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FLASH GENE

Symbol

TGFB3

contributors: mct - updated : 27-09-2021

HGNC name	transforming growth factor, beta 3
HGNC id	11769

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ARVD1 arrhythmogenic right ventricular dysplasia, familial, 1 LDS5 Loeys-Dietz syndrome 5
Location	14q24.3      Physical location : 76.424.441 - 76.448.092
Synonym name	transforming growth factor, beta 3, including the latent-associated peptide
Synonym symbol(s)	ARVD, FLJ16571, TGF-beta3

DNA

TYPE	functioning gene
STRUCTURE	23.65 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   HRE
text structure	a putative FOXE1 consensus site in its promoter region
	cAMP-responsive element (CRE) in TGFB3 promoter is recognized as an important regulatory site for TGFB3 auto-regulation

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_003239 7 - 3183 - 412 - 2002 12239581

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         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 Blood / Hematopoietic bone marrow       Connective         Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum cardiac     Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol   chondrocyte   digestive Blood/Hematopoietic monocyte Blood/Hematopoietic platelet

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal LAP (latency associated peptide)
	prodomains of TGFB1 and TGFB3 contain an RGD motif that is recognized by alpha5 integrins
	EGF repeats
	a C terminal TGFB sequence

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY

TGF beta superfamily

CATEGORY

signaling cytokine growth factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm
	intracellular,nucleus

basic FUNCTION	involved in embryogenesis and cell differentiation
	role in the etiology of Cleft lip/palate among the central European population if the risk allele is inherited from the father
	may actually play a protective role against tumourigenesis in a range of tissues including the skin, breast, oral and gastric mucosa
	TGFB3 signaling is crucial for proper differentiation and morphogenesis of neural crest-derived cells in eye structures
	MSX1 and TGFB3 signaling is crucial for proper differentiation and morphogenesis of neural crest-derived cells in eye structures
	TGFB3 signaling cascade regulates the FasL-Fas-caspase extrinsic apoptosis pathway and is essential for palatal fusion during craniofacial development
	persistent TGFB3 activation increased ROS levels in a NOX4-dependent pathway and subsequently induced autophagy as well as MUC5AC expression in the epithelial cells
	can effectively promote the transformation process from fat stem cells to chondrocytes, thus promoting chondrogenesis
	mainly plays a role through WNT5A/CTNNB, promoting human fat stem cell growing into the cartilage
	TGFB2 and TGFB3 may play a pathological role in fibrosis

CELLULAR PROCESS	cell life, proliferation/growth
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

via the SMAD (MADH2 or MADH3-MADH4) complex

a component

forming a small latent complex by disulfide bonding between TGFB dimer and the propeptide dimer TGF-beta 1 latency associated prolypeptide (LAP)

INTERACTION

DNA

RNA

small molecule

protein	great interaction between TGFB1 and TGFB3 in the developing palate, confirming that TGFB3 has a more active role in midline epithelial seam cell death than TGFB1
	interacting with CDC42 (CDC42 is a crucial regulatory component in the TGFB3-mediated cascade of events that leads to the disruption of the tight junction fibrils above the preleptotene spermatocytes to facilitate their transit (
	interacting with FOXE1 (role of FOXE1 in controlling the expression of MSX1 and TGFB3 relevant in craniofacial development)
	interacting with Wnt/CTNNB (essential role for Wnt/CTNNB signaling in the epithelial component at the step of palate fusion during palate development by controlling the expression of TGFB3 in the medial edge epithelium (MEE))
	IRF6 is involved in TGFB3-mediated palatal fusion

cell & other

epithelial-mesenchymal interactions

REGULATION

induced by

SNAI1, SNAI2 (SNAI1 and SNAI2 promote formation of beta-catenin-T-cell factor (TCF)-4 transcription complexes that bind to the promoter of the TGFB3 gene to increase its transcription)

ASSOCIATED DISORDERS

corresponding disease(s)

ARVD1 , LDS5

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in chondrosarcomas tumoral     --over   in Glioblastoma

Susceptibility

to nonsyndromic cleft lip with or without cleft palate to ossification of the posterior longitudinal ligament of the spine to male infertility to gestational diabetes mellitus (GDM)

Variant & Polymorphism SNP	increasing the risk of ossification of the posterior longitudinal ligament of the spine
	polymorphisms increasing the risk of nonsyndromic cleft lip with or without cleft palate
	heterozygous rs2284792 AG genotype was associated with increased odds for infertility
	AA and AG genotype of TGFB3 rs2284792 polymorphism may be significantly associated with increased risk of GDM

Candidate gene	to nonsyndromic cleft lip with or without cleft palate
Marker
Therapy target
	System Type Disorder Pubmed cancer brain glioma/neuroblstoma targeting TGFB3 may represent a promising strategy interfering with aberrant TGFB signaling in glioblastoma

ANIMAL & CELL MODELS

	abnormal limb development and cleft palate in mice lacking TGFB3
	Tgf-beta3 null mutant palates of two strains of mice (C57/BL/6J (C57), and MF1) that develop cleft palates of different severity