Q8IV16 · HDBP1_HUMAN

  • Protein
    Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
  • Gene
    GPIHBP1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Mediates the transport of lipoprotein lipase LPL from the basolateral to the apical surface of endothelial cells in capillaries (By similarity).
Anchors LPL on the surface of endothelial cells in the lumen of blood capillaries (By similarity).
Protects LPL against loss of activity, and against ANGPTL4-mediated unfolding (PubMed:27929370, PubMed:29899144).
Thereby, plays an important role in lipolytic processing of chylomicrons by LPL, triglyceride metabolism and lipid homeostasis (PubMed:19304573, PubMed:21314738).
Binds chylomicrons and phospholipid particles that contain APOA5 (PubMed:17997385, PubMed:19304573).
Binds high-density lipoprotein (HDL) and plays a role in the uptake of lipids from HDL (By similarity).

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentcatalytic complex
Cellular Componentexternal side of plasma membrane
Cellular Componentextracellular region
Cellular Componentplasma membrane
Molecular Functionacetylcholine receptor inhibitor activity
Molecular Functionchylomicron binding
Molecular Functionlipase binding
Molecular Functionlipid binding
Molecular Functionlipoprotein lipase activator activity
Molecular Functionlipoprotein particle binding
Molecular Functionprotein transporter activity
Biological Processcholesterol homeostasis
Biological Processintracellular protein transport
Biological Processpositive regulation of chylomicron remnant clearance
Biological Processpositive regulation of lipoprotein lipase activity
Biological Processprotein import
Biological Processprotein localization to cell surface
Biological Processprotein stabilization
Biological Processresponse to heparin
Biological Processtranscytosis
Biological Processtriglyceride catabolic process
Biological Processtriglyceride homeostasis

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
  • Short names
    GPI-HBP1; GPI-anchored HDL-binding protein 1
  • Alternative names
    • High density lipoprotein-binding protein 1

Gene names

    • Name
      GPIHBP1
    • Synonyms
      HBP1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q8IV16
  • Secondary accessions
    • Q6P3T2
    • Q86W15

Proteomes

Organism-specific databases

Subcellular Location

Apical cell membrane
; Lipid-anchor, GPI-anchor
Basolateral cell membrane
; Lipid-anchor, GPI-anchor
Cell membrane
; Lipid-anchor, GPI-anchor

Keywords

Disease & Variants

Involvement in disease

Hyperlipoproteinemia 1D (HLPP1D)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An autosomal recessive disorder characterized by hyperlipoproteinemia, decreased plasma LPL levels in some patients, high plasma triglyceride levels, and refractory fasting chylomicronemia.
  • See also
    MIM:615947
Natural variants in HLPP1D
Variant IDPosition(s)ChangeDescription
VAR_07188165C>Sin HLPP1D; does not affect protein expression at the cell surface; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers; dbSNP:rs587777638
VAR_07763465C>Yin HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers; dbSNP:rs587777638
VAR_07188268C>Gin HLPP1D; does not affect protein expression at the cell surface; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs587777639
VAR_07763568C>Rin HLPP1D; uncertain significance; results in decreased GPIHBP1 expression; promotes formation of dimers and oligomers severely reducing number of monomers; does not affect interaction with LPL when associated in cis with F-14; dbSNP:rs587777639
VAR_07763668C>Yin HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers
VAR_07763783C>Rin HLPP1D
VAR_07188389C>Fin HLPP1D; drastically affects interaction with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs587777640
VAR_077638108T>Rin HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs752728823
VAR_058086115Q>Pin HLPP1D; a patient with chylomicronemia; no effect on protein expression at the cell surface; loss of interaction with LPL; loss of interaction with chylomicrons; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs587777637
VAR_077639144S>Fin HLPP1D; dbSNP:rs78367243
VAR_071884175G>Rin HLPP1D; affects protein expression at the cell surface; reduces interaction with LPL; dbSNP:rs145844329

