Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

SIX2

contributors: mct - updated : 13-10-2015

HGNC name	SIX homeobox 2
HGNC id	10888

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	2p21      Physical location : 45.232.324 - 45.236.542
Synonym name	sine oculis homeobox homolog 2 (Drosophila)

DNA

TYPE	functioning gene
STRUCTURE	4.24 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_016932 2 - 2178 NP_058628 32.3 291 - 2000 10773454

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 Endocrine pancreas         Nervous brain         Reproductive male system prostate       Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	six domain
	a helix-turn-helix DNA (homeo) binding domain

HOMOLOGY

interspecies	homolog to Drosophila sine oculis homeo box SIX2
	ortholog to murine Six2
	homolog to C.elegans ceh-33

Homologene

FAMILY

SIX/Sine oculis homeobox family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	involved in limb tendon and ligament development
	its activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud
	acting to mediate HOXA2 control over the insulin-like growth factor pathway during branchial arch development
	required during mammalian kidney organogenesis and is also necessary for the formation of the pyloric sphincter
	combinatorial expression of SIX1, SIX2, and SIX4 is required for the molecular programs governing craniofacial and cerebral development
	functional link between EYA1, SIX2, and MYC in driving the expansion and maintenance of the multipotent progenitors during nephrogenesis

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development

text	embryogenesis and morphogenesis

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

binding

RNA

small molecule

protein	activates GDNF expression (two SIX2 binding sites in the GDNF promoter that show similarity to the consensus DNA binding sequences of other homeobox proteins and harbor short palindromic sequences)
	interacting with TLX1, HOXA2 (loss-of-function of TLX1 leads to loss of SIX2 expression and loss-of-function of HOXA2 leads to expanded SIX2 expression)
	expression of WNT9B in SIX2-positive cells disrupts cell fate decisions in the kidney and the gastrointestinal tract
	SALL1 activates progenitor-related genes in SIX2-positive nephron progenitors and represses gene expression in SIX2-negative differentiating nascent nephrons
	EYA1 interacts with SIX2 and MYC to control self-renewing cell activity
	potent BARX1 functions in intestinal rotation and stomach myogenesis occur through ISL1, PITX1, SIX2 and PITX2, intermediary transcription factors
	important function of SALL1-NuRD interaction in the regulation of SIX2-positive multipotent renal progenitor cells and formation of the loop of Henle

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation     loss of function is a potential congenital cause of anterior cranial base defects in humans constitutional       loss of function of SIX2 and BMP4, could affect kidney development at multiple stages, leading to the congenital anomalies observed in patients with renal hypodysplasia

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Six2-null newborn mice display premature fusion of the bones in the cranial base