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P70340 (SMAD1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Smad1
Synonyms:Madh1, Madr1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length465 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

May form 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. Ref.6 Ref.7 Ref.8 Ref.9

Subcellular location

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.

Tissue specificity

Ubiquitous.

Developmental stage

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.

Post-translational modification

Phosphorylated on serine by BMP type 1 receptor kinase 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.

Sequence similarities

Belongs to the dwarfin/SMAD family.

Contains 1 MH1 (MAD homology 1) domain.

Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
Metal-binding
Zinc
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

MAPK cascade

Inferred from mutant phenotype PubMed 15198985. Source: MGI

SMAD protein complex assembly

Inferred from electronic annotation. Source: Ensembl

bone development

Inferred from genetic interaction PubMed 19224984. Source: MGI

cardiac muscle cell proliferation

Inferred from mutant phenotype PubMed 17350578. Source: MGI

cartilage development

Inferred from genetic interaction PubMed 19224984. Source: MGI

cellular response to BMP stimulus

Inferred from genetic interaction PubMed 20843790. Source: BHF-UCL

cellular response to organic cyclic compound

Inferred from direct assay PubMed 19103752. Source: MGI

embryonic pattern specification

Inferred from sequence or structural similarity. Source: UniProtKB

gamete generation

Inferred from mutant phenotype PubMed 15198985. Source: MGI

hindbrain development

Inferred from mutant phenotype PubMed 15899870. Source: MGI

homeostatic process

Inferred from mutant phenotype PubMed 15198985. Source: MGI

inflammatory response

Inferred from expression pattern PubMed 12151307. Source: UniProtKB

kidney development

Inferred from electronic annotation. Source: Ensembl

mesodermal cell fate commitment

Inferred from genetic interaction Ref.7. Source: MGI

midbrain development

Inferred from mutant phenotype PubMed 15899870. Source: MGI

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 15899870. Source: MGI

negative regulation of muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

osteoblast fate commitment

Inferred from genetic interaction PubMed 15150273. Source: MGI

positive regulation of cartilage development

Inferred from direct assay PubMed 19251704. Source: MGI

positive regulation of dendrite morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from mutant phenotype PubMed 18622394. Source: MGI

positive regulation of osteoblast differentiation

Inferred from genetic interaction PubMed 15150273. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15557274PubMed 16556916PubMed 19251704. Source: MGI

positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus

Inferred from genetic interaction PubMed 20843790. Source: BHF-UCL

protein phosphorylation

Inferred from direct assay PubMed 18776146. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12270938PubMed 14633973. Source: MGI

response to drug

Inferred from electronic annotation. Source: Ensembl

response to organonitrogen compound

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

ureteric bud development

Inferred from expression pattern PubMed 14656760. Source: UniProtKB

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11160896. Source: UniProtKB

nuclear inner membrane

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 12151307. Source: UniProtKB

protein complex

Inferred from sequence orthology PubMed 23610558. Source: MGI

transcription factor complex

Inferred from direct assay PubMed 14633973. Source: MGI

   Molecular_functionRNA polymerase II core promoter sequence-specific DNA binding

Inferred from direct assay PubMed 18692037. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 14633973PubMed 16556916. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Map3k7Q620733EBI-6992047,EBI-1775345

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 465465Mothers against decapentaplegic homolog 1
PRO_0000090848

Regions

Domain12 – 136125MH1
Domain271 – 465195MH2
Compositional bias39 – 457Poly-Lys

Sites

Metal binding641Zinc
Metal binding1091Zinc
Metal binding1211Zinc
Metal binding1261Zinc

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue3221Phosphothreonine; by MINK1, TNIK and MAP4K4
Modified residue4631Phosphoserine By similarity
Modified residue4651Phosphoserine By similarity

Experimental info

Sequence conflict951P → S in AAC52785. Ref.1
Sequence conflict951P → S in AAG41407. Ref.3
Sequence conflict1421R → K in AAC52785. Ref.1
Sequence conflict1421R → K in AAG41407. Ref.3
Sequence conflict199 – 2002SS → QG in AAB18256. Ref.2
Sequence conflict3931A → E in AAB18256. Ref.2

Secondary structure

........................... 465
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P70340 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 07A56FBEE79A1C2A

FASTA46552,157
        10         20         30         40         50         60 
MNVTSLFSFT SPAVKRLLGW KQGDEEEKWA EKAVDALVKK LKKKKGAMEE LEKALSCPGQ 

        70         80         90        100        110        120 
PSNCVTIPRS LDGRLQVSHR KGLPHVIYCR VWRWPDLQSH HELKPLECCE FPFGSKQKEV 

       130        140        150        160        170        180 
CINPYHYKRV ESPVLPPVLV PRHSEYNPQH SLLAQFRNLG QNEPHMPLNA TFPDSFQQPN 

       190        200        210        220        230        240 
SHPFPHSPNS SYPNSPGGSS STYPHSPTSS DPGSPFQMPA DTPPPAYLPP EDPMAQDGSQ 

       250        260        270        280        290        300 
PMDTNMMAPP LPAEISRGDV QAVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT 

       310        320        330        340        350        360 
DPSNNKNRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC 

       370        380        390        400        410        420 
NYHHGFHPTT VCKIPSGCSL KIFNNQEFAQ LLAQSVNHGF ETVYELTKMC TIRMSFVKGW 

       430        440        450        460 
GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPHNP ISSVS 

« Hide

References

« Hide 'large scale' references
[1]"Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth."
Yingling J.M., Das P., Savage C., Zhang M., Padgett R.W., Wang X.-F.
Proc. Natl. Acad. Sci. U.S.A. 93:8940-8944(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Embryo.
[2]"Evidence that Mothers-against-dpp-related 1 (Madr1) plays a role in the initiation and maintenance of spermatogenesis in the mouse."
Zhao G.-Q., Hogan B.L.M.
Mech. Dev. 61:63-73(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Embryonic heart.
[3]"Characterization of the mouse Smad1 gene and its expression pattern in adult mouse tissues."
Huang S., Flanders K.C., Roberts A.B.
Gene 258:43-53(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/Sv.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Embryo and Oviduct.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[6]"Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA."
Miura S., Takeshita T., Asao H., Kimura Y., Murata K., Sasaki Y., Hanai J., Beppu H., Tsukazaki T., Wrana J.L., Miyazono K., Sugamura K.
Mol. Cell. Biol. 20:9346-9355(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HGS.
[7]"Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells."
Suzuki A., Raya A., Kawakami Y., Morita M., Matsui T., Nakashima K., Gage F.H., Rodriguez-Esteban C., Izpisua Belmonte J.C.
Proc. Natl. Acad. Sci. U.S.A. 103:10294-10299(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NANOG.
[8]"Sizn1 is a novel protein that functions as a transcriptional coactivator of bone morphogenic protein signaling."
Cho G., Lim Y., Zand D., Golden J.A.
Mol. Cell. Biol. 28:1565-1572(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZCCHC12.
[9]"Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and TGF-beta effectors."
Baburajendran N., Palasingam P., Narasimhan K., Sun W., Prabhakar S., Jauch R., Kolatkar P.R.
Nucleic Acids Res. 38:3477-3488(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 9-132 IN COMPLEX WITH DNA, ZINC_BINDING SITES, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U58992 mRNA. Translation: AAC52785.1.
U74359 mRNA. Translation: AAB18256.1.
AF295768 expand/collapse EMBL AC list , 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.
RefSeqNP_032565.2. NM_008539.3.
XP_006530809.1. XM_006530746.1.
UniGeneMm.223717.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3KMPX-ray2.70A/B9-132[»]
ProteinModelPortalP70340.
SMRP70340. Positions 9-132, 268-465.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201274. 34 interactions.
IntActP70340. 7 interactions.
MINTMINT-99213.

PTM databases

PhosphoSiteP70340.

Proteomic databases

PaxDbP70340.
PRIDEP70340.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000066091; ENSMUSP00000071035; ENSMUSG00000031681.
GeneID17125.
KEGGmmu:17125.
UCSCuc009mip.2. mouse.

Organism-specific databases

CTD4086.
MGIMGI:109452. Smad1.

Phylogenomic databases

eggNOGNOG330956.
GeneTreeENSGT00600000084186.
HOGENOMHOG000286018.
HOVERGENHBG053353.
InParanoidQ6GT95.
KOK04676.
OMAPRNSEFN.
OrthoDBEOG7W1540.
TreeFamTF314923.

Gene expression databases

ArrayExpressP70340.
BgeeP70340.
CleanExMM_SMAD1.
GenevestigatorP70340.

Family and domain databases

Gene3D2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProIPR013790. 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]
PANTHERPTHR13703. PTHR13703. 1 hit.
PfamPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSMAD1. mouse.
EvolutionaryTraceP70340.
NextBio291304.
PROP70340.
SOURCESearch...

Entry information

Entry nameSMAD1_MOUSE
AccessionPrimary (citable) accession number: P70340
Secondary accession number(s): P70442, Q6GT95, Q9CYK6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot