1. Gene
  2. SMAD6 - SMAD family member 6 Gene

SMAD6 - SMAD family member 6 Gene

Homo sapiens

Also known as AOVD2; MADH6; MADH7; HsT17432

Gene ID: 4091 | Gene type: protein coding

About SMAD6

Cytogenetic location: 15q22.31 Genomic coordinates (GRCh38): 15:66,702,236-66,782,849 (from NCBI)

This gene has 5 transcripts (splice variants), 264 orthologues, 7 paralogues and is associated with 4 phenotypes. Broad expression in lung (RPKM 6.3), placenta (RPKM 2.8) and 18 other tissues.

Summary

The protein encoded by this gene belongs to the Smad Family of proteins, which are related to Drosophila 'mothers against decapentaplegic' (Mad) and C. elegans Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein functions in the negative regulation of BMP and TGF-beta/activin-signalling. Multiple transcript variants have been found for this gene.[provided by RefSeq, Sep 2014]

SMAD6 Products(1)

mRNA Protein Name
NM_005585.5 NP_005576.3 mothers against decapentaplegic homolog 6
Gene Ontology
  • Molecular Function
  • Biological Process
  • Cellular Component
Molecular Function GO Annotation Evidence Reference Source
enables I-SMAD binding IPI
IPI: Inferred from physical interaction
9256479 GOA
enables R-SMAD binding IPI
IPI: Inferred from physical interaction
9256479 GOA
enables chromatin binding IDA
IDA: Inferred from direct assay
16491121 GOA
enables co-SMAD binding IPI
IPI: Inferred from physical interaction
9256479 GOA
enables identical protein binding IPI
IPI: Inferred from physical interaction
9436979 GOA
enables protein binding IPI
IPI: Inferred from physical interaction
9436979 GOA
enables protein sequestering activity IDA
IDA: Inferred from direct assay
33667543 GOA
enables transcription cis-regulatory region binding IDA
IDA: Inferred from direct assay
16491121 GOA
enables transcription regulator inhibitor activity IDA
IDA: Inferred from direct assay
9256479 GOA
enables type I activin receptor binding IDA
IDA: Inferred from direct assay
9436979 GOA
enables type I transforming growth factor beta receptor binding IDA
IDA: Inferred from direct assay
9436979 GOA
enables ubiquitin protein ligase binding IPI
IPI: Inferred from physical interaction
11278251 GOA
Biological Process GO Annotation Evidence Reference Source
involved in BMP signaling pathway IDA
IDA: Inferred from direct assay
23455153 GOA
involved in aortic valve morphogenesis IMP
IMP: Inferred from mutant phenotype
22275001 GOA
involved in cell-substrate adhesion IMP
IMP: Inferred from mutant phenotype
16491121 GOA
involved in fat cell differentiation IDA
IDA: Inferred from direct assay
23455153 GOA
involved in immune response IMP
IMP: Inferred from mutant phenotype
16886151 GOA
involved in negative regulation of BMP signaling pathway IDA
IDA: Inferred from direct assay
9436979 GOA
involved in negative regulation of BMP signaling pathway IMP
IMP: Inferred from mutant phenotype
22275001 GOA
involved in negative regulation of SMAD protein signal transduction IDA
IDA: Inferred from direct assay
9436979 GOA
involved in negative regulation of SMAD protein signal transduction IMP
IMP: Inferred from mutant phenotype
19047146 GOA
involved in negative regulation of activin receptor signaling pathway IDA
IDA: Inferred from direct assay
16720724 GOA
involved in negative regulation of apoptotic process IMP
IMP: Inferred from mutant phenotype
19047146 GOA
involved in negative regulation of cell population proliferation IMP
IMP: Inferred from mutant phenotype
19047146 GOA
involved in negative regulation of osteoblast differentiation IMP
IMP: Inferred from mutant phenotype
22275001 GOA
involved in negative regulation of transforming growth factor beta receptor signaling pathway IDA
IDA: Inferred from direct assay
9256479 GOA
involved in negative regulation of transforming growth factor beta receptor signaling pathway IMP
IMP: Inferred from mutant phenotype
19047146 GOA
involved in response to laminar fluid shear stress IEP
IEP: Inferred from expression pattern
9256479 GOA
involved in response to lipopolysaccharide IDA
IDA: Inferred from direct assay
19193853 GOA
involved in zygotic specification of dorsal/ventral axis IMP
IMP: Inferred from mutant phenotype
9436979 GOA
Cellular Component GO Annotation Evidence Reference Source
is active in cytoplasm IDA
IDA: Inferred from direct assay
33667543 GOA
located in nucleus IDA
IDA: Inferred from direct assay
16491121 GOA
part of protein-containing complex IDA
IDA: Inferred from direct assay
23610558 GOA
EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

SMAD6 Protein Structure

MH1

MH1: MH1 domain (173 - 270)

MH2

MH2: MH2 domain (327 - 495)

  • 0
  • 100
  • 200
  • 300
  • 400
  • 496 a.a.
Protein Preferred Names Protein Names

mothers against decapentaplegic homolog 6

MAD homolog 6

SMAD6 Protein-protein interaction Information

Type
Protein Name Protein ID Interactor Interactor Species Interactor ID Detection Method Reference
Intra
SMAD6 O43541 SMAD1 Homo sapiens Q15797
Anti Tag CoIP
9436979
Intra
SMAD6 O43541 MAPK6 Homo sapiens Q16659
Y2H
21900206
Intra
SMAD6 O43541 ubiq_human Homo sapiens DIP-24261N
Anti Tag CoIP
23610558
Intra
SMAD6 O43541 RUNX2 Homo sapiens Q13950
Anti Tag CoIP
16299379
Intra
SMAD6 O43541 Runx2 Mus musculus Q08775
Anti Tag CoIP
16299379
Intra
SMAD6 O43541 CHRM5 Homo sapiens P08912
Ub Reconstruction
28298427
Intra
SMAD6 O43541 UBE2O Homo sapiens Q9C0C9
Anti Tag CoIP
23455153
Intra
SMAD6 O43541 SMAD6 Homo sapiens O43541
Y2H
9436979
Intra
SMAD6 O43541 SMAD6 Homo sapiens O43541
Anti Tag CoIP
9436979
Intra
SMAD6 O43541 RPS6KA5 Homo sapiens O75582
Y2H
21900206
Cross: Cross-species interaction Intra: Intraspecies interaction

