UniProtKB - Q5SW96 (ARH_HUMAN)
Protein
Low density lipoprotein receptor adapter protein 1
Gene
LDLRAP1
Organism
Homo sapiens (Human)
Status
Functioni
Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity).By similarity1 Publication
GO - Molecular functioni
- amyloid-beta binding Source: BHF-UCL
- AP-1 adaptor complex binding Source: UniProtKB
- AP-2 adaptor complex binding Source: UniProtKB
- clathrin adaptor activity Source: BHF-UCL
- clathrin binding Source: UniProtKB
- low-density lipoprotein particle receptor binding Source: BHF-UCL
- phosphatidylinositol-4,5-bisphosphate binding Source: BHF-UCL
- phosphotyrosine residue binding Source: UniProtKB
- signaling adaptor activity Source: BHF-UCL
- signaling receptor complex adaptor activity Source: UniProtKB
GO - Biological processi
- amyloid precursor protein metabolic process Source: BHF-UCL
- cellular response to cytokine stimulus Source: BHF-UCL
- cholesterol homeostasis Source: BHF-UCL
- cholesterol metabolic process Source: UniProtKB
- cholesterol transport Source: UniProtKB
- low-density lipoprotein particle clearance Source: BHF-UCL
- membrane organization Source: Reactome
- positive regulation of cholesterol metabolic process Source: BHF-UCL
- positive regulation of low-density lipoprotein particle clearance Source: BHF-UCL
- positive regulation of receptor-mediated endocytosis Source: UniProtKB
- positive regulation of receptor-mediated endocytosis involved in cholesterol transport Source: BHF-UCL
- positive regulation of vascular associated smooth muscle cell proliferation Source: BHF-UCL
- receptor internalization Source: BHF-UCL
- receptor-mediated endocytosis Source: BHF-UCL
- receptor-mediated endocytosis involved in cholesterol transport Source: BHF-UCL
- regulation of protein binding Source: UniProtKB
- regulation of protein localization to plasma membrane Source: BHF-UCL
Keywordsi
Biological process | Cholesterol metabolism, Endocytosis, Lipid metabolism, Steroid metabolism, Sterol metabolism |
Enzyme and pathway databases
PathwayCommonsi | Q5SW96 |
Reactomei | R-HSA-8856825, Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828, Clathrin-mediated endocytosis R-HSA-8964026, Chylomicron clearance R-HSA-8964038, LDL clearance |
Protein family/group databases
MoonDBi | Q5SW96, Curated |
Names & Taxonomyi
Protein namesi | Recommended name: Low density lipoprotein receptor adapter protein 1CuratedAlternative name(s): Autosomal recessive hypercholesterolemia protein1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000157978.11 |
HGNCi | HGNC:18640, LDLRAP1 |
MIMi | 605747, gene |
neXtProti | NX_Q5SW96 |
Subcellular locationi
Other locations
- Cytoplasm 1 Publication
Cytoskeleton
- neurofilament Source: BHF-UCL
Cytosol
- cytosol Source: UniProtKB
Endosome
- early endosome Source: UniProtKB
- recycling endosome Source: BHF-UCL
Plasma Membrane
- basal plasma membrane Source: UniProtKB
- cytoplasmic side of plasma membrane Source: BHF-UCL
- plasma membrane Source: Reactome
Other locations
- axon Source: BHF-UCL
- clathrin-coated vesicle membrane Source: Reactome
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Hypercholesterolemia, familial, 4 (FHCL4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL4 inheritance is autosomal recessive.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023320 | 202 | S → H in FHCL4; Lebanon; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs386629678EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 165 | F → A: Abolishes LDLR cytoplasmic tail binding. 1 Publication | 1 | |
Mutagenesisi | 165 | F → V: Abolishes LDLR cytoplasmic tail binding. 1 Publication | 1 | |
Mutagenesisi | 212 – 213 | LL → AA: Abolishes clathrin binding. 1 Publication | 2 | |
Mutagenesisi | 214 | D → A: Abolishes clathrin binding. 1 Publication | 1 | |
Mutagenesisi | 216 | E → A: Abolishes clathrin binding. 1 Publication | 1 | |
Mutagenesisi | 256 | D → R: Abolishes interaction with AP2B1. 1 Publication | 1 | |
Mutagenesisi | 266 | R → A: Abolishes AP-2 complex binding. 1 Publication | 1 |
Keywords - Diseasei
Atherosclerosis, Disease mutation, HyperlipidemiaOrganism-specific databases
DisGeNETi | 26119 |
MalaCardsi | LDLRAP1 |
MIMi | 603813, phenotype |
OpenTargetsi | ENSG00000157978 |
Orphaneti | 391665, Homozygous familial hypercholesterolemia |
PharmGKBi | PA128394641 |
Miscellaneous databases
Pharosi | Q5SW96, Tbio |
Polymorphism and mutation databases
BioMutai | LDLRAP1 |
DMDMi | 116241254 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000064675 | 1 – 308 | Low density lipoprotein receptor adapter protein 1Add BLAST | 308 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 14 | PhosphoserineCombined sources | 1 | |
Modified residuei | 186 | PhosphoserineCombined sources | 1 | |
Modified residuei | 202 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q5SW96 |
jPOSTi | Q5SW96 |
MassIVEi | Q5SW96 |
MaxQBi | Q5SW96 |
PaxDbi | Q5SW96 |
PeptideAtlasi | Q5SW96 |
PRIDEi | Q5SW96 |
ProteomicsDBi | 63967 |
PTM databases
iPTMneti | Q5SW96 |
PhosphoSitePlusi | Q5SW96 |
Expressioni
Tissue specificityi
Expressed at high levels in the kidney, liver, and placenta, with lower levels detectable in brain, heart, muscle, colon, spleen, intestine, lung, and leukocytes.
