SMAD3_RAT
ID SMAD3_RAT Reviewed; 425 AA.
AC P84025; O09064; O09144; O14510; O35273; Q92940; Q93002; Q9GKR4;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Mothers against decapentaplegic homolog 3;
DE Short=MAD homolog 3;
DE Short=Mad3;
DE Short=Mothers against DPP homolog 3;
DE AltName: Full=SMAD family member 3;
DE Short=SMAD 3;
DE Short=Smad3;
GN Name=Smad3; Synonyms=Madh3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=8917532; DOI=10.1073/pnas.93.23.12992;
RA Chen Y., Lebrun J.-J., Vale W.W.;
RT "Regulation of transforming growth factor beta- and activin-induced
RT transcription by mammalian Mad proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12992-12997(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH MEN1.
RX PubMed=11274402; DOI=10.1073/pnas.061358098;
RA Kaji H., Canaff L., Lebrun J.J., Goltzman D., Hendy G.N.;
RT "Inactivation of menin, a Smad3-interacting protein, blocks transforming
RT growth factor type beta signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:3837-3842(2001).
RN [4]
RP INTERACTION WITH CITED2.
RX PubMed=16619037; DOI=10.1038/sj.onc.1209552;
RA Chou Y.T., Wang H., Chen Y., Danielpour D., Yang Y.C.;
RT "Cited2 modulates TGF-beta-mediated upregulation of MMP9.";
RL Oncogene 25:5547-5560(2006).
CC -!- FUNCTION: Receptor-regulated SMAD (R-SMAD) that is an intracellular
CC signal transducer and transcriptional modulator activated by TGF-beta
CC (transforming growth factor) and activin type 1 receptor kinases. Binds
CC the TRE element in the promoter region of many genes that are regulated
CC by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates
CC transcription. Can also form a SMAD3/SMAD4/JUN/FOS complex at the AP-
CC 1/SMAD site to regulate TGF-beta-mediated transcription. Has an
CC inhibitory effect on wound healing probably by modulating both growth
CC and migration of primary keratinocytes and by altering the TGF-mediated
CC chemotaxis of monocytes. This effect on wound healing appears to be
CC hormone-sensitive. Regulator of chondrogenesis and osteogenesis and
CC inhibits early healing of bone fractures. Positively regulates PDPK1
CC kinase activity by stimulating its dissociation from the 14-3-3 protein
CC YWHAQ which acts as a negative regulator (By similarity).
CC {ECO:0000250|UniProtKB:P84022, ECO:0000269|PubMed:8917532}.
CC -!- SUBUNIT: Monomer; in the absence of TGF-beta (By similarity).
CC Homooligomer; in the presence of TGF-beta (By similarity).
CC Heterotrimer; forms a heterotrimer in the presence of TGF-beta
CC consisting of two molecules of C-terminally phosphorylated SMAD2 or
CC SMAD3 and one of SMAD4 to form the transcriptionally active
CC SMAD2/SMAD3-SMAD4 complex (By similarity). Part of a complex consisting
CC of AIP1, ACVR2A, ACVR1B and SMAD3 (By similarity). Forms a complex with
CC SMAD2 and TRIM33 upon addition of TGF-beta (By similarity). Found in a
CC complex composed of SMAD3, RAN and XPO4; within the complex interacts
CC directly with XPO4 (By similarity). Component of the multimeric complex
CC SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for
CC synergistic transcriptional activity in response to TGF-beta (By
CC similarity). Interacts (via an N-terminal domain) with JUN (via its
CC basic DNA binding and leucine zipper domains); this interaction is
CC essential for DNA binding and cooperative transcriptional activity in
CC response to TGF-beta (By similarity). Identified in a complex that
CC contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (By similarity).
CC Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-
CC terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex,
CC nuclear export and termination of TGF-beta signaling (By similarity).
