-low-density lipoprotein particle clearance

Molecular functions

• apolipoprotein binding
• calcium ion binding
• calcium-dependent protein binding
• cargo receptor activity
• low-density lipoprotein particle receptor activity
• reelin receptor activity
• very-low-density lipoprotein particle binding
• very-low-density lipoprotein particle receptor activity

Cellular components

• clathrin-coated pit
• glutamatergic synapse
• lysosomal membrane
• membrane
• plasma membrane
• receptor complex
• very-low-density lipoprotein particle

Protein domainsUniProt · Pfam · InterPro

• LDLR class B repeat
• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• EGF-like calcium-binding domain
• Low-density lipoprotein (LDL) receptor class A repeat
• Six-bladed beta-propeller, TolB-like
• EGF-like calcium-binding, conserved site
• Low-density lipoprotein (LDL) receptor class A, conserved site
• LDL receptor-like superfamily
• NOTCH1, EGF-like calcium-binding domain
• Low-density lipoprotein receptor-related
• Low-density lipoprotein receptor domain class A
• Low-density lipoprotein receptor repeat class B
• Calcium-binding EGF domain
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Cell membrane
• Cholesterol metabolism
• Coated pit
• Disulfide bond
• EGF-like domain
• Endocytosis
• Glycoprotein
• Host-virus interaction
• Intellectual disability
• Isopeptide bond
• Lipid metabolism
• Lipid transport
• Membrane
• Receptor
• Repeat
• Signal
• Steroid metabolism
• Sterol metabolism
• Transmembrane
• Transmembrane helix
• Transport
• Ubl conjugation
• VLDL

InteractionsUniProt · HPA

Protein binding partners of VLDLR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLU
• DAB1
• LDLRAP1
• LRP8
• PAFAH1B2
• PAFAH1B3
• PCSK9
• SNX17
• STX5
• LRPAP1