You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
NameMothers against decapentaplegic homolog 1
Synonyms
  • BSP-1
  • BSP1
  • hSMAD1
  • JV4-1
  • MAD homolog 1
  • Mad-related protein 1
  • MADH1
  • MADR1
  • SMAD 1
  • SMAD family member 1
  • Smad1
  • Transforming growth factor-beta-signaling protein 1
Gene NameSMAD1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009303|Mothers against decapentaplegic homolog 1
MNVTSLFSFTSPAVKRLLGWKQGDEEEKWAEKAVDALVKKLKKKKGAMEELEKALSCPGQ
PSNCVTIPRSLDGRLQVSHRKGLPHVIYCRVWRWPDLQSHHELKPLECCEFPFGSKQKEV
CINPYHYKRVESPVLPPVLVPRHSEYNPQHSLLAQFRNLGQNEPHMPLNATFPDSFQQPN
SHPFPHSPNSSYPNSPGSSSSTYPHSPTSSDPGSPFQMPADTPPPAYLPPEDPMTQDGSQ
PMDTNMMAPPLPSEINRGDVQAVAYEEPKHWCSIVYYELNNRVGEAFHASSTSVLVDGFT
DPSNNKNRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYVGGEVYAECLSDSSIFVQSRNC
NYHHGFHPTTVCKIPSGCSLKIFNNQEFAQLLAQSVNHGFETVYELTKMCTIRMSFVKGW
GAEYHRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS
Number of residues465
Molecular Weight52259.72
Theoretical pINot Available
GO Classification
Functions
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
  • identical protein binding
  • protein kinase binding
  • I-SMAD binding
  • receptor signaling protein activity
  • RNA polymerase II core promoter sequence-specific DNA binding
  • metal ion binding
  • co-SMAD binding
  • transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity
  • transcription factor activity, sequence-specific DNA binding
Processes
  • positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
  • hindbrain development
  • cardiac muscle cell proliferation
  • gamete generation
  • SMAD protein complex assembly
  • MAPK cascade
  • mesodermal cell fate commitment
  • embryonic pattern specification
  • negative regulation of cell proliferation
  • osteoblast fate commitment
  • midbrain development
  • positive regulation of transcription from RNA polymerase II promoter
  • positive regulation of cartilage development
  • ureteric bud development
  • bone development
  • signal transduction
  • homeostatic process
  • transforming growth factor beta receptor signaling pathway
  • positive regulation of gene expression
  • SMAD protein signal transduction
  • BMP signaling pathway
  • inflammatory response
  • cellular response to BMP stimulus
  • positive regulation of osteoblast differentiation
  • transcription from RNA polymerase II promoter
  • primary miRNA processing
  • cartilage development
Components
  • cytosol
  • nucleoplasm
  • intracellular
  • cytoplasm
  • transcription factor complex
  • nuclear inner membrane
  • protein complex
  • nucleus
  • SMAD protein complex
  • integral component of membrane
General FunctionTransforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity
Specific FunctionTranscriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-regulated SMAD (R-SMAD). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ15797
UniProtKB Entry NameSMAD1_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0013729|Mothers against decapentaplegic homolog 1 (SMAD1)
