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Entry version 183 (08 May 2019)
Sequence version 2 (03 Oct 2006)
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Protein

Mothers against decapentaplegic homolog 6

Gene

SMAD6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi205ZincBy similarity1
Metal bindingi247ZincBy similarity1
Metal bindingi260ZincBy similarity1
Metal bindingi265ZincBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

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

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-201451 Signaling by BMP
R-HSA-8941326 RUNX2 regulates bone development

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
O43541

SIGNOR Signaling Network Open Resource

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SIGNORi
O43541

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SMAD6
Synonyms:MADH6
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 15

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:6772 SMAD6

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602931 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O43541

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Aortic valve disease 2 (AOVD2)1 Publication
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
Disease descriptionA 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.
See also OMIM:614823
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_068075415P → L in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 PublicationCorresponds to variant dbSNP:rs387907284EnsemblClinVar.1
Natural variantiVAR_068076484C → F in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 PublicationCorresponds to variant dbSNP:rs387907283EnsemblClinVar.1
Craniosynostosis 7 (CRS7)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry. Rare heterozygous SMAD6 variants are strongly associated with non-syndromic midline craniosynostosis and confer a very high risk for disease development, in the presence of a common risk allele (rs1884302) near the BMP2 locus.1 Publication
Disease descriptionA form of craniosynostosis, a primary abnormality of skull growth involving premature fusion of one or more cranial sutures. The growth velocity of the skull often cannot match that of the developing brain resulting in an abnormal head shape and, in some cases, increased intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability.
See also OMIM:617439
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078924223 – 496Missing in CRS7; associated with disease susceptibility. 1 PublicationAdd BLAST274
Natural variantiVAR_078925287E → K in CRS7; associated with disease susceptibility. 1 PublicationCorresponds to variant dbSNP:rs570279865Ensembl.1
Natural variantiVAR_077592306T → A in CRS7; associated with disease susceptibility. 1 Publication1
Natural variantiVAR_077593323P → L in CRS7; associated with disease susceptibility. 1 PublicationCorresponds to variant dbSNP:rs1374099442Ensembl.1
Natural variantiVAR_078926374 – 496Missing in CRS7; associated with disease susceptibility. 1 PublicationAdd BLAST123
Natural variantiVAR_077594390G → C in CRS7; associated with disease susceptibility; de novo mutation. 1 Publication1
Natural variantiVAR_078927407 – 496Missing in CRS7; associated with disease susceptibility. 1 PublicationAdd BLAST90
Natural variantiVAR_077595465R → C in CRS7; associated with disease susceptibility. 1 PublicationCorresponds to variant dbSNP:rs761888345EnsemblClinVar.1
Natural variantiVAR_078928490I → T in CRS7; associated with disease susceptibility. 1 PublicationCorresponds to variant dbSNP:rs1338294058Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi173K → R: Abolishes monoubiquitination by UBE2O. 1 Publication1
Mutagenesisi435S → A: Loss of in vitro phosphorylation by PRKX. 1 Publication1
Mutagenesisi471G → S: Loss of SMAD1-binding and of inhibition of BMP-SMAD1 signaling. No effect on interaction with BMPR1B and TGFBR1. 1 Publication1
Mutagenesisi478 – 496Missing : Loss of interaction with BMPR1B, TGFBR1 and SMAD1. 1 PublicationAdd BLAST19

Keywords - Diseasei

Craniosynostosis, Disease mutation

Organism-specific databases

DisGeNET

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DisGeNETi
4091

MalaCards human disease database

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MalaCardsi
SMAD6
MIMi614823 phenotype
617439 phenotype

Open Targets

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OpenTargetsi
ENSG00000137834

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
402075 Familial bicuspid aortic valve

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA30529

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
SMAD6

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000908691 – 496Mothers against decapentaplegic homolog 6Add BLAST496

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei75Dimethylated arginine; alternateBy similarity1
Modified residuei75Omega-N-methylarginine; alternateBy similarity1
Modified residuei82Dimethylated arginine; alternateBy similarity1
Modified residuei82Omega-N-methylarginine; alternateBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki173Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei435Phosphoserine; by PRKX; in vitroPROSITE-ProRule annotation1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated by BMP type 1 receptor kinase and by PRKX.1 Publication
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 (PubMed:23455153). Ubiquitinated by WWP1 (By similarity). Ubiquitinated by RNF165, promoting proteasomal degradation, leading to enhance the BMP-Smad signaling (By similarity).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

MaxQB - The MaxQuant DataBase

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MaxQBi
O43541

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O43541

PeptideAtlas

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PeptideAtlasi
O43541

PRoteomics IDEntifications database

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PRIDEi
O43541

ProteomicsDB human proteome resource

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ProteomicsDBi
49038
49039 [O43541-2]
49040 [O43541-4]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O43541

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
O43541

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000137834 Expressed in 213 organ(s), highest expression level in upper lobe of lung

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O43541 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O43541 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
HPA061917

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
110266, 48 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
O43541

Database of interacting proteins

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DIPi
DIP-36708N

Protein interaction database and analysis system

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IntActi
O43541, 13 interactors

Molecular INTeraction database

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MINTi
O43541

STRING: functional protein association networks

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STRINGi
9606.ENSP00000288840

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O43541

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini148 – 275MH1PROSITE-ProRule annotationAdd BLAST128
Domaini331 – 496MH2PROSITE-ProRule annotationAdd BLAST166

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi25 – 33Poly-Gly9
Compositional biasi82 – 85Poly-Arg4
Compositional biasi165 – 168Poly-Leu4
Compositional biasi251 – 254Poly-Ala4
Compositional biasi275 – 278Poly-Pro4

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the dwarfin/SMAD family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG3701 Eukaryota
ENOG410XQKU LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000158146

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O43541

KEGG Orthology (KO)

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KOi
K04677

Identification of Orthologs from Complete Genome Data

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OMAi
CRTVTCC

Database of Orthologous Groups

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OrthoDBi
395665at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O43541

TreeFam database of animal gene trees

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TreeFami
TF314923

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.60.200.10, 1 hit
3.90.520.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View 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

The PANTHER Classification System

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PANTHERi
PTHR13703 PTHR13703, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF03165 MH1, 1 hit
PF03166 MH2, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00523 DWA, 1 hit
SM00524 DWB, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF49879 SSF49879, 1 hit
SSF56366 SSF56366, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS51075 MH1, 1 hit
PS51076 MH2, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YM33H0YM33_HUMAN
Mothers against decapentaplegic hom...
SMAD6
62Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YK80H0YK80_HUMAN
Mothers against decapentaplegic hom...
SMAD6
55Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti21D → N in AAB94137 (PubMed:9436979).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078924223 – 496Missing in CRS7; associated with disease susceptibility. 1 PublicationAdd BLAST274
Natural variantiVAR_078925287E → K in CRS7; associated with disease susceptibility. 1 PublicationCorresponds to variant dbSNP:rs570279865Ensembl.1
Natural variantiVAR_077592306T → A in CRS7; associated with disease susceptibility. 1 Publication1
Natural variantiVAR_077593323P → L in CRS7; associated with disease susceptibility. 1 PublicationCorresponds to variant dbSNP:rs1374099442Ensembl.1
Natural variantiVAR_068074325A → T Found in a patient with congenital mitral valve prolapse. 1 PublicationCorresponds to variant dbSNP:rs199822239EnsemblClinVar.1
Natural variantiVAR_078926374 – 496Missing in CRS7; associated with disease susceptibility. 1 PublicationAdd BLAST123
Natural variantiVAR_077594390G → C in CRS7; associated with disease susceptibility; de novo mutation. 1 Publication1
Natural variantiVAR_078927407 – 496Missing in CRS7; associated with disease susceptibility. 1 PublicationAdd BLAST90
Natural variantiVAR_068075415P → L in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 PublicationCorresponds to variant dbSNP:rs387907284EnsemblClinVar.1
Natural variantiVAR_077595465R → C in CRS7; associated with disease susceptibility. 1 PublicationCorresponds to variant dbSNP:rs761888345EnsemblClinVar.1
Natural variantiVAR_068076484C → F in AOVD2; results in significantly lower activity than wild-type in inhibiting BMP signaling in a transcriptional reporter assay. 1 PublicationCorresponds to variant dbSNP:rs387907283EnsemblClinVar.1
Natural variantiVAR_078928490I → T in CRS7; associated with disease susceptibility. 1 PublicationCorresponds to variant dbSNP:rs1338294058Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0061791 – 261Missing in isoform B. 1 PublicationAdd BLAST261
Alternative sequenceiVSP_006180262 – 273NPYHF…LCGPE → MSRMGKPIETQK in isoform B. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_035489318 – 338DASMS…VAYWE → AADAGIGSRGNRGLESSVPC S in isoform D. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_035490339 – 496Missing in isoform D. 1 PublicationAdd BLAST158

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
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

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS10221.1 [O43541-1]

NCBI Reference Sequences

More...
RefSeqi
NP_005576.3, NM_005585.4 [O43541-1]
XP_011519863.1, XM_011521561.2 [O43541-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000288840; ENSP00000288840; ENSG00000137834 [O43541-1]
ENST00000557916; ENSP00000452955; ENSG00000137834 [O43541-4]

Database of genes from NCBI RefSeq genomes

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GeneIDi
4091

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:4091

UCSC genome browser

More...
UCSCi
uc002aqf.4 human [O43541-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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]
XP_011519863.1, XM_011521561.2 [O43541-2]

3D structure databases

SMRiO43541
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110266, 48 interactors
CORUMiO43541
DIPiDIP-36708N
IntActiO43541, 13 interactors
MINTiO43541
STRINGi9606.ENSP00000288840

PTM databases

iPTMnetiO43541
PhosphoSitePlusiO43541

Polymorphism and mutation databases

BioMutaiSMAD6

Proteomic databases

MaxQBiO43541
PaxDbiO43541
PeptideAtlasiO43541
PRIDEiO43541
ProteomicsDBi49038
49039 [O43541-2]
49040 [O43541-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
4091
DisGeNETi4091

GeneCards: human genes, protein and diseases

More...
GeneCardsi
SMAD6

H-Invitational Database, human transcriptome db

More...
H-InvDBi
HIX0132566
HGNCiHGNC:6772 SMAD6
HPAiHPA061917
MalaCardsiSMAD6
MIMi602931 gene
614823 phenotype
617439 phenotype
neXtProtiNX_O43541
OpenTargetsiENSG00000137834
Orphaneti402075 Familial bicuspid aortic valve
PharmGKBiPA30529

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG3701 Eukaryota
ENOG410XQKU LUCA
GeneTreeiENSGT00940000158146
InParanoidiO43541
KOiK04677
OMAiCRTVTCC
OrthoDBi395665at2759
PhylomeDBiO43541
TreeFamiTF314923

Enzyme and pathway databases

ReactomeiR-HSA-201451 Signaling by BMP
R-HSA-8941326 RUNX2 regulates bone development
SignaLinkiO43541
SIGNORiO43541

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
SMAD6 human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
Mothers_against_decapentaplegic_homolog_6

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
4091

Protein Ontology

More...
PROi
PR:O43541

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000137834 Expressed in 213 organ(s), highest expression level in upper lobe of lung
ExpressionAtlasiO43541 baseline and differential
GenevisibleiO43541 HS

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

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSMAD6_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O43541
Secondary accession number(s): A9J6M5
, O43654, Q15799, Q7Z7L4, Q96E31, Q9UKZ3
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: October 3, 2006
Last modified: May 8, 2019
This is version 183 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>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. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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