SMAD2_MOUSE
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 03-AUG-2022, entry version 215.
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).
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. May act as a tumor suppressor in colorectal carcinoma.
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}.
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). {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}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21145499}. Nucleus
CC {ECO:0000269|PubMed:21145499}. Note=Cytoplasmic and nuclear in the
CC absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus
CC when complexed with SMAD4 (PubMed:21145499). On dephosphorylation by
CC phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported
CC out of the nucleus by interaction with RANBP1 (By similarity).
CC Localized mainly to the nucleus in the early stages of embryo
CC development with expression becoming evident in the cytoplasm at the
CC blastocyst and epiblast stages (PubMed:21145499).
CC {ECO:0000250|UniProtKB:Q15796, ECO:0000269|PubMed:21145499}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=mRNA corresponding to the isoform Long is approximately
CC 20-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}.
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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 iPTMnet; Q62432; -.
DR PhosphoSitePlus; Q62432; -.
DR EPD; Q62432; -.
DR MaxQB; Q62432; -.
DR PaxDb; Q62432; -.
DR PeptideAtlas; Q62432; -.
DR PRIDE; Q62432; -.
DR ProteomicsDB; 258699; -. [Q62432-1]
DR ProteomicsDB; 258700; -. [Q62432-2]
DR ABCD; Q62432; 1 sequenced antibody.
DR Antibodypedia; 9235; 1994 antibodies from 48 providers.
DR DNASU; 17126; -.
DR Ensembl; ENSMUST00000025453; ENSMUSP00000025453; ENSMUSG00000024563. [Q62432-1]
DR Ensembl; ENSMUST00000091831; ENSMUSP00000089439; ENSMUSG00000024563. [Q62432-2]
DR Ensembl; ENSMUST00000168423; ENSMUSP00000130115; ENSMUSG00000024563. [Q62432-1]
DR GeneID; 17126; -.
DR KEGG; mmu:17126; -.
DR UCSC; uc008fqn.2; mouse. [Q62432-1]
DR UCSC; uc008fqo.2; mouse. [Q62432-2]
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; TNMCTIR; -.
DR OrthoDB; 608001at2759; -.
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 76 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 295 other tissues.
DR ExpressionAtlas; Q62432; baseline and differential.
DR Genevisible; Q62432; MM.
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; ISO:MGI.
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:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR GO; GO:0007182; P:common-partner SMAD protein phosphorylation; 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: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:0010629; P:negative regulation of gene expression; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0038092; P:nodal signaling pathway; ISO:MGI.
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: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:1900224; P:positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0009791; P:post-embryonic development; IGI:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0051098; P:regulation of binding; IDA:MGI.
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:0007183; P:SMAD protein complex assembly; 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:0042060; P:wound healing; IEA:Ensembl.
DR GO; GO:0007352; P:zygotic specification of dorsal/ventral axis; ISO:MGI.
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; 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
