ID TGFR1_HUMAN Reviewed; 503 AA. AC P36897; Q6IR47; Q706C0; Q706C1; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 27-MAR-2024, entry version 245. DE RecName: Full=TGF-beta receptor type-1; DE Short=TGFR-1; DE EC=2.7.11.30; DE AltName: Full=Activin A receptor type II-like protein kinase of 53kD; DE AltName: Full=Activin receptor-like kinase 5; DE Short=ALK-5; DE Short=ALK5; DE AltName: Full=Serine/threonine-protein kinase receptor R4; DE Short=SKR4; DE AltName: Full=TGF-beta type I receptor; DE AltName: Full=Transforming growth factor-beta receptor type I; DE Short=TGF-beta receptor type I; DE Short=TbetaR-I; DE Flags: Precursor; GN Name=TGFBR1; Synonyms=ALK5, SKR4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8242743; DOI=10.1016/0092-8674(93)90489-d; RA Franzen P., ten Dijke P., Ichijo H., Yamashita H., Schulz P., Heldin C.-H., RA Miyazono K.; RT "Cloning of a TGF beta type I receptor that forms a heteromeric complex RT with the TGF beta type II receptor."; RL Cell 75:681-692(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9417915; DOI=10.1006/geno.1997.5023; RA Vellucci V.F., Reiss M.; RT "Cloning and genomic organization of the human transforming growth factor- RT beta type I receptor gene."; RL Genomics 46:278-283(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Lynch M.A., Song H., DeGroff V.L., Alam K.Y., Adams E.M., Weghorst C.M.; RT "The genomic structure of the gene encoding the human transforming growth RT factor beta type I receptor."; RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 34-40, SIGNAL SEQUENCE CLEAVAGE SITE, GLYCOSYLATION, RP CHARACTERIZATION OF VARIANT TGFBR1*6A ALA-24--26-ALA DEL, AND VARIANT RP TGFBR1*10A ALA-26 INS. RX PubMed=9661882; RA Pasche B., Luo Y., Rao P.H., Nimer S.D., Dmitrovsky E., Caron P., RA Luzzatto L., Offit K., Cordon-Cardo C., Renault B., Satagopan J.M., RA Murty V.V., Massague J.; RT "Type I transforming growth factor beta receptor maps to 9q22 and exhibits RT a polymorphism and a rare variant within a polyalanine tract."; RL Cancer Res. 58:2727-2732(1998). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [MRNA] OF RP 61-155 (ISOFORM 1), AND ALTERNATIVE SPLICING. RC TISSUE=Prostate; RX PubMed=17845732; DOI=10.1186/1471-2164-8-318; RA Konrad L., Scheiber J.A., Volck-Badouin E., Keilani M.M., Laible L., RA Brandt H., Schmidt A., Aumuller G., Hofmann R.; RT "Alternative splicing of TGF-betas and their high-affinity receptors T beta RT RI, T beta RII and T beta RIII (betaglycan) reveal new variants in human RT prostatic cells."; RL BMC Genomics 8:318-318(2007). RN [9] RP SEQUENCE REVISION (ISOFORM 1). RA Konrad L.; RL Submitted (MAR-2011) to the EMBL/GenBank/DDBJ databases. RN [10] RP FUNCTION, PHOSPHORYLATION AT THR-185; THR-186; SER-187; SER-189 AND SER-191 RP BY TGFBR2, SUBCELLULAR LOCATION, SUBUNIT, AND MUTAGENESIS OF RP 185-THR-THR-186; SER-187; SER-189; SER-191; THR-200 AND THR-204. RX PubMed=7774578; DOI=10.1002/j.1460-2075.1995.tb07214.x; RA Wieser R., Wrana J.L., Massague J.; RT "GS domain mutations that constitutively activate T beta R-I, the RT downstream signaling component in the TGF-beta receptor complex."; RL EMBO J. 14:2199-2208(1995). RN [11] RP FUNCTION IN PHOSPHORYLATION OF SMAD2. RX PubMed=8752209; DOI=10.1016/s0092-8674(00)80128-2; RA Eppert K., Scherer S.W., Ozcelik H., Pirone R., Hoodless P., Kim H., RA Tsui L.-C., Bapat B., Gallinger S., Andrulis I.L., Thomsen G.H., RA Wrana J.L., Attisano L.; RT "MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein RT that is functionally mutated in colorectal carcinoma."; RL Cell 86:543-552(1996). RN [12] RP INTERACTION WITH SMAD2, FUNCTION IN PHOSPHORYLATION OF SMAD2, AND FUNCTION RP IN TRANSCRIPTION REGULATION. RX PubMed=8980228; DOI=10.1016/s0092-8674(00)81817-6; RA Macias-Silva M., Abdollah S., Hoodless P.A., Pirone R., Attisano L., RA Wrana J.L.; RT "MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is RT required for nuclear accumulation and signaling."; RL Cell 87:1215-1224(1996). RN [13] RP INTERACTION WITH FKBP1A, ACTIVITY REGULATION, AND MUTAGENESIS OF LEU-193 RP AND PRO-194. RX PubMed=9233797; DOI=10.1093/emboj/16.13.3866; RA Chen Y.G., Liu F., Massague J.; RT "Mechanism of TGFbeta receptor inhibition by FKBP12."; RL EMBO J. 16:3866-3876(1997). RN [14] RP INTERACTION WITH SMAD3. RX PubMed=9311995; DOI=10.1093/emboj/16.17.5353; RA Nakao A., Imamura T., Souchelnytskyi S., Kawabata M., Ishisaki A., Oeda E., RA Tamaki K., Hanai J., Heldin C.H., Miyazono K., ten Dijke P.; RT "TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4."; RL EMBO J. 16:5353-5362(1997). RN [15] RP INTERACTION WITH SMAD2, FUNCTION IN PHOSPHORYLATION OF SMAD2, AND FUNCTION RP IN TRANSCRIPTION REGULATION. RX PubMed=9346908; DOI=10.1074/jbc.272.44.27678; RA Abdollah S., Macias-Silva M., Tsukazaki T., Hayashi H., Attisano L., RA Wrana J.L.; RT "TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for RT Smad2-Smad4 complex formation and signaling."; RL J. Biol. Chem. 272:27678-27685(1997). RN [16] RP INTERACTION WITH ZFYVE9. RX PubMed=9865696; DOI=10.1016/s0092-8674(00)81701-8; RA Tsukazaki T., Chiang T.A., Davison A.F., Attisano L., Wrana J.L.; RT "SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor."; RL Cell 95:779-791(1998). RN [17] RP HOMODIMERIZATION, AND SUBCELLULAR LOCATION. RX PubMed=9472030; DOI=10.1083/jcb.140.4.767; RA Gilboa L., Wells R.G., Lodish H.F., Henis Y.I.; RT "Oligomeric structure of type I and type II transforming growth factor beta RT receptors: homodimers form in the ER and persist at the plasma membrane."; RL J. Cell Biol. 140:767-777(1998). RN [18] RP INTERACTION WITH SMAD7 AND SMURF2, AND PROTEASOMAL AND LYSOSOMAL RP DEGRADATION. RX PubMed=11163210; DOI=10.1016/s1097-2765(00)00134-9; RA Kavsak P., Rasmussen R.K., Causing C.G., Bonni S., Zhu H., Thomsen G.H., RA Wrana J.L.; RT "Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF- RT beta receptor for degradation."; RL Mol. Cell 6:1365-1375(2000). RN [19] RP INTERACTION WITH SMAD7 AND SMURF1, AND PROTEASOMAL DEGRADATION. RX PubMed=11278251; DOI=10.1074/jbc.c100008200; RA Ebisawa T., Fukuchi M., Murakami G., Chiba T., Tanaka K., Imamura T., RA Miyazono K.; RT "Smurf1 interacts with transforming growth factor-beta type I receptor RT through Smad7 and induces receptor degradation."; RL J. Biol. Chem. 276:12477-12480(2001). RN [20] RP INTERACTION WITH VPS39. RX PubMed=12941698; DOI=10.1093/emboj/cdg428; RA Felici A., Wurthner J.U., Parks W.T., Giam L.R., Reiss M., Karpova T.S., RA McNally J.G., Roberts A.B.; RT "TLP, a novel modulator of TGF-beta signaling, has opposite effects on RT Smad2- and Smad3-dependent signaling."; RL EMBO J. 22:4465-4477(2003). RN [21] RP INTERACTION WITH NEDD4L, AND UBIQUITINATION. RX PubMed=15496141; DOI=10.1042/bj20040738; RA Kuratomi G., Komuro A., Goto K., Shinozaki M., Miyazawa K., Miyazono K., RA Imamura T.; RT "NEDD4-2 (neural precursor cell expressed, developmentally down-regulated RT 4-2) negatively regulates TGF-beta (transforming growth factor-beta) RT signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta RT type I receptor."; RL Biochem. J. 386:461-470(2005). RN [22] RP FUNCTION IN EPITHELIAL TO MESENCHYMAL TRANSITION, SUBCELLULAR LOCATION, RP INTERACTION WITH PARD6A, AND FUNCTION IN PHOSPHORYLATION OF PARD6A. RX PubMed=15761148; DOI=10.1126/science.1105718; RA Ozdamar B., Bose R., Barrios-Rodiles M., Wang H.R., Zhang Y., Wrana J.L.; RT "Regulation of the polarity protein Par6 by TGFbeta receptors controls RT epithelial cell plasticity."; RL Science 307:1603-1609(2005). RN [23] RP FUNCTION IN CELLULAR GROWTH INHIBITION, AND INTERACTION WITH CD109. RX PubMed=16754747; DOI=10.1096/fj.05-5229fje; RA Finnson K.W., Tam B.Y.Y., Liu K., Marcoux A., Lepage P., Roy S., RA Bizet A.A., Philip A.; RT "Identification of CD109 as part of the TGF-beta receptor system in human RT keratinocytes."; RL FASEB J. 20:1525-1527(2006). RN [24] RP INTERACTION WITH RBPMS. RX PubMed=17099224; DOI=10.1093/nar/gkl914; RA Sun Y., Ding L., Zhang H., Han J., Yang X., Yan J., Zhu Y., Li J., Song H., RA Ye Q.; RT "Potentiation of Smad-mediated transcriptional activation by the RNA- RT binding protein RBPMS."; RL Nucleic Acids Res. 34:6314-6326(2006). RN [25] RP FUNCTION IN APOPTOSIS, AND INTERACTION WITH TRAF6 AND MAP3K7. RX PubMed=18758450; DOI=10.1038/ncb1780; RA Sorrentino A., Thakur N., Grimsby S., Marcusson A., von Bulow V., RA Schuster N., Zhang S., Heldin C.H., Landstrom M.; RT "The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor RT kinase-independent manner."; RL Nat. Cell Biol. 10:1199-1207(2008). RN [26] RP REVIEW ON PROCESSES REGULATED BY THE TGF-BETA CYTOKINES. RX PubMed=9759503; DOI=10.1146/annurev.biochem.67.1.753; RA Massague J.; RT "TGF-beta signal transduction."; RL Annu. Rev. Biochem. 67:753-791(1998). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-165, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [28] RP IDENTIFICATION IN A COMPLEX WITH TGFBR2 AND TSC22D1, INTERACTION WITH RP SMAD7, AND SUBCELLULAR LOCATION. RX PubMed=21791611; DOI=10.1128/mcb.05448-11; RA Yan X., Zhang J., Pan L., Wang P., Xue H., Zhang L., Gao X., Zhao X., RA Ning Y., Chen Y.G.; RT "TSC-22 promotes transforming growth factor beta-mediated cardiac RT myofibroblast differentiation by antagonizing Smad7 activity."; RL Mol. Cell. Biol. 31:3700-3709(2011). RN [29] RP UBIQUITINATION, AND DEUBIQUITINATION BY USP15. RX PubMed=22344298; DOI=10.1038/nm.2619; RA Eichhorn P.J., Rodon L., Gonzalez-Junca A., Dirac A., Gili M., RA Martinez-Saez E., Aura C., Barba I., Peg V., Prat A., Cuartas I., RA Jimenez J., Garcia-Dorado D., Sahuquillo J., Bernards R., Baselga J., RA Seoane J.; RT "USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through the RT activation of TGF-beta signaling in glioblastoma."; RL Nat. Med. 18:429-435(2012). RN [30] RP INTERACTION WITH SDCBP AND CAV1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP UBIQUITINATION, AND PROTEASOMAL DEGRADATION. RX PubMed=25893292; DOI=10.1038/onc.2015.100; RA Hwangbo C., Tae N., Lee S., Kim O., Park O.K., Kim J., Kwon S.H., Lee J.H.; RT "Syntenin regulates TGF-beta1-induced Smad activation and the epithelial- RT to-mesenchymal transition by inhibiting caveolin-mediated TGF-beta type I RT receptor internalization."; RL Oncogene 35:389-401(2016). RN [31] RP INTERACTION WITH APPL1. RX PubMed=26583432; DOI=10.18632/oncotarget.6346; RA Song J., Mu Y., Li C., Bergh A., Miaczynska M., Heldin C.H., Landstroem M.; RT "APPL proteins promote TGFbeta-induced nuclear transport of the TGFbeta RT type I receptor intracellular domain."; RL Oncotarget 7:279-292(2016). RN [32] RP INTERACTION WITH GPR50. RX PubMed=29572483; DOI=10.1038/s41467-018-03609-x; RA Wojciech S., Ahmad R., Belaid-Choucair Z., Journe A.S., Gallet S., Dam J., RA Daulat A., Ndiaye-Lobry D., Lahuna O., Karamitri A., Guillaume J.L., RA Do Cruzeiro M., Guillonneau F., Saade A., Clement N., Courivaud T., RA Kaabi N., Tadagaki K., Delagrange P., Prevot V., Hermine O., Prunier C., RA Jockers R.; RT "The orphan GPR50 receptor promotes constitutive TGFbeta receptor signaling RT and protects against cancer development."; RL Nat. Commun. 9:1216-1216(2018). RN [33] RP 3D-STRUCTURE MODELING OF 34-114. RX PubMed=8521960; DOI=10.1016/0014-5793(95)01239-7; RA Jokiranta T.S., Tissari J., Teleman O., Meri S.; RT "Extracellular domain of type I receptor for transforming growth factor- RT beta: molecular modelling using protectin (CD59) as a template."; RL FEBS Lett. 376:31-36(1995). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 162-503 IN COMPLEX WITH FKBP1A. RX PubMed=10025408; DOI=10.1016/s0092-8674(00)80555-3; RA Huse M., Chen Y.-G., Massague J., Kuriyan J.; RT "Crystal structure of the cytoplasmic domain of the type I TGF beta RT receptor in complex with FKBP12."; RL Cell 96:425-436(1999). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 162-503, PHOSPHORYLATION, AND RP INTERACTION WITH SMAD2 AND FKBP1A. RX PubMed=11583628; DOI=10.1016/s1097-2765(01)00332-x; RA Huse M., Muir T.W., Xu L., Chen Y.-G., Kuriyan J., Massague J.; RT "The TGF beta receptor activation process: an inhibitor- to substrate- RT binding switch."; RL Mol. Cell 8:671-682(2001). RN [36] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 175-500 IN COMPLEX WITH SYNTHETIC RP INHIBITOR. RX PubMed=15177479; DOI=10.1016/j.bmcl.2004.04.007; RA Sawyer J.S., Beight D.W., Britt K.S., Anderson B.D., Campbell R.M., RA Goodson T. Jr., Herron D.K., Li H.-Y., McMillen W.T., Mort N., Parsons S., RA Smith E.C.R., Wagner J.R., Yan L., Zhang F., Yingling J.M.; RT "Synthesis and activity of new aryl- and heteroaryl-substituted 5,6- RT dihydro-4H-pyrrolo[1,2-b]pyrazole inhibitors of the transforming growth RT factor-beta type I receptor kinase domain."; RL Bioorg. Med. Chem. Lett. 14:3581-3584(2004). RN [37] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 201-503 IN COMPLEX WITH SYNTHETIC RP INHIBITOR. RX PubMed=15317461; DOI=10.1021/jm0400247; RA Gellibert F., Woolven J., Fouchet M.