TGFBR1 (transforming growth factor beta receptor 1)

Gene

• Entrez ID: 7046
• Gene name: Transforming growth factor beta receptor 1
• Gene symbol: TGFBR1
• Synonyms: AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1, LDS1A, LDS2A, MSSE, SKR4, TBR-i, TBRI, TGFR-1, tbetaR-I
• Chromosome: 9
• Chromosome location: 9q22.33
• Summary: The protein encoded by this gene forms a heteromeric complex with type II TGF-beta receptors when bound to TGF-beta, transducing the TGF-beta signal from the cell surface to the cytoplasm. The encoded protein is a serine/threonine protein kinase. Mutations in this gene have been associated with Loeys-Dietz aortic aneurysm syndrome (LDAS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs11466445	GCGGCGGCGGCGGCG>-,GCG,GCGGCG,GCGGCGGCG,GCGGCGGCGGCG,GCGGCGGCGGCGGCGGCG,GCGGCGGCGGCGGCGGCGGCG,GCGGCGGCGGCGGCGGCGGCGGCG,GCGGCGGCGGCGGCGGCGGCGGCGGCG	Benign, conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign, benign-likely-benign	Intron variant, inframe deletion, inframe insertion, genic upstream transcript variant, coding sequence variant
rs111426349	C>A,G,T	Pathogenic, uncertain-significance	Coding sequence variant, synonymous variant, missense variant
rs111854391	C>A,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant, stop gained
rs113605875	G>A,C,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs121918710	T>G	Pathogenic	Coding sequence variant, missense variant
rs121918711	A>G	Pathogenic	Coding sequence variant, missense variant
rs121918712	C>T	Pathogenic	Coding sequence variant, missense variant
rs121918713	G>T	Pathogenic	Coding sequence variant, missense variant, intron variant
rs145033378	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, 5 prime UTR variant, coding sequence variant
rs148176750	A>G	Likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, intron variant, coding sequence variant
rs190878719	G>A	Conflicting-interpretations-of-pathogenicity, benign-likely-benign, likely-benign	Coding sequence variant, synonymous variant, intron variant
rs387906696	A>G	Uncertain-significance, risk-factor	Missense variant, 5 prime UTR variant, coding sequence variant
rs387906697	C>T	Risk-factor, pathogenic	Stop gained, coding sequence variant
rs587776865	G>C	Uncertain-significance, risk-factor	Missense variant, 5 prime UTR variant, coding sequence variant
rs587776866	A>C	Risk-factor	Splice acceptor variant
rs727503470	G>A,T	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs730880223	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs759805984	T>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs760079636	G>A	Likely-pathogenic, pathogenic-likely-pathogenic	Coding sequence variant, missense variant
rs767589799	G>T	Likely-pathogenic	Coding sequence variant, missense variant
rs772339721	A>G,T	Likely-pathogenic	Coding sequence variant, missense variant
rs863223811	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs863223812	C>T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs863223814	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs863223815	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs863223816	A>C,G	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs863223817	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs863223819	A>G	Pathogenic	Coding sequence variant, missense variant
rs863223822	A>C	Likely-pathogenic	Coding sequence variant, missense variant
rs863223829	AAG>-	Pathogenic	Coding sequence variant, inframe deletion
rs863223832	C>A,T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs869025535	G>A	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs878854714	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant, genic upstream transcript variant, intron variant
rs886038919	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs886038954	->TG	Pathogenic	Coding sequence variant, frameshift variant
rs886039176	T>C,G	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs1057524497	G>A,T	Pathogenic, uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, stop gained, missense variant
