SMAD4_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: SMAD4_MOUSE
• UniProt AC: P97471
• Protein Name: Mothers against decapentaplegic homolog 4
• Gene Name: Smad4
• Organism: Mus musculus (Mouse).
• Sequence Length: 551
• Subcellular Localization: Cytoplasm . Nucleus . In the cytoplasm in the absence of ligand. Migration to the nucleus when complexed with R-SMAD. PDPK1 prevents its nuclear translocation.
• Protein 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 synergistic 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). Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. [PubMed: 15329343 Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions]
• Protein Sequence: MDNMSITNTPTSNDACLSIVHSLMCHRQGGESETFAKRAIESLVKKLKEKKDELDSLITAITTNGAHPSKCVTIQRTLDGRLQVAGRKGFPHVIYARLWRWPDLHKNELKHVKYCQYAFDLKCDSVCVNPYHYERVVSPGIDLSGLTLQSNAPSMLVKDEYVHDFEGQPSLPTEGHSIQTIQHPPSNRASTETYSAPALLAPAESNATSTTNFPNIPVASTSQPASILAGSHSEGLLQIASGPQPGQQQNGFTAQPATYHHNSTTTWTGSRTAPYTPNLPHHQNGHLQHHPPMPPHPGHYWPVHNELAFQPPISNHPAPEYWCSIAYFEMDVQVGETFKVPSSCPVVTVDGYVDPSGGDRFCLGQLSNVHRTEAIERARLHIGKGVQLECKGEGDVWVRCLSDHAVFVQSYYLDREAGRAPGDAVHKIYPSAYIKVFDLRQCHRQMQQQAATAQAAAAAQAAAVAGNIPGPGSVGGIAPAISLSAAAGIGVDDLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLHRALQLLDEVLHTMPIADPQPLD

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
34	Phosphorylation	RQGGESETFAKRAIE CCCCCCHHHHHHHHH	37.87	29514104
37	Acetylation	GESETFAKRAIESLV CCCHHHHHHHHHHHH	37.87	-
45	Ubiquitination	RAIESLVKKLKEKKD HHHHHHHHHHHHCHH	58.65	-
45	Malonylation	RAIESLVKKLKEKKD HHHHHHHHHHHHCHH	58.65	26320211
46	Acetylation	AIESLVKKLKEKKDE HHHHHHHHHHHCHHH	58.26	8275711
48	Acetylation	ESLVKKLKEKKDELD HHHHHHHHHCHHHHH	76.11	155685
113	Ubiquitination	KNELKHVKYCQYAFD HHHCCCCCCCCCCCC	39.77	22790023
170	Phosphorylation	HDFEGQPSLPTEGHS ECCCCCCCCCCCCCC	38.81	25338131
276	Phosphorylation	GSRTAPYTPNLPHHQ CCCCCCCCCCCCCCC	12.49	12801888
427	Acetylation	APGDAVHKIYPSAYI CCCCHHHHHCCHHEE	37.02	23236377
506	Acetylation	ILRMSFVKGWGPDYP HHHHHHHCCCCCCCC	47.11	23236377

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
276	T	Phosphorylation	Kinase	MAPK1	P63085	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Btrc	Q3ULA2	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Trim33	Q99PP7	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
518	K	ubiquitylation	Monoubiquitinated on Lys-518 by E3 ubiquitin-protein ligase TRIM33.	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of SMAD4_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SNAI1_MOUSE	Snai1	physical	19597490
TLX3_MOUSE	Tlx3	physical	20211142
FOXP1_MOUSE	Foxp1	physical	20211142
GATA4_MOUSE	Gata4	physical	14662776
GATA5_MOUSE	Gata5	physical	14662776
GATA6_MOUSE	Gata6	physical	14662776
SMAD2_MOUSE	Smad2	physical	12672795
SMAD3_MOUSE	Smad3	physical	12672795
SMRD3_MOUSE	Smarcd3	physical	15525990
SMAD2_MOUSE	Smad2	physical	17452626
LEF1_MOUSE	Lef1	physical	17452626
LEF1_MOUSE	Lef1	genetic	14691138
PEX6_MOUSE	Pex6	physical	14651998
4ET_MOUSE	Eif4enif1	physical	14651998
ZMYM2_MOUSE	Zmym2	physical	14651998
PBX1_MOUSE	Pbx1	physical	14764653
PKNX1_MOUSE	Pknox1	physical	14764653
SMAD4_MOUSE	Smad4	physical	14764653
PRD16_MOUSE	Prdm16	physical	17467076

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.