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O15198 (SMAD9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mothers against decapentaplegic homolog 9

Short name=MAD homolog 9
Short name=Mothers against DPP homolog 9
Alternative name(s):
Madh6
SMAD family member 9
Short name=SMAD 9
Short name=Smad9
Gene names
Name:SMAD9
Synonyms:MADH6, MADH9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD9 is a receptor-regulated SMAD (R-SMAD).

Subunit structure

Interaction with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Note: In the cytoplasm in the absence of ligand. Migration to the nucleus when complexed with SMAD4 By similarity.

Tissue specificity

Expressed in heart, brain, placenta, lung, skeletal muscle, prostate, testis, ovary and small intestine. Also expressed in fetal brain, lung and kidney.

Post-translational modification

Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.

Involvement in disease

Pulmonary hypertension, primary, 2 (PPH2) [MIM:615342]: 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 pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.
Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities

Belongs to the dwarfin/SMAD family.

Contains 1 MH1 (MAD homology 1) domain.

Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   LigandDNA-binding
Metal-binding
Zinc
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Traceable author statement PubMed 19018011. Source: BHF-UCL

Mullerian duct regression

Inferred from electronic annotation. Source: Ensembl

bone development

Inferred from electronic annotation. Source: Ensembl

cartilage development

Inferred from electronic annotation. Source: Ensembl

cellular response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

hindbrain development

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Traceable author statement PubMed 19018011. Source: GOC

midbrain development

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transforming growth factor beta receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

ureteric bud development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

intracellular

Traceable author statement PubMed 9256479. Source: ProtInc

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement PubMed 19018011. Source: BHF-UCL

transcription factor complex

Inferred from electronic annotation. Source: InterPro

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity

Traceable author statement PubMed 19018011. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

KDM1AO603412EBI-748763,EBI-710124
PRMT6Q96LA82EBI-748763,EBI-912440

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: O15198-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform B (identifier: O15198-2)

The sequence of this isoform differs from the canonical sequence as follows:
     224-260: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 467467Mothers against decapentaplegic homolog 9
PRO_0000090875

Regions

Domain16 – 140125MH1
Domain273 – 467195MH2
Compositional bias43 – 497Poly-Lys

Sites

Metal binding681Zinc By similarity
Metal binding1131Zinc By similarity
Metal binding1251Zinc By similarity
Metal binding1301Zinc By similarity

Natural variations

Alternative sequence224 – 26037Missing in isoform B.
VSP_006182
Natural variant431K → E in PPH2; affects SMAD-mediated signaling. Ref.9
VAR_066871

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: CFC8F982945BC6DD

FASTA46752,493
        10         20         30         40         50         60 
MHSTTPISSL FSFTSPAVKR LLGWKQGDEE EKWAEKAVDS LVKKLKKKKG AMDELERALS 

        70         80         90        100        110        120 
CPGQPSKCVT IPRSLDGRLQ VSHRKGLPHV IYCRVWRWPD LQSHHELKPL ECCEFPFGSK 

       130        140        150        160        170        180 
QKEVCINPYH YRRVETPVLP PVLVPRHSEY NPQLSLLAKF RSASLHSEPL MPHNATYPDS 

       190        200        210        220        230        240 
FQQPPCSALP PSPSHAFSQS PCTASYPHSP GSPSEPESPY QHSVDTPPLP YHATEASETQ 

       250        260        270        280        290        300 
SGQPVDATAD RHVVLSIPNG DFRPVCYEEP QHWCSVAYYE LNNRVGETFQ ASSRSVLIDG 

       310        320        330        340        350        360 
FTDPSNNRNR FCLGLLSNVN RNSTIENTRR HIGKGVHLYY VGGEVYAECV SDSSIFVQSR 

       370        380        390        400        410        420 
NCNYQHGFHP ATVCKIPSGC SLKVFNNQLF AQLLAQSVHH GFEVVYELTK MCTIRMSFVK 

       430        440        450        460 
GWGAEYHRQD VTSTPCWIEI HLHGPLQWLD KVLTQMGSPH NPISSVS 

« Hide

Isoform B [UniParc].

