CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012635
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Mothers against decapentaplegic homolog 2 
Protein Synonyms/Alias
 MAD homolog 2; Mothers against DPP homolog 2; JV18-1; Mad-related protein 2; hMAD-2; SMAD family member 2; SMAD 2; Smad2; hSMAD2 
Gene Name
 SMAD2 
Gene Synonyms/Alias
 MADH2; MADR2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
13PFTPPVVKRLLGWKKubiquitination[1, 2, 3]
19VKRLLGWKKSAGGSGacetylation[4]
20KRLLGWKKSAGGSGGacetylation[4]
39EQNGQEEKWCEKAVKacetylation[5]
54SLVKKLKKTGRLDELubiquitination[3]
157EYAFNLKKDEVCVNPubiquitination[3]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] The DNA binding activities of Smad2 and Smad3 are regulated by coactivator-mediated acetylation.
 Simonsson M, Kanduri M, Grönroos E, Heldin CH, Ericsson J.
 J Biol Chem. 2006 Dec 29;281(52):39870-80. [PMID: 17074756]
 [5] Acetylation of Smad2 by the co-activator p300 regulates activin and transforming growth factor beta response.
 Tu AW, Luo K.
 J Biol Chem. 2007 Jul 20;282(29):21187-96. [PMID: 17478422] 
Functional Description
 Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. 
Sequence Annotation
 DOMAIN 10 176 MH1.
 DOMAIN 274 467 MH2.
 MOTIF 221 225 PY-motif.
 METAL 74 74 Zinc (By similarity).
 METAL 149 149 Zinc (By similarity).
 METAL 161 161 Zinc (By similarity).
 METAL 166 166 Zinc (By similarity).
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 8 8 Phosphothreonine; by MAPK3.
 MOD_RES 19 19 N6-acetyllysine.
 MOD_RES 220 220 Phosphothreonine (Probable).
 MOD_RES 240 240 Phosphoserine; by CAMK2.
 MOD_RES 245 245 Phosphoserine (Probable).
 MOD_RES 250 250 Phosphoserine (Probable).
 MOD_RES 255 255 Phosphoserine (Probable).
 MOD_RES 458 458 Phosphoserine.
 MOD_RES 460 460 Phosphoserine.
 MOD_RES 464 464 Phosphoserine.
 MOD_RES 465 465 Phosphoserine; by TGFBR1.
 MOD_RES 467 467 Phosphoserine; by TGFBR1.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transcription; Transcription regulation; Ubl conjugation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 467 AA 
Protein Sequence
MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK KLKKTGRLDE 60
LEKAITTQNC NTKCVTIPST CSEIWGLSTP NTIDQWDTTG LYSFSEQTRS LDGRLQVSHR 120
KGLPHVIYCR LWRWPDLHSH HELKAIENCE YAFNLKKDEV CVNPYHYQRV ETPVLPPVLV 180
PRHTEILTEL PPLDDYTHSI PENTNFPAGI EPQSNYIPET PPPGYISEDG ETSDQQLNQS 240
MDTGSPAELS PTTLSPVNHS LDLQPVTYSE PAFWCSIAYY ELNQRVGETF HASQPSLTVD 300
GFTDPSNSER FCLGLLSNVN RNATVEMTRR HIGRGVRLYY IGGEVFAECL SDSAIFVQSP 360
NCNQRYGWHP ATVCKIPPGC NLKIFNNQEF AALLAQSVNQ GFEAVYQLTR MCTIRMSFVK 420
GWGAEYRRQT VTSTPCWIEL HLNGPLQWLD KVLTQMGSPS VRCSSMS 467 
Gene Ontology
 GO:0032444; C:activin responsive factor complex; IDA:BHF-UCL.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0071141; C:SMAD protein complex; IDA:UniProtKB.
 GO:0003682; F:chromatin binding; IEA:Compara.
 GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:0030618; F:transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity; IDA:BHF-UCL.
 GO:0009952; P:anterior/posterior pattern specification; ISS:UniProtKB.
 GO:0045165; P:cell fate commitment; ISS:UniProtKB.
 GO:0007182; P:common-partner SMAD protein phosphorylation; IDA:MGI.
 GO:0048589; P:developmental growth; IEA:Compara.
 GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Compara.
 GO:0048617; P:embryonic foregut morphogenesis; IEA:Compara.
 GO:0007492; P:endoderm development; IEA:Compara.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0030073; P:insulin secretion; IEA:Compara.
 GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
 GO:0030324; P:lung development; IEA:Compara.
 GO:0001707; P:mesoderm formation; ISS:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:Reactome.
 GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:0038092; P:nodal signaling pathway; IMP:BHF-UCL.
 GO:0035265; P:organ growth; IEA:Compara.
 GO:0060021; P:palate development; ISS:BHF-UCL.
 GO:0031016; P:pancreas development; IEA:Compara.
 GO:0048340; P:paraxial mesoderm morphogenesis; ISS:UniProtKB.
 GO:0060039; P:pericardium development; IEA:Compara.
 GO:0030513; P:positive regulation of BMP signaling pathway; IMP:BHF-UCL.
 GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:BHF-UCL.
 GO:1900224; P:positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; IMP:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
 GO:0009791; P:post-embryonic development; IEA:Compara.
 GO:0031053; P:primary miRNA processing; TAS:BHF-UCL.
 GO:0051098; P:regulation of binding; ISS:UniProtKB.
 GO:0070723; P:response to cholesterol; IDA:BHF-UCL.
 GO:0009749; P:response to glucose stimulus; IEA:Compara.
 GO:0007183; P:SMAD protein complex assembly; IDA:BHF-UCL.
 GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
 GO:0001657; P:ureteric bud development; IEA:Compara.
 GO:0007352; P:zygotic specification of dorsal/ventral axis; IMP: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