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Conserved domains on  [gi|392900409|ref|NP_001255476|]
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Smad-related protein daf-14 [Caenorhabditis elegans]

Protein Classification

mothers against decapentaplegic homolog; mothers against decapentaplegic homolog 4 family protein( domain architecture ID 10649998)

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
DWB smart00524
Domain B in dwarfin family proteins;
89-264 1.64e-73

Domain B in dwarfin family proteins;


:

Pssm-ID: 197770  Cd Length: 171  Bit Score: 222.96  E-value: 1.64e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409    89 PWCTIFYYELTVRLGKAFEAKVPTITIDGATGASDECRMSLTSQPSS-RNSKSSQIRNTVGAGIQLAYENGELWLTVLTD 167
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDPSDGNRFCLGQLSNVnRNEATELIRKHIGKGVQLSYENGDVWLYNRSD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409   168 QIVFVQCPFLNQTLNKPLKYVFRLQNKGDqkrMKIFDKEQFEQekTLALGPLTEKEVADERMRiFSNIRVSFCKGFGETY 247
Cdd:smart00524  81 SPIFVQSPYLDEPGGRTLDTVHKLPPGYS---IKVFDMEKFAQ--LLARELAKGFEGVYDLAR-MCTIRISFVKGWGPDY 154

                          170
                   ....*....|....*..
gi 392900409   248 SRLKVVNLPCWIEIILH 264
Cdd:smart00524 155 SRQTITSTPCWIEVHLN 171
 
Name Accession Description Interval E-value
DWB smart00524
Domain B in dwarfin family proteins;
89-264 1.64e-73

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 222.96  E-value: 1.64e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409    89 PWCTIFYYELTVRLGKAFEAKVPTITIDGATGASDECRMSLTSQPSS-RNSKSSQIRNTVGAGIQLAYENGELWLTVLTD 167
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDPSDGNRFCLGQLSNVnRNEATELIRKHIGKGVQLSYENGDVWLYNRSD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409   168 QIVFVQCPFLNQTLNKPLKYVFRLQNKGDqkrMKIFDKEQFEQekTLALGPLTEKEVADERMRiFSNIRVSFCKGFGETY 247
Cdd:smart00524  81 SPIFVQSPYLDEPGGRTLDTVHKLPPGYS---IKVFDMEKFAQ--LLARELAKGFEGVYDLAR-MCTIRISFVKGWGPDY 154

                          170
                   ....*....|....*..
gi 392900409   248 SRLKVVNLPCWIEIILH 264
Cdd:smart00524 155 SRQTITSTPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 88-264 5.37e-63

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: 195.92  E-value: 5.37e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409   88 KPWCTIFYYELTVRLGKAFEAKVPTITIDGATGASDECRMSL--TSQPSsRNSKSSQIRNTVGAGIQLAYENGELWLTVL 165
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSPNVTVDGFTDPSDGNRFCLglLSNVN-RNEAVEKVRKHIGKGVRLSYDGGEVWIYNL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  166 TDQIVFVQCPFLNQTLNKPLKYVFRLQNKGdqkRMKIFDKEQFEQEKTLALGPLTEKEVADERMRIfsnIRVSFCKGFGE 245
Cdd:pfam03166  80 SDHPVFVQSPYLNREAGRAPDTVHKVPPGE---SLKVFDMRKFQQLLSQELRRARLGPQDANKLCS---VRISFVKGWGP 153

                         170
                  ....*....|....*....
gi 392900409  246 TYSRLKVVNLPCWIEIILH 264
Cdd:pfam03166 154 DYSRQDITSTPCWIEIHLH 172
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 90-275 1.38e-36

