CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010652
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Mothers against decapentaplegic homolog 4 
Protein Synonyms/Alias
 MAD homolog 4; Mothers against DPP homolog 4; Deletion target in pancreatic carcinoma 4 homolog; SMAD family member 4; SMAD 4; Smad4 
Gene Name
 Smad4 
Gene Synonyms/Alias
 Dpc4; Madh4 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
45RAIESLVKKLKEKKDubiquitination[1]
113KNELKHVKYCQYAFDubiquitination[1]
427APGDAVHKIYPSAYIacetylation[2, 3]
506ILRMSFVKGWGPDYPacetylation[2, 3]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [3] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 
Functional Description
 Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for syngernistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14- 3-3 protein YWHAQ which acts as a negative regulator (By similarity). 
Sequence Annotation
 DOMAIN 18 142 MH1.
 DOMAIN 322 551 MH2.
 REGION 274 319 SAD.
 METAL 71 71 Zinc (By similarity).
 METAL 115 115 Zinc (By similarity).
 METAL 127 127 Zinc (By similarity).
 METAL 132 132 Zinc (By similarity).
 MOD_RES 37 37 N6-acetyllysine (By similarity).
 MOD_RES 427 427 N6-acetyllysine (By similarity).
 MOD_RES 506 506 N6-acetyllysine (By similarity).
 CROSSLNK 518 518 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Complete proteome; Cytoplasm; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 551 AA 
Protein Sequence
MDNMSITNTP TSNDACLSIV HSLMCHRQGG ESETFAKRAI ESLVKKLKEK KDELDSLITA 60
ITTNGAHPSK CVTIQRTLDG RLQVAGRKGF PHVIYARLWR WPDLHKNELK HVKYCQYAFD 120
LKCDSVCVNP YHYERVVSPG IDLSGLTLQS NAPSMLVKDE YVHDFEGQPS LPTEGHSIQT 180
IQHPPSNRAS TETYSAPALL APAESNATST TNFPNIPVAS TSQPASILAG SHSEGLLQIA 240
SGPQPGQQQN GFTAQPATYH HNSTTTWTGS RTAPYTPNLP HHQNGHLQHH PPMPPHPGHY 300
WPVHNELAFQ PPISNHPAPE YWCSIAYFEM DVQVGETFKV PSSCPVVTVD GYVDPSGGDR 360
FCLGQLSNVH RTEAIERARL HIGKGVQLEC KGEGDVWVRC LSDHAVFVQS YYLDREAGRA 420
PGDAVHKIYP SAYIKVFDLR QCHRQMQQQA ATAQAAAAAQ AAAVAGNIPG PGSVGGIAPA 480
ISLSAAAGIG VDDLRRLCIL RMSFVKGWGP DYPRQSIKET PCWIEIHLHR ALQLLDEVLH 540
TMPIADPQPL D 551 
Gene Ontology
 GO:0032444; C:activin responsive factor complex; IEA:Compara.
 GO:0005813; C:centrosome; IEA:Compara.
 GO:0005737; C:cytoplasm; IDA:BHF-UCL.
 GO:0071141; C:SMAD protein complex; IEA:Compara.
 GO:0005667; C:transcription factor complex; IPI:UniProtKB.
 GO:0003682; F:chromatin binding; IDA:MGI.
 GO:0000987; F:core promoter proximal region sequence-specific DNA binding; IEA:Compara.
 GO:0003677; F:DNA binding; IDA:MGI.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0001076; F:RNA polymerase II transcription factor binding transcription factor activity; IDA:BHF-UCL.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:MGI.
 GO:0030616; F:transforming growth factor beta receptor, common-partner cytoplasmic mediator activity; IEA:Compara.
 GO:0036302; P:atrioventricular canal development; IGI:BHF-UCL.
 GO:0003190; P:atrioventricular valve formation; IGI:BHF-UCL.
 GO:0007411; P:axon guidance; IMP:MGI.
 GO:0030509; P:BMP signaling pathway; IEA:Compara.
 GO:0003360; P:brainstem development; IMP:MGI.
 GO:0001658; P:branching involved in ureteric bud morphogenesis; IGI:MGI.
 GO:0003279; P:cardiac septum development; IGI:BHF-UCL.
 GO:0008283; P:cell proliferation; IMP:MGI.
 GO:0048589; P:developmental growth; IMP:MGI.
 GO:0060956; P:endocardial cell differentiation; IMP:BHF-UCL.
 GO:0007492; P:endoderm development; IMP:MGI.
 GO:0042118; P:endothelial cell activation; IMP:BHF-UCL.
 GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; IMP:BHF-UCL.
 GO:0048859; P:formation of anatomical boundary; IMP:MGI.
 GO:0001702; P:gastrulation with mouth forming second; IMP:MGI.
 GO:0001701; P:in utero embryonic development; IMP:MGI.
 GO:0007498; P:mesoderm development; IMP:MGI.
 GO:0072133; P:metanephric mesenchyme morphogenesis; IMP:UniProtKB.
 GO:0060548; P:negative regulation of cell death; IMP:UniProtKB.
 GO:0030308; P:negative regulation of cell growth; IEA:Compara.
 GO:0008285; P:negative regulation of cell proliferation; IGI:MGI.
 GO:0042177; P:negative regulation of protein catabolic process; IEA:Compara.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IEA:Compara.
 GO:0072134; P:nephrogenic mesenchyme morphogenesis; IMP:UniProtKB.
 GO:0014033; P:neural crest cell differentiation; IMP:MGI.
 GO:0048663; P:neuron fate commitment; IMP:MGI.
 GO:0060021; P:palate development; IMP:BHF-UCL.
 GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Compara.
 GO:0003251; P:positive regulation of cell proliferation involved in heart valve morphogenesis; IMP:BHF-UCL.
 GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
 GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IMP:BHF-UCL.
 GO:0060391; P:positive regulation of SMAD protein import into nucleus; IMP:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IEA:Compara.
 GO:0051098; P:regulation of binding; IDA:MGI.
 GO:0051797; P:regulation of hair follicle development; IMP:MGI.
 GO:0032909; P:regulation of transforming growth factor beta2 production; IEA:Compara.
 GO:0001666; P:response to hypoxia; IEA:Compara.
 GO:0048733; P:sebaceous gland development; IMP:MGI.
 GO:0007183; P:SMAD protein complex assembly; IEA:Compara.
 GO:0060395; P:SMAD protein signal transduction; IEA:Compara.
 GO:0032525; P:somite rostral/caudal axis specification; IMP:MGI.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IGI:MGI. 
Interpro
 IPR013790; Dwarfin.
 IPR003619; MAD_homology1_Dwarfin-type.
 IPR013019; MAD_homology_MH1.
 IPR017855; SMAD_dom-like.
 IPR001132; SMAD_dom_Dwarfin-type.
 IPR008984; SMAD_FHA_domain. 
Pfam
 PF03165; MH1
 PF03166; MH2 
SMART
 SM00523; DWA
 SM00524; DWB 
PROSITE
 PS51075; MH1
 PS51076; MH2 
PRINTS