ID SMAD3_HUMAN Reviewed; 425 AA.
AC P84022; A8K4B6; B7Z4Z5; B7Z6M9; B7Z9Q2; F5H383; O09064; O09144; O14510;
AC O35273; Q92940; Q93002; Q9GKR4;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 02-OCT-2024, entry version 211.
DE RecName: Full=Mothers against decapentaplegic homolog 3;
DE Short=MAD homolog 3;
DE Short=Mad3;
DE Short=Mothers against DPP homolog 3;
DE Short=hMAD-3;
DE AltName: Full=JV15-2;
DE AltName: Full=SMAD family member 3;
DE Short=SMAD 3;
DE Short=Smad3;
DE Short=hSMAD3;
GN Name=SMAD3; Synonyms=MADH3;
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), AND PHOSPHORYLATION.
RC TISSUE=Placenta;
RX PubMed=8774881; DOI=10.1038/383168a0;
RA Zhang Y., Feng X.-H., Wu R.-Y., Derynck R.;
RT "Receptor-associated Mad homologues synergize as effectors of the TGF-beta
RT response.";
RL Nature 383:168-172(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8673135; DOI=10.1038/ng0796-347;
RA Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L., Kern S.E.,
RA Hamilton S.R., Willson J.K.V., Markowitz S.D., Kinzler K.W.,
RA Vogelstein B.V.;
RT "Mad-related genes in the human.";
RL Nat. Genet. 13:347-349(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Colon carcinoma;
RX PubMed=9464505; DOI=10.1016/s0304-3835(97)00384-4;
RA Arai T., Akiyama Y., Okabe S., Ando M., Endo M., Yuasa Y.;
RT "Genomic structure of the human Smad3 gene and its infrequent alterations
RT in colorectal cancers.";
RL Cancer Lett. 122:157-163(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Hagiwara K., Yang K., McMenamin M.G., Freeman A.H., Bennett W.P.,
RA Nagashima M., Minter A.R., Miyazono K., Takenoshita S., Harris C.C.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [9]
RP INTERACTION WITH TGFBR1.
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 [10]
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 [11]
RP SUBUNIT.
RX PubMed=9670020; DOI=10.1093/emboj/17.14.4056;
RA Kawabata M., Inoue H., Hanyu A., Imamura T., Miyazono K.;
RT "Smad proteins exist as monomers in vivo and undergo homo- and hetero-
RT oligomerization upon activation by serine/threonine kinase receptors.";
RL EMBO J. 17:4056-4065(1998).
RN [12]
RP PHOSPHORYLATION, AND INTERACTION WITH EP300.
RX PubMed=9843571; DOI=10.1091/mbc.9.12.3309;
RA Shen X., Hu P.P., Liberati N.T., Datto M.B., Frederick J.P., Wang X.F.;
RT "TGF-beta-induced phosphorylation of Smad3 regulates its interaction with
RT coactivator p300/CREB-binding protein.";
RL Mol. Biol. Cell 9:3309-3319(1998).
RN [13]
RP INTERACTION WITH MECOM.
RX PubMed=9665135; DOI=10.1038/27945;
RA Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S.,
RA Yazaki Y., Matsumoto K., Hirai H.;
RT "The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting Smad3.";
RL Nature 394:92-96(1998).
RN [14]
RP IDENTIFICATION AS A COMPONENT OF THE SMAD3/SMAD4/JUN/FOS COMPLEX,
RP INTERACTION WITH JUN AND FOS, DNA-BINDING, AND FUNCTION.
RX PubMed=9732876; DOI=10.1038/29814;
RA Zhang Y., Feng X.H., Derynck R.;
RT "Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced
RT transcription.";
RL Nature 394:909-913(1998).
RN [15]
RP INTERACTION WITH ACVR1B, AND FUNCTION.
RX PubMed=9892009; DOI=10.1210/mend.13.1.0218;
RA Lebrun J.J., Takabe K., Chen Y., Vale W.;
RT "Roles of pathway-specific and inhibitory Smads in activin receptor
RT signaling.";
RL Mol. Endocrinol. 13:15-23(1999).
RN [16]
RP INTERACTION WITH JUN IN THE SMAD3/SMAD4/JUN/FOS COMPLEX, DNA-BINDING,
RP FUNCTION, AND MUTAGENESIS OF LYS-40; LYS-41; LYS-43; LYS-44 AND ARG-74.
RX PubMed=10995748; DOI=10.1074/jbc.m004731200;
RA Qing J., Zhang Y., Derynck R.;
RT "Structural and functional characterization of the transforming growth
RT factor-beta -induced Smad3/c-Jun transcriptional cooperativity.";
RL J. Biol. Chem. 275:38802-38812(2000).
RN [17]
RP INTERACTION WITH DAB2.
RX PubMed=11387212; DOI=10.1093/emboj/20.11.2789;
RA Hocevar B.A., Smine A., Xu X.X., Howe P.H.;
RT "The adaptor molecule Disabled-2 links the transforming growth factor beta
RT receptors to the Smad pathway.";
RL EMBO J. 20:2789-2801(2001).
RN [18]
RP INTERACTION WITH SNW1.
RX PubMed=11278756; DOI=10.1074/jbc.m010815200;
RA Leong G.M., Subramaniam N., Figueroa J., Flanagan J.L., Hayman M.J.,
RA Eisman J.A., Kouzmenko A.P.;
RT "Ski-interacting protein interacts with Smad proteins to augment
RT transforming growth factor-beta-dependent transcription.";
RL J. Biol. Chem. 276:18243-18248(2001).
RN [19]
RP INTERACTION WITH TGIF2.
RX PubMed=11427533; DOI=10.1074/jbc.m103377200;
RA Melhuish T.A., Gallo C.M., Wotton D.;
RT "TGIF2 interacts with histone deacetylase 1 and represses transcription.";
RL J. Biol. Chem. 276:32109-32114(2001).
RN [20]
RP SUBUNIT, PHOSPHORYLATION, AND MUTAGENESIS OF 422-SER--SER-425.
RX PubMed=11224571; DOI=10.1038/84995;
RA Chacko B.M., Qin B., Correia J.J., Lam S.S., de Caestecker M.P., Lin K.;
RT "The L3 loop and C-terminal phosphorylation jointly define Smad protein
RT trimerization.";
RL Nat. Struct. Biol. 8:248-253(2001).
RN [21]
RP INTERACTION WITH MEN1.
RX PubMed=11274402; DOI=10.1073/pnas.061358098;
RA Kaji H., Canaff L., Lebrun J.J., Goltzman D., Hendy G.N.;
RT "Inactivation of menin, a Smad3-interacting protein, blocks transforming
RT growth factor type beta signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3837-3842(2001).
RN [22]
RP INTERACTION WITH ZNF8.
RX PubMed=12370310; DOI=10.1128/mcb.22.21.7633-7644.2002;
RA Jiao K., Zhou Y., Hogan B.L.M.;
RT "Identification of mZnf8, a mouse Kruppel-like transcriptional repressor,
RT as a novel nuclear interaction partner of Smad1.";
RL Mol. Cell. Biol. 22:7633-7644(2002).
RN [23]
RP INTERACTION WITH DACH1.
RX PubMed=14525983; DOI=10.1074/jbc.m310021200;
RA Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K.,
RA Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G.;
RT "DACH1 inhibits transforming growth factor-beta signaling through binding
RT Smad4.";
RL J. Biol. Chem. 278:51673-51684(2003).
RN [24]
RP IDENTIFICATION IN A COMPLEX WITH NEDD9 AND ITCH, AND INTERACTION WITH
RP NEDD9.
RX PubMed=15051726; DOI=10.1074/jbc.m403221200;
RA Feng L., Guedes S., Wang T.;
RT "Atrophin-1-interacting protein 4/human Itch is a ubiquitin E3 ligase for
RT human enhancer of filamentation 1 in transforming growth factor-beta
RT signaling pathways.";
RL J. Biol. Chem. 279:29681-29690(2004).
RN [25]
RP PHOSPHORYLATION AT THR-8; THR-179; SER-204; SER-208 AND SER-213, FUNCTION,
RP AND MUTAGENESIS OF THR-8; THR-179; SER-204; SER-208 AND SER-213.
RX PubMed=15241418; DOI=10.1038/nature02650;
RA Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.;
RT "Cyclin-dependent kinases regulate the antiproliferative function of
RT Smads.";
RL Nature 430:226-231(2004).
RN [26]
RP TRANSCRIPTIONAL ACTIVATION DOMAIN, FUNCTION, PHOSPHORYLATION, SUBUNIT, AND
RP INTERACTION WITH EP300.
RX PubMed=15588252; DOI=10.1042/bj20041820;
RA Wang G., Long J., Matsuura I., He D., Liu F.;
RT "The Smad3 linker region contains a transcriptional activation domain.";
RL Biochem. J. 386:29-34(2005).
RN [27]
RP PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION,
RP FUNCTION, AND MUTAGENESIS OF THR-179; SER-204 AND SER-208.
