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Protein

Mothers against decapentaplegic homolog 2

Gene

Smad2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi74ZincBy similarity1
Metal bindingi149ZincBy similarity1
Metal bindingi161ZincBy similarity1
Metal bindingi166ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-1181150 Signaling by NODAL
R-RNO-1502540 Signaling by Activin
R-RNO-2173788 Downregulation of TGF-beta receptor signaling
R-RNO-2173789 TGF-beta receptor signaling activates SMADs
R-RNO-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-RNO-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-RNO-5689880 Ub-specific processing proteases

Names & Taxonomyi

Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 2
Short name:
MAD homolog 2
Short name:
Mothers against DPP homolog 2
Alternative name(s):
Mad-related protein 2
SMAD family member 2
Short name:
SMAD 2
Short name:
Smad2
Gene namesi
Name:Smad2
Synonyms:Madh2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi3031 Smad2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3885605

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000908542 – 467Mothers against decapentaplegic homolog 2Add BLAST466

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei8PhosphothreonineBy similarity1
Modified residuei19N6-acetyllysineBy similarity1
Modified residuei220PhosphothreonineBy similarity1
Modified residuei240Phosphoserine; by CAMK2PROSITE-ProRule annotationBy similarity1
Modified residuei245PhosphoserineBy similarity1
Modified residuei250PhosphoserineBy similarity1
Modified residuei255PhosphoserineBy similarity1
Modified residuei458PhosphoserinePROSITE-ProRule annotationBy similarity1
Modified residuei460PhosphoserinePROSITE-ProRule annotationBy similarity1
Modified residuei464PhosphoserinePROSITE-ProRule annotationBy similarity1
Modified residuei465Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity1
Modified residuei467Phosphoserine; by TGFBR1PROSITE-ProRule annotationBy similarity1

Post-translational modificationi

In response to TGF-beta, phosphorylated on the C-terminal SXS motif by TGF-beta and activin type 1 receptor kinases, phosphorylation declines progressively in a KMT5A-dependent manner. Phosphorylation in this motif is required for interaction with a number of proteins including SMURF2, SNON and SMAD4 in response to TGF-beta. Dephosphorylated in this motif by PPM1A leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of the TGF-beta signaling. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin. Phosphorylated by PDPK1 (By similarity).By similarity
Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity.By similarity
In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation. Monoubiquitinated, leading to prevent DNA-binding (By similarity). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (By similarity). Ubiquitinated by RNF111, leading to its degradation: only SMAD2 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD2 and regulating its turnover (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO70436
PRIDEiO70436

PTM databases

iPTMnetiO70436
PhosphoSitePlusiO70436

Expressioni

Gene expression databases

BgeeiENSRNOG00000018140 Expressed in 10 organ(s), highest expression level in spleen
ExpressionAtlasiO70436 baseline and differential
GenevisibleiO70436 RN

Interactioni

Subunit structurei

Monomer; the absence of TGF-beta. Interacts with ZNF580. Heterodimer; in the presence of TGF-beta. Forms a heterodimer with co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4. Found in a complex with ACVR1B, SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with SMAD3 and TRIM33. Interacts (via the MH2 domain) with ZFYVE9; may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300, SKI and SNW1. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts (via PY-motif) with SMURF2. Interacts with AIP1 and HGS. Interacts with NEDD4L in response to TGF-beta. Interacts with SKOR1 and SKOR2. Interacts with PRDM16. Interacts (via MH2 domain) with LEMD3. Interacts with RBPMS. Interacts with WWP1. 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. Interacts with PML. Interacts with PDPK1 (via PH domain). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation. Interacts with USP15. Interacts with PPP5C. Interacts with LDLRAD4 (via the SMAD interaction motif). Interacts (via MH2 domain) with PMEPA1 (via the SMAD interaction motif). Interacts with ZFHX3. Interacts with ZNF451. Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4. Interacts weakly with ZNF8. Interacts (when phosphorylated) with RNF111; RNF111 acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD2 inhibitors.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Akt1P471962EBI-7948047,EBI-7204362

GO - Molecular functioni

Protein-protein interaction databases

BioGridi248011, 2 interactors
IntActiO70436, 1 interactor
MINTiO70436
STRINGi10116.ENSRNOP00000048329

Structurei

3D structure databases

ProteinModelPortaliO70436
SMRiO70436
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 176MH1PROSITE-ProRule annotationAdd BLAST167
Domaini274 – 467MH2PROSITE-ProRule annotationAdd BLAST194

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi221 – 225PY-motifBy similarity5

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated

Phylogenomic databases

eggNOGiKOG3701 Eukaryota
ENOG410XQKU LUCA
GeneTreeiENSGT00760000119091
HOGENOMiHOG000286018
HOVERGENiHBG053353
InParanoidiO70436
KOiK04500
OMAiDEICINP
PhylomeDBiO70436
TreeFamiTF314923

Family and domain databases

Gene3Di2.60.200.10, 1 hit
InterProiView 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
PANTHERiPTHR13703 PTHR13703, 1 hit
PfamiView protein in Pfam
PF03165 MH1, 1 hit
PF03166 MH2, 1 hit
SMARTiView protein in SMART
SM00523 DWA, 1 hit
SM00524 DWB, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
SSF56366 SSF56366, 2 hits
PROSITEiView protein in PROSITE
PS51075 MH1, 1 hit
PS51076 MH2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

O70436-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK
60 70 80 90 100
KLKKTGRLDE LEKAITTQNC NTKCVTIPST CSEIWGLSTA NTVDQWDTTG
110 120 130 140 150
LYSFSEQTRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELKAIENCE
160 170 180 190 200
YAFSLKKDEV CVNPYHYQRV ETPVLPPVLV PRHTEILTEL PPLDDYTHSI
210 220 230 240 250
PENTNFPAGI EPQSNYIPET PPPGYISEDG ETSDQQLNQS MDTGSPAELS
260 270 280 290 300
PTTLSPVNHS LDLQPVTYSE PAFWCSIAYY ELNQRVGETF HASQPSLTVD
310 320 330 340 350
GFTDPSNSER FCLGLLSNVN RNATVEMTRR HIGRGVRLYY IGGEVFAECL
360 370 380 390 400
SDSAIFVQSP NCNQRYGWHP ATVCKIPPGC NLKIFNNQEF AALLAQSVNQ
410 420 430 440 450
GFEAVYQLTR MCTIRMSFVK GWGAEYRRQT VTSTPCWIEL HLNGPLQWLD
460
KVLTQMGSPS VRCSSMS
Length:467
Mass (Da):52,239
Last modified:August 1, 1998 - v1
Checksum:i3A775444411F6619
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0G2K0P2A0A0G2K0P2_RAT
Mothers against decapentaplegic hom...
Smad2
411Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017912 mRNA Translation: BAA33453.1
AF056001 mRNA Translation: AAC12780.1
AB010147 mRNA Translation: BAA81909.1
BC127497 mRNA Translation: AAI27498.1
RefSeqiNP_001264379.1, NM_001277450.1
NP_062064.1, NM_019191.2
UniGeneiRn.2755

Genome annotation databases

EnsembliENSRNOT00000046847; ENSRNOP00000048329; ENSRNOG00000018140
ENSRNOT00000092173; ENSRNOP00000075341; ENSRNOG00000018140
GeneIDi29357
KEGGirno:29357

Similar proteinsi

Entry informationi

Entry nameiSMAD2_RAT
AccessioniPrimary (citable) accession number: O70436
Secondary accession number(s): A0JPM1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 1, 1998
Last modified: September 12, 2018
This is version 170 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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