ATGAATGTGACAAGTTTATTTTCCTTTACAAGTCCAGCTGTGAAGAGACTTCTTGGGTGG
AAACAGGGCGATGAAGAAGAAAAATGGGCAGAGAAAGCTGTTGATGCTTTGGTGAAAAAA
CTGAAGAAAAAGAAAGGTGCCATGGAGGAACTGGAAAAGGCCTTGAGCTGCCCAGGGCAA
CCGAGTAACTGTGTCACCATTCCCCGCTCTCTGGATGGCAGGCTGCAAGTCTCCCACCGG
AAGGGACTGCCTCATGTCATTTACTGCCGTGTGTGGCGCTGGCCCGATCTTCAGAGCCAC
CATGAACTAAAACCACTGGAATGCTGTGAGTTTCCTTTTGGTTCCAAGCAGAAGGAGGTC
TGCATCAATCCCTACCACTATAAGAGAGTAGAAAGCCCTGTACTTCCTCCTGTGCTGGTT
CCAAGACACAGCGAATATAATCCTCAGCACAGCCTCTTAGCTCAGTTCCGTAACTTAGGA
CAAAATGAGCCTCACATGCCACTCAACGCCACTTTTCCAGATTCTTTCCAGCAACCCAAC
AGCCACCCGTTTCCTCACTCTCCCAATAGCAGTTACCCAAACTCTCCTGGGAGCAGCAGC
AGCACCTACCCTCACTCTCCCACCAGCTCAGACCCAGGAAGCCCTTTCCAGATGCCAGCT
GATACGCCCCCACCTGCTTACCTGCCTCCTGAAGACCCCATGACCCAGGATGGCTCTCAG
CCGATGGACACAAACATGATGGCGCCTCCCCTGCCCTCAGAAATCAACAGAGGAGATGTT
CAGGCGGTTGCTTATGAGGAACCAAAACACTGGTGCTCTATTGTCTACTATGAGCTCAAC
AATCGTGTGGGTGAAGCGTTCCATGCCTCCTCCACAAGTGTGTTGGTGGATGGTTTCACT
GATCCTTCCAACAATAAGAACCGTTTCTGCCTTGGGCTGCTCTCCAATGTTAACCGGAAT
TCCACTATTGAAAACACCAGGCGGCATATTGGAAAAGGAGTTCATCTTTATTATGTTGGA
GGGGAGGTGTATGCCGAATGCCTTAGTGACAGTAGCATCTTTGTGCAAAGTCGGAACTGC
AACTACCATCATGGATTTCATCCTACTACTGTTTGCAAGATCCCTAGTGGGTGTAGTCTG
AAAATTTTTAACAACCAAGAATTTGCTCAGTTATTGGCACAGTCTGTGAACCATGGATTT
GAGACAGTCTATGAGCTTACAAAAATGTGTACTATACGTATGAGCTTTGTGAAGGGCTGG
GGAGCAGAATACCACCGCCAGGATGTTACTAGCACCCCCTGCTGGATTGAGATACATCTG
CACGGCCCCCTCCAGTGGCTGGATAAAGTTCTTACTCAAATGGGTTCACCTCATAATCCT
ATTTCATCTGTATCTTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:6767
Chromosome Location4
LocusNot Available
References
  1. Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B: Mad-related genes in the human. Nat Genet. 1996 Jul;13(3):347-9. 8673135
  2. Liu F, Hata A, Baker JC, Doody J, Carcamo J, Harland RM, Massague J: A human Mad protein acting as a BMP-regulated transcriptional activator. Nature. 1996 Jun 13;381(6583):620-3. 8637600
  3. Hoodless PA, Haerry T, Abdollah S, Stapleton M, O'Connor MB, Attisano L, Wrana JL: MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell. 1996 May 17;85(4):489-500. 8653785
  4. Lechleider RJ, de Caestecker MP, Dehejia A, Polymeropoulos MH, Roberts AB: Serine phosphorylation, chromosomal localization, and transforming growth factor-beta signal transduction by human bsp-1. J Biol Chem. 1996 Jul 26;271(30):17617-20. 8663601
  5. Zhang Y, Feng X, We R, Derynck R: Receptor-associated Mad homologues synergize as effectors of the TGF-beta response. Nature. 1996 Sep 12;383(6596):168-72. 8774881
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  7. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. 17974005
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  9. Kretzschmar M, Liu F, Hata A, Doody J, Massague J: The TGF-beta family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes Dev. 1997 Apr 15;11(8):984-95. 9136927
  10. Massague J: TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753-91. 9759503
  11. Verschueren K, Huylebroeck D: Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells. Cytokine Growth Factor Rev. 1999 Sep-Dec;10(3-4):187-99. 10647776