RX PubMed=16156666; DOI=10.1021/bi050560g;
RA Matsuura I., Wang G., He D., Liu F.;
RT "Identification and characterization of ERK MAP kinase phosphorylation
RT sites in Smad3.";
RL Biochemistry 44:12546-12553(2005).
RN [28]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LEMD3.
RX PubMed=15601644; DOI=10.1093/hmg/ddi040;
RA Lin F., Morrison J.M., Wu W., Worman H.J.;
RT "MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and
RT Smad3 and antagonizes transforming growth factor-beta signaling.";
RL Hum. Mol. Genet. 14:437-445(2005).
RN [29]
RP INTERACTION WITH TGFB1I1.
RX PubMed=15561701; DOI=10.1074/jbc.m411575200;
RA Wang H., Song K., Sponseller T.L., Danielpour D.;
RT "Novel function of androgen receptor-associated protein 55/Hic-5 as a
RT negative regulator of Smad3 signaling.";
RL J. Biol. Chem. 280:5154-5162(2005).
RN [30]
RP INTERACTION WITH LEMD3.
RX PubMed=15647271; DOI=10.1074/jbc.m411234200;
RA Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S.,
RA Luo K.;
RT "The integral inner nuclear membrane protein MAN1 physically interacts with
RT the R-Smad proteins to repress signaling by the transforming growth
RT factor-{beta} superfamily of cytokines.";
RL J. Biol. Chem. 280:15992-16001(2005).
RN [31]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=15799969; DOI=10.1074/jbc.m500362200;
RA Chen H.B., Rud J.G., Lin K., Xu L.;
RT "Nuclear targeting of transforming growth factor-beta-activated Smad
RT complexes.";
RL J. Biol. Chem. 280:21329-21336(2005).
RN [32]
RP INTERACTION WITH SKOR2.
RX PubMed=16200078; DOI=10.1038/labinvest.3700344;
RA Arndt S., Poser I., Schubert T., Moser M., Bosserhoff A.-K.;
RT "Cloning and functional characterization of a new Ski homolog, Fussel-18,
RT specifically expressed in neuronal tissues.";
RL Lab. Invest. 85:1330-1341(2005).
RN [33]
RP INTERACTION WITH MECOM.
RX PubMed=15897867; DOI=10.1038/sj.onc.1208754;
RA Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S.,
RA Kurokawa M., Hirai H.;
RT "Oligomerization of Evi-1 regulated by the PR domain contributes to
RT recruitment of corepressor CtBP.";
RL Oncogene 24:6165-6173(2005).
RN [34]
RP INTERACTION WITH PPM1A, DEPHOSPHORYLATION, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16751101; DOI=10.1016/j.cell.2006.03.044;
RA Lin X., Duan X., Liang Y.Y., Su Y., Wrighton K.H., Long J., Hu M.,
RA Davis C.M., Wang J., Brunicardi F.C., Shi Y., Chen Y.G., Meng A.,
RA Feng X.H.;
RT "PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling.";
RL Cell 125:915-928(2006).
RN [35]
RP IDENTIFICATION IN A COMPLEX WITH SMAD2 AND TRIM33, AND INTERACTION WITH
RP SMAD2 AND TRIM33.
RX PubMed=16751102; DOI=10.1016/j.cell.2006.03.045;
RA He W., Dorn D.C., Erdjument-Bromage H., Tempst P., Moore M.A., Massague J.;
RT "Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the
RT TGFbeta pathway.";
RL Cell 125:929-941(2006).
RN [36]
RP INTERACTION WITH ZMIZ1.
RX PubMed=16777850; DOI=10.1074/jbc.m508365200;
RA Li X., Thyssen G., Beliakoff J., Sun Z.;
RT "The novel PIAS-like protein hZimp10 enhances Smad transcriptional
RT activity.";
RL J. Biol. Chem. 281:23748-23756(2006).
RN [37]
RP IDENTIFICATION IN A COMPLEX WITH RAN AND XPO4, INTERACTION WITH XPO4, AND
RP MUTAGENESIS OF 422-SER--SER-425.
RX PubMed=16449645; DOI=10.1128/mcb.26.4.1318-1332.2006;
RA Kurisaki A., Kurisaki K., Kowanetz M., Sugino H., Yoneda Y., Heldin C.-H.,
RA Moustakas A.;
RT "The mechanism of nuclear export of Smad3 involves exportin 4 and Ran.";
RL Mol. Cell. Biol. 26:1318-1332(2006).
RN [38]
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 [39]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PDPK1, AND INTERACTION
RP WITH PDPK1.
RX PubMed=17327236; DOI=10.1074/jbc.m609279200;
RA Seong H.A., Jung H., Kim K.T., Ha H.;
RT "3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth
RT factor-beta-induced signaling in a kinase-dependent manner through physical
RT interaction with Smad proteins.";
RL J. Biol. Chem. 282:12272-12289(2007).
RN [40]
RP INTERACTION WITH SKOR1.
RX PubMed=17292623; DOI=10.1016/j.mcn.2007.01.002;
RA Arndt S., Poser I., Moser M., Bosserhoff A.-K.;
RT "Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling.";
RL Mol. Cell. Neurosci. 34:603-611(2007).
RN [41]
RP ACETYLATION AT LYS-378, FUNCTION, AND MUTAGENESIS OF LYS-333; LYS-341;
RP LYS-378; LYS-409 AND 422-SER--SER-425.
RX PubMed=16862174; DOI=10.1038/sj.onc.1209826;
RA Inoue Y., Itoh Y., Abe K., Okamoto T., Daitoku H., Fukamizu A., Onozaki K.,
RA Hayashi H.;
RT "Smad3 is acetylated by p300/CBP to regulate its transactivation
RT activity.";
RL Oncogene 26:500-508(2007).
RN [42]
RP INTERACTION WITH WWTR1.
RX PubMed=18568018; DOI=10.1038/ncb1748;
RA Varelas X., Sakuma R., Samavarchi-Tehrani P., Peerani R., Rao B.M.,
RA Dembowy J., Yaffe M.B., Zandstra P.W., Wrana J.L.;
RT "TAZ controls Smad nucleocytoplasmic shuttling and regulates human
RT embryonic stem-cell self-renewal.";
RL Nat. Cell Biol. 10:837-848(2008).
RN [43]
RP INTERACTION WITH SARS-COV NUCLEOPROTEIN (MICROBIAL INFECTION).
RX PubMed=18055455; DOI=10.1074/jbc.m708033200;
RA Zhao X., Nicholls J.M., Chen Y.G.;
RT "Severe acute respiratory syndrome-associated coronavirus nucleocapsid
RT protein interacts with Smad3 and modulates transforming growth factor-beta
RT signaling.";
RL J. Biol. Chem. 283:3272-3280(2008).
RN [44]
RP INTERACTION WITH CSNK1G2, UBIQUITINATION, PHOSPHORYLATION AT SER-418 BY
RP CSNK1G2/CK1, AND MUTAGENESIS OF SER-418.
RX PubMed=18794808; DOI=10.1038/onc.2008.337;
RA Guo X., Waddell D.S., Wang W., Wang Z., Liberati N.T., Yong S., Liu X.,
RA Wang X.-F.;
RT "Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1
RT gamma 2, an inhibitor of TGF-beta signaling.";
RL Oncogene 27:7235-7247(2008).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [46]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [47]
RP INTERACTION WITH RANBP3, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=19289081; DOI=10.1016/j.devcel.2009.01.022;
RA Dai F., Lin X., Chang C., Feng X.H.;
RT "Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination of
RT TGF-beta signaling.";
RL Dev. Cell 16:345-357(2009).
RN [48]
RP INTERACTION WITH PRDM16; SKI AND HDAC1.
RX PubMed=19049980; DOI=10.1074/jbc.m808989200;
RA Takahata M., Inoue Y., Tsuda H., Imoto I., Koinuma D., Hayashi M.,
RA Ichikura T., Yamori T., Nagasaki K., Yoshida M., Matsuoka M., Morishita K.,
RA Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K., Imamura T.;
RT "SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal
RT in gastric cancer cells.";
RL J. Biol. Chem. 284:3334-3344(2009).
RN [49]
RP PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION,
RP FUNCTION, AND MUTAGENESIS OF THR-179; SER-204 AND SER-208.
RX PubMed=19218245; DOI=10.1074/jbc.m809281200;
RA Wang G., Matsuura I., He D., Liu F.;
RT "Transforming growth factor-{beta}-inducible phosphorylation of Smad3.";
RL J. Biol. Chem. 284:9663-9673(2009).
RN [50]
RP SUBCELLULAR LOCATION.
RX PubMed=21145499; DOI=10.1016/j.devcel.2010.11.012;
RA Varelas X., Samavarchi-Tehrani P., Narimatsu M., Weiss A., Cockburn K.,
RA Larsen B.G., Rossant J., Wrana J.L.;
RT "The Crumbs complex couples cell density sensing to Hippo-dependent control
RT of the TGF-beta-SMAD pathway.";
RL Dev. Cell 19:831-844(2010).
RN [51]
RP INTERACTION WITH MTMR4.