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: 128.65  E-value: 1.38e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  90 WCTIFYYELTVRLGKAFEAKVPTITIDGATGAS---DECRMSLTSQPsSRNSKSSQIRNTVGAGIQLAYENGELWLTVLT 166
Cdd:cd10495    1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDPSnnsDRFCLGLLSNV-NRNATIENTRRHIGRGVHLFYVGGEVYAECLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409 167 DQIVFVQCPFLNQTLNKPLKYVFRLQNKGDqkrMKIFDKEQFEQ--EKTLALGPLTEKEVadERMrifSNIRVSFCKGFG 244
Cdd:cd10495   80 DSAIFVQSRNCNLRHGFHPATVCKIPPGCS---LKIFNNQSFAQllEQSVNRGFEAVYEL--TKM---CTIRISFVKGWG 151

                        170       180       190
                 ....*....|....*....|....*....|.
gi 392900409 245 ETYSRLKVVNLPCWIEIILHEPADEYDTVFR 275
Cdd:cd10495  152 AEYHRQDVTSTPCWIEIHLHGPLQWLDKVLT 182
 
Name Accession Description Interval E-value
DWB smart00524
Domain B in dwarfin family proteins;
89-264 1.64e-73

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 222.96  E-value: 1.64e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409    89 PWCTIFYYELTVRLGKAFEAKVPTITIDGATGASDECRMSLTSQPSS-RNSKSSQIRNTVGAGIQLAYENGELWLTVLTD 167
Cdd:smart00524   1 SWCKIAYYELNTRVGETFKVSSPSVTVDGFTDPSDGNRFCLGQLSNVnRNEATELIRKHIGKGVQLSYENGDVWLYNRSD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409   168 QIVFVQCPFLNQTLNKPLKYVFRLQNKGDqkrMKIFDKEQFEQekTLALGPLTEKEVADERMRiFSNIRVSFCKGFGETY 247
Cdd:smart00524  81 SPIFVQSPYLDEPGGRTLDTVHKLPPGYS---IKVFDMEKFAQ--LLARELAKGFEGVYDLAR-MCTIRISFVKGWGPDY 154

                          170
                   ....*....|....*..
gi 392900409   248 SRLKVVNLPCWIEIILH 264
Cdd:smart00524 155 SRQTITSTPCWIEVHLN 171
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 88-264 5.37e-63

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: 195.92  E-value: 5.37e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409   88 KPWCTIFYYELTVRLGKAFEAKVPTITIDGATGASDECRMSL--TSQPSsRNSKSSQIRNTVGAGIQLAYENGELWLTVL 165
Cdd:pfam03166   1 EIWCSVAYYELNTRVGEAFKVSSPNVTVDGFTDPSDGNRFCLglLSNVN-RNEAVEKVRKHIGKGVRLSYDGGEVWIYNL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  166 TDQIVFVQCPFLNQTLNKPLKYVFRLQNKGdqkRMKIFDKEQFEQEKTLALGPLTEKEVADERMRIfsnIRVSFCKGFGE 245
Cdd:pfam03166  80 SDHPVFVQSPYLNREAGRAPDTVHKVPPGE---SLKVFDMRKFQQLLSQELRRARLGPQDANKLCS---VRISFVKGWGP 153

                         170
                  ....*....|....*....
gi 392900409  246 TYSRLKVVNLPCWIEIILH 264
Cdd:pfam03166 154 DYSRQDITSTPCWIEIHLH 172
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 90-275 1.38e-36

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: 128.65  E-value: 1.38e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  90 WCTIFYYELTVRLGKAFEAKVPTITIDGATGAS---DECRMSLTSQPsSRNSKSSQIRNTVGAGIQLAYENGELWLTVLT 166
Cdd:cd10495    1 WCSISYYELNSRVGEQFKASNPSIIVDGFTDPSnnsDRFCLGLLSNV-NRNATIENTRRHIGRGVHLFYVGGEVYAECLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409 167 DQIVFVQCPFLNQTLNKPLKYVFRLQNKGDqkrMKIFDKEQFEQ--EKTLALGPLTEKEVadERMrifSNIRVSFCKGFG 244
Cdd:cd10495   80 DSAIFVQSRNCNLRHGFHPATVCKIPPGCS---LKIFNNQSFAQllEQSVNRGFEAVYEL--TKM---CTIRISFVKGWG 151

