Seroatlas · Human Serome Atlas

SMAD2

Mothers against decapentaplegic homolog 2

Also known as: JV18-1, MADH2, MADR2, SMAD2_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: Q15796
Gene: SMAD2
Ensembl: ENSG00000175387
Chromosome: 18
Canonical length: 467 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transcription factors
Subcellular location: Nucleoplasm,Nucleoli,Vesicles,Primary cilium transition zone,Cytosol

OverviewNCBI Gene

The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

Canonical amino-acid sequenceUniProt

467 residues, UniProt reviewed canonical sequence.

>Q15796|SMAD2
     1  MSSILPFTPP VVKRLLGWKK SAGGSGGAGG GEQNGQEEKW CEKAVKSLVK KLKKTGRLDE
    61  LEKAITTQNC NTKCVTIPST CSEIWGLSTP NTIDQWDTTG LYSFSEQTRS LDGRLQVSHR
   121  KGLPHVIYCR LWRWPDLHSH HELKAIENCE YAFNLKKDEV CVNPYHYQRV ETPVLPPVLV
   181  PRHTEILTEL PPLDDYTHSI PENTNFPAGI EPQSNYIPET PPPGYISEDG ETSDQQLNQS
   241  MDTGSPAELS PTTLSPVNHS LDLQPVTYSE PAFWCSIAYY ELNQRVGETF HASQPSLTVD
   301  GFTDPSNSER FCLGLLSNVN RNATVEMTRR HIGRGVRLYY IGGEVFAECL SDSAIFVQSP
   361  NCNQRYGWHP ATVCKIPPGC NLKIFNNQEF AALLAQSVNQ GFEAVYQLTR MCTIRMSFVK
   421  GWGAEYRRQT VTSTPCWIEL HLNGPLQWLD KVLTQMGSPS VRCSSMS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMAD2 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): 0.38
Highest tissue expression: 71 nTPM

Expression across tissuesHPA

Tissue

thyroid gland: 71 nTPM
thymus: 68 nTPM
retina: 65 nTPM
ovary: 54 nTPM
skeletal muscle: 54 nTPM
tongue: 52 nTPM

Single-cell type

cone photoreceptor cells: 375 nCPM
sertoli cells: 272 nCPM
late spermatids: 253 nCPM
podocytes: 235 nCPM
urothelial cells: 235 nCPM
renal collecting duct principal cells: 234 nCPM

Immune cell

basophil: 59 nTPM
T-reg: 41 nTPM
eosinophil: 39 nTPM
NK-cell: 39 nTPM
intermediate monocyte: 39 nTPM
naive CD4 T-cell: 35 nTPM

Brain region

white matter: 125 nTPM
medulla oblongata: 111 nTPM
hypothalamus: 107 nTPM
spinal cord: 105 nTPM
cerebellum: 100 nTPM
midbrain: 96 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SMAD2.

Disease | AllUniProt

Conditions SMAD2 is implicated in, by any mechanism.

Congenital heart defects, multiple types, 8, with or without heterotaxy (CHTD8) MIM:619657
Loeys-Dietz syndrome 6 (LDS6) MIM:619656

Disease | GeneticClinVar

40 pathogenic / likely-pathogenic of 511 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Loeys-Dietz syndrome 6
Congenital heart defects, multiple types, 8, with or without heterotaxy
Inborn genetic diseases
SMAD2-related disorder
Loeys-Dietz syndrome

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): 0.26
gnomAD pLI: 1
gnomAD missense Z: 3.66
DepMap mean gene effect: -0.01
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% 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 SMAD2 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 SMAD2 as an antibody target. Whether an autoantibody or antibody against SMAD2 could matter depends on whether native SMAD2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

SMAD2 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 SMAD2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...