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SMAD5 SMAD family member 5 [ Homo sapiens (human) ]

Gene ID: 4090, updated on 3-Apr-2024

Summary

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Official Symbol
SMAD5provided by HGNC
Official Full Name
SMAD family member 5provided by HGNC
Primary source
HGNC:HGNC:6771
See related
Ensembl:ENSG00000113658 MIM:603110; AllianceGenome:HGNC:6771
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
DWFC; JV5-1; MADH5
Summary
The protein encoded by this gene is involved in the transforming growth factor beta signaling pathway that results in an inhibition of the proliferation of hematopoietic progenitor cells. The encoded protein is activated by bone morphogenetic proteins type 1 receptor kinase, and may be involved in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]
Expression
Ubiquitous expression in endometrium (RPKM 14.1), ovary (RPKM 13.4) and 25 other tissues See more
Orthologs
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Genomic context

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See SMAD5 in Genome Data Viewer
Location:
5q31.1
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (136132845..136182733)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (136655373..136705263)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (135468534..135518421)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23176 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23177 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:135388921-135390120 Neighboring gene transforming growth factor beta induced Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16378 Neighboring gene vault RNA 2-1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16379 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23179 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23178 Neighboring gene SMAD5 antisense RNA 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr5:135488895-135490094 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:135527733-135528647 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:135528804-135529321 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr5:135537973-135538930 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr5:135538931-135539888 Neighboring gene small integral membrane protein 32 Neighboring gene TRPC7 antisense RNA 1 Neighboring gene transient receptor potential cation channel subfamily C member 7

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. Smad5 acts as an intracellular pH messenger and maintains bioenergetic homeostasis. Fang Y, et al. Cell Res, 2017 Sep. PMID 28675158, Free PMC Article
  2. Molecular signatures associated with cognitive deficits in schizophrenia: a study of biopsied olfactory neural epithelium. Horiuchi Y, et al. Transl Psychiatry, 2016 Oct 11. PMID 27727244, Free PMC Article
  3. Genetic polymorphism of SMAD5 is associated with Kawasaki disease. Cho JH, et al. Pediatr Cardiol, 2014 Apr. PMID 24163009
  4. BMP-Smad 1/5/8 signalling in the development of the nervous system. Hegarty SV, et al. Prog Neurobiol, 2013 Oct. PMID 23891815
  5. Kaposi's sarcoma-associated herpesvirus-encoded microRNA miR-K12-11 attenuates transforming growth factor beta signaling through suppression of SMAD5. Liu Y, et al. J Virol, 2012 Feb. PMID 22013049, Free PMC Article

See all (152) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Lrg1 silencing attenuates ischemia-reperfusion renal injury by regulating autophagy and apoptosis through the TGFbeta1- Smad1/5 signaling pathway.
    Title: Lrg1 silencing attenuates ischemia-reperfusion renal injury by regulating autophagy and apoptosis through the TGFβ1- Smad1/5 signaling pathway.
  2. Circ_0001825 promotes osteogenic differentiation in human-derived mesenchymal stem cells via miR-1270/SMAD5 axis.
    Title: Circ_0001825 promotes osteogenic differentiation in human-derived mesenchymal stem cells via miR-1270/SMAD5 axis.
  3. Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5.
    Title: Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5.
  4. Dysregulation of MicroRNA-152-3p is Associated with the Pathogenesis of Pulpitis by Modulating SMAD5.
    Title: Dysregulation of MicroRNA-152-3p is Associated with the Pathogenesis of Pulpitis by Modulating SMAD5.
  5. Role of lncRNA LINC01194 in hepatocellular carcinoma via the miR-655-3p/SMAD family member 5 axis.
    Title: Role of lncRNA LINC01194 in hepatocellular carcinoma via the miR-655-3p/SMAD family member 5 axis.
  6. Long non-coding RNA H19 aggravates keloid progression by upregulating SMAD family member 5 expression via miR-196b-5p.
    Title: Long non-coding RNA H19 aggravates keloid progression by upregulating SMAD family member 5 expression via miR-196b-5p.
  7. Silencing of long non-coding RNA HCP5 inhibits proliferation, invasion, migration, and promotes apoptosis via regulation of miR-299-3p/SMAD5 axis in gastric cancer cells.
    Title: Silencing of long non-coding RNA HCP5 inhibits proliferation, invasion, migration, and promotes apoptosis via regulation of miR-299-3p/SMAD5 axis in gastric cancer cells.
  8. Long non-coding RNA LINC01116 accelerates the progression of keloid formation by regulating miR-203/SMAD5 axis.
    Title: Long non-coding RNA LINC01116 accelerates the progression of keloid formation by regulating miR-203/SMAD5 axis.
  9. LINC01410 promotes cell proliferation and migration of cholangiocarcinoma through modulating miR-124-3p/SMAD5 axis.
    Title: LINC01410 promotes cell proliferation and migration of cholangiocarcinoma through modulating miR-124-3p/SMAD5 axis.
  10. KCNQ1OT1 regulates osteogenic differentiation of hBMSC by miR-320a/Smad5 axis.
    Title: KCNQ1OT1 regulates osteogenic differentiation of hBMSC by miR-320a/Smad5 axis.
Submit: New GeneRIF Correction See all GeneRIFs (66)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat-treated pulmonary arterial smooth muscle cells modulate levels of phosphorylated SMAD1/5/8 proteins and SMAD1/5/8-SMAD4 protein complex, which are repressed by cocaine exposure PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • DKFZp781C1895, DKFZp781O1323

