AC T04096
XX
ID T04096
XX
DT 11.12.2000 (created); rio.
DT 10.02.2015 (updated); spk.
CO Copyright (C), QIAGEN.
XX
FA Smad3-isoform1
XX
SY Smad-3.
XX
OS human, Homo sapiens
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
XX
GE G002399 SMAD3; HGNC: SMAD3.
XX
CL C0041; SMAD.
XX
SZ 425 AA; 48.1 kDa (cDNA) (calc.).
XX
SQ MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNV
SQ NTKCITIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEV
SQ CVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETP
SQ PPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYEL
SQ NQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIG
SQ GEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGF
SQ EAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSIR
SQ CSSVS
XX
SC Swiss-Prot#P84022-1
XX
FT 1 145 
binding to HIF-1alpha [13].
FT 1 145 
MH1 domain [3].
FT 10 136 
PS51075; MH1.
FT 26 134 
SM00523; dwAneu5.
FT 28 131 
PF03165; MH1 domain.
FT 40 44 
Nuclear Localization Signal (NLS) [10].
FT 41 41 
Lysin 41 residue is critical for binding to DNA and interaction with c-Jun [6].
FT 71 83 
DNA binding domain [3].
FT 75 82 
beta hairpin [5].
FT 146 231 
Linker region [3].
FT 232 421 binding to HIF-1alpha [13].
FT 232 421 MH2 domain [3].
FT 236 413 PF03166; MH2 domain.
FT 240 411 SM00524; DWB.
FT 242 435 PS51076; MH2.
FT 422 425 SSXS motif [3].
XX
SF conflict between EMBL entry #AB004930 and EMBL entry #U68019, in which an aa-sequence of 425 AAs in length is described based on RNA in contrast to the one based on DNA in EMBL #AB004930;
SF from AA 178 an insertion of 10 AAs (VGTWAAQAGL) is described in EMBL #AB004930;
SF interaction with TGIF T04076 [2];
SF interaction with c-Jun T00133 [6] [7] [9];
SF interaction with JunB T01977 [9];
SF NLS (Nuclear Localization Signal) determines the ligand-induced nuclear translocation [10];
SF a novel DNA-binding motif, a beta hairpin, binds asymmetrically in the DNA major groove and consists of Leu-75, Gln-76, Val-77, Arg-80, Lys-81, Gly-82, Ser-78 and His-79 [5];
SF Smad-2, in comparison, contains the additional exon, also called TID, and is therefore sterically hindered to bind to DNA [12];
XX
EX brain,,,adult; detectable; Northern blot; RNA (undefined); [4].
EX heart,,,adult; detectable; Northern blot; RNA (undefined); [4].
EX kidney (right and left),,,adult; detectable; Northern blot; RNA (undefined); [4].
EX liver,,,adult; detectable; Northern blot; RNA (undefined); [4].
EX lung (right and left),,,adult; detectable; Northern blot; RNA (undefined); [4].
EX muscles,,,adult; high; Northern blot; RNA (undefined); [4].
EX pancreas,,,adult; detectable; Northern blot; RNA (undefined); [4].
EX placenta,,,adult; detectable; Northern blot; RNA (undefined); [4].
XX
FF Evi-1 antagonizes in TGF-beta signaling by quenching Smad3-isoform1 [8];
FF the first zinc finger domain Evi-1 is essential for the interaction with Smad3-isoform1, whereas the MH2 domain of Smad-3 is essential for the interaction with Evi-1 [8];
FF it is indicated that Evi-1 abrogates the interaction of the Smad3-isoform1 complex with ist binding sequence in DNA in the nucleus [8];
XX
IN T08487 AR-isoform1; human, Homo sapiens.
IN T02872 beta-catenin; human, Homo sapiens.
IN T14513 beta-catenin; Mammalia.
IN T05220 Evi-1; human, Homo sapiens.
IN T09366 foxl2; mouse, Mus musculus.
IN T02516 foxm1-isoform2; human, Homo sapiens.
IN T04106 HDAC1; human, Homo sapiens.
IN T08343 HDAC1; human, Homo sapiens.
IN T05490 Hic-5; human, Homo sapiens.
IN T01610 HIF-1alpha; human, Homo sapiens.
IN T03828 HNF-4alpha; human, Homo sapiens.
IN T05288 HNF-4alpha; rat, Rattus norvegicus.
IN T02905 LEF-1-isoform1; human, Homo sapiens.
IN T00930 LEF-1; mouse, Mus musculus.
IN T08862 pitx1; mouse, Mus musculus.
IN T17005 pitx2c; mouse, Mus musculus.
IN T04597 SKIP; human, Homo sapiens.
IN T04095 Smad2-L; human, Homo sapiens.
IN T04292 Smad4; human, Homo sapiens.
IN T02918 TCF-4; human, Homo sapiens.
IN T04076 TGIF; human, Homo sapiens.
XX
MX M00701 V$SMAD3_Q6.
MX M01888 V$SMAD3_Q6_01.
MX M07429 V$SMAD3_Q6_02.
MX M08897 V$SMAD_Q4.
MX M00792 V$SMAD_Q6.
MX M00974 V$SMAD_Q6_01.
XX
BS R09884.
BS R10004.
BS R04874.
BS R04875.
BS R10092.
BS R09955.
BS R13585.
BS R09952.
BS R73962.
BS R09881.
BS R09937.
BS R29688.
BS R14158.
BS R37750.
BS R09967.
BS R10078.
BS R10079.
BS R73965.
BS R26661.
BS R73964.
BS R10061.
BS R10063.
BS R10066.
BS R36891.
BS R13040.
BS R13041.
BS R10069.
XX
DR TRANSPATH: MO000019780.
DR TRANSCOMPEL: C00194.
DR TRANSCOMPEL: C00195.
DR TRANSCOMPEL: C00196.
DR TRANSCOMPEL: C00197.
DR TRANSCOMPEL: C00198.
DR TRANSCOMPEL: C00245.
DR TRANSCOMPEL: C00371.
DR TRANSCOMPEL: C00394.
DR TRANSCOMPEL: C00395.
DR TRANSCOMPEL: C00396.
DR EMBL: AB004930; AB004930.
DR UniProtKB: P84022-1;
XX
RN [1]; RE0006197.
RX PUBMED: 9335507.
RA Nakao A., Afrakhte M., Moren A., Nakayama T., Christian J. L., Heuchel R., Itoh S., Kawabata M., Heldin N. E., Heldin C. H., ten Dijke P.
RT Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling
RL Nature 389:631-635 (1997).
RN [2]; RE0015456.
RX PUBMED: 10199400.
RA Wotton D., Lo R. S., Lee S., Massague J.
RT A Smad transcriptional corepressor
RL Cell 97:29-39 (1999).
RN [3]; RE0015661.
RX PUBMED: 11087923.
RA Beall M. J., McGonigle S., Pearce E. J.
RT Functional conservation of schistosoma mansoni smads in TGF-beta signaling
RL Mol. Biochem. Parasitol. 111:131-142 (2000).
RN [4]; RE0015715.
RX PUBMED: 9503010.
RA Takenoshita S., Mogi A., Nagashima M., Yang K., Yagi K., Hanyu A., Nagamachi Y., Miyazono K., Hagiwara K.
RT Characterization of the MADH2/Smad2 gene, a human Mad homolo responsible for the transforming growth factor-beta and activin signal transduction pathway
RL Genomics 48:1-11 (1998).
RN [5]; RE0015728.
RX PUBMED: 9741623.
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 binding in TGF-beta signaling
RL Cell 94:585-594 (1998).
RN [6]; RE0015799.
RX PUBMED: 10995748.
RA Qing J., Zhang Y., Derynck R.
RT Structural and functional characterization of the transforming growth factor-beta -induced Smad3/c-Jun transcriptional cooperativity
RL J. Biol. Chem. 275:38802-38812 (2000).
RN [7]; RE0015800.
RX PUBMED: 9732876.
RA Zhang Y., Feng X. H., Derynck R.
RT Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription
RL Nature 394:909-913 (1998).
RN [8]; RE0016065.
RX PUBMED: 9665135.
RA Kurokawa M., Mitani K., Irie K., Matsuyama T., Takahashi T., Chiba S., 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 [9]; RE0016071.
RX PUBMED: 10220381.
RA Liberati N. T., Datto M. B., Frederick J. P., Shen X., Wong C., Rougier-Chapman E. M., Wang X. F.
RT Smads bind directly to the Jun family of AP-1 transcription factors.
RL Proc. Natl. Acad. Sci. USA 96:4844-4849 (1999).
RN [10]; RE0016203.
RX PUBMED: 10884415.
RA Xiao Z., Liu X., Henis Y. I., Lodish H. F.
RT A distinct nuclear localization signal in the N terminus of Smad 3 determines its ligand-induced nuclear translocation.
RL Proc. Natl. Acad. Sci. USA 97:7853-7858 (2000).
