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FLASH GENE

Symbol

GTF2I

contributors: shn/npt/pgu - updated : 28-06-2018

HGNC name	general transcription factor IIi
HGNC id	4659

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	Six isoforms resulting from skipping cassette exons 9, 10 and/or 12 an optional intron I35 within non-coding exon 35 in 3'UTR promoter is located upstream of exon 1 and immersed in CpG

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_032999 (transcript variant 1) 35 splicing 4529 NP_127492 120 998 - - full-length transcript NM_033001 (transcript variant 3) 33 splicing 4466 NP_127494 120 977 - - absence of exon 12 NM_033000 (transcript variant 2) 34 splicing 4469 NP_127493 120 978 - - absence of exon 10 NM_001163636 (transcript variant 5) 34 splicing 4463 NP_001157108 120 976 - - NM_001518 (transcript variant 4) 31 splicing 4406 NP_001509 120 957 lack of exons 10 and 12 - DA448103 (transcript variant epsilon) 32 - - - - - - lack exon 9 and 10 but retain exon 12

EXPRESSION

Type	ubiquitous

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       moderately Digestive esophagus       lowly   intestine large intestine colon   lowly   intestine small intestine     lowly   liver       lowly Endocrine pancreas       moderately   thyroid       highly Lymphoid/Immune spleen       lowly   thymus       highly Nervous brain       highly Reproductive female system placenta     moderately   female system ovary     moderately   male system prostate     moderately Respiratory lung       lowly   respiratory tract trachea     moderately Urinary bladder       moderately   kidney       moderately

tissue

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

cell lineage	lymphoblasts lowly, adipose highly
cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	brain highly, early in development, expression is widespread and nearly uniform throughout the brain
	detected at two-cell stage during embryo development

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	leucine zipper
	six copies of a potential helix-loop-helix (HLH) repeat motif
	segment between I-repeats 1 and 2 contains:
	- nuclear localization signal (NLS)
	- two tyrosine phosphorylation sites
	- a consensus MAP kinase interaction domain (D box)
	- a polyproline II domain

conjugated

PhosphoP

mono polymer

homomer , heteromer , dimer

HOMOLOGY

interspecies	ortholog to GTF2I, Pan troglodytes
	ortholog to Gtf2i, Rattus norvegicus
	ortholog to Gtf2i, Mus musculus

intraspecies

paralog to GTF2IRD1

Homologene

FAMILY	TFII-I family transcription factors
	LDLR family

CATEGORY

immunity/defense , regulatory , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	involved in the mental retardation of Williams-Beuren syndrome
	multifunctional phosphoprotein with roles in transcription and signal transduction
	inhibitor of agonist-induced calcium entry
	playing a role in the visuospatial deficit in WBS
	having essential functions in embryonic development
	plays an inhibitory role in regulating genes that are essential in osteogenesis and intersects with the bone-specific transcription factor RUNX2 and the retinoblastoma protein RB1
	act as both a basal transcriptional factor and a transcriptional coactivator through binding to elements within the promoter of a number of genes

CELLULAR PROCESS

nucleotide, transcription, initiation

PHYSIOLOGICAL PROCESS

development , immunity/defense

text	neuronal development, anti-pathogen response

PATHWAY

metabolism

signaling

signal transduction

a component	promoting the formation of stable high-order complexes of SRF and PHOX1
	part of a histone deacetylase complex containing HDAC1, HDAC2, AOF2, RCOR1, ZNF261, ZNF198 and KIAA0182
	GTF2I, PARP1, and SFPQ proteins, each previously implicated in gene regulation, forms a complex controlling transcription of DYX1C1

INTERACTION

DNA	binds independently to two distinct promoter elements, a pyrimidine-rich initiator (Inr) and a recognition site (E-box) for upstream stimulatory factor 1 (USF1)

RNA

small molecule

protein	activating transcription factor 6 (ATF6)
	HDAC1,2 and BHC110, an FAD-binding protein complex
	Histone deacetylase 3 (HDAC3)
	extracellular signal-related kinase (ERK)
	proto-oncoprotein Myc
	RING-like zinc finger containing Miz1/PIASxbeta/Siz2
	cGMP-dependent protein kinase I (G-kinase I)
	c-fos upstream activators SRF, STAT1, and STAT3
	upstream stimulatory factor 1 (USF1)
	Bruton's tyrosine kinase (Btk)
	a negative regulator of agonist-induced calcium entry (ACE)
	ARID3A transiently interacts with sumoylation enzymes, blocks calcium flux and phosphorylation of BTK and GTF2II and is then discharged from lipid rafts as a Sumo-I-modified form
	CFDP1, Sec23 homolog A (SEC23A), and nuclear receptor binding SET domain protein 1 (NSD1), contain consensus GTF2I binding sites in their proximal promoters

cell & other

REGULATION

activated by

Janus kinase 2 (JAK2)

repressed by

hMusTRD1/BEN

Other	phosphorylated on tyrosine residues by BTK in response to B cell receptor cross linking
	ERK regulates the activity of TFII-I by direct phosphorylation
	modulated by the Rho inhibitor, p190RhoGAP (also known as GRLF1) during capillary network formation in human microvascular endothelial cells and retinal angiogenesis

ASSOCIATED DISORDERS

corresponding disease(s)

WBS , DUP7Q11

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --other   haploinsufficiency is associated with the characteristic craniofacial and neurodevelopmental pathologies of WBS

Susceptibility

to separation anxiety

Variant & Polymorphism other	association between a major anxiety disorder and change in copy number of a single gene provides a starting point for understanding the molecular basis of anxiety

Candidate gene	increase in social interaction
	separation anxiety in humans and mice
Marker
Therapy target

ANIMAL & CELL MODELS

heterozygous deletion in the Gtf2i gene in mice exhibits craniofacial and general osteogenic defects