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   17-JUN-2020, entry version 189.
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   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   [25]
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   [26]
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   [27]
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   [28]
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   [29]
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   [30]
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   [31]
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   [32]
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   [33]
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   [34]
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   [35]
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   [36]
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   [37]
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   [38]
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   [39]
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   [40]
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   [41]
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   [42]
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   [43]
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   [44]
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   [45]
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   [46]
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   [47]
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   [48]
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   [49]
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   [50]
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   [51]
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   [52]
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   [53]
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   [54]
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   [55]
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   [56]
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   [57]
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   [58]
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   [59]
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   [60]
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   [61]
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   [62]
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   [63]
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   [64]
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   [65]
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   [66]
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   [67]
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. Homooligomer; in the
CC       presence of TGF-beta. Heterotrimer; forms a heterotrimer in the
CC       presence of TGF-beta consisting of two molecules of C-terminally
CC       phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the
CC       transcriptionally active SMAD2/SMAD3-SMAD4 complex. Interacts with
CC       TGFBR1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3.
CC       Interacts with AIP1, TGFB1I1, TTRAP, FOXL2, PML, PRDM16, HGS, WWP1 and
CC       SNW1. Interacts (via MH2 domain) with CITED2 (via C-terminus).
CC       Interacts with NEDD4L; the interaction requires TGF-beta stimulation.
CC       Interacts (via MH2 domain) with ZFYVE9. Interacts with HDAC1, TGIF and
CC       TGIF2, RUNX3, CREBBP, SKOR1, SKOR2, SNON, ATF2, SMURF2 and TGFB1I1.
CC       Interacts with DACH1; the interaction inhibits the TGF-beta signaling.
CC       Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta. Found
CC       in a complex with SMAD3, RAN and XPO4. Interacts in the complex
CC       directly with XPO4. 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. Interacts with RBPMS. Interacts (via MH2 domain) with
CC       MECOM. Interacts with WWTR1 (via its coiled-coil domain). Interacts
CC       (via the linker region) with EP300 (C-terminal); the interaction
CC       promotes SMAD3 acetylation and is enhanced by TGF-beta phosphorylation
CC       in the C-terminal of SMAD3. This interaction can be blocked by
CC       competitive binding of adenovirus oncoprotein E1A to the same C-
CC       terminal site on EP300, which then results in partially inhibited
CC       SMAD3/SMAD4 transcriptional activity. Interacts with SKI; the
CC       interaction represses SMAD3 transcriptional activity. 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. Interacts (via an N-terminal domain) with JUN (via its basic
CC       DNA binding and leucine zipper domains); this interaction is essential
CC       for DNA binding and cooperative transcriptional activity in response to
CC       TGF-beta. Interacts with PPM1A; the interaction dephosphorylates SMAD3
CC       in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4
CC       complex, nuclear export and termination of TGF-beta signaling.
CC       Interacts (dephosphorylated form via the MH1 and MH2 domains) with
CC       RANBP3 (via its C-terminal R domain); the interaction results in the
CC       export of dephosphorylated SMAD3 out of the nucleus and termination of
CC       the TGF-beta signaling. Interacts with MEN1. Interacts with IL1F7.
CC       Interaction with CSNK1G2. Interacts with PDPK1 (via PH domain).
CC       Interacts with DAB2; the interactions are enhanced upon TGF-beta
CC       stimulation. Interacts with USP15. Interacts with PPP5C; the
CC       interaction decreases SMAD3 phosphorylation and protein levels.
CC       Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts with
CC       PMEPA1. Interacts with ZC3H3 (By similarity). Interacts with ZNF451
CC       (PubMed:24324267). Identified in a complex that contains at least
CC       ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts with ZFHX3.
CC       Interacts weakly with ZNF8 (PubMed:12370310). 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 (By similarity). Interacts with STUB1, HSPA1A,
CC       HSPA1B, HSP90AA1 and HSP90AB1 (PubMed:24613385). Interacts (via MH2
CC       domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling
CC       pathway increases the activity of the SMAD3/SMAD4 transcriptional
CC       complex (PubMed:16777850). {ECO:0000250|UniProtKB:Q8BUN5,
CC       ECO:0000269|PubMed:10995748, ECO:0000269|PubMed:11224571,
CC       ECO:0000269|PubMed:11274402, ECO:0000269|PubMed:11278756,
CC       ECO:0000269|PubMed:11387212, ECO:0000269|PubMed:11427533,
CC       ECO:0000269|PubMed:12154125, ECO:0000269|PubMed:12370310,
CC       ECO:0000269|PubMed:12686552, ECO:0000269|PubMed:14525983,
CC       ECO:0000269|PubMed:15350224, ECO:0000269|PubMed:15561701,
CC       ECO:0000269|PubMed:15588252, ECO:0000269|PubMed:15601644,
CC       ECO:0000269|PubMed:15647271, ECO:0000269|PubMed:15799969,
CC       ECO:0000269|PubMed:15897867, ECO:0000269|PubMed:16200078,
CC       ECO:0000269|PubMed:16449645, ECO:0000269|PubMed:16751101,
CC       ECO:0000269|PubMed:16751102, ECO:0000269|PubMed:16777850,
CC       ECO:0000269|PubMed:17099224, ECO:0000269|PubMed:17292623,
CC       ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:18568018,
CC       ECO:0000269|PubMed:18794808, ECO:0000269|PubMed:19049980,
CC       ECO:0000269|PubMed:19289081, 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:9311995,
CC       ECO:0000269|PubMed:9665135, ECO:0000269|PubMed:9670020,
CC       ECO:0000269|PubMed:9732876, ECO:0000269|PubMed:9843571,
CC       ECO:0000269|PubMed:9865696, ECO:0000269|PubMed:9892009}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with SARS-CoV nucleoprotein.
