LRPAP1 LDL receptor related protein associated protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LRPAP1provided by HGNC
Official Full Name: LDL receptor related protein associated protein 1provided by HGNC
Primary source: HGNC:HGNC:6701
See related: Ensembl:ENSG00000163956 MIM:104225; AllianceGenome:HGNC:6701
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RAP; MRAP; A2RAP; HBP44; MYP23; A2MRAP; alpha-2-MRAP
Summary: This gene encodes a protein that interacts with the low density lipoprotein (LDL) receptor-related protein and facilitates its proper folding and localization by preventing the binding of ligands. Mutations in this gene have been identified in individuals with myopia 23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
Expression: Ubiquitous expression in kidney (RPKM 14.2), placenta (RPKM 12.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4p16.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (3503612..3532422, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (3503365..3532077, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (3505339..3534149, complement)

Chromosome 4 - NC_000004.12 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: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LRPAP1 is released from activated microglia and inhibits microglial phagocytosis and amyloid beta aggregation.
Title: LRPAP1 is released from activated microglia and inhibits microglial phagocytosis and amyloid beta aggregation.
Lrpap1 (RAP) Inhibits Proximal Tubule Clathrin Mediated and Clathrin Independent Endocytosis, Ameliorating Renal Aminoglycoside Nephrotoxicity.
Title: Lrpap1 (RAP) Inhibits Proximal Tubule Clathrin Mediated and Clathrin Independent Endocytosis, Ameliorating Renal Aminoglycoside Nephrotoxicity.
The relationship of ADAMTSL2 and LRPAP1 gene methylation level with rheumatoid arthritis activity.
Title: The relationship of ADAMTSL2 and LRPAP1 gene methylation level with rheumatoid arthritis activity.
Identification of intracellular glycosaminoglycan-interacting proteins by affinity purification mass spectrometry.
Title: Identification of intracellular glycosaminoglycan-interacting proteins by affinity purification mass spectrometry.
Molecular chaperone RAP interacts with LRP1 in a dynamic bivalent mode and enhances folding of ligand-binding regions of other LDLR family receptors.
Title: Molecular chaperone RAP interacts with LRP1 in a dynamic bivalent mode and enhances folding of ligand-binding regions of other LDLR family receptors.
Rhegmatogenous Retinal Detachment in Nonsyndromic High Myopia Associated with Recessive Mutations in LRPAP1.
Title: Rhegmatogenous Retinal Detachment in Nonsyndromic High Myopia Associated with Recessive Mutations in LRPAP1.
LRPAP1 can be used for a novel therapeutic approach that targets mantle cell lymphomas with LRPAP1-reactive BCRs with high specificity
Title: LRPAP1 is a frequent proliferation-inducing antigen of BCRs of mantle cell lymphomas and can be used for specific therapeutic targeting.
data also reveal that D1D2 is able to bind to a second distinct site on LRP1 to form a monovalent complex. The studies confirm the canonical model for ligand recognition by this class of receptors, which is initiated by pairs of lysine residues that dock into acidic pockets on the receptor
Title: High Affinity Binding of the Receptor-associated Protein D1D2 Domains with the Low Density Lipoprotein Receptor-related Protein (LRP1) Involves Bivalent Complex Formation: CRITICAL ROLES OF LYSINES 60 AND 191.
The clinical and biometric features we describe in this report characterize LRPAP1-related high myopia and should raise suspicion for mutations in the gene.
Title: Clinical Characterization of LRPAP1-Related Pediatric High Myopia.
The inhibition caused by reagents that prevented the activation of Rap was reversed by mobilizing intracellular calcium pharmacologically, whereas that caused by acrosome reaction inhibitors that impeded Rab3's binding to GTP was not.
Title: Epac, Rap and Rab3 act in concert to mobilize calcium from sperm's acrosome during exocytosis.