RX PubMed=20061380; DOI=10.1074/jbc.m109.075036;
RA Yu J., Pan L., Qin X., Chen H., Xu Y., Chen Y., Tang H.;
RT "MTMR4 attenuates transforming growth factor beta (TGFbeta) signaling by
RT dephosphorylating R-Smads in endosomes.";
RL J. Biol. Chem. 285:8454-8462(2010).
RN [52]
RP INTERACTION WITH PMEPA1.
RX PubMed=20129061; DOI=10.1016/j.molcel.2009.10.028;
RA Watanabe Y., Itoh S., Goto T., Ohnishi E., Inamitsu M., Itoh F., Satoh K.,
RA Wiercinska E., Yang W., Shi L., Tanaka A., Nakano N., Mommaas A.M.,
RA Shibuya H., Ten Dijke P., Kato M.;
RT "TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad
RT proteins from active participation in TGF-beta signaling.";
RL Mol. Cell 37:123-134(2010).
RN [53]
RP INTERACTION WITH IL1F7.
RX PubMed=20935647; DOI=10.1038/ni.1944;
RA Nold M.F., Nold-Petry C.A., Zepp J.A., Palmer B.E., Bufler P.,
RA Dinarello C.A.;
RT "IL-37 is a fundamental inhibitor of innate immunity.";
RL Nat. Immunol. 11:1014-1022(2010).
RN [54]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [55]
RP UBIQUITINATION, DEUBIQUITINATION BY USP15, DNA-BINDING, INTERACTION WITH
RP USP15, UBIQUITINATION AT LYS-33 AND LYS-81, AND MUTAGENESIS OF LYS-33;
RP LYS-53 AND LYS-81.
RX PubMed=21947082; DOI=10.1038/ncb2346;
RA Inui M., Manfrin A., Mamidi A., Martello G., Morsut L., Soligo S., Enzo E.,
RA Moro S., Polo S., Dupont S., Cordenonsi M., Piccolo S.;
RT "USP15 is a deubiquitylating enzyme for receptor-activated SMADs.";
RL Nat. Cell Biol. 13:1368-1375(2011).
RN [56]
RP INTERACTION WITH PPP5C, AND SUBCELLULAR LOCATION.
RX PubMed=22781750; DOI=10.1016/j.cellsig.2012.07.003;
RA Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.;
RT "Protein phosphatase 5 modulates SMAD3 function in the transforming growth
RT factor-beta pathway.";
RL Cell. Signal. 24:1999-2006(2012).
RN [57]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [58]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [59]
RP INTERACTION WITH STUB1; HSPA1A; HSPA1B; HSP90AA1 AND HSP90AB1,
RP UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
RX PubMed=24613385; DOI=10.1016/j.bbrc.2014.02.124;
RA Shang Y., Xu X., Duan X., Guo J., Wang Y., Ren F., He D., Chang Z.;
RT "Hsp70 and Hsp90 oppositely regulate TGF-beta signaling through
RT CHIP/Stub1.";
RL Biochem. Biophys. Res. Commun. 446:387-392(2014).
RN [60]
RP INTERACTION WITH ZNF451, AND IDENTIFICATION IN A COMPLEX WITH ZNF451; SMAD2
RP AND SMAD4.
RX PubMed=24324267; DOI=10.1074/jbc.m113.526905;
RA Feng Y., Wu H., Xu Y., Zhang Z., Liu T., Lin X., Feng X.H.;
RT "Zinc finger protein 451 is a novel Smad corepressor in transforming growth
RT factor-beta signaling.";
RL J. Biol. Chem. 289:2072-2083(2014).
RN [61]
RP INTERACTION WITH LDLRAD4.
RX PubMed=24627487; DOI=10.1074/jbc.m114.558981;
RA Nakano N., Maeyama K., Sakata N., Itoh F., Akatsu R., Nakata M., Katsu Y.,
RA Ikeno S., Togawa Y., Vo Nguyen T.T., Watanabe Y., Kato M., Itoh S.;
RT "C18 ORF1, a novel negative regulator of transforming growth factor-beta
RT signaling.";
RL J. Biol. Chem. 289:12680-12692(2014).
RN [62]
RP INTERACTION WITH ZFHX3.
RX PubMed=25105025; DOI=10.1155/2014/970346;
RA Sakata N., Kaneko S., Ikeno S., Miura Y., Nakabayashi H., Dong X.Y.,
RA Dong J.T., Tamaoki T., Nakano N., Itoh S.;
RT "TGF-beta signaling cooperates with AT motif-binding factor-1 for
RT repression of the alpha -fetoprotein promoter.";
RL J. Signal Transduct. 2014:970346-970346(2014).
RN [63]
RP ADP-RIBOSYLATION.
RX PubMed=25133494; DOI=10.1371/journal.pone.0103651;
RA Dahl M., Maturi V., Lonn P., Papoutsoglou P., Zieba A., Vanlandewijck M.,
RA van der Heide L.P., Watanabe Y., Soderberg O., Hottiger M.O., Heldin C.H.,
RA Moustakas A.;
RT "Fine-tuning of Smad protein function by poly(ADP-ribose) polymerases and
RT poly(ADP-ribose) glycohydrolase during transforming growth factor beta
RT Signaling.";
RL PLoS ONE 9:E103651-E103651(2014).
RN [64]
RP INTERACTION WITH NEDD9.
RX PubMed=29899023; DOI=10.1126/scitranslmed.aap7294;
RA Samokhin A.O., Stephens T., Wertheim B.M., Wang R.S., Vargas S.O.,
RA Yung L.M., Cao M., Brown M., Arons E., Dieffenbach P.B., Fewell J.G.,
RA Matar M., Bowman F.P., Haley K.J., Alba G.A., Marino S.M., Kumar R.,
RA Rosas I.O., Waxman A.B., Oldham W.M., Khanna D., Graham B.B., Seo S.,
RA Gladyshev V.N., Yu P.B., Fredenburgh L.E., Loscalzo J., Leopold J.A.,
RA Maron B.A.;
RT "NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary
RT arterial hypertension.";
RL Sci. Transl. Med. 10:0-0(2018).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-144.
RX PubMed=9741623; DOI=10.1016/s0092-8674(00)81600-1;
RA Shi Y., Wang Y.-F., Jayaraman L., Yang H., Massague J., Pavletich N.P.;
RT "Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA
RT binding in TGF-beta signaling.";
RL Cell 94:585-594(1998).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 220-425 IN COMPLEX WITH ZFYVE9.
RX PubMed=12154125; DOI=10.1101/gad.1002002;
RA Qin B.Y., Lam S.S., Correia J.J., Lin K.;
RT "Smad3 allostery links TGF-beta receptor kinase activation to
RT transcriptional control.";
RL Genes Dev. 16:1950-1963(2002).
RN [67]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-144 IN COMPLEX WITH DNA, AND
RP ZINC.
RX PubMed=12686552; DOI=10.1074/jbc.c300134200;
RA Chai J., Wu J.W., Yan N., Massague J., Pavletich N.P., Shi Y.;
RT "Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA
RT binding.";
RL J. Biol. Chem. 278:20327-20331(2003).
RN [68]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 228-424 IN COMPLEX WITH SMAD4, AND
RP SUBUNIT.
RX PubMed=15350224; DOI=10.1016/j.molcel.2004.07.016;
RA Chacko B.M., Qin B.Y., Tiwari A., Shi G., Lam S., Hayward L.J.,
RA De Caestecker M., Lin K.;
RT "Structural basis of heteromeric smad protein assembly in TGF-beta
RT signaling.";
RL Mol. Cell 15:813-823(2004).
RN [69]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-393, AND INVOLVEMENT IN COLORECTAL
RP CANCER.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [70]
RP VARIANTS LDS3 VAL-112; LYS-239 AND LYS-279.
RX PubMed=21778426; DOI=10.1161/circresaha.111.248161;
RA Regalado E.S., Guo D.C., Villamizar C., Avidan N., Gilchrist D.,
RA McGillivray B., Clarke L., Bernier F., Santos-Cortez R.L., Leal S.M.,
RA Bertoli-Avella A.M., Shendure J., Rieder M.J., Nickerson D.A.,
RA Milewicz D.M.;
RT "Exome sequencing identifies SMAD3 mutations as a cause of familial
RT thoracic aortic aneurysm and dissection with intracranial and other
RT arterial aneurysms.";
RL Circ. Res. 109:680-686(2011).
RN [71]
RP VARIANTS LDS3 ILE-261 AND TRP-287.
RX PubMed=21217753; DOI=10.1038/ng.744;
RA van de Laar I.M., Oldenburg R.A., Pals G., Roos-Hesselink J.W.,
RA de Graaf B.M., Verhagen J.M., Hoedemaekers Y.M., Willemsen R.,
RA Severijnen L.A., Venselaar H., Vriend G., Pattynama P.M., Collee M.,
RA Majoor-Krakauer D., Poldermans D., Frohn-Mulder I.M., Micha D.,
RA Timmermans J., Hilhorst-Hofstee Y., Bierma-Zeinstra S.M., Willems P.J.,
RA Kros J.M., Oei E.H., Oostra B.A., Wessels M.W., Bertoli-Avella A.M.;
RT "Mutations in SMAD3 cause a syndromic form of aortic aneurysms and
RT dissections with early-onset osteoarthritis.";
RL Nat. Genet. 43:121-126(2011).
