Ldlrap1 low density lipoprotein receptor adaptor protein 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Ldlrap1provided by MGI
Official Full Name: low density lipoprotein receptor adaptor protein 1provided by MGI
Primary source: MGI:MGI:2140175
See related: Ensembl:ENSMUSG00000037295 AllianceGenome:MGI:2140175
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Arh; ARH2; Arh1; FHCB1; FHCB2
Summary: Enables amyloid-beta binding activity. Acts upstream of or within cholesterol homeostasis. Located in early endosome and neurofilament. Is expressed in naris; nasal cavity respiratory epithelium; olfactory epithelium; parietal endoderm; and yolk sac endoderm. Used to study autosomal recessive hypercholesterolemia. Human ortholog(s) of this gene implicated in autosomal recessive hypercholesterolemia. Orthologous to human LDLRAP1 (low density lipoprotein receptor adaptor protein 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in adrenal adult (RPKM 8.3), lung adult (RPKM 7.8) and 26 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 D3; 4 67.09 cM

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (134468865..134495342, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (134741554..134768032, complement)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The combination of Arh and Dab2 is responsible for the majority of adaptor function in LDLR endocytosis and LDLR-mediated cholesterol homeostasis.
Title: Endocytic adaptors Arh and Dab2 control homeostasis of circulatory cholesterol.
cells that depend upon ARH for LDL uptake can control which lipoproteins are internalized by their LDLRs through changes in nitric oxide.
Title: S-nitrosylation of ARH is required for LDL uptake by the LDL receptor.
ARH marks ROMK for clathrin-dependent endocytosis, in concert with the demands of potassium homeostasis
Title: The ARH adaptor protein regulates endocytosis of the ROMK potassium secretory channel in mouse kidney.
the endocytic adaptor protein ARH associates with motor and centrosomal proteins and is involved in centrosome assembly and cytokinesis
Title: The endocytic adaptor protein ARH associates with motor and centrosomal proteins and is involved in centrosome assembly and cytokinesis.
Loss of gamma-secretase function decreased endocytosis of low-density lipoprotein (LDL) receptor
Title: Loss of gamma-secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis.
Taken together, our data suggest that ARH is a multifunctional protein whose spectrum of function in the brain goes beyond the traditionally known metabolism of lipoproteins, and that ARH may be locally synthesized in the axon.
Title: Characterization of the adaptor protein ARH expression in the brain and ARH molecular interactions.
results are consistent with LDL receptor adaptor protein(ARH) playing a critical and specific role in low density lipoprotein receptor endocytosis in the liver
Title: Normal sorting but defective endocytosis of the low density lipoprotein receptor in mice with autosomal recessive hypercholesterolemia.
Hepatocytes do not take-up LDL in vivo without ARH protein, but they normally catabolize LDL in vitro. Thus, the requirement of ARH protein for proper functioning of the LDLR is not cell-specific, but rather may depend on the cellular environment.
Title: Disruption of autosomal recessive hypercholesterolemia gene shows different phenotype in vitro and in vivo.
the LDL receptor alone can account for the clearance of apoE-containing lipoproteins in mice, and the contribution of other receptors is minimal, and b) defects in either increase the sensitivity to apoE-induced hypertriglyceridemia in mice.
Title: LDL receptor deficiency or apoE mutations prevent remnant clearance and induce hypertriglyceridemia in mice.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1) 1 citation
Targeted (1) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables AP-1 adaptor complex binding	ISO Inferred from Sequence Orthology more info
enables AP-2 adaptor complex binding	ISO Inferred from Sequence Orthology more info
enables amyloid-beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables amyloid-beta binding	ISO Inferred from Sequence Orthology more info
enables clathrin adaptor activity	ISO Inferred from Sequence Orthology more info
enables clathrin binding	ISO Inferred from Sequence Orthology more info	PubMed
enables low-density lipoprotein particle receptor binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-4,5-bisphosphate binding	ISO Inferred from Sequence Orthology more info
enables phosphotyrosine residue binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling adaptor activity	ISO Inferred from Sequence Orthology more info
enables signaling receptor binding	ISO Inferred from Sequence Orthology more info	PubMed
enables signaling receptor complex adaptor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in amyloid precursor protein metabolic process	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cytokine stimulus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cholesterol homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within endocytosis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in low-density lipoprotein particle clearance	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of low-density lipoprotein particle clearance	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of receptor-mediated endocytosis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of receptor-mediated endocytosis involved in cholesterol transport	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular associated smooth muscle cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in receptor internalization	ISO Inferred from Sequence Orthology more info
involved_in receptor-mediated endocytosis	ISO Inferred from Sequence Orthology more info
involved_in receptor-mediated endocytosis involved in cholesterol transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein binding	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein localization to plasma membrane	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within steroid metabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in axon	ISO Inferred from Sequence Orthology more info
located_in basal plasma membrane	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
is_active_in early endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	ISO Inferred from Sequence Orthology more info
located_in neurofilament	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: low density lipoprotein receptor adapter protein 1

Names: LDL receptor adaptor protein; autosomal recessive hypercholesterolemia protein homolog

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_145554.2 → NP_663529.2 low density lipoprotein receptor adapter protein 1

See identical proteins and their annotated locations for NP_663529.2

Status: VALIDATED

Source sequence(s)

AK148340, AK167290, BY124598, BY435601

Consensus CDS

CCDS51327.1

UniProtKB/Swiss-Prot

Q3TW86, Q6NWV6, Q8C142, Q8VDQ0

Related

ENSMUSP00000036749.7, ENSMUST00000037828.8

Conserved Domains (1) summary

cd13159
Location:43 → 165

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000070.7 Reference GRCm39 C57BL/6J

Range

134468865..134495342 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006538423.5 → XP_006538486.1 low density lipoprotein receptor adapter protein 1 isoform X1

See identical proteins and their annotated locations for XP_006538486.1

UniProtKB/Swiss-Prot

Q8C142

Conserved Domains (1) summary

cd13159
Location:1 → 121

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold