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    SMAD2 SMAD family member 2 [ Homo sapiens (human) ]

    Gene ID: 4087, updated on 4-Feb-2024

    Summary

    Official Symbol
    SMAD2provided by HGNC
    Official Full Name
    SMAD family member 2provided by HGNC
    Primary source
    HGNC:HGNC:6768
    See related
    Ensembl:ENSG00000175387 MIM:601366; AllianceGenome:HGNC:6768
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    JV18; LDS6; CHTD8; MADH2; MADR2; JV18-1; hMAD-2; hSMAD2
    Summary
    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]
    Expression
    Ubiquitous expression in thyroid (RPKM 6.6), testis (RPKM 4.0) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See SMAD2 in Genome Data Viewer
    Location:
    18q21.1
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (47808957..47930872, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (47999960..48121861, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (45335328..45457243, complement)

    Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene thiopurine S-methyltransferase pseudogene 1 Neighboring gene OCT4-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:45186392-45187015 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:45187016-45187638 Neighboring gene uncharacterized LOC105372100 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9425 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9426 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:45354093-45354738 Neighboring gene MT-CO2 pseudogene 2 Neighboring gene MPRA-validated peak3140 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13287 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr18:45444735-45445347 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9427 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9428 Neighboring gene uncharacterized LOC124904297 Neighboring gene uncharacterized LOC105372101

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Congenital heart defects, multiple types, 8, with or without heterotaxy
    MedGen: C5562042 OMIM: 619657 GeneReviews: Not available
    Compare labs
    Loeys-Dietz syndrome 6
    MedGen: C5562041 OMIM: 619656 GeneReviews: Loeys-Dietz Syndrome
    Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2018-06-28)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2018-06-28)

    ClinGen Genome Curation Page

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    HIV-1 replication is restricted by TGFB1 and SMAD2 in Langerhans cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 and p300 synergistically increase TGF-beta, ATF-2 and activating protein-1 (AP-1) expression leading to tubular cell apoptosis; in addition, HIV-1 gp120 treatment causes phosphorylation of Smad2 and downregulation of c-Jun PubMed
    Tat tat HIV-1 Tat-treated pulmonary arterial smooth muscle cells downregulate levels of phosphorylated SMAD2/3 proteins and SMAD2/3-SMAD4 protein complex, which are repressed by cocaine exposure PubMed
    tat HIV-1 Tat enhances binding of SMAD2, -3 and -4 and their binding partner Fast1 to the JCV DNA control region (CR) to stimulate JCV gene transcription in living cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC22139, MGC34440

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA-binding transcription activator activity, RNA polymerase II-specific ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    contributes_to DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
     
    enables DNA-binding transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables I-SMAD binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables I-SMAD binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables R-SMAD binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables RNA polymerase II-specific DNA-binding transcription factor binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables SMAD binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables cis-regulatory region sequence-specific DNA binding IC
    Inferred by Curator
    more info
    PubMed 
    enables co-SMAD binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables disordered domain specific binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables double-stranded DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables phosphatase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables tau protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    enables transforming growth factor beta receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables type I transforming growth factor beta receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in DNA-templated transcription NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in SMAD protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    acts_upstream_of_or_within SMAD protein signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in SMAD protein signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in SMAD protein signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in activin receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in activin receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in activin receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in adrenal gland development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in anatomical structure morphogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in anterior/posterior pattern specification ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in aortic valve morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cell fate commitment ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to glucose stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in determination of left/right asymmetry in lateral mesoderm IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in embryonic cranial skeleton morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in embryonic foregut morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in endocardial cushion morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in endoderm formation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in gastrulation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in in utero embryonic development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in insulin secretion IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in intracellular signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in lung development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in mesoderm formation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in nodal signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in odontoblast differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in organ growth IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in pancreas development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in paraxial mesoderm morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in pericardium development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of BMP signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of DNA-templated transcription IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of DNA-templated transcription ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of epithelial to mesenchymal transition ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in post-embryonic development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in primary miRNA processing TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in pulmonary valve morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of DNA-templated transcription NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in regulation of binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of transforming growth factor beta receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in response to cholesterol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in secondary palate development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in signal transduction involved in regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in transforming growth factor beta receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in transforming growth factor beta receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in transforming growth factor beta receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in transforming growth factor beta receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in ureteric bud development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in zygotic specification of dorsal/ventral axis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of SMAD protein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of activin responsive factor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of chromatin IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of chromatin ISA
    Inferred from Sequence Alignment
    more info
     