Gene expression databases
Bgeei | ENSG00000157978, Expressed in right hemisphere of cerebellum and 230 other tissues |
Genevisiblei | Q5SW96, HS |
Organism-specific databases
HPAi | ENSG00000157978, Tissue enhanced (brain) |
Interactioni
Subunit structurei
Interacts (via PID domain) with LDLR (via NPXY motif) (PubMed:12221107). Binds to soluble clathrin trimers (PubMed:12221107).
Interacts with AP2B1; the interaction mediates the association with the AP-2 complex (PubMed:12221107).
Interacts with VLDLR (By similarity).
Interacts with LRP2 (By similarity).
By similarity1 PublicationBinary interactionsi
Hide detailsQ5SW96
GO - Molecular functioni
- clathrin adaptor activity Source: BHF-UCL
- clathrin binding Source: UniProtKB
- low-density lipoprotein particle receptor binding Source: BHF-UCL
- phosphotyrosine residue binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 117561, 25 interactors |
ELMi | Q5SW96 |
IntActi | Q5SW96, 22 interactors |
MINTi | Q5SW96 |
STRINGi | 9606.ENSP00000363458 |
Miscellaneous databases
RNActi | Q5SW96, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q5SW96 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q5SW96 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 42 – 196 | PIDPROSITE-ProRule annotationAdd BLAST | 155 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 249 – 276 | AP-2 complex binding1 PublicationAdd BLAST | 28 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 212 – 216 | Clathrin box1 Publication | 5 | |
Motifi | 257 – 266 | [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif1 Publication | 10 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 23 – 26 | Poly-Gly | 4 |
Domaini
The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1.1 Publication
The PID domain mediates interaction with the NPXY internalization motif of LDLR.By similarity
Phylogenomic databases
eggNOGi | KOG3536, Eukaryota |
GeneTreei | ENSGT00940000157118 |
HOGENOMi | CLU_078253_0_0_1 |
InParanoidi | Q5SW96 |
OMAi | ANTTNMD |
OrthoDBi | 1531411at2759 |
PhylomeDBi | Q5SW96 |
TreeFami | TF314159 |
Family and domain databases
Gene3Di | 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR011993, PH-like_dom_sf IPR006020, PTB/PI_dom |
Pfami | View protein in Pfam PF14719, PID_2, 1 hit |
SMARTi | View protein in SMART SM00462, PTB, 1 hit |
PROSITEi | View protein in PROSITE PS01179, PID, 1 hit |
i Sequence
Sequence statusi: Complete.
