Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (hMAD-3) (JV15-2) (SMAD family member 3) (SMAD 3) (Smad3) (hSMAD3)

 SMAD3_HUMAN             Reviewed;         425 AA.
P84022; A8K4B6; B7Z4Z5; B7Z6M9; B7Z9Q2; F5H383; O09064; O09144;
O14510; O35273; Q92940; Q93002; Q9GKR4;
05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
05-JUL-2004, sequence version 1.
27-SEP-2017, entry version 164.
RecName: Full=Mothers against decapentaplegic homolog 3;
Short=MAD homolog 3;
Short=Mad3;
Short=Mothers against DPP homolog 3;
Short=hMAD-3;
AltName: Full=JV15-2;
AltName: Full=SMAD family member 3;
Short=SMAD 3;
Short=Smad3;
Short=hSMAD3;
Name=SMAD3; Synonyms=MADH3;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PHOSPHORYLATION.
TISSUE=Placenta;
PubMed=8774881; DOI=10.1038/383168a0;
Zhang Y., Feng X.-H., Wu R.-Y., Derynck R.;
"Receptor-associated Mad homologues synergize as effectors of the TGF-
beta response.";
Nature 383:168-172(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
PubMed=8673135; DOI=10.1038/ng0796-347;
Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L.,
Kern S.E., Hamilton S.R., Willson J.K.V., Markowitz S.D.,
Kinzler K.W., Vogelstein B.V.;
"Mad-related genes in the human.";
Nat. Genet. 13:347-349(1996).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Colon carcinoma;
PubMed=9464505; DOI=10.1016/S0304-3835(97)00384-4;
Arai T., Akiyama Y., Okabe S., Ando M., Endo M., Yuasa Y.;
"Genomic structure of the human Smad3 gene and its infrequent
alterations in colorectal cancers.";
Cancer Lett. 122:157-163(1998).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Hagiwara K., Yang K., McMenamin M.G., Freeman A.H., Bennett W.P.,
Nagashima M., Minter A.R., Miyazono K., Takenoshita S., Harris C.C.;
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4).
TISSUE=Brain;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16572171; DOI=10.1038/nature04601;
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
Nusbaum C.;
"Analysis of the DNA sequence and duplication history of human
chromosome 15.";
Nature 440:671-675(2006).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Pancreas;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[9]
INTERACTION WITH TGFBR1.
PubMed=9311995; DOI=10.1093/emboj/16.17.5353;
Nakao A., Imamura T., Souchelnytskyi S., Kawabata M., Ishisaki A.,
Oeda E., Tamaki K., Hanai J., Heldin C.H., Miyazono K., ten Dijke P.;
"TGF-beta receptor-mediated signalling through Smad2, Smad3 and
Smad4.";
EMBO J. 16:5353-5362(1997).
[10]
INTERACTION WITH ZFYVE9.
PubMed=9865696; DOI=10.1016/S0092-8674(00)81701-8;
Tsukazaki T., Chiang T.A., Davison A.F., Attisano L., Wrana J.L.;
"SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta
receptor.";
Cell 95:779-791(1998).
[11]
SUBUNIT.
PubMed=9670020; DOI=10.1093/emboj/17.14.4056;
Kawabata M., Inoue H., Hanyu A., Imamura T., Miyazono K.;
"Smad proteins exist as monomers in vivo and undergo homo- and hetero-
oligomerization upon activation by serine/threonine kinase
receptors.";
EMBO J. 17:4056-4065(1998).
[12]
PHOSPHORYLATION, AND INTERACTION WITH EP300.
PubMed=9843571; DOI=10.1091/mbc.9.12.3309;
Shen X., Hu P.P., Liberati N.T., Datto M.B., Frederick J.P.,
Wang X.F.;
"TGF-beta-induced phosphorylation of Smad3 regulates its interaction
with coactivator p300/CREB-binding protein.";
Mol. Biol. Cell 9:3309-3319(1998).
[13]
INTERACTION WITH MECOM.
PubMed=9665135; DOI=10.1038/27945;
Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S.,
Yazaki Y., Matsumoto K., Hirai H.;
"The oncoprotein Evi-1 represses TGF-beta signalling by inhibiting
Smad3.";
Nature 394:92-96(1998).
[14]
IDENTIFICATION AS A COMPONENT OF THE SMAD3/SMAD4/JUN/FOS COMPLEX,
INTERACTION WITH JUN AND FOS, DNA-BINDING, AND FUNCTION.
PubMed=9732876; DOI=10.1038/29814;
Zhang Y., Feng X.H., Derynck R.;
"Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-
induced transcription.";
Nature 394:909-913(1998).
[15]
INTERACTION WITH ACVR1B, AND FUNCTION.
PubMed=9892009; DOI=10.1210/mend.13.1.0218;
Lebrun J.J., Takabe K., Chen Y., Vale W.;
"Roles of pathway-specific and inhibitory Smads in activin receptor
signaling.";
Mol. Endocrinol. 13:15-23(1999).
[16]
INTERACTION WITH JUN IN THE SMAD3/SMAD4/JUN/FOS COMPLEX, DNA-BINDING,
FUNCTION, AND MUTAGENESIS OF LYS-40; LYS-41; LYS-43; LYS-44 AND
ARG-74.
PubMed=10995748; DOI=10.1074/jbc.M004731200;
Qing J., Zhang Y., Derynck R.;
"Structural and functional characterization of the transforming growth
factor-beta -induced Smad3/c-Jun transcriptional cooperativity.";
J. Biol. Chem. 275:38802-38812(2000).
[17]
INTERACTION WITH DAB2.
PubMed=11387212; DOI=10.1093/emboj/20.11.2789;
Hocevar B.A., Smine A., Xu X.X., Howe P.H.;
"The adaptor molecule Disabled-2 links the transforming growth factor
beta receptors to the Smad pathway.";
EMBO J. 20:2789-2801(2001).
[18]
INTERACTION WITH SNW1.
PubMed=11278756; DOI=10.1074/jbc.M010815200;
Leong G.M., Subramaniam N., Figueroa J., Flanagan J.L., Hayman M.J.,
Eisman J.A., Kouzmenko A.P.;
"Ski-interacting protein interacts with Smad proteins to augment
transforming growth factor-beta-dependent transcription.";
J. Biol. Chem. 276:18243-18248(2001).
[19]
INTERACTION WITH TGIF2.
PubMed=11427533; DOI=10.1074/jbc.M103377200;
Melhuish T.A., Gallo C.M., Wotton D.;
"TGIF2 interacts with histone deacetylase 1 and represses
transcription.";
J. Biol. Chem. 276:32109-32114(2001).
[20]
SUBUNIT, PHOSPHORYLATION, AND MUTAGENESIS OF 422-SER--SER-425.
PubMed=11224571; DOI=10.1038/84995;
Chacko B.M., Qin B., Correia J.J., Lam S.S., de Caestecker M.P.,
Lin K.;
"The L3 loop and C-terminal phosphorylation jointly define Smad
protein trimerization.";
Nat. Struct. Biol. 8:248-253(2001).
[21]
INTERACTION WITH MEN1.
PubMed=11274402; DOI=10.1073/pnas.061358098;
Kaji H., Canaff L., Lebrun J.J., Goltzman D., Hendy G.N.;
"Inactivation of menin, a Smad3-interacting protein, blocks
transforming growth factor type beta signaling.";
Proc. Natl. Acad. Sci. U.S.A. 98:3837-3842(2001).
[22]
INTERACTION WITH ZNF8.
PubMed=12370310; DOI=10.1128/MCB.22.21.7633-7644.2002;
Jiao K., Zhou Y., Hogan B.L.M.;
"Identification of mZnf8, a mouse Kruppel-like transcriptional
repressor, as a novel nuclear interaction partner of Smad1.";
Mol. Cell. Biol. 22:7633-7644(2002).
[23]
INTERACTION WITH DACH1.
PubMed=14525983; DOI=10.1074/jbc.M310021200;
Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K.,
Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G.;
"DACH1 inhibits transforming growth factor-beta signaling through
binding Smad4.";
J. Biol. Chem. 278:51673-51684(2003).
[24]
PHOSPHORYLATION AT THR-8; THR-179; SER-204; SER-208 AND SER-213,
FUNCTION, AND MUTAGENESIS OF THR-8; THR-179; SER-204; SER-208 AND
SER-213.
PubMed=15241418; DOI=10.1038/nature02650;
Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.;
"Cyclin-dependent kinases regulate the antiproliferative function of
Smads.";
Nature 430:226-231(2004).
[25]
TRANSCRIPTIONAL ACTIVATION DOMAIN, FUNCTION, PHOSPHORYLATION, SUBUNIT,
AND INTERACTION WITH EP300.
PubMed=15588252; DOI=10.1042/BJ20041820;
Wang G., Long J., Matsuura I., He D., Liu F.;
"The Smad3 linker region contains a transcriptional activation
domain.";
Biochem. J. 386:29-34(2005).