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    part_of heteromeric SMAD protein complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of heteromeric SMAD protein complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of heteromeric SMAD protein complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of heteromeric SMAD protein complex NAS
    Non-traceable Author Statement
    more info
    PubMed 
    part_of homomeric SMAD protein complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of protein-containing complex IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    part_of transcription regulator complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    mothers against decapentaplegic homolog 2
    Names
    MAD homolog 2
    SMAD, mothers against DPP homolog 2
    Sma- and Mad-related protein 2
    mother against DPP homolog 2

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029946.2 RefSeqGene

      Range
      5213..126915
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001003652.4NP_001003652.1  mothers against decapentaplegic homolog 2 isoform 1

      See identical proteins and their annotated locations for NP_001003652.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the longest transcript and encodes the longer isoform (1). Both variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC026898, AC120349, AI453799, BC025699, DB462454
      Consensus CDS
      CCDS11934.1
      UniProtKB/Swiss-Prot
      Q15796
      UniProtKB/TrEMBL
      B7Z5N5, Q53XR6
      Related
      ENSP00000384449.1, ENST00000402690.6
      Conserved Domains (2) summary
      cd10491
      Location:8172
      MH1_SMAD_2_3; N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3
      cd10985
      Location:266456
      MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3
    2. NM_001135937.3NP_001129409.1  mothers against decapentaplegic homolog 2 isoform 2

      See identical proteins and their annotated locations for NP_001129409.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3, also known as SMAD2Deltaexon3) lacks an in-frame exon in the 5' coding region, compared to variant 2, resulting in an isoform (2) that is shorter than isoform 1. There are no publicly available full-length transcripts representing this variant, but it is supported by data in Taekenoshita et al. (1998; PMID: 9503010) and Yagi et al. (1999; PMID: 9873005).
      Source sequence(s)
      AC026898, AC120349, AI453799, AK299218, DB462454
      UniProtKB/TrEMBL
      B7Z5N5
      Related
      ENSP00000349282.4, ENST00000356825.8
      Conserved Domains (2) summary
      cd10491
      Location:8142
      MH1_SMAD_2_3; N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3
      cd10985
      Location:236426
      MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3
    3. NM_005901.6NP_005892.1  mothers against decapentaplegic homolog 2 isoform 1

      See identical proteins and their annotated locations for NP_005892.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) uses an alternate exon (1b) in the 5' UTR compared to variant 2. Both variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      AC026898, AC120349, AI453799, BC014840
      Consensus CDS
      CCDS11934.1
      UniProtKB/Swiss-Prot
      Q15796
      UniProtKB/TrEMBL
      B7Z5N5, Q53XR6
      Related
      ENSP00000262160.6, ENST00000262160.11
      Conserved Domains (2) summary
      cd10491
      Location:8172
      MH1_SMAD_2_3; N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3
      cd10985
      Location:266456
      MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

      Range
      47808957..47930872 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047437508.1XP_047293464.1  mothers against decapentaplegic homolog 2 isoform X1

      UniProtKB/TrEMBL
      K7EJX0
    2. XM_017025749.2XP_016881238.1  mothers against decapentaplegic homolog 2 isoform X1

      UniProtKB/TrEMBL
      K7EJX0
      Related
      ENSP00000465355.1, ENST00000586514.5
    3. XM_047437507.1XP_047293463.1  mothers against decapentaplegic homolog 2 isoform X1

      UniProtKB/TrEMBL
      K7EJX0
      Related
      ENSP00000466254.1, ENST00000587269.5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060942.1 Alternate T2T-CHM13v2.0

      Range
      47999960..48121861 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054318622.1XP_054174597.1  mothers against decapentaplegic homolog 2 isoform X1

      UniProtKB/TrEMBL
      K7EJX0
    2. XM_054318620.1XP_054174595.1  mothers against decapentaplegic homolog 2 isoform X1

      UniProtKB/TrEMBL
      K7EJX0
    3. XM_054318621.1XP_054174596.1  mothers against decapentaplegic homolog 2 isoform X1

      UniProtKB/TrEMBL
      K7EJX0