Q5SW96-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MDALKSAGRA LIRSPSLAKQ SWGGGGRHRK LPENWTDTRE TLLEGMLFSL
60 70 80 90 100
KYLGMTLVEQ PKGEELSAAA IKRIVATAKA SGKKLQKVTL KVSPRGIILT
110 120 130 140 150
DNLTNQLIEN VSIYRISYCT ADKMHDKVFA YIAQSQHNQS LECHAFLCTK
160 170 180 190 200
RKMAQAVTLT VAQAFKVAFE FWQVSKEEKE KRDKASQEGG DVLGARQDCT
210 220 230 240 250
PSLKSLVATG NLLDLEETAK APLSTVSANT TNMDEVPRPQ ALSGSSVVWE
260 270 280 290 300
LDDGLDEAFS RLAQSRTNPQ VLDTGLTAQD MHYAQCLSPV DWDKPDSSGT
EQDDLFSF
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076925 | 56 | T → M Probable disease-associated variant found in patients with hypercholesterolemia. 1 PublicationCorresponds to variant dbSNP:rs752849346Ensembl. | 1 | |
Natural variantiVAR_023320 | 202 | S → H in FHCL4; Lebanon; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs386629678EnsemblClinVar. | 1 | |
Natural variantiVAR_028403 | 202 | S → P5 PublicationsCorresponds to variant dbSNP:rs6687605EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY389348 Genomic DNA Translation: AAQ90407.1 AL117654 mRNA Translation: CAB56030.2 AL606491 Genomic DNA No translation available. BX572623 Genomic DNA No translation available. BC029770 mRNA Translation: AAH29770.2 |
CCDSi | CCDS30639.1 |
PIRi | T17340 |
RefSeqi | NP_056442.2, NM_015627.2 |
Genome annotation databases
Ensembli | ENST00000374338; ENSP00000363458; ENSG00000157978 |
GeneIDi | 26119 |
KEGGi | hsa:26119 |
UCSCi | uc001bkl.5, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY389348 Genomic DNA Translation: AAQ90407.1 AL117654 mRNA Translation: CAB56030.2 AL606491 Genomic DNA No translation available. BX572623 Genomic DNA No translation available. BC029770 mRNA Translation: AAH29770.2 |
CCDSi | CCDS30639.1 |
PIRi | T17340 |
RefSeqi | NP_056442.2, NM_015627.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2G30 | X-ray | 1.60 | P | 252-267 | [»] | |
SMRi | Q5SW96 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 117561, 25 interactors |
ELMi | Q5SW96 |
IntActi | Q5SW96, 22 interactors |
MINTi | Q5SW96 |
STRINGi | 9606.ENSP00000363458 |
Protein family/group databases
MoonDBi | Q5SW96, Curated |
PTM databases
iPTMneti | Q5SW96 |
PhosphoSitePlusi | Q5SW96 |
Polymorphism and mutation databases
BioMutai | LDLRAP1 |
DMDMi | 116241254 |
Proteomic databases
EPDi | Q5SW96 |
jPOSTi | Q5SW96 |
MassIVEi | Q5SW96 |
MaxQBi | Q5SW96 |
PaxDbi | Q5SW96 |
PeptideAtlasi | Q5SW96 |
PRIDEi | Q5SW96 |
ProteomicsDBi | 63967 |
Protocols and materials databases
Antibodypediai | 30473, 519 antibodies |
DNASUi | 26119 |
Genome annotation databases
Ensembli | ENST00000374338; ENSP00000363458; ENSG00000157978 |
GeneIDi | 26119 |
KEGGi | hsa:26119 |
UCSCi | uc001bkl.5, human |
Organism-specific databases
CTDi | 26119 |
DisGeNETi | 26119 |
EuPathDBi | HostDB:ENSG00000157978.11 |
GeneCardsi | LDLRAP1 |
HGNCi | HGNC:18640, LDLRAP1 |
HPAi | ENSG00000157978, Tissue enhanced (brain) |
MalaCardsi | LDLRAP1 |
MIMi | 603813, phenotype 605747, gene |
neXtProti | NX_Q5SW96 |
OpenTargetsi | ENSG00000157978 |
Orphaneti | 391665, Homozygous familial hypercholesterolemia |
PharmGKBi | PA128394641 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3536, Eukaryota |
GeneTreei | ENSGT00940000157118 |
HOGENOMi | CLU_078253_0_0_1 |
InParanoidi | Q5SW96 |
OMAi | ANTTNMD |
OrthoDBi | 1531411at2759 |
PhylomeDBi | Q5SW96 |
TreeFami | TF314159 |
Enzyme and pathway databases
PathwayCommonsi | Q5SW96 |
Reactomei | R-HSA-8856825, Cargo recognition for clathrin-mediated endocytosis R-HSA-8856828, Clathrin-mediated endocytosis R-HSA-8964026, Chylomicron clearance R-HSA-8964038, LDL clearance |
Miscellaneous databases
BioGRID-ORCSi | 26119, 11 hits in 842 CRISPR screens |
ChiTaRSi | LDLRAP1, human |
EvolutionaryTracei | Q5SW96 |
GeneWikii | Low_density_lipoprotein_receptor_adapter_protein_1 |
GenomeRNAii | 26119 |
Pharosi | Q5SW96, Tbio |
PROi | PR:Q5SW96 |
RNActi | Q5SW96, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000157978, Expressed in right hemisphere of cerebellum and 230 other tissues |
Genevisiblei | Q5SW96, HS |
Family and domain databases
Gene3Di | 2.30.29.30, 1 hit |
InterProi | View protein in InterPro IPR011993, PH-like_dom_sf IPR006020, PTB/PI_dom |
Pfami | View protein in Pfam PF14719, PID_2, 1 hit |
SMARTi | View protein in SMART SM00462, PTB, 1 hit |
PROSITEi | View protein in PROSITE PS01179, PID, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ARH_HUMAN | |
Accessioni | Q5SW96Primary (citable) accession number: Q5SW96 Secondary accession number(s): A2BHI5 Q9UFI9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 30, 2005 |
Last sequence update: | October 17, 2006 | |
Last modified: | December 2, 2020 | |
This is version 159 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations