Smad3
entrez
25631
canonical
uniprot
P84025
canonical
ensembl
ENSRNOG00000008620
resolver
ensembl
ENSRNOG00055023531
resolver
ensembl
ENSRNOG00060018232
resolver
ensembl
ENSRNOG00065007937
resolver
ensp
ENSRNOP00000037346
resolver
ensp
ENSRNOP00000081624
resolver
ensp
ENSRNOP00055032868
resolver
ensp
ENSRNOP00060025432
resolver
ensp
ENSRNOP00065009220
resolver
enst
ENSRNOT00000039730
resolver
enst
ENSRNOT00000099327
resolver
enst
ENSRNOT00055040461
resolver
enst
ENSRNOT00060031345
resolver
enst
ENSRNOT00065012522
resolver
genesymbol
Smad3
resolver
genesymbol_syn
Madh3
resolver
genesymbol_syn
Smad2
resolver
uniprot
A0A8I5ZS20
resolver
uniprot
O09064
resolver
uniprot
O09144
resolver
uniprot
O14510
resolver
uniprot
O35273
resolver
uniprot
Q92940
resolver
uniprot
Q93002
resolver
uniprot
Q9GKR4
resolver
uniprot_entry
A0A8I5ZS20_RAT
resolver
uniprot_entry
SMAD3_RAT
resolver
uniprot_sec
O09064
resolver
uniprot_sec
O09144
resolver
uniprot_sec
O14510
resolver
uniprot_sec
O35273
resolver
uniprot_sec
Q92940
resolver
uniprot_sec
Q93002
resolver
uniprot_sec
Q9GKR4
resolver
amino_acid_sequence
MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNVNTKCITIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEVCVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETPPPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYELNQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIGGEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSIRCSSVS
uniprot
proteins
function
FUNCTION: 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 SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator (By similarity). {ECO:0000250|UniProtKB:P84022, ECO:0000269|PubMed:8917532}.
uniprot
proteins
mass_dalton
48081
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G(1)/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Phosphorylated by PDPK1 (By similarity). {ECO:0000250|UniProtKB:P84022}.; PTM: Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta. {ECO:0000250|UniProtKB:P84022}.; PTM: Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes. Ubiquitinated by RNF111, leading to its degradation: only SMAD3 proteins, that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD3 and regulating its turnover. Undergoes STUB1-mediated ubiquitination and degradation. {ECO:0000250|UniProtKB:P84022, ECO:0000250|UniProtKB:Q8BUN5}.; PTM: Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling. {ECO:0000250|UniProtKB:P84022}.
uniprot
proteins
protein_family
Dwarfin/SMAD family
uniprot
proteins
pubmed
11274402
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16619037
uniprot
proteins
pubmed
21791611
uniprot
proteins
pubmed
8917532
uniprot
proteins
sequence_length
425
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P84022}. Nucleus {ECO:0000269|PubMed:8917532}. Note=Cytoplasmic and nuclear in the absence of TGF-beta (By similarity). On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4 (By similarity). Through the action of the phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1 (By similarity). Co-localizes with LEMD3 at the nucleus inner membrane. MAPK-mediated phosphorylation appears to have no effect on nuclear import (By similarity). PDPK1 prevents its nuclear translocation in response to TGF-beta (By similarity). Localized mainly to the nucleus in the early stages of embryo development with expression becoming evident in the cytoplasm of the inner cell mass at the blastocyst stage (By similarity). {ECO:0000250|UniProtKB:P84022, ECO:0000250|UniProtKB:Q8BUN5}.
uniprot
proteins