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Protein

Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1

Gene

GPIHBP1

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

Functioni

Plays a key role in the lipolytic processing of chylomicrons. Required for the transport of lipoprotein lipase LPL into the capillary lumen (By similarity).By similarity

GO - Molecular functioni

  • chylomicron binding Source: BHF-UCL
  • lipase binding Source: BHF-UCL
  • lipid binding Source: UniProtKB-KW
  • lipoprotein particle binding Source: UniProtKB
  • protein transmembrane transporter activity Source: BHF-UCL

GO - Biological processi

  • cholesterol homeostasis Source: BHF-UCL
  • chylomicron remodeling Source: Reactome
  • C-terminal protein lipidation Source: Reactome
  • intracellular protein transport Source: BHF-UCL
  • positive regulation of chylomicron remnant clearance Source: BHF-UCL
  • positive regulation of lipoprotein lipase activity Source: BHF-UCL
  • protein import Source: BHF-UCL
  • protein localization to cell surface Source: BHF-UCL
  • protein stabilization Source: BHF-UCL
  • regulation of lipoprotein lipase activity Source: Reactome
  • response to heparin Source: BHF-UCL
  • retinoid metabolic process Source: Reactome
  • transcytosis Source: BHF-UCL
  • triglyceride homeostasis Source: BHF-UCL

Keywordsi

Biological processTransport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-163125 Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-8963889 Assembly of active LPL and LIPC lipase complexes
R-HSA-8963901 Chylomicron remodeling
R-HSA-975634 Retinoid metabolism and transport

Names & Taxonomyi

Protein namesi
Recommended name:
Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1
Short name:
GPI-HBP1
Short name:
GPI-anchored HDL-binding protein 1
Alternative name(s):
High density lipoprotein-binding protein 1
Gene namesi
Name:GPIHBP1
Synonyms:HBP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000277494.1
HGNCiHGNC:24945 GPIHBP1
MIMi612757 gene
neXtProtiNX_Q8IV16

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

Keywords - Cellular componenti

Cell membrane, HDL, Membrane

Pathology & Biotechi

Involvement in diseasei

Hyperlipoproteinemia 1D (HLPP1D)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by hyperlipoproteinemia, decreased plasma LPL levels in some patients, high plasma triglyceride levels, and refractory fasting chylomicronemia.
See also OMIM:615947
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07188165C → 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. 2 PublicationsCorresponds to variant dbSNP:rs587777638Ensembl.1
Natural variantiVAR_07763465C → Y in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers. 2 PublicationsCorresponds to variant dbSNP:rs587777638Ensembl.1
Natural variantiVAR_07188268C → 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. 2 PublicationsCorresponds to variant dbSNP:rs587777639Ensembl.1
Natural variantiVAR_07763568C → R in HLPP1D; unknown pathological 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 in one individual. 2 Publications1
Natural variantiVAR_07763668C → Y in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers. 2 Publications1
Natural variantiVAR_07763783C → R in HLPP1D. 1 Publication1
Natural variantiVAR_07188389C → F in HLPP1D; drastically affects interaction with LPL; promotes formation of dimers and oligomers reducing number of monomers. 2 PublicationsCorresponds to variant dbSNP:rs587777640Ensembl.1
Natural variantiVAR_077638108T → R in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers. 2 Publications1
Natural variantiVAR_058086115Q → P in HLPP1D; a patient with chylomicronemia; does not affect protein expression at the cell surface; does not interact with LPL; does not interact with chylomicrons; promotes formation of dimers and oligomers reducing number of monomers. 3 PublicationsCorresponds to variant dbSNP:rs587777637Ensembl.1
Natural variantiVAR_077639144S → F in HLPP1D. 1 PublicationCorresponds to variant dbSNP:rs78367243Ensembl.1
Natural variantiVAR_071884175G → R in HLPP1D; affects protein expression at the cell surface; reduces interaction with LPL. 1 PublicationCorresponds to variant dbSNP:rs145844329Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi66Y → A: Promotes formation of dimers and oligomers reducing number of monomers. 1 Publication1
Mutagenesisi71L → A: Promotes formation of dimers and oligomers reducing number of monomers. 1 Publication1
Mutagenesisi91T → A: Promotes formation of dimers and oligomers reducing number of monomers. 1 Publication1
Mutagenesisi92L → A: Only slightly increased formation of dimers and oligomers. No effect on number of monomers. Loss of LPL interaction. 1 Publication1
Mutagenesisi93I → A: Promotes formation of dimers and oligomers reducing number of monomers. 1 Publication1
Mutagenesisi101G → S: Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL. 1 Publication1
Mutagenesisi104T → A: Promotes formation of dimers and oligomers reducing number of monomers. Retained some interaction with LPL. 1 Publication1
Mutagenesisi105T → A: Promotes formation of dimers and oligomers reducing number of monomers. 1 Publication1
Mutagenesisi106H → L: Promotes formation of dimers and oligomers severely reducing number of monomers. 1 Publication1
Mutagenesisi107S → A: Promotes formation of dimers and oligomers reducing number of monomers. 1 Publication1
Mutagenesisi108T → A: Retained some interaction with LPL. No effect on number of monomers. 1 Publication1
Mutagenesisi109W → C, P or T: Promotes formation of dimers and oligomers reducing number of monomers. Loss of LPL interaction. 1 Publication1
Mutagenesisi109W → S, Y, H, A or F: Only slightly increased formation of dimers and oligomers. No effect on number of monomers. Loss of LPL interaction. 1 Publication1
Mutagenesisi115Q → K: No effect on number of monomers. 1 Publication1
Mutagenesisi126V → A: Promotes formation of dimers and oligomers reducing number of monomers. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi338328
MalaCardsiGPIHBP1
MIMi615947 phenotype
Orphaneti411 Hyperlipoproteinemia type 1
70470 Hyperlipoproteinemia type 5
PharmGKBiPA162390135