Related Diseases

Diseases Alias
Craniosynostosis 7

Craniosynostosis 7, Susceptibility To

CRS7

Craniosynostosis 7, Digenic

Crs7, Digenic

Craniosynostosis, Susceptibility To, Type 7

Aortic Valve Disease 2

Aortic Valve Stenosis

Aortic Stenosis

Rheumatic Aortic Stenosis

AOVD2

Bicuspid Aortic Valve

Rheumatic Aortic Valve Stenosis

Valvular Aortic Stenosis

Aortic Valve Disease, Type 2

Aortic Valve Stricture

Aortic Valve Obstruction

Obstructed Aorta Valve

Rheumatic Aortic Obstruction

Rheumatic Aortic Valve Obstruction

Rheumatic Aortic Stricture

Aortic Valve Regurgitation

Aortic Insufficiency With Stenosis

Rheumatic Aortic Valve Stenosis With Insufficiency

Rheumatic Aortic Stenosis With Incompetence

Rheumatic Aortic Stenosis With Regurgitation

Radioulnar Synostosis, Nonsyndromic

RUS

Radioulnar Synostosis, Nonsyndromic, Susceptibility To

Radioulnar Synostosis, Non-Syndromic

Aortic Valve Disease 1

Aortic Valve Disease

Bicuspid Aortic Valve

Aortic Valve Disorder

AOVD1

Bav

Bicuspid Aortic Valve Disease

Familial Bicuspid Aortic Valve

Aortic Valve Calcification

Aovd

Aortic Valve, Bicuspid

Aortic Valve, Calcification Of

Aortic Stenosis, Calcific

Familial Bav

Calcific Aortic Stenosis

Calcification Of Aortic Valve

Abnormality Of The Aortic Valve

Aortic Valve Disease, Type 1

Aortic Valve Disease 2

Bicommissural Aortic Valve

Plagiocephaly

Asymmetric Head

Lateral Curvatures Of Skull Unequal

Unicoronal Synostosis

Radioulnar Synostosis

Radio-Ulnar Synostosis Type 1

Craniosynostosis

Premature Closure Of Cranial Sutures

Craniostenosis

Craniosynostosis Syndrome

Cso

Craniosynostoses

Congenital Ossification Of Cranial Sutures

Congenital Ossification Of Sutures Of Skull

Craniostosis

Imperfect Fusion Of Skull

Congenital Imperfect Closure Skull

Imperfect Closure Skull

Premature Closure Cranium Sutures

Deficiency Of Craniofacial Axis

Polydactyly

Non-Syndromic Polydactyly

Polydactyly, Postaxial

Postaxial Polydactyly

Supernumerary Digit

Extra Digits

Hyperdactyly

Polydactylia

Polydactylism

Supernumerary Digits

Heart Disease

Heart Failure

Congenital Heart Disease

Heart Diseases

Congenital Heart Defects

Congenital Heart Defect

Heart Malformation

Congenital Anomaly Of Heart

Heart Defect

Heart-Congenital Defect

Congenital Heart Disorder

Heart Defects Congenital

Heart Defects, Congenital

Heart Defects

Heart Disease, Congenital

Disease, Heart, Congenital

Congestive Heart Failure

Heart, Malformation Of
Synostosis
Aortic Aneurysm, Familial Thoracic 1

Thoracic Aortic Aneurysm

Annuloaortic Ectasia

Familial Thoracic Aortic Aneurysm And Aortic Dissection

Familial Aortic Dissection

Familial Taad

Familial Thoracic Aortic Aneurysm

Congenital Aneurysm Of Ascending Aorta

Familial Aortic Aneurysm

Familial Thoracic Aortic Aneurysm And Dissection

Aortic Aneurysm, Thoracic

AAT1

Faa1

Aortic Dissection, Familial

Aortic Aneurysm, Familial Thoracic

Aneurysm, Thoracic Aortic

Faa

Ftaad

Taa

Taad

Cystic Medial Necrosis Of Aorta

Familial Non-Syndromic Thoracic Aortic Aneurysm And Aortic Dissection

Aortic Aneurysm Thoracic

Familial Aortic Aneurysms

Aneurysm, Aortic, Thoracic, Familial, Type 1

Aneurysm Of Thoracic Aorta

Intrathoracic Aneurysm

Thoracic Aorta Aneurysm

Thoracic Aortic Aneurysm Without Rupture

Thoracic Aneurysm

Thorax Arterial Aneurysm

Thoracic Artery Aneurysm

Thoracic Arterial Aneurysm

Thorax Aneurysm

Thorax Aortic Aneurysm

Dissection Of Thoracic Aorta

Esophageal Atresia

Tracheoesophageal Fistula

Congenital Atresia Of Esophagus

Congenital Imperforate Esophagus

Imperforate Esophagus

Oesophageal Atresia

Te Fistula

Tef

Tracheoesophageal Fistula With Or Without Esophageal Atresia

Hypoplastic Left Heart Syndrome

Hlhs

Heart, Hypoplastic Left, Syndrome

Hypoplasia Of The Left Heart

Left Heart Hypoplasia Syndrome

Hlhs - [Hypoplastic Left Heart Syndrome]

Hypoplasia Of Aortic Valve, In Hypoplastic Left Heart Syndrome

Atresia Of Mitral Valve, In Hypoplastic Left Heart Syndrome

Atresia Or Marked Hypoplasia Of Aortic Orifice Or Valve, With Hypoplasia Of Ascending Aorta And Defective Development Of Left Ventricle

Atresia Or Marked Hypoplasia, Of Aortic Orifice Or Valve, With Hypoplasia Of Ascending Aorta And Defective Development Of Left Ventricle With Mitral Valve Atresia

Aortic Valve Atresia, In Hypoplastic Left Heart Syndrome

Ascending Aorta Hypoplasia, In Hypoplastic Left Heart Syndrome

Cowden Syndrome 6

CWS6

Cowden Syndrome, Type 6

Spinal Muscular Atrophy, Type Iv

SMA4

Spinal Muscular Atrophy, Adult Form

Spinal Muscular Atrophy 4

Spinal Muscular Atrophy-4

Adult Spinal Muscular Atrophy

Spinal Muscular Atrophy, Proximal, Adult, Autosomal Recessive

Proximal Spinal Muscular Atrophy Type 4

Sma Type 4

Sma Type Iv

Sma-Iv

Sma Iv

Spinal Muscular Atrophy Adult Form

Spinal Muscular Atrophy Proximal Adult Autosomal Recessive

Spinal Muscular Atrophy Type Iv

Atrophy, Muscular, Spinal, Type Iv

Myelopathic Muscular Atrophy

Chronic Pulmonary Heart Disease
Fibrodysplasia Ossificans Progressiva

Myositis Ossificans Progressiva

Progressive Myositis Ossificans

FOP

Progressive Ossifying Myositis

Myositis Ossificans

Stone Man Syndrome

Man Of Stone

Myositis Ossificans Progressive

Diffuse Progressive Ossifying Polymyositis

Fibrodysplasia Ossificans Congenita

Myositis Ossificans Progressiva, Site Unspecified

Münchmeyer Disease

Fop - [Fibrodysplasia Ossificans Progressiva]

