ID SMAD2_MOUSE Reviewed; 467 AA. AC Q62432; Q6GU18; Q6VP00; Q9D8P6; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 14-NOV-2006, sequence version 2. DT 27-MAR-2024, entry version 224. DE RecName: Full=Mothers against decapentaplegic homolog 2; DE Short=MAD homolog 2; DE Short=Mothers against DPP homolog 2; DE AltName: Full=Mad-related protein 2; DE Short=mMad2; DE AltName: Full=SMAD family member 2; DE Short=SMAD 2; DE Short=Smad2; GN Name=Smad2; Synonyms=Madh2, Madr2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RC STRAIN=129/Sv; RX PubMed=8756346; DOI=10.1101/gad.10.15.1880; RA Baker J.C., Harland R.M.; RT "A novel mesoderm inducer, Madr2, functions in the activin signal RT transduction pathway."; RL Genes Dev. 10:1880-1889(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RC STRAIN=A/J, and BALB/cJ; RX PubMed=9328171; DOI=10.1093/carcin/18.9.1751; RA Devereux T.R., Anna C.H., Patel A.C., White C.M., Festing M.F., You M.; RT "Smad4 (homolog of human DPC4) and Smad2 (homolog of human JV18-1): RT candidates for murine lung tumor resistance and suppressor genes."; RL Carcinogenesis 18:1751-1755(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). RX PubMed=14701940; DOI=10.1210/me.2003-0264; RA Bernard D.J.; RT "Both SMAD2 and SMAD3 mediate activin-stimulated expression of the RT follicle-stimulating hormone beta subunit in mouse gonadotrope cells."; RL Mol. Endocrinol. 18:606-623(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC STRAIN=C57BL/6J; TISSUE=Pancreas; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). 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 [6] RP REVIEW. RX PubMed=10708952; DOI=10.1016/s1359-6101(99)00028-3; RA Weinstein M., Yang X., Deng C.-X.; RT "Functions of mammalian Smad genes as revealed by targeted gene disruption RT in mice."; RL Cytokine Growth Factor Rev. 11:49-58(2000). RN [7] RP INTERACTION WITH ZNF8. RX PubMed=12370310; DOI=10.1128/mcb.22.21.7633-7644.2002; RA Jiao K., Zhou Y., Hogan B.L.M.; RT "Identification of mZnf8, a mouse Kruppel-like transcriptional repressor, RT as a novel nuclear interaction partner of Smad1."; RL Mol. Cell. Biol. 22:7633-7644(2002). RN [8] RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH PML AND ZFYVE9/SARA. RX PubMed=15356634; DOI=10.1038/nature02783; RA Lin H.K., Bergmann S., Pandolfi P.P.; RT "Cytoplasmic PML function in TGF-beta signalling."; RL Nature 431:205-211(2004). RN [9] RP INTERACTION WITH WWP1. RX PubMed=15221015; DOI=10.1038/sj.onc.1207885; RA Komuro A., Imamura T., Saitoh M., Yoshida Y., Yamori T., Miyazono K., RA Miyazawa K.; RT "Negative regulation of transforming growth factor-beta (TGF-beta) RT signaling by WW domain-containing protein 1 (WWP1)."; RL Oncogene 23:6914-6923(2004). RN [10] RP ALTERNATIVE SPLICING (ISOFORM SHORT). RX PubMed=15630024; DOI=10.1101/gad.1243205; RA Dunn N.R., Koonce C.H., Anderson D.C., Islam A., Bikoff E.K., RA Robertson E.J.; RT "Mice exclusively expressing the short isoform of Smad2 develop normally RT and are viable and fertile."; RL Genes Dev. 19:152-163(2005). RN [11] RP PHOSPHORYLATION AT SER-465 AND SER-467. RX PubMed=12672795; DOI=10.1074/jbc.m300075200; RA Haller D., Holt L., Kim S.C., Schwabe R.F., Sartor R.B., Jobin C.; RT "Transforming growth factor-beta 1 inhibits non-pathogenic Gram negative RT bacteria-induced NF-kappa B recruitment to the interleukin-6 gene promoter RT in intestinal epithelial cells through modulation of histone acetylation."; RL J. Biol. Chem. 278:23851-23860(2003). RN [12] RP INTERACTION WITH AIP1. RX PubMed=10681527; DOI=10.1074/jbc.275.8.5485; RA Shoji H., Tsuchida K., Kishi H., Yamakawa N., Matsuzaki T., Liu Z., RA Nakamura T., Sugino H.; RT "Identification and characterization of a PDZ protein that interacts with RT activin