CC -!- FUNCTION: Receptor-regulated SMAD (R-SMAD) that is an intracellular
CC signal transducer and transcriptional modulator activated by TGF-beta
CC (transforming growth factor) and activin type 1 receptor kinases. Binds
CC the TRE element in the promoter region of many genes that are regulated
CC by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates
CC transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-
CC 1/SMAD site to regulate TGF-beta-mediated transcription. Has an
CC inhibitory effect on wound healing probably by modulating both growth
CC and migration of primary keratinocytes and by altering the TGF-mediated
CC chemotaxis of monocytes. This effect on wound healing appears to be
CC hormone-sensitive. Regulator of chondrogenesis and osteogenesis and
CC inhibits early healing of bone fractures. Positively regulates PDPK1
CC kinase activity by stimulating its dissociation from the 14-3-3 protein
CC YWHAQ which acts as a negative regulator. {ECO:0000269|PubMed:10995748,
CC ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:15588252,
CC ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101,
CC ECO:0000269|PubMed:16862174, ECO:0000269|PubMed:17327236,
CC ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081,
CC ECO:0000269|PubMed:9732876, ECO:0000269|PubMed:9892009}.
CC -!- SUBUNIT: Monomer; in the absence of TGF-beta (PubMed:9670020).
CC Homooligomer; in the presence of TGF-beta (PubMed:9670020).
CC Heterotrimer; forms a heterotrimer in the presence of TGF-beta
CC consisting of two molecules of C-terminally phosphorylated SMAD2 or
CC SMAD3 and one of SMAD4 to form the transcriptionally active
CC SMAD2/SMAD3-SMAD4 complex (PubMed:11224571, PubMed:15350224,
CC PubMed:15799969, PubMed:9670020). Part of a complex consisting of
CC MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:9892009). Forms a complex
CC with SMAD2 and TRIM33 upon addition of TGF-beta (PubMed:16751102).
CC Found in a complex composed of SMAD3, RAN and XPO4; within the complex
CC interacts directly with XPO4 (PubMed:16449645). Component of the
CC multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter
CC site; required for synergistic transcriptional activity in response to
CC TGF-beta (PubMed:10995748, PubMed:9732876). Part of a ternary complex
CC composed of SMAD3, ITCH/AIP4 and NEDD9/HEF1; within the complex
CC NEDD9/HEF1 interacts (via N-terminus) with ITCH/AIP4; the complex
CC mediates ubiquitination and proteasomal degradation of NEDD9/HEF1
CC (PubMed:15051726). Interacts with NEDD9; the interaction promotes NEDD9
CC ubiquitination and proteasomal degradation (PubMed:15051726). Interacts
CC (via an N-terminal domain) with JUN (via its basic DNA binding and
CC leucine zipper domains); this interaction is essential for DNA binding
CC and cooperative transcriptional activity in response to TGF-beta
CC (PubMed:10995748, PubMed:9732876). Identified in a complex that
CC contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267).
CC Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-
CC terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex,
CC nuclear export and termination of TGF-beta signaling (PubMed:16751101).
CC Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the
CC TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4
CC transcriptional complex (PubMed:16777850). Interacts (when
CC phosphorylated) with RNF111; RNF111 acts as an enhancer of the
CC transcriptional responses by mediating ubiquitination and degradation
CC of SMAD3 inhibitors (PubMed:9311995). Interacts (dephosphorylated form
CC via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain);
CC the interaction results in the export of dephosphorylated SMAD3 out of
CC the nucleus and termination of the TGF-beta signaling
CC (PubMed:19289081). Interacts (via MH2 domain) with LEMD3; the
CC interaction represses SMAD3 transcriptional activity through preventing
CC the formation of the heteromeric complex with SMAD4 and translocation
CC to the nucleus (PubMed:15601644, PubMed:15647271). Interacts (via the
CC linker region) with EP300 (C-terminal); the interaction promotes SMAD3
CC acetylation and is enhanced by TGF-beta phosphorylation in the C-
CC terminal of SMAD3 (PubMed:15588252, PubMed:9843571). This interaction
CC can be blocked by competitive binding of adenovirus oncoprotein E1A to
CC the same C-terminal site on EP300, which then results in partially
CC inhibited SMAD3/SMAD4 transcriptional activity (PubMed:15588252,
CC PubMed:9843571). Interacts with TGFBR1 (PubMed:9311995). Interacts with
CC TGFB1I1 (PubMed:15561701). Interacts with PRDM16 (PubMed:19049980).
CC Interacts with SNW1 (PubMed:11278756). Interacts (via MH2 domain) with
CC ZFYVE9 (PubMed:12154125, PubMed:9865696). Interacts with HDAC1
CC (PubMed:19049980). Interacts with TGIF2 (PubMed:11427533). Interacts
CC with SKOR1 (PubMed:17292623). Interacts with SKOR2 (PubMed:16200078).
CC Interacts with DACH1; the interaction inhibits the TGF-beta signaling
CC (PubMed:14525983). Interacts with RBPMS (PubMed:17099224). Interacts
CC (via MH2 domain) with MECOM (PubMed:15897867, PubMed:9665135).
CC Interacts with WWTR1 (via its coiled-coil domain) (PubMed:18568018).
CC Interacts with SKI; the interaction represses SMAD3 transcriptional
CC activity (PubMed:19049980). Interacts with MEN1 (PubMed:11274402).
CC Interacts with IL1F7 (PubMed:20935647). Interaction with CSNK1G2
CC (PubMed:18794808). Interacts with PDPK1 (via PH domain)
CC (PubMed:17327236). Interacts with DAB2; the interactions are enhanced
CC upon TGF-beta stimulation (PubMed:11387212). Interacts with USP15
CC (PubMed:21947082). Interacts with PPP5C; the interaction decreases
CC SMAD3 phosphorylation and protein levels (PubMed:22781750). Interacts
CC with LDLRAD4 (via the SMAD interaction motif) (PubMed:24627487).
CC Interacts with PMEPA1 (PubMed:20129061). Interacts with ZNF451
CC (PubMed:24324267). Interacts with ZFHX3 (PubMed:25105025). Interacts
CC weakly with ZNF8 (PubMed:12370310). Interacts with STUB1, HSPA1A,
CC HSPA1B, HSP90AA1 and HSP90AB1 (PubMed:24613385). Interacts with YAP1
CC (when phosphorylated at 'Ser-127') (By similarity). Interacts with
CC MAGI2/ARIP1 (By similarity). Interacts (via MH2 domain) with CITED2
CC (via C-terminus) (By similarity). Interacts with HGS (By similarity).
CC Interacts with WWP1 (By similarity). Interacts with TTRAP (By
CC similarity). Interacts with FOXL2 (By similarity). Interacts with PML
CC (By similarity). Interacts with NEDD4L; the interaction requires TGF-
CC beta stimulation (By similarity). Interacts with ZC3H3 (By similarity).
CC Interacts with TGIF. Interacts with CREBBP. Interacts with ATF2.
CC Interacts with NEDD9; the interaction is inhibited by oxidation of
CC NEDD9 (PubMed:29899023). Interacts with MTMR4; negatively regulates
CC TGF-beta signaling through SMAD3 dephosphorylation and retention in
CC endosomes (PubMed:20061380). {ECO:0000250|UniProtKB:P84025,
CC ECO:0000250|UniProtKB:Q8BUN5, ECO:0000269|PubMed:10995748,
CC ECO:0000269|PubMed:11224571, ECO:0000269|PubMed:11274402,
CC ECO:0000269|PubMed:11278756, ECO:0000269|PubMed:11387212,
CC ECO:0000269|PubMed:11427533, ECO:0000269|PubMed:12154125,
CC ECO:0000269|PubMed:12370310, ECO:0000269|PubMed:14525983,
CC ECO:0000269|PubMed:15051726, ECO:0000269|PubMed:15350224,
CC ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:15588252,
CC ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15647271,
CC ECO:0000269|PubMed:15799969, ECO:0000269|PubMed:15897867,
CC ECO:0000269|PubMed:16200078, ECO:0000269|PubMed:16449645,
CC ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:16751102,
CC ECO:0000269|PubMed:16777850, ECO:0000269|PubMed:17099224,
CC ECO:0000269|PubMed:17292623, ECO:0000269|PubMed:17327236,
CC ECO:0000269|PubMed:18568018, ECO:0000269|PubMed:18794808,
CC ECO:0000269|PubMed:19049980, ECO:0000269|PubMed:19289081,
CC ECO:0000269|PubMed:20061380, ECO:0000269|PubMed:20129061,
CC ECO:0000269|PubMed:20935647, ECO:0000269|PubMed:21947082,
CC ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:24324267,
CC ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:24627487,
CC ECO:0000269|PubMed:25105025, ECO:0000269|PubMed:29899023,
CC ECO:0000269|PubMed:9311995, ECO:0000269|PubMed:9665135,
CC ECO:0000269|PubMed:9670020, ECO:0000269|PubMed:9732876,
CC ECO:0000269|PubMed:9843571, ECO:0000269|PubMed:9865696,
CC ECO:0000269|PubMed:9892009}.