-H., Mathews N., Goodland H., RA Lovegrove V., Laroze A., Nguyen V.-L., Sautet S., Wang R., Janson C., RA Smith W., Krysa G., Boullay V., De Gouville A.-C., Huet S., Hartley D.; RT "Identification of 1,5-naphthyridine derivatives as a novel series of RT potent and selective TGF-beta type I receptor inhibitors."; RL J. Med. Chem. 47:4494-4506(2004). RN [38] RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 33-111 IN COMPLEX WITH TGFBR2 AND RP TGFB3, AND DISULFIDE BONDS. RX PubMed=18243111; DOI=10.1016/j.molcel.2007.11.039; RA Groppe J., Hinck C.S., Samavarchi-Tehrani P., Zubieta C., Schuermann J.P., RA Taylor A.B., Schwarz P.M., Wrana J.L., Hinck A.P.; RT "Cooperative assembly of TGF-beta superfamily signaling complexes is RT mediated by two disparate mechanisms and distinct modes of receptor RT binding."; RL Mol. Cell 29:157-168(2008). RN [39] RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 31-115 IN COMPLEX WITH TGFBR2 AND RP TGFB1, RECEPTOR AFFINITY FOR LIGANDS, AND DISULFIDE BONDS. RX PubMed=20207738; DOI=10.1074/jbc.m109.079921; RA Radaev S., Zou Z., Huang T., Lafer E.M., Hinck A.P., Sun P.D.; RT "Ternary complex of transforming growth factor-beta1 reveals isoform- RT specific ligand recognition and receptor recruitment in the superfamily."; RL J. Biol. Chem. 285:14806-14814(2010). RN [40] RP ANALYSIS OF VARIANT TGFBR1*6A ALA-24--26-ALA DEL IN CANCER RISK. RX PubMed=12947057; DOI=10.1200/jco.2003.11.524; RA Kaklamani V.G., Hou N., Bian Y., Reich J., Offit K., Michel L.S., RA Rubinstein W.S., Rademaker A., Pasche B.; RT "TGFBR1*6A and cancer risk: a meta-analysis of seven case-control RT studies."; RL J. Clin. Oncol. 21:3236-3243(2003). RN [41] RP ANALYSIS OF VARIANT TGFBR1*6A ALA-24--26-ALA DEL IN PROSTATE CANCER. RX PubMed=15385056; DOI=10.1186/1471-2156-5-28; RA Kaklamani V.G., Baddi L., Rosman D., Liu J., Ellis N., Oddoux C., RA Ostrer H., Chen Y., Ahsan H., Offit K., Pasche B.; RT "No major association between TGFBR1*6A and prostate cancer."; RL BMC Genet. 5:28-28(2004). RN [42] RP VARIANTS LDS1 ILE-200; ARG-318; GLY-400 AND PRO-487. RX PubMed=15731757; DOI=10.1038/ng1511; RA Loeys B.L., Chen J., Neptune E.R., Judge D.P., Podowski M., Holm T., RA Meyers J., Leitch C.C., Katsanis N., Sharifi N., Xu F.L., Myers L.A., RA Spevak P.J., Cameron D.E., De Backer J.F., Hellemans J., Chen Y., RA Davis E.C., Webb C.L., Kress W., Coucke P.J., Rifkin D.B., De Paepe A.M., RA Dietz H.C.; RT "A syndrome of altered cardiovascular, craniofacial, neurocognitive and RT skeletal development caused by mutations in TGFBR1 or TGFBR2."; RL Nat. Genet. 37:275-281(2005). RN [43] RP ANALYSIS OF VARIANT TGFBR1*6A ALA-24--26-ALA DEL IN PROSTATE CANCER. RX PubMed=15505640; DOI=10.1038/sj.pcan.4500765; RA Suarez B.K., Pal P., Jin C.H., Kaushal R., Sun G., Jin L., Pasche B., RA Deka R., Catalona W.J.; RT "TGFBR1(*)6A is not associated with prostate cancer in men of European RT ancestry."; RL Prostate Cancer Prostatic Dis. 8:50-53(2005). RN [44] RP VARIANT LDS1 LEU-241. RX PubMed=16596670; DOI=10.1002/ajmg.a.31202; RA Ades L.C., Sullivan K., Biggin A., Haan E.A., Brett M., Holman K.J., RA Dixon J., Robertson S., Holmes A.D., Rogers J., Bennetts B.; RT "FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders RT revisited."; RL Am. J. Med. Genet. A 140:1047-1058(2006). RN [45] RP VARIANTS LDS1 LEU-241 AND GLN-487, AND VARIANT HIS-267. RX PubMed=16791849; DOI=10.1002/humu.20353; RA Matyas G., Arnold E., Carrel T., Baumgartner D., Boileau C., Berger W., RA Steinmann B.; RT "Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations RT in Marfan syndrome-related disorders."; RL Hum. Mutat. 27:760-769(2006). RN [46] RP VARIANTS LDS1 GLU-232; TRP-487; PRO-487 AND GLN-487. RX PubMed=16928994; DOI=10.1056/nejmoa055695; RA Loeys B.L., Schwarze U., Holm T., Callewaert B.L., Thomas G.H., Pannu H., RA De Backer J.F., Oswald G.L., Symoens S., Manouvrier S., Roberts A.E., RA Faravelli F., Greco M.A., Pyeritz R.E., Milewicz D.M., Coucke P.J., RA Cameron D.E., Braverman A.C., Byers P.H., De Paepe A.M., Dietz H.C.; RT "Aneurysm syndromes caused by mutations in the TGF-beta receptor."; RL N. Engl. J. Med. 355:788-798(2006). RN [47] RP VARIANTS [LARGE SCALE ANALYSIS] ILE-153 AND CYS-291. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [48] RP VARIANT [LARGE SCALE ANALYSIS] VAL-139. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). RN [49] RP VARIANT LDS1 GLY-351. RX PubMed=19883511; DOI=10.1186/1750-1172-4-24; RA Drera B., Ritelli M., Zoppi N., Wischmeijer A., Gnoli M., Fattori R., RA Calzavara-Pinton P.G., Barlati S., Colombi M.; RT "Loeys-Dietz syndrome type I and type II: clinical findings and novel RT mutations in two Italian patients."; RL Orphanet J. Rare Dis. 4:24-24(2009). RN [50] RP VARIANTS LDS1 TYR-266; ARG-375 AND GLN-487. RX PubMed=22113417; DOI=10.1038/jhg.2011.130; RA Yang J.H., Ki C.S., Han H., Song B.G., Jang S.Y., Chung T.Y., Sung K., RA Lee H.J., Kim D.K.; RT "Clinical features and genetic analysis of Korean patients with Loeys-Dietz RT syndrome."; RL J. Hum. Genet. 57:52-56(2012). RN [51] RP ERRATUM OF PUBMED:22113417. RA Yang J.H., Ki C.S., Han H., Song B.G., Jang S.Y., Chung T.Y., Sung K., RA Lee H.J., Kim D.K.; RL J. Hum. Genet. 57:398-398(2012). RN [52] RP VARIANTS MSSE TYR-41; SER-45; ARG-52 AND LEU-83. RX PubMed=21358634; DOI=10.1038/ng.780; RA Goudie D.R., D'Alessandro M., Merriman B., Lee H., Szeverenyi I., Avery S., RA O'Connor B.D., Nelson S.F., Coats S.E., Stewart A., Christie L., RA Pichert G., Friedel J., Hayes I., Burrows N., Whittaker S., Gerdes A.M., RA Broesby-Olsen S., Ferguson-Smith M.A., Verma C., Lunny D.P., Reversade B., RA Lane E.B.; RT "Multiple self-healing squamous epithelioma is caused by a disease-specific RT spectrum of mutations in TGFBR1."; RL Nat. Genet. 43:365-369(2011). CC -!