types II receptors."; RL J. Biol. Chem. 275:5485-5492(2000). RN [13] RP INTERACTION WITH HGS. RX PubMed=11094085; DOI=10.1128/mcb.20.24.9346-9355.2000; RA Miura S., Takeshita T., Asao H., Kimura Y., Murata K., Sasaki Y., Hanai J., RA Beppu H., Tsukazaki T., Wrana J.L., Miyazono K., Sugamura K.; RT "Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through RT cooperation with SARA."; RL Mol. Cell. Biol. 20:9346-9355(2000). RN [14] RP INTERACTION WITH NEDD4L, AND UBIQUITINATION. RX PubMed=15496141; DOI=10.1042/bj20040738; RA Kuratomi G., Komuro A., Goto K., Shinozaki M., Miyazawa K., Miyazono K., RA Imamura T.; RT "NEDD4-2 (neural precursor cell expressed, developmentally down-regulated RT 4-2) negatively regulates TGF-beta (transforming growth factor-beta) RT signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta RT type I receptor."; RL Biochem. J. 386:461-470(2005). RN [15] RP INTERACTION WITH RNF111, PHOSPHORYLATION, AND UBIQUITINATION. RX PubMed=17341133; DOI=10.1371/journal.pbio.0050067; RA Mavrakis K.J., Andrew R.L., Lee K.L., Petropoulou C., Dixon J.E., RA Navaratnam N., Norris D.P., Episkopou V.; RT "Arkadia enhances Nodal/TGF-beta signaling by coupling phospho-Smad2/3 RT activity and turnover."; RL PLoS Biol. 5:E67-E67(2007). RN [16] RP INTERACTION WITH YAP1 AND SMAD4, AND SUBCELLULAR LOCATION. RX PubMed=21145499; DOI=10.1016/j.devcel.2010.11.012; RA Varelas X., Samavarchi-Tehrani P., Narimatsu M., Weiss A., Cockburn K., RA Larsen B.G., Rossant J., Wrana J.L.; RT "The Crumbs complex couples cell density sensing to Hippo-dependent control RT of the TGF-beta-SMAD pathway."; RL Dev. Cell 19:831-844(2010). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [18] RP INTERACTION WITH PPP5C, AND SUBCELLULAR LOCATION. RX PubMed=22781750; DOI=10.1016/j.cellsig.2012.07.003; RA Bruce D.L., Macartney T., Yong W., Shou W., Sapkota G.P.; RT "Protein phosphatase 5 modulates SMAD3 function in the transforming growth RT factor-beta pathway."; RL Cell. Signal. 24:1999-2006(2012). RN [19] RP FUNCTION, INTERACTION WITH IPO7, AND SUBCELLULAR LOCATION. RX PubMed=33548622; DOI=10.1016/j.bbrc.2021.01.076; RA Zhang Y., Zhang H., Yuan G., Yang G.; RT "Effects of transforming growth factor-beta1 on odontoblastic RT differentiation in dental papilla cells is determined by IPO7 expression RT level."; RL Biochem. Biophys. Res. Commun. 545:105-111(2021). 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 SMAD2/SMAD4 complex, activates CC transcription. Promotes TGFB1-mediated transcription of odontoblastic CC differentiation genes in dental papilla cells (PubMed:33548622). CC Positively regulates PDPK1 kinase activity by stimulating its CC dissociation from the 14-3-3 protein YWHAQ which acts as a negative CC regulator (By similarity). {ECO:0000250|UniProtKB:Q15796, CC ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:33548622}. CC -!- SUBUNIT: Monomer; in the absence of TGF-beta (By similarity). CC Heterodimer; in the presence of TGF-beta (By similarity). Forms a CC heterodimer with co-SMAD, SMAD4, in the nucleus to form the CC transactivation complex SMAD2/SMAD4 (PubMed:21145499). Found in a CC complex with SMAD3 and TRIM33 upon addition of TGF-beta (By CC similarity). Identified in a complex that contains at least ZNF451, CC SMAD2, SMAD3 and SMAD4 (By similarity). Interacts (via the MH2 domain) CC with ZFYVE9; may form trimers with the SMAD4 co-SMAD (PubMed:15356634). CC Interacts with TAZ/WWRT1 (By similarity). Interacts with FOXH1 (By CC similarity). Interacts with SNW1 (By similarity). Interacts with CREB- CC binding protein (CBP) and EP300 (By similarity). Interacts with SNON CC (By similarity). Interacts with ALK4/ACVR1B (By similarity). Interacts CC with SKOR1 (By similarity). Interacts with SKOR2 (By