CC -!- SUBUNIT: (Microbial infection) Interacts with SARS-CoV nucleoprotein.
CC {ECO:0000269|PubMed:18055455}.
CC -!- INTERACTION:
CC P84022; Q06481-5: APLP2; NbExp=3; IntAct=EBI-347161, EBI-25646567;
CC P84022; P05067: APP; NbExp=3; IntAct=EBI-347161, EBI-77613;
CC P84022; Q9H2G9: BLZF1; NbExp=9; IntAct=EBI-347161, EBI-2548012;
CC P84022; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-347161, EBI-1383687;
CC P84022; P29466-3: CASP1; NbExp=3; IntAct=EBI-347161, EBI-12248206;
CC P84022; E9PSE9: CCDC198; NbExp=3; IntAct=EBI-347161, EBI-11748295;
CC P84022; Q8N5R6: CCDC33; NbExp=4; IntAct=EBI-347161, EBI-740841;
CC P84022; Q9H2X0: CHRD; NbExp=2; IntAct=EBI-347161, EBI-947551;
CC P84022; Q8N684: CPSF7; NbExp=3; IntAct=EBI-347161, EBI-746909;
CC P84022; Q8N684-3: CPSF7; NbExp=3; IntAct=EBI-347161, EBI-11523759;
CC P84022; O43186: CRX; NbExp=3; IntAct=EBI-347161, EBI-748171;
CC P84022; Q96PZ7: CSMD1; NbExp=3; IntAct=EBI-347161, EBI-766158;
CC P84022; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-347161, EBI-9087876;
CC P84022; P98082: DAB2; NbExp=3; IntAct=EBI-347161, EBI-1171238;
CC P84022; P17844: DDX5; NbExp=2; IntAct=EBI-347161, EBI-351962;
CC P84022; Q9BZ29: DOCK9; NbExp=3; IntAct=EBI-347161, EBI-2695893;
CC P84022; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-347161, EBI-6658203;
CC P84022; Q01543: FLI1; NbExp=3; IntAct=EBI-347161, EBI-2271018;
CC P84022; O75593: FOXH1; NbExp=4; IntAct=EBI-347161, EBI-1759806;
CC P84022; O43524: FOXO3; NbExp=5; IntAct=EBI-347161, EBI-1644164;
CC P84022; P10070: GLI2; NbExp=4; IntAct=EBI-347161, EBI-10821567;
CC P84022; Q16665: HIF1A; NbExp=6; IntAct=EBI-347161, EBI-447269;
CC P84022; O15397: IPO8; NbExp=2; IntAct=EBI-347161, EBI-358808;
CC P84022; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-347161, EBI-1055254;
CC P84022; P50222: MEOX2; NbExp=6; IntAct=EBI-347161, EBI-748397;
CC P84022; Q9NYA4: MTMR4; NbExp=2; IntAct=EBI-347161, EBI-1052346;
CC P84022; Q99836: MYD88; NbExp=3; IntAct=EBI-347161, EBI-447677;
CC P84022; P46934-3: NEDD4; NbExp=3; IntAct=EBI-347161, EBI-11980721;
CC P84022; Q16822: PCK2; NbExp=2; IntAct=EBI-347161, EBI-2825219;
CC P84022; Q8IXK0: PHC2; NbExp=3; IntAct=EBI-347161, EBI-713786;
CC P84022; Q8IXK0-5: PHC2; NbExp=3; IntAct=EBI-347161, EBI-11527347;
CC P84022; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-347161, EBI-9090282;
CC P84022; Q9BZL4: PPP1R12C; NbExp=2; IntAct=EBI-347161, EBI-721802;
CC P84022; P17612: PRKACA; NbExp=3; IntAct=EBI-347161, EBI-476586;
CC P84022; P20618: PSMB1; NbExp=3; IntAct=EBI-347161, EBI-372273;
CC P84022; Q96EP0: RNF31; NbExp=2; IntAct=EBI-347161, EBI-948111;
CC P84022; P0C264: SBK3; NbExp=3; IntAct=EBI-347161, EBI-17181801;
CC P84022; Q9BYW2: SETD2; NbExp=2; IntAct=EBI-347161, EBI-945869;
CC P84022; P12755: SKI; NbExp=8; IntAct=EBI-347161, EBI-347281;
CC P84022; Q15796: SMAD2; NbExp=3; IntAct=EBI-347161, EBI-1040141;
CC P84022; P84022: SMAD3; NbExp=3; IntAct=EBI-347161, EBI-347161;
CC P84022; Q13485: SMAD4; NbExp=35; IntAct=EBI-347161, EBI-347263;
CC P84022; Q9HAU4: SMURF2; NbExp=8; IntAct=EBI-347161, EBI-396727;
CC P84022; Q13573: SNW1; NbExp=5; IntAct=EBI-347161, EBI-632715;
CC P84022; Q13501: SQSTM1; NbExp=3; IntAct=EBI-347161, EBI-307104;
CC P84022; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-347161, EBI-750487;
CC P84022; Q15583: TGIF1; NbExp=3; IntAct=EBI-347161, EBI-714215;
CC P84022; Q08117: TLE5; NbExp=4; IntAct=EBI-347161, EBI-717810;
CC P84022; Q08117-2: TLE5; NbExp=3; IntAct=EBI-347161, EBI-11741437;
CC P84022; Q9Y3Q8: TSC22D4; NbExp=2; IntAct=EBI-347161, EBI-739485;
CC P84022; Q93009: USP7; NbExp=2; IntAct=EBI-347161, EBI-302474;
CC P84022; Q9H0M0: WWP1; NbExp=9; IntAct=EBI-347161, EBI-742157;
CC P84022; O00308: WWP2; NbExp=7; IntAct=EBI-347161, EBI-743923;
CC P84022; Q5D1E8: ZC3H12A; NbExp=2; IntAct=EBI-347161, EBI-747793;
CC P84022; O95405: ZFYVE9; NbExp=7; IntAct=EBI-347161, EBI-296817;
CC P84022; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-347161, EBI-10251462;
CC P84022; Q64729: Tgfbr1; Xeno; NbExp=6; IntAct=EBI-347161, EBI-2899393;
CC P84022; PRO_0000278742 [O92972]; Xeno; NbExp=6; IntAct=EBI-347161, EBI-9213553;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15799969,
CC ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101,
CC ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19218245,
CC ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:21145499,
CC ECO:0000269|PubMed:22781750}. Nucleus {ECO:0000269|PubMed:15601644,
CC ECO:0000269|PubMed:15799969, ECO:0000269|PubMed:16156666,
CC ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:19218245,
CC ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:21145499,
CC ECO:0000269|PubMed:22781750}. Note=Cytoplasmic and nuclear in the
CC absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus
CC when complexed with SMAD4 (PubMed:15799969, PubMed:21145499). Through
CC the action of the phosphatase PPM1A, released from the SMAD2/SMAD4
CC complex, and exported out of the nucleus by interaction with RANBP1
CC (PubMed:16751101, PubMed:19289081). Co-localizes with LEMD3 at the
CC nucleus inner membrane (PubMed:15601644). MAPK-mediated phosphorylation
CC appears to have no effect on nuclear import (PubMed:19218245). PDPK1
CC prevents its nuclear translocation in response to TGF-beta
CC (PubMed:17327236). Localized mainly to the nucleus in the early stages
CC of embryo development with expression becoming evident in the cytoplasm
CC of the inner cell mass at the blastocyst stage (By similarity).
CC {ECO:0000250|UniProtKB:Q8BUN5, ECO:0000269|PubMed:15601644,
CC ECO:0000269|PubMed:15799969, ECO:0000269|PubMed:16751101,
CC ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19218245,
CC ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:21145499}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P84022-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P84022-2; Sequence=VSP_042900;
CC Name=3;
CC IsoId=P84022-3; Sequence=VSP_043793;
CC Name=4;
CC IsoId=P84022-4; Sequence=VSP_045348;
CC -!- DOMAIN: The MH1 domain is required for DNA binding. Also binds zinc
CC ions which are necessary for the DNA binding.
CC -!- DOMAIN: The MH2 domain is required for both homomeric and heteromeric
CC interactions and for transcriptional regulation. Sufficient for nuclear
CC import.
CC -!- DOMAIN: The linker region is required for the TGFbeta-mediated
CC transcriptional activity and acts synergistically with the MH2 domain.
CC -!- PTM: Phosphorylated on serine and threonine residues. Enhanced
CC phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on
CC EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated
CC phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle
CC dependent manner and inhibits both the transcriptional activity and
CC antiproliferative functions of SMAD3. This phosphorylation is inhibited
CC by flavopiridol. Maximum phosphorylation at the G(1)/S junction. Also
CC phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1
CC and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is
CC required for interaction with SMAD4, nuclear location and
CC transactivational activity, and appears to be a prerequisite for the
CC TGF-beta mediated phosphorylation in the linker region.
