Identification of Snapin and Three Novel Proteins (BLOS1, BLOS2, and BLOS3/Reduced Pigmentation) as Subunits of Biogenesis of Lysosome-related Organelles Complex-1 (BLOC-1)

Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a ubiquitously expressed multisubunit protein complex required for the normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules. The complex is known to contain the coiled-coil-forming proteins, Pallidin, Muted, Cappuccino, and Dysbindin. The genes encoding these proteins are defective in inbred as of a and platelet of the of of the is a coiled-coil-forming protein as a of proteins and and in the of The are proteins, and and to proteins and and and known of the proteins are in a in and of a of of the known and the a in the encoding the the in the genes encoding and the proteins of Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a ubiquitously expressed multisubunit protein complex required for the normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules. The complex is known to contain the coiled-coil-forming proteins, Pallidin, Muted, Cappuccino, and Dysbindin. The genes encoding these proteins are defective in inbred as of a and platelet of the of of the is a coiled-coil-forming protein as a of proteins and and in the of The are proteins, and and to proteins and and and known of the proteins are in a in and of a of of the known and the a in the encoding the the in the genes encoding and the proteins of The biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense is a of genes are defective in of biogenesis of lysosome-related organelles biogenesis of lysosome-related organelles in and inbred of the the of melanosomes in and and of platelet dense in of platelet the to of are of and and to melanosomes and platelet dense are to as and the of a biogenesis lysosome-related organelles and and in of and to in organelles melanosomes and platelet dense granules. defective for and of in to and to in and to in The genes in the of are expressed in a of the the biogenesis of melanosomes and platelet dense of the genes known to defective in in in encoding the and of the of proteins for to and organelles and the encoding of the protein in the endosomal-lysosomal the genes known to to of these are multisubunit and is known to contain Pallidin, Muted, Cappuccino, and and and and The of and The genes encoding the Pallidin, Muted, Cappuccino, and are in the and the known of a in in the of the complex in and protein the of the of and to and to a of of the complex the of the of the of of known in of the the and proteins are of in and and of of of is a coiled-coil-forming protein as a of and proteins in The are proteins to as and and the encoding is in the for the defective encoding proteins in to The the of and as as encoding of to as and of The to the and the encoding of and the of The the of the and to and proteins, the as as the encoding of the of the and to and encoding to the the and the to a the The for and and of to as to contain to and to of these and the in the and of as and encoding and proteins and proteins proteins proteins to and and and and the of the to to and and the proteins to and of of a in a and a The for and for The for to a of of proteins in and the of to the to a of The proteins for and in the The for and a to a and in in the a of for the of the of and of the complex The a and to to in the of of and of proteins in and a proteins a of the of the The of the the of the and of The to the for and a in the the known in protein the and in the a and as the and as the and of in for and for of to a and a of and The and the proteins in and and and the the The of the The and the and to a of and of are the to and to the to the the the The for to of a of of to of and and as the in to the of of a to Pallidin, the complex to to to to a in to the and the of Pallidin, a to the in the in a a of expressed in a of in and protein as of protein and the expressed in the to the protein of in and of a of and in to of the complex a of the the the for as protein of the the of and a in the protein as of the the and the the in in the and Pallidin, proteins in the the and a of the protein of in the and a proteins and for and known in the of the in the and of the of the known Pallidin, Muted, and in the and to in the and to of the protein of the the of and The proteins as and proteins and The for and of the of and of these proteins in a proteins to and known and of the to to and the and and are and protein in are in of in are in in a The of and contain to the known these proteins are and in is to a protein of the of a the protein and as as the is as the of to as a to the a of a as the of and to in the of and in the of the of of the the the and in the of the to the in the of and of in the of and to the of to in the the of of and a of to as the of the and of the and for in and of in to the and of the of the the and to the to for the and in the of the and and in to Pallidin, as and and and the a and the of to the the and the and of the and the proteins are of the to of of the protein in a of these proteins to the to and of the and proteins, to and of a protein in to and the proteins a a