CC       {ECO:0000269|PubMed:18055455}.
CC   -!- INTERACTION:
CC       P84022; Q9H2G9: BLZF1; NbExp=9; IntAct=EBI-347161, EBI-2548012;
CC       P84022; E9PSE9: CCDC198; NbExp=3; IntAct=EBI-347161, EBI-11748295;
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; 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; Q99814: EPAS1; NbExp=2; IntAct=EBI-347161, EBI-447470;
CC       P84022; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-347161, EBI-6658203;
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; 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; Q9BZL4: PPP1R12C; NbExp=2; IntAct=EBI-347161, EBI-721802;
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=2; IntAct=EBI-347161, EBI-1040141;
CC       P84022; P84022: SMAD3; NbExp=3; IntAct=EBI-347161, EBI-347161;
CC       P84022; Q13485: SMAD4; NbExp=33; 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; 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=5; 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:22781750}. Nucleus
CC       {ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15799969,
CC       ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101,
CC       ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081,
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). Through the action of the
CC       phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported
CC       out of the nucleus by interaction with RANBP1 (PubMed:16751101,
CC       PubMed:19289081). Co-localizes with LEMD3 at the nucleus inner membrane
CC       (PubMed:15601644). MAPK-mediated phosphorylation appears to have no
CC       effect on nuclear import (PubMed:19218245). PDPK1 prevents its nuclear
CC       translocation in response to TGF-beta (PubMed:17327236).
CC       {ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15799969,
CC       ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:17327236,
CC       ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081}.
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 mutations affecting the gene represented in this
CC       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       mental retardation. {ECO:0000269|PubMed:21217753,
CC       ECO:0000269|PubMed:21778426}. Note=The disease is caused by mutations
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}.
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   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   SMR; P84022; -.
DR   BioGRID; 110263; 362.
DR   ComplexPortal; CPX-1; SMAD2-SMAD3-SMAD4 complex.
DR   ComplexPortal; CPX-12; SMAD3 homotrimer.
DR   ComplexPortal; CPX-3252; SMAD3-SMAD4 complex.
DR   CORUM; P84022; -.
DR   DIP; DIP-29720N; -.
DR   IntAct; P84022; 195.
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   EPD; P84022; -.
DR   jPOST; P84022; -.
DR   MassIVE; P84022; -.
DR   MaxQB; P84022; -.
DR   PaxDb; P84022; -.
DR   PeptideAtlas; P84022; -.
DR   PRIDE; P84022; -.
DR   ProteomicsDB; 26192; -.
DR   ProteomicsDB; 57743; -. [P84022-1]
DR   ProteomicsDB; 57744; -. [P84022-2]
DR   ProteomicsDB; 57745; -. [P84022-3]
DR   Antibodypedia; 26224; 2214 antibodies.
DR   DNASU; 4088; -.
DR   Ensembl; ENST00000327367; ENSP00000332973; ENSG00000166949. [P84022-1]
DR   Ensembl; ENST00000439724; ENSP00000401133; ENSG00000166949. [P84022-2]
DR   Ensembl; ENST00000537194; ENSP00000445348; ENSG00000166949. [P84022-4]
DR   Ensembl; ENST00000540846; ENSP00000437757; ENSG00000166949. [P84022-3]
DR   GeneID; 4088; -.
DR   KEGG; hsa:4088; -.
DR   UCSC; uc002aqj.4; human. [P84022-1]
DR   CTD; 4088; -.
DR   DisGeNET; 4088; -.
DR   EuPathDB; HostDB:ENSG00000166949.15; -.
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   PharmGKB; PA30526; -.
DR   eggNOG; KOG3701; Eukaryota.
DR   eggNOG; ENOG410XQKU; LUCA.
DR   GeneTree; ENSGT00940000153499; -.
DR   HOGENOM; CLU_026736_0_0_1; -.
DR   InParanoid; P84022; -.
DR   KO; K23605; -.
DR   OMA; NPVSPAH; -.
DR   PhylomeDB; P84022; -.
DR   TreeFam; TF314923; -.
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   SignaLink; P84022; -.
DR   SIGNOR; P84022; -.
DR   BioGRID-ORCS; 4088; 3 hits in 811 CRISPR screens.
DR   ChiTaRS; SMAD3; human.
DR   EvolutionaryTrace; P84022; -.
