TGF beta receptor 1

Transforming growth factor, beta receptor 1
PDB rendering based on 1b6c.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1B6C​, 1IAS​, 1PY5​, 1RW8​, 1TBI​, 1VJY​, 2L5S​, 2PJY​, 2WOT​, 2WOU​, 2X7O​, 3FAA​, 3GXL​, 3HMM​, 3KCF​, 3KFD​, 3TZM​, 4X0M​, 4X2J​, 4X2K​, 4X2N​
Identifiers
Symbols	TGFBR1 ; AAT5; ACVRLK4; ALK-5; ALK5; ESS1; LDS1; LDS1A; LDS2A; MSSE; SKR4; TGFR-1; tbetaR-I
External IDs	OMIM: 190181 MGI: 98728 HomoloGene: 3177 ChEMBL: 4439 GeneCards: TGFBR1 Gene
EC number	2.7.11.30
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • receptor signaling protein serine/threonine kinase activity • transforming growth factor beta-activated receptor activity • transforming growth factor beta receptor activity, type I • receptor signaling protein activity • type II transforming growth factor beta receptor binding • protein binding • ATP binding • growth factor binding • SMAD binding • metal ion binding • transforming growth factor beta binding • I-SMAD binding Cellular component • intracellular • cell • endosome • plasma membrane • bicellular tight junction • membrane • receptor complex • transforming growth factor beta receptor homodimeric complex Biological process • activation of MAPKK activity • skeletal system development • angiogenesis • in utero embryonic development • kidney development • blastocyst development • epithelial to mesenchymal transition • negative regulation of endothelial cell proliferation • positive regulation of endothelial cell proliferation • lens development in camera-type eye • regulation of transcription, DNA-templated • protein phosphorylation • apoptotic process • cell cycle arrest • signal transduction • transforming growth factor beta receptor signaling pathway • heart development • positive regulation of cell proliferation • germ cell migration • male gonad development • post-embryonic development • anterior/posterior pattern specification • regulation of gene expression • positive regulation of gene expression • regulation of epithelial to mesenchymal transition • positive regulation of pathway-restricted SMAD protein phosphorylation • peptidyl-serine phosphorylation • peptidyl-threonine phosphorylation • signal transduction by protein phosphorylation • collagen fibril organization • positive regulation of cell growth • negative regulation of transforming growth factor beta receptor signaling pathway • regulation of protein ubiquitination • negative regulation of chondrocyte differentiation • activin receptor signaling pathway • intracellular signal transduction • wound healing • endothelial cell activation • extracellular structure organization • regulation of protein binding • endothelial cell migration • positive regulation of transcription, DNA-templated • thymus development • neuron fate commitment • embryonic cranial skeleton morphogenesis • skeletal system morphogenesis • mesenchymal cell differentiation • artery morphogenesis • cell motility • positive regulation of cellular component movement • positive regulation of filopodium assembly • positive regulation of protein kinase B signaling • parathyroid gland development • palate development • pharyngeal system development • cardiac epithelial to mesenchymal transition • pathway-restricted SMAD protein phosphorylation • positive regulation of SMAD protein import into nucleus • response to cholesterol • cellular response to transforming growth factor beta stimulus • positive regulation of apoptotic signaling pathway • negative regulation of extrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7046	21812
Ensembl	ENSG00000106799	ENSMUSG00000007613
UniProt	P36897	Q64729
RefSeq (mRNA)	NM_001130916	NM_009370
RefSeq (protein)	NP_001124388	NP_033396
Location (UCSC)	Chr 9: 99.1 – 99.15 Mb	Chr 4: 47.35 – 47.41 Mb
PubMed search

Transforming growth factor, beta receptor I (activin A receptor type II-like kinase, 53kDa) is a TGF beta receptor. TGFBR1 is its human gene.

Function

The protein encoded by this gene forms a heteromeric complex with type II TGF-β receptors when bound to TGF-β, transducing the TGF-β 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 (LDS, LDAS).^[1]

Interactions

TGF beta receptor 1 has been shown to interact with:

• Caveolin 1,^[2]
• Endoglin,^[3][4]
• FKBP1A,^[5][6]
• FNTA,^[7]
• Heat shock protein 90kDa alpha (cytosolic), member A1^[8]
• Mothers against decapentaplegic homolog 7,^{[9][10][11][12][13][14]}
• PPP2R2A,^[15]
• STRAP,^[14][16]
• TGF beta 1,^[17][18] and
• TGF beta receptor 2.^[2][19]

