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Protein

Mothers against decapentaplegic homolog 1

Gene

Smad1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-regulated SMAD (R-SMAD) (By similarity). May play a role in the initiation and maintenance of spermatogenesis. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1 (By similarity). May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (PubMed:15329343).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi64Zinc1
Metal bindingi109Zinc1
Metal bindingi121Zinc1
Metal bindingi126Zinc1

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-201451 Signaling by BMP
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8941326 RUNX2 regulates bone development

Names & Taxonomyi

Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 1
Short name:
MAD homolog 1
Short name:
Mothers against DPP homolog 1
Alternative name(s):
Dwarfin-A
Short name:
Dwf-A
Mothers-against-DPP-related 1
Short name:
Mad-related protein 1
Short name:
mMad1
SMAD family member 1
Short name:
SMAD 1
Short name:
Smad1
Gene namesi
Name:Smad1
Synonyms:Madh1, Madr1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:109452 Smad1

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

ChEMBLiCHEMBL3883282

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000908481 – 465Mothers against decapentaplegic homolog 1Add BLAST465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei322Phosphothreonine; by MINK1, TNIK and MAP4K4By similarity1
Modified residuei463PhosphoserinePROSITE-ProRule annotationBy similarity1
Modified residuei465PhosphoserinePROSITE-ProRule annotationBy similarity1

Post-translational modificationi

Phosphorylation of the C-terminal SVS motif by BMP type 1 receptor kinase activates SMAD1 by promoting dissociation from the receptor and trimerization with SMAD4 (By similarity). Dephosphorylation, probably by PPM1A, induces its export from the nucleus to the cytoplasm (PubMed:25755279).By similarity1 Publication
Ubiquitinated by SMAD-specific E3 ubiquitin ligase SMURF1, leading to its degradation. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP70340
PaxDbiP70340
PeptideAtlasiP70340
PRIDEiP70340

PTM databases

iPTMnetiP70340
PhosphoSitePlusiP70340

Expressioni

Tissue specificityi

Ubiquitous.

Developmental stagei

Ubiquitously expressed during embryogenesis. Expression starts in some seminiferous tubules at 2 weeks of age. After mid-puberty a stage-specific expression is established. During the cycling of the seminiferous epithelium, expression initiates in the pachytene spermatocytes of stage V seminiferous tubules, peaks at stage X, then decreases as pachytene spermatocytes differentiate into secondary spermatocytes and then round spermatids.

Gene expression databases

BgeeiENSMUSG00000031681 Expressed in 328 organ(s), highest expression level in pineal body
CleanExiMM_SMAD1
ExpressionAtlasiP70340 baseline and differential
GenevisibleiP70340 MM

Interactioni

Subunit structurei

Upon C-terminus phosphorylation: forms trimers with another SMAD1 and the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP), p300, SMURF1, SMURF2, USP15 and HOXC8. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with SKOR1. Interacts (via MH2 domain) with LEMD3. Binding to LEMD3 results in at least a partial reduction of receptor-mediated phosphorylation (By similarity). Also interacts with HGS, NANOG and ZCCHC12. Forms a ternary complex with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S proteasome (By similarity). Found in a complex with SMAD4 and YY1. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in a SMAD4-independent manner. Interacts with ZC3H3 (PubMed:16115198). Interacts with TMEM119 (PubMed:21239498). Interacts (via MH1 and MH2 domains) with ZNF8 (PubMed:12370310). Interacts with RANBP3L; the interaction increases when SMAD1 is not phosphorylated and mediates SMAD1 nuclear export (PubMed:25755279).By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Map3k7Q620733EBI-6992047,EBI-1775345

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201274, 34 interactors
ComplexPortaliCPX-145 SMAD1 homotrimer
CPX-146 SMAD1-SMAD4 complex
CORUMiP70340
IntActiP70340, 7 interactors
MINTiP70340
STRINGi10090.ENSMUSP00000071035

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP70340
SMRiP70340
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP70340

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 136MH1PROSITE-ProRule annotationAdd BLAST125
Domaini271 – 465MH2PROSITE-ProRule annotationAdd BLAST195

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni418 – 428L3 loopBy similarityAdd BLAST11

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi39 – 45Poly-Lys7

Domaini

The MH2 domain mediates phosphorylation-dependent trimerization through L3 loop binding of phosphoserines in the adjacent subunit.By similarity

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated

Phylogenomic databases

eggNOGiKOG3701 Eukaryota
ENOG410XQKU LUCA
GeneTreeiENSGT00760000119091
HOGENOMiHOG000286018
HOVERGENiHBG053353
InParanoidiP70340
KOiK04676
OMAiGTPSKCV
OrthoDBiEOG091G082C
TreeFamiTF314923

Family and domain databases

Gene3Di2.60.200.10, 1 hit
3.90.520.10, 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, 1 hit
PROSITEiView protein in PROSITE
PS51075 MH1, 1 hit
PS51076 MH2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

P70340-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNVTSLFSFT SPAVKRLLGW KQGDEEEKWA EKAVDALVKK LKKKKGAMEE
60 70 80 90 100
LEKALSCPGQ PSNCVTIPRS LDGRLQVSHR KGLPHVIYCR VWRWPDLQSH
110 120 130 140 150
HELKPLECCE FPFGSKQKEV CINPYHYKRV ESPVLPPVLV PRHSEYNPQH
160 170 180 190 200
SLLAQFRNLG QNEPHMPLNA TFPDSFQQPN SHPFPHSPNS SYPNSPGGSS
210 220 230 240 250
STYPHSPTSS DPGSPFQMPA DTPPPAYLPP EDPMAQDGSQ PMDTNMMAPP
260 270 280 290 300
LPAEISRGDV QAVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT
310 320 330 340 350
DPSNNKNRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD
360 370 380 390 400
SSIFVQSRNC NYHHGFHPTT VCKIPSGCSL KIFNNQEFAQ LLAQSVNHGF
410 420 430 440 450
ETVYELTKMC TIRMSFVKGW GAEYHRQDVT STPCWIEIHL HGPLQWLDKV
460
LTQMGSPHNP ISSVS
Length:465
Mass (Da):52,157
Last modified:July 27, 2011 - v2
Checksum:i07A56FBEE79A1C2A
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q8C3Y6Q8C3Y6_MOUSE
Mothers against decapentaplegic hom...
Smad1
428Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti95P → S in AAC52785 (PubMed:8799132).Curated1
Sequence conflicti95P → S in AAG41407 (PubMed:11111041).Curated1
Sequence conflicti142R → K in AAC52785 (PubMed:8799132).Curated1
Sequence conflicti142R → K in AAG41407 (PubMed:11111041).Curated1
Sequence conflicti199 – 200SS → QG in AAB18256 (PubMed:9076678).Curated2
Sequence conflicti393A → E in AAB18256 (PubMed:9076678).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58992 mRNA Translation: AAC52785.1
U74359 mRNA Translation: AAB18256.1
AF295768
, AF295763, AF295764, AF295765, AF295766, AF295767 Genomic DNA Translation: AAG41407.1
AK017583 mRNA Translation: BAB30820.1
AK054104 mRNA Translation: BAC35658.1
BC058693 mRNA Translation: AAH58693.1
CCDSiCCDS22437.1
RefSeqiNP_032565.2, NM_008539.3
XP_006530809.1, XM_006530746.3
UniGeneiMm.223717

Genome annotation databases

EnsembliENSMUST00000066091; ENSMUSP00000071035; ENSMUSG00000031681
GeneIDi17125
KEGGimmu:17125
UCSCiuc009mip.2 mouse

Similar proteinsi

Entry informationi

Entry nameiSMAD1_MOUSE
AccessioniPrimary (citable) accession number: P70340
Secondary accession number(s): P70442, Q6GT95, Q9CYK6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: September 12, 2018
This is version 183 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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