TRANSFAC FACTOR TABLE, Release 2017.2 - public - 2017-06-30, (C) QIAGEN

AC T04292 XX ID T04292 XX DT 05.02.2001 (created); dkl. DT 19.01.2016 (updated); sup. CO Copyright (C), QIAGEN. XX FA Smad4 XX SY DPC4 (Deleted in pancreatic cancer); SMAD-4. XX OS human, Homo sapiens OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates XX GE G002389 SMAD4; HGNC: SMAD4. XX HO MEDEA, Drosophila Smad4 T04379 [7]. XX CL C0041; SMAD; XX SF structure of CTD (C-terminal domain or MH2 domain) consists of a beta-sandwich with a three-helix bundle on one end and a collection of three large loops and an alpha-helix on the other [1]; SF CTD contains a primary homo-oligomerization activity [1]; SF a model of hetero-oligomerization is suitable from a structural perspective, in which a heterohexamer between Smad4 and Smad2 trimers is formed [1]; SF transcriptional activity is located in C-terminal domain [2]; SF interaction with JunB T01977 and c-Jun T00133 [8]; SF SAD domain (Smad4 activation domain) within the middle-linker region is essential for mediation of signaling responses [10]; SF NH2-terminal domain augments ligand-dependent activation associated with the middle-linker region, indicating a distinct ligand-response domain within the N terminus [10]; SF defective NLS (Nuclear Localization Signal) in comparison to R-Smads [11]; SF functional NLS (Nuclear Localization Signal) in its MH1 domain is required for the rapid transport to the nucleus, even in absence of TGF-beta [15]; SF Nuclear Export Signal (NES) in exon 3, a functional leucine-rich motif, actively directs nuclear export, which is necessary, but not sufficient for the nuclear export [12] [15]; SF SAD provides transcriptional capability by presenting proline-rich and glutamine-rich surfaces for interaction with transcription partners [13]; SF the structure implicates that sulfate-ion-binding sites are potential receptors for the phosphorylated sequence of R-SMADs in forming a heteromeric complex [13]; SF Smad4 (delta275-322) forms heteromeric complexes with Smad2 and undergoes ligand-dependent nuclear translocation in the presence of overexpressed Smad2 [9]; SF a preservation of the C-terminal structure is suggested in Smad4 (delta275-322) and indicated is the principal effect of SAD deletion is to interfere with the nuclear activities of Smad4 [9]; SF analysis of the genomic sequence reveals that any of the five exons between the end of the MH1 domain (exon 2) and the beginning of the MH2 domain (exon 8) can be deleted while maintaining the correct reading frame, T04554, T04555>, T04557, T04558, T04559>, T04560 [15]; SF interaction via the MH2 domain with an orphan transcriptional activator MSG1 [18]; SF enhancement of transcription by MSG1 depends on TGF-beta [18]; XX FF TGFbeta1 treatment increased the protein level [30]; FF LOX downregulates this protein [30]; FF nuclear translocation depends on receptor activated Smads, like Smad1 or Smad2 in response to BMP4 or TGF-beta [4]; FF it is surmised that activated Smads bind Smad4 in the cytoplasm and carry it into the nucleus [4]; FF forms a ternary complex with Smad1 and FoxH1(=FAST-1) in presence of TGF-beta [4]; FF transcriptional activation by the SAD is functionally dependent on p300, especially the N-terminus [9]; FF it