CC Dephosphorylated in the C-terminal SXS motif by PPM1A. This
CC dephosphorylation disrupts the interaction with SMAD4, promotes nuclear
CC export and terminates TGF-beta-mediated signaling. Phosphorylation at
CC Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and
CC subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-
CC beta responses. Phosphorylated by PDPK1. {ECO:0000269|PubMed:11224571,
CC ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:15588252,
CC ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:17327236,
CC ECO:0000269|PubMed:18794808, ECO:0000269|PubMed:19218245,
CC ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:8774881,
CC ECO:0000269|PubMed:9843571}.
CC -!- PTM: Acetylation in the nucleus by EP300 in the MH2 domain regulates
CC positively its transcriptional activity and is enhanced by TGF-beta.
CC {ECO:0000269|PubMed:16862174}.
CC -!- PTM: Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation
CC negatively regulates SMAD3 transcriptional responses during the course
CC of TGF-beta signaling. {ECO:0000269|PubMed:25133494}.
CC -!- PTM: Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding
CC (PubMed:21947082). Deubiquitination by USP15 alleviates inhibition and
CC promotes activation of TGF-beta target genes (PubMed:21947082).
CC Ubiquitinated by RNF111, leading to its degradation: only SMAD3
CC proteins that are 'in use' are targeted by RNF111, RNF111 playing a key
CC role in activating SMAD3 and regulating its turnover (By similarity).
CC Undergoes STUB1-mediated ubiquitination and degradation
CC (PubMed:24613385). {ECO:0000250|UniProtKB:Q8BUN5,
CC ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:24613385}.
CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
CC characterized by malignant lesions arising from the inner wall of the
CC large intestine (the colon) and the rectum. Genetic alterations are
CC often associated with progression from premalignant lesion (adenoma) to
CC invasive adenocarcinoma. Risk factors for cancer of the colon and
CC rectum include colon polyps, long-standing ulcerative colitis, and
CC genetic family history. {ECO:0000269|PubMed:16959974}. Note=The disease
CC may be caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Loeys-Dietz syndrome 3 (LDS3) [MIM:613795]: An aortic aneurysm
CC syndrome with widespread systemic involvement. The disorder is
CC characterized by the triad of arterial tortuosity and aneurysms,
CC hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also
CC manifest early-onset osteoarthritis. They lack craniosynostosis and
CC intellectual disability. {ECO:0000269|PubMed:21217753,
CC ECO:0000269|PubMed:21778426}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. SMAD3 mutations have been
CC reported to be also associated with thoracic aortic aneurysms and
CC dissection (TAAD) (PubMed:21778426). This phenotype is distinguised
CC from LDS3 by having aneurysms restricted to thoracic aorta. As
CC individuals carrying these mutations also exhibit aneurysms of other
CC arteries, including abdominal aorta, iliac, and/or intracranial
CC arteries (PubMed:21778426), they have been classified as LDS3 by the
CC OMIM resource. {ECO:0000269|PubMed:21778426}.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; U68019; AAB80960.1; -; mRNA.
DR EMBL; U76622; AAB18967.1; -; mRNA.
DR EMBL; AB004930; BAA22032.1; -; Genomic_DNA.
DR EMBL; AF025300; AAL68976.1; -; Genomic_DNA.
DR EMBL; AF025293; AAL68976.1; JOINED; Genomic_DNA.
DR EMBL; AF025294; AAL68976.1; JOINED; Genomic_DNA.
DR EMBL; AF025295; AAL68976.1; JOINED; Genomic_DNA.
DR EMBL; AF025296; AAL68976.1; JOINED; Genomic_DNA.
DR EMBL; AF025297; AAL68976.1; JOINED; Genomic_DNA.
DR EMBL; AF025298; AAL68976.1; JOINED; Genomic_DNA.
DR EMBL; AF025299; AAL68976.1; JOINED; Genomic_DNA.
DR EMBL; AK290881; BAF83570.1; -; mRNA.
DR EMBL; AK298139; BAH12731.1; -; mRNA.
DR EMBL; AK300614; BAH13315.1; -; mRNA.
DR EMBL; AK316017; BAH14388.1; -; mRNA.
DR EMBL; AC012568; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087482; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77788.1; -; Genomic_DNA.
DR EMBL; BC050743; AAH50743.1; -; mRNA.
DR CCDS; CCDS10222.1; -. [P84022-1]
DR CCDS; CCDS45288.1; -. [P84022-2]
DR CCDS; CCDS53950.1; -. [P84022-3]
DR CCDS; CCDS53951.1; -. [P84022-4]
DR PIR; S71798; S71798.
DR RefSeq; NP_001138574.1; NM_001145102.1. [P84022-3]
DR RefSeq; NP_001138575.1; NM_001145103.1. [P84022-2]
DR RefSeq; NP_001138576.1; NM_001145104.1. [P84022-4]
DR RefSeq; NP_005893.1; NM_005902.3. [P84022-1]
DR PDB; 1MHD; X-ray; 2.80 A; A/B=1-132.
DR PDB; 1MJS; X-ray; 1.91 A; A=229-425.
DR PDB; 1MK2; X-ray; 2.74 A; A=220-425.
DR PDB; 1OZJ; X-ray; 2.40 A; A/B=1-144.
DR PDB; 1U7F; X-ray; 2.60 A; A/C=228-425.
DR PDB; 2LAJ; NMR; -; B=202-211.
DR PDB; 2LB2; NMR; -; B=178-189.
DR PDB; 5OD6; X-ray; 2.00 A; A/B=11-135.
DR PDB; 5ODG; X-ray; 2.12 A; A/B=11-135.
DR PDB; 5XOC; X-ray; 2.40 A; A=220-416.
DR PDB; 6YIB; X-ray; 1.70 A; P=417-425.
DR PDB; 6ZMN; X-ray; 2.33 A; A/B=10-136.
DR PDBsum; 1MHD; -.
DR PDBsum; 1MJS; -.
DR PDBsum; 1MK2; -.
DR PDBsum; 1OZJ; -.
DR PDBsum; 1U7F; -.
DR PDBsum; 2LAJ; -.
DR PDBsum; 2LB2; -.
DR PDBsum; 5OD6; -.
DR PDBsum; 5ODG; -.
DR PDBsum; 5XOC; -.
DR PDBsum; 6YIB; -.
DR PDBsum; 6ZMN; -.
DR AlphaFoldDB; P84022; -.
DR SMR; P84022; -.
DR BioGRID; 110263; 423.
DR ComplexPortal; CPX-1; SMAD2-SMAD3-SMAD4 complex.
DR ComplexPortal; CPX-12; SMAD3 homotrimer.
DR ComplexPortal; CPX-3252; SMAD3-SMAD4 complex.
DR ComplexPortal; CPX-6062; SMAD3-TTF-1 complex.
DR CORUM; P84022; -.
DR DIP; DIP-29720N; -.
DR IntAct; P84022; 222.
DR MINT; P84022; -.
DR STRING; 9606.ENSP00000332973; -.
DR BindingDB; P84022; -.
DR ChEMBL; CHEMBL1293258; -.
DR MoonDB; P84022; Predicted.
DR iPTMnet; P84022; -.
DR PhosphoSitePlus; P84022; -.
DR SwissPalm; P84022; -.
DR BioMuta; SMAD3; -.
DR DMDM; 51338669; -.
DR jPOST; P84022; -.
DR MassIVE; P84022; -.
DR PaxDb; 9606-ENSP00000332973; -.
DR PeptideAtlas; P84022; -.
DR ProteomicsDB; 26192; -.
DR ProteomicsDB; 57743; -. [P84022-1]
DR ProteomicsDB; 57744; -. [P84022-2]
DR ProteomicsDB; 57745; -. [P84022-3]
DR Pumba; P84022; -.
DR ABCD; P84022; 2 sequenced antibodies.
DR Antibodypedia; 26224; 2729 antibodies from 45 providers.
DR DNASU; 4088; -.
DR Ensembl; ENST00000327367.9; ENSP00000332973.4; ENSG00000166949.18. [P84022-1]
DR Ensembl; ENST00000439724.7; ENSP00000401133.3; ENSG00000166949.18. [P84022-2]
DR Ensembl; ENST00000537194.6; ENSP00000445348.2; ENSG00000166949.18. [P84022-4]
DR Ensembl; ENST00000540846.6; ENSP00000437757.2; ENSG00000166949.18. [P84022-3]
DR Ensembl; ENST00000558428.6; ENSP00000454165.2; ENSG00000166949.18. [P84022-4]
DR Ensembl; ENST00000558739.2; ENSP00000453684.2; ENSG00000166949.18. [P84022-3]
DR Ensembl; ENST00000558827.2; ENSP00000452767.2; ENSG00000166949.18. [P84022-4]
DR Ensembl; ENST00000559460.6; ENSP00000453082.2; ENSG00000166949.18. [P84022-3]
DR Ensembl; ENST00000679624.1; ENSP00000505445.1; ENSG00000166949.18. [P84022-3]
DR Ensembl; ENST00000681239.1; ENSP00000505641.1; ENSG00000166949.18. [P84022-3]
DR GeneID; 4088; -.
DR KEGG; hsa:4088; -.