                        170       180       190
                 ....*....|....*....|....*....|.
gi 392900409 245 ETYSRLKVVNLPCWIEIILHEPADEYDTVFR 275
Cdd:cd10495  152 AEYHRQDVTSTPCWIEIHLHGPLQWLDKVLT 182
MH2 cd00050
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 90-264 5.50e-31

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: 113.85  E-value: 5.50e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  90 WCTIFYYELTVRLGKAFEAKVPTITIDGATGASDECRMSLtSQPSSRNsKSSQIRNT---VGAGIQLAYENGELWLTVLT 166
Cdd:cd00050    1 WCSIAYYELNTRVGELFHVYSPSVAVDGFTDPSNGDRFCL-GQLSNVN-RNETIERTrrhIGKGVHLYYVGGEVWAECLS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409 167 DQIVFVQCPFLNQTLNKPLKYVFRLQNKGDqkrMKIFDKEQFEQEktLALGPLTEKEVADERMRIFSnIRVSFCKGFGET 246
Cdd:cd00050   79 DHAIFVQSRNLDYPHGRHPLTVCKIPPGCS---IKVFDNQEFAQL--LHQSVNTGFEGVYELTKMCT-IRMSFVKGWGPE 152

                        170
                 ....*....|....*...
gi 392900409 247 YSRLKVVNLPCWIEIILH 264
Cdd:cd00050  153 YHRQDITSTPCWIEIHLH 170
MH2_SMAD_2_3 cd10985
C-terminal Mad Homology 2 (MH2) domain in SMAD2 and SMAD3; The MH2 domain is located at the ...
 80-274 2.83e-29

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: 110.02  E-value: 2.83e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  80 EPKYpkeekpWCTIFYYELTVRLGKAFEAKVPTITIDGATGASDECRMSLTSQPS-SRNSKSSQIRNTVGAGIQLAYENG 158
Cdd:cd10985    5 EPAF------WCSISYYEMNTRVGETFHASQPSLTVDGFTDPSNSERFCLGLLSNvNRNPQVELTRRHIGKGVRLYYIGG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409 159 ELWLTVLTDQIVFVQCPFLNQTLNKPLKYVFRLQNKGDqkrMKIFDKEQFEQEKTLALGPLTEKEVADERMrifSNIRVS 238
Cdd:cd10985   79 EVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCN---LKIFNNQEFAALLSQSVNQGFEAVYQLTRM---CTIRMS 152

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 392900409 239 FCKGFGETYSRLKVVNLPCWIEIILHEPADEYDTVF 274
Cdd:cd10985  153 FVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDRVL 188
MH2_SMAD_1_5_9 cd10497
C-terminal Mad Homology 2 (MH2) domain in SMAD1, SMAD5 and SMAD9; The MH2 domain is located at ...
 80-274 6.96e-26

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: 101.11  E-value: 6.96e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  80 EPKYpkeekpWCTIFYYELTVRLGKAFEAKVPTITIDGATGAS---DECRMSLTSQpSSRNSKSSQIRNTVGAGIQLAYE 156
Cdd:cd10497    3 EPKY------WCSIAYYELNNRVGEAFHASSTSIIVDGFTDPSnnsDRFCLGLLSN-VNRNSTIENTRRHIGKGVHLYYV 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409 157 NGELWLTVLTDQIVFVQCPFLNQTLNKPLKYVFRLQNkgdQKRMKIFDKEQFEQEKTLALGPLTEKEVADERMrifSNIR 236
Cdd:cd10497   76 GGEVYAECLSDSSIFVQSRNCNYHHGFHPTTVCKIPP---GCSLKIFNNQEFAQLLSQSVNHGFEAVYELTKM---CTIR 149

