Format

Send to:

Choose Destination

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

Gene ID: 4087, updated on 4-Oct-2020

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; 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

Genomic context

See SMAD2 in Genome Data Viewer
Location:
18q21.1
Exon count:
18
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 18 NC_000018.10 (47808957..47931188, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (45359466..45457564, 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 uncharacterized LOC105372104 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

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 
DNA-binding transcription activator activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA-binding transcription activator activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription activator activity, RNA polymerase II-specific ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISM
Inferred from Sequence Model
more info
PubMed 
I-SMAD binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
I-SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
R-SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
RNA polymerase II proximal promoter sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
RNA polymerase II proximal promoter sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
activating transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
chromatin binding IEA
Inferred from Electronic Annotation
more info
 
co-SMAD binding IPI
Inferred from Physical Interaction
more info
PubMed 
disordered domain specific binding IPI
Inferred from Physical Interaction
more info
PubMed 
double-stranded DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
phosphatase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
proximal promoter sequence-specific DNA binding IC
Inferred by Curator
more info
PubMed 
tau protein binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
transcription factor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
transforming growth factor beta receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
type I transforming growth factor beta receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
BMP signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SMAD protein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
SMAD protein signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SMAD protein signal transduction IEA
Inferred from Electronic Annotation
more info
 
activin receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
adrenal gland development IEA
Inferred from Electronic Annotation
more info
 
anatomical structure morphogenesis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
anterior/posterior pattern specification ISS
Inferred from Sequence or Structural Similarity
more info
 
cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cell fate commitment ISS
Inferred from Sequence or Structural Similarity
more info
 
common-partner SMAD protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
embryonic cranial skeleton morphogenesis IEA
Inferred from Electronic Annotation
more info
 
embryonic foregut morphogenesis IEA
Inferred from Electronic Annotation
more info
 
endoderm formation IEA
Inferred from Electronic Annotation
more info
 
gastrulation TAS
Traceable Author Statement
more info
PubMed 
in utero embryonic development IEA
Inferred from Electronic Annotation
more info
 
insulin secretion IEA
Inferred from Electronic Annotation
more info
 
intracellular signal transduction ISS
Inferred from Sequence or Structural Similarity
more info
 
lung development IEA
Inferred from Electronic Annotation
more info
 
mesoderm formation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
 
negative regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 
nodal signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
organ growth IEA
Inferred from Electronic Annotation
more info
 
pancreas development IEA
Inferred from Electronic Annotation
more info
 
paraxial mesoderm morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
pericardium development IEA
Inferred from Electronic Annotation
more info
 
positive regulation of BMP signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of epithelial to mesenchymal transition ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription by RNA polymerase II TAS
Traceable Author Statement
more info
 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
post-embryonic development IEA
Inferred from Electronic Annotation
more info
 
primary miRNA processing TAS
Traceable Author Statement
more info
PubMed 
protein deubiquitination TAS
Traceable Author Statement
more info
 
regulation of binding ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to cholesterol IDA
Inferred from Direct Assay
more info
PubMed 
response to glucose IEA
Inferred from Electronic Annotation
more info
 
secondary palate development ISS
Inferred from Sequence or Structural Similarity
more info
 
signal transduction involved in regulation of gene expression IEA
Inferred from Electronic Annotation
more info
 
somatic stem cell population maintenance TAS
Traceable Author Statement
more info
 
transforming growth factor beta receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transforming growth factor beta receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 
ureteric bud development IEA
Inferred from Electronic Annotation
more info
 
wound healing IEA
Inferred from Electronic Annotation
more info
 
zygotic specification of dorsal/ventral axis IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
SMAD protein complex IDA
Inferred from Direct Assay
more info
PubMed 
activin responsive factor complex IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
heteromeric SMAD protein complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
heteromeric SMAD protein complex IDA
Inferred from Direct Assay
more info
PubMed 
nuclear chromatin IDA
Inferred from Direct Assay
more info
PubMed 
nuclear chromatin ISA
Inferred from Sequence Alignment
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
transcription factor 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)

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 109.20200815

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
Support Center