DR MANE-Select; ENST00000327367.9; ENSP00000332973.4; NM_005902.4; NP_005893.1.
DR UCSC; uc002aqj.4; human. [P84022-1]
DR AGR; HGNC:6769; -.
DR CTD; 4088; -.
DR DisGeNET; 4088; -.
DR GeneCards; SMAD3; -.
DR GeneReviews; SMAD3; -.
DR HGNC; HGNC:6769; SMAD3.
DR HPA; ENSG00000166949; Low tissue specificity.
DR MalaCards; SMAD3; -.
DR MIM; 114500; phenotype.
DR MIM; 603109; gene.
DR MIM; 613795; phenotype.
DR neXtProt; NX_P84022; -.
DR OpenTargets; ENSG00000166949; -.
DR Orphanet; 284984; Aneurysm-osteoarthritis syndrome.
DR Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
DR Orphanet; 60030; Loeys-Dietz syndrome.
DR PharmGKB; PA30526; -.
DR VEuPathDB; HostDB:ENSG00000166949; -.
DR eggNOG; KOG3701; Eukaryota.
DR GeneTree; ENSGT00940000153499; -.
DR HOGENOM; CLU_026736_0_0_1; -.
DR InParanoid; P84022; -.
DR OMA; VENCRYS; -.
DR OrthoDB; 2891561at2759; -.
DR PhylomeDB; P84022; -.
DR TreeFam; TF314923; -.
DR PathwayCommons; P84022; -.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR Reactome; R-HSA-1502540; Signaling by Activin.
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-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-3304356; SMAD2/3 Phosphorylation Motif Mutants in Cancer.
DR Reactome; R-HSA-3311021; SMAD4 MH2 Domain Mutants in Cancer.
DR Reactome; R-HSA-3315487; SMAD2/3 MH2 Domain Mutants in Cancer.
DR Reactome; R-HSA-3656532; TGFBR1 KD Mutants in Cancer.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8941855; RUNX3 regulates CDKN1A transcription.
DR Reactome; R-HSA-8952158; RUNX3 regulates BCL2L11 (BIM) transcription.
DR Reactome; R-HSA-9008059; Interleukin-37 signaling.
DR Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR Reactome; R-HSA-9617828; FOXO-mediated transcription of cell cycle genes.
DR Reactome; R-HSA-9735871; SARS-CoV-1 targets host intracellular signalling and regulatory pathways.
DR Reactome; R-HSA-9754189; Germ layer formation at gastrulation.
DR Reactome; R-HSA-9796292; Formation of axial mesoderm.
DR Reactome; R-HSA-9823730; Formation of definitive endoderm.
DR Reactome; R-HSA-9839394; TGFBR3 expression.
DR SignaLink; P84022; -.
DR SIGNOR; P84022; -.
DR BioGRID-ORCS; 4088; 18 hits in 1191 CRISPR screens.
DR ChiTaRS; SMAD3; human.
DR EvolutionaryTrace; P84022; -.
DR GeneWiki; Mothers_against_decapentaplegic_homolog_3; -.
DR GenomeRNAi; 4088; -.
DR Pharos; P84022; Tchem.
DR PRO; PR:P84022; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P84022; protein.
DR Bgee; ENSG00000166949; Expressed in tendon of biceps brachii and 204 other cell types or tissues.
DR ExpressionAtlas; P84022; baseline and differential.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; IDA:BHF-UCL.
DR GO; GO:0005637; C:nuclear inner membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0043235; C:receptor complex; IMP:BHF-UCL.
DR GO; GO:0071141; C:SMAD protein complex; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IEA:Ensembl.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0070410; F:co-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0005518; F:collagen binding; IEA:Ensembl.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IDA:ARUK-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; IDA:ARUK-UCL.
DR GO; GO:0070411; F:I-SMAD binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IPI:CAFA.
DR GO; GO:0031962; F:nuclear mineralocorticoid receptor binding; IPI:CAFA.
DR GO; GO:0016922; F:nuclear receptor binding; IPI:BHF-UCL.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0070412; F:R-SMAD binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0032810; F:sterol response element binding; IGI:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:HGNC-UCL.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; IPI:BHF-UCL.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL.
DR GO; GO:0032924; P:activin receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0045216; P:cell-cell junction organization; IMP:BHF-UCL.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:CAFA.
DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl.
DR GO; GO:0048589; P:developmental growth; IEA:Ensembl.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR GO; GO:0048617; P:embryonic foregut morphogenesis; IEA:Ensembl.
DR GO; GO:0009880; P:embryonic pattern specification; IEA:Ensembl.
DR GO; GO:0007492; P:endoderm development; IEA:Ensembl.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IMP:BHF-UCL.
DR GO; GO:0002520; P:immune system development; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IDA:BHF-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0061767; P:negative regulation of lung blood pressure; IEA:Ensembl.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IMP:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0061045; P:negative regulation of wound healing; IEA:Ensembl.
DR GO; GO:0038092; P:nodal signaling pathway; IMP:BHF-UCL.
DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl.
DR GO; GO:0048340; P:paraxial mesoderm morphogenesis; IEA:Ensembl.
DR GO; GO:0060039; P:pericardium development; IEA:Ensembl.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; NAS:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:BHF-UCL.
DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; IDA:BHF-UCL.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IEA:Ensembl.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; NAS:BHF-UCL.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0032916; P:positive regulation of transforming growth factor beta3 production; IEA:Ensembl.
DR GO; GO:0031053; P:primary miRNA processing; TAS:BHF-UCL.
DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:ComplexPortal.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0050776; P:regulation of immune response; IEA:Ensembl.
DR GO; GO:1902893; P:regulation of miRNA transcription; IC:ARUK-UCL.
DR GO; GO:0016202; P:regulation of striated muscle tissue development; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0032909; P:regulation of transforming growth factor beta2 production; IMP:BHF-UCL.
DR GO; GO:1990776; P:response to angiotensin; IMP:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; IMP:BHF-UCL.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:BHF-UCL.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR GO; GO:0042110; P:T cell activation; IEA:Ensembl.
DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
DR GO; GO:0060290; P:transdifferentiation; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; TAS:BHF-UCL.
DR CDD; cd10491; MH1_SMAD_2_3; 1.
DR CDD; cd10985; MH2_SMAD_2_3; 1.
DR DisProt; DP01648; -.
DR Gene3D; 2.60.200.10; -; 1.
DR Gene3D; 3.90.520.10; SMAD MH1 domain; 1.
DR IDEAL; IID00113; -.
DR InterPro; IPR013790; Dwarfin.
DR InterPro; IPR003619; MAD_homology1_Dwarfin-type.
DR InterPro; IPR013019; MAD_homology_MH1.
DR InterPro; IPR017855; SMAD-like_dom_sf.
DR InterPro; IPR001132; SMAD_dom_Dwarfin-type.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR036578; SMAD_MH1_sf.
DR PANTHER; PTHR13703:SF53; MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 3; 1.
DR PANTHER; PTHR13703; SMAD; 1.
DR Pfam; PF03165; MH1; 1.
DR Pfam; PF03166; MH2; 1.
DR SMART; SM00523; DWA; 1.
DR SMART; SM00524; DWB; 1.
DR SUPFAM; SSF56366; SMAD MH1 domain; 1.
DR SUPFAM; SSF49879; SMAD/FHA domain; 1.
DR PROSITE; PS51075; MH1; 1.
DR PROSITE; PS51076; MH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ADP-ribosylation; Alternative splicing;
KW Aortic aneurysm; Cytoplasm; Disease variant; DNA-binding;
KW Host-virus interaction; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Proteomics identification; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..425
FT /note="Mothers against decapentaplegic homolog 3"
FT /id="PRO_0000090856"
FT DOMAIN 10..136
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 232..425
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 137..231
FT /note="Linker"
FT REGION 165..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..324
FT /note="Sufficient for interaction with XPO4"
FT /evidence="ECO:0000269|PubMed:16449645"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 109
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT SITE 40
FT /note="Required for trimerization"
FT SITE 41
FT /note="Required for interaction with DNA and JUN and for
FT functional cooperation with JUN"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 8
FT /note="Phosphothreonine; by CDK2 and CDK4"
FT /evidence="ECO:0000269|PubMed:15241418"
FT MOD_RES 179
FT /note="Phosphothreonine; by CDK2, CDK4 and MAPK"
FT /evidence="ECO:0000269|PubMed:15241418,
FT ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:19218245"
FT MOD_RES 204
FT /note="Phosphoserine; by GSK3 and MAPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:16156666,
FT ECO:0000269|PubMed:19218245"
FT MOD_RES 208
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:16156666,
FT ECO:0000269|PubMed:19218245"
FT MOD_RES 213
FT /note="Phosphoserine; by CDK2 and CDK4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:15241418"
FT MOD_RES 378
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:16862174"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 418
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439,
FT ECO:0000269|PubMed:18794808"
FT MOD_RES 422
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000250|UniProtKB:Q8BUN5,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 423
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000250|UniProtKB:Q8BUN5,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 425
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000250|UniProtKB:Q8BUN5,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT CROSSLNK 33
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:21947082"
FT CROSSLNK 81
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:21947082"
FT VAR_SEQ 1..195
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045348"
FT VAR_SEQ 1..105
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043793"
FT VAR_SEQ 1..68
FT /note="MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELE
FT KAITTQNVNTKCITIP -> MSCLHPRQTWKGAALVHRKAWWMG (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042900"
FT VARIANT 112
FT /note="A -> V (in LDS3; dbSNP:rs387906854)"
FT /evidence="ECO:0000269|PubMed:21778426"
FT /id="VAR_067051"
FT VARIANT 170
FT /note="I -> V (in dbSNP:rs35874463)"
FT /id="VAR_052021"
FT VARIANT 239
FT /note="E -> K (in LDS3; dbSNP:rs387906853)"
FT /evidence="ECO:0000269|PubMed:21778426"
FT /id="VAR_067047"
FT VARIANT 261
FT /note="T -> I (in LDS3; dbSNP:rs387906851)"
FT /evidence="ECO:0000269|PubMed:21217753"
FT /id="VAR_065578"
FT VARIANT 279
FT /note="R -> K (in LDS3; dbSNP:rs387906852)"
FT /evidence="ECO:0000269|PubMed:21778426"
FT /id="VAR_067048"
FT VARIANT 287
FT /note="R -> W (in LDS3; dbSNP:rs387906850)"
FT /evidence="ECO:0000269|PubMed:21217753"
FT /id="VAR_065579"
FT VARIANT 393
FT /note="P -> L (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036474"
FT MUTAGEN 8
FT /note="T->V: Reduced phosphorylation, increased
FT transcriptional and antiproliferative activities. Further
FT increase in transcriptional and antiproliferative
FT activities; when associated with V-179 and A-213."