  12. Hata A, Seoane J, Lagna G, Montalvo E, Hemmati-Brivanlou A, Massague J: OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell. 2000 Jan 21;100(2):229-40. 10660046
  13. Wrana JL, Attisano L: The Smad pathway. Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):5-13. 10708948
  14. Miyazono K: TGF-beta signaling by Smad proteins. Cytokine Growth Factor Rev. 2000 Mar-Jun;11(1-2):15-22. 10708949
  15. Lin Y, Martin J, Gruendler C, Farley J, Meng X, Li BY, Lechleider R, Huff C, Kim RH, Grasser WA, Paralkar V, Wang T: A novel link between the proteasome pathway and the signal transduction pathway of the bone morphogenetic proteins (BMPs). BMC Cell Biol. 2002 Jun 21;3:15. 12097147
  16. Bond HM, Mesuraca M, Carbone E, Bonelli P, Agosti V, Amodio N, De Rosa G, Di Nicola M, Gianni AM, Moore MA, Hata A, Grieco M, Morrone G, Venuta S: Early hematopoietic zinc finger protein (EHZF), the human homolog to mouse Evi3, is highly expressed in primitive human hematopoietic cells. Blood. 2004 Mar 15;103(6):2062-70. Epub 2003 Nov 20. 14630787
  17. Pan D, Estevez-Salmeron LD, Stroschein SL, Zhu X, He J, Zhou S, Luo K: The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines. J Biol Chem. 2005 Apr 22;280(16):15992-6001. Epub 2005 Jan 12. 15647271
  18. Arndt S, Poser I, Moser M, Bosserhoff AK: Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling. Mol Cell Neurosci. 2007 Apr;34(4):603-11. Epub 2007 Jan 11. 17292623
  19. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  20. Kaneko S, Chen X, Lu P, Yao X, Wright TG, Rajurkar M, Kariya K, Mao J, Ip YT, Xu L: Smad inhibition by the Ste20 kinase Misshapen. Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11127-32. doi: 10.1073/pnas.1104128108. Epub 2011 Jun 20. 21690388
  21. Inui M, Manfrin A, Mamidi A, Martello G, Morsut L, Soligo S, Enzo E, Moro S, Polo S, Dupont S, Cordenonsi M, Piccolo S: USP15 is a deubiquitylating enzyme for receptor-activated SMADs. Nat Cell Biol. 2011 Sep 25;13(11):1368-75. doi: 10.1038/ncb2346. 21947082
  22. Bruce DL, Macartney T, Yong W, Shou W, Sapkota GP: Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor-beta pathway. Cell Signal. 2012 Nov;24(11):1999-2006. doi: 10.1016/j.cellsig.2012.07.003. Epub 2012 Jul 7. 22781750
  23. Nasim MT, Ogo T, Ahmed M, Randall R, Chowdhury HM, Snape KM, Bradshaw TY, Southgate L, Lee GJ, Jackson I, Lord GM, Gibbs JS, Wilkins MR, Ohta-Ogo K, Nakamura K, Girerd B, Coulet F, Soubrier F, Humbert M, Morrell NW, Trembath RC, Machado RD: Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertension. Hum Mutat. 2011 Dec;32(12):1385-9. doi: 10.1002/humu.21605. Epub 2011 Oct 11. 21898662
  24. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  25. Vogt J, Dingwell KS, Herhaus L, Gourlay R, Macartney T, Campbell D, Smith JC, Sapkota GP: Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling. Open Biol. 2014 Feb 19;4:130210. doi: 10.1098/rsob.130210. 24554596
  26. Qin BY, Chacko BM, Lam SS, de Caestecker MP, Correia JJ, Lin K: Structural basis of Smad1 activation by receptor kinase phosphorylation. Mol Cell. 2001 Dec;8(6):1303-12. 11779505