5qB2. View the map and BAC contig (data from UCSC genome browser).
Cno/NM_133724: 1 exons (intronless), 1,500bp, chr5:35,128,851-35,130,340.
The figure below shows the map of the known isoform (data from UCSC genome browser).
Search the 5'UTR and 1kb upstream regions (human and mouse) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).
Tissue specificity: Widely expressed, highest in lung, skin, pancreas, stomach, and placenta. Two mRNA transcripts of ~1.1kb and 1.4kb are present on northern blots (Ciciotte, et al).
Affymetrix microarray expression pattern in SymAtlas from GNF is shown below.
|Protein||NP_060836 (217aa)||XP_344256 (215aa)||140268 (210aa)||XP_315539 (184aa)||NP_648414 (169aa)|
View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.
(1) Domains predicted by SMART:
a) low complexity: 27 - 42
b) low complexity: 80 - 93
c) coiled coil: 141-162
(2) Transmembrane domains predicted by SOSUI: none.
(1) Predicted results by ScanProsite:
a) Casein kinase II phosphorylation site :
15 - 18: SteE, 87 - 90: SleE
b) N-myristoylation site :
23 - 28: GAawSG, 145 - 150: GSsvAR.
c) Cell attachment sequence :
106 - 108: RGD.
(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=23,312Da, pI=5.03 (NP_598485).
Involved in the development of lysosome-related organelles, such as melanosomes and platelet-dense granules.
Interacts with pallidin, muted, dysbindin, and snapin directly(Ciciotte, et al; Li, et al (2004); Starcevic, et al). The Cno protein is a subunit of the biogenesis of lysosome-related organelles complex 1 (BLOC-1), in which it interacts with the products of seven other HPS genes, mu, pa, sdy, rp, Snapap, Blos1, Blos2 (Ciciotte, et al; Falcon-Perez , et al; Li, et al (2003); Moriyama, et al; Starcevic, et al) (view diagram of BLOC-1 complex here).
Cno drosophila homolog CG14149 interaction information in CuraGen interaction database.
Nguyen, et al found that the greatest percentages of immature melanosomes were observed in the BLOC-1 mutants pa and cno, which suggests the maturation of melanosome is blocked between the multivesicular body stage and stage I (view diagram of melanosome blockage here). The cappuccino gene encodes a product involved in an AP-3-independent mechanism critical to the biogenesis of lysosome-related organelles (Gwynn, et al). (view diagram of BLOC-1 and AP-3 pathway here)
|Exon 1||403G~413A del||403G~413A del||D135del 11bp||frame-shift, 207X||cno (C3H/HeJ)||Ciciotte, et al|
The deletion removes a TaqI site. Expression and subcellular localization of the protein are not affected by this mutation. The mutation does affect the stability of other subunits such as pallidin and muted of BLOC-1 complex.
Mutation in the Cno gene is the cause of cappuccino mutant (Ciciotte, et al), a mouse model of Hermansky-Pudlak syndrome (OMIM 605695). The cno allele arose from C3H/HeJ. Homozygous mutant animals exhibit a very dilute coat and eye color due to a reduced number of melanosomes. 75% of homozygous mutant animals exhibit some form of posture or balance abnormality, with variable severity. Platelet dense bodies are markedly deficient leading to prolonged bleeding (Gwynn, et al). The phenotype is described in more detail in MGI.