TGFR1_HUMAN
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 03-AUG-2022, entry version 236.
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 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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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. Interacts with CD109; inhibits
CC TGF-beta receptor activation in keratinocytes. Interacts with RBPMS.
CC Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1
CC phosphorylation by TGFBR2 and stabilizes it in the inactive
CC conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits
CC SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and
CC MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A;
CC involved in TGF-beta induced epithelial to mesenchymal transition.
CC Interacts with SMAD7, NEDD4L, SMURF1 and SMURF2; SMAD7 recruits NEDD4L,
CC SMURF1 and SMURF2 to the TGF-beta receptor. Interacts with USP15 and
CC VPS39. Interacts with SDCBP (via C-terminus) (PubMed:25893292)
CC Interacts with CAV1 and this interaction is impaired in the presence of
CC SDCBP (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 {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:25893292, ECO:0000269|PubMed:26583432,
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:25893292,
CC ECO:0000269|PubMed:9472030}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:9472030}. Cell junction, tight junction
CC {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 -!- CAUTION: One report originally reported variant Ile-375
CC (PubMed:22113417). This variant has been subsequently corrected to Arg-
CC 375 by the same authors (Ref.49). {ECO:0000269|PubMed:22113417,
CC ECO:0000269|Ref.49}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tgfbr1/";
CC ---------------------------------------------------------------------------
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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; 249.
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; 24.
DR MINT; P36897; -.
DR STRING; 9606.ENSP00000364133; -.
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 GlyGen; P36897; 1 site.
DR iPTMnet; P36897; -.
DR PhosphoSitePlus; P36897; -.
DR BioMuta; TGFBR1; -.
DR DMDM; 547777; -.
DR EPD; P36897; -.
DR jPOST; P36897; -.
DR MassIVE; P36897; -.
DR MaxQB; P36897; -.
DR PaxDb; P36897; -.
DR PeptideAtlas; P36897; -.
DR PRIDE; P36897; -.
DR ProteomicsDB; 55234; -. [P36897-1]
DR ProteomicsDB; 55235; -. [P36897-2]
DR ProteomicsDB; 55236; -. [P36897-3]
DR Antibodypedia; 29038; 621 antibodies from 43 providers.
DR DNASU; 7046; -.
DR Ensembl; ENST00000374990.6; ENSP00000364129.2; ENSG00000106799.13. [P36897-3]
DR Ensembl; ENST00000374994.9; ENSP00000364133.4; ENSG00000106799.13. [P36897-1]
DR Ensembl; ENST00000552516.5; ENSP00000447297.1; ENSG00000106799.13. [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 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; 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; EMINMNH; -.
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; 51 hits in 1097 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 189 other tissues.
DR ExpressionAtlas; P36897; baseline and differential.
DR Genevisible; P36897; HS.
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:UniProtKB.
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:0005114; F:type II transforming growth factor beta receptor binding; IDA: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: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:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:BHF-UCL.
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: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: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:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; 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:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL.
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:0010717; P:regulation of epithelial to mesenchymal transition; ISS:AgBase.
DR GO; GO:0010468; P:regulation of gene expression; ISS:AgBase.
DR GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:HGNC-UCL.
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 Gene3D; 2.10.60.10; -; 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; PTHR23255; 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; SSF56112; 1.
DR SUPFAM; SSF57302; SSF57302; 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.
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)"
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 A-
FT 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 A-
FT 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 A-
FT 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
