Seroatlas · Human Serome Atlas

SMAD4

Mothers against decapentaplegic homolog 4

Also known as: DPC4, MADH4, SMAD4_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q13485
Gene
SMAD4
Ensembl
ENSG00000141646
Chromosome
18
Canonical length
552 aa
Protein class
Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
Subcellular location
Nucleoplasm,Primary cilium tip,Centrosome,Basal body,Cytosol

OverviewNCBI Gene

This gene encodes a member of the Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor (TGF)-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The protein acts as a tumor suppressor and inhibits epithelial cell proliferation. It may also have an inhibitory effect on tumors by reducing angiogenesis and increasing blood vessel hyperpermeability. The encoded protein is a crucial component of the bone morphogenetic protein signaling pathway. The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, May 2022]

Canonical amino-acid sequenceUniProt

552 residues, UniProt reviewed canonical sequence.

>Q13485|SMAD4
     1  MDNMSITNTP TSNDACLSIV HSLMCHRQGG ESETFAKRAI ESLVKKLKEK KDELDSLITA
    61  ITTNGAHPSK CVTIQRTLDG RLQVAGRKGF PHVIYARLWR WPDLHKNELK HVKYCQYAFD
   121  LKCDSVCVNP YHYERVVSPG IDLSGLTLQS NAPSSMMVKD EYVHDFEGQP SLSTEGHSIQ
   181  TIQHPPSNRA STETYSTPAL LAPSESNATS TANFPNIPVA STSQPASILG GSHSEGLLQI
   241  ASGPQPGQQQ NGFTGQPATY HHNSTTTWTG SRTAPYTPNL PHHQNGHLQH HPPMPPHPGH
   301  YWPVHNELAF QPPISNHPAP EYWCSIAYFE MDVQVGETFK VPSSCPIVTV DGYVDPSGGD
   361  RFCLGQLSNV HRTEAIERAR LHIGKGVQLE CKGEGDVWVR CLSDHAVFVQ SYYLDREAGR
   421  APGDAVHKIY PSAYIKVFDL RQCHRQMQQQ AATAQAAAAA QAAAVAGNIP GPGSVGGIAP
   481  AISLSAAAGI GVDDLRRLCI LRMSFVKGWG PDYPRQSIKE TPCWIEIHLH RALQLLDEVL
   541  HTMPIADPQP LD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMAD4 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)
0.42
Highest tissue expression
18 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 18 nTPM
  • cerebellum: 15 nTPM
  • retina: 13 nTPM
  • tongue: 11 nTPM
  • colon: 11 nTPM
  • endometrium: 11 nTPM

Single-cell type

  • prostatic glandular cells: 91 nCPM
  • microglia: 87 nCPM
  • choroid plexus epithelial cells: 86 nCPM
  • bergmann glia: 73 nCPM
  • sertoli cells: 67 nCPM
  • thymic myoid cells: 67 nCPM

Immune cell

  • T-reg: 1.7 nTPM
  • naive CD8 T-cell: 1.6 nTPM
  • myeloid DC: 1.3 nTPM
  • MAIT T-cell: 1.2 nTPM
  • gdT-cell: 1.1 nTPM
  • naive CD4 T-cell: 1.1 nTPM

Brain region

  • cerebellum: 49 nTPM
  • hypothalamus: 32 nTPM
  • hippocampal formation: 31 nTPM
  • white matter: 30 nTPM
  • choroid plexus: 28 nTPM
  • basal ganglia: 27 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SMAD4.

Disease | AllUniProt

Conditions SMAD4 is implicated in, by any mechanism.

Disease | GeneticClinVar

307 pathogenic / likely-pathogenic of 2,592 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)
0.22
gnomAD pLI
1
gnomAD missense Z
4.13
DepMap mean gene effect
-0.1
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 SMAD4 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 SMAD4 as an antibody target. Whether an autoantibody or antibody against SMAD4 could matter depends on whether native SMAD4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SMAD4 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 SMAD4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SMAD4. 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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