HUMAN:SMAD6

Species (Taxon ID)	Homo sapiens (Human). (9606)
Gene Name(s)	SMAD6 (synonyms: MADH6)
Protein Name(s)	Mothers against decapentaplegic homolog 6 MAD homolog 6 Mothers against DPP homolog 6 SMAD family member 6 SMAD 6 Smad6 hSMAD6
External Links
UniProt	O43541
EMBL	U59914 AF035528 AF043640 AF037469 AF041065 AF041062 AF041063 AF041064 AM909653 BC012986 AF101474
CCDS	CCDS10221.1
RefSeq	NP_005576.3 XP_011519863.1
UniGene	Hs.153863
ProteinModelPortal	O43541
SMR	O43541
BioGrid	110266
DIP	DIP-36708N
IntAct	O43541
MINT	MINT-1198639
STRING	9606.ENSP00000288840
PhosphoSite	O43541
BioMuta	SMAD6
MaxQB	O43541
PaxDb	O43541
PRIDE	O43541
Ensembl	ENST00000288840 ENST00000557916
GeneID	4091
KEGG	hsa:4091
UCSC	uc002aqf.3 uc002aqg.3
CTD	4091
GeneCards	GC15P066994
H-InvDB	HIX0132566
HGNC	HGNC:6772
MIM	602931 614823
neXtProt	NX_O43541
Orphanet	402075
PharmGKB	PA30529
eggNOG	NOG309572
GeneTree	ENSGT00760000119091
HOVERGEN	HBG053021
InParanoid	O43541
KO	K04677
OMA	CRTVTCC
OrthoDB	EOG7GN2PK
PhylomeDB	O43541
TreeFam	TF314923
Reactome	REACT_12034
SignaLink	O43541
ChiTaRS	SMAD6
GeneWiki	Mothers_against_decapentaplegic_homolog_6
GenomeRNAi	4091
NextBio	16042
PRO	PR:O43541
Proteomes	UP000005640
Bgee	O43541
CleanEx	HS_SMAD6
ExpressionAtlas	O43541
Genevisible	O43541
GO	GO:0005737 GO:0005829 GO:0005634 GO:0043234 GO:0005667 GO:0003682 GO:0070410 GO:0070411 GO:0042802 GO:0046872 GO:0070412 GO:0000978 GO:0003700 GO:0044212 GO:0030617 GO:0070698 GO:0034713 GO:0031625 GO:0030509 GO:0031589 GO:0045444 GO:0006955 GO:0035556 GO:0043066 GO:0030514 GO:0008285 GO:0060394 GO:0010991 GO:0030512 GO:0043627 GO:0034616 GO:0006351 GO:0007179 GO:0001657 GO:0007352
Gene3D	2.60.200.10 3.90.520.10
InterPro	IPR013790 IPR003619 IPR013019 IPR017855 IPR001132 IPR008984
PANTHER	PTHR13703
Pfam	PF03165 PF03166
SMART	SM00523 SM00524
SUPFAM	SSF49879 SSF56366
PROSITE	PS51075 PS51076

