LRPAP1

Protein identityUniProt · HPA

UniProt accession

P30533

Gene

LRPAP1

Ensembl

ENSG00000163956

Chromosome

4

Canonical length

357 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Endoplasmic reticulum

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

357 residues, UniProt reviewed canonical sequence.

>P30533|LRPAP1
     1  MAPRRVRSFL RGLPALLLLL LFLGPWPAAS HGGKYSREKN QPKPSPKRES GEEFRMEKLN
    61  QLWEKAQRLH LPPVRLAELH ADLKIQERDE LAWKKLKLDG LDEDGEKEAR LIRNLNVILA
   121  KYGLDGKKDA RQVTSNSLSG TQEDGLDDPR LEKLWHKAKT SGKFSGEELD KLWREFLHHK
   181  EKVHEYNVLL ETLSRTEEIH ENVISPSDLS DIKGSVLHSR HTELKEKLRS INQGLDRLRR
   241  VSHQGYSTEA EFEEPRVIDL WDLAQSANLT DKELEAFREE LKHFEAKIEK HNHYQKQLEI
   301  AHEKLRHAES VGDGERVSRS REKHALLEGR TKELGYTVKK HLQDLSGRIS RARHNEL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LRPAP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

15 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LRPAP1.

Disease | AllUniProt

Conditions LRPAP1 is implicated in, by any mechanism.

• Myopia 23, autosomal recessive (MYP23) MIM:615431

Disease | GeneticClinVar

7 pathogenic / likely-pathogenic of 132 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Myopia 23, autosomal recessive
• Rare isolated myopia

Disease | ImmuneIEDB

Conditions an epitope on LRPAP1 was assayed in.

• lung non-small cell carcinoma T cell

ReferencesPubMed · IEDB

Publications for LRPAP1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.17

gnomAD pLI

0

gnomAD missense Z

-1.03

DepMap mean gene effect

0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid-beta clearance by transcytosis
• extracellular negative regulation of signal transduction
• negative regulation of amyloid-beta clearance
• negative regulation of receptor internalization
• negative regulation of very-low-density lipoprotein particle clearance
• positive regulation of amyloid-beta clearance
• signal transduction
• regulation of receptor-mediated endocytosis

Molecular functions

• amyloid-beta binding
• heparin binding
• lipase binding
• low-density lipoprotein particle receptor binding
• receptor antagonist activity
• receptor ligand activity
• signaling receptor binding
• very-low-density lipoprotein particle receptor binding

Cellular components

• cell surface
• cis-Golgi network
• endomembrane system
• endoplasmic reticulum
• endoplasmic reticulum-Golgi intermediate compartment
• endosome
• endosome lumen
• extracellular region
• Golgi apparatus
• Golgi lumen
• plasma membrane
• rough endoplasmic reticulum lumen

Protein domainsUniProt · Pfam · InterPro

• Alpha-2-macroglobulin receptor-associated protein, domain 1
• Alpha-2-macroglobulin RAP, C-terminal
• RAP domain superfamily
• Alpha-2-macroglobulin RAP, domain 3
• Alpha-2-macroglobulin RAP, domain 2
• Alpha-2-macroglobulin receptor-associated protein
• Alpha-2-macroglobulin RAP, N-terminal domain
• Alpha-2-macroglobulin RAP, C-terminal domain

KeywordsUniProt

• Coiled coil
• Endoplasmic reticulum
• Endosome
• Glycoprotein
• Golgi apparatus
• Heparin-binding
• Phosphoprotein
• Signal

InteractionsUniProt · HPA

Protein binding partners of LRPAP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LDLR
• LRP1
• LRP1B
• SORL1
• LRP8
• SORT1
• VLDLR