FT /evidence="ECO:0000269|PubMed:15241418"
FT MUTAGEN 33
FT /note="K->R: Slightly decreased monoubiquitination."
FT /evidence="ECO:0000269|PubMed:21947082"
FT MUTAGEN 40
FT /note="K->A: Little effect on interaction with DNA or JUN.
FT Abolishes interaction with DNA and JUN; when associated
FT with A-41; A-43 and A-44."
FT /evidence="ECO:0000269|PubMed:10995748"
FT MUTAGEN 41
FT /note="K->A: Greatly reduced interaction with DNA and JUN.
FT Abolishes interaction with DNA and JUN; when associated
FT with A-40; A-44 and A-43."
FT /evidence="ECO:0000269|PubMed:10995748"
FT MUTAGEN 43
FT /note="K->A: Little effect on interaction with DNA or JUN.
FT Abolishes interaction with DNA and JUN; when associated
FT with A-40; A-41 and A-44."
FT /evidence="ECO:0000269|PubMed:10995748"
FT MUTAGEN 44
FT /note="K->A: Little effect on interaction with DNA or JUN.
FT Abolishes interaction with JUN; when associated with A-40;
FT A-41 and A-43."
FT /evidence="ECO:0000269|PubMed:10995748"
FT MUTAGEN 53
FT /note="K->R: Slightly decreased monoubiquitination."
FT /evidence="ECO:0000269|PubMed:21947082"
FT MUTAGEN 74
FT /note="R->D: Reduced interaction with JUN. Loss of
FT transcriptional activity and cooperation with JUN."
FT /evidence="ECO:0000269|PubMed:10995748"
FT MUTAGEN 81
FT /note="K->R: Decreased monoubiquitination."
FT /evidence="ECO:0000269|PubMed:21947082"
FT MUTAGEN 179
FT /note="T->V: Reduced phosphorylation, increased
FT transcriptional and increased antiproliferative activities.
FT Further increase in transcriptional and antiproliferative
FT activities; when associated with V-8 and A-213."
FT /evidence="ECO:0000269|PubMed:15241418,
FT ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:19218245"
FT MUTAGEN 204
FT /note="S->A: Increased transcriptional activity. Further
FT increased transcriptional activity; when associated with S-
FT 208."
FT /evidence="ECO:0000269|PubMed:15241418,
FT ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:19218245"
FT MUTAGEN 208
FT /note="S->A: Increased transcriptional activity. Further
FT increased transcriptional activity; when associated with S-
FT 208."
FT /evidence="ECO:0000269|PubMed:15241418,
FT ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:19218245"
FT MUTAGEN 213
FT /note="S->A: Reduced phosphorylation. Increased
FT transcriptional and antiproliferative activities. Further
FT increase in transcriptional and antiproliferative
FT activities; when associated with V-8 and V-179."
FT /evidence="ECO:0000269|PubMed:15241418"
FT MUTAGEN 333
FT /note="K->R: No effect on acetylation. Completely abolishes
FT acetylation and 97% reduction in transcriptional activity;
FT when associated with R-341; R-378 and R-409."
FT /evidence="ECO:0000269|PubMed:16862174"
FT MUTAGEN 341
FT /note="K->R: No effect on acetylation. Completely abolishes
FT acetylation and 97% reduction in transcriptional activity;
FT when associated with R-333; R-378 and R-409."
FT /evidence="ECO:0000269|PubMed:16862174"
FT MUTAGEN 378
FT /note="K->Q: Increased transcriptional activity. No further
FT increase in transcriptional activity with EP300."
FT /evidence="ECO:0000269|PubMed:16862174"
FT MUTAGEN 378
FT /note="K->R: Greatly reduced acetylation and 85% reduction
FT in transcriptional activity. Completely abolishes
FT acetylation and 97% reduction in transcriptional activity;
FT when associated with R-333; R-341 and R-409."
FT /evidence="ECO:0000269|PubMed:16862174"
FT MUTAGEN 409
FT /note="K->R: No effect on acetylation. Completely abolishes
FT acetylation and 97% reduction in transcriptional activity;
FT when associated with R-333; R-341 and R-378."
FT /evidence="ECO:0000269|PubMed:16862174"
FT MUTAGEN 418
FT /note="S->A: Increased constitutive activity."
FT /evidence="ECO:0000269|PubMed:18794808"
FT MUTAGEN 418
FT /note="S->D: Decreased activity."
FT /evidence="ECO:0000269|PubMed:18794808"
FT MUTAGEN 422..425
FT /note="SSVS->AAVA: Does not abolish protein nuclear export.
FT Abolishes almost completely acetylation."
FT /evidence="ECO:0000269|PubMed:11224571,
FT ECO:0000269|PubMed:16449645, ECO:0000269|PubMed:16862174"
FT MUTAGEN 422..425
FT /note="SSVS->EEVE: Forms heterotrimers."
FT /evidence="ECO:0000269|PubMed:11224571,
FT ECO:0000269|PubMed:16449645, ECO:0000269|PubMed:16862174"
FT MUTAGEN 422..425
FT /note="SSVS->RRVR: Diminishes cargo protein export."
FT /evidence="ECO:0000269|PubMed:11224571,
FT ECO:0000269|PubMed:16449645, ECO:0000269|PubMed:16862174"
FT CONFLICT 178
FT /note="E -> EVGTWAAQAGL (in Ref. 3; BAA22032)"
FT /evidence="ECO:0000305"
FT CONFLICT 360
FT /note="F -> L (in Ref. 5; BAH13315)"
FT /evidence="ECO:0000305"
FT HELIX 11..17
FT /evidence="ECO:0007829|PDB:5OD6"
FT HELIX 25..44
FT /evidence="ECO:0007829|PDB:5OD6"
FT HELIX 48..57
FT /evidence="ECO:0007829|PDB:5OD6"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:5OD6"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5OD6"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:6ZMN"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:5OD6"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:5OD6"
FT HELIX 84..92
FT /evidence="ECO:0007829|PDB:5OD6"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:5OD6"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:5OD6"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:5OD6"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:5OD6"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:5OD6"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:5OD6"
FT STRAND 221..225
FT /evidence="ECO:0007829|PDB:1MK2"
FT STRAND 231..239
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 242..250
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 252..258
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:1MJS"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:1U7F"
FT HELIX 281..290
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 302..307
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:1MJS"
FT HELIX 318..321
FT /evidence="ECO:0007829|PDB:1MJS"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:1MK2"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 339..343
FT /evidence="ECO:0007829|PDB:1MJS"
FT HELIX 345..358
FT /evidence="ECO:0007829|PDB:1MJS"
FT HELIX 360..364
FT /evidence="ECO:0007829|PDB:1MJS"
FT HELIX 365..370
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 371..377
FT /evidence="ECO:0007829|PDB:1MJS"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:1MK2"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:5XOC"
FT STRAND 392..400
FT /evidence="ECO:0007829|PDB:1MJS"
FT HELIX 401..413
FT /evidence="ECO:0007829|PDB:1MJS"
SQ SEQUENCE 425 AA; 48081 MW; 46DF5E8B371321AC CRC64;
MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE LEKAITTQNV
NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELRAMELCE FAFNMKKDEV
CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF PPLDDYSHSI PENTNFPAGI EPQSNIPETP
PPGYLSEDGE TSDHQMNHSM DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL
NQRVGETFHA SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA LLAQSVNQGF
EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL NGPLQWLDKV LTQMGSPSIR
CSSVS
//