Seroatlas · Human Serome Atlas

SMAD3

Mothers against decapentaplegic homolog 3

Also known as: HsT17436, JV15-2, MADH3, SMAD3_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
P84022
Gene
SMAD3
Ensembl
ENSG00000166949
Chromosome
15
Canonical length
425 aa
Protein class
Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
Subcellular location
Nucleoplasm,Vesicles,Primary cilium transition zone,Basal body
Quaternary structure
Homooligomer

OverviewNCBI Gene

The SMAD family of proteins are a group of intracellular signal transducer proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. The SMAD3 protein functions in the transforming growth factor-beta signaling pathway, and transmits signals from the cell surface to the nucleus, regulating gene activity and cell proliferation. This protein forms a complex with other SMAD proteins and binds DNA, functioning both as a transcription factor and tumor suppressor. Mutations in this gene are associated with aneurysms-osteoarthritis syndrome and Loeys-Dietz Syndrome 3. [provided by RefSeq, May 2022]

Canonical amino-acid sequenceUniProt

425 residues, UniProt reviewed canonical sequence.

>P84022|SMAD3
     1  MSSILPFTPP IVKRLLGWKK GEQNGQEEKW CEKAVKSLVK KLKKTGQLDE LEKAITTQNV
    61  NTKCITIPRS LDGRLQVSHR KGLPHVIYCR LWRWPDLHSH HELRAMELCE FAFNMKKDEV
   121  CVNPYHYQRV ETPVLPPVLV PRHTEIPAEF PPLDDYSHSI PENTNFPAGI EPQSNIPETP
   181  PPGYLSEDGE TSDHQMNHSM DAGSPNLSPN PMSPAHNNLD LQPVTYCEPA FWCSISYYEL
   241  NQRVGETFHA SQPSMTVDGF TDPSNSERFC LGLLSNVNRN AAVELTRRHI GRGVRLYYIG
   301  GEVFAECLSD SAIFVQSPNC NQRYGWHPAT VCKIPPGCNL KIFNNQEFAA LLAQSVNQGF
   361  EAVYQLTRMC TIRMSFVKGW GAEYRRQTVT STPCWIELHL NGPLQWLDKV LTQMGSPSIR
   421  CSSVS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMAD3 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)
0.34
Highest tissue expression
52 nTPM

Expression across tissuesHPA

Tissue

  • skeletal muscle: 52 nTPM
  • esophagus: 48 nTPM
  • urinary bladder: 41 nTPM
  • tongue: 36 nTPM
  • vagina: 32 nTPM
  • thyroid gland: 30 nTPM

Single-cell type

  • urothelial cells: 1,010 nCPM
  • endometrial glandular cells: 778 nCPM
  • myonuclei: 587 nCPM
  • ocular epithelial cells: 586 nCPM
  • papillary tip epithelial cells: 456 nCPM
  • pancreatic duct cells: 428 nCPM

Immune cell

  • memory CD4 T-cell: 3.6 nTPM
  • memory CD8 T-cell: 3.4 nTPM
  • MAIT T-cell: 3.3 nTPM
  • gdT-cell: 3.2 nTPM
  • naive B-cell: 2.8 nTPM
  • eosinophil: 2.3 nTPM

Brain region

  • choroid plexus: 74 nTPM
  • basal ganglia: 55 nTPM
  • amygdala: 45 nTPM
  • medulla oblongata: 45 nTPM
  • hippocampal formation: 42 nTPM
  • cerebral cortex: 41 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SMAD3.

Disease | AllUniProt

Conditions SMAD3 is implicated in, by any mechanism.

Disease | GeneticClinVar

206 pathogenic / likely-pathogenic of 1,279 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)
0.4
gnomAD pLI
0.8
gnomAD missense Z
3.48
DepMap mean gene effect
-0.05
DepMap dependency class
none

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 SMAD3 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 SMAD3 as an antibody target. Whether an autoantibody or antibody against SMAD3 could matter depends on whether native SMAD3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SMAD3 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 SMAD3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/SMAD3. 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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