[26]
PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION,
FUNCTION, AND MUTAGENESIS OF THR-179; SER-204 AND SER-208.
PubMed=16156666; DOI=10.1021/bi050560g;
Matsuura I., Wang G., He D., Liu F.;
"Identification and characterization of ERK MAP kinase phosphorylation
sites in Smad3.";
Biochemistry 44:12546-12553(2005).
[27]
SUBCELLULAR LOCATION, AND INTERACTION WITH LEMD3.
PubMed=15601644; DOI=10.1093/hmg/ddi040;
Lin F., Morrison J.M., Wu W., Worman H.J.;
"MAN1, an integral protein of the inner nuclear membrane, binds Smad2
and Smad3 and antagonizes transforming growth factor-beta signaling.";
Hum. Mol. Genet. 14:437-445(2005).
[28]
INTERACTION WITH TGFB1I1.
PubMed=15561701; DOI=10.1074/jbc.M411575200;
Wang H., Song K., Sponseller T.L., Danielpour D.;
"Novel function of androgen receptor-associated protein 55/Hic-5 as a
negative regulator of Smad3 signaling.";
J. Biol. Chem. 280:5154-5162(2005).
[29]
INTERACTION WITH LEMD3.
PubMed=15647271; DOI=10.1074/jbc.M411234200;
Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J.,
Zhou S., Luo K.;
"The integral inner nuclear membrane protein MAN1 physically interacts
with the R-Smad proteins to repress signaling by the transforming
growth factor-{beta} superfamily of cytokines.";
J. Biol. Chem. 280:15992-16001(2005).
[30]
SUBUNIT, AND SUBCELLULAR LOCATION.
PubMed=15799969; DOI=10.1074/jbc.M500362200;
Chen H.B., Rud J.G., Lin K., Xu L.;
"Nuclear targeting of transforming growth factor-beta-activated Smad
complexes.";
J. Biol. Chem. 280:21329-21336(2005).
[31]
INTERACTION WITH SKOR2.
PubMed=16200078; DOI=10.1038/labinvest.3700344;
Arndt S., Poser I., Schubert T., Moser M., Bosserhoff A.-K.;
"Cloning and functional characterization of a new Ski homolog, Fussel-
18, specifically expressed in neuronal tissues.";
Lab. Invest. 85:1330-1341(2005).
[32]
INTERACTION WITH MECOM.
PubMed=15897867; DOI=10.1038/sj.onc.1208754;
Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S.,
Kurokawa M., Hirai H.;
"Oligomerization of Evi-1 regulated by the PR domain contributes to
recruitment of corepressor CtBP.";
Oncogene 24:6165-6173(2005).
[33]
INTERACTION WITH PPM1A, DEPHOSPHORYLATION, FUNCTION, AND SUBCELLULAR
LOCATION.
PubMed=16751101; DOI=10.1016/j.cell.2006.03.044;
Lin X., Duan X., Liang Y.Y., Su Y., Wrighton K.H., Long J., Hu M.,
Davis C.M., Wang J., Brunicardi F.C., Shi Y., Chen Y.G., Meng A.,
Feng X.H.;
"PPM1A functions as a Smad phosphatase to terminate TGFbeta
signaling.";
Cell 125:915-928(2006).
[34]
IDENTIFICATION IN A COMPLEX WITH SMAD2 AND TRIM33, AND INTERACTION
WITH SMAD2 AND TRIM33.
PubMed=16751102; DOI=10.1016/j.cell.2006.03.045;
He W., Dorn D.C., Erdjument-Bromage H., Tempst P., Moore M.A.,
Massague J.;
"Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of
the TGFbeta pathway.";
Cell 125:929-941(2006).
[35]
IDENTIFICATION IN A COMPLEX WITH RAN AND XPO4, INTERACTION WITH XPO4,
AND MUTAGENESIS OF 422-SER--SER-425.
PubMed=16449645; DOI=10.1128/MCB.26.4.1318-1332.2006;
Kurisaki A., Kurisaki K., Kowanetz M., Sugino H., Yoneda Y.,
Heldin C.-H., Moustakas A.;
"The mechanism of nuclear export of Smad3 involves exportin 4 and
Ran.";
Mol. Cell. Biol. 26:1318-1332(2006).
[36]
INTERACTION WITH RBPMS.
PubMed=17099224; DOI=10.1093/nar/gkl914;
Sun Y., Ding L., Zhang H., Han J., Yang X., Yan J., Zhu Y., Li J.,
Song H., Ye Q.;
"Potentiation of Smad-mediated transcriptional activation by the RNA-
binding protein RBPMS.";
Nucleic Acids Res. 34:6314-6326(2006).
[37]
FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION BY PDPK1, AND
INTERACTION WITH PDPK1.
PubMed=17327236; DOI=10.1074/jbc.M609279200;
Seong H.A., Jung H., Kim K.T., Ha H.;
"3-Phosphoinositide-dependent PDK1 negatively regulates transforming
growth factor-beta-induced signaling in a kinase-dependent manner
through physical interaction with Smad proteins.";
J. Biol. Chem. 282:12272-12289(2007).
[38]
INTERACTION WITH SKOR1.
PubMed=17292623; DOI=10.1016/j.mcn.2007.01.002;
Arndt S., Poser I., Moser M., Bosserhoff A.-K.;
"Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP
signaling.";
Mol. Cell. Neurosci. 34:603-611(2007).
[39]
ACETYLATION AT LYS-378, FUNCTION, AND MUTAGENESIS OF LYS-333; LYS-341;
LYS-378; LYS-409 AND 422-SER--SER-425.
PubMed=16862174; DOI=10.1038/sj.onc.1209826;
Inoue Y., Itoh Y., Abe K., Okamoto T., Daitoku H., Fukamizu A.,
Onozaki K., Hayashi H.;
"Smad3 is acetylated by p300/CBP to regulate its transactivation
activity.";
Oncogene 26:500-508(2007).
[40]
INTERACTION WITH WWTR1.
PubMed=18568018; DOI=10.1038/ncb1748;
Varelas X., Sakuma R., Samavarchi-Tehrani P., Peerani R., Rao B.M.,
Dembowy J., Yaffe M.B., Zandstra P.W., Wrana J.L.;
"TAZ controls Smad nucleocytoplasmic shuttling and regulates human
embryonic stem-cell self-renewal.";
Nat. Cell Biol. 10:837-848(2008).
[41]
INTERACTION WITH CSNK1G2, UBIQUITINATION, PHOSPHORYLATION AT SER-418
BY CSNK1G2/CK1, AND MUTAGENESIS OF SER-418.
PubMed=18794808; DOI=10.1038/onc.2008.337;
Guo X., Waddell D.S., Wang W., Wang Z., Liberati N.T., Yong S.,
Liu X., Wang X.-F.;
"Ligand-dependent ubiquitination of Smad3 is regulated by casein
kinase 1 gamma 2, an inhibitor of TGF-beta signaling.";
Oncogene 27:7235-7247(2008).
[42]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[43]
ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19413330; DOI=10.1021/ac9004309;
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
Mohammed S.;
"Lys-N and trypsin cover complementary parts of the phosphoproteome in
a refined SCX-based approach.";
Anal. Chem. 81:4493-4501(2009).
[44]
INTERACTION WITH RANBP3, SUBCELLULAR LOCATION, AND FUNCTION.
PubMed=19289081; DOI=10.1016/j.devcel.2009.01.022;
Dai F., Lin X., Chang C., Feng X.H.;
"Nuclear export of Smad2 and Smad3 by RanBP3 facilitates termination
of TGF-beta signaling.";
Dev. Cell 16:345-357(2009).
[45]
INTERACTION WITH PRDM16; SKI AND HDAC1.
PubMed=19049980; DOI=10.1074/jbc.M808989200;
Takahata M., Inoue Y., Tsuda H., Imoto I., Koinuma D., Hayashi M.,
Ichikura T., Yamori T., Nagasaki K., Yoshida M., Matsuoka M.,
Morishita K., Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K.,
Imamura T.;
"SKI and MEL1 cooperate to inhibit transforming growth factor-beta
signal in gastric cancer cells.";
J. Biol. Chem. 284:3334-3344(2009).
[46]
PHOSPHORYLATION AT THR-179; SER-204 AND SER-208, SUBCELLULAR LOCATION,
FUNCTION, AND MUTAGENESIS OF THR-179; SER-204 AND SER-208.
PubMed=19218245; DOI=10.1074/jbc.M809281200;
Wang G., Matsuura I., He D., Liu F.;
"Transforming growth factor-{beta}-inducible phosphorylation of
Smad3.";
J. Biol. Chem. 284:9663-9673(2009).
[47]
INTERACTION WITH PMEPA1.
PubMed=20129061; DOI=10.1016/j.molcel.2009.10.028;
Watanabe Y., Itoh S., Goto T., Ohnishi E., Inamitsu M., Itoh F.,
Satoh K., Wiercinska E., Yang W., Shi L., Tanaka A., Nakano N.,
Mommaas A.M., Shibuya H., Ten Dijke P., Kato M.;
"TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad
proteins from active participation in TGF-beta signaling.";
Mol. Cell 37:123-134(2010).
[48]
INTERACTION WITH IL1F7.
PubMed=20935647; DOI=10.1038/ni.1944;
Nold M.F., Nold-Petry C.A., Zepp J.A., Palmer B.E., Bufler P.,
Dinarello C.A.;
"IL-37 is a fundamental inhibitor of innate immunity.";
Nat. Immunol. 11:1014-1022(2010).
[49]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[50]
UBIQUITINATION, DEUBIQUITINATION BY USP15, DNA-BINDING, INTERACTION
WITH USP15, UBIQUITINATION AT LYS-33 AND LYS-81, AND MUTAGENESIS OF
LYS-33; LYS-53 AND LYS-81.
PubMed=21947082; DOI=10.1038/ncb2346;
Inui M., Manfrin A., Mamidi A., Martello G., Morsut L., Soligo S.,
Enzo E., Moro S., Polo S., Dupont S., Cordenonsi M., Piccolo S.;
"USP15 is a deubiquitylating enzyme for receptor-activated SMADs.";
Nat. Cell Biol. 13:1368-1375(2011).
[51]
INTERACTION WITH PPP5C, AND SUBCELLULAR LOCATION.
PubMed=22781750; DOI=10.1016/j.cellsig.2012.07.003;
Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.;
"Protein phosphatase 5 modulates SMAD3 function in the transforming
growth factor-beta pathway.";
Cell. Signal. 24:1999-2006(2012).
[52]
ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22814378; DOI=10.1073/pnas.1210303109;
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
Aldabe R.;
"N-terminal acetylome analyses and functional insights of the N-
terminal acetyltransferase NatB.";
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
[53]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[54]
INTERACTION WITH STUB1; HSPA1A; HSPA1B; HSP90AA1 AND HSP90AB1,
UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
PubMed=24613385; DOI=10.1016/j.bbrc.2014.02.124;
Shang Y., Xu X., Duan X., Guo J., Wang Y., Ren F., He D., Chang Z.;
"Hsp70 and Hsp90 oppositely regulate TGF-beta signaling through
CHIP/Stub1.";
Biochem. Biophys. Res. Commun. 446:387-392(2014).
[55]
INTERACTION WITH ZNF451, AND IDENTIFICATION IN A COMPLEX WITH ZNF451;
SMAD2 AND SMAD4.
PubMed=24324267; DOI=10.1074/jbc.M113.526905;
Feng Y., Wu H., Xu Y., Zhang Z., Liu T., Lin X., Feng X.H.;
"Zinc finger protein 451 is a novel Smad corepressor in transforming
growth factor-beta signaling.";
J. Biol. Chem. 289:2072-2083(2014).
[56]
INTERACTION WITH LDLRAD4.
PubMed=24627487; DOI=10.1074/jbc.M114.558981;
Nakano N., Maeyama K., Sakata N., Itoh F., Akatsu R., Nakata M.,
Katsu Y., Ikeno S., Togawa Y., Vo Nguyen T.T., Watanabe Y., Kato M.,
Itoh S.;
"C18 ORF1, a novel negative regulator of transforming growth factor-
beta signaling.";
J. Biol. Chem. 289:12680-12692(2014).
[57]
INTERACTION WITH ZFHX3.
PubMed=25105025; DOI=10.1155/2014/970346;
Sakata N., Kaneko S., Ikeno S., Miura Y., Nakabayashi H., Dong X.Y.,
Dong J.T., Tamaoki T., Nakano N., Itoh S.;
"TGF-beta signaling cooperates with AT motif-binding factor-1 for
repression of the alpha -fetoprotein promoter.";
J. Signal Transduct. 2014:970346-970346(2014).
[58]
ADP-RIBOSYLATION.
PubMed=25133494; DOI=10.1371/journal.pone.0103651;
Dahl M., Maturi V., Lonn P., Papoutsoglou P., Zieba A.,
Vanlandewijck M., van der Heide L.P., Watanabe Y., Soderberg O.,
Hottiger M.O., Heldin C.H., Moustakas A.;
"Fine-tuning of Smad protein function by poly(ADP-ribose) polymerases
and poly(ADP-ribose) glycohydrolase during transforming growth factor
beta Signaling.";
PLoS ONE 9:E103651-E103651(2014).
[59]
X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-144.
PubMed=9741623; DOI=10.1016/S0092-8674(00)81600-1;
Shi Y., Wang Y.-F., Jayaraman L., Yang H., Massague J.,
Pavletich N.P.;
"Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA
binding in TGF-beta signaling.";
Cell 94:585-594(1998).
[60]
X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 220-425 IN COMPLEX WITH
ZFYVE9.
PubMed=12154125; DOI=10.1101/gad.1002002;
Qin B.Y., Lam S.S., Correia J.J., Lin K.;
"Smad3 allostery links TGF-beta receptor kinase activation to
transcriptional control.";
Genes Dev. 16:1950-1963(2002).
[61]
X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-144 IN COMPLEX WITH DNA,
AND ZINC.
PubMed=12686552; DOI=10.1074/jbc.C300134200;
Chai J., Wu J.W., Yan N., Massague J., Pavletich N.P., Shi Y.;
"Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA
binding.";
J. Biol. Chem. 278:20327-20331(2003).
[62]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 228-424 IN COMPLEX WITH
SMAD4, AND SUBUNIT.
PubMed=15350224; DOI=10.1016/j.molcel.2004.07.016;
Chacko B.M., Qin B.Y., Tiwari A., Shi G., Lam S., Hayward L.J.,
De Caestecker M., Lin K.;
"Structural basis of heteromeric smad protein assembly in TGF-beta
signaling.";
Mol. Cell 15:813-823(2004).
[63]
VARIANT [LARGE SCALE ANALYSIS] LEU-393, AND INVOLVEMENT IN COLORECTAL
CANCER.
PubMed=16959974; DOI=10.1126/science.1133427;
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal
cancers.";
Science 314:268-274(2006).
[64]
VARIANTS LDS3 VAL-112; LYS-239 AND LYS-279.
PubMed=21778426; DOI=10.1161/CIRCRESAHA.111.248161;
Regalado E.S., Guo D.C., Villamizar C., Avidan N., Gilchrist D.,
McGillivray B., Clarke L., Bernier F., Santos-Cortez R.L., Leal S.M.,
Bertoli-Avella A.M., Shendure J., Rieder M.J., Nickerson D.A.,
Milewicz D.M.;
"Exome sequencing identifies SMAD3 mutations as a cause of familial
thoracic aortic aneurysm and dissection with intracranial and other
arterial aneurysms.";
Circ. Res. 109:680-686(2011).
[65]
VARIANTS LDS3 ILE-261 AND TRP-287.
PubMed=21217753; DOI=10.1038/ng.744;
van de Laar I.M., Oldenburg R.A., Pals G., Roos-Hesselink J.W.,
de Graaf B.M., Verhagen J.M., Hoedemaekers Y.M., Willemsen R.,
Severijnen L.A., Venselaar H., Vriend G., Pattynama P.M., Collee M.,
Majoor-Krakauer D., Poldermans D., Frohn-Mulder I.M., Micha D.,
Timmermans J., Hilhorst-Hofstee Y., Bierma-Zeinstra S.M.,
Willems P.J., Kros J.M., Oei E.H., Oostra B.A., Wessels M.W.,
Bertoli-Avella A.M.;
"Mutations in SMAD3 cause a syndromic form of aortic aneurysms and
dissections with early-onset osteoarthritis.";
Nat. Genet. 43:121-126(2011).
-!- FUNCTION: Receptor-regulated SMAD (R-SMAD) that is an
intracellular signal transducer and transcriptional modulator
activated by TGF-beta (transforming growth factor) and activin
type 1 receptor kinases. Binds the TRE element in the promoter
region of many genes that are regulated by TGF-beta and, on
formation of the SMAD3/SMAD4 complex, activates transcription.
Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site
to regulate TGF-beta-mediated transcription. Has an inhibitory
effect on wound healing probably by modulating both growth and
migration of primary keratinocytes and by altering the TGF-
mediated chemotaxis of monocytes. This effect on wound healing
appears to be hormone-sensitive. Regulator of chondrogenesis and
osteogenesis and inhibits early healing of bone fractures.
Positively regulates PDPK1 kinase activity by stimulating its
dissociation from the 14-3-3 protein YWHAQ which acts as a
negative regulator. {ECO:0000269|PubMed:10995748,
ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:15588252,
ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101,
ECO:0000269|PubMed:16862174, ECO:0000269|PubMed:17327236,
ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081,
ECO:0000269|PubMed:9732876, ECO:0000269|PubMed:9892009}.
