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Conserved domains on  [gi|1734326496|ref|NP_001360602|]
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MH2 domain-containing protein [Caenorhabditis elegans]

Protein Classification

mothers against decapentaplegic homolog; mothers against decapentaplegic homolog 4 family protein( domain architecture ID 10180375)

mothers against decapentaplegic homolog such as SMAD1, SMAD5 and SMAD9 (also known as SMAD8); 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| mothers against decapentaplegic homolog 4 family protein such as 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)

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 68-251 4.87e-120

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: 340.13  E-value: 4.87e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  68 WATVSYYELNTRVGEQVKVSSTTITIDGFTDPCINGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVRsnGSLFAQCE 147
Cdd:cd10495     1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDPSNNSDRFCLGLLSNVNRNATIENTRRHIGRGVHLFYVG--GEVYAECL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 148 SDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEYQRQD 227
Cdd:cd10495    79 SDSAIFVQSRNCNLRHGFHPATVCKIPPGCSLKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGWGAEYHRQD 158

                         170       180
                  ....*....|....*....|....
gi 1734326496 228 VTSTPCWIEIHLHAPLAWLDRVLS 251
Cdd:cd10495   159 VTSTPCWIEIHLHGPLQWLDKVLT 182
 
Name Accession Description Interval E-value
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 68-251 4.87e-120

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: 340.13  E-value: 4.87e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  68 WATVSYYELNTRVGEQVKVSSTTITIDGFTDPCINGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVRsnGSLFAQCE 147
Cdd:cd10495     1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDPSNNSDRFCLGLLSNVNRNATIENTRRHIGRGVHLFYVG--GEVYAECL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 148 SDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEYQRQD 227
Cdd:cd10495    79 SDSAIFVQSRNCNLRHGFHPATVCKIPPGCSLKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGWGAEYHRQD 158

                         170       180
                  ....*....|....*....|....
gi 1734326496 228 VTSTPCWIEIHLHAPLAWLDRVLS 251
Cdd:cd10495   159 VTSTPCWIEIHLHGPLQWLDKVLT 182
DWB smart00524
Domain B in dwarfin family proteins;
67-240 7.98e-92

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 268.41  E-value: 7.98e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496   67 FWATVSYYELNTRVGEQVKVSSTTITIDGFTDPcINGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVrsNGSLFAQC 146
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDP-SDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYE--NGDVWLYN 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  147 ESDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEYQRQ 226
Cdd:smart00524  78 RSDSPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSRQ 157

                          170
                   ....*....|....
gi 1734326496  227 DVTSTPCWIEIHLH 240
Cdd:smart00524 158 TITSTPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 66-240 8.90e-86

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: 252.93  E-value: 8.90e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  66 QFWATVSYYELNTRVGEQVKVSSTTITIDGFTDPCiNGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVrsNGSLFAQ 145
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSPNVTVDGFTDPS-DGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYD--GGEVWIY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 146 CESDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEYQR 225
Cdd:pfam03166  78 NLSDHPVFVQSPYLNREAGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKGWGPDYSR 157

                         170
                  ....*....|....*
gi 1734326496 226 QDVTSTPCWIEIHLH 240
Cdd:pfam03166 158 QDITSTPCWIEIHLH 172
 
Name Accession Description Interval E-value
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 68-251 4.87e-120

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: 340.13  E-value: 4.87e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  68 WATVSYYELNTRVGEQVKVSSTTITIDGFTDPCINGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVRsnGSLFAQCE 147
Cdd:cd10495     1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDPSNNSDRFCLGLLSNVNRNATIENTRRHIGRGVHLFYVG--GEVYAECL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 148 SDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEYQRQD 227
Cdd:cd10495    79 SDSAIFVQSRNCNLRHGFHPATVCKIPPGCSLKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGWGAEYHRQD 158

                         170       180
                  ....*....|....*....|....
gi 1734326496 228 VTSTPCWIEIHLHAPLAWLDRVLS 251
Cdd:cd10495   159 VTSTPCWIEIHLHGPLQWLDKVLT 182
MH2_SMAD_1_5_9 cd10497
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ...
 64-264 9.83e-101

