19q13.32. View the map and BAC contig (data from UCSC genome browser).
BLOC1S3/NM_212550: 1 exon, 610 bp, chr19:50,374,394-50,375,003.
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).
Tissue specificity: Ubiquitously expressed (by similarity).
BMR: Bone marrow; SPL: Spleen; TMS: Thymus; BRN: Brain; SPC: Spinal cord; HRT: Heart; MSL: Skeletal muscle; LVR; Liver; PNC: Pancreas; PST: Prostate; KDN: Kidney; LNG: Lung. (data from GeneCards )
BLOC-1 subunit 3
Synonym: Hermansky-Pudlak syndrome 8 protein.
|Protein||NP_808360 (195aa)||XP_218422 (195aa)|
View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.
(1) Domains of predicted by SMART:
low complexity: 6-14, 21-38, 41-55, 59-77, 140-157
(2) Transmembrane domains predicted by SOSUI: none.
(1) Predicted results by ScanProsite:
a) Alanine-rich region profile : [occurs frequently]
90 - 171: score=9.353
b) Amidation site : [occurs frequently]
4 - 7: qGRR.
c) Casein kinase II phosphorylation site : [occurs frequently]
23 - 26: TetD, 25 - 28: TdsE, 32 - 35: SssE, 33 - 36: SseE, 34 - 37: SeeE, 63 - 66: TdsE, 65 - 68: SepE, 89 - 92: SaeE, 192 - 195: TepE.
d) Protein kinase C phosphorylation site : [occurs frequently]
27 - 29: SeR, 159 - 161: SvR.
e) N-myristoylation site : [occurs frequently]
53 - 58: GLrvAG, 153 - 158: GLaaAH, 188 - 193: GVpgTE.
f) Cell attachment sequence : [occurs frequently]
164 - 166: RGD
g) Tyrosine sulfation site : [occurs frequently]
33 - 47: sseeeelYlgpsgpt.
(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=21,256Da, pI=5.08.
(1) May play a role in intracellular vesicle trafficking.
(2) Protein interaction in BLOC-1.
BLOC-1 subunit 2 is a subunit of the biogenesis of lysosome-related organelles complex 1 (BLOC-1), where it resides with the products of seven other HPS genes, DTNBP1, MU, PLDN, CNO, BLOS1, BLOS2, SNAPAP (Ciciotte, et al; Falcon-Perez , et al; Li, et al; Moriyama, et al; Starcevic, et al). BLOS3 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).
SNPs deposited in dbSNP.
|Exon 1||131C>A||131C>A||S44X||nonsense||Iranian||Cullinane, et al|
|Exon 1||448delC||448delC||Q150delC||frame-shift, 225X||Pakistani||Morgan, et al|
(Numbering of genomic and cDNA sequence is based on the start codon of RefSeq NM_212550.)
The mutant GFP-tagged protein (224aa) was mislocalized in nucleus compared to a cytoplasmic wild-type protein. No nonsense-mediated decay and destabilization of the BLOC-1 complex was observed to the S44X and Q150delC mutation (Cullinane, et al; Morgan, et al). Aberrant localization of TYRP1, with increased plasma-membrane trafficking, was observed (Cullinane, et al). The residues after Q150 may be important for its normal function (Morgan, et al).
Morgan, et al described a large Pakistani family with six HPS-8 patients. Autozygosity mapping studies have shown these patients were caused by a homozygous frameshift mutation in the BLOC1S3 gene. All patients present cardinal HPS features: hypopigmentation, platelet dysfunction, and visual defects (nystagmus, iris transilluminancy, foveal hypoplasia, reduced visual acuity, and evidence of optic pathway misrouting). Skin biopsy demonstrated abnormal aggregates of melanosomes within basal epidermal keratinocytes. A nonsense mutation in the murine orthologue of BLOC1S3 causes reduced pigmentation (rp) in mouse (Starcevic, et al).