Checksum: 6C9E4BB90DEB4B1B
Show »

FASTA43048,640

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel member of the human Mad gene family (MADH6)."
Watanabe T.K., Suzuki M., Omori Y., Hishigaki H., Horie M., Kanemoto N., Fujiwara T., Nakamura Y., Takahashi E.
Genomics 42:446-451(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
Tissue: Fetal brain.
[2]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
Tissue: Brain and Eye.
[5]"TGF-beta signal transduction."
Massague J.
Annu. Rev. Biochem. 67:753-791(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[6]"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells."
Verschueren K., Huylebroeck D.
Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[7]"The Smad pathway."
Wrana J.L., Attisano L.
Cytokine Growth Factor Rev. 11:5-13(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[8]"TGF-beta signaling by Smad proteins."
Miyazono K.
Cytokine Growth Factor Rev. 11:15-22(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]"Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertension."
Nasim M.T., Ogo T., Ahmed M., Randall R., Chowdhury H.M., Snape K.M., Bradshaw T.Y., Southgate L., Lee G.J., Jackson I., Lord G.M., Gibbs J.S., Wilkins M.R., Ohta-Ogo K., Nakamura K., Girerd B., Coulet F., Soubrier F. expand/collapse author list , Humbert M., Morrell N.W., Trembath R.C., Machado R.D.
Hum. Mutat. 32:1385-1389(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PPH2 GLU-43, CHARACTERIZATION OF VARIANT PPH2 GLU-43.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D83760 mRNA. Translation: BAA21128.1.
D83761 mRNA. Translation: BAA21129.1.
AL138706 Genomic DNA. Translation: CAI14007.1.
AL138706 Genomic DNA. Translation: CAM19158.1.
CH471075 Genomic DNA. Translation: EAX08571.1.
CH471075 Genomic DNA. Translation: EAX08572.1.
BC011559 mRNA. Translation: AAH11559.1.
BC104760 mRNA. Translation: AAI04761.1.
BC104762 mRNA. Translation: AAI04763.1.
BC143240 mRNA. Translation: AAI43241.1.
RefSeqNP_001120689.1. NM_001127217.2.
NP_005896.1. NM_005905.5.
UniGeneHs.123119.

3D structure databases

ProteinModelPortalO15198.
SMRO15198. Positions 13-136, 270-467.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110268. 108 interactions.
IntActO15198. 99 interactions.
MINTMINT-1179670.
STRING9606.ENSP00000369154.

PTM databases

PhosphoSiteO15198.

Proteomic databases

PaxDbO15198.
PRIDEO15198.

Protocols and materials databases

DNASU4093.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000350148; ENSP00000239885; ENSG00000120693. [O15198-2]
ENST00000379826; ENSP00000369154; ENSG00000120693. [O15198-1]
ENST00000399275; ENSP00000382216; ENSG00000120693. [O15198-1]
GeneID4093.
KEGGhsa:4093.
UCSCuc001uvw.3. human. [O15198-1]
uc001uvx.3. human. [O15198-2]

Organism-specific databases

CTD4093.
GeneCardsGC13M037418.
HGNCHGNC:6774. SMAD9.
HPACAB009119.
MIM603295. gene.
615342. phenotype.
neXtProtNX_O15198.
Orphanet275777. Heritable pulmonary arterial hypertension.
PharmGKBPA30531.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG330956.
HOGENOMHOG000286018.
HOVERGENHBG053353.
InParanoidO15198.
KOK16791.
OMAFQQPPCP.
OrthoDBEOG7W1540.
PhylomeDBO15198.
TreeFamTF314923.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeO15198.
CleanExHS_SMAD9.
GenevestigatorO15198.

Family and domain databases

Gene3D2.60.200.10. 1 hit.
3.90.520.10. 1 hit.
InterProIPR013790. Dwarfin.
IPR003619. MAD_homology1_Dwarfin-type.
IPR013019. MAD_homology_MH1.
IPR017855. SMAD_dom-like.
IPR001132. SMAD_dom_Dwarfin-type.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PANTHERPTHR13703. PTHR13703. 1 hit.
PfamPF03165. MH1. 1 hit.
PF03166. MH2. 1 hit.
[Graphical view]
SMARTSM00523. DWA. 1 hit.
SM00524. DWB. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
SSF56366. SSF56366. 1 hit.
PROSITEPS51075. MH1. 1 hit.
PS51076. MH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMothers_against_decapentaplegic_homolog_9.
GenomeRNAi4093.
NextBio16050.
PROO15198.
SOURCESearch...

Entry information

Entry nameSMAD9_HUMAN
AccessionPrimary (citable) accession number: O15198
Secondary accession number(s): A2A2Y6, O14989, Q5TBA1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 4, 2001
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM