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FLASH GENE

Symbol

TGFBR1

contributors: mct/pgu - updated : 05-11-2014

HGNC name	transforming growth factor, beta receptor 1
HGNC id	11772

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	FRLS Furlong syndrome FTAA4 aortic aneurysm, familial thoracic 4 LDS1A Loeys-Dietz syndrome, type 1A MSSE multiple self-healing squamous epithelioma
Location	9q22.33      Physical location : 101.867.411 - 101.916.471
Synonym name	activin A receptor like kinase
	serine/threonine-protein kinase receptor R4
	transforming growth factor, beta receptor I
	transforming growth factor, beta receptor I (activin A receptor type II-like kinase, 53kDa)
Synonym symbol(s)	ACVRLK4, ALK5, SKR4, TGFR-1, LDS1A, LDS2A, AAT5, TbetaRI
EC.number	2.7.11.30, 2.7.1.37

DNA

TYPE	functioning gene
STRUCTURE	49.06 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	alternatively spliced in vascular smooth cells (Valcourt)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001130916 8 - 6244 NP_001124388 - 426 - 2002 12239581 NM_004612 9 - 6475 NP_004603 - 503 - 2002 12239581

EXPRESSION

Type	ubiquitous

constitutive of

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 neuroendocrine pituitary     highly Hearing/Equilibrium ear       highly Respiratory respiratory tract larynx     highly

cells

System Cell Pubmed Species Stage Rna symbol Skeleton osteoblast

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	24 aa signal peptide with a 2,3 kDa molecular weight
	cysteine-rich N terminal extracellular domain involved in ligand binding
	a single transmembrane domain
	glycine-serine-rich domain
	a regulatory segment called the GS region and a C terminal serine/threonine kinase domain with a stretch of alanine (GCC) repeats

conjugated

GlycoP

mono polymer

homomer , dimer

isoforms

Precursor

479 aa mature peptide with a 53,6 kDa molecular weight

HOMOLOGY

interspecies	homolog to rattus Tgfbr1 (97,18 pc)
	homolog to murine Tgfbr1 (97,19 pc)

Homologene

FAMILY	ser/thr protein kinase family
	TGFB receptor subfamily

CATEGORY

signaling growth factor , receptor membrane

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm

basic FUNCTION	mediating the induction of several genes involved in cell-matrix interactions
	TGFB1-TGFBR1-MAPK signaling in tumor cells promotes tumor angiogenesis
	TGFBR1/ACVRL1 balance regulates leptin expression in mesenchymal stem cells (MSC)
	ACVRL1 and TGFBR1 play antagonistic roles in transforming growth factor beta-induced podosome formation in aortic endothelial cells

CELLULAR PROCESS	cell cycle
	cell life, proliferation/growth
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development , ossification

PATHWAY

metabolism

signaling

a component	hererodimerizing with TGFBR2
	SMAD7-APC complex links the TGFBR1 to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFB1

INTERACTION

DNA

RNA

small molecule	cofactor,
	magnesium or manganese

protein	binding TGFB when coexpressed with TGFBR
	interacting with TGFBRAP1
	interaction with GATA6 (promotes angiogenic function and survival in endothelial cells by suppression of TGFBR1)
	GIPC1, ACVR1, BMPR1A, and TGFBR1 are signaling components required for TGFBR3-mediated endothelial cell epithelial-mesenchymal transformation
	expression of NPNT is regulated by the TGFBR1-SMAD2 signaling pathway in osteoblasts
	TOLLIP cooperates with SMAD7 to modulate intracellular trafficking and degradation of ubiquitinated TGFBR1, whereby negatively regulates TGFB signaling pathway
	UCHL5 is also required for high glucose-induced TGFBR1 protein deubiquitination, CDKN1A and fibronectin protein expression and cell hypertrophy
	SIK1 is involved in high glucose-induced mesangial cell proliferation mediated by the TGFBR1 signaling pathway
	DAB2 interacts with TGFBR1 to restrict its lateral diffusion at the plasma membrane and enhance its clathrin-mediated endocytosis
	APPL1 and APPL2 are associated with TGFBR1 in a TRAF6-dependent manner

cell & other

REGULATION

activated by

Vitamin D3 increasing TGFB1 binding to osteoblasts via TGFBRs

induced by

RUNX2 transcription regulation

repressed by

negatively regulated and degradated by SMURF1 through MADH7 (Smad7)

ASSOCIATED DISORDERS

corresponding disease(s)

LDS1A , FRLS , FTAA4 , MSSE

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         somatic acquisition of the common TGFBR*6A hypomorphic variant in colorectal and head and neck tumors is a critical event in early stage of cancer development

Susceptibility

to colorectal cancer to abdominal aortic aneurysm (AAA)

Variant & Polymorphism SNP , other	including two variants TGFBR1, 6A and TGFBR1, 10A
	germline allele-specific expression increasing the risk of colorectal cancer
	SNP rs1626340 associated to abdominal aortic aneurysm (AAA)

Candidate gene
Marker	APPL, APPL2-TGFBR1 complex may serve as a prognostic marker, in prostate cancer
Therapy target

ANIMAL & CELL MODELS