Gene Symbol: Hps4
Description: HPS4, biogenesis of lysosomal organelles complex 3 subunit 2
Alias: 2010205O06Rik, AU040608, BLOC-3, C130020P05Rik, mKIAA1667, Hermansky-Pudlak syndrome 4 protein homolog, Hermansky-Pudlak syndrome 4 homolog, light ear, light-ear protein
Species: mouse
Products:     Hps4

Top Publications

  1. Meng R, Wu J, Harper D, Wang Y, Kowalska M, Abrams C, et al. Defective release of α granule and lysosome contents from platelets in mouse Hermansky-Pudlak syndrome models. Blood. 2015;125:1623-32 pubmed publisher
  2. Paigen B, Holmes P, Novak E, Swank R. Analysis of atherosclerosis susceptibility in mice with genetic defects in platelet function. Arteriosclerosis. 1990;10:648-52 pubmed
    ..distinct mutants with increased bleeding times and abnormal dense granules were used: maroon (ru-2mr), light ear (le), ruby eye (ru), beige (bg1), and pale ear (ep)...
  3. Meng R, Wang Y, Yao Y, Zhang Z, Harper D, Heijnen H, et al. SLC35D3 delivery from megakaryocyte early endosomes is required for platelet dense granule biogenesis and is differentially defective in Hermansky-Pudlak syndrome models. Blood. 2012;120:404-14 pubmed publisher
  4. Suzuki T, Li W, Zhang Q, Karim A, Novak E, Sviderskaya E, et al. Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene. Nat Genet. 2002;30:321-4 pubmed
    ..Mouse ep has a phenotype identical to another mutant, light ear (le), which suggests that the human homolog of le is a possible human HPS locus...
  5. Dennis M, Delevoye C, Acosta Ruiz A, Hurbain I, Romao M, Hesketh G, et al. BLOC-1 and BLOC-3 regulate VAMP7 cycling to and from melanosomes via distinct tubular transport carriers. J Cell Biol. 2016;214:293-308 pubmed publisher
  6. Schlagel C, Ahmed A. Evidence for genetic control of microwave-induced augmentation of complement receptor-bearing B lymphocytes. J Immunol. 1982;129:1530-3 pubmed
    ..The C57BL/6JTy-le strain remained nonresponsive. This places the essential regulatory gene to the right of the PgM-1 locus and to the left of the rd locus on chromosome 5. ..
  7. Owen F, Riblet R. Genes for the mouse T cell alloantigens Tpre, Tthy, Tind, and Tsu are closely linked near Igh on chromosome 12. J Exp Med. 1984;159:313-7 pubmed
    ..These loci are located in a tightly linked cluster between the immunoglobulin heavy chain constant region gene cluster, Igh-C, and the serum prealbumin locus Pre-1, in this manner: centromere--Igh-C--(Tthy, Tind)-Tsu-Tpre--Pre-1. ..
  8. Lane P. Linkage groups 3 and XVII in the mouse and the position of the light-ear locus. J Hered. 1967;58:21-4 pubmed
  9. Marubashi S, Shimada H, Fukuda M, Ohbayashi N. RUTBC1 Functions as a GTPase-activating Protein for Rab32/38 and Regulates Melanogenic Enzyme Trafficking in Melanocytes. J Biol Chem. 2016;291:1427-40 pubmed publisher
    ..These results collectively indicate that proper spatiotemporal regulation of Rab32/38 is essential for the trafficking of all three melanogenic enzymes in mouse melanocytes. ..

More Information


  1. Yamamoto S, Oka S, Saito Ohara F, Inazawa J, Kawasaki T. Molecular cloning and genomic analysis of mouse glucuronyltransferase involved in biosynthesis of the HNK-1 epitope. J Biochem. 2002;131:337-47 pubmed
    ..Thus, this minimal promoter region of GlcAT-P is suggested to be associated with the regulation of HNK-1 expression. ..