RN [11]; RE0016380.
RX PUBMED: 11074002.
RA Pierreux C. E., Nicolas F. J., Hill C. S.
RT Transforming growth factor beta-independent shuttling of Smad4 between the cytoplasm and nucleus.
RL Mol. Cell. Biol. 20:9041-9054 (2000).
RN [12]; RE0016515.
RX PUBMED: 10102636.
RA Dennler S., Huet S., Gauthier J. M.
RT A short amino-acid sequence in MH1 domain is responsible for functional differences between Smad2 and Smad3.
RL Oncogene 18:1643-1648 (1999).
RN [13]; RE0022199.
RX PUBMED: 11486006.
RA Sanchez-Elsner T., Botella L. M., Velasco B., Corbi A., Attisano L., Bernabeu C.
RT Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression.
RL J. Biol. Chem. 276:38527-38535 (2001).
RN [14]; RE0028090.
RX PUBMED: 11438668.
RA Furuhashi M., Yagi K., Yamamoto H., Furukawa Y., Shimada S., Nakamura Y., Kikuchi A., Miyazono K., Kato M.
RT Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway.
RL Mol. Cell. Biol. 21:5132-41 (2001).
RN [15]; RE0031346.
RX PUBMED: 12650946.
RA Warner D. R., Pisano M. M., Roberts E. A., Greene R. M.
RT Identification of three novel Smad binding proteins involved in cell polarity.
RL FEBS Lett. 539:167-73 (2003).
RN [16]; RE0041859.
RX PUBMED: 11306568.
RA Liberati N. T., Moniwa M., Borton A. J., Davie J. R., Wang X. F.
RT An essential role for Mad homology domain 1 in the association of Smad3 with histone deacetylase activity*
RL J. Biol. Chem. 276:22595-603 (2001).
RN [17]; RE0042994.
RX PUBMED: 14651998.
RA Warner D. R., Roberts E. A., Greene R. M., Pisano M. M.
RT Identification of novel Smad binding proteins
RL Biochem. Biophys. Res. Commun. 312:1185-90 (2003).
RN [18]; RE0048068.
RX PUBMED: 15464984.
RA Warner D. R., Bhattacherjee V., Yin X., Singh S., Mukhopadhyay P., Pisano M. M., Greene R. M.
RT Functional interaction between Smad, CREB binding protein, and p68 RNA helicase.
RL Biochem. Biophys. Res. Commun. 324:70-76 (2004).
RN [19]; RE0048069.
RX PUBMED: 14559231.
RA Ellis L. R., Warner D. R., Greene R. M., Pisano M. M.
RT Interaction of Smads with collagen types I, III, and V.
RL Biochem. Biophys. Res. Commun. 310:1117-1123 (2003).
RN [20]; RE0064308.
RX PUBMED: 18056415.
RA Morita T., Mayanagi T., Sobue K.
RT Dual roles of myocardin-related transcription factors in epithelial mesenchymal transition via slug induction and actin remodeling.
RL J. Cell Biol. 179:1027-1042 (2007).
RN [21]; RE0068203.
RX PUBMED: 18339718.
RA Lamba P., Khivansara V., D'Alessio A. C., Santos M. M., Bernard D. J.
RT Paired-like homeodomain transcription factors 1 and 2 regulate follicle-stimulating hormone beta-subunit transcription through a conserved cis-element.
RL Endocrinology 149:3095-3108 (2008).
RN [22]; RE0070931.
RX PUBMED: 20592275.
RA Giroux M., Delisle J. S., O Brien A., Hebert M. J., Perreault C.
RT T cell activation leads to protein kinase C theta-dependent inhibition of TGF-beta signaling.
RL J. Immunol. 185:1568-1576 (2010).
RN [23]; RE0071921.
RX PUBMED: 18321991.
RA Kim W., Seok Kang Y., Soo Kim J., Shin N. Y., Hanks S. K., Song W. K.
RT The integrin-coupled signaling adaptor p130Cas suppresses Smad3 function in transforming growth factor-beta signaling.
RL Mol. Biol. Cell 19:2135-2146 (2008).
RN [24]; RE0072535.
RX PUBMED: 18568018.
RA Varelas X., Sakuma R., Samavarchi-Tehrani P., Peerani R., Rao B. M., Dembowy J., Yaffe M. B., Zandstra P. W., Wrana J. L.
RT TAZ controls Smad nucleocytoplasmic shuttling and regulates human embryonic stem-cell self-renewal.
RL Nat. Cell Biol. 10:837-848 (2008).
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