rs1060502040	C>T	Pathogenic	Coding sequence variant, intron variant, stop gained
rs1060502042	G>A	Likely-pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs1131691342	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1554700603	->TGG	Pathogenic	Coding sequence variant, inframe insertion
rs1554700672	G>T	Pathogenic	Coding sequence variant, stop gained
rs1554701881	A>C,G	Likely-pathogenic	Splice acceptor variant
rs1554701911	G>T	Pathogenic	Coding sequence variant, missense variant
rs1554701914	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1554702262	G>A	Pathogenic	Splice donor variant
rs1554702463	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1564161224	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1588585506	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1588585570	C>T	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT000687	hsa-let-7c-5p	qRT-PCR, Luciferase reporter assay, Western blot	19841744
MIRT003271	hsa-miR-204-5p	Luciferase reporter assay	20056717
MIRT004650	hsa-miR-128-3p	Luciferase reporter assay, Western blot	20054641
MIRT004650	hsa-miR-128-3p	CLASH	23622248
MIRT004650	hsa-miR-128-3p	PAR-CLIP	23592263
MIRT007379	hsa-miR-140-5p	Luciferase reporter assay	23401231
MIRT021634	hsa-miR-142-3p	Microarray	17612493
MIRT021634	hsa-miR-142-3p	HITS-CLIP	22473208
MIRT021634	hsa-miR-142-3p	Luciferase reporter assay, qRT-PCR, Western blot	24558198
MIRT021634	hsa-miR-142-3p	Western blot	28146434
MIRT027382	hsa-miR-101-3p	Sequencing	20371350
MIRT027382	hsa-miR-101-3p	Immunofluorescence, qRT-PCR	24817606
MIRT027865	hsa-miR-98-5p	Microarray	19088304
MIRT032178	hsa-let-7d-5p	Sequencing	20371350
MIRT053633	hsa-let-7f-5p	Microarray	22942087
MIRT053635	hsa-miR-130a-3p	Microarray	22942087
MIRT053663	hsa-miR-181a-5p	Microarray	22942087
MIRT053663	hsa-miR-181a-5p	Luciferase reporter assay, qRT-PCR, Western blot	22714950
MIRT054663	hsa-let-7g-5p	Luciferase reporter assay, qRT-PCR, Western blot	24291274
MIRT054832	hsa-let-7b-5p	GFP reporter assay, Western blot, ELISA	24978044
MIRT106691	hsa-miR-1343-3p	HITS-CLIP	23313552
MIRT106693	hsa-miR-6783-3p	HITS-CLIP	23313552
MIRT173470	hsa-miR-202-5p	Luciferase reporter assay, Western blot	28373289
MIRT173481	hsa-miR-1283	PAR-CLIP	22291592
MIRT173515	hsa-miR-4668-5p	HITS-CLIP	23313552
MIRT173532	hsa-miR-8083	PAR-CLIP	23592263
MIRT323787	hsa-miR-27a-3p	PAR-CLIP	23592263
MIRT323788	hsa-miR-216a-3p	PAR-CLIP	23592263
MIRT323789	hsa-miR-27b-3p	PAR-CLIP	23592263
MIRT323789	hsa-miR-27b-3p	Luciferase reporter assay, Western blot	28095798
MIRT323791	hsa-miR-3681-3p	PAR-CLIP	23592263
MIRT372394	hsa-miR-3927-3p	HITS-CLIP	23313552
MIRT372395	hsa-miR-6831-5p	HITS-CLIP	23313552
MIRT437849	hsa-miR-376c-3p	Luciferase reporter assay, qRT-PCR, Western blot	23424236
MIRT438737	hsa-miR-135b-5p	ChIP-seq, Luciferase reporter assay, qRT-PCR, Western blot	24802670
MIRT466408	hsa-miR-6826-3p	PAR-CLIP	23592263
MIRT466409	hsa-miR-6795-3p	PAR-CLIP	23592263
MIRT466410	hsa-miR-6887-3p	PAR-CLIP	23592263
MIRT466411	hsa-miR-3156-5p	PAR-CLIP	23592263
MIRT496743	hsa-miR-4480	PAR-CLIP	22291592
MIRT496744	hsa-miR-8063	PAR-CLIP	22291592
MIRT698502	hsa-miR-6888-3p	HITS-CLIP	23313552
MIRT698503	hsa-miR-466	HITS-CLIP	23313552
MIRT698504	hsa-miR-6739-5p	HITS-CLIP	23313552
MIRT698505	hsa-miR-6733-5p	HITS-CLIP	23313552
MIRT698506	hsa-miR-3153	HITS-CLIP	23313552
MIRT698507	hsa-miR-4646-5p	HITS-CLIP	23313552
MIRT698508	hsa-miR-204-3p	HITS-CLIP	23313552
MIRT698509	hsa-miR-6742-3p	HITS-CLIP	23313552
MIRT698510	hsa-miR-6852-5p	HITS-CLIP	23313552
MIRT698511	hsa-miR-939-3p	HITS-CLIP	23313552
MIRT698512	hsa-miR-4643	HITS-CLIP	23313552
MIRT698513	hsa-miR-4789-3p	HITS-CLIP	23313552
MIRT698514	hsa-miR-3529-5p	HITS-CLIP	23313552
MIRT698515	hsa-miR-379-5p	HITS-CLIP	23313552
MIRT732226	hsa-miR-490-3p	Luciferase reporter assay, Western blot	26714817
MIRT734034	hsa-miR-20a-5p	Immunoblot, Immunofluorescence, Luciferase reporter assay, qRT-PCR	26729221
MIRT734924	hsa-miR-181c-5p	Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	26682928
MIRT735136	hsa-miR-199a-5p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	25938468

Transcription factors

Transcription factor	Regulation	Reference
SMAD7	Repression	15221015
WWP1	Repression	15221015

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000186	Process	Activation of MAPKK activity	IDA	18625725
GO:0001501	Process	Skeletal system development	ISS
GO:0001701	Process	In utero embryonic development	ISS
GO:0001822	Process	Kidney development	ISS
GO:0001824	Process	Blastocyst development	IEA
GO:0001837	Process	Epithelial to mesenchymal transition	IDA	15761148
GO:0001937	Process	Negative regulation of endothelial cell proliferation	IEA
GO:0001938	Process	Positive regulation of endothelial cell proliferation	ISS
GO:0002088	Process	Lens development in camera-type eye	IEA
GO:0003222	Process	Ventricular trabecula myocardium morphogenesis	ISS
GO:0003223	Process	Ventricular compact myocardium morphogenesis	ISS
GO:0003342	Process	Proepicardium development	ISS
GO:0004672	Function	Protein kinase activity	IDA	19736306
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	12065756, 18625725
GO:0005024	Function	Transforming growth factor beta-activated receptor activity	IC	1326540
GO:0005024	Function	Transforming growth factor beta-activated receptor activity	IDA	12015308, 14633705
GO:0005024	Function	Transforming growth factor beta-activated receptor activity	IMP	18625725
GO:0005024	Function	Transforming growth factor beta-activated receptor activity	IMP	1333888
GO:0005025	Function	Transforming growth factor beta receptor activity, type I	IBA	21873635
GO:0005025	Function	Transforming growth factor beta receptor activity, type I	IDA	8752209
GO:0005114	Function	Type II transforming growth factor beta receptor binding	IDA	11157754
GO:0005114	Function	Type II transforming growth factor beta receptor binding	IPI	1333888
GO:0005515	Function	Protein binding	IPI	8622651, 10025408, 11278302, 11279102, 11583628, 12015308, 14517293, 14580334, 15702480, 15761148, 17099224, 18243111, 18625725, 18758450, 18974388, 19732720, 20856203, 22344298, 23723426, 24263861, 24658140, 25893292, 26583432
GO:0005524	Function	ATP binding	IDA	12065756
GO:0005634	Component	Nucleus	IDA	26583432
GO:0005768	Component	Endosome	IDA	26583432
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IDA	17878231, 25893292
GO:0005886	Component	Plasma membrane	TAS
GO:0005923	Component	Bicellular tight junction	IDA	15761148
GO:0006355	Process	Regulation of transcription, DNA-templated	IDA	14517293
GO:0006355	Process	Regulation of transcription, DNA-templated	IMP	15702480
GO:0006468	Process	Protein phosphorylation	IBA	21873635
GO:0006468	Process	Protein phosphorylation	IDA	12015308, 12065756
GO:0006915	Process	Apoptotic process	IEA
GO:0007050	Process	Cell cycle arrest	TAS	9759503
GO:0007165	Process	Signal transduction	IDA	14633705
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IBA	21873635
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IC	1326540
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IDA	9389648, 11157754
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	IMP	1333888
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	ISS
GO:0007179	Process	Transforming growth factor beta receptor signaling pathway	TAS
GO:0007399	Process	Nervous system development	IBA	21873635
GO:0007507	Process	Heart development	IBA	21873635
GO:0007507	Process	Heart development	ISS
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	14633705
GO:0008354	Process	Germ cell migration	ISS
GO:0008584	Process	Male gonad development	IEA
GO:0009791	Process	Post-embryonic development	IEA
GO:0009952	Process	Anterior/posterior pattern specification	ISS
GO:0009986	Component	Cell surface	IDA	25893292
GO:0010628	Process	Positive regulation of gene expression	IMP	27162619
GO:0010717	Process	Regulation of epithelial to mesenchymal transition	ISS
GO:0010718	Process	Positive regulation of epithelial to mesenchymal transition	ISS
GO:0010862	Process	Positive regulation of pathway-restricted SMAD protein phosphorylation	IDA	9311995, 9389648