DR   GeneWiki; Mothers_against_decapentaplegic_homolog_3; -.
DR   GenomeRNAi; 4088; -.
DR   Pharos; P84022; Tbio.
DR   PRO; PR:P84022; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; P84022; protein.
DR   Bgee; ENSG00000166949; Expressed in amniotic fluid and 228 other tissues.
DR   ExpressionAtlas; P84022; baseline and differential.
DR   Genevisible; P84022; HS.
DR   GO; GO:0005623; C:cell; IEA:GOC.
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:0000790; C:nuclear chromatin; 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 factor 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:0035326; F:cis-regulatory region binding; IC:BHF-UCL.
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:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP: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:0035259; F:glucocorticoid receptor binding; IPI:CAFA.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0031962; F:mineralocorticoid receptor binding; IPI:CAFA.
DR   GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR   GO; GO:0070878; F:primary miRNA binding; IPI:BHF-UCL.
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:0001102; F:RNA polymerase II activating transcription factor binding; IPI:BHF-UCL.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
DR   GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR   GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB.
DR   GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL.
DR   GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
DR   GO; GO:0005160; F:transforming growth factor beta receptor binding; IPI:BHF-UCL.
DR   GO; GO:0030618; F:transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity; IDA: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:0097296; P:activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IEA:Ensembl.
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:0007050; P:cell cycle arrest; IMP:BHF-UCL.
DR   GO; GO:0045216; P:cell-cell junction organization; IMP:BHF-UCL.
DR   GO; GO:0071345; P:cellular response to cytokine stimulus; TAS:Reactome.
DR   GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:CAFA.
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: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: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: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:0045930; P:negative regulation of mitotic cell cycle; 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:BHF-UCL.
DR   GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
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:0010694; P:positive regulation of alkaline phosphatase activity; 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: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: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:1902895; P:positive regulation of pri-miRNA transcription by RNA polymerase II; IMP:BHF-UCL.
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:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
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:0016579; P:protein deubiquitination; TAS:Reactome.
DR   GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR   GO; GO:0051098; P:regulation of binding; IEA:Ensembl.
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: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; IMP:BHF-UCL.
DR   GO; GO:0032909; P:regulation of transforming growth factor beta2 production; 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:0007183; P:SMAD protein complex assembly; IDA:BHF-UCL.
DR   GO; GO:0060395; P:SMAD protein signal transduction; NAS: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   DisProt; DP01648; -.
DR   Gene3D; 2.60.200.10; -; 1.
DR   Gene3D; 3.90.520.10; -; 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; PTHR13703; 1.
DR   Pfam; PF03165; MH1; 1.
DR   Pfam; PF03166; MH2; 1.
DR   SMART; SM00523; DWA; 1.
DR   SMART; SM00524; DWB; 1.
DR   SUPFAM; SSF49879; SSF49879; 1.
DR   SUPFAM; SSF56366; SSF56366; 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 mutation; DNA-binding;
KW   Host-virus interaction; Isopeptide bond; Metal-binding; Nucleus;
KW   Phosphoprotein; Polymorphism; Reference proteome; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000244|PubMed:19413330,
FT                   ECO:0000244|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          271..324
FT                   /note="Sufficient for interaction with XPO4"
FT                   /evidence="ECO:0000269|PubMed:16449645"
FT   METAL           64
FT                   /note="Zinc"
FT   METAL           109
FT                   /note="Zinc"
FT   METAL           121
FT                   /note="Zinc"
FT   METAL           126
FT                   /note="Zinc"
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:0000244|PubMed:19413330,
FT                   ECO:0000244|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:0000244|PubMed:18669648,
FT                   ECO:0000244|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:0000244|PDB:5OD6"
FT   HELIX           25..44
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   HELIX           48..57
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   STRAND          60..62
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   STRAND          66..68
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   STRAND          75..77
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   STRAND          80..82
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   HELIX           84..92
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   HELIX           100..102
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   STRAND          103..105
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   HELIX           113..115
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   STRAND          118..121
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   HELIX           124..126
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   STRAND          127..129
FT                   /evidence="ECO:0000244|PDB:5OD6"
FT   STRAND          221..225
FT                   /evidence="ECO:0000244|PDB:1MK2"
FT   STRAND          231..239
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          242..250
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          252..258
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          268..270
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   HELIX           271..273
FT                   /evidence="ECO:0000244|PDB:1U7F"
FT   HELIX           281..290
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          294..299
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          302..307
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          309..311
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          313..316
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   HELIX           318..321
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   HELIX           323..325
FT                   /evidence="ECO:0000244|PDB:1MK2"
FT   STRAND          332..334
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          339..343
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   HELIX           345..358
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   HELIX           360..364
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   HELIX           365..370
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          371..377
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   STRAND          384..386
FT                   /evidence="ECO:0000244|PDB:1MK2"
FT   HELIX           389..391
FT                   /evidence="ECO:0000244|PDB:5XOC"
FT   STRAND          392..400
FT                   /evidence="ECO:0000244|PDB:1MJS"
FT   HELIX           401..413
FT                   /evidence="ECO:0000244|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
//