UniProtKB - P84024 (SMAD3_PIG)
Mothers against decapentaplegic homolog 3
SMAD3
Functioni
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 40 | Required for trimerizationBy similarity | 1 | |
Sitei | 41 | Required for interaction with DNA and JUN and for functional cooperation with JUNBy similarity | 1 | |
Metal bindingi | 64 | ZincBy similarity | 1 | |
Metal bindingi | 109 | ZincBy similarity | 1 | |
Metal bindingi | 121 | ZincBy similarity | 1 | |
Metal bindingi | 126 | ZincBy similarity | 1 |
GO - Molecular functioni
- cis-regulatory region sequence-specific DNA binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription factor activity Source: UniProtKB
- I-SMAD binding Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- transcription factor binding Source: GO_Central
- ubiquitin protein ligase binding Source: GO_Central
GO - Biological processi
- anatomical structure morphogenesis Source: GO_Central
- BMP signaling pathway Source: GO_Central
- cell differentiation Source: GO_Central
- positive regulation of transcription by RNA polymerase II Source: GO_Central
- SMAD protein signal transduction Source: GO_Central
- transforming growth factor beta receptor signaling pathway Source: UniProtKB
Keywordsi
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: Mothers against decapentaplegic homolog 3Short name: MAD homolog 3 Short name: Mad3 Short name: Mothers against DPP homolog 3 Alternative name(s): SMAD family member 3 Short name: SMAD 3 Short name: Smad3 |
Gene namesi | Name:SMAD3 Synonyms:MADH3 |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:93217, SMAD3 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Cytoplasm By similarity
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 (By similarity). 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).By similarity
Nucleus
- heteromeric SMAD protein complex Source: GO_Central
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- SMAD protein complex Source: UniProtKB
- transcription regulator complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000090858 | 2 – 425 | Mothers against decapentaplegic homolog 3Add BLAST | 424 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylserineBy similarity | 1 | |
Modified residuei | 8 | Phosphothreonine; by CDK2 and CDK4By similarity | 1 | |
Cross-linki | 33 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 81 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 179 | Phosphothreonine; by CDK2, CDK4 and MAPKBy similarity | 1 | |
Modified residuei | 204 | Phosphoserine; by GSK3 and MAPKPROSITE-ProRule annotationBy similarity | 1 | |
Modified residuei | 208 | Phosphoserine; by MAPKPROSITE-ProRule annotationBy similarity | 1 | |
Modified residuei | 213 | Phosphoserine; by CDK2 and CDK4PROSITE-ProRule annotationBy similarity | 1 | |
Modified residuei | 378 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 416 | PhosphoserinePROSITE-ProRule annotationBy similarity | 1 | |
Modified residuei | 418 | Phosphoserine; by CK1PROSITE-ProRule annotationBy similarity | 1 | |
Modified residuei | 422 | Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity | 1 | |
Modified residuei | 423 | Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity | 1 | |
Modified residuei | 425 | Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, ADP-ribosylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | P84024 |
PeptideAtlasi | P84024 |
PRIDEi | P84024 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
Monomer; in the absence of TGF-beta (By similarity). Homooligomer; in the presence of TGF-beta (By similarity). Heterotrimer; forms a heterotrimer in the presence of TGF-beta consisting of two molecules of C-terminally phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the transcriptionally active SMAD2/SMAD3-SMAD4 complex (By similarity).
Part of a complex consisting of AIP1, ACVR2A, ACVR1B and SMAD3 (By similarity).
Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta (By similarity).
Found in a complex composed of SMAD3, RAN and XPO4; within the complex interacts directly with XPO4 (By similarity).
Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta (By similarity).
Interacts (via an N-terminal domain) with JUN (via its basic DNA binding and leucine zipper domains); this interaction is essential for DNA binding and cooperative transcriptional activity in response to TGF-beta (By similarity).
Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (By similarity).
Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling (By similarity).
Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4 transcriptional complex (By similarity).
Interacts (when phosphorylated) with RNF111; RNF111 acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD3 inhibitors (By similarity).
Interacts (dephosphorylated form via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling (By similarity).
Interacts (via MH2 domain) with LEMD3; the interaction represses SMAD3 transcriptional activity through preventing the formation of the heteromeric complex with SMAD4 and translocation to the nucleus (By similarity).
Interacts (via the linker region) with EP300 (C-terminal); the interaction promotes SMAD3 acetylation and is enhanced by TGF-beta phosphorylation in the C-terminal of SMAD3 (By similarity). This interaction can be blocked by competitive binding of adenovirus oncoprotein E1A to the same C-terminal site on EP300, which then results in partially inhibited SMAD3/SMAD4 transcriptional activity (By similarity).
Interacts with TGFBR1 (By similarity).
Interacts with TGFB1I1 (By similarity).
Interacts with PRDM16 (By similarity).
Interacts with SNW1 (By similarity).
Interacts (via MH2 domain) with ZFYVE9 (By similarity).
Interacts with HDAC1 (By similarity).
Interacts with TGIF2 (By similarity).
Interacts with SKOR1 (By similarity).
Interacts with SKOR2 (By similarity).
Interacts with DACH1; the interaction inhibits the TGF-beta signaling (By similarity).
Interacts with RBPMS (By similarity).
Interacts (via MH2 domain) with MECOM (By similarity).
Interacts with WWTR1 (via its coiled-coil domain) (By similarity).
Interacts with SKI; the interaction represses SMAD3 transcriptional activity (By similarity).
Interacts with MEN1 (By similarity).
Interacts with IL1F7 (By similarity). Interaction with CSNK1G2 (By similarity).
Interacts with PDPK1 (via PH domain) (By similarity).
Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation (By similarity).
Interacts with USP15 (By similarity).
Interacts with PPP5C; the interaction decreases SMAD3 phosphorylation and protein levels (By similarity).
Interacts with LDLRAD4 (via the SMAD interaction motif) (By similarity).
Interacts with PMEPA1 (By similarity).
Interacts with ZNF451 (By similarity).
Interacts with ZFHX3 (By similarity).
Interacts weakly with ZNF8 (By similarity).
Interacts with STUB1, HSPA1A, HSPA1B, HSP90AA1 and HSP90AB1 (By similarity).
Interacts with YAP1 (when phosphorylated at 'Ser-55') (By similarity).
Interacts with AIP1 (By similarity).
Interacts (via MH2 domain) with CITED2 (via C-terminus) (By similarity).
Interacts with HGS (By similarity).
Interacts with WWP1 (By similarity).
Interacts with TTRAP (By similarity).
Interacts with FOXL2 (By similarity).
Interacts with PML (By similarity).
Interacts with NEDD4L; the interaction requires TGF-beta stimulation (By similarity).
Interacts with ZC3H3 (By similarity).
Interacts with TGIF.
Interacts with CREBBP.
Interacts with ATF2.
By similarityGO - Molecular functioni
- I-SMAD binding Source: GO_Central
- transcription factor binding Source: GO_Central
- ubiquitin protein ligase binding Source: GO_Central
Protein-protein interaction databases
MINTi | P84024 |
STRINGi | 9823.ENSSSCP00000005327 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 10 – 136 | MH1PROSITE-ProRule annotationAdd BLAST | 127 | |
Domaini | 232 – 425 | MH2PROSITE-ProRule annotationAdd BLAST | 194 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 137 – 231 | LinkerAdd BLAST | 95 | |
Regioni | 271 – 324 | Sufficient for interaction with XPO4By similarityAdd BLAST | 54 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3701, Eukaryota |
GeneTreei | ENSGT00940000153499 |
InParanoidi | P84024 |
OMAi | NPVSPAH |
OrthoDBi | 608001at2759 |
Family and domain databases
Gene3Di | 2.60.200.10, 1 hit 3.90.520.10, 1 hit |
InterProi | View protein in InterPro IPR013790, Dwarfin IPR003619, MAD_homology1_Dwarfin-type IPR013019, MAD_homology_MH1 IPR017855, SMAD-like_dom_sf IPR001132, SMAD_dom_Dwarfin-type IPR008984, SMAD_FHA_dom_sf IPR036578, SMAD_MH1_sf |
PANTHERi | PTHR13703, PTHR13703, 1 hit |
Pfami | View protein in Pfam PF03165, MH1, 1 hit PF03166, MH2, 1 hit |
SMARTi | View protein in SMART SM00523, DWA, 1 hit SM00524, DWB, 1 hit |
SUPFAMi | SSF49879, SSF49879, 1 hit SSF56366, SSF56366, 1 hit |
PROSITEi | View protein in PROSITE PS51075, MH1, 1 hit PS51076, MH2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE
60 70 80 90 100
LEKAITTQNV NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH
110 120 130 140 150
HELRAMELCE FAFNMKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF
160 170 180 190 200
PPLDDYSHSI PENTNFPAGI EPQSNIPETP PPGYLSEDGE TSDHQMNHSM
210 220 230 240 250
DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL NQRVGETFHA
260 270 280 290 300
SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG
310 320 330 340 350
GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA
360 370 380 390 400
LLAQSVNQGF EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL
410 420
NGPLQWLDKV LTQMGSPSIR CSSVS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A5G2RC27 | A0A5G2RC27_PIG | Mothers against decapentaplegic hom... | SMAD3 | 434 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB052738 mRNA Translation: BAB19634.1 |
RefSeqi | NP_999302.1, NM_214137.1 |
Genome annotation databases
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB052738 mRNA Translation: BAB19634.1 |
RefSeqi | NP_999302.1, NM_214137.1 |
3D structure databases
SMRi | P84024 |
ModBasei | Search... |
Protein-protein interaction databases
MINTi | P84024 |
STRINGi | 9823.ENSSSCP00000005327 |
Proteomic databases
PaxDbi | P84024 |
PeptideAtlasi | P84024 |
PRIDEi | P84024 |
Genome annotation databases
Organism-specific databases
CTDi | 4088 |
VGNCi | VGNC:93217, SMAD3 |
Phylogenomic databases
eggNOGi | KOG3701, Eukaryota |
GeneTreei | ENSGT00940000153499 |
InParanoidi | P84024 |
OMAi | NPVSPAH |
OrthoDBi | 608001at2759 |
Family and domain databases
Gene3Di | 2.60.200.10, 1 hit 3.90.520.10, 1 hit |
InterProi | View protein in InterPro IPR013790, Dwarfin IPR003619, MAD_homology1_Dwarfin-type IPR013019, MAD_homology_MH1 IPR017855, SMAD-like_dom_sf IPR001132, SMAD_dom_Dwarfin-type IPR008984, SMAD_FHA_dom_sf IPR036578, SMAD_MH1_sf |
PANTHERi | PTHR13703, PTHR13703, 1 hit |
Pfami | View protein in Pfam PF03165, MH1, 1 hit PF03166, MH2, 1 hit |
SMARTi | View protein in SMART SM00523, DWA, 1 hit SM00524, DWB, 1 hit |
SUPFAMi | SSF49879, SSF49879, 1 hit SSF56366, SSF56366, 1 hit |
PROSITEi | View protein in PROSITE PS51075, MH1, 1 hit PS51076, MH2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SMAD3_PIG | |
Accessioni | P84024Primary (citable) accession number: P84024 Secondary accession number(s): O09064 Q9GKR4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 5, 2004 |
Last sequence update: | July 5, 2004 | |
Last modified: | December 2, 2020 | |
This is version 135 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families