Gene Symbol: Bloc1s6
Description: biogenesis of lysosomal organelles complex-1, subunit 6, pallidin
Alias: BLOC-1, Pldn, Stx13bp1, biogenesis of lysosome-related organelles complex 1 subunit 6, BLOC-1 subunit 6, biogenesis of organelles complex-1, subunit 6, pallidin, pallid protein, pallidin, syntaxin 13 binding protein 1, syntaxin 13-interacting protein pallid
Species: mouse
Products:     Bloc1s6

Top Publications

  1. 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
    ..adaptor complex AP-3; biogenesis of lysosome-related organelles complex 1 (BLOC-1), consisting of 4 HPS proteins (pallidin, muted, cappuccino, HPS7/sandy); BLOC-2, consisting of HPS6/ruby-eye, HPS5/ruby-eye-2, and HPS3/cocoa; and BLOC-3,..
  2. Setty S, Tenza D, Truschel S, Chou E, Sviderskaya E, Theos A, et al. BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes toward lysosome-related organelles. Mol Biol Cell. 2007;18:768-80 pubmed
  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. 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...
  5. Newell Litwa K, Chintala S, Jenkins S, Pare J, McGaha L, Smith Y, et al. Hermansky-Pudlak protein complexes, AP-3 and BLOC-1, differentially regulate presynaptic composition in the striatum and hippocampus. J Neurosci. 2010;30:820-31 pubmed publisher
    ..Loss-of-function alleles of BLOC-1, Pldn(pa/pa), and Muted(mu/mu) revealed that this complex acts as a brain-region-specific regulator of AP-3...
  6. Swank R, Novak E, McGarry M, Rusiniak M, Feng L. Mouse models of Hermansky Pudlak syndrome: a review. Pigment Cell Res. 1998;11:60-80 pubmed
  7. Huang L, Kuo Y, Gitschier J. The pallid gene encodes a novel, syntaxin 13-interacting protein involved in platelet storage pool deficiency. Nat Genet. 1999;23:329-32 pubmed
    ..It encodes a ubiquitously expressed, highly charged 172-amino-acid protein (termed pallidin) with no homology to known proteins...
  8. Hoyle D, Rodriguez Fernandez I, Dell Angelica E. Functional interactions between OCA2 and the protein complexes BLOC-1, BLOC-2, and AP-3 inferred from epistatic analyses of mouse coat pigmentation. Pigment Cell Melanoma Res. 2011;24:275-81 pubmed publisher
    ..These observations suggest functional links between OCA2 and these three protein complexes involved in melanosome biogenesis. ..
  9. Larimore J, Tornieri K, Ryder P, Gokhale A, Zlatic S, Craige B, et al. The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse. Mol Biol Cell. 2011;22:4854-67 pubmed publisher
    ..Our findings indicate a novel vesicle transport mechanism requiring BLOC-1 and AP-3 complexes for cargo sorting from neuronal cell bodies to neurites and nerve terminals...

More Information


  1. Gokhale A, Larimore J, Werner E, So L, Moreno De Luca A, Lese Martin C, et al. Quantitative proteomic and genetic analyses of the schizophrenia susceptibility factor dysbindin identify novel roles of the biogenesis of lysosome-related organelles complex 1. J Neurosci. 2012;32:3697-711 pubmed publisher
    ..Thus, our quantitative proteomic studies expand the functional repertoire of the BLOC-1 complex and provide insight into putative molecular pathways of schizophrenia susceptibility. ..
  2. Salazar G, Craige B, Styers M, Newell Litwa K, Doucette M, Wainer B, et al. BLOC-1 complex deficiency alters the targeting of adaptor protein complex-3 cargoes. Mol Biol Cell. 2006;17:4014-26 pubmed
    ..These results indicate that the BLOC-1 and AP-3 protein complexes affect the targeting of SNARE and non-SNARE AP-3 cargoes and suggest a function of the BLOC-1 complex in membrane protein sorting. ..
  3. Ciciotte S, Gwynn B, Moriyama K, Huizing M, Gahl W, Bonifacino J, et al. Cappuccino, a mouse model of Hermansky-Pudlak syndrome, encodes a novel protein that is part of the pallidin-muted complex (BLOC-1). Blood. 2003;101:4402-7 pubmed
    ..that the wild-type cno gene encodes a novel, ubiquitously expressed cytoplasmic protein that coassembles with pallidin and the muted protein in the BLOC-1 complex. Further, we identify a frameshift mutation in mutant cno/cno mice...