CC Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the
CC TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4
CC transcriptional complex (By similarity). Interacts (when
CC phosphorylated) with RNF111; RNF111 acts as an enhancer of the
CC transcriptional responses by mediating ubiquitination and degradation
CC of SMAD3 inhibitors (By similarity). Interacts (dephosphorylated form
CC via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain);
CC the interaction results in the export of dephosphorylated SMAD3 out of
CC the nucleus and termination of the TGF-beta signaling (By similarity).
CC Interacts (via MH2 domain) with LEMD3; the interaction represses SMAD3
CC transcriptional activity through preventing the formation of the
CC heteromeric complex with SMAD4 and translocation to the nucleus (By
CC similarity). Interacts (via the linker region) with EP300 (C-terminal);
CC the interaction promotes SMAD3 acetylation and is enhanced by TGF-beta
CC phosphorylation in the C-terminal of SMAD3 (By similarity). This
CC interaction can be blocked by competitive binding of adenovirus
CC oncoprotein E1A to the same C-terminal site on EP300, which then
CC results in partially inhibited SMAD3/SMAD4 transcriptional activity (By
CC similarity). Interacts with TGFBR1 (By similarity). Interacts with
CC TGFB1I1 (By similarity). Interacts with PRDM16 (By similarity).
CC Interacts with SNW1 (By similarity). Interacts (via MH2 domain) with
CC ZFYVE9 (By similarity). Interacts with HDAC1 (By similarity). Interacts
CC with TGIF2 (By similarity). Interacts with SKOR1 (By similarity).
CC Interacts with SKOR2 (By similarity). Interacts with DACH1; the
CC interaction inhibits the TGF-beta signaling (By similarity). Interacts
CC with RBPMS (By similarity). Interacts (via MH2 domain) with MECOM (By
CC similarity). Interacts with WWTR1 (via its coiled-coil domain) (By
CC similarity). Interacts with SKI; the interaction represses SMAD3
CC transcriptional activity (By similarity). Interacts with MEN1
CC (PubMed:11274402). Interacts with IL1F7 (By similarity). Interaction
CC with CSNK1G2 (By similarity). Interacts with PDPK1 (via PH domain) (By
CC similarity). Interacts with DAB2; the interactions are enhanced upon
CC TGF-beta stimulation (By similarity). Interacts with USP15 (By
CC similarity). Interacts with PPP5C; the interaction decreases SMAD3
CC phosphorylation and protein levels (By similarity). Interacts with
CC LDLRAD4 (via the SMAD interaction motif) (By similarity). Interacts
CC with PMEPA1 (By similarity). Interacts with ZNF451 (By similarity).
CC Interacts with ZFHX3 (By similarity). Interacts weakly with ZNF8 (By
CC similarity). Interacts with STUB1, HSPA1A, HSPA1B, HSP90AA1 and
CC HSP90AB1 (By similarity). Interacts with YAP1 (when phosphorylated at
CC 'Ser-112') (By similarity). Interacts with AIP1 (By similarity).
CC Interacts (via MH2 domain) with CITED2 (via C-terminus)
CC (PubMed:16619037). Interacts with HGS (By similarity). Interacts with
CC WWP1 (By similarity). Interacts with TTRAP (By similarity). Interacts
CC with FOXL2 (By similarity). Interacts with PML (By similarity).
CC Interacts with NEDD4L; the interaction requires TGF-beta stimulation
CC (By similarity). Interacts with ZC3H3 (By similarity). Interacts with
CC TGIF. Interacts with CREBBP. Interacts with ATF2.
CC {ECO:0000250|UniProtKB:P84022, ECO:0000250|UniProtKB:Q8BUN5,
CC ECO:0000269|PubMed:11274402, ECO:0000269|PubMed:16619037}.
CC -!- INTERACTION:
CC P84025; P47196: Akt1; NbExp=4; IntAct=EBI-7201857, EBI-7204362;
CC P84025; P59595: N; Xeno; NbExp=4; IntAct=EBI-7201857, EBI-7602718;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P84022}. Nucleus
CC {ECO:0000269|PubMed:8917532}. Note=Cytoplasmic and nuclear in the
CC absence of TGF-beta (By similarity). On TGF-beta stimulation, migrates
CC to the nucleus when complexed with SMAD4 (By similarity). Through the
CC action of the phosphatase PPM1A, released from the SMAD2/SMAD4 complex,
CC and exported out of the nucleus by interaction with RANBP1 (By
CC similarity). Co-localizes with LEMD3 at the nucleus inner membrane.