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: 292.17  E-value: 9.83e-101
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  64 EEQFWATVSYYELNTRVGEQVKVSSTTITIDGFTDPCINGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVrsNGSLF 143
Cdd:cd10497     3 EPKYWCSIAYYELNNRVGEAFHASSTSIIVDGFTDPSNNSDRFCLGLLSNVNRNSTIENTRRHIGKGVHLYYV--GGEVY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 144 AQCESDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEY 223
Cdd:cd10497    81 AECLSDSSIFVQSRNCNYHHGFHPTTVCKIPPGCSLKIFNNQEFAQLLSQSVNHGFEAVYELTKMCTIRMSFVKGWGAEY 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1734326496 224 QRQDVTSTPCWIEIHLHAPLAWLDRVLSTMGPTPRPISSIS 264
Cdd:cd10497   161 HRQDVTSTPCWIEIHLHGPLQWLDKVLTQMGSPHNPISSVS 201
DWB smart00524
Domain B in dwarfin family proteins;
67-240 7.98e-92

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 268.41  E-value: 7.98e-92
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496   67 FWATVSYYELNTRVGEQVKVSSTTITIDGFTDPcINGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVrsNGSLFAQC 146
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDP-SDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYE--NGDVWLYN 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  147 ESDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEYQRQ 226
Cdd:smart00524  78 RSDSPIFVQSPYLDEPGGRTLDTVHKLPPGYSIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKGWGPDYSRQ 157

                          170
                   ....*....|....
gi 1734326496  227 DVTSTPCWIEIHLH 240
Cdd:smart00524 158 TITSTPCWIEVHLN 171
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 64-253 6.48e-88

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: 259.48  E-value: 6.48e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  64 EEQFWATVSYYELNTRVGEQVKVSSTTITIDGFTDPCiNGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVrsNGSLF 143
Cdd:cd10985     5 EPAFWCSISYYEMNTRVGETFHASQPSLTVDGFTDPS-NSERFCLGLLSNVNRNPQVELTRRHIGKGVRLYYI--GGEVF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 144 AQCESDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEY 223
Cdd:cd10985    82 AECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLSQSVNQGFEAVYQLTRMCTIRMSFVKGWGAEY 161

                         170       180       190
                  ....*....|....*....|....*....|
gi 1734326496 224 QRQDVTSTPCWIEIHLHAPLAWLDRVLSTM 253
Cdd:cd10985   162 RRQTVTSTPCWIELHLNGPLQWLDRVLTQM 191
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 66-240 8.90e-86

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: 252.93  E-value: 8.90e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  66 QFWATVSYYELNTRVGEQVKVSSTTITIDGFTDPCiNGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVrsNGSLFAQ 145
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSPNVTVDGFTDPS-DGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYD--GGEVWIY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 146 CESDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEYQR 225
Cdd:pfam03166  78 NLSDHPVFVQSPYLNREAGRAPDTVHKVPPGESLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKGWGPDYSR 157

                         170
                  ....*....|....*
gi 1734326496 226 QDVTSTPCWIEIHLH 240
Cdd:pfam03166 158 QDITSTPCWIEIHLH 172
MH2 cd00050
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 68-240 1.49e-78

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: 234.81  E-value: 1.49e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  68 WATVSYYELNTRVGEQVKVSSTTITIDGFTDPCiNGSKISLGLFSNVNRNATIENTRRHIGNGVKLTYVrsNGSLFAQCE 147
Cdd:cd00050     1 WCSIAYYELNTRVGELFHVYSPSVAVDGFTDPS-NGDRFCLGQLSNVNRNETIERTRRHIGKGVHLYYV--GGEVWAECL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 148 SDSAIFVQSSNCNYINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKMTFIRMSFVKGWGAEYQRQD 227
Cdd:cd00050    78 SDHAIFVQSRNLDYPHGRHPLTVCKIPPGCSIKVFDNQEFAQLLHQSVNTGFEGVYELTKMCTIRMSFVKGWGPEYHRQD 157

                         170
                  ....*....|...
gi 1734326496 228 VTSTPCWIEIHLH 240
Cdd:cd00050   158 ITSTPCWIEIHLH 170
MH2_SMAD_4 cd10498
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ...
 66-250 5.15e-46

