MUTED (MU)

GENOMIC

Mapping

6p24.3. View the map and BAC clones of FISH (data from UCSC genome browser).

Structure

(assembly 7/03)
MUTED/NM_201280: 5 exons, 50,431bp, Chr6: 7,959,216-8,009,646.

The figure below shows the structure of the MU gene (data from UCSC genome browser).
Note that the longer transcript variant of TXDNC5/NM_022085 contains exons 1-4 of MUTED.

Regulatory Element

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

TRANSCRIPT

RefSeq/ORF

MUTED (NM_201280), 2,282bp, view ORF and the alignment to genomic.
Note: Some transcripts of the downstream gene TXNDC5 overlap this gene, but they do not contain an open reading frame for this gene.

Expression Pattern

Tissue specificity: Widely Expressed.

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

Muted protein homolog (NP_958437): 187aa, ExPaSy NiceProt view of Swiss-Prot:Q8TDH9.

Ortholog

Species	Mouse	Chimp	Chicken	Rat	FuguFish
GeneView	mu/Muted	17708	012782	Loc306868	156809
Protein	NP_620702 (185aa)	30229 (187aa)	20823 (196aa)	XP_225255 (187aa)	177063 (139aa)
Identities	76%/143aa	76%/143aa	63%/108aa	81%/152aa	46%/68aa

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

Domain

(1) Domains predicted by SMART:
a) coiled coil: 154 - 186.

(2) Transmembrane domains predicted by SOSUI: None.

Motif/Site

(1) Predicted results by ScanProsite:
a) Protein kinase C phosphorylation site : [occurs frequently]
20 - 22: SkK, 97 - 99: TmR, 137 - 139: SeK.

b) cAMP- and cGMP-dependent protein kinase phosphorylation site : [occurs frequently]
22 - 25: KRdS.

c) N-myristoylation site : [occurs frequently]
27 - 32: GTagSA.

d) Casein kinase II phosphorylation site : [occurs frequently]
97 - 100: TmrD.

e) N-glycosylation site : [occurs frequently]
113 - 116: NDSV.

(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 TLPK at 90
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.

3D Model

(1) ModBase No entry found.

(2) 3D models 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=21,609Da, pI=7.14 (NP_958437).

FUNCTION

Ontology

(1) Process: pigmentation, vesicle-mediated transport.
(2) Protein interaction in BLOC-1.

Location

Cytoplasmic.

Interaction

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).

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

Zhang, et al performed mutation screening of the human MU gene in those HPS patients with no mutations with known HPS genes by amplification of genomic DNAs and sequencing. No defects were observed.

SNPs deposited in dbSNP.

Distribution

(none)

Effect