Submit: New GeneRIF Correction See all GeneRIFs (33)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Myopia 23, autosomal recessive MedGen: C3809482 OMIM: 615431 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiethnic meta-analysis of genome-wide association studies in &gt;100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

SHGC-31233 (e-PCR)
- UniSTS:3351

GDB:197442 (e-PCR)
- UniSTS:155931

STS-L33987 (e-PCR)
- UniSTS:18988

HUEST-L33987 (e-PCR)
- UniSTS:18988

GDB:607744 (e-PCR)
- UniSTS:158276

D4S125 (e-PCR)
- UniSTS:147269

SHGC-51659 (e-PCR)
- UniSTS:74312

STS-U06976 (e-PCR)
- UniSTS:20579

GDB:574135 (e-PCR)
- UniSTS:157808

GDB:574140 (e-PCR)
- UniSTS:157809

D1S1425 (e-PCR)
- UniSTS:149621

NoName (e-PCR)
- UniSTS:488061

G33876 (e-PCR)
- UniSTS:50838

SHGC-59848 (e-PCR)
- UniSTS:57765

G59595 (e-PCR)
- UniSTS:136899

WI-22663 (e-PCR)
- UniSTS:32250

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables amyloid-beta binding	TAS Traceable Author Statement more info	PubMed
enables heparin binding	IEA Inferred from Electronic Annotation more info
enables lipase binding	IBA Inferred from Biological aspect of Ancestor more info
enables low-density lipoprotein particle receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables low-density lipoprotein particle receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables low-density lipoprotein particle receptor binding	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor antagonist activity	IBA Inferred from Biological aspect of Ancestor more info
enables receptor antagonist activity	IDA Inferred from Direct Assay more info	PubMed
enables receptor antagonist activity	TAS Traceable Author Statement more info	PubMed
enables receptor ligand activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor binding	TAS Traceable Author Statement more info	PubMed
enables very-low-density lipoprotein particle receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables very-low-density lipoprotein particle receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in amyloid-beta clearance by transcytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in extracellular negative regulation of signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of amyloid-beta clearance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of protein binding	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of receptor internalization	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of receptor internalization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of very-low-density lipoprotein particle clearance	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of very-low-density lipoprotein particle clearance	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of amyloid-beta clearance	TAS Traceable Author Statement more info	PubMed
involved_in regulation of receptor-mediated endocytosis	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi lumen	IEA Inferred from Electronic Annotation more info
located_in cell surface	IEA Inferred from Electronic Annotation more info
is_active_in cis-Golgi network	IBA Inferred from Biological aspect of Ancestor more info
located_in cis-Golgi network	IDA Inferred from Direct Assay more info	PubMed
is_active_in endomembrane system	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info
is_active_in endoplasmic reticulum-Golgi intermediate compartment	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum-Golgi intermediate compartment	IDA Inferred from Direct Assay more info	PubMed
is_active_in endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome lumen	IEA Inferred from Electronic Annotation more info
located_in extracellular region	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in rough endoplasmic reticulum lumen	IBA Inferred from Biological aspect of Ancestor more info
located_in rough endoplasmic reticulum lumen	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: alpha-2-macroglobulin receptor-associated protein

Names: 39 kDa receptor-associated protein; low density lipoprotein receptor-related protein associated protein 1; low density lipoprotein-related protein-associated protein 1 (alpha-2-macroglobulin receptor-associated protein 1)

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.

Genomic

NG_033873.1 RefSeqGene

Range

5076..33886

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1299

mRNA and Protein(s)

NM_002337.4 → NP_002328.1 alpha-2-macroglobulin receptor-associated protein precursor

See identical proteins and their annotated locations for NP_002328.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the protein.

Source sequence(s)

AK222504, AL590235, BC112067, BX647984, DB035408

Consensus CDS

CCDS3371.1

UniProtKB/Swiss-Prot

D3DVR9, P30533, Q2M310, Q53HQ3, Q53HS6

UniProtKB/TrEMBL

B2R6S9

Related

ENSP00000497444.1, ENST00000650182.1

Conserved Domains (3) summary

cd14806
Location:58 → 67

RAP_D1; 3-helical coiled coil [structural motif]

pfam06400
Location:25 → 131

Alpha-2-MRAP_N; Alpha-2-macroglobulin RAP, N-terminal domain

pfam06401
Location:146 → 357

Alpha-2-MRAP_C; Alpha-2-macroglobulin RAP, C-terminal domain

RNA

NR_110005.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' terminal exon, compared to variant 1. This variant is represented as non-coding because it lacks an in-frame open reading frame compared to variant 1.

Source sequence(s)

AK222504, AK311600, AL590235, BX647984