CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-000376
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Mothers against decapentaplegic homolog 7 
Protein Synonyms/Alias
 MAD homolog 7; Mothers against DPP homolog 7; Mothers against decapentaplegic homolog 8; MAD homolog 8; Mothers against DPP homolog 8; SMAD family member 7; SMAD 7; Smad7; hSMAD7 
Gene Name
 SMAD7 
Gene Synonyms/Alias
 MADH7; MADH8 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
64RAGCCLGKAVRGAKGacetylation[1, 2]
64RAGCCLGKAVRGAKGubiquitination[3]
70GKAVRGAKGHHHPHPacetylation[1]
70GKAVRGAKGHHHPHPubiquitination[3]
Reference
 [1] Control of Smad7 stability by competition between acetylation and ubiquitination.
 Grönroos E, Hellman U, Heldin CH, Ericsson J.
 Mol Cell. 2002 Sep;10(3):483-93. [PMID: 12408818]
 [2] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789
Functional Description
 Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A- PP1 complex to TGFBR1, which promotes its dephosphorylation. 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 64 207 MH1.
 DOMAIN 261 426 MH2.
 REGION 208 217 Important for interaction with SMURF2.
 MOTIF 208 211 PY-motif.
 METAL 125 125 Zinc (By similarity).
 METAL 180 180 Zinc (By similarity).
 METAL 192 192 Zinc (By similarity).
 METAL 197 197 Zinc (By similarity).
 MOD_RES 64 64 N6-acetyllysine; alternate.
 MOD_RES 70 70 N6-acetyllysine; alternate.
 MOD_RES 249 249 Phosphoserine (By similarity).
 CROSSLNK 64 64 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 70 70 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 426 AA 
Protein Sequence
MFRTKRSALV RRLWRSRAPG GEDEEEGAGG GGGGGELRGE GATDSRAHGA GGGGPGRAGC 60
CLGKAVRGAK GHHHPHPPAA GAGAAGGAEA DLKALTHSVL KKLKERQLEL LLQAVESRGG 120
TRTACLLLPG RLDCRLGPGA PAGAQPAQPP SSYSLPLLLC KVFRWPDLRH SSEVKRLCCC 180
ESYGKINPEL VCCNPHHLSR LCELESPPPP YSRYPMDFLK PTADCPDAVP SSAETGGTNY 240
LAPGGLSDSQ LLLEPGDRSH WCVVAYWEEK TRVGRLYCVQ EPSLDIFYDL PQGNGFCLGQ 300
LNSDNKSQLV QKVRSKIGCG IQLTREVDGV WVYNRSSYPI FIKSATLDNP DSRTLLVHKV 360
FPGFSIKAFD YEKAYSLQRP NDHEFMQQPW TGFTVQISFV KGWGQCYTRQ FISSCPCWLE 420
VIFNSR 426 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; IDA:BHF-UCL.
 GO:0005667; C:transcription factor complex; IEA:InterPro.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
 GO:0030617; F:transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity; IDA:BHF-UCL.
 GO:0034333; P:adherens junction assembly; IMP:BHF-UCL.
 GO:0048844; P:artery morphogenesis; ISS:BHF-UCL.
 GO:0030509; P:BMP signaling pathway; TAS:Reactome.
 GO:0034629; P:cellular protein complex localization; IDA:BHF-UCL.
 GO:0035556; P:intracellular signal transduction; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; TAS:BHF-UCL.
 GO:0030514; P:negative regulation of BMP signaling pathway; IDA:BHF-UCL.
 GO:0030336; P:negative regulation of cell migration; TAS:BHF-UCL.
 GO:0010719; P:negative regulation of epithelial to mesenchymal transition; TAS:BHF-UCL.
 GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
 GO:0033137; P:negative regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IDA:BHF-UCL.
 GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:BHF-UCL.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
 GO:0051444; P:negative regulation of ubiquitin-protein ligase activity; IDA:BHF-UCL.
 GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:BHF-UCL.
 GO:0022409; P:positive regulation of cell-cell adhesion; IDA:BHF-UCL.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
 GO:0031398; P:positive regulation of protein ubiquitination; IDA:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; TAS:Reactome.
 GO:0050821; P:protein stabilization; IDA:BHF-UCL.
 GO:0032925; P:regulation of activin receptor signaling pathway; IDA:BHF-UCL.
 GO:0055117; P:regulation of cardiac muscle contraction; ISS:BHF-UCL.
 GO:0060373; P:regulation of ventricular cardiac muscle cell membrane depolarization; IC:BHF-UCL.
 GO:0034616; P:response to laminar fluid shear stress; IEP:BHF-UCL.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:0001657; P:ureteric bud development; IEA:Compara.
 GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
 GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL. 
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