similarity). CC Interacts with PRDM16 (By similarity). Interacts (via MH2 domain) with CC LEMD3 (By similarity). Interacts with RBPMS (By similarity). Interacts CC with WWP1. Interacts (dephosphorylated form, via the MH1 and MH2 CC domains) with RANBP3 (via its C-terminal R domain); the interaction CC results in the export of dephosphorylated SMAD3 out of the nucleus and CC termination of the TGF-beta signaling (By similarity). Interacts with CC PDPK1 (via PH domain) (By similarity). Interacts with DAB2; the CC interactions are enhanced upon TGF-beta stimulation (By similarity). CC Interacts with USP15 (By similarity). Interacts with PPP5C CC (PubMed:22781750). Interacts with LDLRAD4 (via the SMAD interaction CC motif) (By similarity). Interacts (via MH2 domain) with PMEPA1 (via the CC SMAD interaction motif) (By similarity). Interacts with ZFHX3 (By CC similarity). Interacts with ZNF451 (By similarity). Interacts with CC SMURF2 when phosphorylated on Ser-465/467 (By similarity). Interacts CC with PPM1A (By similarity). Interacts with TGF-beta (By similarity). CC Interacts with TGFBR1 (By similarity). Interacts with TGIF (By CC similarity). Interacts with SMAD3 and TRIM33 (By similarity). Interacts CC with ZNF580 (By similarity). Interacts with NEDD4L in response to TGF- CC beta (PubMed:15496141). Interacts with HGS (PubMed:11094085). Interacts CC with AIP1 (PubMed:10681527). Interacts with WWP1 (PubMed:15221015). CC Interacts with PML (PubMed:15356634). Interacts weakly with ZNF8 CC (PubMed:12370310). Interacts (when phosphorylated) with RNF111; RNF111 CC acts as an enhancer of the transcriptional responses by mediating CC ubiquitination and degradation of SMAD2 inhibitors (PubMed:17341133). CC Interacts with YAP1 (when phosphorylated at 'Ser-112') CC (PubMed:21145499). Interacts when phosphorylated with IPO7; the CC interaction facilitates translocation of SMAD2 to the nucleus CC (PubMed:33548622). {ECO:0000250|UniProtKB:Q15796, CC ECO:0000269|PubMed:10681527, ECO:0000269|PubMed:11094085, CC ECO:0000269|PubMed:12370310, ECO:0000269|PubMed:15221015, CC ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:15496141, CC ECO:0000269|PubMed:17341133, ECO:0000269|PubMed:21145499, CC ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:33548622}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21145499, CC ECO:0000269|PubMed:33548622}. Nucleus {ECO:0000269|PubMed:21145499, CC ECO:0000269|PubMed:33548622}. Note=Cytoplasmic and nuclear in the CC absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus CC when complexed with SMAD4 or with IPO7 (PubMed:21145499, CC PubMed:33548622). On dephosphorylation by phosphatase PPM1A, released CC from the SMAD2/SMAD4 complex, and exported out of the nucleus by CC interaction with RANBP1 (By similarity). Localized mainly to the CC nucleus in the early stages of embryo development with expression CC becoming evident in the cytoplasm at the blastocyst and epiblast stages CC (PubMed:21145499). {ECO:0000250|UniProtKB:Q15796, CC ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:33548622}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=mRNA corresponding to the isoform Long is approximately 20- CC fold more abundant. Both forms are coexpressed throughout mouse CC development.; CC Name=Long; CC IsoId=Q62432-1; Sequence=Displayed; CC Name=Short; Synonyms=Deltaexon3; CC IsoId=Q62432-2; Sequence=VSP_021571; CC -!- PTM: In response to TGF-beta, phosphorylated on the C-terminal SXS CC motif by TGF-beta and activin type 1 receptor kinases, phosphorylation CC declines progressively in a KMT5A-dependent manner. Phosphorylation in CC this motif is required for interaction with a number of proteins CC including SMURF2, SNON and SMAD4 in response to TGF-beta. CC Dephosphorylated in this motif by PPM1A leading to disruption of the CC SMAD2/3-SMAD4 complex, nuclear export and termination of the TGF-beta CC signaling. In response to decorin, the naturally occurring inhibitor of CC TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated CC by MAPK3 upon EGF stimulation; which increases transcriptional activity CC and stability, and is blocked by calmodulin. Phosphorylated by PDPK1. CC {ECO:0000269|PubMed:12672795, ECO:0000269|PubMed:15356634, CC ECO:0000269|PubMed:17341133}. CC -!- PTM: In response to TGF-beta, ubiquitinated by NEDD4L; which promotes CC its degradation. Monoubiquitinated, leading to prevent DNA-binding CC (PubMed:15496141). Deubiquitination by USP15 alleviates inhibition and CC promotes activation of TGF-beta target genes (By similarity). CC Ubiquitinated by RNF111, leading to its degradation: only SMAD2 CC proteins that are 'in use' are targeted by RNF111, RNF111 playing a key CC role in activating SMAD2 and regulating its turnover (PubMed:17341133). CC {ECO:0000250|UniProtKB:Q15796, ECO:0000269|PubMed:15496141, CC ECO:0000269|PubMed:17341133}. CC -!- PTM: Acetylated on Lys-19 by coactivators in response to TGF-beta CC signaling, which increases transcriptional activity. CC {ECO:0000250|UniProtKB:Q15796}. CC -!- SIMILARITY: Belongs to the dwarfin/SMAD family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U60530; AAB03612.1; -; mRNA. DR EMBL; AF005743; AAB62269.1; -; mRNA. DR EMBL; AK007817; BAB25282.1; -; mRNA. DR EMBL; AY334552; AAR00933.1; -; mRNA. DR EMBL; BC021342; AAH21342.1; -; mRNA. DR EMBL; BC089184; AAH89184.1; -; mRNA. DR CCDS; CCDS29350.1; -. [Q62432-1] DR CCDS; CCDS79664.1; -. [Q62432-2] DR RefSeq; NP_001239410.1; NM_001252481.1. [Q62432-1] DR RefSeq; NP_001297999.1; NM_001311070.1. [Q62432-2] DR RefSeq; NP_034884.2; NM_010754.5. [Q62432-1] DR RefSeq; XP_006525762.1; XM_006525699.2. [Q62432-1] DR RefSeq; XP_017173331.1; XM_017317842.1. [Q62432-2] DR AlphaFoldDB; Q62432; -. DR SMR; Q62432; -. DR BioGRID; 201275; 34. DR ComplexPortal; CPX-10; SMAD2-SMAD3-SMAD4 complex. DR ComplexPortal; CPX-13; SMAD2 homotrimer. DR ComplexPortal; CPX-3251; SMAD2-SMAD4 complex. DR CORUM; Q62432; -. DR IntAct; Q62432; 6. DR MINT; Q62432; -. DR STRING; 10090.ENSMUSP00000130115; -. DR ChEMBL; CHEMBL4523335; -. DR GlyGen; Q62432; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q62432; -. DR PhosphoSitePlus; Q62432; -. DR SwissPalm; Q62432; -. DR EPD; Q62432; -. DR MaxQB; Q62432; -. DR PaxDb; 10090-ENSMUSP00000130115; -. DR PeptideAtlas; Q62432; -. DR ProteomicsDB; 258699; -. [Q62432-1] DR ProteomicsDB; 258700; -. [Q62432-2] DR Pumba; Q62432; -. DR ABCD; Q62432; 1 sequenced antibody. DR Antibodypedia; 9235; 2760 antibodies from 48 providers. DR DNASU; 17126; -. DR Ensembl; ENSMUST00000025453.15; ENSMUSP00000025453.9; ENSMUSG00000024563.17. [Q62432-1] DR Ensembl; ENSMUST00000091831.13; ENSMUSP00000089439.7; ENSMUSG00000024563.17. [Q62432-2] DR Ensembl; ENSMUST00000168423.9; ENSMUSP00000130115.2; ENSMUSG00000024563.17. [Q62432-1] DR GeneID; 17126; -. DR KEGG; mmu:17126; -. DR UCSC; uc008fqn.2; mouse. [Q62432-1] DR UCSC; uc008fqo.2; mouse. [Q62432-2] DR AGR; MGI:108051; -. DR CTD; 4087; -. DR MGI; MGI:108051; Smad2. DR VEuPathDB; HostDB:ENSMUSG00000024563; -. DR eggNOG; KOG3701; Eukaryota. DR GeneTree; ENSGT00940000153499; -. DR HOGENOM; CLU_026736_0_2_1; -. DR InParanoid; Q62432; -. DR OMA; RAIEHCE; -. DR OrthoDB; 2891561at2759; -. DR PhylomeDB; Q62432; -. DR TreeFam; TF314923; -. DR Reactome; R-MMU-1181150; Signaling by NODAL. DR Reactome; R-MMU-1502540; Signaling by Activin. DR Reactome; R-MMU-2173788; Downregulation of TGF-beta receptor signaling. DR Reactome; R-MMU-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-MMU-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR Reactome; R-MMU-9617828; FOXO-mediated transcription of cell cycle genes. DR BioGRID-ORCS; 17126; 3 hits in 81 CRISPR screens. DR ChiTaRS; Smad2; mouse. DR PRO; PR:Q62432; -. DR Proteomes; UP000000589; Chromosome 18. DR RNAct; Q62432; Protein. DR Bgee; ENSMUSG00000024563; Expressed in saccule of membranous labyrinth and 299 other cell types or tissues. DR ExpressionAtlas; Q62432; baseline and differential. DR GO; GO:0032444; C:activin responsive factor complex; ISO:MGI. DR GO; GO:0000785; C:chromatin; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0071144; C:heteromeric SMAD protein complex; ISO:MGI. DR GO; GO:0071142; C:homomeric SMAD protein complex; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0071141; C:SMAD protein complex; ISO:MGI. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0070410; F:co-SMAD binding; ISO:MGI. DR GO; GO:0097718; F:disordered domain specific binding; ISO:MGI. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IPI:ARUK-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:MGI. DR GO; GO:0070411; F:I-SMAD binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; IPI:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0019902; F:phosphatase binding; ISO:MGI. DR GO; GO:0070412; F:R-SMAD binding; ISO:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0046332; F:SMAD binding; IPI:UniProtKB. DR GO; GO:0048156; F:tau protein binding; IDA:ARUK-UCL. DR GO; GO:0005160; F:transforming growth factor beta receptor binding; ISO:MGI. DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; ISO:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0032924; P:activin receptor signaling pathway; ISO:MGI. DR GO; GO:0030325; P:adrenal gland development; ISO:MGI. DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central. DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI. DR GO; GO:0003180; P:aortic valve morphogenesis; IGI:BHF-UCL. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0045165; P:cell fate commitment; IMP:MGI. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0003140; P:determination of left/right asymmetry in lateral mesoderm; ISO:MGI. DR GO; GO:0048589; P:developmental growth; IGI:MGI. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IGI:MGI. DR GO; GO:0048617; P:embryonic foregut morphogenesis; IGI:MGI. DR GO; GO:0009880; P:embryonic pattern specification; IGI:MGI. DR GO; GO:0003203; P:endocardial cushion morphogenesis; IGI:BHF-UCL. DR GO; GO:0007492; P:endoderm development; IGI:MGI. DR GO; GO:0001706; P:endoderm formation; IMP:MGI. DR GO; GO:0007369; P:gastrulation; IGI:MGI. DR GO; GO:0007507; P:heart development; IGI:MGI. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0030073; P:insulin secretion; IGI:MGI. DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI. DR GO; GO:0030324; P:lung development; IGI:MGI. DR GO; GO:0001707; P:mesoderm formation; IMP:MGI. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI. DR GO; GO:0038092; P:nodal signaling pathway; ISO:MGI. DR GO; GO:0071895; P:odontoblast differentiation; IMP:UniProtKB. DR GO; GO:0035265; P:organ growth; IGI:MGI. DR GO; GO:0031016; P:pancreas development; IGI:MGI. DR GO; GO:0048340; P:paraxial mesoderm morphogenesis; IMP:MGI. DR GO; GO:0007389; P:pattern specification process; IGI:MGI. DR GO; GO:0060039; P:pericardium development; IGI:MGI. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0009791; P:post-embryonic development; IGI:MGI. DR GO; GO:0003184; P:pulmonary valve morphogenesis; IGI:BHF-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; NAS:ComplexPortal. DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI. DR GO; GO:0070723; P:response to cholesterol; ISO:MGI. DR GO; GO:0009749; P:response to glucose; IGI:MGI. DR GO; GO:0062009; P:secondary palate development; IMP:BHF-UCL. DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; ISO:MGI. DR GO; GO:0060395; P:SMAD protein signal transduction; IGI:MGI. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:MGI. DR GO; GO:0001657; P:ureteric bud development; IEP:UniProtKB. DR GO; GO:0007352; P:zygotic specification of dorsal/ventral axis; ISO:MGI. DR CDD; cd10491; MH1_SMAD_2_3; 1. DR CDD; cd10985; MH2_SMAD_2_3; 1. DR Gene3D; 2.60.200.10; -; 1. DR Gene3D; 3.90.520.10; SMAD MH1 domain; 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:SF42; MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 2; 1. DR PANTHER; PTHR13703; SMAD; 1. DR Pfam; PF03165; MH1; 1. DR Pfam; PF03166; MH2; 1. DR SMART; SM00523; DWA; 1. DR SMART; SM00524; DWB; 1. DR SUPFAM; SSF56366; SMAD MH1 domain; 1. DR SUPFAM; SSF49879; SMAD/FHA domain; 1. DR PROSITE; PS51075; MH1; 1. DR PROSITE; PS51076; MH2; 1. DR Genevisible; Q62432; MM. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cytoplasm; DNA-binding; 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:Q15796" FT CHAIN 2..467 FT /note="Mothers against decapentaplegic homolog 2" FT /id="PRO_0000090853" FT DOMAIN 10..176 FT /note="MH1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438" FT DOMAIN 274..467 FT /note="MH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439" FT REGION 207..251 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 221..225 FT /note="PY-motif" FT /evidence="ECO:0000250" FT COMPBIAS 229..251 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 74 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 149 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 161 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 166 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:Q15796" FT MOD_RES 8 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q15796" FT MOD_RES 19 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q15796" FT MOD_RES 220 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q15796" FT MOD_RES 240 FT /note="Phosphoserine; by CAMK2" FT /evidence="ECO:0000250|UniProtKB:Q15796, FT ECO:0000255|PROSITE-ProRule:PRU00439" FT MOD_RES 245 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15796" FT MOD_RES 250 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15796" FT MOD_RES 255 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15796" FT MOD_RES 458 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15796, FT ECO:0000255|PROSITE-ProRule:PRU00439" FT MOD_RES 460 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15796, FT ECO:0000255|PROSITE-ProRule:PRU00439" FT MOD_RES 464 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15796, FT ECO:0000255|PROSITE-ProRule:PRU00439" FT MOD_RES 465 FT /note="Phosphoserine; by TGFBR1" FT /evidence="ECO:0000250|UniProtKB:Q15796, FT ECO:0000255|PROSITE-ProRule:PRU00439" FT MOD_RES 467 FT /note="Phosphoserine; by TGFBR1" FT /evidence="ECO:0000250|UniProtKB:Q15796, FT ECO:0000255|PROSITE-ProRule:PRU00439" FT VAR_SEQ 79..108 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:14701940" FT /id="VSP_021571" FT CONFLICT 42 FT /note="E -> Q (in Ref. 1; AAB03612 and 2; AAB62269)" FT /evidence="ECO:0000305" SQ SEQUENCE 467 AA; 52266 MW; 31A2A36D463DB3E9 CRC64; MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK KLKKTGRLDE LEKAITTQNC NTKCVTIPST CSEIWGLSTA NTVDQWDTTG LYSFSEQTRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELKAIENCE YAFNLKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEILTEL PPLDDYTHSI PENTNFPAGI EPQSNYIPET PPPGYISEDG ETSDQQLNQS MDTGSPAELS PTTLSPVNHS LDLQPVTYSE PAFWCSIAYY ELNQRVGETF HASQPSLTVD GFTDPSNSER FCLGLLSNVN RNATVEMTRR HIGRGVRLYY IGGEVFAECL SDSAIFVQSP NCNQRYGWHP ATVCKIPPGC NLKIFNNQEF AALLAQSVNQ GFEAVYQLTR MCTIRMSFVK GWGAEYRRQT VTSTPCWIEL HLNGPLQWLD KVLTQMGSPS VRCSSMS //