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DEAD/H-box RNA helicase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables DNA-binding transcription factor activity IC
Inferred by Curator
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 repressor activity, RNA polymerase II-specific IEA
Inferred from Electronic Annotation
more info
  
enables I-SMAD binding IBA
Inferred from Biological aspect of Ancestor
more info
  
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 metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
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
  
involved_in BMP signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in BMP signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in Mullerian duct regression IEA
Inferred from Electronic Annotation
more info
  
involved_in SMAD protein signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in SMAD protein signal transduction ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in SMAD protein signal transduction NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in anatomical structure morphogenesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in bone development IEA
Inferred from Electronic Annotation
more info
  
involved_in cardiac conduction system development NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in cardiac muscle contraction IEA
Inferred from Electronic Annotation
more info
  
involved_in cartilage development IEA
Inferred from Electronic Annotation
more info
  
involved_in cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cellular response to organic cyclic compound IEA
Inferred from Electronic Annotation
more info
  
involved_in embryonic pattern specification ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in erythrocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in germ cell development IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within negative regulation of Fas signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of negative regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
involved_in osteoblast differentiation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in osteoblast fate commitment IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of DNA-templated transcription NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in positive regulation of osteoblast differentiation 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 by RNA polymerase II TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in signal transduction NAS
Non-traceable Author Statement
more info
 PubMed 
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 NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in ureteric bud development IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of SMAD protein complex NAS
Non-traceable Author Statement
more info
 PubMed 
part_of chromatin ISA
Inferred from Sequence Alignment
more info
  
located_in cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of heteromeric SMAD protein complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in nucleus NAS
Non-traceable Author Statement
more info
 PubMed 
located_in nucleus TAS
Traceable Author Statement
more info
 PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
mothers against decapentaplegic homolog 5
Names
MAD, mothers against decapentaplegic homolog 5
SMA- and MAD-related protein 5
SMAD, mothers against DPP homolog 5
mothers against decapentaplegic, drosophila, homolog of, 5

NCBI Reference Sequences (RefSeq)

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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_032037.1 RefSeqGene

    Range
    4999..54887
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001001419.3 → NP_001001419.1  mothers against decapentaplegic homolog 5

    See identical proteins and their annotated locations for NP_001001419.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the longest transcript. Variants 1-3 encode the same protein.
    Source sequence(s)
    AF071108, AK313397, BK001394, CR749366
    Consensus CDS
    CCDS75308.1
    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7, Q6I9T1
    Conserved Domains (2) summary
    cd10490
    Location:10 → 133
    MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
    cd10497
    Location:265 → 465
    MH2_SMAD_1_5_9; C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9

  2. NM_001001420.3 → NP_001001420.1  mothers against decapentaplegic homolog 5

    See identical proteins and their annotated locations for NP_001001420.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 2. Variants 1-3 encode the same protein.
    Source sequence(s)
    AF071106, AK313397, BK001394, CR749366
    Consensus CDS
    CCDS75308.1
    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7, Q6I9T1
    Related
    ENSP00000446474.2, ENST00000545620.5
    Conserved Domains (2) summary
    cd10490
    Location:10 → 133
    MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
    cd10497
    Location:265 → 465
    MH2_SMAD_1_5_9; C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9

  3. NM_005903.7 → NP_005894.3  mothers against decapentaplegic homolog 5

    See identical proteins and their annotated locations for NP_005894.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 2. Variants 1-3 encode the same protein.
    Source sequence(s)
    AK313397, BK001394, CR749366
    Consensus CDS
    CCDS75308.1
    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7, Q6I9T1
    Related
    ENSP00000441954.2, ENST00000545279.6
    Conserved Domains (2) summary
    cd10490
    Location:10 → 133
    MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
    cd10497
    Location:265 → 465
    MH2_SMAD_1_5_9; C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9

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_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    136132845..136182733
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024446047.2 → XP_024301815.1  mothers against decapentaplegic homolog 5 isoform X1

    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7, Q6I9T1
    Related
    ENSP00000426696.2, ENST00000509297.6
    Conserved Domains (2) summary
    cd10490
    Location:10 → 133
    MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
    cd10497
    Location:265 → 465
    MH2_SMAD_1_5_9; C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9

  2. XM_024446046.2 → XP_024301814.1  mothers against decapentaplegic homolog 5 isoform X1

    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7, Q6I9T1
    Conserved Domains (2) summary
    cd10490
    Location:10 → 133
    MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
    cd10497
    Location:265 → 465
    MH2_SMAD_1_5_9; C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9

  3. XM_017009470.3 → XP_016864959.1  mothers against decapentaplegic homolog 5 isoform X1

    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7, Q6I9T1
    Conserved Domains (2) summary
    cd10490
    Location:10 → 133
    MH1_SMAD_1_5_9; N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8)
    cd10497
    Location:265 → 465
    MH2_SMAD_1_5_9; C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    136655373..136705263
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054352585.1 → XP_054208560.1  mothers against decapentaplegic homolog 5 isoform X1

    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7

  2. XM_054352586.1 → XP_054208561.1  mothers against decapentaplegic homolog 5 isoform X1

    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7

  3. XM_054352587.1 → XP_054208562.1  mothers against decapentaplegic homolog 5 isoform X1

    UniProtKB/Swiss-Prot
    O14688, Q15798, Q99717, Q9UQA1
    UniProtKB/TrEMBL
    Q68DB7
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q99717.1 GenPept UniProtKB/Swiss-Prot:Q99717

Gene LinkOut

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