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_04450314it may act as a disease modifier preserving from severe HLPP1D; when associated in cis with R-68; does not affect interaction with LPL when associated in cis with R-68; dbSNP:rs11538389
Mutagenesis38Loss of sulfotyrosine formation.
Natural variantVAR_04450456no discernible effect on interaction with LPL, chylomicrons or APOA5; dbSNP:rs587777636
Natural variantVAR_07188165in HLPP1D; does not affect protein expression at the cell surface; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers; dbSNP:rs587777638
Natural variantVAR_07763465in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers; dbSNP:rs587777638
Mutagenesis66Promotes formation of dimers and oligomers reducing number of monomers.
Natural variantVAR_07188268in HLPP1D; does not affect protein expression at the cell surface; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs587777639
Natural variantVAR_07763568in HLPP1D; uncertain significance; results in decreased GPIHBP1 expression; promotes formation of dimers and oligomers severely reducing number of monomers; does not affect interaction with LPL when associated in cis with F-14; dbSNP:rs587777639
Natural variantVAR_07763668in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers
Mutagenesis71Promotes formation of dimers and oligomers reducing number of monomers.
Natural variantVAR_07763783in HLPP1D
Natural variantVAR_07188389in HLPP1D; drastically affects interaction with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs587777640
Mutagenesis91Promotes formation of dimers and oligomers reducing number of monomers.
Mutagenesis92Only slightly increased formation of dimers and oligomers. No effect on number of monomers. Loss of LPL interaction.
Mutagenesis93Promotes formation of dimers and oligomers reducing number of monomers.
Mutagenesis101Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL.
Mutagenesis104Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL.
Mutagenesis105Promotes formation of dimers and oligomers reducing number of monomers.
Mutagenesis106Promotes formation of dimers and oligomers severely reducing number of monomers.
Mutagenesis107Promotes formation of dimers and oligomers reducing number of monomers.
Natural variantVAR_077638108in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs752728823
Mutagenesis108Retained some interaction with LPL. No effect on number of monomers.
Mutagenesis109Promotes formation of dimers and oligomers reducing number of monomers. Loss of LPL interaction.
Mutagenesis109Loss of interaction with LPL. Only slightly increased formation of dimers and oligomers. No effect on number of monomers.
Natural variantVAR_058086115in HLPP1D; a patient with chylomicronemia; no effect on protein expression at the cell surface; loss of interaction with LPL; loss of interaction with chylomicrons; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs587777637
Mutagenesis115No effect on number of monomers.
Mutagenesis126Promotes formation of dimers and oligomers reducing number of monomers.
Natural variantVAR_077639144in HLPP1D; dbSNP:rs78367243
Natural variantVAR_071884175in HLPP1D; affects protein expression at the cell surface; reduces interaction with LPL; dbSNP:rs145844329

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 258 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for signal, chain, modified residue, disulfide bond, glycosylation, lipidation, propeptide.

TypeIDPosition(s)Description
Signal1-20
ChainPRO_000031820821-151Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
Modified residue38Sulfotyrosine
Disulfide bond65↔89
Disulfide bond68↔77
Glycosylation78N-linked (GlcNAc...) asparagine
Disulfide bond83↔110
Disulfide bond114↔130
Disulfide bond131↔136
Lipidation151GPI-anchor amidated glycine
PropeptidePRO_0000429858152-184Removed in mature form

Post-translational modification

Glycosylation of Asn-78 is critical for cell surface localization.
Sulfation of a Tyr in the N-terminal acidic region increases the affinity for LPL.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Mostly monomer, but also homodimer and homooligomer (PubMed:25387803).
Interacts with lipoprotein lipase (LPL) with 1:1 stoichiometry (PubMed:17997385, PubMed:19304573, PubMed:25387803, PubMed:26725083, PubMed:27929370, PubMed:29899144, PubMed:30559189).
Interacts with high affinity with high-density lipoprotein (HDL) (By similarity).
Interacts with chylomicrons. Interacts with APOA5 (PubMed:17997385).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q8IV16HTT P428583EBI-9080234, EBI-466029
BINARY Q8IV16LPL P068587EBI-9080234, EBI-715909

Complex viewer

View interactors in UniProtKB
View CPX-6091 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Structure

3D structure databases

Family & Domains

Features

Showing features for region, compositional bias, domain.

TypeIDPosition(s)Description
Region21-35Disordered
Compositional bias24-50Acidic residues
Region27-50Important for LPL transport to the lumenal surface of endothelial cells
Domain63-148UPAR/Ly6
Region103-109Important for interaction with LPL

Domain

The N-terminal acidic region is intrinsically disordered (PubMed:26725083).
This region contributes to LPL binding, stabilizes LPL and protects LPL against loss of activity (PubMed:26725083, PubMed:27929370).

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    184
  • Mass (Da)
    19,850
  • Last updated
    2022-02-23 v3
  • Checksum
    8F22D5A4D9886D31
MKALGAVLLALLLFGRPGRGQTQQEEEEEDEDHGPDDYDEEDEDEVEEEETNRLPGGRSRVLLRCYTCKSLPRDERCNLTQNCSHGQTCTTLIAHGNTESGLLTTHSTWCTDSCQPITKTVEGTQVTMTCCQSSLCNVPPWQSSRVQDPTGKGAGGPRGSSETVGAALLLNLLAGLGAMGARRP

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias24-50Acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY245915
EMBL· GenBank· DDBJ
AAO86519.1
EMBL· GenBank· DDBJ
mRNA
CH471162
EMBL· GenBank· DDBJ
EAW82276.1
EMBL· GenBank· DDBJ
Genomic DNA
BC035810
EMBL· GenBank· DDBJ
AAH35810.2
EMBL· GenBank· DDBJ
mRNA
BC063857
EMBL· GenBank· DDBJ
AAH63857.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any 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. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp