Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

O43541

- SMAD6_HUMAN

UniProt

O43541 - SMAD6_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Mothers against decapentaplegic homolog 6

Gene

SMAD6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Acts as a mediator of TGF-beta and BMP antiflammatory activity. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of proinflammatory genes. May block the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding. Binds to regulatory elements in target promoter regions.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi205 – 2051ZincBy similarity
Metal bindingi247 – 2471ZincBy similarity
Metal bindingi260 – 2601ZincBy similarity
Metal bindingi265 – 2651ZincBy similarity

GO - Molecular functioni

  1. chromatin binding Source: UniProtKB
  2. co-SMAD binding Source: BHF-UCL
  3. I-SMAD binding Source: BHF-UCL
  4. metal ion binding Source: UniProtKB-KW
  5. R-SMAD binding Source: BHF-UCL
  6. sequence-specific DNA binding transcription factor activity Source: InterPro
  7. transcription regulatory region DNA binding Source: UniProtKB
  8. transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity Source: BHF-UCL
  9. type I activin receptor binding Source: BHF-UCL
  10. type I transforming growth factor beta receptor binding Source: BHF-UCL
  11. ubiquitin protein ligase binding Source: BHF-UCL

GO - Biological processi

  1. BMP signaling pathway Source: UniProtKB
  2. cell-substrate adhesion Source: UniProtKB
  3. fat cell differentiation Source: UniProtKB
  4. immune response Source: BHF-UCL
  5. intracellular signal transduction Source: GOC
  6. negative regulation of apoptotic process Source: BHF-UCL
  7. negative regulation of BMP signaling pathway Source: BHF-UCL
  8. negative regulation of cell proliferation Source: BHF-UCL
  9. negative regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  10. negative regulation of SMAD protein complex assembly Source: BHF-UCL
  11. negative regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
  12. response to estrogen Source: Ensembl
  13. response to laminar fluid shear stress Source: BHF-UCL
  14. transcription, DNA-templated Source: UniProtKB-KW
  15. transforming growth factor beta receptor signaling pathway Source: InterPro
  16. ureteric bud development Source: Ensembl
  17. zygotic specification of dorsal/ventral axis Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_12034. Signaling by BMP.
SignaLinkiO43541.

Names & Taxonomyi

Protein namesi
Recommended name:
Mothers against decapentaplegic homolog 6
Short name:
MAD homolog 6
Short name:
Mothers against DPP homolog 6
Alternative name(s):
SMAD family member 6
Short name:
SMAD 6
Short name:
Smad6
Short name:
hSMAD6
Gene namesi
Name:SMAD6
Synonyms:MADH6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:6772. SMAD6.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. cytosol Source: Reactome
  3. nucleus Source: UniProtKB
  4. protein complex Source: MGI
  5. transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Aortic valve disease 2 (AOVD2) [MIM:614823]: A common defect in the aortic valve in which two rather than three leaflets are present. It is often associated with aortic valve calcification, stenosis and insufficiency. In extreme cases, the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry. SMAD6 variants may contribute to increased risk of congenital cardiovascular malformations (CVM). CVM is a major cause of mortality and morbidity in childhood. In most sporadic cases that cannot be attributed to particular malformation syndromes or teratogenic exposures, there remains a substantial excess familial risk, indicating a significant genetic contribution to disease susceptibility (PubMed:22275001).1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti415 – 4151P → L in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 Publication
VAR_068075
Natural varianti484 – 4841C → F in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 Publication
VAR_068076

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi173 – 1731K → R: Abolishes monoubiquitination by UBE2O. 1 Publication
Mutagenesisi435 – 4351S → A: Loss of in vitro phosphorylation by PRKX. 1 Publication
Mutagenesisi471 – 4711G → S: Loss of SMAD1-binding and of inhibition of BMP-SMAD1 signaling. No effect on interaction with BMPR1B and TGFBR1. 1 Publication
Mutagenesisi478 – 49619Missing: Loss of interaction with BMPR1B, TGFBR1 and SMAD1. 1 PublicationAdd
BLAST

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi614823. phenotype.
Orphaneti1244. Bicuspid aortic valve.
PharmGKBiPA30529.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 496496Mothers against decapentaplegic homolog 6PRO_0000090869Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei75 – 751Dimethylated arginine; alternateBy similarity
Modified residuei75 – 751Omega-N-methylarginine; alternateBy similarity
Modified residuei82 – 821Dimethylated arginine; alternateBy similarity
Modified residuei82 – 821Omega-N-methylarginine; alternateBy similarity
Cross-linki173 – 173Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei435 – 4351Phosphoserine; by PRKX; in vitro1 PublicationPROSITE-ProRule annotation

Post-translational modificationi

Phosphorylated by BMP type 1 receptor kinase and by PRKX.1 Publication
Ubiquitinated by WWP1 (By similarity). Monoubiquitinated at Lys-173 by the E2/E3 hybrid ubiquitin-protein ligase UBE2O, leading to reduced binding affinity for the activated BMP type I receptor ACVR1/ALK2, thereby enhancing BMP7 and regulating adipocyte differentiation.By similarity1 Publication
Arginine methylation by PRMT1, which is recruited by BMPR2, initiates BMP-Induced signaling and induces dissociation from the BMPR1B receptor at the cell surface leading to derepress downstream Smad1/Smad5 signaling.By similarity

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO43541.
PaxDbiO43541.
PRIDEiO43541.

PTM databases

PhosphoSiteiO43541.

Expressioni

Tissue specificityi

Ubiquitous in various organs, with higher levels in lung. Isoform B is up-regulated in diseased heart tissue.

Gene expression databases

BgeeiO43541.
CleanExiHS_SMAD6.
ExpressionAtlasiO43541. baseline and differential.
GenevestigatoriO43541.

Interactioni

Subunit structurei

Interacts with NEDD4L (By similarity). Interacts with WWP1 (By similarity). Interacts with STAMBP and PRKX. Interacts with RNF111 and AXIN1. Interacts with TGF-beta type I receptor superfamily members, including ACVR1B, BMPR1B and TGFBR1. In response to BMP2, but not to TGFB treatment, interacts with SMAD1, but not with SMAD2, nor with SMAD4; this interaction may inhibit SMAD1 binding to SMAD4. Interacts with HOXC8 and HOXC9. Interacts with PELI1; this interaction interferes with PELI1 complex formation with TRAF6, IRAK1, IRAK4 and MYD88 in response to IL1B and hence negatively regulates IL1R-TLR signaling.By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PRKXP518175EBI-976374,EBI-4302903
RUNX2Q139503EBI-976374,EBI-976402
STAMBPO956302EBI-4324970,EBI-396676

Protein-protein interaction databases

BioGridi110266. 48 interactions.
DIPiDIP-36708N.
IntActiO43541. 10 interactions.
MINTiMINT-1198639.
STRINGi9606.ENSP00000288840.

Structurei

3D structure databases

ProteinModelPortaliO43541.
SMRiO43541. Positions 192-269, 328-493.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini148 – 275128MH1PROSITE-ProRule annotationAdd
BLAST
Domaini331 – 496166MH2PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi25 – 339Poly-Gly
Compositional biasi82 – 854Poly-Arg
Compositional biasi165 – 1684Poly-Leu
Compositional biasi251 – 2544Poly-Ala
Compositional biasi275 – 2784Poly-Pro

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

eggNOGiNOG309572.
GeneTreeiENSGT00760000119091.
HOVERGENiHBG053021.
InParanoidiO43541.
KOiK04677.
OMAiWRSRLIP.
OrthoDBiEOG7GN2PK.
PhylomeDBiO43541.
TreeFamiTF314923.

Family and domain databases

Gene3Di2.60.200.10. 1 hit.
3.90.520.10. 2 hits.
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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform A (identifier: O43541-1) [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
MFRSKRSGLV RRLWRSRVVP DREEGGSGGG GGGDEDGSLG SRAEPAPRAR
60 70 80 90 100
EGGGCGRSEV RPVAPRRPRD AVGQRGAQGA GRRRRAGGPP RPMSEPGAGA
110 120 130 140 150
GSSLLDVAEP GGPGWLPESD CETVTCCLFS ERDAAGAPRD ASDPLAGAAL
160 170 180 190 200
EPAGGGRSRE ARSRLLLLEQ ELKTVTYSLL KRLKERSLDT LLEAVESRGG
210 220 230 240 250
VPGGCVLVPR ADLRLGGQPA PPQLLLGRLF RWPDLQHAVE LKPLCGCHSF
260 270 280 290 300
AAAADGPTVC CNPYHFSRLC GPESPPPPYS RLSPRDEYKP LDLSDSTLSY
310 320 330 340 350
TETEATNSLI TAPGEFSDAS MSPDATKPSH WCSVAYWEHR TRVGRLYAVY
360 370 380 390 400
DQAVSIFYDL PQGSGFCLGQ LNLEQRSESV RRTRSKIGFG ILLSKEPDGV
410 420 430 440 450
WAYNRGEHPI FVNSPTLDAP GGRALVVRKV PPGYSIKVFD FERSGLQHAP
460 470 480 490
EPDAADGPYD PNSVRISFAK GWGPCYSRQF ITSCPCWLEI LLNNPR
Length:496
Mass (Da):53,497
Last modified:October 3, 2006 - v2
Checksum:iA4B928AE2D34EBC2
GO
Isoform B (identifier: O43541-2) [UniParc]FASTAAdd to Basket

Also known as: Smad 6S

The sequence of this isoform differs from the canonical sequence as follows:
     1-261: Missing.
     262-273: NPYHFSRLCGPE → MSRMGKPIETQK

Show »
Length:235
Mass (Da):26,236
Checksum:i0847C2C84DC0B2A2
GO
Isoform D (identifier: O43541-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     318-338: DASMSPDATKPSHWCSVAYWE → AADAGIGSRGNRGLESSVPCS
     339-496: Missing.

