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Protein

Mothers against decapentaplegic homolog 1

Gene

SMAD1

Organism
Homo sapiens (Human)
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). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. May act synergistically with SMAD4 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi64ZincBy similarity1
Metal bindingi109ZincBy similarity1
Metal bindingi121ZincBy similarity1
Metal bindingi126ZincBy similarity1

GO - Molecular functioni

  • co-SMAD binding Source: BHF-UCL
  • DEAD/H-box RNA helicase binding Source: BHF-UCL
  • DNA binding transcription factor activity Source: BHF-UCL
  • identical protein binding Source: IntAct
  • I-SMAD binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • primary miRNA binding Source: BHF-UCL
  • protein heterodimerization activity Source: Ensembl
  • protein homodimerization activity Source: Ensembl
  • protein kinase binding Source: UniProtKB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • signal transducer activity, downstream of receptor Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: BHF-UCL

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-201451 Signaling by BMP
R-HSA-5689880 Ub-specific processing proteases
R-HSA-8941326 RUNX2 regulates bone development
SignaLinkiQ15797
SIGNORiQ15797

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):
JV4-1
Mad-related protein 1
SMAD family member 1
Short name:
SMAD 1
Short name:
Smad1
Short name:
hSMAD1
Transforming growth factor-beta-signaling protein 1
Short name:
BSP-1
Gene namesi
Name:SMAD1
Synonyms:BSP1, MADH1, MADR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000170365.9
HGNCiHGNC:6767 SMAD1
MIMi601595 gene
neXtProtiNX_Q15797

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

Involvement in diseasei

SMAD1 variants may be associated with susceptibility to pulmonary hypertension, a disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi297D → H: Reduced trimerization. 1 Publication1
Mutagenesisi317V → D: Reduced trimerization. 1 Publication1
Mutagenesisi373K → S: Reduced trimerization. 1 Publication1
Mutagenesisi418K → S: Reduced trimerization. 1 Publication1
Mutagenesisi419G → S: Loss of phosphorylation. 1 Publication1
Mutagenesisi424Y → F: Reduced trimerization. 1 Publication1
Mutagenesisi426R → S: Reduced trimerization. 1 Publication1
Mutagenesisi448D → H: Reduced trimerization. 1 Publication1
Mutagenesisi463 – 465SVS → AVA: Increases interaction with RANBPL3. 1 Publication3
Mutagenesisi463 – 465SVS → DVD: Decreases interaction with RANBPL3. 1 Publication3

Organism-specific databases

DisGeNETi4086
OpenTargetsiENSG00000170365
PharmGKBiPA30524

Polymorphism and mutation databases

BioMutaiSMAD1
DMDMi13633915

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000908471 – 465Mothers against decapentaplegic homolog 1Add BLAST465

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine1 Publication1
Modified residuei322Phosphothreonine; by MINK1, TNIK and MAP4K41 Publication1
Modified residuei463PhosphoserinePROSITE-ProRule annotation2 Publications1
Modified residuei465PhosphoserinePROSITE-ProRule annotation2 Publications1

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 SMAD4.3 Publications
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. Dephosphorylation, probably by PPM1A, induces its export from the nucleus to the cytoplasm (By similarity).By similarity1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15797
MaxQBiQ15797
PaxDbiQ15797
PeptideAtlasiQ15797
PRIDEiQ15797

PTM databases

iPTMnetiQ15797
PhosphoSitePlusiQ15797

Expressioni

Tissue specificityi

Ubiquitous. Highest expression seen in the heart and skeletal muscle.

Gene expression databases

BgeeiENSG00000170365
CleanExiHS_SMAD1
ExpressionAtlasiQ15797 baseline and differential
GenevisibleiQ15797 HS

Organism-specific databases

HPAiCAB005389

Interactioni

Subunit structurei

Found in a complex with SMAD4 and YY1. Interacts with HGS, NANOG and ZCCHC12 (By similarity). 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. Forms a ternary complex with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S proteasome. Found in a macromolecular complex with FAM83G. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in a SMAD4-independent manner. Interacts with ZC3H3 (By similarity). Interacts with TMEM119 (By similarity). Interacts (via MH1 and MH2 domains) with ZNF8 (By similarity). Interacts with RANBP3L; the interaction increases when SMAD1 is not phosphorylated and mediates SMAD1 nuclear export (PubMed:25755279).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • co-SMAD binding Source: BHF-UCL
  • DEAD/H-box RNA helicase binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • I-SMAD binding Source: BHF-UCL
  • protein heterodimerization activity Source: Ensembl
  • protein homodimerization activity Source: Ensembl
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110261, 122 interactors
CORUMiQ15797
DIPiDIP-38538N
IntActiQ15797, 94 interactors
MINTiQ15797
STRINGi9606.ENSP00000305769

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi272 – 278Combined sources7
Beta strandi291 – 299Combined sources9
Beta strandi305 – 310Combined sources6
Helixi321 – 327Combined sources7
Beta strandi334 – 338Combined sources5
Beta strandi340 – 347Combined sources8
Beta strandi349 – 351Combined sources3
Beta strandi353 – 356Combined sources4
Helixi358 – 363Combined sources6
Beta strandi372 – 374Combined sources3
Beta strandi379 – 384Combined sources6
Helixi385 – 393Combined sources9
Turni394 – 398Combined sources5
Helixi400 – 404Combined sources5
Helixi405 – 410Combined sources6
Beta strandi411 – 417Combined sources7
Helixi429 – 431Combined sources3
Beta strandi432 – 440Combined sources9
Helixi441 – 451Combined sources11
Beta strandi461 – 463Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KHUX-ray2.50A/B/C/D248-465[»]
2LAWNMR-B222-233[»]
2LAXNMR-B201-209[»]
2LAYNMR-B201-209[»]
2LAZNMR-B210-217[»]
2LB0NMR-B208-217[»]
2LB1NMR-B220-233[»]
3Q47X-ray1.70C456-464[»]
3Q4AX-ray1.54C456-465[»]
ProteinModelPortaliQ15797
SMRiQ15797
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15797

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 loop1 PublicationAdd BLAST11

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi39 – 45Poly-Lys7
Compositional biasi198 – 201Poly-Ser4

Domaini

The MH2 domain mediates phosphorylation-dependent trimerization through L3 loop binding of phosphoserines in the adjacent subunit.1 Publication

Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated

Phylogenomic databases

eggNOGiKOG3701 Eukaryota
ENOG410XQKU LUCA
GeneTreeiENSGT00760000119091
HOGENOMiHOG000286019
HOVERGENiHBG053353
InParanoidiQ15797
KOiK04676
OMAiGTPSKCV
OrthoDBiEOG091G082C
PhylomeDBiQ15797
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15797-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 SYPNSPGSSS
210 220 230 240 250
STYPHSPTSS DPGSPFQMPA DTPPPAYLPP EDPMTQDGSQ PMDTNMMAPP
260 270 280 290 300
LPSEINRGDV 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):52,260
Last modified:November 1, 1996 - v1
Checksum:i2DD34B7F434DBC7E
GO
Isoform 2 (identifier: Q15797-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MNVTSLFSFTSP → MFVLLFFPFLFL
     13-133: Missing.
     220-258: ADTPPPAYLP...PPLPSEINRG → GRLECSVMFC...EGGFQPWYMT
     259-465: Missing.

Note: No experimental confirmation available.
Show »
Length:137
Mass (Da):15,406
Checksum:iA43324EACCA53062
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0668693V → A Found in a patient with primary pulmonary hypertension; unknown pathological significance; affects SMAD-mediated signaling. 1 PublicationCorresponds to variant dbSNP:rs587777018Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0571631 – 12MNVTS…SFTSP → MFVLLFFPFLFL in isoform 2. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_05716413 – 133Missing in isoform 2. 1 PublicationAdd BLAST121
Alternative sequenceiVSP_057165220 – 258ADTPP…EINRG → GRLECSVMFCSHIRQCYHSV TEKLGQPAVEGGFQPWYMT in isoform 2. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_057166259 – 465Missing in isoform 2. 1 PublicationAdd BLAST207

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U59912 mRNA Translation: AAC50790.1
U59423 mRNA Translation: AAB06852.1
U54826 mRNA Translation: AAC50493.1
U57456 mRNA Translation: AAC50621.1
BT007386 mRNA Translation: AAP36050.1
AK293055 mRNA Translation: BAF85744.1
AL117396 Genomic DNA Translation: CAB55898.1
CH471056 Genomic DNA Translation: EAX05037.1
CH471056 Genomic DNA Translation: EAX05038.1
CH471056 Genomic DNA Translation: EAX05039.1
CH471056 Genomic DNA Translation: EAX05040.1
BC001878 mRNA Translation: AAH01878.1
CCDSiCCDS3765.1 [Q15797-1]
PIRiS68987
RefSeqiNP_001003688.1, NM_001003688.1 [Q15797-1]
NP_005891.1, NM_005900.2 [Q15797-1]
XP_005263049.1, XM_005262992.3
XP_006714280.1, XM_006714217.2
XP_011530263.1, XM_011531961.1
XP_011530264.1, XM_011531962.1 [Q15797-1]
XP_011530265.1, XM_011531963.1
XP_011530266.1, XM_011531964.1 [Q15797-1]
UniGeneiHs.604588

Genome annotation databases

EnsembliENST00000302085; ENSP00000305769; ENSG00000170365 [Q15797-1]
ENST00000394092; ENSP00000377652; ENSG00000170365 [Q15797-1]
ENST00000515385; ENSP00000426568; ENSG00000170365 [Q15797-1]
GeneIDi4086
KEGGihsa:4086
UCSCiuc003ikc.4 human [Q15797-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSMAD1_HUMAN
AccessioniPrimary (citable) accession number: Q15797
Secondary accession number(s): A8KAJ0
, D3DNZ9, Q16636, Q9UFT8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: November 1, 1996
Last modified: April 25, 2018
This is version 201 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
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Main funding by: National Institutes of Health