ID SMAD1_MOUSE Reviewed; 465 AA. AC P70340; P70442; Q6GT95; Q9CYK6; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 212. DE RecName: Full=Mothers against decapentaplegic homolog 1; DE Short=MAD homolog 1; DE Short=Mothers against DPP homolog 1; DE AltName: Full=Dwarfin-A; DE Short=Dwf-A; DE AltName: Full=Mothers-against-DPP-related 1; DE Short=Mad-related protein 1; DE Short=mMad1; DE AltName: Full=SMAD family member 1; DE Short=SMAD 1; DE Short=Smad1; GN Name=Smad1; Synonyms=Madh1, Madr1; 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]. RC TISSUE=Embryo; RX PubMed=8799132; DOI=10.1073/pnas.93.17.8940; RA Yingling J.M., Das P., Savage C., Zhang M., Padgett R.W., Wang X.-F.; RT "Mammalian dwarfins are phosphorylated in response to transforming growth RT factor beta and are implicated in control of cell growth."; RL Proc. Natl. Acad. Sci. U.S.A. 93:8940-8944(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Embryonic heart; RX PubMed=9076678; DOI=10.1016/s0925-4773(96)00622-3; RA Zhao G.-Q., Hogan B.L.M.; RT "Evidence that Mothers-against-dpp-related 1 (Madr1) plays a role in the RT initiation and maintenance of spermatogenesis in the mouse."; RL Mech. Dev. 61:63-73(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=129/Sv; RX PubMed=11111041; DOI=10.1016/s0378-1119(00)00396-6; RA Huang S., Flanders K.C., Roberts A.B.; RT "Characterization of the mouse Smad1 gene and its expression pattern in RT adult mouse tissues."; RL Gene 258:43-53(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Embryo, and Oviduct; 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]. RC STRAIN=C57BL/6J; TISSUE=Brain; 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 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 [7] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=11566864; DOI=10.1242/dev.128.18.3609; RA Tremblay K.D., Dunn N.R., Robertson E.J.; RT "Mouse embryos lacking Smad1 signals display defects in extra-embryonic RT tissues and germ cell formation."; RL Development 128:3609-3621(2001). RN [8] 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 [9] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH SMAD4 AND YY1. RX PubMed=15329343; DOI=10.1242/dev.01344; RA Lee K.H., Evans S., Ruan T.Y., Lassar A.B.; RT "SMAD-mediated modulation of YY1 activity regulates the BMP response and RT cardiac-specific expression of a GATA4/5/6-dependent chick Nkx2.5 RT enhancer."; RL Development 131:4709-4723(2004). RN [10] RP INTERACTION WITH ZC3H3. RX PubMed=16115198; DOI=10.1111/j.1365-2443.2005.00887.x; RA Collart C., Remacle J.E., Barabino S., van Grunsven L.A., Nelles L., RA Schellens A., Van de Putte T., Pype S., Huylebroeck D., Verschueren K.; RT "Smicl is a novel Smad interacting protein and cleavage and polyadenylation RT specificity factor associated protein."; RL Genes Cells 10:897-906(2005). RN [11] RP INTERACTION WITH NANOG. RX PubMed=16801560; DOI=10.1073/pnas.0506945103; RA Suzuki A., Raya A., Kawakami Y., Morita M., Matsui T., Nakashima K., RA Gage F.H., Rodriguez-Esteban C., Izpisua Belmonte J.C.; RT "Nanog binds to Smad1 and blocks bone morphogenetic protein-induced RT differentiation of embryonic stem cells."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10294-10299(2006). RN [12] RP INTERACTION WITH ZCCHC12. RX PubMed=18160706; DOI=10.1128/mcb.01038-07; RA Cho G., Lim Y., Zand D., Golden J.A.; RT "Sizn1 is a novel protein that functions as a transcriptional coactivator RT of bone morphogenic protein signaling."; RL Mol. Cell. Biol. 28:1565-1572(2008). RN [13] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=21420501; DOI=10.1016/j.joca.2011.03.004; RA Wang M., Jin H., Tang D., Huang S., Zuscik M.J., Chen D.; RT "Smad1 plays an essential role in bone development and postnatal bone RT formation."; RL Osteoarthritis Cartilage 19:751-762(2011). RN [14] RP INTERACTION WITH TMEM119. RX