  4. Li W, Zhang Q, Oiso N, Novak E, Gautam R, O Brien E, et al. Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Nat Genet. 2003;35:84-9 pubmed
    ..9-11), which regulates trafficking to lysosome-related organelles and includes the proteins pallidin, muted and cappuccino, which are associated with HPS in mice...
  5. Bossi G, Booth S, Clark R, Davis E, Liesner R, Richards K, et al. Normal lytic granule secretion by cytotoxic T lymphocytes deficient in BLOC-1, -2 and -3 and myosins Va, VIIa and XV. Traffic. 2005;6:243-51 pubmed
    ..These results reveal differences in the protein machinery required for biogenesis and/or secretion of lysosome-related organelles in CTL and melanocytes...
  6. Falcon Perez J, Starcevic M, Gautam R, Dell Angelica E. BLOC-1, a novel complex containing the pallidin and muted proteins involved in the biogenesis of melanosomes and platelet-dense granules. J Biol Chem. 2002;277:28191-9 pubmed
    ..We report that these two proteins, pallidin and muted, are components of a novel protein complex...
  7. Pedroza M, Welschhans R, Agarwal S. Targeting of cadherin-11 decreases skin fibrosis in the tight skin-1 mouse model. PLoS ONE. 2017;12:e0187109 pubmed publisher
    ..These data add to the growing evidence for the important role of CDH11 in tissue fibrosis and fibrotic disease such as systemic sclerosis. ..
  8. Falcon Perez J, Dell Angelica E. The pallidin (Pldn) gene and the role of SNARE proteins in melanosome biogenesis. Pigment Cell Res. 2002;15:82-6 pubmed
    This review focuses on the product of the pallidin (Pldn) gene, one of a number of genes that in mice are associated with pigmentation defects and platelet dense granule deficiency...
  9. Kakizoe E, Shiota N, Tanabe Y, Shimoura K, Kobayashi Y, Okunishi H. Isoform-selective upregulation of mast cell chymase in the development of skin fibrosis in scleroderma model mice. J Invest Dermatol. 2001;116:118-23 pubmed
    ..These results strongly support the contention that the connective-tissue-type mast cell chymase plays a crucial role in fibroproliferative remodeling of the skin. ..
  10. Ito S, Bartolak Suki E, Shipley J, Parameswaran H, Majumdar A, Suki B. Early emphysema in the tight skin and pallid mice: roles of microfibril-associated glycoproteins, collagen, and mechanical forces. Am J Respir Cell Mol Biol. 2006;34:688-94 pubmed
    ..Our findings suggest the possibility that MAGP-2-related abnormal collagen assembly, combined with mechanical forces, is involved in the progression of emphysema in the Tsk mice. ..
  11. Korsgren C, Cohen C. cDNA sequence, gene sequence, and properties of murine pallidin (band 4.2), the protein implicated in the murine pallid mutation. Genomics. 1994;21:478-85 pubmed
    ..2 cDNA sequence containing an open reading frame of 2073 bp and coding for 691 amino acids. This is the same size as the human erythrocyte protein, with which the murine protein shares a 72% amino acid identity. ..
  12. Sitaram A, Dennis M, Chaudhuri R, De Jesus Rojas W, Tenza D, Setty S, et al. Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes. Mol Biol Cell. 2012;23:3178-92 pubmed
    ..These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs...
  13. Graff R, Hauptfeld V, Riordan K, Kurtz M. Continued mapping of chromosome 2 genes. Immunogenetics. 1994;40:21-6 pubmed
    ..The order of the bracketed genes is not known. H-44 maps centromeric to IR-H-Y. The genes encoding the antigens that stimulate lymphocyte clones 2G7, 2C10, 1F6, 1B10, and 1H10 map centromeric to H-45. ..
  14. Monis W, Faundez V, Pazour G. BLOC-1 is required for selective membrane protein trafficking from endosomes to primary cilia. J Cell Biol. 2017;216:2131-2150 pubmed publisher
    ..This is the first demonstration of a role for BLOC-1 in ciliary assembly and highlights the complexity of pathways taken to the cilium. ..
