Human BLOC-1 subunit 2 (BLOC1S2, BLOS2, CEAP)






GENOMIC

Mapping

10q24.31. View the map and BAC contig (data from UCSC genome browser).

Structure

(assembly 07/03)
Isoform a/NM_173809: 5 exons, 12,728bp, chr12:54,396,087-54,399,751.
Isoform b/NM_001001342: 4 exons, 12, 402bp, chr10:101698300-101710701.

Alternative splicing of 5' exons causes the two different isoforms. Isoform b lacks the N-terminal 43aa of isoform a.

The figure below shows the structures of the BLOC1S2 genes (data from UCSC genome browser).

Regulatory Element

Search the 5'UTR and 1kb upstream regions (seq1=human BLOC1S2, seq2=mouse Bloc1s2) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).






TRANSCRIPT

RefSeq/ORF

Variant 1 (NM_173809): 1,958 bp, view ORF and the alignment to genomic.
Variant 2 (NM_ 001001342): 2,024 bp, view ORF and the alignment to genomic.

Expression Pattern

Tissue specificity: Ubiquitously expressed (by similarity)
(isoform b).

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 )






PROTEIN

Sequence

BLOC-1 subunit 2, isoform a (NP_776170): 142aa.
BLOC-1 subunit 2, isoform b (NP_001001342): 99aa.

Ortholog

(Isoform a)

Species Mouse Rat Drosophila Mosquito Worm
GeneView Bloc1s2 LOC293938 CG14145 1276061 4H99
Protein XP_193940 (143aa) XP_215245 (142aa) NP_648427 (159aa) XP_315366 (141aa) NP_500967 (132aa)
Identities 94%/143aa 96%/142aa 44%/155aa 39%/133aa 36%/106aa

View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.

Domain

(isoform a)

(1) Domains of predicted by SMART:
a) low complexity: 17 - 36
b) coiled coil: 111-127

(2) Transmembrane domains predicted by SOSUI: none.

(3) CDD domain: KOG4559.

Motif/Site

(isoform a)

(1) Predicted results by ScanProsite:
a) N-myristoylation site : [occurs frequently]
7 - 12: GVlaTR.

b) Casein kinase II phosphorylation site : [occurs frequently]
11 - 14: TrsD, 25 - 28: TaeE, 59 - 62: TseD.

c) Protein kinase C phosphorylation site : [occurs frequently]
74 - 76: SlK, 129 - 131: SkK.

d) N-glycosylation site : [occurs frequently]
86 - 89: NISR.

e) Leucine zipper pattern : [occurs frequently]
118 - 139: LeqaaykLdayskkLeakykkL.

f) Tyrosine kinase phosphorylation site : [occurs frequently]
130 - 136: Kkl.Eak.Y

g) Tyrosine sulfation site : [occurs frequently]
56 - 70: ltatsedYkllenmn.

(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: KKXX-like motif in the C-terminus: KLEK
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
j) DNA binding motif: Leucine zipper pattern (PS00029): found at 118.

3D Model

(1) ModBase: none.

(2) 3D models of isoform (a) predicted by SPARKS (fold recognition) below. View the models by PDB2MGIF.

2D-PAGE

This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=15,961Da, pI=4.78 (isoform a).
Computed theoretical MW=11,489Da, pI=8.69 (isoform b).






FUNCTION

Ontology

(1) May play a role in intracellular vesicle trafficking.
(2) Protein interaction in BLOC-1.

Location

Cytoplasmic. BLOS2 also localizes to centrosomes or the pericentrosomal region, and perhaps mitochondia.

Interaction

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, BLOS3, SNAPAP (Ciciotte, et al; Falcon-Perez , et al; Li, et al; Moriyama, et al; Starcevic, et al). BLOS2 interacts with cno, muted, snapin, BLOS1, and BLOS3 within the complex ( Starcevic, et al) (view diagram of BLOC-1 complex here). In addition to BLOS2, WASH also interacts with centrosomal gamma-tubulin and with pallidin, suggesting WASH may be an additional component of the BLOC-1 complex ( Monfregola, et al).

Two alternatively human spliced isoforms of BLOS2, which are named as Ceap-11 (isoform b) and Ceap-16 (isoform a), are co-immunoprecipitated and colocalized with gamma-tubulin (Wang, et al). Ceap-16 interacts with BRD7 (bromodomain containing protein 7), a negative regulator of cell proliferation and growth. The C-terminus of BRD7 and the central region of Ceap-16 mediated the interaction. Ceap-16 may translocate from cytoplasm to the nucleus where it selectively inhibited the transcriptional suppression activity of BRD7. Furthermore, Ceap-16, BRD7 and histone H3/H4 could form a complex and Ceap-16 did not compete with the BRD7 binding to histones, suggesting a novel function for Ceap-16 in the transcriptional regulation through BRD7 (Sun, et al). AATF/Che-1 is a coactivator of several transcription factors, including steroid hormone receptors. BLOS2 was identified as an AATF interacting protein from a rat cDNA library. BLOS2 is conserved with a high degree of homology to yeast She3p. BLOS2 functions as an adapter in processes such as protein and vesicle processing and transport, and perhaps transcription (Felten, et al). In yeast two-hybrid screen, BLOS2 was identified as a novel HIPPI (HIP-1 protein interactor) interacting protein. In co-immunoprecipitation assays, BLOS2 specifically associates with HIPPI, but not with HIP-1 (Huntingtin-interacting protein-1), suggesting that BLOS2 might play an important functional role in cancer and neurodegenerative diseases (Gdynia, et al). In Arabidopsis, BLOS2 interacts with SNX1 to modulate the vacuole degradation of auxin effluxers PIN1/2 to regulate root development ( Cui, et al).

BLOS2 drosophila homolog CG14145 interaction information in CuraGen interaction database.

Pathway

Involved in the development of lysosome-related organelles, such as melanosomes and platelet-dense granules (view diagram of BLOC-1 pathway here).






MUTATION

Allele or SNP

No mutation has been reported in human patients.

SNPs deposited in dbSNP.

Distribution

(none)

Effect

(none)






PHENOTYPE

(none)






REFERENCE

  1. Ciciotte SL, Gwynn B, Moriyama K, Huizing M, Gahl WA, Bonifacino JS, Peters LL. 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. PMID: 12576321
  2. Cui Y, Li X, Chen Q, He X, Yang Q, Zhang A, Yu X, Chen H, Liu N, Xie Q, Yang W, Zuo J, Palme K, Li W. BLOS1, a putative BLOC-1 subunit, interacts with SNX1 and modulates root growth in Arabidopsis. J Cell Sci 2010; 123: 3727-33. PMID: 20971704
  3. Falcon-Perez JM, Starcevic M, Gautam R, Dell'Angelica EC. 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. PMID: 12019270
  4. Felten A, Leister P, Burgdorf S, Uhlmann L, Scheidtmann KH. Characterization of rat BLOS2/Ceap, a putative yeast She3 homolog, as interaction partner of apoptosis antagonizing transcription factor/Che-1. Biol Chem 2007; 388: 569-82.PMID: 17552904
  5. Gdynia G, Lehmann-Koch J, Sieber S, Tagscherer KE, Fassl A, Zentgraf H, Matsuzawa S, Reed JC, Roth W. BLOC1S2 interacts with the HIPPI protein and sensitizes NCH89 glioblastoma cells to apoptosis. Apoptosis 2008; 13: 437-47. PMID: 18188704
  6. Li W, Zhang Q, Oiso N, Novak EK, Gautam R, O'Brien EP, Tinsley CL, Blake DJ, Spritz RA, Copeland NG, Jenkins NA, Amato D, Roe BA, Starcevic M, Dell'Angelica EC, Elliott RW, Mishra V, Kingsmore SF, Paylor RE, Swank RT. 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. PMID: 12923531
  7. Monfregola J, Napolitano G, D'Urso M, Lappalainen P, Ursini MV. Functional characterization of Wiskott-Aldrich syndrome protein and scar homolog (WASH), a bi-modular nucleation-promoting factor able to interact with biogenesis of lysosome-related organelle subunit 2 (BLOS2) and gamma-tubulin. J Biol Chem 2010; 285: 16951-7. PMID: 20308062
  8. Moriyama K, Bonifacino JS. Pallidin is a component of a multi-protein complex involved in the biogenesis of lysosome-related organelles. Traffic 2002; 3: 666-77. PMID: 12191018
  9. Starcevic M, Dell'Angelica EC. 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). J Biol Chem 2004; 279: 28393-401. PMID: 15102850
  10. Sun J, Nie J, Hao B, Li L, Xing G, Wang Z, Zhou Y, Sun Q, Li G, Zhang L, He F. Ceap/BLOS2 interacts with BRD7 and selectively inhibits its transcription-suppressing effect on cellular proliferation-associated genes. Cell Signal 2008; 20: 1151-8. PMID: 18329849
  11. Wang Z, Wei H, Yu Y, Sun J, Yang Y, Xing G, Wu S, Zhou Y, Zhu Y, Zhang C, Zhou T, Zhao X, Sun Q, He F. Characterization of Ceap-11 and Ceap-16, two novel splicing-variant-proteins, associated with centrosome, microtubule aggregation and cell proliferation. J Mol Biol 2004; 343: 71-82. PMID: 15381421

EDIT HISTORY:
Created by Wei Li, 07/08/2004
Updated by Wei Li, 03/12/2009
Updated by Wei Li, 05/26/2011

(Back to Index) (Back to Homepage)