7qA3. View the map and BAC contig (data from UCSC genome browser).
Bloc1s3/NM_177692: 2 exons, 1,883 bp, chr7:16,504,517-16,506,399.
The figure below shows the structure of the Bloc1s3 gene (data from UCSC genome browser).
Search the 5'UTR and 1kb upstream regions (seq1=human BLOC1S3, seq2=mouse rp) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).
|Protein||NP_997715 (202aa)||XP_218422 (195aa)|
View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.
(1) Domains of predicted by SMART:
a) low complexity: 18 - 51
b) low complexity: 55 - 79
c) low complexity: 126 - 150
(2) Transmembrane domains predicted by SOSUI: none.
(1) Predicted results by ScanProsite:
a) Amidation site : [occurs frequently]
5 - 8: qGRR.
b) Casein kinase II phosphorylation site : [occurs frequently]
22 - 25: TdsE, 29 - 32: SssE, 30 - 33: SseE, 31 - 34: SeeE, 59 - 62: TdsE, 61 - 64: SepE, 111 - 114: TrlD.
c) N-myristoylation site : [occurs frequently]
49 - 54: GLrvAG, 118 - 123: XAavSG, 146 - 151: GLaaAH.
d) Protein kinase C phosphorylation site : [occurs frequently]
152 - 154: SvR.
e) Cell attachment sequence : [occurs frequently]
157 - 159: RGD.
f) Tyrosine sulfation site : [occurs frequently]
29 - 43: ssseeelYlgpsgpt.
(2) Predicted results of subprograms by PSORT II:
a) N-terminal signal peptide: none
b) KDEL ER retention motif in the C-terminus: none
c) ER membrane retention signals: none
d) VAC possible vacuolar targeting motif: none
e) Actinin-type actin-binding motif: type 1: none; type 2: none
f) Prenylation motif: none
g) memYQRL transport motif from cell surface to Golgi: none
h) Tyrosines in the tail: none
i) Dileucine motif in the tail: none
(1) ModBase: none.
(2) 3D models predicted by SPARKS (fold recognition) below. View the models by PDB2MGIF.
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=20,445Da, pI=4.84.
The phosphorylated form migrates slower than the unphosphorylated form (Gwynn, et al).
(1) May play a role in intracellular vesicle trafficking.
(2) Protein interaction in BLOC-1.
BLOC-1 subunit 3 is a subunit of the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which resides with the products of seven other HPS genes, sdy, mu, pa, cno, Snapap, Blos1, Blos2 (Ciciotte, et al; Falcon-Perez , et al; Li, et al; Moriyama, et al; Starcevic, et al). It interacts with Blos2 within the complex ( Starcevic, et al) (view diagram of BLOC-1 complex here). More details about the function of BLOC-1 are described in the HPS7 profile.
Involved in the development of lysosome-related organelles, such as melanosomes and platelet-dense granules (view diagram of BLOC-1 pathway here). Nguyen, et al found that the maturation of melanosomes is blocked in early stages (view diagram of melanosome blockage here).
SNPs deposited in dbSNP.
|Exon 2||238C>T||238C>T||Q80X||nonsense||rp (B6)||Starcevic, et al|
The Q80X mutation is not subject to nonsense mediated decay, but no detectable Blos3 protein in liver extracts of rp mutants. The mutation does affect the stability of other subunits such as pallidin and muted of BLOC-1 complex, but does not completely disrupt BLOC-1 assembly (Starcevic, et al).
Mutation in the Bloc1s3 gene is the cause of reduced pigmentation (rp) mutant (Starcevic, et al). The rp allele arose from C57BL/Tb. The strain is described in more detail in JAX Mice database (C57BL-Bloc1s1rp/J) Homozygotes have a hypopigmented coat color and show phenotypic similarity to human Hermansky-Pudlak Syndrome (Gibb, et al; Swank, et al). The rp mice exhibit a less pronounced pigmentation defect than pallid mice, suggesting that rp mice may retain some residual BLOC-1 function (Starcevic, et al). The phenotype is described in more detailin Mouse Locus Catalog#Bloc1s3. Both double homozygotes of rp/rp-cno/cno and rp/rp-pa/pa do not show exacerbation of the HPS phenotype compared to the single mutants. However, doubly homozygous offspring (rp/rp-ru/ru) shows an exacerbated coat-color phenotype compared to either single homozygotes alone, which suggests that BLOC-1 and BLOC-2 define functionally independent pathways in the biogenesis of LROs (Gwynn, et al).