  15. Graff R, Kurtz M, Paul R, Martin D, Roopenian D. Additional mapping of mouse chromosome 2 genes. Immunogenetics. 1991;33:96-100 pubmed
    ..Hd-1 typing indicated that Hd-1 maps distal to [H-42, H-44] and proximal to un. The gene order [pa, B2m, H-3], we, [H-42, H-45], Hd-1, un, H-13, at, with H-44 mapping centromeric to Hd-1, is indicated by the data. ..
  16. Peters J, Ball S, von Deimling A. Localization of Blvr, biliverdin reductase, on mouse chromosome 2. Genomics. 1989;5:270-4 pubmed
  17. 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...
  18. Maltais L, Lane P, Beamer W. Anorexia, a recessive mutation causing starvation in preweanling mice. J Hered. 1984;75:468-72 pubmed
    ..Data suggest that the mutant mice are not ingesting the levels of nutrients necessary to sustain life. This mutation may provide an important tool for studying the neurobiology of suckling behavior in the preweanling animal. ..
  19. Matsushita T, Fujimoto M, Hasegawa M, Matsushita Y, Komura K, Ogawa F, et al. BAFF antagonist attenuates the development of skin fibrosis in tight-skin mice. J Invest Dermatol. 2007;127:2772-80 pubmed
    ..The results suggest that BAFF/BAFF receptor system is critical for the development of skin fibrosis in TSK/+ mice and could be a potent therapeutical target. ..
  20. Alexander J, Jacob A, Cunningham P, Hensley L, Quigg R. TNF is a key mediator of septic encephalopathy acting through its receptor, TNF receptor-1. Neurochem Int. 2008;52:447-56 pubmed
  21. Bayle J, Fitch J, Jacobsen K, Kumar R, Lafyatis R, Lemaire R. Increased expression of Wnt2 and SFRP4 in Tsk mouse skin: role of Wnt signaling in altered dermal fibrillin deposition and systemic sclerosis. J Invest Dermatol. 2008;128:871-81 pubmed
    ..Lesional skin from SSc patients also showed large increases in SFRP4 mRNA and protein levels in the deep dermis compared to healthy skin, suggesting that the Wnt pathway might regulate skin fibrosis in SSc. ..
  22. Endlich N, Schordan E, Cohen C, Kretzler M, Lewko B, Welsch T, et al. Palladin is a dynamic actin-associated protein in podocytes. Kidney Int. 2009;75:214-26 pubmed publisher
    ..Our study shows that palladin is expressed in podocytes and plays an important role in actin dynamics. ..
  23. Blasius A, Arnold C, Georgel P, Rutschmann S, Xia Y, Lin P, et al. Slc15a4, AP-3, and Hermansky-Pudlak syndrome proteins are required for Toll-like receptor signaling in plasmacytoid dendritic cells. Proc Natl Acad Sci U S A. 2010;107:19973-8 pubmed publisher
    ..These proteins are not necessary for TLR7 or TLR9 signaling in conventional DCs and thus comprise a membrane trafficking pathway uniquely required for endosomal TLR signaling in pDCs. ..
  24. Sullo N, Roviezzo F, Matteis M, Spaziano G, Del Gaudio S, Lombardi A, et al. Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema: formoterol and skeletal muscle dysfunction. Am J Respir Cell Mol Biol. 2013;48:198-203 pubmed publisher
    ..In conclusion, in emphysematous mice that showed an increased mtDNA content, exposure to inhaled LABA can improve mitochondrial skeletal muscle oxidative processes. PGC-1? may serve as a possible mediator of this effect. ..
  25. Min S, Suzuki A, Stalker T, Zhao L, Wang Y, McKennan C, et al. Loss of PIKfyve in platelets causes a lysosomal disease leading to inflammation and thrombosis in mice. Nat Commun. 2014;5:4691 pubmed publisher
    ..Our findings identify PIKfyve as an essential regulator for platelet lysosome homeostasis, and demonstrate the contributions of platelet lysosomes to inflammation, arterial thrombosis and macrophage biology. ..
  26. Lemaire R, Farina G, Bayle J, Dimarzio M, Pendergrass S, Milano A, et al. Antagonistic effect of the matricellular signaling protein CCN3 on TGF-beta- and Wnt-mediated fibrillinogenesis in systemic sclerosis and Marfan syndrome. J Invest Dermatol. 2010;130:1514-23 pubmed publisher
    ..Together, these data indicate that CCN3 counter-regulates positive signals from TGF-beta and Wnt for fibrillin fibrillogenesis and profibrotic gene expression. ..
