13pA3.3. View the map and BAC contig (data from UCSC genome browser).
Isoform a (NM_139063): 5 exons, 32,403bp, Chr13: 38,579,419-38,611,821.
Isoform b (NM_178054): 5 exons, 23,228bp, Chr13: 38,588,546-38,611,773.
The C-termini are different between isoform (a) and (b) because of alternative 3' exons.
The figure below shows the structures of the known isoforms (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 with the highest levels in gall bladder, small intestine, and testis, but ralative lower amounts in skeletal muscle. A ~1.8kb band is present on PolyA+ northern blots (Zhang, et al).
Affymetrix microarray expression pattern in SymAtlas from GNF is shown below.
|Protein||NP_958437 (187aa)||30229 (187aa)||20823 (196aa)||XP_225255 (187aa)||177063 (139aa)|
View multiple sequence alignment (PDF file) by ClustalW and GeneDoc.
(1) Domains predicted by SMART:
a) coiled coil: 156 - 184.
(2) Transmembrane domains predicted by SOSUI: None.
(1) Predicted results by ScanProsite:
a) Amidation site : [occurs frequently]
17 - 20: gGKK.
b) cAMP- and cGMP-dependent protein kinase phosphorylation site : [occurs frequently]
20 - 23: KRdS.
c) N-myristoylation site : [occurs frequently]
25 - 30: GTpgAA, 99 - 104: GLgeTL.
d) Casein kinase II phosphorylation site : [occurs frequently]
51 - 54: TqgE, 80 - 83: TiqE, 133 - 136: TasE.
e) N-glycosylation site : [occurs frequently]
111 - 114: NDSI
f) Protein kinase C phosphorylation site : [occurs frequently]
135 - 137: SeK.
g) Bipartite nuclear targeting sequence : [occurs frequently]
124 - 140: RKkvindyltasekrrl, 125 - 141: KKvindyltasekrrlv.
(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: found KKXX-like motif in C-terminus, KFST
d) VAC possible vacuolar targeting motif: found KLPI at 815
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: too long of a tail
i) Dileucine motif in the tail: None.
(1) ModBase No entry found.
(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=21,283Da, pI=6.92 (NP_620702, isoform a).
Computed theoretical MW=18,770Da, pI=6.44 (NP_835155, isoform b).
(1) Process: pigmentation, vesicle-mediated transport.
(2) Protein interaction in BLOC-1.
Interacts with pallidin, cno, dysbindin, and Blos2 (Ciciotte, et al; Li, et al (2004); Starcevic, et al). The muted 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, sdy, pa, cno, 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).
Involved in the development of lysosome-related organelles, such as melanosomes and platelet-dense granules (view diagram of BLOC-1 pathway here).
|Exon 1||60Gdel||60Gdel||K20delG||frame-shift, 59X||mu (CHMU/Le)||Zhang, et al|
|Intron 3||+2362A insEtn, 2357G~2362Adup||319Tins 183bp||L107ins 183bp||in-frame||mu-J (T18H)||Zhang, et al|
A very small quantity of a larger band (2.0kb in mu/mu vs. 1.8kb in wildtype) is present on PolyA+ Northern blot (Zhang, et al ). Rare or no band was observed on the Western blots. The mutation does affect the stability of other subunits such as dysbindin and pallidin of BLOC-1 complex (Li, et al (2003)).
Mutation in the Muted gene is the cause of muted mutant (Zhang, et al), a mouse model of Hermansky-Pudlak syndrome (OMIM 607289). The mu allele arose from CHMU/Le ch+/+mu. The mutant is described in more detail in JAX Mice database (B6.C3-Mutedmu/J). The muJ mutation occurred spontaneously on the T18H stock. The mutants present pigment dilution, prolonged bleeding time, and inner ear abnormalities, modeling Hermansky-Pudlak Syndrome (Swank, et al). Total numbers of melanosomes are reduced severely within the retinal pigment epithelium (RPE) and significantly reduced within choroids (Zhang, et al). The phenotype is described in more detail in Mouse Locus Catalog#Muted.