Q8IV16 · HDBP1_HUMAN
- ProteinGlycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
- GeneGPIHBP1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids184 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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 annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGlycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
- Short namesGPI-HBP1; GPI-anchored HDL-binding protein 1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8IV16
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Apical cell membrane ; Lipid-anchor, GPI-anchor
Basolateral cell membrane ; Lipid-anchor, GPI-anchor
Cell membrane ; Lipid-anchor, GPI-anchor
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Hyperlipoproteinemia 1D (HLPP1D)
- Note
- DescriptionAn autosomal recessive disorder characterized by hyperlipoproteinemia, decreased plasma LPL levels in some patients, high plasma triglyceride levels, and refractory fasting chylomicronemia.
- See alsoMIM:615947
Natural variants in HLPP1D
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_071881 | 65 | C>S | in 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_077634 | 65 | C>Y | in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers; dbSNP:rs587777638 | |
VAR_071882 | 68 | C>G | in 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_077635 | 68 | C>R | in 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_077636 | 68 | C>Y | in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers | |
VAR_077637 | 83 | C>R | in HLPP1D | |
VAR_071883 | 89 | C>F | in HLPP1D; drastically affects interaction with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs587777640 | |
VAR_077638 | 108 | T>R | in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs752728823 | |
VAR_058086 | 115 | Q>P | in 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_077639 | 144 | S>F | in HLPP1D; dbSNP:rs78367243 | |
VAR_071884 | 175 | G>R | in HLPP1D; affects protein expression at the cell surface; reduces interaction with LPL; dbSNP:rs145844329 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_044503 | 14 | it 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 | |||
Sequence: F → C | ||||||
Mutagenesis | 38 | Loss of sulfotyrosine formation. | ||||
Sequence: Y → F | ||||||
Natural variant | VAR_044504 | 56 | no discernible effect on interaction with LPL, chylomicrons or APOA5; dbSNP:rs587777636 | |||
Sequence: G → R | ||||||
Natural variant | VAR_071881 | 65 | in 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 | |||
Sequence: C → S | ||||||
Natural variant | VAR_077634 | 65 | in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers; dbSNP:rs587777638 | |||
Sequence: C → Y | ||||||
Mutagenesis | 66 | Promotes formation of dimers and oligomers reducing number of monomers. | ||||
Sequence: Y → A | ||||||
Natural variant | VAR_071882 | 68 | in 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 | |||
Sequence: C → G | ||||||
Natural variant | VAR_077635 | 68 | in 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 | |||
Sequence: C → R | ||||||
Natural variant | VAR_077636 | 68 | in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers | |||
Sequence: C → Y | ||||||
Mutagenesis | 71 | Promotes formation of dimers and oligomers reducing number of monomers. | ||||
Sequence: L → A | ||||||
Natural variant | VAR_077637 | 83 | in HLPP1D | |||
Sequence: C → R | ||||||
Natural variant | VAR_071883 | 89 | in HLPP1D; drastically affects interaction with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs587777640 | |||
Sequence: C → F | ||||||
Mutagenesis | 91 | Promotes formation of dimers and oligomers reducing number of monomers. | ||||
Sequence: T → A | ||||||
Mutagenesis | 92 | Only slightly increased formation of dimers and oligomers. No effect on number of monomers. Loss of LPL interaction. | ||||
Sequence: L → A | ||||||
Mutagenesis | 93 | Promotes formation of dimers and oligomers reducing number of monomers. | ||||
Sequence: I → A | ||||||
Mutagenesis | 101 | Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL. | ||||
Sequence: G → S | ||||||
Mutagenesis | 104 | Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL. | ||||