PubMed=21239498; DOI=10.1074/jbc.m110.179127; RA Hisa I., Inoue Y., Hendy G.N., Canaff L., Kitazawa R., Kitazawa S., RA Komori T., Sugimoto T., Seino S., Kaji H.; RT "Parathyroid hormone-responsive Smad3-related factor, Tmem119, promotes RT osteoblast differentiation and interacts with the bone morphogenetic RT protein-Runx2 pathway."; RL J. Biol. Chem. 286:9787-9796(2011). RN [15] RP INTERACTION WITH RANBP3L, DEPHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=25755279; DOI=10.1128/mcb.00121-15; RA Chen F., Lin X., Xu P., Zhang Z., Chen Y., Wang C., Han J., Zhao B., RA Xiao M., Feng X.H.; RT "Nuclear export of Smads by RanBP3L regulates bone morphogenetic protein RT signaling and mesenchymal stem cell differentiation."; RL Mol. Cell. Biol. 35:1700-1711(2015). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 9-132 IN COMPLEX WITH DNA, RP ZINC_BINDING SITES, AND SUBUNIT. RX PubMed=20147459; DOI=10.1093/nar/gkq046; RA Baburajendran N., Palasingam P., Narasimhan K., Sun W., Prabhakar S., RA Jauch R., Kolatkar P.R.; RT "Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of RT BMP and TGF-beta effectors."; RL Nucleic Acids Res. 38:3477-3488(2010). RN [17] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=34995814; DOI=10.1016/j.cdev.2021.203763; RA She Y., Zhang Y., Xiao Z., Yuan G., Yang G.; RT "The regulation of Msx1 by BMP4/pSmad1/5 signaling is mediated by importin7 RT in dental mesenchymal cells."; RL Cells Dev. 169:203763-203763(2022). RN [18] RP FUNCTION, INTERACTION WITH EGR1, AND PHOSPHORYLATION. RX PubMed=35594155; DOI=10.1002/1873-3468.14407; RA Chiba N., Noguchi Y., Seong C.H., Ohnishi T., Matsuguchi T.; RT "EGR1 plays an important role in BMP9-mediated osteoblast differentiation RT by promoting SMAD1/5 phosphorylation."; RL FEBS Lett. 596:1720-1732(2022). CC -!- FUNCTION: Transcriptional modulator that plays a role in various CC cellular processes, including embryonic development, cell CC differentiation, and tissue homeostasis (PubMed:11566864, CC PubMed:15329343, PubMed:21420501, PubMed:35594155). Upon BMP ligand CC binding to their receptors at the cell surface, is phosphorylated by CC activated type I BMP receptors (BMPRIs) and associates with SMAD4 to CC form an heteromeric complex which translocates into the nucleus acting CC as transcription factor. In turn, the hetero-trimeric complex CC recognizes cis-regulatory elements containing Smad Binding Elements CC (SBEs) to modulate the outcome of the signaling network. CC SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 CC repressor SNIP1 (By similarity). Positively regulates BMP4-induced CC expression of odontogenic development regulator MSX1 following IPO7- CC mediated nuclear import (PubMed:34995814). CC {ECO:0000250|UniProtKB:Q15797, ECO:0000269|PubMed:11566864, CC ECO:0000269|PubMed:15329343, ECO:0000269|PubMed:21420501, CC ECO:0000269|PubMed:34995814, ECO:0000269|PubMed:35594155}. CC -!- SUBUNIT: Found in a complex with SMAD4 and YY1. Interacts with HGS, CC NANOG and ZCCHC12 (PubMed:11094085, PubMed:18160706). Upon C-terminus CC phosphorylation: forms trimers with another SMAD1 and the co-SMAD SMAD4 CC (By similarity). Interacts with PEBP2-alpha subunit, CREB-binding CC protein (CBP), p300, SMURF1, SMURF2, USP15 and HOXC8. Associates with CC ZNF423 or ZNF521 in response to BMP2 leading to activate transcription CC of BMP target genes. Interacts with SKOR1. Interacts (via MH2 domain) CC with LEMD3. Binding to LEMD3 results in at least a partial reduction of CC receptor-mediated phosphorylation. Forms a ternary complex with PSMB4 CC and OAZ1 before PSMB4 is incorporated into the 20S proteasome. Found in CC a macromolecular complex with FAM83G. Interacts (via MH2 domain) with CC FAM83G (via MH2 domain); in a SMAD4-independent manner. Interacts with CC ZC3H3 (PubMed:16115198). Interacts with TMEM119 (PubMed:21239498). CC