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SMAD1/MADH1; mothers against decapentaplegic homolog 1; mothers against DPP homolog 1; MAD homolog 1; Mad-related protein 1; SMAD family member 1; SMAD 1; smad1; hSMAD1; transforming growth factor-beta-signaling protein 1; BSP-1; JV4-1; dwarfin A (SMAD1, BSP1, MADH1, MADR1)

Function: - transcriptional modulator activated by BMP 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 - phosphorylated on Ser by BMP type 1 receptor kinase - ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1 - interacts with HGS, NANOG & ZCCHC12 (putative) - may form trimers with another SMAD1 & the co-SMAD SMAD4 - interacts with PEBP2-alpha subunit, CREB-binding protein (CBP), p300, SMURF1, SMURF2 & HOXC8. associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes - interacts with LBXCOR1. - interacts (via MH2 domain) with LEMD3 - binding to LEMD3 results in at least a partial reduction of receptor-mediated phosphorylation - forms a ternary complex with PSMB4 & OAZ1 before PSMB4 is incorporated into the 20S proteasome Structure: - belongs to the dwarfin/SMAD family - contains 1 MH1 (MAD homology 1) domain - contains 1 MH2 (MAD homology 2) domain Compartment: - cytoplasm, nucleus - cytoplasmic in the absence of ligand - migrates to the nucleus when complexed with SMAD4 - co-localizes with LEMD3 at the nucleus inner membrane Expression: - ubiquitous - highest expression seen in the heart & skeletal muscle

Interactions

molecular events

General

phosphoprotein SMAD protein

Properties

SIZE: entity length = 465 aa MW = 52 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl MH1 domain {12-136} MOTIF: lysine-rich region {39-45} MOTIF: lysine residue (SEVERAL) serine-rich region {198-201} MOTIF: serine residue (SEVERAL) MH2 domain {271-465} MOTIF: Ser phosphorylation site {S463} Ser phosphorylation site {S465}

References

  1. Derynck R et al Nomenclature: vertebrate mediators of TGFbeta family signals. Cell 87:173, 1996 PMID: 8861901
  2. Izzi L & Attisano L Regulation of the TGFbeta signalling pathway by ubiquitin-mediated degradation. Oncogene 23:2071-8, 2004 PMID: 15021894
  3. UniProt :accession Q15797

Databases & Figures

OMIM 601595 UniProt Q15797 PFAM correlations Entrez Gene 4086 Kegg hsa:4086 TGF-beta/BMP signaling