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Conserved domains on  [gi|24652852|ref|NP_725091|]
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expansion, isoform A [Drosophila melanogaster]

Protein Classification

mothers against decapentaplegic homolog; mothers against decapentaplegic homolog 4 family protein( domain architecture ID 10748959)

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 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 55-226 6.07e-52

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: 179.74  E-value: 6.07e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852     55 EIWAKVIVFERNRRVAKAYAR-APVLTINGSDDGFDGMRIGLCGFDNPMRDQKTDEMKRVIGQGVKIKMDDaGNILIRRY 133
Cdd:pfam03166    1 EIWCSVAYYELNTRVGEAFKVsSPNVTVDGFTDPSDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDG-GEVWIYNL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852    134 AKSNVYVKSTaSSPNEETSIGAEILKLPNQAlesekIVKLFDMKKFQSNVNRELRRAYPDRRRLETQCLSAVAFVK---- 209
Cdd:pfam03166   80 SDHPVFVQSP-YLNREAGRAPDTVHKVPPGE-----SLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKgwgp 153

                          170
                   ....*....|....*....
gi 24652852    210 --SENDILECPIWVLIVNV 226
Cdd:pfam03166  154 dySRQDITSTPCWIEIHLH 172
 
Name Accession Description Interval E-value
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 55-226 6.07e-52

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: 179.74  E-value: 6.07e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852     55 EIWAKVIVFERNRRVAKAYAR-APVLTINGSDDGFDGMRIGLCGFDNPMRDQKTDEMKRVIGQGVKIKMDDaGNILIRRY 133
Cdd:pfam03166    1 EIWCSVAYYELNTRVGEAFKVsSPNVTVDGFTDPSDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDG-GEVWIYNL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852    134 AKSNVYVKSTaSSPNEETSIGAEILKLPNQAlesekIVKLFDMKKFQSNVNRELRRAYPDRRRLETQCLSAVAFVK---- 209
Cdd:pfam03166   80 SDHPVFVQSP-YLNREAGRAPDTVHKVPPGE-----SLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKgwgp 153

                          170
                   ....*....|....*....
gi 24652852    210 --SENDILECPIWVLIVNV 226
Cdd:pfam03166  154 dySRQDITSTPCWIEIHLH 172
DWB smart00524
Domain B in dwarfin family proteins;
56-224 6.81e-39

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 142.45  E-value: 6.81e-39
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852      56 IWAKVIVFERNRRVAKAYAR-APVLTINGSDDGFDGMRIGLCGFDNPMRDQKTDEMKRVIGQGVKIKMDDaGNILIRRYA 134
Cdd:smart00524    1 SWCKIAYYELNTRVGETFKVsSPSVTVDGFTDPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYEN-GDVWLYNRS 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852     135 KSNVYVKSTASSpNEETSIGAEILKLPNQAlesekIVKLFDMKKFQSNVNRELRRAYPDRRRLETQCLSAVAFVK----- 209
Cdd:smart00524   80 DSPIFVQSPYLD-EPGGRTLDTVHKLPPGY-----SIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKgwgpd 153

                           170
                    ....*....|....*.
gi 24652852     210 -SENDILECPIWVLIV 224
Cdd:smart00524  154 ySRQTITSTPCWIEVH 169
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 57-223 2.38e-09

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: 57.77  E-value: 2.38e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852   57 WAKVIVFERNRRVAKAY-ARAPVLTING-SDDGFDGMRIGLCGFDNPMRDQKTDEMKRVIGQGVKIkMDDAGNILIRRYA 134
Cdd:cd10495    1 WCSISYYELNSRVGEQFkASNPSIIVDGfTDPSNNSDRFCLGLLSNVNRNATIENTRRHIGRGVHL-FYVGGEVYAECLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852  135 KSNVYVKstasSPNEETSIGAE---ILKLPNQALesekiVKLFDMKKFQSNVNRELRRAYPDRRRLETQCLSAVAFVKS- 210
Cdd:cd10495   80 DSAIFVQ----SRNCNLRHGFHpatVCKIPPGCS-----LKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGw 150

                        170
                 ....*....|....*...
gi 24652852  211 -----ENDILECPIWVLI 223
Cdd:cd10495  151 gaeyhRQDVTSTPCWIEI 168
 
Name Accession Description Interval E-value
MH2 pfam03166
MH2 domain; This is the MH2 (MAD homology 2) domain found at the carboxy terminus of MAD ...
 55-226 6.07e-52