  2. Meisler M. Synthesis and secretion of kidney beta-galactosidase in mutant le/le mice. J Biol Chem. 1978;253:3129-34 pubmed
    We have found that the pigmentation mutant light ear in the mouse has a striking effect on lysosomes in the kidney. Male mice homozygous for the le mutant allele have a 4-fold elevated concentration of kidney beta-galactosidase (EC 3.2.1...
  3. Meisler M, Wanner L, Strahler J. Pigmentation and lysosomal phenotypes in mice doubly homozygous for both light-ear and pale-ear mutant alleles. J Hered. 1984;75:103-6 pubmed
    ..The close similarity in phenotypes of light ear, pale ear, and light-pale mice suggest that the le and ep loci encode different subunits of a multimeric protein,..
  4. Patarca R, Freeman G, Singh R, Wei F, Durfee T, Blattner F, et al. Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection. J Exp Med. 1989;170:145-61 pubmed
    ..Eta-1 gene expression appears to be part of a surprisingly rapid T cell-dependent response to bacterial infection that may precede classical forms of T cell-dependent immunity. ..
  5. Gwynn B, Martina J, Bonifacino J, Sviderskaya E, Lamoreux M, Bennett D, et al. Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOC-1 complex. Blood. 2004;104:3181-9 pubmed
    ..consisting of HPS6/ruby-eye, HPS5/ruby-eye-2, and HPS3/cocoa; and BLOC-3, consisting of HPS1/pale ear and HPS4/light ear. Here, we report the cloning of the mouse HPS mutation reduced pigmentation (rp)...
  6. Chiang P, Oiso N, Gautam R, Suzuki T, Swank R, Spritz R. The Hermansky-Pudlak syndrome 1 (HPS1) and HPS4 proteins are components of two complexes, BLOC-3 and BLOC-4, involved in the biogenesis of lysosome-related organelles. J Biol Chem. 2003;278:20332-7 pubmed
    ..different loci have been associated with HPS in humans, the most frequent of which are mutations of the HPS1 and HPS4 genes...
  7. McGarry M, Reddington M, Novak E, Swank R. Survival and lung pathology of mouse models of Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Proc Soc Exp Biol Med. 1999;220:162-8 pubmed
    ..were apparent in the pearl, pallid, and cocoa mutants whereas minimal effects were noted in ruby eye, muted, light ear, and cocoa mutants. Enlarged air spaces were noted in histologic sections of lungs of several of the mutants...
  8. Meisler M, Levy J, Sansone F, Gordon M. Morphologic and biochemical abnormalities of kidney lysosomes in mice with an inherited albinism. Am J Pathol. 1980;101:581-93 pubmed
    ..In addition, a striking accumulation of ceroidlike pigment was observed. The molecular lesions responsible for the melanolysosomal syndromes in mice and man are still unidentified. ..
  9. Nguyen T, Novak E, Kermani M, Fluhr J, Peters L, Swank R, et al. Melanosome morphologies in murine models of hermansky-pudlak syndrome reflect blocks in organelle development. J Invest Dermatol. 2002;119:1156-64 pubmed
    ..In contrast, the hypopigmentation seen in the gunmetal strain is due to the retention of melanosomes in melanocytes, and inefficient transfer into keratinocytes...
  10. Salazar G, Zlatic S, Craige B, Peden A, Pohl J, Faundez V. Hermansky-Pudlak syndrome protein complexes associate with phosphatidylinositol 4-kinase type II alpha in neuronal and non-neuronal cells. J Biol Chem. 2009;284:1790-802 pubmed publisher
    ..These results suggest that AP-3 and BLOC-1 act, either in concert or sequentially, to specify sorting of PI4KIIalpha along the endocytic route...
  11. Kloer D, Rojas R, Ivan V, Moriyama K, van Vlijmen T, Murthy N, et al. Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) and its interaction with Rab9. J Biol Chem. 2010;285:7794-804 pubmed publisher
    ..HPS arises from mutations in any of 8 genes in humans and 16 genes in mice. Two of these genes, HPS1 and HPS4, encode components of the biogenesis of lysosome-related organelles complex-3 (BLOC-3)...