-!- SUBUNIT: Monomer; in the absence of TGF-beta. Homooligomer; in the
presence of TGF-beta. Heterotrimer; forms a heterotrimer in the
presence of TGF-beta consisting of two molecules of C-terminally
phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the
transcriptionally active SMAD2/SMAD3-SMAD4 complex. Interacts with
TGFBR1. Part of a complex consisting of AIP1, ACVR2A, ACVR1B and
SMAD3. Interacts with AIP1, TGFB1I1, TTRAP, FOXL2, PML, PRDM16,
HGS, WWP1 and SNW1. Interacts (via MH2 domain) with CITED2 (via C-
terminus). Interacts with NEDD4L; the interaction requires TGF-
beta stimulation. Interacts (via the MH2 domain) with ZFYVE9.
Interacts with HDAC1, VDR, TGIF and TGIF2, RUNX3, CREBBP, SKOR1,
SKOR2, SNON, ATF2, SMURF2 and TGFB1I1. Interacts with DACH1; the
interaction inhibits the TGF-beta signaling. Forms a complex with
SMAD2 and TRIM33 upon addition of TGF-beta. Found in a complex
with SMAD3, RAN and XPO4. Interacts in the complex directly with
XPO4. Interacts (via the MH2 domain) with LEMD3; the interaction
represses SMAD3 transcriptional activity through preventing the
formation of the heteromeric complex with SMAD4 and translocation
to the nucleus. Interacts with RBPMS. Interacts (via MH2 domain)
with MECOM. Interacts with WWTR1 (via its coiled-coil domain).
Interacts (via the linker region) with EP300 (C-terminal); the
interaction promotes SMAD3 acetylation and is enhanced by TGF-beta
phosphorylation in the C-terminal of SMAD3. This interaction can
be blocked by competitive binding of adenovirus oncoprotein E1A to
the same C-terminal site on EP300, which then results in partially
inhibited SMAD3/SMAD4 transcriptional activity. Interacts with
SKI; the interaction represses SMAD3 transcriptional activity.
Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which
forms at the AP1 promoter site; required for synergistic
transcriptional activity in response to TGF-beta. Interacts (via
an N-terminal domain) with JUN (via its basic DNA binding and
leucine zipper domains); this interaction is essential for DNA
binding and cooperative transcriptional activity in response to
TGF-beta. Interacts with PPM1A; the interaction dephosphorylates
SMAD3 in the C-terminal SXS motif leading to disruption of the
SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta
signaling. Interacts (dephosphorylated form via the MH1 and MH2
domains) with RANBP3 (via its C-terminal R domain); the
interaction results in the export of dephosphorylated SMAD3 out of
the nucleus and termination of the TGF-beta signaling. Interacts
with MEN1. Interacts with IL1F7. Interaction with CSNK1G2.
Interacts with PDPK1 (via PH domain). Interacts with DAB2; the
interactions are enhanced upon TGF-beta stimulation. Interacts
with USP15. Interacts with PPP5C; the interaction decreases SMAD3
phosphorylation and protein levels. Interacts with LDLRAD4 (via
the SMAD interaction motif). Interacts with PMEPA1. Interacts with
ZC3H3 (By similarity). Interacts with ZNF451 (PubMed:24324267).
Identified in a complex that contains at least ZNF451, SMAD2,
SMAD3 and SMAD4 (PubMed:24324267). Interacts with ZFHX3. Interacts
weakly with ZNF8 (PubMed:12370310). Interacts (when
phosphorylated) with RNF111; RNF111 acts as an enhancer of the
transcriptional responses by mediating ubiquitination and
degradation of SMAD3 inhibitors (By similarity). Interacts with
STUB1, HSPA1A, HSPA1B, HSP90AA1 and HSP90AB1 (PubMed:24613385).
{ECO:0000250|UniProtKB:Q8BUN5, ECO:0000269|PubMed:10995748,
ECO:0000269|PubMed:11224571, ECO:0000269|PubMed:11274402,
ECO:0000269|PubMed:11278756, ECO:0000269|PubMed:11387212,
ECO:0000269|PubMed:11427533, ECO:0000269|PubMed:12154125,
ECO:0000269|PubMed:12370310, ECO:0000269|PubMed:12686552,
ECO:0000269|PubMed:14525983, ECO:0000269|PubMed:15350224,
ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:15588252,
ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15647271,
ECO:0000269|PubMed:15799969, ECO:0000269|PubMed:15897867,
ECO:0000269|PubMed:16200078, ECO:0000269|PubMed:16449645,
ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:16751102,
ECO:0000269|PubMed:17099224, ECO:0000269|PubMed:17292623,
ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:18568018,
ECO:0000269|PubMed:18794808, ECO:0000269|PubMed:19049980,
ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:20129061,
ECO:0000269|PubMed:20935647, ECO:0000269|PubMed:21947082,
ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:24324267,
ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:24627487,
ECO:0000269|PubMed:25105025, ECO:0000269|PubMed:9311995,
ECO:0000269|PubMed:9665135, ECO:0000269|PubMed:9670020,
ECO:0000269|PubMed:9732876, ECO:0000269|PubMed:9843571,
ECO:0000269|PubMed:9865696, ECO:0000269|PubMed:9892009}.
-!- INTERACTION:
Self; NbExp=3; IntAct=EBI-347161, EBI-347161;
O92972:- (xeno); NbExp=6; IntAct=EBI-347161, EBI-9213553;
P60709:ACTB; NbExp=3; IntAct=EBI-347161, EBI-353944;
Q08117:AES; NbExp=3; IntAct=EBI-347161, EBI-717810;
Q08117-2:AES; NbExp=3; IntAct=EBI-347161, EBI-11741437;
Q9H2G9:BLZF1; NbExp=8; IntAct=EBI-347161, EBI-2548012;
Q9H2X0:CHRD; NbExp=2; IntAct=EBI-347161, EBI-947551;
Q8N684:CPSF7; NbExp=3; IntAct=EBI-347161, EBI-746909;
Q8N684-3:CPSF7; NbExp=3; IntAct=EBI-347161, EBI-11523759;
O43186:CRX; NbExp=3; IntAct=EBI-347161, EBI-748171;
P98082:DAB2; NbExp=3; IntAct=EBI-347161, EBI-1171238;
Q9BZ29:DOCK9; NbExp=3; IntAct=EBI-347161, EBI-2695893;
P51141:Dvl1 (xeno); NbExp=2; IntAct=EBI-347161, EBI-1538407;
Q99814:EPAS1; NbExp=2; IntAct=EBI-347161, EBI-447470;
O75593:FOXH1; NbExp=5; IntAct=EBI-347161, EBI-1759806;
O43524:FOXO3; NbExp=5; IntAct=EBI-347161, EBI-1644164;
P10070:GLI2; NbExp=4; IntAct=EBI-347161, EBI-10821567;
Q9UBR4-2:LHX3; NbExp=4; IntAct=EBI-347161, EBI-12039345;
P50222:MEOX2; NbExp=6; IntAct=EBI-347161, EBI-748397;
Q9NYA4:MTMR4; NbExp=4; IntAct=EBI-347161, EBI-1052346;
Q99836:MYD88; NbExp=3; IntAct=EBI-347161, EBI-447677;
Q16822:PCK2; NbExp=2; IntAct=EBI-347161, EBI-2825219;
Q8IXK0:PHC2; NbExp=3; IntAct=EBI-347161, EBI-713786;
Q8IXK0-5:PHC2; NbExp=3; IntAct=EBI-347161, EBI-11527347;
Q9BZL4:PPP1R12C; NbExp=2; IntAct=EBI-347161, EBI-721802;
P24158:PRTN3; NbExp=2; IntAct=EBI-347161, EBI-465028;
Q96EP0:RNF31; NbExp=2; IntAct=EBI-347161, EBI-948111;
Q9BYW2:SETD2; NbExp=2; IntAct=EBI-347161, EBI-945869;
P12755:SKI; NbExp=11; IntAct=EBI-347161, EBI-347281;
Q15796:SMAD2; NbExp=2; IntAct=EBI-347161, EBI-1040141;
Q13485:SMAD4; NbExp=24; IntAct=EBI-347161, EBI-347263;
Q9HAU4:SMURF2; NbExp=9; IntAct=EBI-347161, EBI-396727;
Q13573:SNW1; NbExp=5; IntAct=EBI-347161, EBI-632715;
Q13501:SQSTM1; NbExp=3; IntAct=EBI-347161, EBI-307104;
Q12772:SREBF2; NbExp=3; IntAct=EBI-347161, EBI-465059;
Q05066:SRY; NbExp=3; IntAct=EBI-347161, EBI-464987;
Q8WW24:TEKT4; NbExp=3; IntAct=EBI-347161, EBI-750487;
Q9Y3Q8:TSC22D4; NbExp=2; IntAct=EBI-347161, EBI-739485;
Q93009:USP7; NbExp=2; IntAct=EBI-347161, EBI-302474;
Q9H0M0:WWP1; NbExp=8; IntAct=EBI-347161, EBI-742157;
O00308:WWP2; NbExp=7; IntAct=EBI-347161, EBI-743923;
Q5D1E8:ZC3H12A; NbExp=2; IntAct=EBI-347161, EBI-747793;
O95405:ZFYVE9; NbExp=2; IntAct=EBI-347161, EBI-296817;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15799969,
ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101,
ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19218245,
ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:22781750}. Nucleus
{ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15799969,
ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101,
ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081,
ECO:0000269|PubMed:22781750}. Note=Cytoplasmic and nuclear in the
absence of TGF-beta. On TGF-beta stimulation, migrates to the
nucleus when complexed with SMAD4 (PubMed:15799969). Through the
action of the phosphatase PPM1A, released from the SMAD2/SMAD4
complex, and exported out of the nucleus by interaction with
RANBP1 (PubMed:16751101, PubMed:19289081). Co-localizes with LEMD3
at the nucleus inner membrane (PubMed:15601644). MAPK-mediated
phosphorylation appears to have no effect on nuclear import
(PubMed:19218245). PDPK1 prevents its nuclear translocation in
response to TGF-beta (PubMed:17327236).
{ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15799969,
ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:17327236,
ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Name=1;
IsoId=P84022-1; Sequence=Displayed;
Name=2;
IsoId=P84022-2; Sequence=VSP_042900;
Note=No experimental confirmation available.;
Name=3;
IsoId=P84022-3; Sequence=VSP_043793;
Name=4;
IsoId=P84022-4; Sequence=VSP_045348;
Note=No experimental confirmation available.;
-!- DOMAIN: The MH1 domain is required for DNA binding. Also binds
zinc ions which are necessary for the DNA binding.
-!- DOMAIN: The MH2 domain is required for both homomeric and
heteromeric interactions and for transcriptional regulation.
Sufficient for nuclear import.
-!- DOMAIN: The linker region is required for the TGFbeta-mediated
transcriptional activity and acts synergistically with the MH2
domain.
-!- PTM: Phosphorylated on serine and threonine residues. Enhanced
phosphorylation in the linker region on Thr-179, Ser-204 and Ser-
208 on EGF and TGF-beta treatment. Ser-208 is the main site of
MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs
in a cell-cycle dependent manner and inhibits both the
transcriptional activity and antiproliferative functions of SMAD3.
This phosphorylation is inhibited by flavopiridol. Maximum
phosphorylation at the G(1)/S junction. Also phosphorylated on
serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1.
TGFBR1-mediated phosphorylation at these C-terminal sites is
required for interaction with SMAD4, nuclear location and
transactivational activity, and appears to be a prerequisite for
the TGF-beta mediated phosphorylation in the linker region.
Dephosphorylated in the C-terminal SXS motif by PPM1A. This
dephosphorylation disrupts the interaction with SMAD4, promotes
nuclear export and terminates TGF-beta-mediated signaling.
Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-
dependent ubiquitination and subsequent proteasome degradation,
thus inhibiting SMAD3-mediated TGF-beta responses. Phosphorylated
by PDPK1. {ECO:0000269|PubMed:11224571,
ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:15588252,
ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:17327236,
ECO:0000269|PubMed:18794808, ECO:0000269|PubMed:19218245,
ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:8774881,
ECO:0000269|PubMed:9843571}.
-!- PTM: Acetylation in the nucleus by EP300 in the MH2 domain
regulates positively its transcriptional activity and is enhanced
by TGF-beta. {ECO:0000269|PubMed:16862174}.
-!- PTM: Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation
negatively regulates SMAD3 transcriptional responses during the
course of TGF-beta signaling. {ECO:0000269|PubMed:25133494}.
-!- PTM: Ubiquitinated. Monoubiquitinated, leading to prevent DNA-
binding (PubMed:21947082). Deubiquitination by USP15 alleviates
inhibition and promotes activation of TGF-beta target genes
(PubMed:21947082). Ubiquitinated by RNF111, leading to its
degradation: only SMAD3 proteins that are 'in use' are targeted by
RNF111, RNF111 playing a key role in activating SMAD3 and
regulating its turnover (By similarity). Undergoes STUB1-mediated
ubiquitination and degradation (PubMed:24613385).
{ECO:0000250|UniProtKB:Q8BUN5, ECO:0000269|PubMed:21947082,
ECO:0000269|PubMed:24613385}.
-!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
characterized by malignant lesions arising from the inner wall of
the large intestine (the colon) and the rectum. Genetic
alterations are often associated with progression from
premalignant lesion (adenoma) to invasive adenocarcinoma. Risk
factors for cancer of the colon and rectum include colon polyps,
long-standing ulcerative colitis, and genetic family history.
{ECO:0000269|PubMed:16959974}. Note=The disease may be caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Loeys-Dietz syndrome 3 (LDS3) [MIM:613795]: An aortic
aneurysm syndrome with widespread systemic involvement. The
disorder is characterized by the triad of arterial tortuosity and
aneurysms, hypertelorism, and bifid uvula or cleft palate.
Patients with LDS3 also manifest early-onset osteoarthritis. They
lack craniosynostosis and mental retardation.
{ECO:0000269|PubMed:21217753, ECO:0000269|PubMed:21778426}.
Note=The disease is caused by mutations affecting the gene
represented in this entry. SMAD3 mutations have been reported to
be also associated with thoracic aortic aneurysms and dissection
(TAAD) (PubMed:21778426). This phenotype is distinguised from LDS3
by having aneurysms restricted to thoracic aorta. As individuals
carrying these mutations also exhibit aneurysms of other arteries,
including abdominal aorta, iliac, and/or intracranial arteries
(PubMed:21778426), they have been classified as LDS3 by the OMIM
resource. {ECO:0000269|PubMed:21778426}.
-!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; U68019; AAB80960.1; -; mRNA.
EMBL; U76622; AAB18967.1; -; mRNA.
EMBL; AB004930; BAA22032.1; -; Genomic_DNA.
EMBL; AF025300; AAL68976.1; -; Genomic_DNA.
EMBL; AF025293; AAL68976.1; JOINED; Genomic_DNA.
EMBL; AF025294; AAL68976.1; JOINED; Genomic_DNA.
EMBL; AF025295; AAL68976.1; JOINED; Genomic_DNA.
EMBL; AF025296; AAL68976.1; JOINED; Genomic_DNA.
EMBL; AF025297; AAL68976.1; JOINED; Genomic_DNA.
EMBL; AF025298; AAL68976.1; JOINED; Genomic_DNA.
EMBL; AF025299; AAL68976.1; JOINED; Genomic_DNA.
EMBL; AK290881; BAF83570.1; -; mRNA.
EMBL; AK298139; BAH12731.1; -; mRNA.
EMBL; AK300614; BAH13315.1; -; mRNA.
EMBL; AK316017; BAH14388.1; -; mRNA.
EMBL; AC012568; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC087482; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471082; EAW77788.1; -; Genomic_DNA.
EMBL; BC050743; AAH50743.1; -; mRNA.
CCDS; CCDS10222.1; -. [P84022-1]
CCDS; CCDS45288.1; -. [P84022-2]
CCDS; CCDS53950.1; -. [P84022-3]
CCDS; CCDS53951.1; -. [P84022-4]
PIR; S71798; S71798.
RefSeq; NP_001138574.1; NM_001145102.1. [P84022-3]
RefSeq; NP_001138575.1; NM_001145103.1. [P84022-2]
RefSeq; NP_001138576.1; NM_001145104.1. [P84022-4]
RefSeq; NP_005893.1; NM_005902.3. [P84022-1]
UniGene; Hs.727986; -.
UniGene; Hs.742270; -.
PDB; 1MHD; X-ray; 2.80 A; A/B=1-132.
PDB; 1MJS; X-ray; 1.91 A; A=229-425.
PDB; 1MK2; X-ray; 2.74 A; A=220-425.
PDB; 1OZJ; X-ray; 2.40 A; A/B=1-144.
PDB; 1U7F; X-ray; 2.60 A; A/C=228-425.
PDB; 2LAJ; NMR; -; B=202-211.
PDB; 2LB2; NMR; -; B=178-189.
PDBsum; 1MHD; -.
PDBsum; 1MJS; -.
PDBsum; 1MK2; -.
PDBsum; 1OZJ; -.
PDBsum; 1U7F; -.
PDBsum; 2LAJ; -.
PDBsum; 2LB2; -.
ProteinModelPortal; P84022; -.
SMR; P84022; -.
BioGrid; 110263; 346.
CORUM; P84022; -.
DIP; DIP-29720N; -.
IntAct; P84022; 196.
MINT; MINT-193987; -.
