Disease relevance of LRPAP1

• For both, genomic cosmid clones were isolated, and for the human gene a bacteriophage P1 clone containing the entire A2MRAP gene was also retrieved [1].
• Comparative sequence analysis revealed that alpha 2M receptor-associated protein has 73% identity with a rat protein reported to be a pathogenic domain of Heymann nephritis antigen gp 330 and 77% identity to a mouse heparin-binding protein termed HBP-44 [2].
• Using a recombinant form of HBP-44 expressed in Escherichia coli cells as a highly specific ligand for LRP, we demonstrated that HBP-44 coated on cell culture plates mediates the cell-substratum adhesion of mouse 3T3 fibroblasts in a dose-dependent manner, with 50% attachment at the concentration of 0.2 micrograms/ml [3].

High impact information on LRPAP1

• In this report, we have investigated the relationship between gp330, C14p, and alpha 2-MRAP [4].
• In contrast, the other patient, with karyotype 46,XY,del4(p15.3-pter), displayed no signal for LRPAP1 on the deleted chromosome [1].
• Metaphase spreads of two such patients were analyzed by fluorescence in situ hybridization with an LRPAP1 genomic probe [1].
• Cloning, characterization, and chromosomal localization to 4p16 of the human gene (LRPAP1) coding for the alpha 2-macroglobulin receptor-associated protein and structural comparison with the murine gene coding for the 44-kDa heparin-binding protein [1].
• For MRAP, 0.1 mmol/kg gadopentetate dimeglumine was injected into the superior mesenteric artery [5].

Biological context of LRPAP1

• Localization of the alpha 2-macroglobulin receptor-associated protein 1 gene (LRPAP1) and other gene fragments to human chromosome 4p16.3 by direct cDNA selection [6].
• Intron 5 insertion/deletion polymorphism of RAP gene (LRPAP1) has been implicated in other diseases sharing etiology with gallstone disease (GSD) [7].
• CONCLUSIONS: LRPAP1, II genotype carrier females may have increased risk for gallstone disease [8].
• These results suggest genetic variations at the LRPAP1 locus may modulate AD phenotype beyond risk for disease [9].
• The location of binding sites for alpha 2-MRAP in rat kidney was also examined, using an alpha 2-MRAP-IgG fusion protein [10].

Anatomical context of LRPAP1

• The human LRPAP1 locus was assigned to chromosome 4 by PCR of human-hamster hybrid cell lines and by fluorescence in situ hybridization to band 4p16 [1].
• After PLP fixation, alpha 2-MRAP was detected almost exclusively in rough endoplasmic reticulum (RER) cisternae; cell surface staining was virtually absent [10].
• A series of experiments showed that during incubation of snap-frozen tissues, endogenous alpha 2-MRAP is released in soluble form from its intracellular location (i.e., the RER) and binds to gp330 on the brush border of proximal tubules [10].

Other interactions of LRPAP1

• Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1) [11].
• Three coding polymorphisms of LRP1 (exon 3, C766T; exon 14, A217V; and exon 39, D2080N), together with an insertion/deletion polymorphism within the first intron of lipoprotein receptor-associated protein (LRPAP1), have been identified [12].
• A LRPAP1 intronic insertion/deletion polymorphism and phenotypic variability in Alzheimer disease [9].

Analytical, diagnostic and therapeutic context of LRPAP1

• The LRPAP1 gene was amplified from genomic DNA in four long-range PCR amplicons, 2.4 to 7.6 kb in size [13].
• The purpose of this study was to explore the relationship between a polymorphism in the Low Density Lipoprotein Receptor Related Protein-Associated Protein (LRPAP1) gene (4p16.3) and repeated measures of cognition, function, and behavior in persons with AD, using outcome data collected in two caregiver intervention studies [9].
• Further, immunoblotting analysis on the purified complex indicates that the 44-kDa associated protein shares immunological identity to C14p and alpha 2-MRAP [4].
• Magnetic resonance (MR) imaging with arterial portography (MRAP) was compared with computed tomography with arterial portography (CTAP) and conventional MR imaging for preoperative evaluation of hepatic masses in eight patients (nine studies) [5].

References