Progressive Myositis Ossificans Calcification

Giant Axonal Neuropathy 1, Autosomal Recessive

Giant Axonal Neuropathy

Giant Axonal Neuropathy 1

Gan

GAN1

Giant Axonal Neuropathy-1

Neuropathy, Giant Axonal

Giant Axonal Disease

Neuropathy, Axonal, Giant, Type 1

Loeys-Dietz Syndrome

Loeys-Dietz Aortic Aneurysm Syndrome

Lds

Aortic Aneurysm Syndrome Due To Tgf-Beta Receptors Anomalies

Furlong Syndrome

Pancreatic Cancer

Pancreatic Carcinoma

Carcinoma Of Pancreas

Familial Pancreatic Carcinoma

Pancreatic Neoplasm

Pancreatic Carcinoma, Familial

Malignant Neoplasm Of Pancreas

Pancreatic Acinar Carcinoma

Pancreatic Tumor

Familial Pancreatic Cancer

Neoplasm Of The Pancreas

Cancer Of The Pancreas

Pancreatic Carcinoma, Somatic

Pancreatic Cancer, Somatic

Ca Body Of Pancreas

Ca Head Of Pancreas

Ca Tail Of Pancreas

Malignant Neoplasm Of Body Of Pancreas

Malignant Neoplasm Of Head Of Pancreas

Malignant Neoplasm Of Tail Of Pancreas

Pancreas Neoplasm

Exocrine Cancer

Exocrine Pancreas Carcinoma

Hereditary Pancreatic Cancer

Hereditary Pancreatic Carcinoma

PNCA

Pancreatic Cancer, Susceptibility To

Carcinoma Of Head Of Pancreas

Pancreatic Neoplasms

Pancreatic Tumors

Cancer, Pancreatic

Cancer Of Pancreas

Mixed Islet Cell With Exocrine Carcinoma Of Unspecified Site

Brachydactyly, Type A2

Brachydactyly Type A2

BDA2

Mohr-Wriedt Type Brachydactyly

Brachymesophalangy Ii

Brachymesophalangy Type 2

Brachymesophalangy 2

Brachydactyly, Mohr-Wriedt Type

Brachydactyly A2

Breast Cancer

Breast Carcinoma

Male Breast Cancer

Breast Cancer, Familial

Malignant Neoplasm Of Breast

Breast Cancer, Susceptibility To

Breast Cancer, Early-Onset

Malignant Tumor Of Breast

Carcinoma Of Male Breast

Breast Cancer, Invasive Ductal

Breast Cancer, Protection Against

Breast Cancer, Somatic

Breast Cancer, Male

Breast Cancer, Lobular, Somatic

Breast Tumor

Mammary Cancer

Mammary Tumor

Malignant Neoplasm Of Male Breast

Mammary Carcinoma

Male Breast Carcinoma

Familial Cancer Of Breast

Invasive Ductal Breast Carcinoma

Breast Cancer Susceptibility

Breast Cancer, Male, Susceptibility To

Breast Cancer, Early-Onset, Susceptibility To

Malignant Tumor Of The Breast

Mammary Neoplasm

Primary Breast Cancer

Neoplasm Of Male Breast

Carcinoma Of Breast

Breast Cancer In Men

Familial Breast Cancer

Cancer Of Breast

BC

Breast Cancer Familial

Breast Cancer Familial Male

Breast Cancer, Familial Male

Breast Male Carcinoma

Breast Neoplasms

Breast Neoplasms, Male

Mammary Tumors

Mammary Carcinomas

Cancer, Breast

Cancer, Breast, Susceptibility

Invasive Breast Ductal Carcinoma

Breast Neoplasm

Susceptibility To Breast Cancer

Mammary Neoplasms

Animal Mammary Neoplasms

Primary Malignant Neoplasm Of Breast

Infiltrating Ductal Carcinoma Of Breast

Infiltrating Duct Carcinoma Of Unspecified Site

Infiltrating Ductular Carcinoma Of Unspecified Site

Invasive Breast Carcinoma Of No Special Type

Microinvasive Carcinoma Of Breast

Carcinoma With Apocrine Differentiation

Hereditary Hemorrhagic Telangiectasia

Rendu-Osler-Weber Disease

Hht

Osler-Weber-Rendu Disease

Telangiectasia, Hereditary Hemorrhagic

Osler Hemorrhagic Telangiectasia Syndrome

Orw Disease

Osler Weber Rendu Syndrome

Osler-Rendu-Weber Disease

Osler-Weber-Rendu Syndrome

Rendu-Osler Disease

Telangiectasia Hereditary Hemorrhagic

Telangiectasia Hemorrhagic, Hereditary

Hht - [Hereditary Haemorrhagic Telangiectasia]

Osler Haemorrhagic Telangiectasia Syndrome

Diseases Alias
Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Macroglobulinemia Of Waldenstrom

Lymphoplasmacytic Lymphoma With Igm Gammopathy

Lymphoplasmacytic Lymphoma

Waldenstroem'S Macroglobulinemia

Waldenstroem'S Macroglobulinemia

Macroglobulinemia Of Waldenstrom

Lymphoplasmacytic Lymphoma With Igm Gammopathy

Lymphoplasmacytic Lymphoma

Orthologs Information

Species Symbol Source ID
Macaca mulatta SMAD6 VGNC VGNC:77814
Bos taurus SMAD6 VGNC VGNC:34979
Rattus norvegicus SMAD6 RGD RGD:1305069
Felis catus SMAD6 VGNC VGNC:80841
Canis familiaris SMAD6 VGNC VGNC:46523
Mus musculus SMAD6 MGD MGI:1336883
Others SMAD6 NCBI