Sequence: T → A | ||||||
Mutagenesis | 105 | Promotes formation of dimers and oligomers reducing number of monomers. | ||||
Sequence: T → A | ||||||
Mutagenesis | 106 | Promotes formation of dimers and oligomers severely reducing number of monomers. | ||||
Sequence: H → L | ||||||
Mutagenesis | 107 | Promotes formation of dimers and oligomers reducing number of monomers. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_077638 | 108 | in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers; dbSNP:rs752728823 | |||
Sequence: T → R | ||||||
Mutagenesis | 108 | Retained some interaction with LPL. No effect on number of monomers. | ||||
Sequence: T → A | ||||||
Mutagenesis | 109 | Promotes formation of dimers and oligomers reducing number of monomers. Loss of LPL interaction. | ||||
Sequence: W → C, P, or T | ||||||
Mutagenesis | 109 | Loss of interaction with LPL. Only slightly increased formation of dimers and oligomers. No effect on number of monomers. | ||||
Sequence: W → S, Y, H, A, or F | ||||||
Natural variant | VAR_058086 | 115 | in 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 | |||
Sequence: Q → P | ||||||
Mutagenesis | 115 | No effect on number of monomers. | ||||
Sequence: Q → K | ||||||
Mutagenesis | 126 | Promotes formation of dimers and oligomers reducing number of monomers. | ||||
Sequence: V → A | ||||||
Natural variant | VAR_077639 | 144 | in HLPP1D; dbSNP:rs78367243 | |||
Sequence: S → F | ||||||
Natural variant | VAR_071884 | 175 | in HLPP1D; affects protein expression at the cell surface; reduces interaction with LPL; dbSNP:rs145844329 | |||
Sequence: G → R |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, modified residue, disulfide bond, glycosylation, lipidation, propeptide.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MKALGAVLLALLLFGRPGRG | ||||||
Chain | PRO_0000318208 | 21-151 | Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 | |||
Sequence: QTQQEEEEEDEDHGPDDYDEEDEDEVEEEETNRLPGGRSRVLLRCYTCKSLPRDERCNLTQNCSHGQTCTTLIAHGNTESGLLTTHSTWCTDSCQPITKTVEGTQVTMTCCQSSLCNVPPWQSSRVQDPTG | ||||||
Modified residue | 38 | Sulfotyrosine | ||||
Sequence: Y | ||||||
Disulfide bond | 65↔89 | |||||
Sequence: CYTCKSLPRDERCNLTQNCSHGQTC | ||||||
Disulfide bond | 68↔77 | |||||
Sequence: CKSLPRDERC | ||||||
Glycosylation | 78 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 83↔110 | |||||
Sequence: CSHGQTCTTLIAHGNTESGLLTTHSTWC | ||||||
Disulfide bond | 114↔130 | |||||
Sequence: CQPITKTVEGTQVTMTC | ||||||
Disulfide bond | 131↔136 | |||||
Sequence: CQSSLC | ||||||
Lipidation | 151 | GPI-anchor amidated glycine | ||||
Sequence: G | ||||||
Propeptide | PRO_0000429858 | 152-184 | Removed in mature form | |||
Sequence: KGAGGPRGSSETVGAALLLNLLAGLGAMGARRP |
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
- PTM
Proteomic databases
PTM 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).
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
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8IV16 | HTT P42858 | 3 | EBI-9080234, EBI-466029 | |
BINARY | Q8IV16 | LPL P06858 | 7 | EBI-9080234, EBI-715909 |
Complex viewer
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 21-35 | Disordered | ||||
Sequence: QTQQEEEEEDEDHGP | ||||||
Compositional bias | 24-50 | Acidic residues | ||||
Sequence: QEEEEEDEDHGPDDYDEEDEDEVEEEE | ||||||
Region | 27-50 | Important for LPL transport to the lumenal surface of endothelial cells | ||||
Sequence: EEEDEDHGPDDYDEEDEDEVEEEE | ||||||
Domain | 63-148 | UPAR/Ly6 | ||||
Sequence: LRCYTCKSLPRDERCNLTQNCSHGQTCTTLIAHGNTESGLLTTHSTWCTDSCQPITKTVEGTQVTMTCCQSSLCNVPPWQSSRVQD | ||||||
Region | 103-109 | Important for interaction with LPL | ||||
Sequence: LTTHSTW |
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).
This region contributes to LPL binding, stabilizes LPL and protects LPL against loss of activity (PubMed:26725083, PubMed:27929370).
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length184
- Mass (Da)19,850
- Last updated2022-02-23 v3
- Checksum8F22D5A4D9886D31
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 24-50 | Acidic residues | ||||
Sequence: QEEEEEDEDHGPDDYDEEDEDEVEEEE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |