P70340 (SMAD1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Smad1
Synonyms:	Madh1, Madr1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Co-localizes 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 process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding Metal-binding Zinc
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP 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: Compara 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: Compara 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 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: Compara positive regulation of osteoblast differentiation Inferred from genetic interaction PubMed 15150273. 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 response to drug Inferred from electronic annotation. Source: Compara response to organic nitrogen Inferred from electronic annotation. Source: Compara transcription, DNA-dependent 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: Compara
Cellular_component	cytoplasm Inferred from direct assay PubMed 11160896. Source: UniProtKB nuclear inner membrane Inferred from electronic annotation. Source: Compara transcription factor complex Inferred from direct assay PubMed 14633973. Source: MGI
Molecular_function	RNA 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...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 465

465

Mothers against decapentaplegic homolog 1

PRO_0000090848

Regions

Domain

12 – 136

125

MH1

Domain

271 – 465

195

MH2

Compositional bias

39 – 45

7

Poly-Lys

Sites

Metal binding

64

1

Zinc

Metal binding

109

1

Zinc

Metal binding

121

1

Zinc

Metal binding

126

1

Zinc

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

322

1

Phosphothreonine; by MINK1, TNIK and MAP4K4

Modified residue

463

1

Phosphoserine By similarity

Modified residue

465

1

Phosphoserine By similarity

Experimental info

Sequence conflict

95

1

P → S in AAC52785. Ref.1

Sequence conflict

95

1

P → S in AAG41407. Ref.3

Sequence conflict

142

1

R → K in AAC52785. Ref.1

Sequence conflict

142

1

R → K in AAG41407. Ref.3

Sequence conflict

199 – 200

2

SS → QG in AAB18256. Ref.2

Sequence conflict

393

1

A → E in AAB18256. Ref.2

Secondary structure

1

.

.

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.

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.

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465

Helix Strand Turn

Details...

Helix

12 – 19

8

Helix

25 – 41

17

Helix

47 – 56

10

Beta strand

66 – 68

3

Beta strand

71 – 73

3

Beta strand

75 – 77

3

Beta strand

80 – 82

3

Helix

84 – 92

9

Helix

100 – 102

3

Beta strand

103 – 105

3

Helix

113 – 115

3

Beta strand

118 – 121

4

Helix

124 – 126

3

Beta strand

127 – 129

3

Sequences

	Sequence		Length	Mass (Da)
	P70340 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 07A56FBEE79A1C2A	FASTA	465	52,157
	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

References

	« Hide 'large scale' referencesShow '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. , 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 , 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.

IPI

IPI00108171.

RefSeq

NP_032565.2. NM_008539.3.

UniGene

Mm.223717.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3KMP	X-ray	2.70	A/B	9-132	[»]

ProteinModelPortal

P70340.

SMR

P70340. Positions 9-132, 268-465.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-99213.

PTM databases

PhosphoSite

P70340.

Proteomic databases

PaxDb

P70340.

PRIDE

P70340.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000066091; ENSMUSP00000071035; ENSMUSG00000031681.

GeneID

17125.

KEGG

mmu:17125.

Organism-specific databases

CTD

4086.

MGI

MGI:109452. Smad1.

Phylogenomic databases

eggNOG

NOG330956.

GeneTree

ENSGT00600000084186.

HOGENOM

HOG000286018.

HOVERGEN

HBG053353.

InParanoid

Q6GT95.

KO

K04676.

OMA

QPMDTNL.

OrthoDB

EOG4HDSTH.

Gene expression databases

ArrayExpress

P70340.

Bgee

P70340.

CleanEx

MM_SMAD1.

Genevestigator

P70340.

GermOnline

ENSMUSG00000031681. Mus musculus.

Family and domain databases

Gene3D

2.60.200.10. 1 hit.
3.90.520.10. 1 hit.

InterPro

IPR013790. 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]

PANTHER

PTHR13703. PTHR13703. 1 hit.

Pfam

PF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]

SMART

SM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]

SUPFAM

SSF56366. MAD_MH1. 1 hit.
SSF49879. SMAD_FHA. 1 hit.

PROSITE

PS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SMAD1. mouse.

EvolutionaryTrace

P70340.

NextBio

291304.

SOURCE

Search...

Entry information

Entry name

SMAD1_MOUSE

Accession

Primary (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 3, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program