Smad protein daf-3 [Caenorhabditis elegans]
Protein Classification
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||
| MH1_SMAD_4 | cd10492 | N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present ... |
184-309 | 2.83e-61 | |||||
N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 belongs to SMAD4, a common mediator SMAD (co-SMAD), which belongs to the Dwarfin family of proteins and is involved in many cell functions such as differentiation, apoptosis, gastrulation, embryonic development and cell cycle. SMAD4 binds receptor regulated SMADs (R-SMADs) such as SMAD1 or SMAD2, and forms an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD4 is often mutated in several cancers, such as multiploid colorectal cancer and pancreatic carcinoma, as well as in juvenile polyposis syndrome (JPS). : Pssm-ID: 199816 Cd Length: 125 Bit Score: 203.07 E-value: 2.83e-61
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| DWB | smart00524 | Domain B in dwarfin family proteins; |
622-823 | 4.17e-61 | |||||
Domain B in dwarfin family proteins; : Pssm-ID: 197770 Cd Length: 171 Bit Score: 204.47 E-value: 4.17e-61
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| Atrophin-1 super family | cl38111 | Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ... |
318-523 | 2.02e-04 | |||||
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity. The actual alignment was detected with superfamily member pfam03154: Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 45.14 E-value: 2.02e-04
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| Name | Accession | Description | Interval | E-value | |||||
| MH1_SMAD_4 | cd10492 | N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present ... |
184-309 | 2.83e-61 | |||||
N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 belongs to SMAD4, a common mediator SMAD (co-SMAD), which belongs to the Dwarfin family of proteins and is involved in many cell functions such as differentiation, apoptosis, gastrulation, embryonic development and cell cycle. SMAD4 binds receptor regulated SMADs (R-SMADs) such as SMAD1 or SMAD2, and forms an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD4 is often mutated in several cancers, such as multiploid colorectal cancer and pancreatic carcinoma, as well as in juvenile polyposis syndrome (JPS). Pssm-ID: 199816 Cd Length: 125 Bit Score: 203.07 E-value: 2.83e-61
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| DWB | smart00524 | Domain B in dwarfin family proteins; |
622-823 | 4.17e-61 | |||||
Domain B in dwarfin family proteins; Pssm-ID: 197770 Cd Length: 171 Bit Score: 204.47 E-value: 4.17e-61
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| MH2 | pfam03166 | MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ... |
621-823 | 2.61e-57 | |||||
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five alpha helices and three loops enclosing a beta sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C-terminus of MH2. Pssm-ID: 460834 Cd Length: 172 Bit Score: 193.99 E-value: 2.61e-57
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| MH1 | pfam03165 | MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ... |
208-308 | 4.23e-40 | |||||
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localization signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx. Pssm-ID: 460833 Cd Length: 103 Bit Score: 142.90 E-value: 4.23e-40
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| DWA | smart00523 | Domain A in dwarfin family proteins; |
202-311 | 6.28e-40 | |||||
Domain A in dwarfin family proteins; Pssm-ID: 214708 Cd Length: 109 Bit Score: 142.90 E-value: 6.28e-40
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| MH2_SMAD_4 | cd10498 | C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ... |
621-834 | 2.34e-28 | |||||
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain. SMAD4, which belongs to the Dwarfin family of proteins, is involved in many cell functions such as differentiation, apoptosis, gastrulation, embryonic development and the cell cycle. SMAD4 binds receptor regulated SMADs (R-SMADs) such as SMAD1 or SMAD2, and forms an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD4 is often mutated in several cancers, such as multiploid colorectal cancer, cervical cancer and pancreatic carcinoma, as well as in juvenile polyposis syndrome. Pssm-ID: 199823 Cd Length: 222 Bit Score: 113.72 E-value: 2.34e-28
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| Atrophin-1 | pfam03154 | Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ... |
318-523 | 2.02e-04 | |||||
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity. Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 45.14 E-value: 2.02e-04
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| Name | Accession | Description | Interval | E-value | |||||
| MH1_SMAD_4 | cd10492 | N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present ... |
184-309 | 2.83e-61 | |||||
N-terminal Mad Homology 1 (MH1) domain in SMAD4; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 belongs to SMAD4, a common mediator SMAD (co-SMAD), which belongs to the Dwarfin family of proteins and is involved in many cell functions such as differentiation, apoptosis, gastrulation, embryonic development and cell cycle. SMAD4 binds receptor regulated SMADs (R-SMADs) such as SMAD1 or SMAD2, and forms an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD4 is often mutated in several cancers, such as multiploid colorectal cancer and pancreatic carcinoma, as well as in juvenile polyposis syndrome (JPS). Pssm-ID: 199816 Cd Length: 125 Bit Score: 203.07 E-value: 2.83e-61
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| DWB | smart00524 | Domain B in dwarfin family proteins; |
622-823 | 4.17e-61 | |||||
Domain B in dwarfin family proteins; Pssm-ID: 197770 Cd Length: 171 Bit Score: 204.47 E-value: 4.17e-61
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| MH2 | pfam03166 | MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ... |
621-823 | 2.61e-57 | |||||
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD related proteins such as Smads. This domain is separated from the MH1 domain by a non-conserved linker region. The MH2 domain mediates interaction with a wide variety of proteins and provides specificity and selectivity to Smad function and also is critical for mediating interactions in Smad oligomers. Unlike MH1, MH2 does not bind DNA. The well-studied MH2 domain of Smad4 is composed of five alpha helices and three loops enclosing a beta sandwich. Smads are involved in the propagation of TGF-beta signals by direct association with the TGF-beta receptor kinase which phosphorylates the last two Ser of a conserved 'SSXS' motif located at the C-terminus of MH2. Pssm-ID: 460834 Cd Length: 172 Bit Score: 193.99 E-value: 2.61e-57
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| MH1 | pfam03165 | MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related ... |
208-308 | 4.23e-40 | |||||
MH1 domain; The MH1 (MAD homology 1) domain is found at the amino terminus of MAD related proteins such as Smads. This domain is separated from the MH2 domain by a non-conserved linker region. The crystal structure of the MH1 domain shows that a highly conserved 11 residue beta hairpin is used to bind the DNA consensus sequence GNCN in the major groove, shown to be vital for the transcriptional activation of target genes. Not all examples of MH1 can bind to DNA however. Smad2 cannot bind DNA and has a large insertion within the hairpin that presumably abolishes DNA binding. A basic helix (H2) in MH1 with the nuclear localization signal KKLKK has been shown to be essential for Smad3 nuclear import. Smads also use the MH1 domain to interact with transcription factors such as Jun, TFE3, Sp1, and Runx. Pssm-ID: 460833 Cd Length: 103 Bit Score: 142.90 E-value: 4.23e-40
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| DWA | smart00523 | Domain A in dwarfin family proteins; |
202-311 | 6.28e-40 | |||||
Domain A in dwarfin family proteins; Pssm-ID: 214708 Cd Length: 109 Bit Score: 142.90 E-value: 6.28e-40
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| MH1 | cd00049 | N-terminal Mad Homology 1 (MH1) domain; The MH1 is a small DNA-binding domain present in SMAD ... |
199-309 | 6.90e-29 | |||||
N-terminal Mad Homology 1 (MH1) domain; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. Receptor-regulated SMAD proteins (R-SMADs, including SMAD1, SMAD2, SMAD3, SMAD5, and SMAD9) are activated by phosphorylation by transforming growth factor (TGF)-beta type I receptors. The active R-SMAD associates with a common mediator SMAD (Co-SMAD or SMAD4) and other cofactors, which together translocate to the nucleus to regulate gene expression. The inhibitory or antagonistic SMADs (I-SMADs, including SMAD6 and SMAD7) negatively regulate TGF-beta signaling by competing with R-SMADs for type I receptor or Co-SMADs. MH1 domains of R-SMAD and SMAD4 contain a nuclear localization signal as well as DNA-binding activity. The activated R-SMAD/SMAD4 complex then binds with very low affinity to a DNA sequence CAGAC called SMAD-binding element (SBE) via the MH1 domain. Pssm-ID: 199811 Cd Length: 121 Bit Score: 111.91 E-value: 6.90e-29
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| MH2_SMAD_4 | cd10498 | C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ... |
621-834 | 2.34e-28 | |||||
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain. SMAD4, which belongs to the Dwarfin family of proteins, is involved in many cell functions such as differentiation, apoptosis, gastrulation, embryonic development and the cell cycle. SMAD4 binds receptor regulated SMADs (R-SMADs) such as SMAD1 or SMAD2, and forms an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD4 is often mutated in several cancers, such as multiploid colorectal cancer, cervical cancer and pancreatic carcinoma, as well as in juvenile polyposis syndrome. Pssm-ID: 199823 Cd Length: 222 Bit Score: 113.72 E-value: 2.34e-28
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| MH1_SMAD_2_3 | cd10491 | N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding ... |