Interacts (via MH1 and MH2 domains) with ZNF8 (PubMed:12370310). CC Interacts with RANBP3L; the interaction increases when SMAD1 is not CC phosphorylated and mediates SMAD1 nuclear export (PubMed:25755279). CC Interacts with EGR1; this interaction inhibits SMAD1 dephosphorylation CC (PubMed:35594155). Interacts with SMAD6 (By similarity). Interacts with CC YAP1 (By similarity). {ECO:0000250|UniProtKB:Q15797, CC ECO:0000269|PubMed:11094085, ECO:0000269|PubMed:12370310, CC ECO:0000269|PubMed:15329343, ECO:0000269|PubMed:16115198, CC ECO:0000269|PubMed:16801560, ECO:0000269|PubMed:18160706, CC ECO:0000269|PubMed:20147459, ECO:0000269|PubMed:21239498, CC ECO:0000269|PubMed:25755279, ECO:0000269|PubMed:35594155}. CC -!- INTERACTION: CC P70340; Q62073: Map3k7; NbExp=3; IntAct=EBI-6992047, EBI-1775345; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25755279}. Nucleus CC {ECO:0000269|PubMed:25755279, ECO:0000269|PubMed:34995814}. CC Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when CC complexed with SMAD4. Co-localizes with LEMD3 at the nucleus inner CC membrane (By similarity). Exported from the nucleus to the cytoplasm CC when dephosphorylated PubMed:25755279. {ECO:0000250|UniProtKB:Q15797, CC ECO:0000269|PubMed:25755279}. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed during embryogenesis. CC Expression starts in some seminiferous tubules at 2 weeks of age. After CC mid-puberty a stage-specific expression is established. During the CC cycling of the seminiferous epithelium, expression initiates in the CC pachytene spermatocytes of stage V seminiferous tubules, peaks at stage CC X, then decreases as pachytene spermatocytes differentiate into CC secondary spermatocytes and then round spermatids. CC -!- DOMAIN: The MH2 domain mediates phosphorylation-dependent trimerization CC through L3 loop binding of phosphoserines in the adjacent subunit. CC {ECO:0000250|UniProtKB:Q15797}. CC -!- PTM: Phosphorylation of the C-terminal SVS motif by BMP type 1 receptor CC kinase activates SMAD1 by promoting dissociation from the receptor and CC trimerization with SMAD4. Phosphorylation by ERK2 MAP kinase in CC response to EGF or HGF prevents SMAD1 nuclear accumulation and CC transcriptional activity in response to BMP (By similarity). CC Dephosphorylation, probably by PPM1A, induces its export from the CC nucleus to the cytoplasm (PubMed:25755279). Dephosphorylation is CC inhibited by association with EGR1 (PubMed:35594155). Phosphorylation CC by CDK8/9 creates binding sites for YAP1, and subsequent CC phosphorylation by GSK3 switches off YAP1 binding and adds binding CC sites for SMURF1 (By similarity). {ECO:0000250|UniProtKB:Q15797, CC ECO:0000269|PubMed:25755279, ECO:0000269|PubMed:35594155}. CC -!- PTM: Ubiquitinated by SMAD-specific E3 ubiquitin ligase SMURF1, leading CC to its degradation. Monoubiquitinated, leading to prevent DNA-binding. CC Deubiquitination by USP15 alleviates inhibition and promotes activation CC of TGF-beta target genes. Dephosphorylation, probably by PPM1A, induces CC its export from the nucleus to the cytoplasm (By similarity). Phospho- CC SMAD1 is ubiquitinated by CHIP leading to disruption of the SMAD1-SMAD4 CC complex (By similarity). {ECO:0000250|UniProtKB:Q15797}. CC -!- DISRUPTION PHENOTYPE: SMAD1 deletion results in early embryonic CC lethality due to failure of the allantois to fuse to the chorion CC (PubMed:11566864). Chondrocyte-specific conditional knockout show a CC delay in calvarial bone mineralization and reduction of postnatal bone CC formation (PubMed:21420501). {ECO:0000269|PubMed:11566864, CC ECO:0000269|PubMed:21420501}. 