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O15198

- SMAD9_HUMAN

UniProt

O15198 - SMAD9_HUMAN

Protein

Mothers against decapentaplegic homolog 9

Gene

SMAD9

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 155 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi68 – 681ZincBy similarity
    Metal bindingi113 – 1131ZincBy similarity
    Metal bindingi125 – 1251ZincBy similarity
    Metal bindingi130 – 1301ZincBy similarity

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. protein binding Source: IntAct
    4. sequence-specific DNA binding transcription factor activity Source: InterPro
    5. transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: BHF-UCL

    GO - Biological processi

    1. BMP signaling pathway Source: BHF-UCL
    2. bone development Source: Ensembl
    3. cartilage development Source: Ensembl
    4. cellular response to organic cyclic compound Source: Ensembl
    5. hindbrain development Source: Ensembl
    6. intracellular signal transduction Source: GOC
    7. midbrain development Source: Ensembl
    8. Mullerian duct regression Source: Ensembl
    9. positive regulation of cell differentiation Source: Ensembl
    10. positive regulation of transcription, DNA-templated Source: Ensembl
    11. protein phosphorylation Source: Ensembl
    12. response to hypoxia Source: Ensembl
    13. transcription, DNA-templated Source: UniProtKB-KW
    14. transforming growth factor beta receptor signaling pathway Source: InterPro
    15. ureteric bud development Source: Ensembl

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_12034. Signaling by BMP.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:SMAD9
    Synonyms:MADH6, MADH9
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 13

    Organism-specific databases

    HGNCiHGNC:6774. SMAD9.

    Subcellular locationi

    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.By similarity

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. intracellular Source: ProtInc
    3. nucleoplasm Source: Reactome
    4. nucleus Source: BHF-UCL
    5. transcription factor complex Source: InterPro

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    Note: The disease may be caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti43 – 431K → E in PPH2; affects SMAD-mediated signaling. 1 Publication
    VAR_066871

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi615342. phenotype.
    Orphaneti275777. Heritable pulmonary arterial hypertension.
    PharmGKBiPA30531.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 467467Mothers against decapentaplegic homolog 9PRO_0000090875Add
    BLAST

    Post-translational modificationi

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

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO15198.
    PaxDbiO15198.
    PRIDEiO15198.

    PTM databases

    PhosphoSiteiO15198.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    BgeeiO15198.
    CleanExiHS_SMAD9.
    GenevestigatoriO15198.

    Organism-specific databases

    HPAiCAB009119.

    Interactioni

    Subunit structurei

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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    KDM1AO603412EBI-748763,EBI-710124
    PRMT6Q96LA82EBI-748763,EBI-912440

    Protein-protein interaction databases

    BioGridi110268. 108 interactions.
    IntActiO15198. 99 interactions.
    MINTiMINT-1179670.
    STRINGi9606.ENSP00000369154.

    Structurei

    3D structure databases

    ProteinModelPortaliO15198.
    SMRiO15198. Positions 13-136, 270-467.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini16 – 140125MH1PROSITE-ProRule annotationAdd
    BLAST
    Domaini273 – 467195MH2PROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi43 – 497Poly-Lys

    Sequence similaritiesi

    Belongs to the dwarfin/SMAD family.Curated
    Contains 1 MH1 (MAD homology 1) domain.PROSITE-ProRule annotation
    Contains 1 MH2 (MAD homology 2) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG330956.
    HOGENOMiHOG000286018.
    HOVERGENiHBG053353.
    InParanoidiO15198.
    KOiK16791.
    OMAiFQQPPCP.
    OrthoDBiEOG7W1540.
    PhylomeDBiO15198.
    TreeFamiTF314923.

    Family and domain databases

    Gene3Di2.60.200.10. 1 hit.
    3.90.520.10. 1 hit.
    InterProiIPR013790. 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]
    PANTHERiPTHR13703. PTHR13703. 1 hit.
    PfamiPF03165. MH1. 1 hit.
    PF03166. MH2. 1 hit.
    [Graphical view]
    SMARTiSM00523. DWA. 1 hit.
    SM00524. DWB. 1 hit.
    [Graphical view]
    SUPFAMiSSF49879. SSF49879. 1 hit.
    SSF56366. SSF56366. 1 hit.
    PROSITEiPS51075. MH1. 1 hit.
    PS51076. MH2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform A (identifier: O15198-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MHSTTPISSL FSFTSPAVKR LLGWKQGDEE EKWAEKAVDS LVKKLKKKKG    50
    AMDELERALS CPGQPSKCVT IPRSLDGRLQ VSHRKGLPHV IYCRVWRWPD 100
    LQSHHELKPL ECCEFPFGSK QKEVCINPYH YRRVETPVLP PVLVPRHSEY 150
    NPQLSLLAKF RSASLHSEPL MPHNATYPDS FQQPPCSALP PSPSHAFSQS 200
    PCTASYPHSP GSPSEPESPY QHSVDTPPLP YHATEASETQ SGQPVDATAD 250
    RHVVLSIPNG DFRPVCYEEP QHWCSVAYYE LNNRVGETFQ ASSRSVLIDG 300
    FTDPSNNRNR FCLGLLSNVN RNSTIENTRR HIGKGVHLYY VGGEVYAECV 350
    SDSSIFVQSR NCNYQHGFHP ATVCKIPSGC SLKVFNNQLF AQLLAQSVHH 400
    GFEVVYELTK MCTIRMSFVK GWGAEYHRQD VTSTPCWIEI HLHGPLQWLD 450
    KVLTQMGSPH NPISSVS 467
    Length:467
    Mass (Da):52,493
    Last modified:January 1, 1998 - v1
    Checksum:iCFC8F982945BC6DD
    GO
    Isoform B (identifier: O15198-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:430
    Mass (Da):48,640
    Checksum:i6C9E4BB90DEB4B1B
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti43 – 431K → E in PPH2; affects SMAD-mediated signaling. 1 Publication
    VAR_066871

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei224 – 26037Missing in isoform B. 2 PublicationsVSP_006182Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS45032.1. [O15198-1]
    CCDS9360.1. [O15198-2]
    RefSeqiNP_001120689.1. NM_001127217.2. [O15198-1]
    NP_005896.1. NM_005905.5. [O15198-2]
    UniGeneiHs.123119.

    Genome annotation databases

    EnsembliENST00000350148; ENSP00000239885; ENSG00000120693. [O15198-2]
    ENST00000379826; ENSP00000369154; ENSG00000120693. [O15198-1]
    ENST00000399275; ENSP00000382216; ENSG00000120693. [O15198-1]
    GeneIDi4093.
    KEGGihsa:4093.
    UCSCiuc001uvw.3. human. [O15198-1]
    uc001uvx.3. human. [O15198-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS45032.1. [O15198-1 ]
    CCDS9360.1. [O15198-2 ]
    RefSeqi NP_001120689.1. NM_001127217.2. [O15198-1 ]
    NP_005896.1. NM_005905.5. [O15198-2 ]
    UniGenei Hs.123119.

    3D structure databases

    ProteinModelPortali O15198.
    SMRi O15198. Positions 13-136, 270-467.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110268. 108 interactions.
    IntActi O15198. 99 interactions.
    MINTi MINT-1179670.
    STRINGi 9606.ENSP00000369154.

    PTM databases

    PhosphoSitei O15198.

    Proteomic databases

    MaxQBi O15198.
    PaxDbi O15198.
    PRIDEi O15198.

    Protocols and materials databases

    DNASUi 4093.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000350148 ; ENSP00000239885 ; ENSG00000120693 . [O15198-2 ]
    ENST00000379826 ; ENSP00000369154 ; ENSG00000120693 . [O15198-1 ]
    ENST00000399275 ; ENSP00000382216 ; ENSG00000120693 . [O15198-1 ]
    GeneIDi 4093.
    KEGGi hsa:4093.
    UCSCi uc001uvw.3. human. [O15198-1 ]
    uc001uvx.3. human. [O15198-2 ]

    Organism-specific databases

    CTDi 4093.
    GeneCardsi GC13M037418.
    HGNCi HGNC:6774. SMAD9.
    HPAi CAB009119.
    MIMi 603295. gene.
    615342. phenotype.
    neXtProti NX_O15198.
    Orphaneti 275777. Heritable pulmonary arterial hypertension.
    PharmGKBi PA30531.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG330956.
    HOGENOMi HOG000286018.
    HOVERGENi HBG053353.
    InParanoidi O15198.
    KOi K16791.
    OMAi FQQPPCP.
    OrthoDBi EOG7W1540.
    PhylomeDBi O15198.
    TreeFami TF314923.

    Enzyme and pathway databases

    Reactomei REACT_12034. Signaling by BMP.

    Miscellaneous databases

    GeneWikii Mothers_against_decapentaplegic_homolog_9.
    GenomeRNAii 4093.
    NextBioi 16050.
    PROi O15198.
    SOURCEi Search...

    Gene expression databases

    Bgeei O15198.
    CleanExi HS_SMAD9.
    Genevestigatori O15198.

    Family and domain databases

    Gene3Di 2.60.200.10. 1 hit.
    3.90.520.10. 1 hit.
    InterProi IPR013790. 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 ]
    PANTHERi PTHR13703. PTHR13703. 1 hit.
    Pfami PF03165. MH1. 1 hit.
    PF03166. MH2. 1 hit.
    [Graphical view ]
    SMARTi SM00523. DWA. 1 hit.
    SM00524. DWB. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49879. SSF49879. 1 hit.
    SSF56366. SSF56366. 1 hit.
    PROSITEi PS51075. MH1. 1 hit.
    PS51076. MH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. Cited for: REVIEW.
    8. Cited for: REVIEW.
    9. Cited for: VARIANT PPH2 GLU-43, CHARACTERIZATION OF VARIANT PPH2 GLU-43.

    Entry informationi

    Entry nameiSMAD9_HUMAN
    AccessioniPrimary (citable) accession number: O15198
    Secondary accession number(s): A2A2Y6, O14989, Q5TBA1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 4, 2001
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 155 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 13
      Human chromosome 13: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3