4WSN,4D10,4D18,6R7F


Conserved Protein Domain Family
MPN_CSN5

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cd08069: MPN_CSN5 (This model is not part of the current CDD release)
MPN domain of signalosome complex subunit CSN5
This family contains signalosomal CSN5 (COP9 signalosome complex subunit 5; COP9 complex homolog subunit 5; c-Jun activation domain-binding protein-1; CSN5/JAB1; JAB1). COP9 signalosome (CSN) and the proteasome lid are paralogous complexes and their respective subunits CSN5 and Rpn11 are most closely related between the two complexes, both containing the conserved JAMM (JAB1/MPN/Mov34 metalloenzyme) motif involved in zinc ion coordination and providing the active site for isopeptidase activity. CSN5, one of the eight subunits of CSN, is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27, and Smad4. Its MPN+ domain is critical for the physical interaction of RUNX3 and Jab1. It has been suggested that the direct interaction of CSN5/JAB1 with p27 provides p27 with a leucine-rich nuclear export signal (NES), which is required for binding to chromosomal region maintenance 1 (CRM1), and facilitates nuclear export. The over-expression of CSN5/JAB1 also has been implicated in cancer initiation and progression, including cancer of the lung, pancreas, mouth, thyroid, and breast, suggesting that the oncogenic activity of CSN5 is associated with the down-regulation of RUNX3.
Statistics
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PSSM-Id: 501538
Aligned: 98 rows
Threshold Bit Score: 250.886
Created: 5-Oct-2009
Updated: 30-Oct-2024
Structure
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Program:
Drawing:
Aligned Rows:
 
Zn binding siteMPN+ (JAMM)oligomer
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1: Zn binding site [ion binding site], 4 residue positions
Conserved feature residue pattern:[DE] H H DClick to see conserved feature residue pattern help
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                        
4WSN_E        35 PWTKDHHYFKYCkISALALLKMVMHARS--------------------------GGNLEVMGLMLGK------------- 75  human
CBH13612      27 PWKSAPRYFRSVrVSVLAVLQMLSHSDRgrpnvvlsdgqailsspqtttdtqrrENWFEVMGLLLGH------------- 93  Trypanosoma bru...
XP_001464572  59 PWRFDSLFFESVsVSLAATVKMFLHGTRgcpdm-----------------sqgrFNWFEVMGLLIGH------------- 108 Leishmania infa...
CUI15207      53 PWAADPRYFTSIrMSALAALKILIHAKTgqgkkg--------------tishdkNNWVEVMGLVQGH------------- 105 Bodo saltans
CAD2212728    62 PWKEEMKYFTEVkVTALAALKMFIHTKTgspdr-----------------lkgrADWYEVMGLMTGH------------- 111 Angomonas deanei
CDJ52933      42 SGLQSPVTFTDVwVSDVALTKMMAHAER--------------------------GGKIEVMGLLLGKavvtpetvdagsv 95  Eimeria brunetti
KAI2506189    51 PWTTETKYFTSVaISPSAIMKMMMHCQSgvnkg-----------------vqkgGNPIEVMGMLLGRpd----------- 102 Fragilaria crot...
OEU23059      64 SNRPVAKFFESIsLSPSAVTKIMMHCQSgvekg-----------------vaqgGNPIEVMGLMLGRpd----------- 115 Fragilariopsis ...
XP_026189912  42 VKAESPVVFTDVwVSDLALTKMMLHAEK--------------------------GGRIEVMGLLLGKavtveptdpaphf 95  Cyclospora caye...
XP_011130917   5 HAASDEDIYKVVrVSAAAMTKMIEHADK--------------------------GGEQEVMGIVFGK------------- 45  Gregarina nipha...
Feature 1                                                                   #                    
4WSN_E        76 ----------------------------------------VDGETMIIMDSFALPVEGTETRVNAQa---AAYEYMAayi 112 human
CBH13612      94 ----------------------------------------FQENELIVTSTFALPVDASEVECSMNe---ASQMYMLeyl 130 Trypanosoma bru...
XP_001464572 109 ----------------------------------------FSHRELILTDSFSLPVAASEVECSMTe---ASQIYMAnyl 145 Leishmania infa...
CUI15207     106 ----------------------------------------FFENTLVVTDAFALPVDASEVECSMNd---RSISYMLaql 142 Bodo saltans
CAD2212728   112 ----------------------------------------FYNNTLIVTDSFSLPVEASEVECSMDdrslIYQATYLn-- 149 Angomonas deanei
CDJ52933      96 gegtlst-------------hcesascasdidrkeeeeqeVQRGYFVVTDCFALPVEGTETRVNAAe---EANEFMIq-- 157 Eimeria brunetti
KAI2506189   103 ---------------------------------------pDTPHTLVVTDAFPLPIEGFETRVVADd--vDVVNHMIalg 141 Fragilaria crot...
OEU23059     116 ---------------------------------------pFKPTNLIVTDAFPLPIEGFETRVIADd--qSVINHMIslg 154 Fragilariopsis ...
XP_026189912  96 sdsvsfvappkdgdvreqscdpacmhaegdggaeagrqieRRRGYFVVTDCFALPVEGTETRVNAAe---DANEYMIq-- 170 Cyclospora caye...
XP_011130917  46 ----------------------------------------HSPQTFEIIDAVALPVQGTDTRITADa---STDEWLVnys 82  Gregarina nipha...
Feature 1                                            # #                   #                     
4WSN_E       113 eNAKQVGRl--------------------ENAIGWYHSHP---------GYGCWLSGIDVSTQMLNQQFq----EPFVAV 159 human
CBH13612     131 qYHQRTGFgvkcgwnaeeekevdeeieeaECCVGWYHSHP---------GYTCFLSGTDVATQRVGQAAq----DPWLAI 197 Trypanosoma bru...
XP_001464572 146 eYHRRLGKa-------------------ePGCLGWYHTHP---------GYSCFLSGIDVTTQRDSQQMq----DPWVAL 193 Leishmania infa...
CUI15207     143 eYSSQQGKp-------------------dAGCVGWYHSHP---------GYSCFLSGIDVNTQRVNQSVq----DPWVAI 190 Bodo saltans
CAD2212728   150 -YHRNLGKp-------------------dAGCIGWYHSHP---------GYTCFLSGIDVNTQREGQAFr----DPWLSI 196 Angomonas deanei
CDJ52933     158 -FLEAAEKip-----------------mqQKVVGWYHSHP---------NYGCWLSGIDVRTQQLQQQHq----DPFLAI 206 Eimeria brunetti
KAI2506189   142 eCLELTRH---------------------EKFMGWYHSHPfdl----gpNSHCFLSQTDLSTQLQWQRAedphgNPFVAL 196 Fragilaria crot...
OEU23059     155 eRLEGTRK---------------------EKFMGWYHSHPfdlvvgeesRSHCFLSQTDLSTQLQWQRAedphgNPFAAI 213 Fragilariopsis ...
XP_026189912 171 -YLEEAEKip-----------------tpQKVVGWYHSHP---------NYGCWLSGIDVRTQQLQQQHq----DPFLAI 219 Cyclospora caye...
XP_011130917  83 mQLEQMGCk--------------------ISAVGWYHTHP---------GYKCWLSGIDIDTQRRYQTHm----DPWVAL 129 Gregarina nipha...
Feature 1                                                                                        
4WSN_E       160 VIDPTRTi------SAGKVNLGAFRTYPKGykp------------------------pdEGPSEYQTIPLNkie---dfG 206 human
CBH13612     198 VVDPVRTi------STGRVDMRAFRTFPEGavgdgtes-------------tsadstgiGAAPRQCGFHDPlvr---eyG 255 Trypanosoma bru...
XP_001464572 194 VIDPVKTl------RTGQFSMKAFRTYPEGdfqgqrprsashsavdgaqpaaspasataSTMSDDYGLPPSnrv--kefG 265 Leishmania infa...
CUI15207     191 VVDPVQTa------ATGKIEIRAFRTLPERaagggpqlsaaatgaaaggaggsttapsqLTSLDASSIPAEkia---efG 261 Bodo saltans
CAD2212728   197 VVDPVRTi------ATGQLDFKAFRTFPTNem--------------------------kRGNERPETVPDMpskrikefG 244 Angomonas deanei
CDJ52933     207 VVDPIRTi------SNRCIELGSFRTFMPGeakre--------------------degdDEAASSQLLPAEkvn---dfG 257 Eimeria brunetti
KAI2506189   197 VVDPLRSi------HRGVPEIKAFRAYPPEyna-----------------------piaNECPDGSIVTDEqtrl-elwG 246 Fragilaria crot...
OEU23059     214 VVDPLRSm------HLGTPQLKAFRAYPPEyqs-----------------------kiaNECPDGSIITSErvrl-erwG 263 Fragilariopsis ...
XP_026189912 220 VLGAFRT-------FLPGEERRHIDEMDKA-----------------------------EPLLPEDKVHDF--------G 255 Cyclospora caye...
XP_011130917 130 VIDPTNQdqieigaFRLAGTNKNFPTFVPAp----------------------------GYATNSSHGQSK--------P 173 Gregarina nipha...
Feature 1                        
4WSN_E       207 VHCKQYYALEVSYFKS 222 human
CBH13612     256 AHGHCYYELPITLVRS 271 Trypanosoma brucei gambiense DAL972
XP_001464572 266 MHAHRYYELPVRIVQS 281 Leishmania infantum JPCM5
CUI15207     262 VYVNEYYELPITLVRS 277 Bodo saltans
CAD2212728   245 MYANCYYELPITIVRS 260 Angomonas deanei
CDJ52933     258 AHWKQYYQLRVHWCSN 273 Eimeria brunetti
KAI2506189   247 SCWNRYYALQVEYFMS 262 Fragilaria crotonensis
OEU23059     264 SCWNRYYEMNVEYYMS 279 Fragilariopsis cylindrus CCMP1102
XP_026189912 256 VHWQHYYPLKVHYCCN 271 Cyclospora cayetanensis
XP_011130917 174 RQEDCYYSIPVELVQP 189 Gregarina niphandrodes

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