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: 179.74  E-value: 6.07e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852     55 EIWAKVIVFERNRRVAKAYAR-APVLTINGSDDGFDGMRIGLCGFDNPMRDQKTDEMKRVIGQGVKIKMDDaGNILIRRY 133
Cdd:pfam03166    1 EIWCSVAYYELNTRVGEAFKVsSPNVTVDGFTDPSDGNRFCLGLLSNVNRNEAVEKVRKHIGKGVRLSYDG-GEVWIYNL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852    134 AKSNVYVKSTaSSPNEETSIGAEILKLPNQAlesekIVKLFDMKKFQSNVNRELRRAYPDRRRLETQCLSAVAFVK---- 209
Cdd:pfam03166   80 SDHPVFVQSP-YLNREAGRAPDTVHKVPPGE-----SLKVFDMRKFQQLLSQELRRARLGPQDANKLCSVRISFVKgwgp 153

                          170
                   ....*....|....*....
gi 24652852    210 --SENDILECPIWVLIVNV 226
Cdd:pfam03166  154 dySRQDITSTPCWIEIHLH 172
DWB smart00524
Domain B in dwarfin family proteins;
56-224 6.81e-39

Domain B in dwarfin family proteins;


Pssm-ID: 197770  Cd Length: 171  Bit Score: 142.45  E-value: 6.81e-39
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852      56 IWAKVIVFERNRRVAKAYAR-APVLTINGSDDGFDGMRIGLCGFDNPMRDQKTDEMKRVIGQGVKIKMDDaGNILIRRYA 134
Cdd:smart00524    1 SWCKIAYYELNTRVGETFKVsSPSVTVDGFTDPSDGNRFCLGQLSNVNRNEATELIRKHIGKGVQLSYEN-GDVWLYNRS 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852     135 KSNVYVKSTASSpNEETSIGAEILKLPNQAlesekIVKLFDMKKFQSNVNRELRRAYPDRRRLETQCLSAVAFVK----- 209
Cdd:smart00524   80 DSPIFVQSPYLD-EPGGRTLDTVHKLPPGY-----SIKVFDMEKFAQLLARELAKGFEGVYDLARMCTIRISFVKgwgpd 153

                           170
                    ....*....|....*.
gi 24652852     210 -SENDILECPIWVLIV 224
Cdd:smart00524  154 ySRQTITSTPCWIEVH 169
MH2_R-SMAD cd10495
C-terminal Mad Homology 2 (MH2) domain in receptor regulated SMADs; The MH2 domain is located ...
 57-223 2.38e-09

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: 57.77  E-value: 2.38e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852   57 WAKVIVFERNRRVAKAY-ARAPVLTING-SDDGFDGMRIGLCGFDNPMRDQKTDEMKRVIGQGVKIkMDDAGNILIRRYA 134
Cdd:cd10495    1 WCSISYYELNSRVGEQFkASNPSIIVDGfTDPSNNSDRFCLGLLSNVNRNATIENTRRHIGRGVHL-FYVGGEVYAECLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852  135 KSNVYVKstasSPNEETSIGAE---ILKLPNQALesekiVKLFDMKKFQSNVNRELRRAYPDRRRLETQCLSAVAFVKS- 210
Cdd:cd10495   80 DSAIFVQ----SRNCNLRHGFHpatVCKIPPGCS-----LKIFNNQSFAQLLEQSVNRGFEAVYELTKMCTIRISFVKGw 150

                        170
                 ....*....|....*...
gi 24652852  211 -----ENDILECPIWVLI 223
Cdd:cd10495  151 gaeyhRQDVTSTPCWIEI 168
MH2 cd00050
C-terminal Mad Homology 2 (MH2) domain; The MH2 domain is found in the SMAD (small mothers ...
 57-223 1.00e-05

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: 46.83  E-value: 1.00e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852   57 WAKVIVFERNRRVAKAYA-RAPVLTINGSDDGFDGMRIGLCGFDNPMRDQKTDEMKRVIGQGVKIKMdDAGNILIRRYAK 135
Cdd:cd00050    1 WCSIAYYELNTRVGELFHvYSPSVAVDGFTDPSNGDRFCLGQLSNVNRNETIERTRRHIGKGVHLYY-VGGEVWAECLSD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24652852  136 SNVYVKstasSPN---EETSIGAEILKLPNQALesekiVKLFDMKKFQSNVNRELRRAYPDRRRLETQCLSAVAFVK--- 209
Cdd:cd00050   80 HAIFVQ----SRNldyPHGRHPLTVCKIPPGCS-----IKVFDNQEFAQLLHQSVNTGFEGVYELTKMCTIRMSFVKgwg 150

                        170
                 ....*....|....*..
gi 24652852  210 ---SENDILECPIWVLI 223
Cdd:cd00050  151 peyHRQDITSTPCWIEI 167
 
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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