Annotations

Qualifier	GO ID	GO term name	Reference	ECO ID	ECO term name	with/from	Aspect	Extension	Notes	Status
involved_in	GO:0003180	aortic valve morphogenesis	PMID:22275001^[1]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0030514	negative regulation of BMP signaling pathway	PMID:22275001^[1]	ECO:0000315	mutant phenotype evidence used in manual assertion		P	part_of:(GO:0003180)	Seeded From UniProt	complete
involved_in	GO:0032496	response to lipopolysaccharide	PMID:19193853^[2]	ECO:0000314	direct assay evidence used in manual assertion		P	occurs_in:(CL:0000451) part_of:(GO:0032496)	Seeded From UniProt	complete
involved_in	GO:0045668	negative regulation of osteoblast differentiation	PMID:22275001^[1]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0030279	negative regulation of ossification	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:O35182	P	occurs_in:(UBERON:0004145)	Seeded From UniProt	complete
involved_in	GO:0003184	pulmonary valve morphogenesis	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:O35182	P		Seeded From UniProt	complete
involved_in	GO:0003148	outflow tract septum morphogenesis	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:O35182	P		Seeded From UniProt	complete
involved_in	GO:0003183	mitral valve morphogenesis	GO_REF:0000024	ECO:0000250	sequence similarity evidence used in manual assertion	UniProtKB:O35182	P		Seeded From UniProt	complete
enables	GO:0000978	RNA polymerase II proximal promoter sequence-specific DNA binding	PMID:16491121^[3]	ECO:0000314	direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
enables	GO:0000981	DNA-binding transcription factor activity, RNA polymerase II-specific	GO_REF:0000113	ECO:0005556	multiple sequence alignment evidence used in manual assertion	UniProtKB:P97454	F		Seeded From UniProt	complete
enables	GO:0070698	type I activin receptor binding	PMID:9436979^[4]	ECO:0000314	direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
enables	GO:0070412	R-SMAD binding	PMID:9256479^[5]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:Q15796	F		Seeded From UniProt	complete
enables	GO:0070412	R-SMAD binding	PMID:9436979^[4]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:Q15797	F		Seeded From UniProt	complete
enables	GO:0070411	I-SMAD binding	PMID:9256479^[5]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:O15105	F		Seeded From UniProt	complete
enables	GO:0070410	co-SMAD binding	PMID:9256479^[5]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:Q13485	F		Seeded From UniProt	complete
involved_in	GO:0060394	negative regulation of pathway-restricted SMAD protein phosphorylation	PMID:19047146^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0060394	negative regulation of pathway-restricted SMAD protein phosphorylation	PMID:9436979^[4]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0043066	negative regulation of apoptotic process	PMID:19047146^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
enables	GO:0034713	type I transforming growth factor beta receptor binding	PMID:9436979^[4]	ECO:0000314	direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
involved_in	GO:0034616	response to laminar fluid shear stress	PMID:9256479^[5]	ECO:0000270	expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete
enables	GO:0031625	ubiquitin protein ligase binding	PMID:11278251^[7]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:Q9HCE7	F		Seeded From UniProt	complete
enables	GO:0030617	transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity	PMID:19047146^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		F		Seeded From UniProt	complete
enables	GO:0030617	transforming growth factor beta receptor, inhibitory cytoplasmic mediator activity	PMID:9256479^[5]	ECO:0000314	direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
involved_in	GO:0030514	negative regulation of BMP signaling pathway	PMID:9436979^[4]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway	PMID:19047146^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0010991	negative regulation of SMAD protein complex assembly	PMID:9436979^[4]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0008285	negative regulation of cell population proliferation	PMID:19047146^[6]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0007352	zygotic specification of dorsal/ventral axis	PMID:9436979^[4]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0006955	immune response	PMID:16886151^[8]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0045444	fat cell differentiation	PMID:23455153^[9]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
enables	GO:0044212	transcription regulatory region DNA binding	PMID:16491121^[3]	ECO:0000314	direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
involved_in	GO:0031589	cell-substrate adhesion	PMID:16491121^[3]	ECO:0000315	mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
involved_in	GO:0030509	BMP signaling pathway	PMID:23455153^[9]	ECO:0000314	direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
part_of	GO:0005634	nucleus	PMID:16491121^[3]	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
enables	GO:0003682	chromatin binding	PMID:16491121^[3]	ECO:0000314	direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
part_of	GO:0032991	protein-containing complex	PMID:23610558^[10]	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
enables	GO:0042802	identical protein binding	PMID:9436979^[4]	ECO:0000353	physical interaction evidence used in manual assertion	UniProtKB:O43541	F		Seeded From UniProt	complete
part_of	GO:0016604	nuclear body	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005829	cytosol	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005794	Golgi apparatus	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005634	nucleus	GO_REF:0000052	ECO:0000314	direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
involved_in	GO:0043627	response to estrogen	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:D3ZAQ2 ensembl:ENSRNOP00000012155	P		Seeded From UniProt	complete
involved_in	GO:1902895	positive regulation of pri-miRNA transcription by RNA polymerase II	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0060976	coronary vasculature development	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0035904	aorta development	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0030279	negative regulation of ossification	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0003281	ventricular septum development	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0003184	pulmonary valve morphogenesis	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0003183	mitral valve morphogenesis	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0003170	heart valve development	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0003148	outflow tract septum morphogenesis	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
involved_in	GO:0001657	ureteric bud development	GO_REF:0000107	ECO:0000265	sequence orthology evidence used in automatic assertion	UniProtKB:O35182 ensembl:ENSMUSP00000036285	P		Seeded From UniProt	complete
enables	GO:0003700	DNA-binding transcription factor activity	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR013019	F		Seeded From UniProt	complete
part_of	GO:0005667	transcription factor complex	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR013019	C		Seeded From UniProt	complete
involved_in	GO:0006355	regulation of transcription, DNA-templated	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR001132 InterPro:IPR003619 InterPro:IPR013019 InterPro:IPR013790	P		Seeded From UniProt	complete
involved_in	GO:0007179	transforming growth factor beta receptor signaling pathway	GO_REF:0000002	ECO:0000256	match to sequence model evidence used in automatic assertion	InterPro:IPR013019 InterPro:IPR036578	P		Seeded From UniProt	complete
part_of	GO:0005737	cytoplasm	PMID:19018011^[11]	ECO:0000304	author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
involved_in	GO:0030509	BMP signaling pathway	Reactome:R-HSA-201451	ECO:0000304	author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete
part_of	GO:0005829	cytosol	Reactome:R-HSA-8878023 Reactome:R-HSA-202626 Reactome:R-HSA-201821 Reactome:R-HSA-201475	ECO:0000304	author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
part_of	GO:0005634	nucleus	GO_REF:0000037 GO_REF:0000039	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0539 UniProtKB-SubCell:SL-0191	C		Seeded From UniProt	complete
enables	GO:0046872	metal ion binding	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0479	F		Seeded From UniProt	complete
enables	GO:0003677	DNA binding	GO_REF:0000037	ECO:0000322	imported manually asserted information used in automatic assertion	UniProtKB-KW:KW-0238	F		Seeded From UniProt	complete
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Notes