  27. Gokhale A, Hartwig C, Freeman A, Das R, Zlatic S, Vistein R, et al. The Proteome of BLOC-1 Genetic Defects Identifies the Arp2/3 Actin Polymerization Complex to Function Downstream of the Schizophrenia Susceptibility Factor Dysbindin at the Synapse. J Neurosci. 2016;36:12393-12411 pubmed
    ..Our studies indicate that a central cellular structure affected by schizophrenia susceptibility loci is the actin cytoskeleton, an organelle necessary for synaptic function in the presynaptic and postsynaptic compartment. ..
  28. Marie I, Beny J. Endothelial dysfunction in murine model of systemic sclerosis: tight-skin mice 1. J Invest Dermatol. 2002;119:1379-87 pubmed
  29. Erway L, Fraser A, Hurley L. Prevention of congenital otolith defect in pallid mutant mice by manganese supplementation. Genetics. 1971;67:97-108 pubmed
  30. Trune D, Lim D. A morphometric study of the pallid mutant mouse inner ear. Am J Otolaryngol. 1983;4:261-72 pubmed
    ..Since the significant vestibular influences of the pallid gene are limited primarily to the otoconia, behavioral abnormalities reported for these otoconia-deficient mice are apparently due only to gravity receptor hypostimulation...
  31. Phelps R, Daian C, Shibata S, Fleischmajer R, Bona C. Induction of skin fibrosis and autoantibodies by infusion of immunocompetent cells from tight skin mice into C57BL/6 Pa/Pa mice. J Autoimmun. 1993;6:701-18 pubmed
    ..Our results strongly demonstrate, for the first time, that immunocompetent cells can play a role in the activation of collagen synthesis leading to skin fibrosis. ..
  32. de Santi M, Martorana P, Cavarra E, Lungarella G. Pallid mice with genetic emphysema. Neutrophil elastase burden and elastin loss occur without alteration in the bronchoalveolar lavage cell population. Lab Invest. 1995;73:40-7 pubmed
    ..The presence of similar structures in alveolar macrophages from mice or other animal species may be indicative of connective tissue breakdown or remodeling of tissue collagen. ..
  33. Green M, Sweet H, Bunker L. Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton. Am J Pathol. 1976;82:493-512 pubmed
  34. Swank R, Reddington M, Howlett O, Novak E. Platelet storage pool deficiency associated with inherited abnormalities of the inner ear in the mouse pigment mutants muted and mocha. Blood. 1991;78:2036-44 pubmed
  35. Wei A, Zang D, Zhang Z, Liu X, He X, Yang L, et al. Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. J Invest Dermatol. 2013;133:1834-40 pubmed publisher
    ..Our results suggest that SLC24A5 is a previously unreported nonsyndromic OCA candidate gene and that the SLC24A5 transporter is transported into mature melanosomes by HPS protein complexes. ..
  36. Novak E, McGarry M, Swank R. Correction of symptoms of platelet storage pool deficiency in animal models for Chediak-Higashi syndrome and Hermansky-Pudlak syndrome. Blood. 1985;66:1196-201 pubmed
    ..Also, the studies suggest that in severe cases, platelet SPD may be successfully treated by bone marrow transplantation. ..
  37. Hearing V, Phillips P, Lutzner M. The fine structure of melanogenesis in coat color mutants of the mouse. J Ultrastruct Res. 1973;43:88-106 pubmed
  38. Doute R, Clark S. Tight-skin (Tsk) maps on mouse chromosome 2 within the region of linkage homology with human chromosome 15. Genomics. 1994;22:223-5 pubmed
    ..To facilitate the positional cloning of Tsk, an interspecific backcross between C57BL/6J Tsk/+ and Mus spretus has been conducted. Our data link Tsk to cloned genetic markers and indicate the order pa-B2m-Tsk-Fbn-1-II-1a-a. ..
  39. Xie T, Nguyen T, Hupe M, Wei M. Multidrug resistance decreases with mutations of melanosomal regulatory genes. Cancer Res. 2009;69:992-9 pubmed publisher
    ..Independent mutations in three separate genes that regulate melanosome biogenesis (Dtnbp1, Pldn, Vps33a) also result in increased cis-platin sensitivity...
  40. Swank R, Novak E, McGarry M, Zhang Y, Li W, Zhang Q, et al. Abnormal vesicular trafficking in mouse models of Hermansky-Pudlak syndrome. Pigment Cell Res. 2000;13 Suppl 8:59-67 pubmed
    ..Recent physiological studies have shown that mouse HPS mutants, like their human HPS counterparts, have variably reduced lifespans and may have lung abnormalities...
