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Protein

Mothers against decapentaplegic homolog 1

Gene

Smad1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • BMP signaling pathway Source: UniProtKB
  • bone development Source: MGI
  • cardiac muscle cell proliferation Source: MGI
  • cartilage development Source: MGI
  • cellular response to BMP stimulus Source: BHF-UCL
  • cellular response to organic cyclic compound Source: MGI
  • embryonic pattern specification Source: UniProtKB
  • gamete generation Source: MGI
  • hindbrain development Source: MGI
  • homeostatic process Source: MGI
  • inflammatory response Source: UniProtKB
  • MAPK cascade Source: MGI
  • mesodermal cell fate commitment Source: MGI
  • midbrain development Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • osteoblast fate commitment Source: MGI
  • positive regulation of cartilage development Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of osteoblast differentiation Source: MGI
  • positive regulation of pri-miRNA transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
  • protein phosphorylation Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • SMAD protein complex assembly Source: MGI
  • SMAD protein signal transduction Source: BHF-UCL
  • transforming growth factor beta receptor signaling pathway Source: InterPro
  • ureteric bud development Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-201451. Signaling by BMP.
R-MMU-5689880. Ub-specific processing proteases.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:109452. Smad1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: In the cytoplasm in the absence of ligand. Migration to the nucleus when complexed with SMAD4. Colocalizes with LEMD3 at the nucleus inner membrane.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nuclear inner membrane Source: MGI
  • nucleus Source: UniProtKB
  • protein complex Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

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
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.
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).By similarity8 Publications

Binary interactionsi

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

GO - Molecular functioni

  • co-SMAD binding Source: MGI
  • identical protein binding Source: MGI
  • I-SMAD binding Source: MGI
  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: MGI
  • protein kinase binding Source: MGI

Protein-protein interaction databases

BioGridi201274. 35 interactors.
IntActiP70340. 7 interactors.
MINTiMINT-99213.
STRINGi10090.ENSMUSP00000071035.

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 19Combined sources8
Helixi25 – 41Combined sources17
Helixi47 – 56Combined sources10
Beta strandi66 – 68Combined sources3
Beta strandi71 – 73Combined sources3
Beta strandi75 – 77Combined sources3
Beta strandi80 – 82Combined sources3
Helixi84 – 92Combined sources9
Helixi100 – 102Combined sources3
Beta strandi103 – 105Combined sources3
Helixi113 – 115Combined sources3
Beta strandi118 – 121Combined sources4
Helixi124 – 126Combined sources3
Beta strandi127 – 129Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KMPX-ray2.70A/B9-132[»]
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
Contains 1 MH1 (MAD homology 1) domain.PROSITE-ProRule annotation
Contains 1 MH2 (MAD homology 2) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3701. Eukaryota.
ENOG410XQKU. LUCA.
GeneTreeiENSGT00760000119091.
HOGENOMiHOG000286018.
HOVERGENiHBG053353.
InParanoidiP70340.
KOiK04676.
OMAiMTHDTSQ.
OrthoDBiEOG091G082C.
TreeFamiTF314923.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProiIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PANTHERiPTHR13703. PTHR13703. 1 hit.
PfamiPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTiSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEiPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KMPX-ray2.70A/B9-132[»]
ProteinModelPortaliP70340.
SMRiP70340.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201274. 35 interactors.
IntActiP70340. 7 interactors.
MINTiMINT-99213.
STRINGi10090.ENSMUSP00000071035.

PTM databases

iPTMnetiP70340.
PhosphoSitePlusiP70340.

Proteomic databases

MaxQBiP70340.
PaxDbiP70340.
PeptideAtlasiP70340.
PRIDEiP70340.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4086.
MGIiMGI:109452. Smad1.

Phylogenomic databases

eggNOGiKOG3701. Eukaryota.
ENOG410XQKU. LUCA.
GeneTreeiENSGT00760000119091.
HOGENOMiHOG000286018.
HOVERGENiHBG053353.
InParanoidiP70340.
KOiK04676.
OMAiMTHDTSQ.
OrthoDBiEOG091G082C.
TreeFamiTF314923.

Enzyme and pathway databases

ReactomeiR-MMU-201451. Signaling by BMP.
R-MMU-5689880. Ub-specific processing proteases.

Miscellaneous databases

ChiTaRSiSmad1. mouse.
EvolutionaryTraceiP70340.
PROiP70340.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031681.
CleanExiMM_SMAD1.
ExpressionAtlasiP70340. baseline and differential.
GenevisibleiP70340. MM.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProiIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PANTHERiPTHR13703. PTHR13703. 1 hit.
PfamiPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTiSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEiPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSMAD1_MOUSE
AccessioniPrimary (citable) accession number: P70340
Secondary accession number(s): P70442, Q6GT95, Q9CYK6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 168 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.