References

See Help:References for how to manage references in GONUTS.

↑ ^1.0 ^1.1 ^1.2 Tan, HL et al. (2012) Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation. Hum. Mutat. 33 720-7 PubMed GONUTS page
↑ Ceppi, M et al. (2009) MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 106 2735-40 PubMed GONUTS page
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 Glesne, D & Huberman, E (2006) Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation. Oncogene 25 4086-98 PubMed GONUTS page
↑ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 ^4.7 Hata, A et al. (1998) Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 12 186-97 PubMed GONUTS page
↑ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 Topper, JN et al. (1997) Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc. Natl. Acad. Sci. U.S.A. 94 9314-9 PubMed GONUTS page
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 Jeon, HS et al. (2008) SMAD6 contributes to patient survival in non-small cell lung cancer and its knockdown reestablishes TGF-beta homeostasis in lung cancer cells. Cancer Res. 68 9686-92 PubMed GONUTS page
↑ Ebisawa, T et al. (2001) Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J. Biol. Chem. 276 12477-80 PubMed GONUTS page
↑ Adewoye, AH et al. (2006) Association of polymorphisms of IGF1R and genes in the transforming growth factor- beta /bone morphogenetic protein pathway with bacteremia in sickle cell anemia. Clin. Infect. Dis. 43 593-8 PubMed GONUTS page
↑ ^9.0 ^9.1 Zhang, X et al. (2013) Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6. EMBO J. 32 996-1007 PubMed GONUTS page
↑ Kelly, CE et al. (2013) Rnf165/Ark2C enhances BMP-Smad signaling to mediate motor axon extension. PLoS Biol. 11 e1001538 PubMed GONUTS page
↑ Hoover, LL & Kubalak, SW (2008) Holding their own: the noncanonical roles of Smad proteins. Sci Signal 1 pe48 PubMed GONUTS page

[PMID:22275001-1] 1.0 ^1.1 ^1.2 Tan, HL et al. (2012) Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation. Hum. Mutat. 33 720-7 PubMed GONUTS page

[PMID:19193853-2] Ceppi, M et al. (2009) MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 106 2735-40 PubMed GONUTS page

[PMID:16491121-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 Glesne, D & Huberman, E (2006) Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation. Oncogene 25 4086-98 PubMed GONUTS page

[PMID:9436979-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 ^4.7 Hata, A et al. (1998) Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 12 186-97 PubMed GONUTS page

[PMID:9256479-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 Topper, JN et al. (1997) Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc. Natl. Acad. Sci. U.S.A. 94 9314-9 PubMed GONUTS page

[PMID:19047146-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 Jeon, HS et al. (2008) SMAD6 contributes to patient survival in non-small cell lung cancer and its knockdown reestablishes TGF-beta homeostasis in lung cancer cells. Cancer Res. 68 9686-92 PubMed GONUTS page

[PMID:11278251-7] Ebisawa, T et al. (2001) Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J. Biol. Chem. 276 12477-80 PubMed GONUTS page

[PMID:16886151-8] Adewoye, AH et al. (2006) Association of polymorphisms of IGF1R and genes in the transforming growth factor- beta /bone morphogenetic protein pathway with bacteremia in sickle cell anemia. Clin. Infect. Dis. 43 593-8 PubMed GONUTS page

[PMID:23455153-9] 9.0 ^9.1 Zhang, X et al. (2013) Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6. EMBO J. 32 996-1007 PubMed GONUTS page

[PMID:23610558-10] Kelly, CE et al. (2013) Rnf165/Ark2C enhances BMP-Smad signaling to mediate motor axon extension. PLoS Biol. 11 e1001538 PubMed GONUTS page

[PMID:19018011-11] Hoover, LL & Kubalak, SW (2008) Holding their own: the noncanonical roles of Smad proteins. Sci Signal 1 pe48 PubMed GONUTS page

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HUMAN:SMAD6

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