Seroatlas · Human Serome Atlas

SMAD6

Mothers against decapentaplegic homolog 6

Also known as: HsT17432, MADH6, MADH7, SMAD6_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
O43541
Gene
SMAD6
Ensembl
ENSG00000137834
Chromosome
15
Canonical length
496 aa
Protein class
Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Transcription factors
Subcellular location
Nucleoplasm,Nuclear bodies,Primary cilium,Basal body,Cytosol

OverviewNCBI Gene

The protein encoded by this gene belongs to the SMAD family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]

Canonical amino-acid sequenceUniProt

496 residues, UniProt reviewed canonical sequence.

>O43541|SMAD6
     1  MFRSKRSGLV RRLWRSRVVP DREEGGSGGG GGGDEDGSLG SRAEPAPRAR EGGGCGRSEV
    61  RPVAPRRPRD AVGQRGAQGA GRRRRAGGPP RPMSEPGAGA GSSLLDVAEP GGPGWLPESD
   121  CETVTCCLFS ERDAAGAPRD ASDPLAGAAL EPAGGGRSRE ARSRLLLLEQ ELKTVTYSLL
   181  KRLKERSLDT LLEAVESRGG VPGGCVLVPR ADLRLGGQPA PPQLLLGRLF RWPDLQHAVE
   241  LKPLCGCHSF AAAADGPTVC CNPYHFSRLC GPESPPPPYS RLSPRDEYKP LDLSDSTLSY
   301  TETEATNSLI TAPGEFSDAS MSPDATKPSH WCSVAYWEHR TRVGRLYAVY DQAVSIFYDL
   361  PQGSGFCLGQ LNLEQRSESV RRTRSKIGFG ILLSKEPDGV WAYNRGEHPI FVNSPTLDAP
   421  GGRALVVRKV PPGYSIKVFD FERSGLQHAP EPDAADGPYD PNSVRISFAK GWGPCYSRQF
   481  ITSCPCWLEI LLNNPR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMAD6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.46
Highest tissue expression
29 nTPM

Expression across tissuesHPA

Tissue

  • heart muscle: 29 nTPM
  • lung: 26 nTPM
  • blood vessel: 16 nTPM
  • thyroid gland: 15 nTPM
  • adipose tissue: 9 nTPM
  • kidney: 8.4 nTPM

Single-cell type

  • podocytes: 219 nCPM
  • vascular endothelial cells: 148 nCPM
  • adipocytes: 127 nCPM
  • pituitary stem cells: 59 nCPM
  • choroid plexus epithelial cells: 52 nCPM
  • microglia: 46 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • choroid plexus: 18 nTPM
  • medulla oblongata: 16 nTPM
  • thalamus: 14 nTPM
  • pons: 12 nTPM
  • midbrain: 11 nTPM
  • amygdala: 10 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SMAD6.

Disease | AllUniProt

Conditions SMAD6 is implicated in, by any mechanism.

Disease | GeneticClinVar

84 pathogenic / likely-pathogenic of 1,331 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
1.98
gnomAD pLI
0
gnomAD missense Z
-0.59
DepMap mean gene effect
-0.03
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of SMAD6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads SMAD6 as an antibody target. Whether an autoantibody or antibody against SMAD6 could matter depends on whether native SMAD6 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SMAD6 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label SMAD6 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SMAD6. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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