Polymorphism and mutation databases

BioMutaiGPIHBP1
DMDMi74728020

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000031820821 – 151Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1Add BLAST131
PropeptideiPRO_0000429858152 – 184Removed in mature formCuratedAdd BLAST33

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi65 ↔ 89By similarity
Disulfide bondi68 ↔ 77By similarity
Glycosylationi78N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi83 ↔ 110By similarity
Disulfide bondi114 ↔ 130By similarity
Disulfide bondi131 ↔ 136By similarity
Lipidationi151GPI-anchor amidated glycineBy similarity1

Post-translational modificationi

Glycosylation of Asn-78 is critical for cell surface localization and the binding of chylomicrons and lipoprotein lipase.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiQ8IV16
PeptideAtlasiQ8IV16
PRIDEiQ8IV16

PTM databases

iPTMnetiQ8IV16
PhosphoSitePlusiQ8IV16

Expressioni

Gene expression databases

BgeeiENSG00000277494
CleanExiHS_GPIHBP1
HS_HBP1
GenevisibleiQ8IV16 HS

Organism-specific databases

HPAiHPA066302

Interactioni

Subunit structurei

Mostly monomer, but also homodimer and homooligomer (PubMed:25387803). Interacts with high affinity with high-density lipoprotein (HDL) (By similarity). Only monomer interacts with lipoprotein lipase (LPL) (PubMed:25387803, PubMed:17997385). Interacts with chylomicrons and APOA5 (PubMed:17997385).By similarity2 Publications

GO - Molecular functioni

  • lipase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi1307126 interactors.
IntActiQ8IV16 1 interactor.
STRINGi9606.ENSP00000329266

Structurei

3D structure databases

ProteinModelPortaliQ8IV16
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini63 – 148UPAR/Ly6Add BLAST86

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi25 – 31Poly-Glu7
Compositional biasi40 – 50Poly-GluAdd BLAST11

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J46G Eukaryota
ENOG41116TR LUCA
HOGENOMiHOG000112872
InParanoidiQ8IV16
KOiK20001
OrthoDBiEOG091G0UW5
PhylomeDBiQ8IV16
TreeFamiTF338440

Family and domain databases

InterProiView protein in InterPro
IPR016054 LY6_UPA_recep-like
PfamiView protein in Pfam
PF00021 UPAR_LY6, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q8IV16-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKALGAVLLA LLLCGRPGRG QTQQEEEEED EDHGPDDYDE EDEDEVEEEE
60 70 80 90 100
TNRLPGGRSR VLLRCYTCKS LPRDERCNLT QNCSHGQTCT TLIAHGNTES
110 120 130 140 150
GLLTTHSTWC TDSCQPITKT VEGTQVTMTC CQSSLCNVPP WQSSRVQDPT
160 170 180
GKGAGGPRGS SETVGAALLL NLLAGLGAMG ARRP
Length:184
Mass (Da):19,806
Last modified:December 7, 2004 - v2
Checksum:i89FF61B08A008C70
GO

Polymorphismi

The missense variant Arg-56 may be associated with severe hypertriglyceridemia and chylomicronemia.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04450314C → F Polymorphism; it may act as a disease modifier contributing to severe HLPP1D when associated with R-68 or F-89; results in decreased GPIHBP1 expression at the cell surface; does not affect interaction with LPL when associated in cis with R-68 in one individual. 3 PublicationsCorresponds to variant dbSNP:rs11538389Ensembl.1
Natural variantiVAR_04450456G → R Polymorphism; no discernible effect on interaction with LPL, chylomicrons or APOA5. 2 PublicationsCorresponds to variant dbSNP:rs587777636Ensembl.1
Natural variantiVAR_07188165C → 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. 2 PublicationsCorresponds to variant dbSNP:rs587777638Ensembl.1
Natural variantiVAR_07763465C → Y in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers. 2 PublicationsCorresponds to variant dbSNP:rs587777638Ensembl.1
Natural variantiVAR_07188268C → 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. 2 PublicationsCorresponds to variant dbSNP:rs587777639Ensembl.1
Natural variantiVAR_07763568C → R in HLPP1D; unknown pathological 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 in one individual. 2 Publications1
Natural variantiVAR_07763668C → Y in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers severely reducing number of monomers. 2 Publications1
Natural variantiVAR_07763783C → R in HLPP1D. 1 Publication1
Natural variantiVAR_07188389C → F in HLPP1D; drastically affects interaction with LPL; promotes formation of dimers and oligomers reducing number of monomers. 2 PublicationsCorresponds to variant dbSNP:rs587777640Ensembl.1
Natural variantiVAR_077638108T → R in HLPP1D; does not interact with LPL; promotes formation of dimers and oligomers reducing number of monomers. 2 Publications1
Natural variantiVAR_058086115Q → P in HLPP1D; a patient with chylomicronemia; does not affect protein expression at the cell surface; does not interact with LPL; does not interact with chylomicrons; promotes formation of dimers and oligomers reducing number of monomers. 3 PublicationsCorresponds to variant dbSNP:rs587777637Ensembl.1
Natural variantiVAR_077639144S → F in HLPP1D. 1 PublicationCorresponds to variant dbSNP:rs78367243Ensembl.1
Natural variantiVAR_071884175G → R in HLPP1D; affects protein expression at the cell surface; reduces interaction with LPL. 1 PublicationCorresponds to variant dbSNP:rs145844329Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY245915 mRNA Translation: AAO86519.1
CH471162 Genomic DNA Translation: EAW82276.1
BC035810 mRNA Translation: AAH35810.2
BC063857 mRNA Translation: AAH63857.1
CCDSiCCDS34954.1
RefSeqiNP_001288701.1, NM_001301772.1
NP_835466.2, NM_178172.5
UniGeneiHs.426410

Genome annotation databases

EnsembliENST00000622500; ENSP00000480053; ENSG00000277494
GeneIDi338328
KEGGihsa:338328
UCSCiuc033cbs.1 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHDBP1_HUMAN
AccessioniPrimary (citable) accession number: Q8IV16
Secondary accession number(s): Q6P3T2, Q86W15
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: December 7, 2004
Last modified: January 31, 2018
This is version 121 of the entry and version 2 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

Complete proteome, Reference proteome