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

Gene ID: 4087, updated on 5-Jan-2022

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
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
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Genomic context

See SMAD2 in Genome Data Viewer
Location:
18q21.1
Exon count:
18
Annotation release Status Assembly Chr Location
109.20211119 current GRCh38.p13 (GCF_000001405.39) 18 NC_000018.10 (47808957..47931188, complement)
105.20201022 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 uncharacterized LOC105372100 Neighboring gene thiopurine S-methyltransferase pseudogene 1 Neighboring gene MT-CO2 pseudogene 2 Neighboring gene uncharacterized LOC105372101 Neighboring gene zinc finger and BTB domain containing 7C Neighboring gene ZBTB7C antisense RNA 1 Neighboring gene RNA, U6 small nuclear 708, pseudogene

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: CN305192 OMIM: 619657 GeneReviews: Not available
Compare labs
LOEYS-DIETZ SYNDROME 6
MedGen: CN305191 OMIM: 619656 GeneReviews: Loeys-Dietz Syndrome
not available

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

Homology

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
PubMed 
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
PubMed 
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
PubMed 
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 IEA
Inferred from Electronic Annotation
more info
 
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 BMP signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in SMAD protein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
involved_in SMAD protein signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in activin receptor signaling pathway IMP
Inferred from Mutant Phenotype
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
PubMed 
involved_in anterior/posterior pattern specification ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in cell fate commitment ISS
Inferred from Sequence or Structural Similarity
more info
 
acts_upstream_of_or_within common-partner SMAD protein phosphorylation IDA
Inferred from Direct Assay
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 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 cell population proliferation IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in nodal signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
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 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 nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry IMP
Inferred from Mutant Phenotype
more info
PubMed 
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 positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of transcription, DNA-templated 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 regulation of binding ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 response to glucose IEA
Inferred from Electronic Annotation
more info
 
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
PubMed 
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 ureteric bud development IEA
Inferred from Electronic Annotation
more info
 
involved_in wound healing 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 
located_in chromatin IDA
Inferred from Direct Assay
more info
PubMed 
located_in 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
PubMed 
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 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_029946.1 RefSeqGene

    Range
    5546..103050
    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
    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
    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: Homo sapiens Updated Annotation Release 109.20211119

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p13 Primary Assembly

    Range
    47808957..47931188 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017025747.2XP_016881236.1  mothers against decapentaplegic homolog 2 isoform X4

  2. XM_017025746.2XP_016881235.1  mothers against decapentaplegic homolog 2 isoform X2

    UniProtKB/Swiss-Prot
    Q15796
    Related
    ENSP00000466193.1, ENST00000586040.5
    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. XM_011525985.3XP_011524287.1  mothers against decapentaplegic homolog 2 isoform X5

    Conserved Domains (2) summary
    cd10985
    Location:213403
    MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3
    cl00055
    Location:56119
    MH1; N-terminal Mad Homology 1 (MH1) domain
  4. XM_017025745.2XP_016881234.1  mothers against decapentaplegic homolog 2 isoform X1

    UniProtKB/Swiss-Prot
    Q15796
    UniProtKB/TrEMBL
    Q53XR6
    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
  5. XM_017025750.2XP_016881239.1  mothers against decapentaplegic homolog 2 isoform X7

    Conserved Domains (1) summary
    cd10985
    Location:26216
    MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3
  6. XM_006722451.4XP_006722514.1  mothers against decapentaplegic homolog 2 isoform X1

    See identical proteins and their annotated locations for XP_006722514.1

    UniProtKB/Swiss-Prot
    Q15796
    UniProtKB/TrEMBL
    Q53XR6
    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
  7. XM_017025748.2XP_016881237.1  mothers against decapentaplegic homolog 2 isoform X5

    Conserved Domains (2) summary
    cd10985
    Location:213403
    MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3
    cl00055
    Location:56119
    MH1; N-terminal Mad Homology 1 (MH1) domain
  8. XM_024451173.1XP_024306941.1  mothers against decapentaplegic homolog 2 isoform X1

    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
  9. XM_011525984.2XP_011524286.1  mothers against decapentaplegic homolog 2 isoform X3

    Conserved Domains (2) summary
    cd10985
    Location:224414
    MH2_SMAD_2_3; C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3
    cl00055
    Location:67130
    MH1; N-terminal Mad Homology 1 (MH1) domain
  10. XM_005258259.4XP_005258316.1  mothers against decapentaplegic homolog 2 isoform X1

    See identical proteins and their annotated locations for XP_005258316.1

    UniProtKB/Swiss-Prot
    Q15796
    UniProtKB/TrEMBL
    Q53XR6
    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
  11. XM_017025749.1XP_016881238.1  mothers against decapentaplegic homolog 2 isoform X6

    Related
    ENSP00000466254.1, ENST00000587269.5
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