Show »
Length:338
Mass (Da):35,467
Checksum:iC4D02353D7FD76CE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti21 – 211D → N in AAB94137. (PubMed:9436979)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti325 – 3251A → T Found in a patient with congenital mitral valve prolapse. 1 Publication
Corresponds to variant rs199822239 [ dbSNP | Ensembl ].
VAR_068074
Natural varianti415 – 4151P → L in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 Publication
VAR_068075
Natural varianti484 – 4841C → F in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 Publication
VAR_068076

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 261261Missing in isoform B. 1 PublicationVSP_006179Add
BLAST
Alternative sequencei262 – 27312NPYHF…LCGPE → MSRMGKPIETQK in isoform B. 1 PublicationVSP_006180Add
BLAST
Alternative sequencei318 – 33821DASMS…VAYWE → AADAGIGSRGNRGLESSVPC S in isoform D. 1 PublicationVSP_035489Add
BLAST
Alternative sequencei339 – 496158Missing in isoform D. 1 PublicationVSP_035490Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U59914 mRNA. Translation: AAC50792.1.
AF035528 mRNA. Translation: AAB94137.1.
AF043640 mRNA. Translation: AAC00497.1.
AF037469 mRNA. Translation: AAC82331.1.
AF041065
, AF041062, AF041063, AF041064 Genomic DNA. Translation: AAF14343.1.
AM909653 mRNA. Translation: CAP20377.1.
BC012986 mRNA. Translation: AAH12986.1.
AF101474 Genomic DNA. Translation: AAF06841.1.
CCDSiCCDS10221.1. [O43541-1]
RefSeqiNP_005576.3. NM_005585.4. [O43541-1]
UniGeneiHs.153863.

Genome annotation databases

EnsembliENST00000288840; ENSP00000288840; ENSG00000137834. [O43541-1]
ENST00000557916; ENSP00000452955; ENSG00000137834. [O43541-4]
GeneIDi4091.
KEGGihsa:4091.
UCSCiuc002aqf.3. human. [O43541-1]
uc002aqg.3. human. [O43541-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U59914 mRNA. Translation: AAC50792.1 .
AF035528 mRNA. Translation: AAB94137.1 .
AF043640 mRNA. Translation: AAC00497.1 .
AF037469 mRNA. Translation: AAC82331.1 .
AF041065
, AF041062 , AF041063 , AF041064 Genomic DNA. Translation: AAF14343.1 .
AM909653 mRNA. Translation: CAP20377.1 .
BC012986 mRNA. Translation: AAH12986.1 .
AF101474 Genomic DNA. Translation: AAF06841.1 .
CCDSi CCDS10221.1. [O43541-1 ]
RefSeqi NP_005576.3. NM_005585.4. [O43541-1 ]
UniGenei Hs.153863.

3D structure databases

ProteinModelPortali O43541.
SMRi O43541. Positions 192-269, 328-493.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110266. 48 interactions.
DIPi DIP-36708N.
IntActi O43541. 10 interactions.
MINTi MINT-1198639.
STRINGi 9606.ENSP00000288840.

PTM databases

PhosphoSitei O43541.

Proteomic databases

MaxQBi O43541.
PaxDbi O43541.
PRIDEi O43541.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000288840 ; ENSP00000288840 ; ENSG00000137834 . [O43541-1 ]
ENST00000557916 ; ENSP00000452955 ; ENSG00000137834 . [O43541-4 ]
GeneIDi 4091.
KEGGi hsa:4091.
UCSCi uc002aqf.3. human. [O43541-1 ]
uc002aqg.3. human. [O43541-2 ]

Organism-specific databases

CTDi 4091.
GeneCardsi GC15P066994.
H-InvDB HIX0132566.
HGNCi HGNC:6772. SMAD6.
MIMi 602931. gene.
614823. phenotype.
neXtProti NX_O43541.
Orphaneti 1244. Bicuspid aortic valve.
PharmGKBi PA30529.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG309572.
GeneTreei ENSGT00760000119091.
HOVERGENi HBG053021.
InParanoidi O43541.
KOi K04677.
OMAi WRSRLIP.
OrthoDBi EOG7GN2PK.
PhylomeDBi O43541.
TreeFami TF314923.

Enzyme and pathway databases

Reactomei REACT_12034. Signaling by BMP.
SignaLinki O43541.

Miscellaneous databases

ChiTaRSi SMAD6. human.
GeneWikii Mothers_against_decapentaplegic_homolog_6.
GenomeRNAii 4091.
NextBioi 16042.
PROi O43541.
SOURCEi Search...

Gene expression databases

Bgeei O43541.
CleanExi HS_SMAD6.
ExpressionAtlasi O43541. baseline and differential.
Genevestigatori O43541.

Family and domain databases

Gene3Di 2.60.200.10. 1 hit.
3.90.520.10. 2 hits.
InterProi 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 ]
PANTHERi PTHR13703. PTHR13703. 1 hit.
Pfami PF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view ]
SMARTi SM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view ]
SUPFAMi SSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEi PS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
  2. "Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor."
    Hata A., Lagna G., Massague J., Hemmati-Brivanlou A.
    Genes Dev. 12:186-197(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, INTERACTION WITH ACVR1B; BMPR1B; SMAD1 AND TGFBR1, MUTAGENESIS OF GLY-471 AND 478-ARG--ARG-496.
    Tissue: T-cell.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
    Tissue: Placenta.
  4. Hagiwara K., Freeman A.H., McMenamin M.G., Bennett W.P., Nagashima M., Minter A.R., Yang K., Takenoshita S., Harris C.C.
    Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM A).
  5. "Identification of a new SMAD6 variant in human."
    Konrad L., Scheiber J.A., Brandt H., Eickelberg O., Hofmann R.
    Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D).
    Tissue: Prostatic carcinoma.
  6. "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] (ISOFORM A).
    Tissue: Uterus.
  7. "Determination of the genomic structure of human Smad3, Smad6 and Smad7 and the cloning of the human Smad3 promoter."
    Hagiwara K., Freeman A.A.H., McMenamin M.G., Bennett W.P., Yang K., Takenoshita S., Harris C.C.
    Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM B).
  8. Cited for: REVIEW.
  9. "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells."
    Verschueren K., Huylebroeck D.
    Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  10. Cited for: REVIEW.
  11. Cited for: REVIEW.
  12. "Smad6 as a transcriptional corepressor."
    Bai S., Shi X., Yang X., Cao X.
    J. Biol. Chem. 275:8267-8270(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HOXC8.
  13. "Human truncated Smad 6 (Smad 6s) inhibits the BMP pathway in Xenopus laevis."
    Krishnan P., King M.W., Neff A.W., Sandusky G.E., Bierman K.L., Grinnell B., Smith R.C.
    Dev. Growth Differ. 43:115-132(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM B).
  14. "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads."
    Itoh F., Asao H., Sugamura K., Heldin C.-H., ten Dijke P., Itoh S.
    EMBO J. 20:4132-4142(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH STAMBP.
  15. "Arkadia amplifies TGF-beta superfamily signaling through degradation of Smad7."
    Koinuma D., Shinozaki M., Komuro A., Goto K., Saitoh M., Hanyu A., Ebina M., Nukiwa T., Miyazawa K., Imamura T., Miyazono K.
    EMBO J. 22:6458-6470(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RNF111.
  16. "Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia."
    Liu W., Rui H., Wang J., Lin S., He Y., Chen M., Li Q., Ye Z., Zhang S., Chan S.C., Chen Y.-G., Han J., Lin S.-C.
    EMBO J. 25:1646-1658(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AXIN1.
  17. "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1."
    Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S., Kim I.H., Kim S.J., Park S.H.
    Nat. Immunol. 7:1057-1065(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PELI1.
  18. "Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation."
    Glesne D., Huberman E.
    Oncogene 25:4086-4098(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PRKX, MUTAGENESIS OF SER-435, PHOSPHORYLATION AT SER-435.
  19. "Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation."
    Tan H.L., Glen E., Topf A., Hall D., O'Sullivan J.J., Sneddon L., Wren C., Avery P., Lewis R.J., ten Dijke P., Arthur H.M., Goodship J.A., Keavney B.D.
    Hum. Mutat. 33:720-727(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CONGENITAL CARDIOVASCULAR MALFORMATIONS, VARIANT THR-325, VARIANTS AOVD2 LEU-415 AND PHE-484, CHARACTERIZATION OF VARIANTS AOVD2 LEU-415 AND PHE-484.
  20. "Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6."
    Zhang X., Zhang J., Bauer A., Zhang L., Selinger D.W., Lu C.X., Ten Dijke P.
    EMBO J. 32:996-1007(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION AT LYS-173, MUTAGENESIS OF LYS-173.

Entry informationi

Entry nameiSMAD6_HUMAN
AccessioniPrimary (citable) accession number: O43541
Secondary accession number(s): A9J6M5
, O43654, Q15799, Q7Z7L4, Q96E31, Q9UKZ3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: October 3, 2006
Last modified: October 29, 2014
This is version 142 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3