Inhibitors

• GW-788,388
• LY-2109761
• Galunisertib (LY-2157299)
• SB-431,542
• SB-525,334

See also

• TGF beta receptors

References

1. "Entrez Gene: TGFBR1 transforming growth factor, beta receptor I (activin A receptor type II-like kinase, 53kDa)".
2. Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP (Mar 2001). "Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor". The Journal of Biological Chemistry 276 (9): 6727–38. doi:10.1074/jbc.M008340200. PMID 11102446.
3. Guerrero-Esteo M, Sanchez-Elsner T, Letamendia A, Bernabeu C (Aug 2002). "Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-beta receptors I and II". The Journal of Biological Chemistry 277 (32): 29197–209. doi:10.1074/jbc.M111991200. PMID 12015308.
4. Barbara NP, Wrana JL, Letarte M (Jan 1999). "Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily". The Journal of Biological Chemistry 274 (2): 584–94. doi:10.1074/jbc.274.2.584. PMID 9872992.
5. Wang T, Donahoe PK, Zervos AS (Jul 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science 265 (5172): 674–6. doi:10.1126/science.7518616. PMID 7518616.
6. Liu F, Ventura F, Doody J, Massagué J (Jul 1995). "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Molecular and Cellular Biology 15 (7): 3479–86. doi:10.1128/mcb.15.7.3479. PMC 230584. PMID 7791754.
7. Kawabata M, Imamura T, Miyazono K, Engel ME, Moses HL (Dec 1995). "Interaction of the transforming growth factor-beta type I receptor with farnesyl-protein transferase-alpha". The Journal of Biological Chemistry 270 (50): 29628–31. doi:10.1074/jbc.270.50.29628. PMID 8530343.
8. Wrighton KH, Lin X, Feng XH (Jul 2008). "Critical regulation of TGFbeta signaling by Hsp90". Proceedings of the National Academy of Sciences of the United States of America 105 (27): 9244–9. doi:10.1073/pnas.0800163105. PMC 2453700. PMID 18591668.
9. Mochizuki T, Miyazaki H, Hara T, Furuya T, Imamura T, Watabe T, Miyazono K (Jul 2004). "Roles for the MH2 domain of Smad7 in the specific inhibition of transforming growth factor-beta superfamily signaling". The Journal of Biological Chemistry 279 (30): 31568–74. doi:10.1074/jbc.M313977200. PMID 15148321.
10. Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K (Jan 2004). "Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts". The Journal of Clinical Investigation 113 (2): 253–64. doi:10.1172/JCI16269. PMC 310747. PMID 14722617.
11. Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, Ebina M, Nukiwa T, Miyazawa K, Imamura T, Miyazono K (Dec 2003). "Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7". The EMBO Journal 22 (24): 6458–70. doi:10.1093/emboj/cdg632. PMC 291827. PMID 14657019.
12. Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, Wrana JL (Dec 2000). "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation". Molecular Cell 6 (6): 1365–75. doi:10.1016/s1097-2765(00)00134-9. PMID 11163210.
13. Hayashi H, Abdollah S, Qiu Y, Cai J, Xu YY, Grinnell BW, Richardson MA, Topper JN, Gimbrone MA, Wrana JL, Falb D (Jun 1997). "The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling". Cell 89 (7): 1165–73. doi:10.1016/s0092-8674(00)80303-7. PMID 9215638.
14. Datta PK, Moses HL (May 2000). "STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling". Molecular and Cellular Biology 20 (9): 3157–67. doi:10.1128/mcb.20.9.3157-3167.2000. PMC 85610. PMID 10757800.
15. Griswold-Prenner I, Kamibayashi C, Maruoka EM, Mumby MC, Derynck R (Nov 1998). "Physical and functional interactions between type I transforming growth factor beta receptors and Balpha, a WD-40 repeat subunit of phosphatase 2A". Molecular and Cellular Biology 18 (11): 6595–604. doi:10.1128/mcb.18.11.6595. PMC 109244. PMID 9774674.
16. Datta PK, Chytil A, Gorska AE, Moses HL (Dec 1998). "Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling". The Journal of Biological Chemistry 273 (52): 34671–4. doi:10.1074/jbc.273.52.34671. PMID 9856985.
17. Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R (Nov 1993). "Determination of type I receptor specificity by the type II receptors for TGF-beta or activin". Science 262 (5135): 900–2. doi:10.1126/science.8235612. PMID 8235612.
18. Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (Mar 2000). "Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis". Proceedings of the National Academy of Sciences of the United States of America 97 (6): 2626–31. doi:10.1073/pnas.97.6.2626. PMC 15979. PMID 10716993.
19. Kawabata M, Chytil A, Moses HL (Mar 1995). "Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor". The Journal of Biological Chemistry 270 (10): 5625–30. doi:10.1074/jbc.270.10.5625. PMID 7890683.

Further reading

• Massagué J (Jun 1992). "Receptors for the TGF-beta family". Cell 69 (7): 1067–70. doi:10.1016/0092-8674(92)90627-O. PMID 1319842.
• Wrana JL (1998). "TGF-beta receptors and signalling mechanisms". Mineral and Electrolyte Metabolism 24 (2-3): 120–30. doi:10.1159/000057359. PMID 9525694.
• Josso N, di Clemente N, Gouédard L (Jun 2001). "Anti-Müllerian hormone and its receptors". Molecular and Cellular Endocrinology 179 (1-2): 25–32. doi:10.1016/S0303-7207(01)00467-1. PMID 11420127.

External links

• GeneReviews/NIH/NCBI/UW entry on Thoracic Aortic Aneurysms and Aortic Dissections
• GeneReviews/NCBI/NIH/UW entry on Loeys-Dietz Syndrome