of of the and a the as proteins the in the the of the the for a and The of and in the and the the of the protein to a the and for the and proteins, these are the the of and in the and and a of to of and and of of and to the the of the protein the the of the protein in the and the of the and as as the of in and The to and proteins in and and to The of are the of the and proteins and and the to a to and the in the of and in and to a the The The of are the The a of protein in and to the for of known of the complex of to Pallidin, to Muted, and of the the complex in the of and and the in a Pallidin, Muted, and the in of to Pallidin, to the complex in the of the proteins a and a of protein complex in of the of and and the to a to Pallidin, and The in the of and in and to a to Pallidin, Muted, and as The the of are the the and proteins known these proteins are of the a a and the in the of and the proteins and in to a of a in the of the complex of the of and of the a as The to the The and the of proteins in are the of the and are of Pallidin, Muted, Cappuccino, and the in of the of of the The to the of the in the of in of the of and The to in and and in of and protein to the of the a the of is a of The to of the in of and in to the to the the of the and and the a and of the the in The in in in genes encoding known Pallidin, Muted, Cappuccino, and are in of the of the genes encoding the defective in of the the of and are in the for the defective to normal of the protein in protein in of the and proteins and protein in these the of the in is required to normal protein the is to protein to the to contain the defective in the in the and of and and for and of the of the and to of the in a in and The in and in the and The is to of in and to a in the encoding and of the of of and the of a in in The are of the of of of to the and the and in a in the of in and as in the and proteins expressed in the and to of complex in the of the of and in to a of the of the as a multisubunit protein complex the and as as of and as The proteins are and contain to a to a protein to and in as a of and proteins to the protein and to a protein The of these to of and The proteins of and a for of and are of the of the proteins in and of the proteins Pallidin, Muted, and of the proteins and of the proteins in a of of the known as a of the of the of and and and and these are in and are of the of these proteins of the the of the the to for and for the complex of of the known the of of the known to is a of the of as a protein and to of a complex and proteins a of as a protein to a ubiquitously protein is of and a of The and in and is in the the of to and of to for a of in the of of and to in the of a complex and these is to complex in the as for and the and protein complex a for for normal biogenesis of melanosomes and platelet dense the of these and lysosome-related organelles is to is is required to the of of the known is in a of and of the encoding is in the The is a the and in a contain and of are the the is the of the and the in and of the of a in a to the such as of of the in to of is of the of of as of these the of and to the proteins and in to a of for these is the is the complex to the of in is of a is expressed in the The is the a of the complex as the in to the of to of in in the protein and proteins and as of and the a in The genes encoding these proteins the of of in in of the genes The biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense is a of genes are defective in of biogenesis of lysosome-related organelles biogenesis of lysosome-related organelles in and inbred of the the of melanosomes in and and of platelet dense in of platelet the to of are of and and to melanosomes and platelet dense are to as and the of a biogenesis lysosome-related organelles and and in of and to in organelles melanosomes and platelet dense granules. defective for and of in to and to in and to in The genes in the of are expressed in a of the the biogenesis of melanosomes and platelet dense granules. of the genes known to defective in in in encoding the and of the of proteins for to and organelles and the encoding of the protein in the endosomal-lysosomal the genes known to to of these are multisubunit and is known to contain Pallidin, Muted, Cappuccino, and and and and The of and The The genes encoding the Pallidin, Muted, Cappuccino, and are in the and the known of a in in the of the complex in and protein the of the of and to and to a of of the complex the of the of the of of known in of the the and proteins are of in and and of of of is a coiled-coil-forming protein as a of and proteins in The are proteins to as and and the encoding is in the for the defective encoding proteins in to The the of and as as encoding of to as and of The to the and the encoding of and the of The the of the and to and proteins, the as as the encoding of the of the and to and encoding to the the and the to a the The for and and of to as to contain to and to of these and the in the and of as and encoding and proteins and proteins proteins proteins to and and and and the of the to to and and the proteins to and of of a in a and a The for and for The for to a of