  41. Weihrauch D, Xu H, Shi Y, Wang J, Brien J, Jones D, et al. Effects of D-4F on vasodilation, oxidative stress, angiostatin, myocardial inflammation, and angiogenic potential in tight-skin mice. Am J Physiol Heart Circ Physiol. 2007;293:H1432-41 pubmed
    ..As SSc patients have increased plasma p-HDL and angiostatin levels similar to the Tsk(-/+) mice, D-4F may be effective at treating vascular complications in patients with SSc. ..
  42. Hurley L. Interaction of genes and metals in development. Fed Proc. 1976;35:2271-5 pubmed
    ..It is proposed that in man as in animals teratogenesis might involve genetic-nutritional interactions as well as multifractorial interactions including genes, nutrients, drugs, and other environmental agents. ..
  43. Dimitriu Bona A, Fillit H. Studies of the cellular immune response to heparan sulfate proteoglycan in the tight skin mouse. Cell Immunol. 1993;150:321-32 pubmed
    ..Further studies are necessary to determine the mechanisms which link autoimmunity to HSPG with the pathology seen in TSK mice, particularly the overproduction of extracellular matrix and fibrosis. ..
  44. Jones S, Erway L, Johnson K, Yu H, Jones T. Gravity receptor function in mice with graded otoconial deficiencies. Hear Res. 2004;191:34-40 pubmed
    ..It also shows that behavior alone may be an unreliable indicator of the extent of gravity receptor deficits...
  45. 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
    ..Also, the results emphasize the genetic, morphological, and functional interrelatedness of three organelles: melanosomes, lysosomes, and platelet dense granules. ..
  46. Andrews S, Peters J. Linkage analyses and biochemical genetics of sorbitol dehydrogenase-1 (Sdh-1) in the mouse. Biochem Genet. 1983;21:809-17 pubmed
    ..9 +/- 1.4--pa--16.4 +/- 3.6--a--3.9 +/- 1.9--bp. ..
  47. Gwynn B, Korsgren C, Cohen C, Ciciotte S, Peters L. The gene encoding protein 4.2 is distinct from the mouse platelet storage pool deficiency mutation pallid. Genomics. 1997;42:532-5 pubmed
    ..2 mRNA. As the pa mutation originally arose in a wild M. domesticus mouse, we conclude that the Epb4.2 mRNA characteristic of pallid is a normal polymorphism derived from its wild ancestor and that Epb4.2 and pa are distinct loci. ..
  48. Huang L, Gitschier J. A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet. 1997;17:292-7 pubmed
    ..The lethal milk mutant has a nonsense mutation at arginine codon 297 in the Znt4 gene. ..
  49. Ong C, Ip S, Teh S, Wong C, Jirik F, Grusby M, et al. A role for T helper 2 cells in mediating skin fibrosis in tight-skin mice. Cell Immunol. 1999;196:60-8 pubmed
    ..2 gene segment by T cells was sufficient to prevent skin fibrosis in Tsk/+ mice. This result suggests that the exclusive use of this Vbeta gene segment by T cells may have prevented the development of fibrosis-causing Th2 cells. ..
  50. Graff R, Simmons D, Meyer J, Martin Morgan D, Kurtz M. Abnormal bone production associated with mutant mouse genes pa and we. J Hered. 1986;77:109-13 pubmed
    ..The posited synergism is further supported by the finding that we, which functions as a recessive gene in mice of the pa/+ genotype, appears to function as a dominant gene in mice possessing the pa/pa genotype. ..
  51. 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
  52. Mann K, Deutzmann R, Aumailley M, Timpl R, Raimondi L, Yamada Y, et al. Amino acid sequence of mouse nidogen, a multidomain basement membrane protein with binding activity for laminin, collagen IV and cells. EMBO J. 1989;8:65-72 pubmed
    ..The latter was shown to be functional in cell attachment to nidogen. Binding sites for laminin and collagen IV are present on the C-terminal globule but not yet precisely localized. ..
  53. McGaha T, Saito S, Phelps R, Gordon R, Noben Trauth N, Paul W, et al. Lack of skin fibrosis in tight skin (TSK) mice with targeted mutation in the interleukin-4R alpha and transforming growth factor-beta genes. J Invest Dermatol. 2001;116:136-43 pubmed