Conserved Protein Domain Family
MPN_RPN11_CSN5

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cd08069: MPN_RPN11_CSN5 
Mov34/MPN/PAD-1 family: proteasomal regulatory protein Rpn11 and signalosome complex subunit CSN5
This family contains proteasomal regulatory protein Rpn11 (26S proteasome regulatory subunit rpn11; PAD1; POH1; RPN11; PSMD14; Rpn11 subunit of the 19S-proteasome; regulatory particle number 11) and 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. Rpn11 is responsible for substrate deubiquitination during proteasomal degradation. It is essential for maintaining a correct cell cycle and normal mitochondrial morphology and physiology; mutations in Rpn11 cause cell cycle and mitochondrial defects, temperature sensitivity and sensitivity to DNA damaging reagents such as UV. It has been shown that the C-terminal region of Rpn11 is involved in the regulation of the mitochondrial fission and tubulation processes. 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: 163700
View PSSM: cd08069
Aligned: 73 rows
Threshold Bit Score: 260.648
Threshold Setting Gi: 239977110
Created: 5-Oct-2009
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
MPN+ (JAMM)Zinc-binding
Feature 1:MPN+ (JAMM) motif
Evidence:
  • Comment:Based on literature and mutation studies

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                        #                                               
O00487        20 TDAPAVDTAEQVyISSLALLKMLKHGRAGVPMEVMGLMLGEfVDDYTVRVIDVFAMPQSGTGVSVEAVdpVFQAKMLd-- 97  horse
XP_002552100  64 EQKHNSRHFKRVmLSNMASYKILQHALKGGDVEIMGMLVGS-TDRDSIIVFDCYPLPVEGTETRVNAQl-ESYEYMVqy- 140 Lachancea therm...
Q6BMQ3        52 PWKSNAKYFKKTyISSLALCKMSVHAKSGGAIEVMGMMTGK-IIKNSIIVMDVYPLPVEGTETRVNAQa-EGYEYMVqy- 128 Debaryomyces ha...
Q75E19        62 LWKQDPTYFQKAaLSALACMKILRHAFDGGDMEVLGMLLGY-VQDEMIVVVDSYRLPVEGTETRVNAQm-ESYEYTVq-- 137 Ashbya gossypii...
XP_001730201  45 PWRRDRQYFRRVrVSVIALLKMLLHARSGGELEVMGLMQGH-VRGDTVYVIDVFALPVHGTETRVNAQn-EAYEYMVmh- 121 Malassezia glob...
XP_002619034  53 PWKKSARFFENArISTLALTKMSMHAKFGGSIEVMGMLTGK-IVGSSIVVCDVYPLPVEGTETRVNAQn-EAYEYMVqy- 129 Clavispora lusi...
Q6CRJ8        55 DLKRNPCHFQKClISRLATTKMLSHAVDGGDIEVMGMLVGY-TSNDMIVVKDCYSLPVQGTETRVNAHm-ESYEYMVq-- 130 Kluyveromyces l...
XP_002496073  62 PWSNNPRFFSSVsISRLACLKALEHALRGGNIEVMGMLIGT-TMNDQFVIFDIFELPVEGTETRVNAQt-ESYEYMVq-- 137 Zygosaccharomyc...
Q6FT36        63 STKNSPLFYQNVlLSKLACSKILCHATKGGNIEVMGMLLGN-VIGNTFVIFDCFELPVEGTETMVNAHm-ESYEYMVqfy 140 Candida glabrat...
A6ZXB7        60 QSSTDIPSYTHVlISKLSCEKITHYAVRGGNIEIMGILMGF-TLKDNIVVMDCFNLPVVGTETRVNAQl-ESYEYMVqyi 137 Saccharomyces c...
Feature 1                                  # #       #  #                                        
O00487        98 ------MLKQTGRp-----EMVVGWYHSHPGFGCWLSGVDINTQQSFEALsERAVAVVVDPIQS-VKGKVVIDAFRLINA 165 horse
XP_002552100 141 ----mnEVYDSCSh----pKNIVGWYHSHPGYGCWLSGIDVQTQELNQTFqDPYIAVVVDPKKSaEDKRLSIGAFRTLNE 212 Lachancea therm...
Q6BMQ3       129 ----leNSKQVGRd-----ENIVGWYHSHPGYGCWLSGIDVATQSLNQNFqDPYLAIVIDPMKTeDQGKVEIGAFRTFPD 199 Debaryomyces ha...
Q75E19       138 -----yLETAVPEg-----LAIVGWYHSHPGYGCWLSGIDAETQTLNQNFqDPYLAIVVDPKRSkASGVIDIGAFRTMPE 207 Ashbya gossypii...
XP_001730201 122 ----leASQRVHRl-----ENAIGWYHSHPGYGCWLSGIDVQTQQTNQQQ-DPFIAVVIDPLRTmSSGHIDLGAFRTWPQ 191 Malassezia glob...
XP_002619034 130 ----ldLLKMVQRe-----EHIVGWYHSHPGYGCWLSGIDVATQSLNQNFqDPYLAIVVDPIRTiRQRKVDIGAFRAFPP 200 Clavispora lusi...
Q6CRJ8       131 -----yLDAFVTKe-----DKIVGWYHSHPGYGCWLSNIDIQTQSLNQNYqDPYLAIVVDPKKSlSGNTLDIGAFRTLPS 200 Kluyveromyces l...
XP_002496073 138 -----yVDEMLPAn-----QNIVGWYHSHPGYDCWLSSIDMHTQQLNQNFqDPYVAIVIDPHKSiKERKLCIGAFRTIQE 207 Zygosaccharomyc...
Q6FT36       141 ---hemVERSYTRne--enLNIIGWYHSHPGYDCWLSNIDMQTQSLNQQHqDPYLAIVVDPHKSkNDQKVRIGSFRTYQD 215 Candida glabrat...
A6ZXB7       138 demynhNDGGDGRdykgakLNVVGWFHSHPGYDCWLSNIDIQTQDLNQRFqDPYVAIVVDPLKSlEDKILRMGAFRTIES 217 Saccharomyces c...
Feature 1                                                                                        
O00487       166 NmmvlgheprQTTSNLGHLNKPsiq----aliHGLNRHYYSIt-------INYRKNELEQKMLl------------nLHK 222 horse
XP_002552100 213 D---------EIPENVDQYGDSr--------yGHHSHKYYELe-------VKIFTSIFDTTLEq-------------LQL 255 Lachancea therm...
Q6BMQ3       200 Nyksp--dsaAPTNNTRGVPPSkqk-----dfGVHSDKYYSLd-------IQIFKSNLDTEILn------------iISN 253 Debaryomyces ha...
Q75E19       208 Ta--------DTRSVSSHSNASr--------yGHHSARYYELe-------VSYFEVPQERRWCdsrlsveppkpadaTER 264 Ashbya gossypii...
XP_001730201 192 Dqe-----adDTQPMRQHIPASkma-----eyGAHASKYYALd-------VQYFKNAADRPLYd------------qLWH 242 Malassezia glob...
XP_002619034 201 G---------HASSKKSIRSPShvakskrqdyGMHADQFYSLn-------ISFYHAVYDSKFId------------tILD 252 Clavispora lusi...
Q6CRJ8       201 Kdnne--hvdYYPLNIQLYQNSld------vnISKLKLKFKVd-------PAIQNNPNEPELMke----------lhECV 255 Kluyveromyces l...
XP_002496073 208 Pgvq----qdDELLEFYELKTSife-----srFDSSLGSSKLk-------IDTPKSDSLSDILlir---------rlFDT 262 Zygosaccharomyc...
Q6FT36       216 Q---------NDDTNFYELNTTvfd-----seLNKLENPLSV--------KIPFNSIESRNLEs------------nYLQ 261 Candida glabrat...
A6ZXB7       218 Ks--------DDNSATSYYELEtiif---dseLNRALFETKLnlhcviedDESEQISLNRLIDs------------mKQY 274 Saccharomyces c...
Feature 1                                                                                        
O00487       223 KSWMEGLtlqdysehck-------hnesvvkemlELAKNYNKaveeedkm--------------------tpeqlaiKNV 275 horse
XP_002552100 256 RFDISASetpessmv-----------leqllesvRNWNNFRKltnpnqflvqnsrq--------sdfsvqdhevdmgAEF 316 Lachancea therm...
Q6BMQ3       254 KSWIGKLiksvntanhq--------eqnmienvfKLINKLQKkevnqln----------------------rfeisfIKK 303 Debaryomyces ha...
Q75E19       265 AMLAQLLeaakacknvkrlqtvdralvpesigpyALREQADQdlqfrrplrs---------------fssnsiarrsSTE 329 Ashbya gossypii...
XP_001730201 243 KYWAQALcvgtstsmsmpa----htqqaepsrqpQIPPSLELqrihelreqmqdt---------vasirstnllpggVSY 309 Malassezia glob...
XP_002619034 253 KSWVSKLlesiegkn-----------dyhrrfvsKVQELLKLfqepilieskewrr--------mhelceefisrtlEPS 313 Clavispora lusi...
Q6CRJ8       256 ENWFHAKkvmkstvg-----------fnaigstvVNETEIGNedfthersnsi--------------sstsslttrhTTD 310 Kluyveromyces l...
XP_002496073 263 MKQWNTFne------------------------mITEPQLDDkgnvefdranp--------------lvtggkeqvmRRS 304 Zygosaccharomyc...
Q6FT36       262 KLSETVKqwr----------------------nfKIMEKIENtahtedtttnksistpgriiqtahefafaatsngnGSR 319 Candida glabrat...
A6ZXB7       275 SYLMDSKnvrtr------------------iklaTTSERVSNenkkni------------------------dyqnrSTR 312 Saccharomyces c...
Feature 1                                           
O00487       276 GKqd------------------------pKRHLEE 286 horse
XP_002552100 317 SSfsrrssrassv------tsskdestgsDVDMIS 345 Lachancea thermotolerans CBS 6340
Q6BMQ3       304 FDlife-------------------diisKKLMND 319 Debaryomyces hansenii
Q75E19       330 VAlgnaneeldplptladanlrnhdspsaDMAMDN 364 Ashbya gossypii ATCC 10895
XP_001730201 310 AQtartv------------------prsaDVDLHA 326 Malassezia globosa CBS 7966
XP_002619034 314 SNasd----------------------sdSLQAIL 326 Clavispora lusitaniae ATCC 42720
Q6CRJ8       311 VEmddqe------------------saqsSLDIPA 327 Kluyveromyces lactis NRRL Y-1140
XP_002496073 305 RQmdlsrrrsrsns----vlsvtsnenesDVDMDN 335 Zygosaccharomyces rouxii CBS 732
Q6FT36       320 VNimrsnsv-------------ssigsssDIEMED 341 Candida glabrata CBS 138
A6ZXB7       313 SQfclntqrgdstet-ssfgsmfsgdntsDVDMED 346 Saccharomyces cerevisiae YJM789

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