- FUNCTION: Transmembrane serine/threonine kinase forming with the TGF- CC beta type II serine/threonine kinase receptor, TGFBR2, the non- CC promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. CC Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to CC the cytoplasm and is thus regulating a plethora of physiological and CC pathological processes including cell cycle arrest in epithelial and CC hematopoietic cells, control of mesenchymal cell proliferation and CC differentiation, wound healing, extracellular matrix production, CC immunosuppression and carcinogenesis. The formation of the receptor CC complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound CC to the cytokine dimer results in the phosphorylation and the activation CC of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 CC phosphorylates SMAD2 which dissociates from the receptor and interacts CC with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the CC nucleus where it modulates the transcription of the TGF-beta-regulated CC genes. This constitutes the canonical SMAD-dependent TGF-beta signaling CC cascade. Also involved in non-canonical, SMAD-independent TGF-beta CC signaling pathways. For instance, TGFBR1 induces TRAF6 CC autoubiquitination which in turn results in MAP3K7 ubiquitination and CC activation to trigger apoptosis. Also regulates epithelial to CC mesenchymal transition through a SMAD-independent signaling pathway CC through PARD6A phosphorylation and activation. CC {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, CC ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:7774578, CC ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, CC ECO:0000269|PubMed:9346908}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[receptor-protein] = ADP + H(+) + O-phospho- CC L-threonyl-[receptor-protein]; Xref=Rhea:RHEA:44880, Rhea:RHEA- CC COMP:11024, Rhea:RHEA-COMP:11025, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, CC ChEBI:CHEBI:456216; EC=2.7.11.30; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[receptor-protein] = ADP + H(+) + O-phospho-L- CC seryl-[receptor-protein]; Xref=Rhea:RHEA:18673, Rhea:RHEA-COMP:11022, CC Rhea:RHEA-COMP:11023, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; CC EC=2.7.11.30; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Kept in an inactive conformation by FKBP1A CC preventing receptor activation in absence of ligand. CD109 is another CC inhibitor of the receptor. {ECO:0000269|PubMed:9233797}. CC -!- SUBUNIT: Homodimer; in the endoplasmic reticulum but also at the cell CC membrane. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands CC assemble a functional receptor composed of two TGFBR1 and TGFBR2 CC heterodimers to form a ligand-receptor heterohexamer. The respective CC affinity of TGBRB1 and TGFBR2 for the ligands may modulate the kinetics CC of assembly of the receptor and may explain the different biological CC activities of TGFB1, TGFB2 and TGFB3. Component of a complex composed CC of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the interaction between CC TSC22D1 and TGFBR1 is inhibited by SMAD7 and promoted by TGFB1 CC (PubMed:21791611). Interacts with CD109; inhibits TGF-beta receptor CC activation in keratinocytes. Interacts with RBPMS. Interacts CC (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by CC TGFBR2 and stabilizes it in the inactive conformation. Interacts with CC SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF- CC beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 CC activation by TRAF6. Interacts with PARD6A; involved in TGF-beta CC induced epithelial to mesenchymal transition. Interacts with NEDD4L CC (PubMed:15496141). Interacts with SMAD7, SMURF1 and SMURF2; SMAD7 CC recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor CC (PubMed:11163210, PubMed:11278251). Interacts with USP15 and VPS39. CC Interacts with SDCBP (via C-terminus) (PubMed:25893292). Interacts with CC CAV1 and this interaction is impaired in the presence of SDCBP CC (PubMed:25893292). Interacts with APPL1; interaction is TGF beta CC dependent; mediates trafficking of the TGFBR1 from the endosomes to the CC nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432). CC Interacts with GPR50; this interaction promotes the constitutive CC activation of SMAD signaling pathway (PubMed:29572483). CC {ECO:0000269|PubMed:10025408, ECO:0000269|PubMed:11163210, CC ECO:0000269|PubMed:11278251, ECO:0000269|PubMed:11583628, CC ECO:0000269|PubMed:12941698, ECO:0000269|PubMed:15177479, CC ECO:0000269|PubMed:15317461, ECO:0000269|PubMed:15496141, CC ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, CC ECO:0000269|PubMed:17099224, ECO:0000269|PubMed:18243111, CC ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:20207738, CC ECO:0000269|PubMed:21791611, ECO:0000269|PubMed:25893292, CC ECO:0000269|PubMed:26583432, ECO:0000269|PubMed:29572483, CC ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8980228, CC ECO:0000269|PubMed:9233797, ECO:0000269|PubMed:9311995, CC ECO:0000269|PubMed:9346908, ECO:0000269|PubMed:9865696}. CC -!- INTERACTION: CC P36897; P62942: FKBP1A; NbExp=2; IntAct=EBI-1027557, EBI-1027571; CC P36897; P01137: TGFB1; NbExp=2; IntAct=EBI-1027557, EBI-779636; CC P36897; P63104: YWHAZ; NbExp=4; IntAct=EBI-1027557, EBI-347088; CC P36897; PRO_0000045599 [Q99IB8]; Xeno; NbExp=5; IntAct=EBI-1027557, EBI-6858501; CC P36897-1; P02750: LRG1; NbExp=6; IntAct=EBI-16065417, EBI-9083443; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21791611, CC ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:9472030}; Single-pass CC type I membrane protein {ECO:0000269|PubMed:9472030}. Cell junction, CC tight junction {ECO:0000269|PubMed:15761148}. Cell surface CC {ECO:0000269|PubMed:25893292}. Membrane raft CC {ECO:0000269|PubMed:25893292}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P36897-1; Sequence=Displayed; CC Name=2; Synonyms=B; CC IsoId=P36897-2; Sequence=VSP_041326; CC Name=3; CC IsoId=P36897-3; Sequence=VSP_041327; CC -!- TISSUE SPECIFICITY: Found in all tissues examined, most abundant in CC placenta and least abundant in brain and heart. Expressed in a variety CC of cancer cell lines (PubMed:25893292). {ECO:0000269|PubMed:25893292}. CC -!- PTM: Phosphorylated at basal levels in the absence of ligand. Activated CC upon phosphorylation by TGFBR2, mainly in the GS domain. CC Phosphorylation in the GS domain abrogates FKBP1A-binding. CC {ECO:0000269|PubMed:11583628, ECO:0000269|PubMed:7774578}. CC -!- PTM: N-Glycosylated. {ECO:0000269|PubMed:9661882}. CC -!- PTM: Ubiquitinated; undergoes ubiquitination catalyzed by several E3 CC ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the CC proteasomal and/or lysosomal degradation of the receptor thereby CC negatively regulating its activity. Deubiquitinated by USP15, leading CC to stabilization of the protein and enhanced TGF-beta signal. Its CC ubiquitination and proteasome-mediated degradation is negatively CC regulated by SDCBP (PubMed:25893292). {ECO:0000269|PubMed:15496141, CC ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:25893292}. CC -!- DISEASE: Loeys-Dietz syndrome 1 (LDS1) [MIM:609192]: An aortic aneurysm CC syndrome with widespread systemic involvement, characterized by CC arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or CC cleft palate. Physical findings include prominent joint laxity, easy CC bruising, wide and atrophic scars, velvety and translucent skin with CC easily visible veins, spontaneous rupture of the spleen or bowel, and CC catastrophic complications of pregnancy, including rupture of the CC gravid uterus and the arteries, either during pregnancy or in the CC immediate postpartum period. Some patients have craniosynostosis, CC exotropy, micrognathia and retrognathia, structural brain CC abnormalities, and intellectual deficit. {ECO:0000269|PubMed:15731757, CC ECO:0000269|PubMed:16596670, ECO:0000269|PubMed:16791849, CC ECO:0000269|PubMed:16928994, ECO:0000269|PubMed:19883511, CC ECO:0000269|PubMed:22113417}. Note=The disease is caused by variants CC affecting the gene represented in this entry. TGFBR1 mutation Gln-487 CC has been reported to be associated with thoracic aortic aneurysms and CC dissection (TAAD) (PubMed:16791849). This phenotype, also known as CC thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS1 by CC having aneurysms restricted to thoracic aorta. It is unclear, however, CC if this condition is fulfilled in individuals bearing Gln-487 mutation, CC that is why they are considered as LDS1 by the OMIM resource. CC {ECO:0000269|PubMed:16791849}. CC -!- DISEASE: Multiple self-healing squamous epithelioma (MSSE) CC [MIM:132800]: A disorder characterized by multiple skin tumors that CC undergo spontaneous regression. Tumors appear most often on sun-exposed CC regions, are locally invasive, and undergo spontaneous resolution over CC a period of months leaving pitted scars. {ECO:0000269|PubMed:21358634}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr CC protein kinase family. TGFB receptor subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/tgfbr1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L11695; AAA16073.1; -; mRNA. DR EMBL; AF054598; AAC08998.1; -; Genomic_DNA. DR EMBL; AF054590; AAC08998.1; JOINED; Genomic_DNA. DR EMBL; AF054591; AAC08998.1; JOINED; Genomic_DNA. DR EMBL; AF054592; AAC08998.1; JOINED; Genomic_DNA. DR EMBL; AF054593; AAC08998.1; JOINED; Genomic_DNA. DR EMBL; AF054594; AAC08998.1; JOINED; Genomic_DNA. DR EMBL; AF054595; AAC08998.1; JOINED; Genomic_DNA. DR EMBL; AF054596; AAC08998.1; JOINED; Genomic_DNA. DR EMBL; AF054597; AAC08998.1; JOINED; Genomic_DNA. DR EMBL; AF035670; AAD02042.1; -; Genomic_DNA. DR EMBL; AF035662; AAD02042.1; JOINED; Genomic_DNA. DR EMBL; AF035663; AAD02042.1; JOINED; Genomic_DNA. DR EMBL; AF035664; AAD02042.1; JOINED; Genomic_DNA. DR EMBL; AF035665; AAD02042.1; JOINED; Genomic_DNA. DR EMBL; AF035666; AAD02042.1; JOINED; Genomic_DNA. DR EMBL; AF035667; AAD02042.1; JOINED; Genomic_DNA. DR EMBL; AF035668; AAD02042.1; JOINED; Genomic_DNA. DR EMBL; AF035669; AAD02042.1; JOINED; Genomic_DNA. DR EMBL; AY497473; AAR32097.1; -; Genomic_DNA. DR EMBL; AL162427; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC071181; AAH71181.1; -; mRNA. DR EMBL; AJ619019; CAF02096.2; -; mRNA. DR EMBL; AJ619020; CAF02097.1; -; mRNA. DR CCDS; CCDS47998.1; -. [P36897-3] DR CCDS; CCDS6738.1; -. [P36897-1] DR CCDS; CCDS78413.1; -. [P36897-2] DR PIR; A49432; A49432. DR RefSeq; NP_001124388.1; NM_001130916.2. [P36897-3] DR RefSeq; NP_001293139.1; NM_001306210.1. [P36897-2] DR RefSeq; NP_004603.1; NM_004612.3. [P36897-1] DR PDB; 1B6C; X-ray; 2.60 A; B/D/F/H=162-503. DR PDB; 1IAS; X-ray; 2.90 A; A/B/C/D/E=162-503. DR PDB; 1PY5; X-ray; 2.30 A; A=175-500. DR PDB; 1RW8; X-ray; 2.40 A; A=200-500. DR PDB; 1VJY; X-ray; 2.00 A; A=201-503. DR PDB; 2L5S; NMR; -; A=31-115. DR PDB; 2PJY; X-ray; 3.00 A; C=33-111. DR PDB; 2WOT; X-ray; 1.85 A; A=200-503. DR PDB; 2WOU; X-ray; 2.30 A; A=200-503. DR PDB; 2X7O; X-ray; 3.70 A; A/B/C/D/E=162-503. DR PDB; 3FAA; X-ray; 3.35 A; A/B/C/D/E=162-503. DR PDB; 3GXL; X-ray; 1.80 A; A=201-503. DR PDB; 3HMM; X-ray; 1.70 A; A=201-503. DR PDB; 3KCF; X-ray; 2.80 A; A/B/C/D/E=162-503. DR PDB; 3KFD; X-ray; 3.00 A; I/J/K/L=31-115. DR PDB; 3TZM; X-ray; 1.70 A; A=200-503. DR PDB; 4X0M; X-ray; 1.68 A; A=200-503. DR PDB; 4X2F; X-ray; 1.49 A; A=200-503. DR PDB; 4X2G; X-ray; 1.51 A; A=200-503. DR PDB; 4X2J; X-ray; 1.69 A; A=200-503. DR PDB; 4X2K; X-ray; 1.69 A; A=200-503. DR PDB; 4X2N; X-ray; 1.80 A; A=200-503. DR PDB; 5E8S; X-ray; 1.45 A; A=200-503. DR PDB; 5E8T; X-ray; 1.70 A; A=200-503. DR PDB; 5E8U; X-ray; 2.03 A; A=200-503. DR PDB; 5E8W; X-ray; 1.86 A; A=200-503. DR PDB; 5E8X; X-ray; 1.45 A; A=200-503. DR PDB; 5E8Z; X-ray; 1.51 A; A=200-503. DR PDB; 5E90; X-ray; 2.05 A; A=200-503. DR PDB; 5FRI; X-ray; 2.00 A; A=200-498. DR PDB; 5QIK; X-ray; 1.58 A; A=200-503. DR PDB; 5QIL; X-ray; 1.98 A; A=200-503. DR PDB; 5QIM; X-ray; 1.75 A; A=200-503. DR PDB; 5QTZ; X-ray; 1.83 A; A=200-503. DR PDB; 5QU0; X-ray; 1.67 A; A=200-503. DR PDB; 5USQ; X-ray; 2.55 A; A=200-498. DR PDB; 6B8Y; X-ray; 1.65 A; A=200-503. DR PDB; 6MAC; X-ray; 2.34 A; K=33-112. DR PDBsum; 1B6C; -. DR PDBsum; 1IAS; -. DR PDBsum; 1PY5; -. DR PDBsum; 1RW8; -. DR PDBsum; 1VJY; -. DR PDBsum; 2L5S; -. DR PDBsum; 2PJY; -. DR PDBsum; 2WOT; -. DR PDBsum; 2WOU; -. DR PDBsum; 2X7O; -. DR PDBsum; 3FAA; -. DR PDBsum; 3GXL; -. DR PDBsum; 3HMM; -. DR PDBsum; 3KCF; -. DR PDBsum; 3KFD; -. DR PDBsum; 3TZM; -. DR PDBsum; 4X0M; -. DR PDBsum; 4X2F; -. DR PDBsum; 4X2G; -. DR PDBsum; 4X2J; -. DR PDBsum; 4X2K; -. DR PDBsum; 4X2N; -. DR PDBsum; 5E8S; -. DR PDBsum; 5E8T; -. DR PDBsum; 5E8U; -. DR PDBsum; 5E8W; -. DR PDBsum; 5E8X; -. DR PDBsum; 5E8Z; -. DR PDBsum; 5E90; -. DR PDBsum; 5FRI; -. DR PDBsum; 5QIK; -. DR PDBsum; 5QIL; -. DR PDBsum; 5QIM; -. DR PDBsum; 5QTZ; -. DR PDBsum; 5QU0; -. DR PDBsum; 5USQ; -. DR PDBsum; 6B8Y; -. DR PDBsum; 6MAC; -. DR AlphaFoldDB; P36897; -. DR BMRB; P36897; -. DR SMR; P36897; -. DR BioGRID; 112904; 256. DR ComplexPortal; CPX-2544; TGF-beta-3-TGFR complex. DR ComplexPortal; CPX-529; TGF-beta-1-TGFR complex. DR ComplexPortal; CPX-834; TGF-beta-2-TGFR complex. DR CORUM; P36897; -. DR DIP; DIP-5935N; -. DR IntAct; P36897; 26. DR MINT; P36897; -. DR STRING; 9606.ENSP00000447297; -. DR BindingDB; P36897; -. DR ChEMBL; CHEMBL4439; -. DR DrugBank; DB07267; 2-(6-methylpyridin-2-yl)-N-pyridin-4-ylquinazolin-4-amine. DR DrugBank; DB04480; 3-(4-Fluorophenyl)-2-(6-Methylpyridin-2-Yl)-5,6-Dihydro-4h-Pyrrolo[1,2-B]Pyrazole. DR DrugBank; DB03921; 4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinoline. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB08450; N-1H-indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine. DR DrugBank; DB07152; N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-yl]acetamide. DR DrugBank; DB04434; Naphthyridine Inhibitor. DR DrugCentral; P36897; -. DR GuidetoPHARMACOLOGY; 1788; -. DR GlyCosmos; P36897; 1 site, No reported glycans. DR GlyGen; P36897; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; P36897; -. DR PhosphoSitePlus; P36897; -. DR SwissPalm; P36897; -. DR BioMuta; TGFBR1; -. DR DMDM; 547777; -. DR CPTAC; CPTAC-3123; -. DR CPTAC; CPTAC-3124; -. DR EPD; P36897; -. DR jPOST; P36897; -. DR MassIVE; P36897; -. DR MaxQB; P36897; -. DR PaxDb; 9606-ENSP00000364133; -. DR PeptideAtlas; P36897; -. DR ProteomicsDB; 55234; -. [P36897-1] DR ProteomicsDB; 55235; -. [P36897-2] DR ProteomicsDB; 55236; -. [P36897-3] DR Pumba; P36897; -. DR Antibodypedia; 29038; 723 antibodies from 43 providers. DR DNASU; 7046; -. DR Ensembl; ENST00000374990.6; ENSP00000364129.2; ENSG00000106799.14. [P36897-3] DR Ensembl; ENST00000374994.9; ENSP00000364133.4; ENSG00000106799.14. [P36897-1] DR Ensembl; ENST00000552516.5; ENSP00000447297.1; ENSG00000106799.14. [P36897-2] DR GeneID; 7046; -. DR KEGG; hsa:7046; -. DR MANE-Select; ENST00000374994.9; ENSP00000364133.4; NM_004612.4; NP_004603.1. DR UCSC; uc004azd.4; human. [P36897-1] DR AGR; HGNC:11772; -. DR CTD; 7046; -. DR DisGeNET; 7046; -. DR GeneCards; TGFBR1; -. DR GeneReviews; TGFBR1; -. DR HGNC; HGNC:11772; TGFBR1. DR HPA; ENSG00000106799; Low tissue specificity. DR MalaCards; TGFBR1; -. DR MIM; 132800; phenotype. DR MIM; 190181; gene. DR MIM; 609192; phenotype. DR neXtProt; NX_P36897; -. DR OpenTargets; ENSG00000106799; -. DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection. DR Orphanet; 60030; Loeys-Dietz syndrome. DR Orphanet; 284973; Marfan syndrome type 2. DR Orphanet; 65748; Multiple self-healing squamous epithelioma. DR PharmGKB; PA36485; -. DR VEuPathDB; HostDB:ENSG00000106799; -. DR eggNOG; KOG2052; Eukaryota. DR GeneTree; ENSGT00940000156394; -. DR HOGENOM; CLU_000288_8_1_1; -. DR InParanoid; P36897; -. DR OMA; VPHCCDK; -. DR OrthoDB; 3900892at2759; -. DR PhylomeDB; P36897; -. DR TreeFam; TF314724; -. DR BRENDA; 2.7.10.2; 2681. DR BRENDA; 2.7.11.30; 2681. DR PathwayCommons; P36897; -. DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling. DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-HSA-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition). DR Reactome; R-HSA-3304356; SMAD2/3 Phosphorylation Motif Mutants in Cancer. DR Reactome; R-HSA-3645790; TGFBR2 Kinase Domain Mutants in Cancer. DR Reactome; R-HSA-3656532; TGFBR1 KD Mutants in Cancer. DR Reactome; R-HSA-3656535; TGFBR1 LBD Mutants in Cancer. DR Reactome; R-HSA-5689603; UCH proteinases. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR SignaLink; P36897; -. DR SIGNOR; P36897; -. DR BioGRID-ORCS; 7046; 59 hits in 1182 CRISPR screens. DR ChiTaRS; TGFBR1; human. DR EvolutionaryTrace; P36897; -. DR GeneWiki; TGF_beta_receptor_1; -. DR GenomeRNAi; 7046; -. DR Pharos; P36897; Tchem. DR PRO; PR:P36897; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P36897; Protein. DR Bgee; ENSG00000106799; Expressed in saphenous vein and 191 other cell types or tissues. DR ExpressionAtlas; P36897; baseline and differential. DR GO; GO:0048179; C:activin receptor complex; IBA:GO_Central. DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:AgBase. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL. DR GO; GO:0070021; C:transforming growth factor beta ligand-receptor complex; IPI:ComplexPortal. DR GO; GO:0048185; F:activin binding; IBA:GO_Central. DR GO; GO:0016361; F:activin receptor activity, type I; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IDA:HGNC-UCL. DR GO; GO:0070411; F:I-SMAD binding; IPI:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IDA:BHF-UCL. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:HGNC-UCL. DR GO; GO:0046332; F:SMAD binding; IDA:HGNC-UCL. DR GO; GO:0050431; F:transforming growth factor beta binding; IDA:HGNC-UCL. DR GO; GO:0005024; F:transforming growth factor beta receptor activity; IDA:BHF-UCL. DR GO; GO:0005025; F:transforming growth factor beta receptor activity, type I; IDA:BHF-UCL. DR GO; GO:0004675; F:transmembrane receptor protein serine/threonine kinase activity; IDA:BHF-UCL. DR GO; GO:0005114; F:type II transforming growth factor beta receptor binding; IDA:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL. DR GO; GO:0032924; P:activin receptor signaling pathway; ISS:AgBase. DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; ISS:BHF-UCL. DR GO; GO:0009952; P:anterior/posterior pattern specification; ISS:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0048844; P:artery morphogenesis; ISS:BHF-UCL. DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl. DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISS:AgBase. DR GO; GO:0048870; P:cell motility; IMP:BHF-UCL. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IBA:GO_Central. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:BHF-UCL. DR GO; GO:0030199; P:collagen fibril organization; ISS:BHF-UCL. DR GO; GO:0060982; P:coronary artery morphogenesis; ISS:BHF-UCL. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISS:BHF-UCL. DR GO; GO:0042118; P:endothelial cell activation; ISS:AgBase. DR GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl. DR GO; GO:0001935; P:endothelial cell proliferation; IEA:Ensembl. DR GO; GO:1905223; P:epicardium morphogenesis; ISS:BHF-UCL. DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:UniProtKB. DR GO; GO:0043062; P:extracellular structure organization; TAS:UniProtKB. DR GO; GO:0046847; P:filopodium assembly; IEA:Ensembl. DR GO; GO:0008354; P:germ cell migration; ISS:BHF-UCL. DR GO; GO:0007507; P:heart development; ISS:AgBase. DR GO; GO:0001701; P:in utero embryonic development; ISS:BHF-UCL. DR GO; GO:0035556; P:intracellular signal transduction; ISS:AgBase. DR GO; GO:0001822; P:kidney development; ISS:BHF-UCL. DR GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0048762; P:mesenchymal cell differentiation; ISS:AgBase. DR GO; GO:0036446; P:myofibroblast differentiation; IMP:BHF-UCL. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:BHF-UCL. DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISS:BHF-UCL. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IEA:Ensembl. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:BHF-UCL. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0048663; P:neuron fate commitment; ISS:BHF-UCL. DR GO; GO:0060017; P:parathyroid gland development; ISS:BHF-UCL. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB. DR GO; GO:0060037; P:pharyngeal system development; ISS:BHF-UCL. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0030307; P:positive regulation of cell growth; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:HGNC-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:AgBase. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:BHF-UCL. DR GO; GO:1905007; P:positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation; ISS:BHF-UCL. DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; IMP:BHF-UCL. DR GO; GO:0051491; P:positive regulation of filopodium assembly; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL. DR GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; IGI:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISS:BHF-UCL. DR GO; GO:1905075; P:positive regulation of tight junction disassembly; ISS:BHF-UCL. DR GO; GO:1904018; P:positive regulation of vasculature development; IMP:BHF-UCL. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; ISS:BHF-UCL. DR GO; GO:0051726; P:regulation of cell cycle; TAS:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:HGNC-UCL. DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; ISS:AgBase. DR GO; GO:0010468; P:regulation of gene expression; ISS:AgBase. DR GO; GO:0031396; P:regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0070723; P:response to cholesterol; IDA:BHF-UCL. DR GO; GO:0060021; P:roof of mouth development; ISS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; IDA:HGNC-UCL. DR GO; GO:0001501; P:skeletal system development; ISS:BHF-UCL. DR GO; GO:0048705; P:skeletal system morphogenesis; ISS:BHF-UCL. DR GO; GO:0048538; P:thymus development; ISS:BHF-UCL. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; ISS:BHF-UCL. DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL. DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; ISS:BHF-UCL. DR GO; GO:0042060; P:wound healing; TAS:UniProtKB. DR CDD; cd14143; STKc_TGFbR1_ACVR1b_ACVR1c; 1. DR Gene3D; 2.10.60.10; CD59; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID00413; -. DR InterPro; IPR000472; Activin_recp. DR InterPro; IPR003605; GS_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR045860; Snake_toxin-like_sf. DR InterPro; IPR000333; TGFB_receptor. DR PANTHER; PTHR23255:SF61; TGF-BETA RECEPTOR TYPE-1; 1. DR PANTHER; PTHR23255; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR TYPE I AND II; 1. DR Pfam; PF01064; Activin_recp; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF08515; TGF_beta_GS; 1. DR SMART; SM00467; GS; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF57302; Snake toxin-like; 1. DR PROSITE; PS51256; GS; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P36897; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Aortic aneurysm; Apoptosis; KW ATP-binding; Cell junction; Cell membrane; Craniosynostosis; KW Differentiation; Direct protein sequencing; Disease variant; KW Disulfide bond; Glycoprotein; Growth regulation; Isopeptide bond; Kinase; KW Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding; KW Phosphoprotein; Receptor; Reference proteome; KW Serine/threonine-protein kinase; Signal; Tight junction; Transferase; KW Transmembrane; Transmembrane helix; Ubl conjugation. FT SIGNAL 1..33 FT /evidence="ECO:0000269|PubMed:9661882" FT CHAIN 34..503 FT /note="TGF-beta receptor type-1" FT /id="PRO_0000024423" FT TOPO_DOM 34..126 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 127..147 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 148..503 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 175..204 FT /note="GS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00585" FT DOMAIN 205..495 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOTIF 193..194 FT /note="FKBP1A-binding" FT ACT_SITE 333 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 211..219 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 232 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 165 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 185 FT /note="Phosphothreonine; by TGFBR2" FT /evidence="ECO:0000269|PubMed:7774578" FT MOD_RES 186 FT /note="Phosphothreonine; by TGFBR2" FT /evidence="ECO:0000269|PubMed:7774578" FT MOD_RES 187 FT /note="Phosphoserine; by TGFBR2" FT /evidence="ECO:0000269|PubMed:7774578" FT MOD_RES 189 FT /note="Phosphoserine; by TGFBR2" FT /evidence="ECO:0000269|PubMed:7774578" FT MOD_RES 191 FT /note="Phosphoserine; by TGFBR2" FT /evidence="ECO:0000269|PubMed:7774578" FT CARBOHYD 45 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 36..54 FT /evidence="ECO:0000269|PubMed:18243111, FT ECO:0000269|PubMed:20207738" FT DISULFID 38..41 FT /evidence="ECO:0000269|PubMed:18243111, FT ECO:0000269|PubMed:20207738" FT DISULFID 48..71 FT /evidence="ECO:0000269|PubMed:18243111, FT ECO:0000269|PubMed:20207738" FT DISULFID 86..100 FT /evidence="ECO:0000269|PubMed:18243111, FT ECO:0000269|PubMed:20207738" FT DISULFID 101..106 FT /evidence="ECO:0000269|PubMed:18243111, FT ECO:0000269|PubMed:20207738" FT CROSSLNK 391 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000250" FT VAR_SEQ 114 FT /note="T -> TGPFS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17845732" FT /id="VSP_041326" FT VAR_SEQ 115..191 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_041327" FT VARIANT 24..26 FT /note="Missing (in allele TGFBR1*6A; could be a tumor FT susceptibility allele)" FT /id="VAR_022342" FT VARIANT 26 FT /note="A -> AA (in allele TGFBR1*10A)" FT /evidence="ECO:0000269|PubMed:9661882" FT /id="VAR_022343" FT VARIANT 41 FT /note="C -> Y (in MSSE; hypomorphic variant)" FT /evidence="ECO:0000269|PubMed:21358634" FT /id="VAR_065826" FT VARIANT 45 FT /note="N -> S (in MSSE; hypomorphic variant; FT dbSNP:rs387906696)" FT /evidence="ECO:0000269|PubMed:21358634" FT /id="VAR_065827" FT VARIANT 52 FT /note="G -> R (in MSSE; hypomorphic variant; FT dbSNP:rs587776865)" FT /evidence="ECO:0000269|PubMed:21358634" FT /id="VAR_065828" FT VARIANT 83 FT /note="P -> L (in MSSE; hypomorphic variant; FT dbSNP:rs757374917)" FT /evidence="ECO:0000269|PubMed:21358634" FT /id="VAR_065829" FT VARIANT 139 FT /note="I -> V (in dbSNP:rs148176750)" FT /evidence="ECO:0000269|PubMed:18987736" FT /id="VAR_054160" FT VARIANT 153 FT /note="V -> I (in dbSNP:rs56014374)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041412" FT VARIANT 200 FT /note="T -> I (in LDS1; dbSNP:rs121918712)" FT /evidence="ECO:0000269|PubMed:15731757" FT /id="VAR_022344" FT VARIANT 232 FT /note="K -> E (in LDS1)" FT /evidence="ECO:0000269|PubMed:16928994" FT /id="VAR_029481" FT VARIANT 241 FT /note="S -> L (in LDS1; dbSNP:rs111854391)" FT /evidence="ECO:0000269|PubMed:16596670, FT ECO:0000269|PubMed:16791849" FT /id="VAR_029482" FT VARIANT 266 FT /note="D -> Y (in LDS1)" FT /evidence="ECO:0000269|PubMed:22113417" FT /id="VAR_066720" FT VARIANT 267 FT /note="N -> H (in a patient with Marfan syndrome)" FT /evidence="ECO:0000269|PubMed:16791849" FT /id="VAR_029483" FT VARIANT 291 FT /note="Y -> C (in dbSNP:rs35974499)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041413" FT VARIANT 318 FT /note="M -> R (in LDS1; dbSNP:rs121918710)" FT /evidence="ECO:0000269|PubMed:15731757" FT /id="VAR_022345" FT VARIANT 351 FT /note="D -> G (in LDS1)" FT /evidence="ECO:0000269|PubMed:19883511" FT /id="VAR_066721" FT VARIANT 375 FT /note="T -> R (in LDS1; dbSNP:rs1827743139)" FT /evidence="ECO:0000269|PubMed:22113417" FT /id="VAR_066722" FT VARIANT 400 FT /note="D -> G (in LDS1; dbSNP:rs121918711)" FT /evidence="ECO:0000269|PubMed:15731757" FT /id="VAR_022346" FT VARIANT 487 FT /note="R -> P (in LDS1; dbSNP:rs113605875)" FT /evidence="ECO:0000269|PubMed:15731757, FT ECO:0000269|PubMed:16928994" FT /id="VAR_022347" FT VARIANT 487 FT /note="R -> Q (in LDS1; dbSNP:rs113605875)" FT /evidence="ECO:0000269|PubMed:16791849, FT ECO:0000269|PubMed:16928994, ECO:0000269|PubMed:22113417" FT /id="VAR_029484" FT VARIANT 487 FT /note="R -> W (in LDS1; dbSNP:rs111426349)" FT /evidence="ECO:0000269|PubMed:16928994" FT /id="VAR_029485" FT MUTAGEN 185..186 FT /note="TT->VV: Loss of phosphorylation on threonine FT residues. Loss of threonine phosphorylation, reduced FT phosphorylation on serine residues and loss of response to FT TGF-beta; when associated with A-187; A-189 and A-191." FT /evidence="ECO:0000269|PubMed:7774578" FT MUTAGEN 187 FT /note="S->A: Loss of threonine phosphorylation, reduced FT phosphorylation on serine residues and loss of response to FT TGF-beta; when associated with 185-VV-186; A-189 and FT A-191." FT /evidence="ECO:0000269|PubMed:7774578" FT MUTAGEN 189 FT /note="S->A: Loss of threonine phosphorylation, reduced FT phosphorylation on serine residues and loss of response to FT TGF-beta; when associated with 185-VV-186; A-187 and FT A-191." FT /evidence="ECO:0000269|PubMed:7774578" FT MUTAGEN 191 FT /note="S->A: Loss of threonine phosphorylation, reduced FT phosphorylation on serine residues and loss of response to FT TGF-beta; when associated with 185-VV-186; A-187 and FT A-189." FT /evidence="ECO:0000269|PubMed:7774578" FT MUTAGEN 193 FT /note="L->G: Loss of interaction with FKBP1A." FT /evidence="ECO:0000269|PubMed:9233797" FT MUTAGEN 194 FT /note="P->K: Loss of interaction with FKBP1A." FT /evidence="ECO:0000269|PubMed:9233797" FT MUTAGEN 200 FT /note="T->D: Loss of response to TGF-beta." FT /evidence="ECO:0000269|PubMed:7774578" FT MUTAGEN 200 FT /note="T->V: Loss of phosphorylation. Loss of response to FT TGF-beta." FT /evidence="ECO:0000269|PubMed:7774578" FT MUTAGEN 204 FT /note="T->D: Constitutive activation." FT /evidence="ECO:0000269|PubMed:7774578" FT MUTAGEN 204 FT /note="T->V: Reduced phosphorylation. Reduced response to FT TGF-beta." FT /evidence="ECO:0000269|PubMed:7774578" FT STRAND 35..37 FT /evidence="ECO:0007829|PDB:6MAC" FT TURN 42..46 FT /evidence="ECO:0007829|PDB:6MAC" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:6MAC" FT STRAND 51..63 FT /evidence="ECO:0007829|PDB:6MAC" FT STRAND 65..72 FT /evidence="ECO:0007829|PDB:6MAC" FT HELIX 74..76 FT /evidence="ECO:0007829|PDB:6MAC" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:6MAC" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:3KFD" FT STRAND 89..91 FT /evidence="ECO:0007829|PDB:6MAC" FT STRAND 94..101 FT /evidence="ECO:0007829|PDB:6MAC" FT STRAND 102..105 FT /evidence="ECO:0007829|PDB:3KFD" FT HELIX 107..109 FT /evidence="ECO:0007829|PDB:2L5S" FT HELIX 177..183 FT /evidence="ECO:0007829|PDB:1B6C" FT STRAND 187..190 FT /evidence="ECO:0007829|PDB:3KCF" FT STRAND 191..193 FT /evidence="ECO:0007829|PDB:1B6C" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 205..213 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 215..224 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 227..234 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 239..249 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 251..253 FT /evidence="ECO:0007829|PDB:3KCF" FT STRAND 262..269 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 271..281 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 288..294 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 299..317 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 322..324 FT /evidence="ECO:0007829|PDB:5E8X" FT STRAND 328..330 FT /evidence="ECO:0007829|PDB:5E8Z" FT HELIX 336..338 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 339..341 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 347..349 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 352..354 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 356..359 FT /evidence="ECO:0007829|PDB:5E8S" FT TURN 360..363 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 364..367 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 368..371 FT /evidence="ECO:0007829|PDB:5E8X" FT HELIX 376..378 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 381..384 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 393..413 FT /evidence="ECO:0007829|PDB:5E8S" FT STRAND 417..419 FT /evidence="ECO:0007829|PDB:3KCF" FT TURN 427..431 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 438..445 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 456..460 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 462..474 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 479..481 FT /evidence="ECO:0007829|PDB:5E8S" FT HELIX 485..497 FT /evidence="ECO:0007829|PDB:5E8S" SQ SEQUENCE 503 AA; 55960 MW; 179F11404725DDCB CRC64; MEAAVAAPRP RLLLLVLAAA AAAAAALLPG ATALQCFCHL CTKDNFTCVT DGLCFVSVTE TTDKVIHNSM CIAEIDLIPR DRPFVCAPSS KTGSVTTTYC CNQDHCNKIE LPTTVKSSPG LGPVELAAVI AGPVCFVCIS LMLMVYICHN RTVIHHRVPN EEDPSLDRPF ISEGTTLKDL IYDMTTSGSG SGLPLLVQRT IARTIVLQES IGKGRFGEVW RGKWRGEEVA VKIFSSREER SWFREAEIYQ TVMLRHENIL GFIAADNKDN GTWTQLWLVS DYHEHGSLFD YLNRYTVTVE GMIKLALSTA SGLAHLHMEI VGTQGKPAIA HRDLKSKNIL VKKNGTCCIA DLGLAVRHDS ATDTIDIAPN HRVGTKRYMA PEVLDDSINM KHFESFKRAD IYAMGLVFWE IARRCSIGGI HEDYQLPYYD LVPSDPSVEE MRKVVCEQKL RPNIPNRWQS CEALRVMAKI MRECWYANGA ARLTALRIKK TLSQLSQQEG IKM //