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: 153.39  E-value: 5.15e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  66 QFWATVSYYELNTRVGEQVKVSST--TITIDGFTDPCiNGSKISLGLFSNVNRNATIENTRRHIGNGVKLTyVRSNGSLF 143
Cdd:cd10498     2 EYWCSIAYFELDTQVGETFKVPSScpTVTVDGYVDPS-GGNRFCLGQLSNVHRTEASERARLHIGKGVQLD-CKGEGDVW 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 144 AQCESDSAIFVQSsncNYINGFHS----TTVVKIANKCSLKIFDM-EIFRQLLEDCSRRGFDASF--------------- 203
Cdd:cd10498    80 LRCLSDHSVFVQS---YYLDREAGrapgDAVHKIYPSAYIKVFDLrQCHRQMQQQAATAQAAAAAqaaavagnipgpgsv 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734326496 204 ------------------DLQKMTFIRMSFVKGWGAEYQRQDVTSTPCWIEIHLHAPLAWLDRVL 250
Cdd:cd10498   157 ggiapaislsaaagigvdDLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLHRALQLLDEVL 221
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 68-239 1.72e-29

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: 108.98  E-value: 1.72e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  68 WATVSYYELNTRVGEQVKVSSTTITIdgFTDpCINGSKISLG-LFSNVNRNATIENTRRHIGNGVKLTyvRSNGSLFAQC 146
Cdd:cd10496     1 WCTIAYWELRERVGRLYPVKQPAVNI--FDD-LPKGDGFCLGaLNRQGNASEAVARVRSKIGLGVTLS--REPDGVWIYN 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 147 ESDSAIFVQSSNCNYINGfHSTTVVKIANKCSLKIFDmeifRQLLEDCSRRGFDASFDLQKMTF-IRMSFVKGWGAEYQR 225
Cdd:cd10496    76 RSEYPIFVNSPTLDSPPS-RNLLVTKVPPGYSLKVFD----YERAALLQRRDDHFSPQGPVDPNsVRISFVKGWGPNYSR 150

                         170
                  ....*....|....
gi 1734326496 226 QDVTSTPCWIEIHL 239
Cdd:cd10496   151 QFITSCPCWLEILL 164
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 68-241 1.71e-25

C-terminal Mad Homology 2 (MH2) domain in SMAD6; 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, an inhibitory or antagonistic SMAD (I-SMAD), acts as a negative regulator of signaling mediated by the TGF-beta superfamily of 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. SMAD6 and SMAD7 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.


Pssm-ID: 199824  Cd Length: 174  Bit Score: 98.74  E-value: 1.71e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  68 WATVSYYELNTRVGEQVKVSSTTITIdgFTD-PciNGSKISLGLFSNVNRNATIENTRRHIGNGVKLTyvRSNGSLFAQC 146
Cdd:cd10499    10 WCSVAYWEHRTRVGRLYAVYDQSVSI--FYDlP--QGSGFCLGQLNLEQRSESVRRTRSKIGYGILLS--KEPDGVWAYN 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 147 ESDSAIFVQSSNCNyINGFHSTTVVKIANKCSLKIFDMEIFRQLLEDCSRRGFDASFDLQKmtfIRMSFVKGWGAEYQRQ 226
Cdd:cd10499    84 RSEHPIFVNSPTLD-IPGSRTLVVRKVPPGYSIKVFDYERSCLLQHTAEPELADGPYDPNS---VRISFAKGWGPCYSRQ 159

                         170
                  ....*....|....*
gi 1734326496 227 DVTSTPCWIEIHLHA 241
Cdd:cd10499   160 FITSCPCWLEILLNN 174
MH2_SMAD_7 cd10500
C-terminal Mad Homology 2 (MH2) domain in SMAD7; The MH2 domain is located at the C-terminus ...
 64-237 3.77e-16

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: 73.92  E-value: 3.77e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496  64 EEQFWATVSYYELNTRVGEQVKVSSTTITIdgFTDpCINGSKISLGLFSNVNRNATIENTRRHIGNGVKLTyvRSNGSLF 143
Cdd:cd10500     4 DQSHWCVVAYWEEKTRVGRLYSVQEPSLDI--FYD-LPQGNGFCLGQLNSDNKSQLVQKVRSKIGYGIQLT--REVDGVW 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734326496 144 AQCESDSAIFVQSSNCNYINGfHSTTVVKIANKCSLKIFDMEIFRQLledcsRRGFDASFDLQKMT--FIRMSFVKGWGA 221
Cdd:cd10500    79 VYNRSSYPIFIKSATLDNPDS-RTLLVHKVFPGFSIKAFDYEKAYSL-----QRPNDHEFMQQPWTgfTVQISFVKGWGQ 152

                         170
                  ....*....|....*.
gi 1734326496 222 EYQRQDVTSTPCWIEI 237
Cdd:cd10500   153 CYTRQFISSCPCWLEV 168
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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