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Protein

Mothers against decapentaplegic homolog 9

Gene

SMAD9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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)DescriptionActionsGraphical viewLength
Metal bindingi68ZincBy similarity1
Metal bindingi113ZincBy similarity1
Metal bindingi125ZincBy similarity1
Metal bindingi130ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000120693-MONOMER.
ReactomeiR-HSA-201451. Signaling by BMP.
SIGNORiO15198.

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
Proteomesi
  • UP000005640 Componenti: 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

  • cytoplasm Source: BHF-UCL
  • cytosol Source: Reactome
  • intracellular Source: ProtInc
  • nucleoplasm Source: HPA
  • nucleus Source: BHF-UCL
  • SMAD protein complex Source: BHF-UCL
  • transcription factor complex Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Pulmonary hypertension, primary, 2 (PPH2)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615342
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06687143K → E in PPH2; affects SMAD-mediated signaling. 1 PublicationCorresponds to variant rs397514715dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4093.
MalaCardsiSMAD9.
MIMi615342. phenotype.
OpenTargetsiENSG00000120693.
Orphaneti275777. Heritable pulmonary arterial hypertension.
PharmGKBiPA30531.

Polymorphism and mutation databases

BioMutaiSMAD9.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000908751 – 467Mothers against decapentaplegic homolog 9Add BLAST467

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO15198.
PaxDbiO15198.
PeptideAtlasiO15198.
PRIDEiO15198.

PTM databases

iPTMnetiO15198.
PhosphoSitePlusiO15198.

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

BgeeiENSG00000120693.
CleanExiHS_SMAD9.
ExpressionAtlasiO15198. baseline and differential.
GenevisibleiO15198. HS.

Organism-specific databases

HPAiCAB009119.
HPA031162.

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. 111 interactors.
IntActiO15198. 99 interactors.
MINTiMINT-1179670.
STRINGi9606.ENSP00000369154.

Structurei

3D structure databases

ProteinModelPortaliO15198.
SMRiO15198.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 140MH1PROSITE-ProRule annotationAdd BLAST125
Domaini273 – 467MH2PROSITE-ProRule annotationAdd BLAST195

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi43 – 49Poly-Lys7

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

eggNOGiKOG3701. Eukaryota.
ENOG410XQKU. LUCA.
GeneTreeiENSGT00760000119091.
HOGENOMiHOG000286018.
HOVERGENiHBG053353.
InParanoidiO15198.
KOiK16791.
OMAiFQQPPCP.
OrthoDBiEOG091G082C.
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. AlignAdd to basket

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

        10         20         30         40         50
MHSTTPISSL FSFTSPAVKR LLGWKQGDEE EKWAEKAVDS LVKKLKKKKG
60 70 80 90 100
AMDELERALS CPGQPSKCVT IPRSLDGRLQ VSHRKGLPHV IYCRVWRWPD
110 120 130 140 150
LQSHHELKPL ECCEFPFGSK QKEVCINPYH YRRVETPVLP PVLVPRHSEY
160 170 180 190 200
NPQLSLLAKF RSASLHSEPL MPHNATYPDS FQQPPCSALP PSPSHAFSQS
210 220 230 240 250
PCTASYPHSP GSPSEPESPY QHSVDTPPLP YHATEASETQ SGQPVDATAD
260 270 280 290 300
RHVVLSIPNG DFRPVCYEEP QHWCSVAYYE LNNRVGETFQ ASSRSVLIDG
310 320 330 340 350
FTDPSNNRNR FCLGLLSNVN RNSTIENTRR HIGKGVHLYY VGGEVYAECV
360 370 380 390 400
SDSSIFVQSR NCNYQHGFHP ATVCKIPSGC SLKVFNNQLF AQLLAQSVHH
410 420 430 440 450
GFEVVYELTK MCTIRMSFVK GWGAEYHRQD VTSTPCWIEI HLHGPLQWLD
460
KVLTQMGSPH NPISSVS
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_06687143K → E in PPH2; affects SMAD-mediated signaling. 1 PublicationCorresponds to variant rs397514715dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006182224 – 260Missing in isoform B. 2 PublicationsAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliO15198.
SMRiO15198.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110268. 111 interactors.
IntActiO15198. 99 interactors.
MINTiMINT-1179670.
STRINGi9606.ENSP00000369154.

PTM databases

iPTMnetiO15198.
PhosphoSitePlusiO15198.

Polymorphism and mutation databases

BioMutaiSMAD9.

Proteomic databases

MaxQBiO15198.
PaxDbiO15198.
PeptideAtlasiO15198.
PRIDEiO15198.

Protocols and materials databases

DNASUi4093.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi4093.
DisGeNETi4093.
GeneCardsiSMAD9.
HGNCiHGNC:6774. SMAD9.
HPAiCAB009119.
HPA031162.
MalaCardsiSMAD9.
MIMi603295. gene.
615342. phenotype.
neXtProtiNX_O15198.
OpenTargetsiENSG00000120693.
Orphaneti275777. Heritable pulmonary arterial hypertension.
PharmGKBiPA30531.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3701. Eukaryota.
ENOG410XQKU. LUCA.
GeneTreeiENSGT00760000119091.
HOGENOMiHOG000286018.
HOVERGENiHBG053353.
InParanoidiO15198.
KOiK16791.
OMAiFQQPPCP.
OrthoDBiEOG091G082C.
PhylomeDBiO15198.
TreeFamiTF314923.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000120693-MONOMER.
ReactomeiR-HSA-201451. Signaling by BMP.
SIGNORiO15198.

Miscellaneous databases

ChiTaRSiSMAD9. human.
GeneWikiiMothers_against_decapentaplegic_homolog_9.
GenomeRNAii4093.
PROiO15198.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120693.
CleanExiHS_SMAD9.
ExpressionAtlasiO15198. baseline and differential.
GenevisibleiO15198. HS.

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]
ProtoNetiSearch...

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: November 2, 2016
This is version 177 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.