STRING; 9606.ENSP00000332973; -.
BindingDB; P84022; -.
ChEMBL; CHEMBL1293258; -.
iPTMnet; P84022; -.
PhosphoSitePlus; P84022; -.
BioMuta; SMAD3; -.
DMDM; 51338669; -.
EPD; P84022; -.
MaxQB; P84022; -.
PaxDb; P84022; -.
PeptideAtlas; P84022; -.
PRIDE; P84022; -.
DNASU; 4088; -.
Ensembl; ENST00000327367; ENSP00000332973; ENSG00000166949. [P84022-1]
Ensembl; ENST00000439724; ENSP00000401133; ENSG00000166949. [P84022-2]
Ensembl; ENST00000537194; ENSP00000445348; ENSG00000166949. [P84022-4]
Ensembl; ENST00000540846; ENSP00000437757; ENSG00000166949. [P84022-3]
GeneID; 4088; -.
KEGG; hsa:4088; -.
UCSC; uc002aqj.4; human. [P84022-1]
CTD; 4088; -.
DisGeNET; 4088; -.
EuPathDB; HostDB:ENSG00000166949.15; -.
GeneCards; SMAD3; -.
GeneReviews; SMAD3; -.
HGNC; HGNC:6769; SMAD3.
HPA; CAB008094; -.
HPA; CAB069409; -.
HPA; HPA046386; -.
HPA; HPA067203; -.
MalaCards; SMAD3; -.
MIM; 114500; phenotype.
MIM; 603109; gene.
MIM; 613795; phenotype.
neXtProt; NX_P84022; -.
OpenTargets; ENSG00000166949; -.
Orphanet; 284984; Aneurysm - osteoarthritis syndrome.
Orphanet; 91387; Familial thoracic aortic aneurysm and aortic dissection.
PharmGKB; PA30526; -.
eggNOG; KOG3701; Eukaryota.
eggNOG; ENOG410XQKU; LUCA.
GeneTree; ENSGT00760000119091; -.
HOGENOM; HOG000286018; -.
HOVERGEN; HBG053353; -.
InParanoid; P84022; -.
KO; K04500; -.
OMA; SDHQMTH; -.
OrthoDB; EOG091G082C; -.
PhylomeDB; P84022; -.
TreeFam; TF314923; -.
Reactome; R-HSA-1181150; Signaling by NODAL.
Reactome; R-HSA-1502540; Signaling by Activin.
Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling.
Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs.
Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
Reactome; R-HSA-3304356; SMAD2/3 Phosphorylation Motif Mutants in Cancer.
Reactome; R-HSA-3311021; SMAD4 MH2 Domain Mutants in Cancer.
Reactome; R-HSA-3315487; SMAD2/3 MH2 Domain Mutants in Cancer.
Reactome; R-HSA-3656532; TGFBR1 KD Mutants in Cancer.
Reactome; R-HSA-5689880; Ub-specific processing proteases.
Reactome; R-HSA-8941855; RUNX3 regulates CDKN1A transcription.
Reactome; R-HSA-8952158; RUNX3 regulates BCL2L11 (BIM) transcription.
SignaLink; P84022; -.
SIGNOR; P84022; -.
ChiTaRS; SMAD3; human.
EvolutionaryTrace; P84022; -.
GeneWiki; Mothers_against_decapentaplegic_homolog_3; -.
GenomeRNAi; 4088; -.
PRO; PR:P84022; -.
Proteomes; UP000005640; Chromosome 15.
Bgee; ENSG00000166949; -.
CleanEx; HS_SMAD3; -.
ExpressionAtlas; P84022; baseline and differential.
Genevisible; P84022; HS.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL.
GO; GO:0005637; C:nuclear inner membrane; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
GO; GO:0043235; C:receptor complex; IMP:BHF-UCL.
GO; GO:0071141; C:SMAD protein complex; IDA:UniProtKB.
GO; GO:0071144; C:SMAD2-SMAD3 protein complex; IDA:BHF-UCL.
GO; GO:0005667; C:transcription factor complex; IDA:UniProtKB.
GO; GO:0008013; F:beta-catenin binding; IEA:Ensembl.
GO; GO:0043425; F:bHLH transcription factor binding; IPI:BHF-UCL.
GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
GO; GO:0070410; F:co-SMAD binding; IPI:BHF-UCL.
GO; GO:0005518; F:collagen binding; IEA:Ensembl.
GO; GO:0000987; F:core promoter proximal region sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:BHF-UCL.
GO; GO:0035326; F:enhancer binding; IC:BHF-UCL.
GO; GO:0035259; F:glucocorticoid receptor binding; IPI:CAFA.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0031962; F:mineralocorticoid receptor binding; IPI:CAFA.
GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
GO; GO:0070878; F:primary miRNA binding; IPI:BHF-UCL.
GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
GO; GO:0070412; F:R-SMAD binding; IPI:UniProtKB.
GO; GO:0001102; F:RNA polymerase II activating transcription factor binding; IPI:BHF-UCL.
GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0000983; F:transcription factor activity, RNA polymerase II core promoter sequence-specific; IDA:NTNU_SB.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL.
GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
GO; GO:0005160; F:transforming growth factor beta receptor binding; IPI:BHF-UCL.
GO; GO:0030618; F:transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity; IDA:BHF-UCL.
GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL.
GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL.
GO; GO:0097296; P:activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IEA:Ensembl.
GO; GO:0032924; P:activin receptor signaling pathway; IMP:BHF-UCL.
GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
GO; GO:0007050; P:cell cycle arrest; IMP:BHF-UCL.
GO; GO:0045216; P:cell-cell junction organization; IMP:BHF-UCL.
GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:CAFA.
GO; GO:0048589; P:developmental growth; IEA:Ensembl.
GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
GO; GO:0048617; P:embryonic foregut morphogenesis; IEA:Ensembl.
GO; GO:0009880; P:embryonic pattern specification; IEA:Ensembl.
GO; GO:0007492; P:endoderm development; IEA:Ensembl.
GO; GO:0019049; P:evasion or tolerance of host defenses by virus; IDA:BHF-UCL.
GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:BHF-UCL.
GO; GO:0001947; P:heart looping; IEA:Ensembl.
GO; GO:0006955; P:immune response; IMP:BHF-UCL.
GO; GO:0002520; P:immune system development; IEA:Ensembl.
GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl.
GO; GO:0001889; P:liver development; IEA:Ensembl.
GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; IEA:Ensembl.
GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; IDA:BHF-UCL.
GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:BHF-UCL.
GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
GO; GO:0061767; P:negative regulation of lung blood pressure; IEA:Ensembl.
GO; GO:0045930; P:negative regulation of mitotic cell cycle; IMP:BHF-UCL.
GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEA:Ensembl.
GO; GO:0042177; P:negative regulation of protein catabolic process; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
GO; GO:0061045; P:negative regulation of wound healing; IEA:Ensembl.
GO; GO:0038092; P:nodal signaling pathway; IMP:BHF-UCL.
GO; GO:0002076; P:osteoblast development; IEA:Ensembl.
GO; GO:0048340; P:paraxial mesoderm morphogenesis; IEA:Ensembl.
GO; GO:0060039; P:pericardium development; IEA:Ensembl.
GO; GO:0010694; P:positive regulation of alkaline phosphatase activity; IEA:Ensembl.
GO; GO:0030501; P:positive regulation of bone mineralization; IEA:Ensembl.
GO; GO:0035413; P:positive regulation of catenin import into nucleus; IEA:Ensembl.
GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IEA:Ensembl.
GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:BHF-UCL.
GO; GO:1901203; P:positive regulation of extracellular matrix assembly; IDA:BHF-UCL.
GO; GO:0051894; P:positive regulation of focal adhesion assembly; IEA:Ensembl.
GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL.
GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
GO; GO:0050927; P:positive regulation of positive chemotaxis; IEA:Ensembl.
GO; GO:1902895; P:positive regulation of pri-miRNA transcription from RNA polymerase II promoter; IMP:BHF-UCL.
GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl.
GO; GO:0042993; P:positive regulation of transcription factor import into nucleus; IDA:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
GO; GO:0032916; P:positive regulation of transforming growth factor beta3 production; IEA:Ensembl.
GO; GO:0031053; P:primary miRNA processing; TAS:BHF-UCL.
GO; GO:0016579; P:protein deubiquitination; TAS:Reactome.
GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
GO; GO:0051098; P:regulation of binding; IEA:Ensembl.
GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl.
GO; GO:0050776; P:regulation of immune response; IEA:Ensembl.
GO; GO:0016202; P:regulation of striated muscle tissue development; IEA:Ensembl.
GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB.
GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL.
GO; GO:0032909; P:regulation of transforming growth factor beta2 production; IMP:BHF-UCL.
GO; GO:0001666; P:response to hypoxia; IMP:BHF-UCL.
GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
GO; GO:0007183; P:SMAD protein complex assembly; IDA:BHF-UCL.
GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
GO; GO:0042110; P:T cell activation; IEA:Ensembl.
GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0060290; P:transdifferentiation; IEA:Ensembl.
GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
GO; GO:0006810; P:transport; IDA:BHF-UCL.
GO; GO:0001657; P:ureteric bud development; IEA:Ensembl.
GO; GO:0042060; P:wound healing; TAS:BHF-UCL.
Gene3D; 2.60.200.10; -; 1.
Gene3D; 3.90.520.10; -; 1.
InterPro; IPR013790; Dwarfin.
InterPro; IPR003619; MAD_homology1_Dwarfin-type.
InterPro; IPR013019; MAD_homology_MH1.
InterPro; IPR017855; SMAD_dom-like.
InterPro; IPR001132; SMAD_dom_Dwarfin-type.
InterPro; IPR008984; SMAD_FHA_domain.
PANTHER; PTHR13703; PTHR13703; 1.
Pfam; PF03165; MH1; 1.
Pfam; PF03166; MH2; 1.
SMART; SM00523; DWA; 1.
SMART; SM00524; DWB; 1.
SUPFAM; SSF49879; SSF49879; 1.
SUPFAM; SSF56366; SSF56366; 1.
PROSITE; PS51075; MH1; 1.
PROSITE; PS51076; MH2; 1.
1: Evidence at protein level;
3D-structure; Acetylation; ADP-ribosylation; Alternative splicing;
Aortic aneurysm; Complete proteome; Cytoplasm; Disease mutation;
DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
Polymorphism; Reference proteome; Transcription;
Transcription regulation; Ubl conjugation; Zinc.
INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330,
ECO:0000244|PubMed:22814378}.
CHAIN 2 425 Mothers against decapentaplegic homolog
3.
/FTId=PRO_0000090856.
DOMAIN 10 136 MH1. {ECO:0000255|PROSITE-
ProRule:PRU00438}.
DOMAIN 232 425 MH2. {ECO:0000255|PROSITE-
ProRule:PRU00439}.
REGION 137 231 Linker.
REGION 271 324 Sufficient for interaction with XPO4.
{ECO:0000269|PubMed:16449645}.
METAL 64 64 Zinc.
METAL 109 109 Zinc.
METAL 121 121 Zinc.
METAL 126 126 Zinc.
SITE 40 40 Required for trimerization.
SITE 41 41 Required for interaction with DNA and JUN
and for functional cooperation with JUN.
MOD_RES 2 2 N-acetylserine.
{ECO:0000244|PubMed:19413330,
ECO:0000244|PubMed:22814378}.
MOD_RES 8 8 Phosphothreonine; by CDK2 and CDK4.
{ECO:0000269|PubMed:15241418}.
MOD_RES 179 179 Phosphothreonine; by CDK2, CDK4 and MAPK.
{ECO:0000269|PubMed:15241418,
ECO:0000269|PubMed:16156666,
ECO:0000269|PubMed:19218245}.
MOD_RES 204 204 Phosphoserine; by GSK3 and MAPK.
{ECO:0000255|PROSITE-ProRule:PRU00439,
ECO:0000269|PubMed:15241418,
ECO:0000269|PubMed:16156666,
ECO:0000269|PubMed:19218245}.
MOD_RES 208 208 Phosphoserine; by MAPK.
{ECO:0000255|PROSITE-ProRule:PRU00439,
ECO:0000269|PubMed:15241418,
ECO:0000269|PubMed:16156666,
ECO:0000269|PubMed:19218245}.
MOD_RES 213 213 Phosphoserine; by CDK2 and CDK4.
{ECO:0000255|PROSITE-ProRule:PRU00439,
ECO:0000269|PubMed:15241418}.
MOD_RES 378 378 N6-acetyllysine.
{ECO:0000269|PubMed:16862174}.
MOD_RES 416 416 Phosphoserine.
{ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:23186163}.
MOD_RES 418 418 Phosphoserine; by CK1.
{ECO:0000255|PROSITE-ProRule:PRU00439,
ECO:0000269|PubMed:18794808}.
MOD_RES 422 422 Phosphoserine; by TGFBR1.
{ECO:0000250|UniProtKB:Q8BUN5,
ECO:0000255|PROSITE-ProRule:PRU00439}.
MOD_RES 423 423 Phosphoserine; by TGFBR1.
{ECO:0000250|UniProtKB:Q8BUN5,
ECO:0000255|PROSITE-ProRule:PRU00439}.
MOD_RES 425 425 Phosphoserine; by TGFBR1.
{ECO:0000250|UniProtKB:Q8BUN5,
ECO:0000255|PROSITE-ProRule:PRU00439}.
CROSSLNK 33 33 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000305|PubMed:21947082}.
CROSSLNK 81 81 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000305|PubMed:21947082}.
VAR_SEQ 1 195 Missing (in isoform 4).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_045348.
VAR_SEQ 1 105 Missing (in isoform 3).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_043793.
VAR_SEQ 1 68 MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKK
LKKTGQLDELEKAITTQNVNTKCITIP -> MSCLHPRQTW
KGAALVHRKAWWMG (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_042900.
VARIANT 112 112 A -> V (in LDS3; dbSNP:rs387906854).
{ECO:0000269|PubMed:21778426}.
/FTId=VAR_067051.
VARIANT 170 170 I -> V (in dbSNP:rs35874463).
/FTId=VAR_052021.
VARIANT 239 239 E -> K (in LDS3; dbSNP:rs387906853).
{ECO:0000269|PubMed:21778426}.
/FTId=VAR_067047.
VARIANT 261 261 T -> I (in LDS3; dbSNP:rs387906851).
{ECO:0000269|PubMed:21217753}.
/FTId=VAR_065578.
VARIANT 279 279 R -> K (in LDS3; dbSNP:rs387906852).
{ECO:0000269|PubMed:21778426}.
/FTId=VAR_067048.
VARIANT 287 287 R -> W (in LDS3; dbSNP:rs387906850).
{ECO:0000269|PubMed:21217753}.
/FTId=VAR_065579.
VARIANT 393 393 P -> L (in a colorectal cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036474.
MUTAGEN 8 8 T->V: Reduced phosphorylation, increased
transcriptional and antiproliferative
activities. Further increase in
transcriptional and antiproliferative
activities; when associated with V-179
and A-213. {ECO:0000269|PubMed:15241418}.
MUTAGEN 33 33 K->R: Slightly decreased
monoubiquitination.
{ECO:0000269|PubMed:21947082}.
MUTAGEN 40 40 K->A: Little effect on interaction with
DNA or JUN. Abolishes interaction with
DNA and JUN; when associated with A-41;
A-43 and A-44.
{ECO:0000269|PubMed:10995748}.
MUTAGEN 41 41 K->A: Greatly reduced interaction with
DNA and JUN. Abolishes interaction with
DNA and JUN; when associated with A-40;
A-44 and A-43.
{ECO:0000269|PubMed:10995748}.
MUTAGEN 43 43 K->A: Little effect on interaction with
DNA or JUN. Abolishes interaction with
DNA and JUN; when associated with A-40;
A-41 and A-44.
{ECO:0000269|PubMed:10995748}.
MUTAGEN 44 44 K->A: Little effect on interaction with
DNA or JUN. Abolishes interaction with
JUN; when associated with A-40; A-41 and
A-43. {ECO:0000269|PubMed:10995748}.
MUTAGEN 53 53 K->R: Slightly decreased
monoubiquitination.
{ECO:0000269|PubMed:21947082}.
MUTAGEN 74 74 R->D: Reduced interaction with JUN. Loss
of transcriptional activity and
cooperation with JUN.
{ECO:0000269|PubMed:10995748}.
MUTAGEN 81 81 K->R: Decreased monoubiquitination.
{ECO:0000269|PubMed:21947082}.
MUTAGEN 179 179 T->V: Reduced phosphorylation, increased
transcriptional and increased
antiproliferative activities. Further
increase in transcriptional and
antiproliferative activities; when
associated with V-8 and A-213.
{ECO:0000269|PubMed:15241418,
ECO:0000269|PubMed:16156666,
ECO:0000269|PubMed:19218245}.
MUTAGEN 204 204 S->A: Increased transcriptional activity.
Further increased transcriptional
activity; when associated with S-208.
{ECO:0000269|PubMed:15241418,
ECO:0000269|PubMed:16156666,
ECO:0000269|PubMed:19218245}.
MUTAGEN 208 208 S->A: Increased transcriptional activity.
Further increased transcriptional
activity; when associated with S-208.
{ECO:0000269|PubMed:15241418,
ECO:0000269|PubMed:16156666,
ECO:0000269|PubMed:19218245}.
MUTAGEN 213 213 S->A: Reduced phosphorylation. Increased
transcriptional and antiproliferative
activities. Further increase in
transcriptional and antiproliferative
activities; when associated with V-8 and
V-179. {ECO:0000269|PubMed:15241418}.
MUTAGEN 333 333 K->R: No effect on acetylation.
Completely abolishes acetylation and 97%
reduction in transcriptional activity;
when associated with R-341; R-378 and R-
409. {ECO:0000269|PubMed:16862174}.
MUTAGEN 341 341 K->R: No effect on acetylation.
Completely abolishes acetylation and 97%
reduction in transcriptional activity;
when associated with R-333; R-378 and R-
409. {ECO:0000269|PubMed:16862174}.
MUTAGEN 378 378 K->Q: Increased transcriptional activity.
No further increase in transcriptional
activity with EP300.
{ECO:0000269|PubMed:16862174}.
MUTAGEN 378 378 K->R: Greatly reduced acetylation and 85%
reduction in transcriptional activity.
Completely abolishes acetylation and 97%
reduction in transcriptional activity;
when associated with R-333; R-341 and R-
409. {ECO:0000269|PubMed:16862174}.
MUTAGEN 409 409 K->R: No effect on acetylation.
Completely abolishes acetylation and 97%
reduction in transcriptional activity;
when associated with R-333; R-341 and R-
378. {ECO:0000269|PubMed:16862174}.
MUTAGEN 418 418 S->A: Increased constitutive activity.
{ECO:0000269|PubMed:18794808}.
MUTAGEN 418 418 S->D: Decreased activity.
{ECO:0000269|PubMed:18794808}.
MUTAGEN 422 425 SSVS->AAVA: Does not abolish protein
nuclear export. Abolishes almost
completely acetylation.
{ECO:0000269|PubMed:11224571,
ECO:0000269|PubMed:16449645,
ECO:0000269|PubMed:16862174}.
MUTAGEN 422 425 SSVS->EEVE: Forms heterotrimers.
{ECO:0000269|PubMed:11224571,
ECO:0000269|PubMed:16449645,
ECO:0000269|PubMed:16862174}.
MUTAGEN 422 425 SSVS->RRVR: Diminishes cargo protein
export. {ECO:0000269|PubMed:11224571,
ECO:0000269|PubMed:16449645,
ECO:0000269|PubMed:16862174}.
CONFLICT 178 178 E -> EVGTWAAQAGL (in Ref. 3; BAA22032).
{ECO:0000305}.
CONFLICT 360 360 F -> L (in Ref. 5; BAH13315).
{ECO:0000305}.
HELIX 10 16 {ECO:0000244|PDB:1OZJ}.
HELIX 25 44 {ECO:0000244|PDB:1OZJ}.
HELIX 48 57 {ECO:0000244|PDB:1OZJ}.
STRAND 60 62 {ECO:0000244|PDB:1MHD}.
STRAND 66 68 {ECO:0000244|PDB:1OZJ}.
STRAND 75 77 {ECO:0000244|PDB:1OZJ}.
STRAND 80 82 {ECO:0000244|PDB:1OZJ}.
HELIX 84 92 {ECO:0000244|PDB:1OZJ}.
HELIX 100 102 {ECO:0000244|PDB:1OZJ}.
STRAND 103 105 {ECO:0000244|PDB:1OZJ}.
HELIX 113 115 {ECO:0000244|PDB:1OZJ}.
STRAND 118 121 {ECO:0000244|PDB:1OZJ}.
HELIX 124 126 {ECO:0000244|PDB:1OZJ}.
STRAND 127 129 {ECO:0000244|PDB:1OZJ}.
STRAND 221 225 {ECO:0000244|PDB:1MK2}.
STRAND 231 239 {ECO:0000244|PDB:1MJS}.
STRAND 242 250 {ECO:0000244|PDB:1MJS}.
STRAND 252 258 {ECO:0000244|PDB:1MJS}.
STRAND 268 270 {ECO:0000244|PDB:1MJS}.
HELIX 271 273 {ECO:0000244|PDB:1U7F}.
HELIX 281 290 {ECO:0000244|PDB:1MJS}.
STRAND 294 299 {ECO:0000244|PDB:1MJS}.
STRAND 302 307 {ECO:0000244|PDB:1MJS}.
STRAND 309 311 {ECO:0000244|PDB:1MJS}.
STRAND 313 316 {ECO:0000244|PDB:1MJS}.
HELIX 318 321 {ECO:0000244|PDB:1MJS}.
HELIX 323 325 {ECO:0000244|PDB:1MK2}.
STRAND 332 334 {ECO:0000244|PDB:1MJS}.
STRAND 339 343 {ECO:0000244|PDB:1MJS}.
HELIX 345 358 {ECO:0000244|PDB:1MJS}.
HELIX 360 364 {ECO:0000244|PDB:1MJS}.
HELIX 365 370 {ECO:0000244|PDB:1MJS}.
STRAND 371 377 {ECO:0000244|PDB:1MJS}.
STRAND 384 386 {ECO:0000244|PDB:1MK2}.
HELIX 389 391 {ECO:0000244|PDB:1U7F}.
STRAND 392 400 {ECO:0000244|PDB:1MJS}.
HELIX 401 413 {ECO:0000244|PDB:1MJS}.
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


Related products :

Catalog number Product name Quantity
E2185h ELISA hMAD-3,Homo sapiens,hSMAD3,Human,JV15-2,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3 96T
U2185h CLIA kit hMAD-3,Homo sapiens,hSMAD3,Human,JV15-2,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3 96T
U2185h CLIA hMAD-3,Homo sapiens,hSMAD3,Human,JV15-2,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3 96T
E2185h ELISA kit hMAD-3,Homo sapiens,hSMAD3,Human,JV15-2,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3 96T
E2185h hMAD-3,Homo sapiens,hSMAD3,Human,JV15-2,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3
18-003-42992 Mothers against decapentaplegic homolog 3 - SMAD 3; Mothers against DPP homolog 3; Mad3; hMAD-3; JV15-2; hSMAD3 Polyclonal 0.1 mg Protein A
U2185m CLIA MAD homolog 3,Mad3,Madh3,mMad3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Mouse,Mus musculus,SMAD 3,SMAD family member 3,Smad3,Smad3 96T
E2185m ELISA MAD homolog 3,Mad3,Madh3,mMad3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Mouse,Mus musculus,SMAD 3,SMAD family member 3,Smad3,Smad3 96T
E2185m ELISA kit MAD homolog 3,Mad3,Madh3,mMad3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Mouse,Mus musculus,SMAD 3,SMAD family member 3,Smad3,Smad3 96T
U2185m CLIA kit MAD homolog 3,Mad3,Madh3,mMad3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Mouse,Mus musculus,SMAD 3,SMAD family member 3,Smad3,Smad3 96T
E2185m MAD homolog 3,Mad3,Madh3,mMad3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Mouse,Mus musculus,SMAD 3,SMAD family member 3,Smad3,Smad3
U2185r CLIA kit MAD homolog 3,Mad3,Madh3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Rat,Rattus norvegicus,SMAD 3,SMAD family member 3,Smad3,Smad3 96T
E2185r ELISA kit MAD homolog 3,Mad3,Madh3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Rat,Rattus norvegicus,SMAD 3,SMAD family member 3,Smad3,Smad3 96T
U2185r CLIA MAD homolog 3,Mad3,Madh3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Rat,Rattus norvegicus,SMAD 3,SMAD family member 3,Smad3,Smad3 96T
E2185r ELISA MAD homolog 3,Mad3,Madh3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Rat,Rattus norvegicus,SMAD 3,SMAD family member 3,Smad3,Smad3 96T
E2185r MAD homolog 3,Mad3,Madh3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Rat,Rattus norvegicus,SMAD 3,SMAD family member 3,Smad3,Smad3
E2185p ELISA kit MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Pig,SMAD 3,SMAD family member 3,Smad3,SMAD3,Sus scrofa 96T
E2185p ELISA MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Pig,SMAD 3,SMAD family member 3,Smad3,SMAD3,Sus scrofa 96T
U2185p CLIA kit MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Pig,SMAD 3,SMAD family member 3,Smad3,SMAD3,Sus scrofa 96T
U2185p CLIA MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Pig,SMAD 3,SMAD family member 3,Smad3,SMAD3,Sus scrofa 96T
E2185p MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,Pig,SMAD 3,SMAD family member 3,Smad3,SMAD3,Sus scrofa
U2185c CLIA Chicken,Gallus gallus,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3 96T
E2185c ELISA kit Chicken,Gallus gallus,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3 96T
E2185c ELISA Chicken,Gallus gallus,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3 96T
U2185c CLIA kit Chicken,Gallus gallus,MAD homolog 3,Mad3,MADH3,Mothers against decapentaplegic homolog 3,Mothers against DPP homolog 3,SMAD 3,SMAD family member 3,Smad3,SMAD3 96T


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur





GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017

BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG

france@gentaur.com | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur