Disease relevance of HPS3

• HPS-3 manifests with mild hypopigmentation and bleeding [1].

High impact information on HPS3

• The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal how new vesicles form in specialized cells [2].
• Here we have identified and characterized endogenous HPS3 and HPS4 proteins from HeLa cells [3].
• A third HPS-causing gene, HPS3, was recently identified on the basis of homozygosity mapping of a genetic isolate of HPS in central Puerto Rico [4].
• A 15-year-old Irish/English boy was heterozygous for an 89-bp insertion between exons 16 and 17 resulting from abnormal splicing; his fibroblast HPS3 mRNA is normal in amount but is increased in size [4].
• To assess the role of the HPS3 protein in melanization, cultured melanocytes developed from HPS-3 patients were evaluated biochemically and histologically for activity and localization of melanocyte-specific proteins [5].

Biological context of HPS3

• The Hermansky-Pudlak syndrome 3 (cocoa) protein is a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2) [6].
• The HPS3 gene deletion is most frequent in central PR (1:32; 3.1%) [7].
• RESULTS: Snellen visual acuity was 20/160-2 in the HPS-1 group and 20/125+2 in the HPS-3 group (P = 0.017) [8].
• Its location on human chromosome 3q24 suggested that the mouse model corresponding to HPS-3 disease might be subtle gray [9].

Anatomical context of HPS3

• The endogenous HPS3, HPS5 and HPS6 proteins from human HeLa cells coimmunoprecipitated with each other from crude extracts as well as from fractions resulting from size-exclusion chromatography and density gradient centrifugation [10].
• Ultrastructurally, HPS-3 melanocytes contained morphologically normal melanosomes, predominantly of stage I and II with minimal stage III and few stage IV melanosomes [5].
• Unique to HPS-3 melanocytes were numerous DOPA-positive 50-nm vesicles and tubular elements present throughout the cell body and dendrites [5].

Associations of HPS3 with chemical compounds

• This review discusses the biochemical and functional properties of the products of identified HPS genes, which include subunits of the AP-3 complex and the novel proteins HPS1p, HPS3p, HPS4p, pallidin and muted [11].

Other interactions of HPS3

• However, the functions of the HPS1, HPS3, and HPS4 gene products remain unknown [12].
• These complications are common among Puerto Rican HPS-1 patients but have not appeared in HPS-2 or HPS-3 patients [13].

Analytical, diagnostic and therapeutic context of HPS3

• Immunoelectron microscopy of normal melanocytes expressing GFP-HPS3 showed co-localization of GFP-HPS3 with clathrin, predominantly on small vesicles in the perinuclear region [14].

References