Human Gene SMAD5 (uc003lbl.1) Description and Page Index
  Description: Homo sapiens SMAD family member 5 (SMAD5), transcript variant 3, mRNA.
RefSeq Summary (NM_001001420): 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].
Transcript (Including UTRs)
   Position: hg19 chr5:135,468,536-135,518,422 Size: 49,887 Total Exon Count: 8 Strand: +
Coding Region
   Position: hg19 chr5:135,489,450-135,513,168 Size: 23,719 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:135,468,536-135,518,422)mRNA (may differ from genome)Protein (465 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
H-INVHGNCLynxMGIneXtProtOMIM
PubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: SMAD5_HUMAN
DESCRIPTION: RecName: Full=Mothers against decapentaplegic homolog 5; Short=MAD homolog 5; Short=Mothers against DPP homolog 5; AltName: Full=JV5-1; AltName: Full=SMAD family member 5; Short=SMAD 5; Short=Smad5; Short=hSmad5;
FUNCTION: Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).
SUBUNIT: May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1.
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.
TISSUE SPECIFICITY: Ubiquitous.
PTM: Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.
PTM: Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.
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): SMAD5
CDC HuGE Published Literature: SMAD5

-  MalaCards Disease Associations
  MalaCards Gene Search: SMAD5
Diseases sorted by gene-association score: deafness, autosomal dominant 52 (3)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           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: 13.30 RPKM in Ovary
Total median expression: 349.54 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 -102.10285-0.358 Picture PostScript Text
3' UTR -1344.745254-0.256 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

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

ModBase Predicted Comparative 3D Structure on Q99717
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 BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
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: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:0030618 transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity
GO:0031625 ubiquitin protein ligase binding
GO:0046872 metal ion binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001503 ossification
GO:0001657 ureteric bud development
GO:0001880 Mullerian duct regression
GO:0002051 osteoblast fate commitment
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006468 protein phosphorylation
GO:0007165 signal transduction
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007281 germ cell development
GO:0009880 embryonic pattern specification
GO:0030218 erythrocyte differentiation
GO:0030509 BMP signaling pathway
GO:0045669 positive regulation of osteoblast differentiation
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0051216 cartilage development
GO:0060048 cardiac muscle contraction
GO:0060348 bone development
GO:0060395 SMAD protein signal transduction
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

Cellular Component:
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0032991 macromolecular complex
GO:0071141 SMAD protein complex


-  Descriptions from all associated GenBank mRNAs
  AK313397 - Homo sapiens cDNA, FLJ93932, Homo sapiens MAD, mothers against decapentaplegic homolog 5 (Drosophila) (MADH5), mRNA.
AF009745 - Homo sapiens MAD homolog Smad5 mRNA, 5'UTR.
AF071106 - Homo sapiens SMAD5 splice variant A (SMAD5) mRNA, 5'UTR and partial cds.
AF071107 - Homo sapiens SMAD5 splice variant B (SMAD5) mRNA, 5'UTR and partial cds.
AF071108 - Homo sapiens SMAD5 splice variant C (SMAD5) mRNA, 5'UTR and partial cds.
AK311231 - Homo sapiens cDNA, FLJ18273.
CR749366 - Homo sapiens mRNA; cDNA DKFZp781C1895 (from clone DKFZp781C1895).
BX648328 - Homo sapiens mRNA; cDNA DKFZp686H02163 (from clone DKFZp686H02163).
CR749473 - Homo sapiens mRNA; cDNA DKFZp781O1323 (from clone DKFZp781O1323).
AF071109 - Homo sapiens SMAD5 splice variant D (SMAD5) mRNA, 5'UTR and partial cds.
AF071110 - Homo sapiens SMAD5 splice variant E (SMAD5) mRNA, 5'UTR and partial cds.
BC009682 - Homo sapiens SMAD family member 5, mRNA (cDNA clone MGC:8960 IMAGE:3906006), complete cds.
JD087422 - Sequence 68446 from Patent EP1572962.
U73825 - Homo sapiens Smad5 mRNA, complete cds.
AF010601 - Homo sapiens SMAD5 (Smad5) mRNA, complete cds.
U59913 - Human chromosome 5 Mad homolog Smad5 mRNA, complete cds.
AF009678 - Homo sapiens Smad5 (Smad5) mRNA, complete cds.
CU679439 - Synthetic construct Homo sapiens gateway clone IMAGE:100017326 5' read SMAD5 mRNA.
AB464214 - Synthetic construct DNA, clone: pF1KB7706, Homo sapiens SMAD5 gene for SMAD family member 5, without stop codon, in Flexi system.
HQ448272 - Synthetic construct Homo sapiens clone IMAGE:100071675; CCSB000163_03 SMAD family member 5 (SMAD5) gene, encodes complete protein.
KJ891569 - Synthetic construct Homo sapiens clone ccsbBroadEn_00963 SMAD5 gene, encodes complete protein.
CR457424 - Homo sapiens full open reading frame cDNA clone RZPDo834A1214D for gene MADH5, MAD, mothers against decapentaplegic homolog 5 (Drosophila); complete cds, incl. stopcodon.
JD023842 - Sequence 4866 from Patent EP1572962.
JD025999 - Sequence 7023 from Patent EP1572962.
JD031699 - Sequence 12723 from Patent EP1572962.
JD027719 - Sequence 8743 from Patent EP1572962.
JD022963 - Sequence 3987 from Patent EP1572962.
JD028527 - Sequence 9551 from Patent EP1572962.
JD317081 - Sequence 298105 from Patent EP1572962.
JD378923 - Sequence 359947 from Patent EP1572962.
JD354212 - Sequence 335236 from Patent EP1572962.
JD072801 - Sequence 53825 from Patent EP1572962.
AK055211 - Homo sapiens cDNA FLJ30649 fis, clone CTONG2006562.
AK001036 - Homo sapiens cDNA FLJ10174 fis, clone HEMBA1003959.

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

BioCarta from NCI Cancer Genome Anatomy Project
h_alkPathway - ALK in cardiac myocytes
h_ctcfPathway - CTCF: First Multivalent Nuclear Factor

Reactome (by CSHL, EBI, and GO)

Protein Q99717 (Reactome details) participates in the following event(s):

R-HSA-201648 An anchoring protein, Endofin, recruits R-Smad1/5/8
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-201476 Activated type I receptor phosphorylates R-Smad1/5/8 directly
R-HSA-201423 SKI complexes with the Smad complex, suppressing BMP2 signalling
R-HSA-201472 The phospho-R-Smad1/5/8:Co-Smad transfers to the nucleus
R-HSA-201451 Signaling by BMP
R-HSA-9006936 Signaling by TGF-beta family members
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: MADH5, NM_001001420, NP_001001420, O14688, Q15798, Q99717, Q9UQA1, SMAD5_HUMAN
UCSC ID: uc003lbl.1
RefSeq Accession: NM_001001420
Protein: Q99717 (aka SMAD5_HUMAN or SMA5_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001001420.1
exon count: 7CDS single in 3' UTR: no RNA size: 6937
ORF size: 1397CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2773.00frame shift in genome: yes % Coverage: 99.96
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.