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; U58992; AAC52785.1; -; mRNA. DR EMBL; U74359; AAB18256.1; -; mRNA. DR EMBL; AF295768; AAG41407.1; -; Genomic_DNA. DR EMBL; AF295763; AAG41407.1; JOINED; Genomic_DNA. DR EMBL; AF295764; AAG41407.1; JOINED; Genomic_DNA. DR EMBL; AF295765; AAG41407.1; JOINED; Genomic_DNA. DR EMBL; AF295766; AAG41407.1; JOINED; Genomic_DNA. DR EMBL; AF295767; AAG41407.1; JOINED; Genomic_DNA. DR EMBL; AK017583; BAB30820.1; -; mRNA. DR EMBL; AK054104; BAC35658.1; -; mRNA. DR EMBL; BC058693; AAH58693.1; -; mRNA. DR CCDS; CCDS22437.1; -. DR RefSeq; NP_032565.2; NM_008539.3. DR RefSeq; XP_006530809.1; XM_006530746.3. DR PDB; 3KMP; X-ray; 2.70 A; A/B=9-132. DR PDBsum; 3KMP; -. DR AlphaFoldDB; P70340; -. DR SMR; P70340; -. DR BioGRID; 201274; 35. DR ComplexPortal; CPX-145; SMAD1 homotrimer. DR ComplexPortal; CPX-146; SMAD1-SMAD4 complex. DR CORUM; P70340; -. DR IntAct; P70340; 9. DR MINT; P70340; -. DR STRING; 10090.ENSMUSP00000071035; -. DR ChEMBL; CHEMBL3883282; -. DR iPTMnet; P70340; -. DR PhosphoSitePlus; P70340; -. DR SwissPalm; P70340; -. DR EPD; P70340; -. DR MaxQB; P70340; -. DR PaxDb; 10090-ENSMUSP00000071035; -. DR PeptideAtlas; P70340; -. DR ProteomicsDB; 261254; -. DR Pumba; P70340; -. DR Antibodypedia; 3950; 1581 antibodies from 43 providers. DR DNASU; 17125; -. DR Ensembl; ENSMUST00000066091.14; ENSMUSP00000071035.8; ENSMUSG00000031681.17. DR GeneID; 17125; -. DR KEGG; mmu:17125; -. DR UCSC; uc009mip.2; mouse. DR AGR; MGI:109452; -. DR CTD; 4086; -. DR MGI; MGI:109452; Smad1. DR VEuPathDB; HostDB:ENSMUSG00000031681; -. DR eggNOG; KOG3701; Eukaryota. DR GeneTree; ENSGT00940000154391; -. DR HOGENOM; CLU_026736_0_2_1; -. DR InParanoid; P70340; -. DR OMA; WASVAYY; -. DR OrthoDB; 2891561at2759; -. DR PhylomeDB; P70340; -. DR TreeFam; TF314923; -. DR Reactome; R-MMU-201451; Signaling by BMP. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR Reactome; R-MMU-8941326; RUNX2 regulates bone development. DR BioGRID-ORCS; 17125; 4 hits in 81 CRISPR screens. DR ChiTaRS; Smad1; mouse. DR EvolutionaryTrace; P70340; -. DR PRO; PR:P70340; -. DR Proteomes; UP000000589; Chromosome 8. DR RNAct; P70340; Protein. DR Bgee; ENSMUSG00000031681; Expressed in ileal epithelium and 299 other cell types or tissues. DR ExpressionAtlas; P70340; baseline and differential. DR GO; GO:0000785; C:chromatin; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0071144; C:heteromeric SMAD protein complex; ISO:ComplexPortal. DR GO; GO:0071142; C:homomeric SMAD protein complex; IPI:ComplexPortal. DR GO; GO:0005637; C:nuclear inner membrane; 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:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0070410; F:co-SMAD binding; ISO:MGI. DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; ISO:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; 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:0070878; F:primary miRNA binding; IDA:BHF-UCL. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central. DR GO; GO:0030509; P:BMP signaling pathway; IDA:MGI. DR GO; GO:0060348; P:bone development; IGI:MGI. DR GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:MGI. DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; ISO:MGI. DR GO; GO:0051216; P:cartilage development; IGI:MGI. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0008283; P:cell population proliferation; IMP:MGI. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI. DR GO; GO:0006351; P:DNA-templated transcription; ISO:ComplexPortal. DR GO; GO:0009880; P:embryonic pattern specification; ISS:UniProtKB. DR GO; GO:0007276; P:gamete generation; IMP:MGI. DR GO; GO:0030902; P:hindbrain development; IMP:MGI. DR GO; GO:0042592; P:homeostatic process; IMP:MGI. DR GO; GO:0006954; P:inflammatory response; IEP:UniProtKB. DR GO; GO:0000165; P:MAPK cascade; IMP:MGI. DR GO; GO:0001710; P:mesodermal cell fate commitment; IGI:MGI. DR GO; GO:0030901; P:midbrain development; IMP:MGI. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI. DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IDA:MGI. DR GO; GO:0001503; P:ossification; ISO:MGI. DR GO; GO:0001649; P:osteoblast differentiation; IDA:MGI. DR GO; GO:0002051; P:osteoblast fate commitment; IGI:MGI. DR GO; GO:0061036; P:positive regulation of cartilage development; IDA:MGI. DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IMP:BHF-UCL. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IGI:MGI. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI. DR GO; GO:0060395; P:SMAD protein signal transduction; IGI:BHF-UCL. DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:ComplexPortal. DR GO; GO:0001657; P:ureteric bud development; IEP:UniProtKB. DR CDD; cd10490; MH1_SMAD_1_5_9; 1. DR CDD; cd10497; MH2_SMAD_1_5_9; 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:SF23; MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 1; 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; P70340; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; DNA-binding; Metal-binding; Nucleus; KW Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation; Ubl conjugation; Zinc. FT CHAIN 1..465 FT /note="Mothers against decapentaplegic homolog 1" FT /id="PRO_0000090848" FT DOMAIN 12..136 FT /note="MH1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00438" FT DOMAIN 271..465 FT /note="MH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00439" FT REGION 162..246 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 418..428 FT /note="L3 loop" FT /evidence="ECO:0000250|UniProtKB:Q15797" FT COMPBIAS 171..216 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 217..231 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 64 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 109 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 121 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 126 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:Q15797" FT MOD_RES 322 FT /note="Phosphothreonine; by MINK1, TNIK and MAP4K4" FT /evidence="ECO:0000250|UniProtKB:Q15797" FT MOD_RES 463 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15797, FT ECO:0000255|PROSITE-ProRule:PRU00439" FT MOD_RES 465 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15797, FT ECO:0000255|PROSITE-ProRule:PRU00439" FT CONFLICT 95 FT /note="P -> S (in Ref. 1; AAC52785 and 3; AAG41407)" FT /evidence="ECO:0000305" FT CONFLICT 142 FT /note="R -> K (in Ref. 1; AAC52785 and 3; AAG41407)" FT /evidence="ECO:0000305" FT CONFLICT 199..200 FT /note="SS -> QG (in Ref. 2; AAB18256)" FT /evidence="ECO:0000305" FT CONFLICT 393 FT /note="A -> E (in Ref. 2; AAB18256)" FT /evidence="ECO:0000305" FT HELIX 12..19 FT /evidence="ECO:0007829|PDB:3KMP" FT HELIX 25..41 FT /evidence="ECO:0007829|PDB:3KMP" FT HELIX 47..56 FT /evidence="ECO:0007829|PDB:3KMP" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:3KMP" FT STRAND 71..73 FT /evidence="ECO:0007829|PDB:3KMP" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:3KMP" FT STRAND 80..82 FT /evidence="ECO:0007829|PDB:3KMP" FT HELIX 84..92 FT /evidence="ECO:0007829|PDB:3KMP" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:3KMP" FT STRAND 103..105 FT /evidence="ECO:0007829|PDB:3KMP" FT HELIX 113..115 FT /evidence="ECO:0007829|PDB:3KMP" FT STRAND 118..121 FT /evidence="ECO:0007829|PDB:3KMP" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:3KMP" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:3KMP" SQ SEQUENCE 465 AA; 52157 MW; 07A56FBEE79A1C2A CRC64; MNVTSLFSFT SPAVKRLLGW KQGDEEEKWA EKAVDALVKK LKKKKGAMEE LEKALSCPGQ PSNCVTIPRS LDGRLQVSHR KGLPHVIYCR VWRWPDLQSH HELKPLECCE FPFGSKQKEV CINPYHYKRV ESPVLPPVLV PRHSEYNPQH SLLAQFRNLG QNEPHMPLNA TFPDSFQQPN SHPFPHSPNS SYPNSPGGSS STYPHSPTSS DPGSPFQMPA DTPPPAYLPP EDPMAQDGSQ PMDTNMMAPP LPAEISRGDV QAVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT DPSNNKNRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC NYHHGFHPTT VCKIPSGCSL KIFNNQEFAQ LLAQSVNHGF ETVYELTKMC TIRMSFVKGW GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPHNP ISSVS //