appears that germ line mutations cannot account for many of the familial aggregations of pancreatic carcinoma [5]; FF important role in the development of gastrointestinal tumors [14]; FF this mutant form is predicted to be truncated at the C-terminus and lack sequences required for normal function [14]; FF a four base pair deletion was detected in exon 9, resulting in deletion of codons 414 to 416, causing a frameshift that creates a new stop codon at the end of exon 9, codon 434 [14]; FF the C-domain is required for the transcriptional activation by receptor-regulated Smads, like Smad1 and Smad2 [4]; FF sequences of exons 5, 6, and 7 are all required for full TGF-beta induced activation by Smad4 [15]; FF co-activation of PAI-1 promoter together with Smad3 T04431 and p300 [16]; FF in the absence of TGF-beta, SnoN (SKI-RELATED ONCOGENE SNO-N) binds to the nuclear Smad4 and represses TGF-beta responsive promoter activity through recruitment of a nuclear repressor complex [17]; FF TGF-beta induces activation and nuclear translocation of Smad2, Smad3 and Smad4 [17]; FF Smad3 causes degradation of SnoN, allowing a Smad2 and Smad4 complex to activate TGF-beta target genes [17]; XX IN T30493 Alpha-1-antitrypsin; human, Homo sapiens. IN T02872 beta-catenin; human, Homo sapiens. IN T02211 BTEB2; human, Homo sapiens. IN T08470 Daxx-isoform1; human, Homo sapiens. IN T02944 Daxx; human, Homo sapiens. IN T08100 EWS; human, Homo sapiens. IN T10353 FOXO1A; human, Homo sapiens. IN T02938 FOXO3a; human, Homo sapiens. IN T03403 foxo4; human, Homo sapiens. IN T00330 GLI; human, Homo sapiens. IN T03828 HNF-4alpha; human, Homo sapiens. IN T05288 HNF-4alpha; rat, Rattus norvegicus. IN T00930 LEF-1; mouse, Mus musculus. IN T22348 NF-1; human, Homo sapiens. IN T21984 p300; human, Homo sapiens. IN T03885 Smad1; human, Homo sapiens. IN T04095 Smad2-L; human, Homo sapiens. IN T10683 Smad2; human, Homo sapiens. IN T04096 Smad3-isoform1; human, Homo sapiens. IN T10378 Smad3; human, Homo sapiens. IN T04220 Smad6; human, Homo sapiens. IN T04238 Smad8; rat, Rattus norvegicus. IN T05997 Smad8; human, Homo sapiens. IN T00759 Sp1; human, Homo sapiens. IN T02338 Sp3; human, Homo sapiens. IN T04946 TIF1g; human, Homo sapiens. XX MX M07368 V$SMAD4_Q4. MX M00733 V$SMAD4_Q6. MX M01889 V$SMAD4_Q6_01. MX M08897 V$SMAD_Q4. MX M00792 V$SMAD_Q6. MX M00974 V$SMAD_Q6_01. XX BS R10004. BS R10101. BS R25992. BS R26001. BS R38826. BS R38828. BS R38829. BS R38830. BS R38831. BS R04874. BS R32454. BS R62063. BS R67615. BS R64275. BS R64276. BS R64277. BS R64278. BS R24229. BS R33954. BS R39142. BS R23966. BS R24272. BS R68470. BS R66363. BS R09952. BS R73962. BS R72866. BS R72867. BS R72868. BS R72869. BS R36817. BS R40912. BS R26795. BS R09937. BS R39147. BS R39152. BS R29688. BS R64236. BS R57121. BS R62271. BS R32033. BS R29441. BS R23083. BS R09967. BS R10078. BS R10079. BS R30322. BS R32452. BS R34710. BS R23469. BS R21773. BS R23189. BS R25990. BS R10061. BS R09916. BS R10093. BS R13039. BS R13040. BS R13041. BS R10069. BS R10070. BS R10099. XX DR TRANSPATH: MO000020402. DR TRANSCOMPEL: C00194. DR TRANSCOMPEL: C00195. DR TRANSCOMPEL: C00199. DR TRANSCOMPEL: C00539. DR TRANSCOMPEL: C00574. DR PATHODB: MT010816. DR PATHODB: MT010817. DR PATHODB: MT010818. DR PATHODB: MT010820. DR PATHODB: MT010824. DR PATHODB: MT010825. DR PATHODB: MT010826. DR PATHODB: MT010827. DR PATHODB: MT010828. DR PATHODB: MT010830. DR PATHODB: MT010831. DR PATHODB: MT010832. DR PATHODB: MT010834. DR PATHODB: MT010835. DR PATHODB: MT010836. DR PATHODB: MT010837. DR PATHODB: MT010838. DR PATHODB: MT010839. DR PATHODB: MT010840. DR PATHODB: MT010841. DR PATHODB: MT010842. DR PATHODB: MT010843. DR PATHODB: MT010844. DR PATHODB: MT010845. DR PATHODB: MT010846. DR PATHODB: MT010847. DR PATHODB: MT010848. DR PATHODB: MT010849. DR PATHODB: MT010850. DR PATHODB: MT010857. DR UniProtKB: Q13485; Q13485. XX RN [1]; RE0006139. RX PUBMED: 9214508. RA Shi Y., Hata A., Lo R. S., Massague J., Pavletich N. P. RT A strucural basis for mutational inactivation of the tumour suppressor Smad4 RL Nature 388:87-93 (1997). RN [2]; RE0015117. RX PUBMED: 8637600. RA Liu F., Hata A., Baker J.C., Doody J., Carcamo J., Harland R.M., Massague J. RT A human Mad protein acting as a BMP-regulated transcriptional activator RL Nature 381:620-623 (1996). RN [3]; RE0015642. RX PUBMED: 9335505. RA Imamura T., Takase M., Nishihara A., Oeda E., Hanai J., Kawabata M., Miyazono K. RT Smad6 inhibits signalling by the TGF-beta superfamily RL Nature 389:622-626 (1997). RN [4]; RE0015707. RX PUBMED: 9389648. RA Liu F., Pouponnot C., Massague J. RT Dual role of the Smad4/DPC4 tumor suppressor in TGFbeta-inducible transcriptional complexes RL Genes Dev. 11:3157-3167 (1997). RN [5]; RE0015713. RX PUBMED: 9098646. RA Moskaluk C. A., Hruban R. H., Schutte M., Lietman A. S., Smyrk T., Fusaro L., Fusaro R., Lynch J., Yeo C. J., Jackson C. E., Lynch H. T., Kern S. E. RT Genomic sequencing of DPC4 in the analysis of familial pancreatic carcinoma RL Diagn. Mol. Pathol. 6:85-90 (1997). RN [6]; RE0015714. RX PUBMED: 8553070. RA Hahn S. A., Schutte M., Hoque A. T., Moskaluk C. A., da Costa L. T., Rozenblum E., Weinstein C. L., Fischer A., Yeo C. J., Hruban R. H., Kern S. E. RT DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1 RL Science 271:350-353 (1996). RN [7]; RE0015899. RX PUBMED: 9502722. RA Hudson J. B., Podos S. D., Keith K., Simpson S. L., Ferguson E. L. RT The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4. RL Development 125:1407-1420 (1998). RN [8]; 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 [9]; RE0016085. RX PUBMED: 10636916. RA de Caestecker M. P., Yahata T., Wang D., Parks W. T., Huang S., Hill C. S., Shioda T., Roberts A. B., Lechleider R. J. RT The Smad4 activation domain (SAD) is a proline-rich, p300-dependent transcriptional activation domain. RL J. Biol. Chem. 275:2115-2122 (2000). RN [10]; RE0016086. RX PUBMED: 9153220. RA de Caestecker M. P., Hemmati P., Larisch-Bloch S., Ajmera R., Roberts A. B., Lechleider R. J. RT Characterization of functional domains within Smad4/DPC4. RL J. Biol. Chem. 272:13690-13696 (1997). RN [11]; 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 [12]; RE0016210. RX PUBMED: 11265759. RA Watanabe M., Masuyama N., Fukuda M., Nishida E. RT Regulation of intracellular dynamics of Smad4 by its leucine-rich nuclear export signal. RL EMBO J. 1:176-182 (2000). RN [13]; RE0016218. RX PUBMED: 10647180. RA Qin B., Lam S. S., Lin K. RT Crystal structure of a transcriptionally active Smad4 fragment. RL Structure 7:1493-1503 (1999). RN [14]; RE0016377. RX PUBMED: 9582123. RA Howe J. R., Roth S., Ringold J. C., Summers R. W., Jarvinen H. J., Sistonen P., Tomlinson I. P., Houlston R. S., Bevan S., Mitros F. A., Stone E. M., Aaltonen L. A. RT Mutations in the SMAD4/DPC4 gene in juvenile polyposis. RL Science 280:1086-1088 (1998). RN [15]; 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 [16]; RE0016417. RX PUBMED: 9679056. RA Janknecht R., Wells N. J., Hunter T. RT TGF-beta-stimulated cooperation of smad proteins with the coactivators CBP/p300. RL Genes Dev. 12:2114-2119 (1998). RN [17]; RE0016418. RX PUBMED: 10531062. RA Stroschein S. L., Wang W., Zhou S., Zhou Q., Luo K. RT Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. RL Science 286:771-774 (1999). RN [18]; RE0016518. RX PUBMED: 9707553. RA Shioda T., Lechleider R. J., Dunwoodie S. L., Li H., Yahata T., de Caestecker M. P., Fenner M. H., Roberts A. B., Isselbacher K. J. RT Transcriptional activating activity of Smad4: roles of SMAD hetero-oligomerization and enhancement by an associating transactivator. RL Proc. Natl. Acad. Sci. USA 95:9785-9790 (1998). RN [19]; RE0021468. RX PUBMED: 11792802. RA Moustakas A., Souchelnytskyi S., Heldin C. H. RT Smad regulation in TGF-beta signal transduction RL J. Cell Sci. 114:4359-4369 (2001). RN [20]; RE0030982. RX PUBMED: 15084259. RA Seoane J., Le H. V., Shen L., Anderson S. A., Massague J. RT Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. RL Cell 117:211-23 (2004). RN [21]; 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 [22]; RE0032276. RX PUBMED: 14612411. RA Kim D. W., Lassar A. B. RT Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. RL Mol. Cell. Biol. 23:8704-17 (2003). RN [23]; 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 [24]; RE0043321. RX PUBMED: 14612439. RA Lee H. J., Lee J. K., Miyake S., Kim S. J. RT A novel E1A-like inhibitor of differentiation (EID) family member, EID-2, suppresses transforming growth factor (TGF)-beta signaling by blocking TGF-beta-induced formation of Smad3-Smad4 complexes RL J. Biol. Chem. 279:2666-72 (2004). RN [25]; RE0047907. RX PUBMED: 12193595. RA Funaba M., Zimmerman C. M., Mathews L. S. RT Modulation of Smad2-mediated signaling by extracellular signal-regulated kinase. RL J. Biol. Chem. 277:41361-41368 (2002). RN [26]; 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 [27]; 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 [28]; RE0048843. RX PUBMED: 15637079. RA Chang C. C., Lin D. Y., Fang H. I., Chen R. H., Shih H. M. RT Daxx mediates the small ubiquitin-like modifier-dependent transcriptional repression of Smad4. RL J. Biol. Chem. 280:10164-10173 (2005). RN [29]; RE0049583. RX PUBMED: 17327236. RA Seong H. A., Jung H., Kim K. T., Ha H. RT 3-phosphoinositide-dependent protein kinase-1 (PDK1) negatively regulates TGF-beta -induced signaling in a kinase-dependent manner through physical interaction with Smad proteins. RL J. Biol. Chem. 282:12272-12289 (2007). 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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 [34]; RE0073068. RX PUBMED: 18519565. RA Yao X., Chen X., Cottonham C., Xu L. RT Preferential utilization of Imp7/8 in nuclear import of Smads. RL J. Biol. Chem. 283:22867-22874 (2008). XX //