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FLASH GENE

Symbol

SIX3

contributors: mct - updated : 27-09-2015

HGNC name	SIX homeobox 3
HGNC id	10889

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	25.02 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005413 2 - 2533 NP_005404 35.3 332 - 2008 18836447

EXPRESSION

Type

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 Nervous brain forebrain       Homo sapiens Visual eye lens         eye retina

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining retinal pigment epithelium (RPE)

cells

System Cell Pubmed Species Stage Rna symbol Nervous ependymal cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	very early during eye development in midline forebrain and in anterior region of the neural plate especially inner retina and later in ganglion cells and in cells of the inner nuclear layer

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal Groucho-binding EH1-like motif mutated in HPE (Domene 2008)
	six domain thought to participate in transcriptional activation
	a helix-turn-helix DNA (homeo domain) binding domain

HOMOLOGY

interspecies

homolog to Drosophila sine oculis homeo box SIX3

intraspecies

homolog to SIX6

Homologene

FAMILY

SIX/Sine oculis homeobox family

CATEGORY

DNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	involved in regulation of eye and neural plate development
	playing a second and distinct role as a constituent component of a complex network of eye field transcription factors that regulate eye and lens development (Domene 2008)
	is necessary for ependymal cell maturation during postnatal stages of brain development
	exerts multiple functions in the development of anterior neural tissue of vertebrate embryos
	promotes ventral telencephalic fates through transient regulation of FOXG1A expression and repression of the WNT/CTNNB pathway
	direct regulatory link between SOX2 and SIX3 during forebrain development
	may play an important role as a novel suppressor in human lung cancer
	PAX6 or SIX3 is sufficient to induce ES cells to adopt a lens fate, potentially via non-cell autonomous mechanisms

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	with GMNN(to control the balance betwween proliferation and differentiation during early eye development)
	with NR4A3(required in the developing visual system)
	association with members of the groucho co-receptor sub-family (Domene 2008)
	SIX3 is a SOX2 transcriptional target (directly regulates a previously unidentified long-range forebrain enhancer to activate SIX3 expression in the rostral diencephalon)

cell & other

REGULATION

Other

regulated by PAX6

ASSOCIATED DISORDERS

corresponding disease(s)

HPE2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   by methylation of the SIX3 promoter, in lung adenocarcinoma tissues compared to their matched adjacent normal tissues

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	has potential as a novel prognostic biomarker for patients with lung adenocarcinomas
Therapy target

ANIMAL & CELL MODELS