  12. Park H, Tan C, Faulkner A, Jabbar S, Schmid G, Abey J, et al. Retinal degeneration increases susceptibility to myopia in mice. Mol Vis. 2013;19:2068-79 pubmed
    ..Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism...
  13. Lane P, Green E. Pale ear and light ear in the house mouse. Mimic mutations in linkage groups XII and XVII. J Hered. 1967;58:17-20 pubmed
  14. Novak E, Hui S, Swank R. Platelet storage pool deficiency in mouse pigment mutations associated with seven distinct genetic loci. Blood. 1984;63:536-44 pubmed
    ..In the present study, five other mutants with defective lysosomal enzyme secretion--pearl, pallid, light ear, maroon, and ruby-eye--were likewise found to have abnormally prolonged bleeding times after experimental injury...
  15. LaVail M, Sidman R. C57BL-6J mice with inherited retinal degeneration. Arch Ophthalmol. 1974;91:394-400 pubmed
  16. Delprato A, Raghavan S, Lyerla T. An established light ear mutant (C57BL/6J-Pdeb(rd1) le) mouse cell line exhibits a block to secretion of lysosomal enzymes. Exp Cell Res. 2000;256:315-20 pubmed
    The hypopigment mutant mice, light ear, pallid, and beige, possess defects in melanosomes, lysosomes, and platelet dense granules, suggesting that these organelles share a common biogenesis and processing...
  17. Nazarian R, Falcon Perez J, Dell Angelica E. Biogenesis of lysosome-related organelles complex 3 (BLOC-3): a complex containing the Hermansky-Pudlak syndrome (HPS) proteins HPS1 and HPS4. Proc Natl Acad Sci U S A. 2003;100:8770-5 pubmed
    ..Several HPS genes encode proteins of unknown function including HPS1, HPS3, and HPS4. Here we have identified and characterized endogenous HPS3 and HPS4 proteins from HeLa cells...
  18. Morin L, Studholme K. Separation of function for classical and ganglion cell photoreceptors with respect to circadian rhythm entrainment and induction of photosomnolence. Neuroscience. 2011;199:213-24 pubmed publisher
  19. McGarry M, Novak E, Swank R. Progenitor cell defect correctable by bone marrow transplantation in five independent mouse models of platelet storage pool deficiency. Exp Hematol. 1986;14:261-5 pubmed
    ..bone marrow transplantations were carried out between normal C57Bl/6J mice and five of these mutants, pearl, light ear, pale ear, ruby-eye, and maroon, to test whether the platelet defects are due to platelet progenitor cells or to ..
  20. Martina J, Moriyama K, Bonifacino J. BLOC-3, a protein complex containing the Hermansky-Pudlak syndrome gene products HPS1 and HPS4. J Biol Chem. 2003;278:29376-84 pubmed
    ..HPS4-deficient fibroblasts from light ear mice display normal distribution and trafficking of the lysosomal membrane protein, Lamp-2, in contrast to ..
  21. Chan W, Sherer N, Uchil P, Novak E, Swank R, Mothes W. Murine leukemia virus spreading in mice impaired in the biogenesis of secretory lysosomes and Ca2+-regulated exocytosis. PLoS ONE. 2008;3:e2713 pubmed publisher
    ..Retroviruses have been observed to bud intracellularly into multivesicular bodies (MVB), in addition to the plasma membrane. Release from MVB is thought to occur by Ca(2+)-regulated fusion with the plasma membrane...
  22. Borowska J, Trenholm S, Awatramani G. An intrinsic neural oscillator in the degenerating mouse retina. J Neurosci. 2011;31:5000-12 pubmed publisher
    ..Together, these results indicate that an electrically coupled network of ON cone bipolar/AII amacrine cells constitutes an intrinsic oscillator in the rd1 retina that is likely to drive synaptic activity in downstream circuits. ..