GO:0016361	Function	Activin receptor activity, type I	IBA	21873635
GO:0016579	Process	Protein deubiquitination	TAS
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	15761148
GO:0018107	Process	Peptidyl-threonine phosphorylation	IDA	19736306
GO:0019838	Function	Growth factor binding	IPI	14517293
GO:0030199	Process	Collagen fibril organization	ISS
GO:0030307	Process	Positive regulation of cell growth	IDA	18625725
GO:0030335	Process	Positive regulation of cell migration	IDA	19736306
GO:0030512	Process	Negative regulation of transforming growth factor beta receptor signaling pathway	TAS
GO:0031396	Process	Regulation of protein ubiquitination	IDA	18758450
GO:0032331	Process	Negative regulation of chondrocyte differentiation	ISS
GO:0032924	Process	Activin receptor signaling pathway	IBA	21873635
GO:0032924	Process	Activin receptor signaling pathway	ISS
GO:0035556	Process	Intracellular signal transduction	ISS
GO:0042060	Process	Wound healing	TAS	9759503
GO:0042118	Process	Endothelial cell activation	ISS
GO:0043062	Process	Extracellular structure organization	TAS	9759503
GO:0043235	Component	Receptor complex	IBA	21873635
GO:0043235	Component	Receptor complex	IDA	8774881, 14517293
GO:0043393	Process	Regulation of protein binding	IEA
GO:0043542	Process	Endothelial cell migration	IEA
GO:0045121	Component	Membrane raft	IDA	25893292
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	9311995, 9389648
GO:0046332	Function	SMAD binding	IBA	21873635
GO:0046332	Function	SMAD binding	IDA	12065756, 18625725
GO:0046332	Function	SMAD binding	IPI	8980228, 9311995
GO:0046872	Function	Metal ion binding	IEA
GO:0048179	Component	Activin receptor complex	IBA	21873635
GO:0048185	Function	Activin binding	IBA	21873635
GO:0048538	Process	Thymus development	ISS
GO:0048663	Process	Neuron fate commitment	ISS
GO:0048701	Process	Embryonic cranial skeleton morphogenesis	ISS
GO:0048705	Process	Skeletal system morphogenesis	ISS
GO:0048762	Process	Mesenchymal cell differentiation	TAS	9759503
GO:0048844	Process	Artery morphogenesis	ISS
GO:0048870	Process	Cell motility	IMP	18625725
GO:0050431	Function	Transforming growth factor beta binding	IDA	14633705
GO:0050431	Function	Transforming growth factor beta binding	IDA	11157754
GO:0050431	Function	Transforming growth factor beta binding	IMP	1333888
GO:0050431	Function	Transforming growth factor beta binding	IPI	1326540
GO:0051272	Process	Positive regulation of cellular component movement	IMP	18625725
GO:0051491	Process	Positive regulation of filopodium assembly	IEA
GO:0051496	Process	Positive regulation of stress fiber assembly	ISS
GO:0051897	Process	Positive regulation of protein kinase B signaling	IDA	18625725
GO:0060017	Process	Parathyroid gland development	ISS
GO:0060021	Process	Roof of mouth development	ISS
GO:0060037	Process	Pharyngeal system development	ISS
GO:0060043	Process	Regulation of cardiac muscle cell proliferation	ISS
GO:0060317	Process	Cardiac epithelial to mesenchymal transition	ISS
GO:0060389	Process	Pathway-restricted SMAD protein phosphorylation	IDA	11157754, 12015308, 18625725, 19736306
GO:0060391	Process	Positive regulation of SMAD protein signal transduction	IDA	9389648
GO:0060412	Process	Ventricular septum morphogenesis	ISS
GO:0060978	Process	Angiogenesis involved in coronary vascular morphogenesis	ISS
GO:0060982	Process	Coronary artery morphogenesis	ISS
GO:0070411	Function	I-SMAD binding	IPI	11278251
GO:0070723	Process	Response to cholesterol	IDA	17878231
GO:0071363	Process	Cellular response to growth factor stimulus	IBA	21873635
GO:0071560	Process	Cellular response to transforming growth factor beta stimulus	IDA	19494318
GO:1905007	Process	Positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation	ISS
GO:1905075	Process	Positive regulation of tight junction disassembly	ISS
GO:1905223	Process	Epicardium morphogenesis	ISS
GO:2001235	Process	Positive regulation of apoptotic signaling pathway	IDA	18758450
GO:2001237	Process	Negative regulation of extrinsic apoptotic signaling pathway	IMP	18625725

Other IDs

• MIM: 190181
• HGNC: 11772
• e!Ensembl: ENSG00000106799

Protein

• UniProt ID: P36897
• Protein name: TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I)
• Protein function: Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.
• PDB: 1B6C, 1IAS, 1PY5, 1RW8, 1TBI, 1VJY, 2L5S, 2PJY, 2WOT, 2WOU, 2X7O, 3FAA, 3GXL, 3HMM, 3KCF, 3KFD, 3TZM, 4X0M, 4X2F, 4X2G, 4X2J, 4X2K, 4X2N, 5E8S, 5E8T, 5E8U, 5E8W, 5E8X, 5E8Z, 5E90, 5FRI, 5QIK, 5QIL, 5QIM, 5QTZ, 5QU0, 5USQ, 6B8Y, 6MAC
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01064	Activin_recp	34 → 110	Activin types I and II receptor domain	Domain
  PF08515	TGF_beta_GS	176 → 203	Transforming growth factor beta type I GS-motif	Family
  PF00069	Pkinase	205 → 492	Protein kinase domain	Domain

• Sequence:

  MEAAVAAPRPRLLLLVLAAAAAAAAALLPGATALQCFCHLCTKDNFTCVTDGLCFVSVTE
  TTDKVIHNSMCIAEIDLIPRDRPFVCAPSSKTGSVTTTYCCNQDHCNKIELPTTVKSSPG
  LGPVELAAVIAGPVCFVCISLMLMVYICHNRTVIHHRVPNEEDPSLDRPFISEGTTLKDL
  IYDMTTSGSGSGLPLLVQRTIARTIVLQESIGKGRFGEVWRGKWRGEEVAVKIFSSREER
  SWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWLVSDYHEHGSLFDYLNRYTVTVE
  GMIKLALSTASGLAHLHMEIVGTQGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVRHDS
  ATDTIDIAPNHRVGTKRYMAPEVLDDSINMKHFESFKRADIYAMGLVFWEIARRCSIGGI
  HEDYQLPYYDLVPSDPSVEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANGA
  ARLTALRIKKTLSQLSQQEGIKM

• Sequence length: 503