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FLASH GENE

Symbol

LARGE

contributors: mct - updated : 22-11-2011

HGNC name	like-glycosyltransferase
HGNC id	6511

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	MDC1D muscular dystrophy,congenital, 1D WLKWS3 Walker-Warburg syndrome 3
Location	22q12.3      Physical location : 33.669.062 - 34.316.416
Synonym name	acetylglucosaminyltransferase-like protein
Synonym symbol(s)	KIAA0609, CTA-282F2.1, MDC1D, MDDGA6, MDDGB6

DNA

TYPE	functioning gene
STRUCTURE	647.36 kb     16 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

regionally located

localized in the meningioma critical region,see also MN1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004737 16 - 4201 - 756 - Peyrard NM_133642 15 - 4138 - 756 - Peyrard

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Hearing/Equilibrium ear inner cochlea   highly Nervous brain           nerve cranial nerve     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal targeting/membrane anchoring domain of glycosyltransferase followed by two coiled-coil domains
	two catalytic domains with three DXD motifs, may be involved in the catalytic activity of this domain
	a C terminal catalytic domain

HOMOLOGY

intraspecies

homolog to GYLTL1B

Homologene

FAMILY

glycosyltransferase family 8

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi

basic FUNCTION	N-acetylglucosaminyl transferase, may be playing a role in tumor-specific genomic rearrangements
	involved in alpha-dystroglycan glycosylation and playing an essential role for expression of functional dystroglycan
	may be invoved in in neuronal migration
	its repression is responsible for the defects in dystroglycan-mediated cell adhesion that are observed in epithelium-derived cancer cells and point to a defect of dystroglycan glycosylation as a factor in cancer progression
	its expression mediates phosphoryl glycosylation
	of not only O-mannosyl glycans including those on alpha-dystroglycan but also N-glycans on proteins other than alpha-dystroglycan
	could act as a bifunctional glycosyltransferase, with both xylosyltransferase and glucuronyltransferase activities
	LARGE and GYLTL1B catalyze the same glycosylation reactions for the functional modification of DAG1, but that they have different biochemical properties
	LARGE and GYLTL1B may be functionally redundant

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	implicated in the postphosphoryl modification pathway that assembles the laminin-binding moiety onto the phosphorylated O-mannose of DAG1
	DAG1 function requires xylosyl- and glucuronyltransferase activities of LARGE to bind laminin-G domain-containing ECM ligands

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

MDC1D , WLKWS3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in FCMD, MEB, WLKWS, LGMD2I tumoral         repression of LARGE is responsible for the defects in dystroglycan-mediated cell adhesion in epithelium-derived cancer cells (de Bernabé 2009)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neuromuscular myopathy   potential therapies in the dystroglycanopathies based on LARGE upregulation and alpha-dystroglycan hyperglycosylation in muscle should be safe

ANIMAL & CELL MODELS