200-307 | 8.27e-27 | |||||
N-terminal Mad Homology 1 (MH1) domain in SMAD2 and SMAD3; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 is found in SMAD2 as well as SMAD3. SMAD2 mediates the signal of the transforming growth factor (TGF)-beta, and thereby regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. It plays a role in the transmission of extracellular signals from ligands of the TGF-beta superfamily growth factors into the cell nucleus. SMAD3 modulates signals of activin and TGF-beta. It binds SMAD4, enabling its transmigration into the nucleus where it forms complexes with other proteins and acts as a transcription factor. Increased SMAD3 activity has been implicated in the pathogenesis of scleroderma. Pssm-ID: 199815 Cd Length: 124 Bit Score: 106.07 E-value: 8.27e-27
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| MH1_R-SMAD | cd10488 | N-terminal Mad Homology 1 (MH1) domain of receptor regulated SMADs; The MH1 is a small ... |
199-307 | 6.25e-25 | |||||
N-terminal Mad Homology 1 (MH1) domain of receptor regulated SMADs; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. It binds to the major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in all receptor regulated SMADs (R-SMADs) including SMAD1, SMAD2, SMAD3, SMAD5 and SMAD9. SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD2 regulates multiple cellular processes, such as cell proliferation, apoptosis and differentiation, while SMAD3 modulates signals of activin and TGF-beta. SMAD4, a common mediator SMAD (co-SMAD) binds R-SMADs, forming an oligomeric complex that binds to DNA and serves as a transcription factor. SMAD5 is involved in bone morphogenetic proteins (BMP) signal modulation, possibly playing a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 (also known as SMAD8) can mediate the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway Pssm-ID: 199812 Cd Length: 123 Bit Score: 100.34 E-value: 6.25e-25
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| MH2 | cd00050 | C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ... |
623-823 | 3.11e-24 | |||||
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers against decapentaplegic) family of proteins and is responsible for type I receptor interactions, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain which prevents it from forming a complex with SMAD4. The MH2 domain is multifunctional and provides SMADs with their specificity and selectivity, as well as transcriptional activity. Several transcriptional co-activators and repressors have also been reported to regulate SMAD signaling by interacting with the MH2 domain. Mutations in the MH2 domains of SMAD2 and especially SMAD4 have been detected in colorectal and other human cancers. Pssm-ID: 199819 Cd Length: 170 Bit Score: 100.37 E-value: 3.11e-24
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| MH1_SMAD_1_5_9 | cd10490 | N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The ... |
203-307 | 1.81e-23 | |||||
N-terminal Mad Homology 1 (MH1) domain in SMAD1, SMAD5 and SMAD9 (also known as SMAD8); The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in SMAD1, SMAD5 and SMAD9, all closely related receptor regulated SMADs (R-SMADs). SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD5 is involved in bone morphogenetic proteins (BMP) signal modulation and may also play a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway. Pssm-ID: 199814 Cd Length: 124 Bit Score: 96.42 E-value: 1.81e-23
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| MH2_R-SMAD | cd10495 | C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ... |
623-830 | 5.09e-19 | |||||
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain. Receptor regulated SMADs (R-SMADs) include SMAD1, SMAD2, SMAD3, SMAD5 and SMAD9. SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD2 regulates multiple cellular processes, such as cell proliferation, apoptosis and differentiation, while SMAD3 modulates signals of activin and TGF-beta. SMAD5 is involved in BMP signal modulation, possibly playing a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 (also known as SMAD8) can mediate the differentiation of mesenchymal stem cells into tendon-like cells by inhibiting the osteogenic pathway. Pssm-ID: 199820 Cd Length: 182 Bit Score: 85.51 E-value: 5.09e-19
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| MH2_I-SMAD | cd10496 | C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ... |
623-823 | 7.36e-14 | |||||
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD6 and SMAD7 are inhibitory SMADs (I-SMADs) that function as negative regulators of signaling mediated by the TGF-beta superfamily. SMAD6 specifically inhibits bone morphogenetic protein (BMP) type I receptor mediated signaling, while SMAD7 enhances muscle differentiation and is often associated with cancer, tissue fibrosis and inflammatory diseases. Pssm-ID: 199821 Cd Length: 165 Bit Score: 70.08 E-value: 7.36e-14
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| MH2_SMAD_2_3 | cd10985 | C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ... |
623-832 | 6.66e-11 | |||||
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain. SMAD2 and SMAD3 are receptor regulated SMADs (R-SMADs). SMAD2 regulates multiple cellular processes, such as cell proliferation, apoptosis and differentiation, while SMAD3 modulates signals of activin and TGF-beta. Pssm-ID: 199826 Cd Length: 191 Bit Score: 62.25 E-value: 6.66e-11
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| MH2_SMAD_7 | cd10500 | C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus ... |
623-823 | 1.98e-09 | |||||
C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD7, an inhibitory or antagonistic SMAD (I-SMAD), acts as a negative regulator of signaling mediated by the TGF-beta superfamily of ligands, by blocking TGF-beta type 1 and activin association with the receptor as well as access to SMAD2. SMAD7 enhances muscle differentiation, playing pivotal roles in embryonic development and adult homoeostasis. SMAD7 and SMAD6 act as critical mediators for effective TGF-beta I-mediated suppression of Interleukin-1/Toll-like receptor (IL-1R/TLR) signaling through simultaneous binding to Pellino-1, an adaptor protein of interleukin-1 receptor associated kinase 1(IRAK1), via their MH2 domains. Altered expression of SMAD7 is often associated with cancer, tissue fibrosis and inflammatory diseases. Pssm-ID: 199825 Cd Length: 171 Bit Score: 57.74 E-value: 1.98e-09
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| MH2_SMAD_1_5_9 | cd10497 | C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ... |
623-832 | 1.38e-07 | |||||
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at the C-terminus of the SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. The MH2 domain is responsible for type I receptor interaction, phosphorylation-triggered homo- and hetero-oligomerization, and transactivation. It is negatively regulated by the N-terminal MH1 domain, which prevents it from forming a complex with SMAD4. SMAD1, SMAD5 and SMAD9 (also known as SMAD8), are receptor regulated SMADs (R-SMADs). SMAD1 plays an essential role in bone development and postnatal bone formation through activation by bone morphogenetic protein (BMP) type 1 receptor kinase. SMAD5 is involved in BMP signal modulation and may also play a role in the pathway involving inhibition of hematopoietic progenitor cells by TGF-beta. SMAD9 mediates the differentiation of mesenchymal stem cells (MSCs) into tendon-like cells by inhibiting the osteogenic pathway. Pssm-ID: 199822 Cd Length: 201 Bit Score: 52.96 E-value: 1.38e-07
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| MH1_SMAD_6 | cd10493 | N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present ... |
228-309 | 2.27e-07 | |||||
N-terminal Mad Homology 1 (MH1) domain in SMAD6; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 belongs to SMAD6, an inhibitory SMAD (I-SMAD) or antagonistic SMAD, which acts as a negative regulator of signaling mediated by TGF-beta superfamily ligands, by competing with SMAD4 and preventing the transcription of SMAD4's gene products. SMAD6 specifically inhibits bone morphogenetic protein (BMP) type I receptor mediated signaling. Pssm-ID: 199817 Cd Length: 113 Bit Score: 50.15 E-value: 2.27e-07
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| MH1_SMAD_6_7 | cd10489 | N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding ... |
227-308 | 1.08e-05 | |||||
N-terminal Mad Homology 1 (MH1) domain in SMAD6 and SMAD7; The MH1 is a small DNA-binding domain present in SMAD (small mothers against decapentaplegic) family of proteins, which are signal transducers and transcriptional modulators that mediate multiple signaling pathways. MH1 binds to the DNA major groove in an unusual manner via a beta hairpin structure. It negatively regulates the functions of the MH2 domain, the C-terminal domain of SMAD. This MH1 domain is found in SMAD6 and SMAD7, both inhibitory SMADs (I-SMADs) and negative regulators of signaling mediated by TGF-beta superfamily. SMAD6 specifically inhibits bone morphogenetic protein (BMP) type I receptor mediated signaling while SMAD7 enhances muscle differentiation and is often associated with cancer, tissue fibrosis and inflammatory diseases. Pssm-ID: 199813 Cd Length: 119 Bit Score: 45.45 E-value: 1.08e-05
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| Atrophin-1 | pfam03154 | Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ... |
318-523 | 2.02e-04 | |||||
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity. Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 45.14 E-value: 2.02e-04
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| Atrophin-1 | pfam03154 | Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ... |
317-525 | 5.51e-04 | |||||
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity. Pssm-ID: 460830 [Multi-domain] Cd Length: 991 Bit Score: 43.60 E-value: 5.51e-04
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