of proteins in and the of to the to a of The proteins for and in the The for and a to a and in in the a of for the of the of and of the complex The a and to to in the of of and of proteins in and a proteins a of the of the The of the the of the and of The to the for and a in the the known in protein the and in the a and as the and as the and of in for and for of to a and a of and The and the proteins in and and and the the The of the The and the and to a of and of are the to and to the to the the the The for to of a encoding proteins in to The the of and as as encoding of to as and of The to the and the encoding of and the of The the of the and to and proteins, the as as the encoding of the of the and to and encoding to the the and the to a the The for and and of to as to contain to and to of these and the in the and of as and encoding and proteins and proteins proteins proteins to and and and and the of the to to and and the proteins to and of of a in a and a The for and for The for to a of of proteins in and the of to the to a of The proteins for and in the The for and a to a and in in the a of for the of the of and of the complex The a and to to in the of of and of proteins in and a proteins a of the of the The of the the of the and of The to the for and a in the the known in protein the and in the a and as the and as the and of in for and for of to a and a of and The and the proteins in and and and the the The of the The and the and to a of and of are the to and to the to the the the The for to of a of of to of and and as the in to the of of a to Pallidin, the complex to to to to a in to the and the of Pallidin, a to the in the in a a of expressed in a of in and protein as of protein and the expressed in the to the protein of in and of a of and in to of the complex a of the the the for as protein of the the of and a in the protein as of the the and the the in in the and Pallidin, proteins in the the and a of the protein of in the and a proteins and for and known in the of the in the and of the of the known Pallidin, Muted, and in the and to in the and to of the protein of the the of and The proteins as and proteins and The for and of the of and of these proteins in a proteins to and known and of the to to and the and and are and protein in are in of in are in in a The of and contain to the known these proteins are and in is to a protein of the of a the protein and as as the is as the of to as a to the a of a as the of and to in the of and in the of the of of the the the and in the of the to the in the of and of in the of and to the of to in the the of of and a of to as the of the and of the and for in and of in to the and of the of the the and to the to for the and of the and the proteins are of the to of of the protein in a of these proteins to the to and of the and proteins, to and of a protein in to and the proteins a a of of the and a the as proteins the in the the of the the for a and The of and in the and the the of the protein to a the and for the and proteins, these are the the of and in the and and a of to of and and of of and to the the of the protein the the of the protein in the and the of the and as as the of in and The to and proteins in and and to The of are the of the and proteins and and the to a to and the in the of and in and to a the The The of are the The a of protein in and to the for of known of the complex of to Pallidin, to Muted, and of the the complex in the of and and the in a Pallidin, Muted, and the in of to Pallidin, to the complex in the of the proteins a and a of protein complex in of the of and and the to a to Pallidin, and The in the of and in and to a to Pallidin, Muted, and as The the of are the the and proteins known these proteins are of the a a and the in the of and the proteins and in to a of a in the of the complex of the of and of the a as The to the The and the of proteins in are the of the and are of Pallidin, Muted, Cappuccino, and the in of the of of the The to the of the in the of in of the of and The to in and and in of and protein to the of the a the of is a of The to of the in of and in to the to the the of the and and the a and of the the in The in in in genes encoding known Pallidin, Muted, Cappuccino, and are in of the of the genes encoding the defective in of the the of and are in the for the defective to normal of the protein in protein in of the and proteins and protein in these the of the in is required to normal protein the is to protein to the to contain the defective in the in the and of and and for and of the of the and to of the in a in and The in and in the and The is to of in and to a in the encoding and of the of of and the of a in in The are of the of of of to the and the and in a in the of in and as in the and proteins expressed in the and to of complex in the of the of and in to a of the of the of of to of and The and as the in to the of of a to Pallidin, the complex to to to to a in to the and the of Pallidin, a to the in the in a a of expressed in a of in and protein as of protein and the expressed in the to the protein of in and of a of and in to of the complex a of the the the for as protein of the the of and a in the protein as of the the and the the in in the and Pallidin, proteins in the the and a of the protein of in the and a proteins and for and known in the of the in the and of the of the known Pallidin, Muted, and in the and to in the and to of the protein of the the of and The proteins as and proteins and The for and of the of and of these proteins in a proteins to and The of and contain to the known these proteins are and in is to a protein of the of a the protein and as as the is as the of to as a to the a of a as the of and to in the of and in the of the of of the the the and in the of the to the in the of and of in the of and to the of to in the the of of and a of to as the of the and of the and for in and of in to the and of the of the the and to the to for the and of the and the proteins are of the to of of the protein in a of these proteins to the to and of the and proteins, to and of a protein in to and the proteins a a of of the and a the as proteins the in the the of the the for a and The of and in the and the the of the protein to a the and for the and proteins, these are the the of and in the and and a of to for of known of the complex of to Pallidin, to Muted, and of the the complex in the of and and the in a Pallidin, Muted, and the in of to Pallidin, to the complex in the of the proteins a and a of protein complex in of the the and proteins known these proteins are of the a a and the in the of and the proteins and in to a of a in the of the complex of the and are of Pallidin, Muted, Cappuccino, and the in of the of of the The to the of the in the of in of the of and The to in and and in of and protein to the of the a the of is a of The to of the in The in genes encoding known Pallidin, Muted, Cappuccino, and are in of the of the genes encoding the defective in of the the of and are in the for the defective to normal of the protein in protein in of the and proteins and protein in these the of the in is required to normal protein the is to protein to the to contain the defective in the in the and of and and for and of the of the and to of the in a in and The in and in the and The is to of in and to in a in the of in and as in the and proteins expressed in the and to of complex in the of the of and in to a of the of the as a multisubunit protein complex the and as as of and as The proteins are and contain to a to a protein to and in as a of and proteins to the protein and to a protein The of these to of and The proteins of and a for of and are of the of the proteins in and of the proteins Pallidin, Muted, and of the proteins and of the proteins in a of of the known as a of the of the of and and and and these are in and are of the of these proteins of the the of the the to for and for the complex of of the known the of of the known to is a of the of as a protein and to of a complex and proteins a of as a protein to a ubiquitously protein is of and a of The and in and is in the the of to and of to for a of in the of of and to in the of a complex and these is to complex in the as for and the and protein complex a for for normal biogenesis of melanosomes and platelet dense the of these and lysosome-related organelles is to is is required to the of of the known is in a of and of the encoding is in the The is a the and in a contain and of are the the is the of the and the in and of the of a in a to the such as of of the in to of is of the of of as of these the of and to the proteins and in to a of for these is the is the complex to the of in is of a is expressed in the The is the a of the complex as the in to the of to of in in the protein and proteins and as of and the a in The genes encoding these proteins the of of in in of the genes as a multisubunit protein complex the and as as of and as The proteins are and contain to a to a protein to and in as a of and proteins to the protein and to a protein The of these to of and The proteins of and a for of and are of the of the proteins in and of the proteins Pallidin, Muted, and of the proteins and of the proteins in a of of the known as a of the of the of and and and and these are in and are of the of these proteins of the the of the the to for and for the complex of of the known the of of the known to is a of the of as a protein and to of a complex and proteins a of as a protein to a ubiquitously protein is of and a of The and in and is in the the of to and of to for a of in the of of and to in the of a complex and these is to complex in the as for and the and protein complex a for for normal biogenesis of melanosomes and platelet dense the of these and lysosome-related organelles is to is is required to the of of the known is in a of and of the encoding is in the The is a the and in a contain and of are the the is the of the and the in and of the of a in a to the such as of of the in to The of is of the of of as of these the of and to the proteins and in to a of for these is the is the complex to the of in is of a is expressed in the The is the a of the complex as the in to the of to of in in the protein and proteins and as of and the a in The genes encoding these proteins the of of in in of the genes are to and for the for and and the of for of the