Human Gene SMAD1 (uc003ikc.3) Description and Page Index
  Description: Homo sapiens SMAD family member 1 (SMAD1), transcript variant 1, mRNA.
RefSeq Summary (NM_005900): 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 signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation. This protein is a target for SMAD-specific E3 ubiquitin ligases, such as SMURF1 and SMURF2, and undergoes ubiquitination and proteasome-mediated degradation. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr4:146,402,951-146,480,325 Size: 77,375 Total Exon Count: 7 Strand: +
Coding Region
   Position: hg19 chr4:146,435,766-146,479,086 Size: 43,321 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr4:146,402,951-146,480,325)mRNA (may differ from genome)Protein (465 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDHuman Cortex Gene ExpressionLynx
MGIneXtProtOMIMPubMedReactomeStanford SOURCE
TreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: SMAD1_HUMAN
DESCRIPTION: RecName: Full=Mothers against decapentaplegic homolog 1; Short=MAD homolog 1; Short=Mothers against DPP homolog 1; AltName: Full=JV4-1; AltName: Full=Mad-related protein 1; AltName: Full=SMAD family member 1; Short=SMAD 1; Short=Smad1; Short=hSMAD1; AltName: Full=Transforming growth factor-beta-signaling protein 1; Short=BSP-1;
FUNCTION: Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-regulated SMAD (R-SMAD). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.
SUBUNIT: Interacts with HGS, NANOG and ZCCHC12 (By similarity). May form trimers with another SMAD1 and the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP), p300, SMURF1, SMURF2, USP15 and HOXC8. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with SKOR1. Interacts (via MH2 domain) with LEMD3. Binding to LEMD3 results in at least a partial reduction of receptor-mediated phosphorylation. Forms a ternary complex with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S proteasome.
INTERACTION: P46937:YAP1; NbExp=3; IntAct=EBI-1567153, EBI-1044059;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4. Co-localizes with LEMD3 at the nucleus inner membrane.
TISSUE SPECIFICITY: Ubiquitous. Highest expression seen in the heart and skeletal muscle.
PTM: Phosphorylated on serine by BMP type 1 receptor kinase.
PTM: Ubiquitinated by SMAD-specific E3 ubiquitin ligase SMURF1, leading to its degradation. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes.
DISEASE: Defects in SMAD1 may be a cause of primary pulmonary hypertension (PPH1) [MIM:178600]. A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial PPH1 is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.
SIMILARITY: Belongs to the dwarfin/SMAD family.
SIMILARITY: Contains 1 MH1 (MAD homology 1) domain.
SIMILARITY: Contains 1 MH2 (MAD homology 2) domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): SMAD1
CDC HuGE Published Literature: SMAD1

-  MalaCards Disease Associations
  MalaCards Gene Search: SMAD1
Diseases sorted by gene-association score: buschke-ollendorff syndrome (9), osteopoikilosis (9), hereditary hemorrhagic telangiectasia (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C006780 bisphenol A
  • C006253 pirinixic acid
  • C017947 sodium arsenite
  • D015632 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • C016403 2,4-dinitrotoluene
  • C532162 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine
  • C009505 4,4'-diaminodiphenylmethane
  • C027576 4-hydroxy-2-nonenal
  • C022909 5-methoxypsoralen
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.62 RPKM in Breast - Mammary Tissue
Total median expression: 185.27 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -170.10416-0.409 Picture PostScript Text
3' UTR -304.391239-0.246 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013790 - Dwarfin
IPR003619 - MAD_homology1_Dwarfin-type
IPR013019 - MAD_homology_MH1
IPR017855 - SMAD_dom-like
IPR001132 - SMAD_dom_Dwarfin-type
IPR008984 - SMAD_FHA_domain

Pfam Domains:
PF03165 - MH1 domain
PF03166 - MH2 domain
PF10401 - Interferon-regulatory factor 3

SCOP Domains:
49879 - SMAD/FHA domain
56366 - SMAD MH1 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1KHU
- X-ray

2LAW
- NMR MuPIT

2LAX
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2LAY - NMR MuPIT 2LAZ - NMR MuPIT 2LB0 - NMR MuPIT
2LB1 - NMR MuPIT


ModBase Predicted Comparative 3D Structure on Q15797
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0017151 DEAD/H-box RNA helicase binding
GO:0019901 protein kinase binding
GO:0030618 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding
GO:0046982 protein heterodimerization activity
GO:0070410 co-SMAD binding
GO:0070411 I-SMAD binding
GO:0070878 primary miRNA binding

Biological Process:
GO:0000165 MAPK cascade
GO:0001657 ureteric bud development
GO:0001710 mesodermal cell fate commitment
GO:0002051 osteoblast fate commitment
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0006468 protein phosphorylation
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007183 SMAD protein complex assembly
GO:0007276 gamete generation
GO:0008285 negative regulation of cell proliferation
GO:0009880 embryonic pattern specification
GO:0010628 positive regulation of gene expression
GO:0016579 protein deubiquitination
GO:0030509 BMP signaling pathway
GO:0030901 midbrain development
GO:0030902 hindbrain development
GO:0031053 primary miRNA processing
GO:0042592 homeostatic process
GO:0045669 positive regulation of osteoblast differentiation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051216 cartilage development
GO:0060038 cardiac muscle cell proliferation
GO:0060348 bone development
GO:0060395 SMAD protein signal transduction
GO:0061036 positive regulation of cartilage development
GO:0071407 cellular response to organic cyclic compound
GO:0071773 cellular response to BMP stimulus
GO:1901522 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter
GO:1903672 positive regulation of sprouting angiogenesis

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005637 nuclear inner membrane
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016021 integral component of membrane
GO:0032991 macromolecular complex
GO:0071141 SMAD protein complex


-  Descriptions from all associated GenBank mRNAs
  U59423 - Human Smad1 mRNA, complete cds.
BC001878 - Homo sapiens SMAD family member 1, mRNA (cDNA clone MGC:1376 IMAGE:3546771), complete cds.
U59912 - Human chromosome 4 Mad homolog Smad1 mRNA, complete cds.
U54826 - Human mad-related protein MADR1 mRNA, complete cds.
AK293055 - Homo sapiens cDNA FLJ75507 complete cds, highly similar to Homo sapiens SMAD, mothers against DPP homolog 1 (Drosophila) (SMAD1), transcript variant 2, mRNA.
JD560435 - Sequence 541459 from Patent EP1572962.
JD464132 - Sequence 445156 from Patent EP1572962.
U57456 - Human transforming growth factor-beta signaling protein-1 (bsp-1) mRNA, complete cds.
JD175030 - Sequence 156054 from Patent EP1572962.
JD287285 - Sequence 268309 from Patent EP1572962.
CU674906 - Synthetic construct Homo sapiens gateway clone IMAGE:100019525 5' read SMAD1 mRNA.
AB463262 - Synthetic construct DNA, clone: pF1KB5319, Homo sapiens SMAD1 gene for SMAD family member 1, without stop codon, in Flexi system.
DQ895724 - Synthetic construct Homo sapiens clone IMAGE:100010184; FLH187013.01L; RZPDo839C1162D SMAD, mothers against DPP homolog 1 (Drosophila) (SMAD1) gene, encodes complete protein.
BT007386 - Homo sapiens MAD, mothers against decapentaplegic homolog 1 (Drosophila) mRNA, complete cds.
DQ892510 - Synthetic construct clone IMAGE:100005140; FLH187017.01X; RZPDo839C1172D SMAD, mothers against DPP homolog 1 (Drosophila) (SMAD1) gene, encodes complete protein.
KJ891566 - Synthetic construct Homo sapiens clone ccsbBroadEn_00960 SMAD1 gene, encodes complete protein.
BC069711 - Homo sapiens cDNA clone IMAGE:7262571, with apparent retained intron.
BC069781 - Homo sapiens cDNA clone IMAGE:7262583, with apparent retained intron.
BC069804 - Homo sapiens cDNA clone IMAGE:7262595, with apparent retained intron.
AK096624 - Homo sapiens cDNA FLJ39305 fis, clone OCBBF2013091.
JD238859 - Sequence 219883 from Patent EP1572962.
JD503473 - Sequence 484497 from Patent EP1572962.
JD304735 - Sequence 285759 from Patent EP1572962.
JD103557 - Sequence 84581 from Patent EP1572962.
JD566335 - Sequence 547359 from Patent EP1572962.
JD369088 - Sequence 350112 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04350 - TGF-beta signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q15797 (Reactome details) participates in the following event(s):

R-HSA-201422 Phospho-R-Smad1/5/8 forms a complex with Co-Smad
R-HSA-202626 I-Smad competes with Co-Smad for R-Smad1/5/8
R-HSA-201453 Phospho-R-Smad1/5/8 dissociates from the receptor complex
R-HSA-201648 An anchoring protein, Endofin, recruits R-Smad1/5/8
R-HSA-8877941 RUNX2 binds SMAD1 in the nucleus
R-HSA-201472 The phospho-R-Smad1/5/8:Co-Smad transfers to the nucleus
R-HSA-201476 Activated type I receptor phosphorylates R-Smad1/5/8 directly
R-HSA-6781764 USP15 deubiquitinates SMAD1,SMAD2,SMAD3, SMAD7:SMURF,KEAP1
R-HSA-8878013 RUNX2 and SMAD1 complex binds the SMAD6 gene promoter
R-HSA-201423 SKI complexes with the Smad complex, suppressing BMP2 signalling
R-HSA-201451 Signaling by BMP
R-HSA-8941326 RUNX2 regulates bone development
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-5689880 Ub-specific processing proteases
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-162582 Signal Transduction
R-HSA-5688426 Deubiquitination
R-HSA-212436 Generic Transcription Pathway
R-HSA-597592 Post-translational protein modification
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-392499 Metabolism of proteins
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A8KAJ0, BSP1, D3DNZ9, MADH1, MADR1, NM_005900, NP_005891, Q15797, Q16636, SMAD1_HUMAN
UCSC ID: uc003ikc.3
RefSeq Accession: NM_005900
Protein: Q15797 (aka SMAD1_HUMAN or SMA1_HUMAN)
CCDS: CCDS3765.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005900.2
exon count: 7CDS single in 3' UTR: no RNA size: 3056
ORF size: 1398CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2954.00frame shift in genome: no % Coverage: 99.90
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.