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 392900409 237 VSFCKGFGETYSRLKVVNLPCWIEIILHEPADEYDTVF 274
Cdd:cd10497  150 MSFVKGWGAEYHRQDVTSTPCWIEIHLHGPLQWLDKVL 187
MH2_I-SMAD cd10496
C-terminal Mad Homology 2 (MH2) domain in Inhibitory SMADs; The MH2 domain is located at the ...
 90-263 8.07e-22

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: 89.34  E-value: 8.07e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  90 WCTIFYYELTVRLGKAFEAKVPTITIDGATGASDE-CRMSLTSQpSSRNSKSSQIRNTVGAGIQLAYENGELWLTVLTDQ 168
Cdd:cd10496    1 WCTIAYWELRERVGRLYPVKQPAVNIFDDLPKGDGfCLGALNRQ-GNASEAVARVRSKIGLGVTLSREPDGVWIYNRSEY 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409 169 IVFVQCPFLNQTLNKPLKyVFRLQnkgDQKRMKIFDKEQFEQEKTL-----ALGPLTekevadermrIFSnIRVSFCKGF 243
Cdd:cd10496   80 PIFVNSPTLDSPPSRNLL-VTKVP---PGYSLKVFDYERAALLQRRddhfsPQGPVD----------PNS-VRISFVKGW 144

                        170       180
                 ....*....|....*....|
gi 392900409 244 GETYSRLKVVNLPCWIEIIL 263
Cdd:cd10496  145 GPNYSRQFITSCPCWLEILL 164
MH2_SMAD_4 cd10498
C-terminal Mad Homology 2 (MH2) domain in SMAD4; The MH2 domain is located at the C-terminus ...
 90-273 2.77e-21

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: 89.45  E-value: 2.77e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  90 WCTIFYYELTVRLGKAFeaKVP----TITIDGATGASDECRMSLTSQPS-SRNSKSSQIRNTVGAGIQLAYE-NGELWLT 163
Cdd:cd10498    4 WCSIAYFELDTQVGETF--KVPsscpTVTVDGYVDPSGGNRFCLGQLSNvHRTEASERARLHIGKGVQLDCKgEGDVWLR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409 164 VLTDQIVFVQCPFLNQTLNK-PLKYVFRLQNKGDqkrMKIFD----KEQFEQEKTLA----------------------- 215
Cdd:cd10498   82 CLSDHSVFVQSYYLDREAGRaPGDAVHKIYPSAY---IKVFDlrqcHRQMQQQAATAqaaaaaqaaavagnipgpgsvgg 158

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392900409 216 -LGPLTEKEVAD---ERMRIFSNIRVSFCKGFGETYSRLKVVNLPCWIEIILHEPADEYDTV 273
Cdd:cd10498  159 iAPAISLSAAAGigvDDLRRLCILRMSFVKGWGPDYPRQSIKETPCWIEIHLHRALQLLDEV 220
MH2_SMAD_6 cd10499
C-terminal Mad Homology 2 (MH2) domain in SMAD6; The MH2 domain is located at the C-terminus ...
 90-263 1.14e-15

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: 72.93  E-value: 1.14e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409  90 WCTIFYYELTVRLGKAFEAKVPTITI--DGATGaSDECRMSLTSqpSSRNSKSSQIRNTVGAGIQLAYENGELWLTVLTD 167
Cdd:cd10499   10 WCSVAYWEHRTRVGRLYAVYDQSVSIfyDLPQG-SGFCLGQLNL--EQRSESVRRTRSKIGYGILLSKEPDGVWAYNRSE 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392900409 168 QIVFVQCPflnqTLNKPLKYVFRLQNKGDQKRMKIFDkeqFEQEKTLALGPltEKEVADERMRIFSnIRVSFCKGFGETY 247
Cdd:cd10499   87 HPIFVNSP----TLDIPGSRTLVVRKVPPGYSIKVFD---YERSCLLQHTA--EPELADGPYDPNS-VRISFAKGWGPCY 156

                        170
                 ....*....|....*.
gi 392900409 248 SRLKVVNLPCWIEIIL 263
Cdd:cd10499  157 SRQFITSCPCWLEILL 172
 
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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