O15198 (SMAD9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SMAD9
Synonyms:	MADH6, MADH9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Protein existence	Evidence 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	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. 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 process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	DNA-binding Metal-binding Zinc
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Traceable author statement PubMed 19018011. Source: BHF-UCL Mullerian duct regression Inferred from electronic annotation. Source: Compara bone development Inferred from electronic annotation. Source: Compara cartilage development Inferred from electronic annotation. Source: Compara cellular response to organic cyclic compound Inferred from electronic annotation. Source: Compara hindbrain development Inferred from electronic annotation. Source: Compara midbrain development Inferred from electronic annotation. Source: Compara positive regulation of cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara protein phosphorylation Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara transcription, DNA-dependent 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: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular_function	DNA 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...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 467	467	Mothers against decapentaplegic homolog 9		PRO_0000090875
Regions
	Domain	16 – 140	125	MH1
	Domain	273 – 467	195	MH2
	Compositional bias	43 – 49	7	Poly-Lys
Sites
	Metal binding	68	1	Zinc By similarity
	Metal binding	113	1	Zinc By similarity
	Metal binding	125	1	Zinc By similarity
	Metal binding	130	1	Zinc By similarity
Natural variations
	Alternative sequence	224 – 260	37	Missing in isoform B.		VSP_006182
	Natural variant	43	1	K → E in PPH1; affects SMAD-mediated signaling. Ref.9		VAR_066871

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified January 1, 1998. Version 1. Checksum: CFC8F982945BC6DD	FASTA	467	52,493
	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
	Isoform B [UniParc]. Checksum: 6C9E4BB90DEB4B1B	FASTA	430	48,640
	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 QHSDFRPVCY EEPQHWCSVA 250 260 270 280 290 300 YYELNNRVGE TFQASSRSVL IDGFTDPSNN RNRFCLGLLS NVNRNSTIEN TRRHIGKGVH 310 320 330 340 350 360 LYYVGGEVYA ECVSDSSIFV QSRNCNYQHG FHPATVCKIP SGCSLKVFNN QLFAQLLAQS 370 380 390 400 410 420 VHHGFEVVYE LTKMCTIRMS FVKGWGAEYH RQDVTSTPCW IEIHLHGPLQ WLDKVLTQMG 430 SPHNPISSVS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , Humbert M., Morrell N.W., Trembath R.C., Machado R.D. Hum. Mutat. 32:1385-1389(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PPH1 GLU-43, CHARACTERIZATION OF VARIANT PPH1 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.
IPI	IPI00005223. IPI00216093.
RefSeq	NP_001120689.1. NM_001127217.2. NP_005896.1. NM_005905.5.
UniGene	Hs.123119.
3D structure databases
ProteinModelPortal	O15198.
ModBase	Search...
Protein-protein interaction databases
IntAct	O15198. 1 interaction.
MINT	MINT-1179670.
STRING	9606.ENSP00000369154.
PTM databases
PhosphoSite	O15198.
Proteomic databases
PaxDb	O15198.
PRIDE	O15198.
Protocols and materials databases
DNASU	4093.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000350148; ENSP00000239885; ENSG00000120693. ENST00000379826; ENSP00000369154; ENSG00000120693. ENST00000399275; ENSP00000382216; ENSG00000120693.
GeneID	4093.
KEGG	hsa:4093.
UCSC	uc001uvw.3. human. uc001uvx.3. human.
Organism-specific databases
CTD	4093.
GeneCards	GC13M037418.
HGNC	HGNC:6774. SMAD9.
HPA	CAB009119.
MIM	178600. phenotype. 603295. gene.
neXtProt	NX_O15198.
Orphanet	275777. Heritable pulmonary arterial hypertension. 275766. Idiopathic pulmonary arterial hypertension.
PharmGKB	PA30531.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG330956.
HOGENOM	HOG000286018.
HOVERGEN	HBG053353.
InParanoid	O15198.
KO	K16791.
OMA	SDFRPVC.
OrthoDB	EOG4HDSTH.
PhylomeDB	O15198.
Enzyme and pathway databases
Pathway_Interaction_DB	bmppathway. BMP receptor signaling.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	O15198.
CleanEx	HS_SMAD9.
Genevestigator	O15198.
GermOnline	ENSG00000120693. Homo sapiens.
Family and domain databases
Gene3D	2.60.200.10. 1 hit. 3.90.520.10. 1 hit.
InterPro	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]
PANTHER	PTHR13703. PTHR13703. 1 hit.
Pfam	PF03165. MH1. 1 hit. PF03166. MH2. 1 hit. [Graphical view]
SMART	SM00523. DWA. 1 hit. SM00524. DWB. 1 hit. [Graphical view]
SUPFAM	SSF56366. MAD_MH1. 1 hit. SSF49879. SMAD_FHA. 1 hit.
PROSITE	PS51075. MH1. 1 hit. PS51076. MH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4093.
NextBio	16050.
SOURCE	Search...

Entry information

Entry name

SMAD9_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 141 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.