CC MAPK-mediated phosphorylation appears to have no effect on nuclear
CC import (By similarity). PDPK1 prevents its nuclear translocation in
CC response to TGF-beta (By similarity). Localized mainly to the nucleus
CC in the early stages of embryo development with expression becoming
CC evident in the cytoplasm of the inner cell mass at the blastocyst stage
CC (By similarity). {ECO:0000250|UniProtKB:P84022,
CC ECO:0000250|UniProtKB:Q8BUN5}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain and ovary. Detected
CC in the pyramidal cells of the hippocampus, granule cells of the dentate
CC gyrus, granular cells of the cerebral cortex and the granulosa cells of
CC the ovary.
CC -!- DOMAIN: The MH1 domain is required for DNA binding (By similarity).
CC Also binds zinc ions which are necessary for the DNA binding.
CC {ECO:0000250}.
CC -!- DOMAIN: The MH2 domain is required for both homomeric and heteromeric
CC interactions and for transcriptional regulation. Sufficient for nuclear
CC import (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The linker region is required for the TGFbeta-mediated
CC transcriptional activity and acts synergistically with the MH2 domain.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine and threonine residues. Enhanced
CC phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on
CC EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated
CC phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle
CC dependent manner and inhibits both the transcriptional activity and
CC antiproliferative functions of SMAD3. This phosphorylation is inhibited
CC by flavopiridol. Maximum phosphorylation at the G(1)/S junction. Also
CC phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1
CC and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is
CC required for interaction with SMAD4, nuclear location and
CC transactivational activity, and appears to be a prerequisite for the
CC TGF-beta mediated phosphorylation in the linker region.
CC Dephosphorylated in the C-terminal SXS motif by PPM1A. This
CC dephosphorylation disrupts the interaction with SMAD4, promotes nuclear
CC export and terminates TGF-beta-mediated signaling. Phosphorylation at
CC Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and
CC subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-
CC beta responses. Phosphorylated by PDPK1 (By similarity).
CC {ECO:0000250|UniProtKB:P84022}.
CC -!- PTM: Acetylation in the nucleus by EP300 in the MH2 domain regulates
CC positively its transcriptional activity and is enhanced by TGF-beta.
CC {ECO:0000250|UniProtKB:P84022}.
CC -!- PTM: Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding.
CC Deubiquitination by USP15 alleviates inhibition and promotes activation
CC of TGF-beta target genes. Ubiquitinated by RNF111, leading to its
CC degradation: only SMAD3 proteins, that are 'in use' are targeted by
CC RNF111, RNF111 playing a key role in activating SMAD3 and regulating
CC its turnover. Undergoes STUB1-mediated ubiquitination and degradation.
CC {ECO:0000250|UniProtKB:P84022, ECO:0000250|UniProtKB:Q8BUN5}.
CC -!- PTM: Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation
CC negatively regulates SMAD3 transcriptional responses during the course
CC of TGF-beta signaling. {ECO:0000250|UniProtKB:P84022}.
CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}.
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DR EMBL; U66479; AAC52944.1; -; mRNA.
DR EMBL; BC064437; AAH64437.1; -; mRNA.
DR RefSeq; NP_037227.1; NM_013095.3.
DR AlphaFoldDB; P84025; -.
DR SMR; P84025; -.
DR BioGRID; 247660; 3.
DR CORUM; P84025; -.
DR IntAct; P84025; 2.
DR MINT; P84025; -.
DR STRING; 10116.ENSRNOP00000037346; -.
DR ChEMBL; CHEMBL3784913; -.
DR iPTMnet; P84025; -.
DR PhosphoSitePlus; P84025; -.
DR jPOST; P84025; -.
DR PaxDb; P84025; -.
DR PRIDE; P84025; -.
DR Ensembl; ENSRNOT00000039730; ENSRNOP00000037346; ENSRNOG00000008620.
DR GeneID; 25631; -.
DR KEGG; rno:25631; -.
DR UCSC; RGD:3032; rat.
DR CTD; 4088; -.
DR RGD; 3032; Smad3.
DR eggNOG; KOG3701; Eukaryota.
DR GeneTree; ENSGT00940000153499; -.
DR HOGENOM; CLU_026736_0_0_1; -.
DR InParanoid; P84025; -.
DR OMA; MKHRLGA; -.
DR OrthoDB; 608001at2759; -.
DR PhylomeDB; P84025; -.
DR TreeFam; TF314923; -.
DR Reactome; R-RNO-1181150; Signaling by NODAL.
DR Reactome; R-RNO-1502540; Signaling by Activin.
DR Reactome; R-RNO-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-RNO-2173789; TGF-beta receptor signaling activates SMADs.
DR Reactome; R-RNO-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-RNO-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-8941855; RUNX3 regulates CDKN1A transcription.
DR Reactome; R-RNO-9617828; FOXO-mediated transcription of cell cycle genes.
DR PRO; PR:P84025; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000008620; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; P84025; RN.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0071144; C:heteromeric SMAD protein complex; ISO:RGD.
DR GO; GO:0005637; C:nuclear inner membrane; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0071141; C:SMAD protein complex; ISS:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:RGD.
DR GO; GO:0008013; F:beta-catenin binding; IDA:BHF-UCL.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0070410; F:co-SMAD binding; ISO:RGD.
DR GO; GO:0005518; F:collagen binding; ISO:RGD.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IDA:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0001217; F:DNA-binding transcription repressor activity; ISO:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0070411; F:I-SMAD binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; ISO:RGD.
DR GO; GO:0031962; F:nuclear mineralocorticoid receptor binding; ISO:RGD.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:RGD.
DR GO; GO:0019902; F:phosphatase binding; ISO:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0070412; F:R-SMAD binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0046332; F:SMAD binding; IPI:RGD.
DR GO; GO:0032810; F:sterol response element binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:RGD.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; ISO:RGD.
DR GO; GO:0043130; F:ubiquitin binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0097296; P:activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IMP:RGD.
DR GO; GO:0032924; P:activin receptor signaling pathway; ISO:RGD.
DR GO; GO:0030325; P:adrenal gland development; IDA:RGD.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045216; P:cell-cell junction organization; ISO:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISO:RGD.
DR GO; GO:0048589; P:developmental growth; ISO:RGD.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISO:RGD.
DR GO; GO:0048617; P:embryonic foregut morphogenesis; ISO:RGD.
DR GO; GO:0009880; P:embryonic pattern specification; ISO:RGD.
DR GO; GO:0007492; P:endoderm development; ISO:RGD.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0007369; P:gastrulation; ISO:RGD.
DR GO; GO:0001947; P:heart looping; ISO:RGD.
DR GO; GO:0006955; P:immune response; ISO:RGD.
DR GO; GO:0002520; P:immune system development; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR GO; GO:0070306; P:lens fiber cell differentiation; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0001707; P:mesoderm formation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; IGI:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0061767; P:negative regulation of lung blood pressure; IGI:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; ISO:RGD.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:CACAO.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0061045; P:negative regulation of wound healing; ISO:RGD.
DR GO; GO:0038092; P:nodal signaling pathway; ISO:RGD.
DR GO; GO:0002076; P:osteoblast development; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
DR GO; GO:0048340; P:paraxial mesoderm morphogenesis; ISO:RGD.
DR GO; GO:0060039; P:pericardium development; ISO:RGD.
DR GO; GO:0010694; P:positive regulation of alkaline phosphatase activity; IDA:RGD.
DR GO; GO:0030501; P:positive regulation of bone mineralization; IDA:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; ISO:RGD.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; ISO:RGD.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IDA:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IMP:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IGI:BHF-UCL.
DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IDA:RGD.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0032916; P:positive regulation of transforming growth factor beta3 production; IMP:RGD.
DR GO; GO:0050821; P:protein stabilization; IMP:BHF-UCL.
DR GO; GO:0051098; P:regulation of binding; ISO:RGD.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0050776; P:regulation of immune response; ISO:RGD.
DR GO; GO:0016202; P:regulation of striated muscle tissue development; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0032909; P:regulation of transforming growth factor beta2 production; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0001501; P:skeletal system development; ISO:RGD.
DR GO; GO:0007183; P:SMAD protein complex assembly; IPI:RGD.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISO:RGD.
DR GO; GO:0001756; P:somitogenesis; ISO:RGD.
DR GO; GO:0042110; P:T cell activation; ISO:RGD.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR GO; GO:0060290; P:transdifferentiation; IDA:RGD.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0001657; P:ureteric bud development; ISO:RGD.
DR Gene3D; 2.60.200.10; -; 1.
DR Gene3D; 3.90.520.10; -; 1.
DR InterPro; IPR013790; Dwarfin.
DR InterPro; IPR003619; MAD_homology1_Dwarfin-type.
DR InterPro; IPR013019; MAD_homology_MH1.
DR InterPro; IPR017855; SMAD-like_dom_sf.
DR InterPro; IPR001132; SMAD_dom_Dwarfin-type.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR036578; SMAD_MH1_sf.
DR PANTHER; PTHR13703; PTHR13703; 1.
DR Pfam; PF03165; MH1; 1.
DR Pfam; PF03166; MH2; 1.
DR SMART; SM00523; DWA; 1.
DR SMART; SM00524; DWB; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF56366; SSF56366; 1.
DR PROSITE; PS51075; MH1; 1.
DR PROSITE; PS51076; MH2; 1.
PE 1: Evidence at protein level;
KW Acetylation; ADP-ribosylation; Cytoplasm; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT CHAIN 2..425
FT /note="Mothers against decapentaplegic homolog 3"
FT /id="PRO_0000090859"
FT DOMAIN 10..136
FT /note="MH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438"
FT DOMAIN 232..425
FT /note="MH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439"
FT REGION 137..231
FT /note="Linker"
FT REGION 165..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..324
FT /note="Sufficient for interaction with XPO4"
FT /evidence="ECO:0000250"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 109
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT SITE 40
FT /note="Required for trimerization"
FT /evidence="ECO:0000250"
FT SITE 41
FT /note="Required for interaction with DNA and JUN and for
FT functional cooperation with JUN"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT MOD_RES 8
FT /note="Phosphothreonine; by CDK2 and CDK4"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT MOD_RES 179
FT /note="Phosphothreonine; by CDK2, CDK4 and MAPK"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT MOD_RES 204
FT /note="Phosphoserine; by GSK3 and MAPK"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 208
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 213
FT /note="Phosphoserine; by CDK2 and CDK4"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 378
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 418
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:P84022,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 422
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000250|UniProtKB:Q8BUN5,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 423
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000250|UniProtKB:Q8BUN5,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT MOD_RES 425
FT /note="Phosphoserine; by TGFBR1"
FT /evidence="ECO:0000250|UniProtKB:Q8BUN5,
FT ECO:0000255|PROSITE-ProRule:PRU00439"
FT CROSSLNK 33
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P84022"
FT CROSSLNK 81
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P84022"
SQ SEQUENCE 425 AA; 48081 MW; 46DF5E8B371321AC CRC64;
MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE LEKAITTQNV
NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELRAMELCE FAFNMKKDEV
CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF PPLDDYSHSI PENTNFPAGI EPQSNIPETP
PPGYLSEDGE TSDHQMNHSM DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL
NQRVGETFHA SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA LLAQSVNQGF
EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL NGPLQWLDKV LTQMGSPSIR
CSSVS
