NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|33563284|ref|NP_036132|]
View 

COP9 signalosome complex subunit 6 [Mus musculus]

Protein Classification

COP9 signalosome complex subunit 6( domain architecture ID 10169151)

COP9 signalosome complex subunit 6 is a component of the COP9 signalosome complex (CSN), an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes

Gene Ontology:  GO:0000338|GO:0008180|GO:0045116|GO:2000434
MEROPS:  M67
PubMed:  22575649|18926707

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
MPN_CSN6 cd08063
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 ...
 36-318 1.20e-170

Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 signalosome complex subunit 6; CSN6 (COP9 signalosome subunit 6; COP9 subunit 6; MOV34 homolog, 34 kD) is one of the eight subunits of COP9 signalosome, a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. CSN6 is an MPN-domain protein that directly interacts with the MPN+-domain subunit CSN5. It is cleaved during apoptosis by activated caspases. CSN6 processing occurs in CSN/CRL (cullin-RING Ub ligase) complexes and is followed by the cleavage of Rbx1, the direct interaction partner of CSN6. CSN6 cleavage enhances CSN-mediated deneddylating activity (i.e. cleavage of ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. The cleavage of Rbx1 and increased deneddylation of cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final apoptotic steps. While CSN6 shows a typical MPN metalloprotease fold, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.


:

Pssm-ID: 163694 [Multi-domain]  Cd Length: 288  Bit Score: 474.82  E-value: 1.20e-170
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  36 VSVALHPLVILNISDHWIRMRSQEGR-PMQVIGALIGKQEGRNIEVMNSFELLSHTVE-EKIIIDKEYYYTKEEQFKQVF 113
Cdd:cd08063   1 LSVKLHPLVILNISDHITRHRAQSQSePPRVVGALLGQQDGREIEIENSFELKYDTNEdGEIVLDKEFLETRLEQFKQVF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 114 KELEFLGWYTTG-GPPDPSDIHVHKQVCEIIESPLFLKLNPMT--KHTDLPVSVFESVIDIINGEATMLFAELTYTLATE 190
Cdd:cd08063  81 KDLDFVGWYTTGpGGPTESDLPIHKQILEINESPVLLLLDPEAnaSGKDLPVTIYESVLELVDGEATLRFRELPYTIETG 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 191 EAERIGVDHVARMTATGSGENSTVAEHLIAQHSAIKMLHSRVKLILEYVKASEAGEVPFNHEILREAYALCHCLPVLSTD 270
Cdd:cd08063 161 EAERIGVDHVARGGASGSSEKSTVAAHLQAQHNAIKMLNSRVELILEYLKAVPVGEVPPDHSILRSISALCSRLPVLKSE 240

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 33563284 271 KFKTDFYDQCNDVGLMAYLGTITKTCNTMNQFVNKFNVLYDRQGIGRR 318
Cdd:cd08063 241 AFREELLAEYNDVLLVAYLATLTKGCNTLNELVDKFNVVYDRKGSGRR 288
 
Name Accession Description Interval E-value
MPN_CSN6 cd08063
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 ...
 36-318 1.20e-170

Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 signalosome complex subunit 6; CSN6 (COP9 signalosome subunit 6; COP9 subunit 6; MOV34 homolog, 34 kD) is one of the eight subunits of COP9 signalosome, a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. CSN6 is an MPN-domain protein that directly interacts with the MPN+-domain subunit CSN5. It is cleaved during apoptosis by activated caspases. CSN6 processing occurs in CSN/CRL (cullin-RING Ub ligase) complexes and is followed by the cleavage of Rbx1, the direct interaction partner of CSN6. CSN6 cleavage enhances CSN-mediated deneddylating activity (i.e. cleavage of ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. The cleavage of Rbx1 and increased deneddylation of cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final apoptotic steps. While CSN6 shows a typical MPN metalloprotease fold, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.


Pssm-ID: 163694 [Multi-domain]  Cd Length: 288  Bit Score: 474.82  E-value: 1.20e-170
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  36 VSVALHPLVILNISDHWIRMRSQEGR-PMQVIGALIGKQEGRNIEVMNSFELLSHTVE-EKIIIDKEYYYTKEEQFKQVF 113
Cdd:cd08063   1 LSVKLHPLVILNISDHITRHRAQSQSePPRVVGALLGQQDGREIEIENSFELKYDTNEdGEIVLDKEFLETRLEQFKQVF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 114 KELEFLGWYTTG-GPPDPSDIHVHKQVCEIIESPLFLKLNPMT--KHTDLPVSVFESVIDIINGEATMLFAELTYTLATE 190
Cdd:cd08063  81 KDLDFVGWYTTGpGGPTESDLPIHKQILEINESPVLLLLDPEAnaSGKDLPVTIYESVLELVDGEATLRFRELPYTIETG 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 191 EAERIGVDHVARMTATGSGENSTVAEHLIAQHSAIKMLHSRVKLILEYVKASEAGEVPFNHEILREAYALCHCLPVLSTD 270
Cdd:cd08063 161 EAERIGVDHVARGGASGSSEKSTVAAHLQAQHNAIKMLNSRVELILEYLKAVPVGEVPPDHSILRSISALCSRLPVLKSE 240

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 33563284 271 KFKTDFYDQCNDVGLMAYLGTITKTCNTMNQFVNKFNVLYDRQGIGRR 318
Cdd:cd08063 241 AFREELLAEYNDVLLVAYLATLTKGCNTLNELVDKFNVVYDRKGSGRR 288
JAB_MPN smart00232
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
 38-168 8.49e-30

JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal subunits. Domain at Mpr1p and Pad1p N-termini. Domain of unknown function.


Pssm-ID: 214573  Cd Length: 135  Bit Score: 110.54  E-value: 8.49e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284     38 VALHPLVILNISDHWIRMRsqegrPMQVIGALIGKQEGRNIEVMNSFELLSHTVEEKI-IIDKEYYYTKEEQFKQVFKEL 116
Cdd:smart00232   2 VKVHPLVPLNILKHAIRDG-----PEEVCGVLLGKSNKDRPEVKEVFAVPNEPQDDSVqEYDEDYSHLMDEELKKVNKDL 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 33563284    117 EFLGWYTTGG--PPDPS--DIHVHKQVCEIIESPLFLKLNPM-TKHTDLPVSVFESV 168
Cdd:smart00232  77 EIVGWYHSHPdeSPFPSevDVATHESYQAPWPISVVLIVDPIkSFQGRLSLRAFRLT 133
JAB pfam01398
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ...
 33-145 2.61e-28

JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. This family is also known as the MPN domain and PAD-1-like domain, JABP1 domain or JAMM domain. These are metalloenzymes that function as the ubiquitin isopeptidase/ deubiquitinase in the ubiquitin-based signalling and protein turnover pathways in eukaryotes. Versions of the domain in prokaryotic cognates of the ubiquitin-modification pathway are shown to have a similar role, and the archael protein from Haloferax volcanii is found to cleave ubiquitin-like small archaeal modifier proteins (SAMP1/2) from protein conjugates.


Pssm-ID: 396120  Cd Length: 117  Bit Score: 105.89  E-value: 2.61e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284    33 TGSVSVALHPLVILNISDHWIRMRSQEGRpmqVIGALIGKQEGR-NIEVMNSFELLSHTVEEK---IIIDKEYYYTKEEQ 108
Cdd:pfam01398   1 SSVRTVIIHPLVLLKILDHANRGGKIGEE---VMGVLLGKLEGDgTIEITNSFALPQEETEDDvnaVALDQEYMENMHEM 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 33563284   109 FKQVFKELEFLGWYTTGGP---PDPSDIHVHKQVCEIIES 145
Cdd:pfam01398  78 LKKVNRKEEVVGWYHTHPGlcwLSSVDVHTHALYQRMIPE 117
PLN03246 PLN03246
26S proteasome regulatory subunit; Provisional
 38-304 2.60e-26

26S proteasome regulatory subunit; Provisional


Pssm-ID: 215645 [Multi-domain]  Cd Length: 303  Bit Score: 105.59  E-value: 2.60e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284   38 VALHPLVILNISDHWIRMrsQEGRPMQVIGALIGKQEGRNIEVMNSFELlshTVEEKI------IIDKEYYYTKEEQFKQ 111
Cdd:PLN03246   8 VVVHPLVLLSIVDHYNRV--AKDTRKRVVGVLLGSSFRGRVDVTNSFAV---PFEEDDkdpsiwFLDHNYLESMFGMFKR 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  112 VFKELEFLGWYTTGGPPDPSDIHVHKQVCEIIESPLFLKLNPMTKHTDLPVSVFESVIDI-ING--EATMLFAELTYTLA 188
Cdd:PLN03246  83 INAKEHVVGWYSTGPKLRENDLDIHELFNDYVPNPVLVIIDVQPKELGIPTKAYYAVEEVkENAtqKSQKVFVHVPSEIG 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  189 TEEAERIGVDHVAR--MTATgsgeNSTVAEHLIAQHSAIKMLHSRVKLILEYVKASEAGEVPFNHEILREAYALCHCLPV 266
Cdd:PLN03246 163 AHEAEEIGVEHLLRdvKDTT----VSTLATEVTGKLTALKGLDARLREIRSYLDLVVEGKLPLNHEILYHLQDVFNLLPN 238

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 33563284  267 LSTDKFKTDFYDQCNDVGLMAYLGTITKTCNTMNQFVN 304
Cdd:PLN03246 239 LNVEELVKAFAVKTNDMMLVIYLSSLIRSVIALHNLIN 276
 
Name Accession Description Interval E-value
MPN_CSN6 cd08063
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 ...
 36-318 1.20e-170

Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 signalosome complex subunit 6; CSN6 (COP9 signalosome subunit 6; COP9 subunit 6; MOV34 homolog, 34 kD) is one of the eight subunits of COP9 signalosome, a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. CSN6 is an MPN-domain protein that directly interacts with the MPN+-domain subunit CSN5. It is cleaved during apoptosis by activated caspases. CSN6 processing occurs in CSN/CRL (cullin-RING Ub ligase) complexes and is followed by the cleavage of Rbx1, the direct interaction partner of CSN6. CSN6 cleavage enhances CSN-mediated deneddylating activity (i.e. cleavage of ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. The cleavage of Rbx1 and increased deneddylation of cullins inactivate CRLs and presumably stabilize pro-apoptotic factors for final apoptotic steps. While CSN6 shows a typical MPN metalloprotease fold, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.


Pssm-ID: 163694 [Multi-domain]  Cd Length: 288  Bit Score: 474.82  E-value: 1.20e-170
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  36 VSVALHPLVILNISDHWIRMRSQEGR-PMQVIGALIGKQEGRNIEVMNSFELLSHTVE-EKIIIDKEYYYTKEEQFKQVF 113
Cdd:cd08063   1 LSVKLHPLVILNISDHITRHRAQSQSePPRVVGALLGQQDGREIEIENSFELKYDTNEdGEIVLDKEFLETRLEQFKQVF 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 114 KELEFLGWYTTG-GPPDPSDIHVHKQVCEIIESPLFLKLNPMT--KHTDLPVSVFESVIDIINGEATMLFAELTYTLATE 190
Cdd:cd08063  81 KDLDFVGWYTTGpGGPTESDLPIHKQILEINESPVLLLLDPEAnaSGKDLPVTIYESVLELVDGEATLRFRELPYTIETG 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 191 EAERIGVDHVARMTATGSGENSTVAEHLIAQHSAIKMLHSRVKLILEYVKASEAGEVPFNHEILREAYALCHCLPVLSTD 270
Cdd:cd08063 161 EAERIGVDHVARGGASGSSEKSTVAAHLQAQHNAIKMLNSRVELILEYLKAVPVGEVPPDHSILRSISALCSRLPVLKSE 240

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*...
gi 33563284 271 KFKTDFYDQCNDVGLMAYLGTITKTCNTMNQFVNKFNVLYDRQGIGRR 318
Cdd:cd08063 241 AFREELLAEYNDVLLVAYLATLTKGCNTLNELVDKFNVVYDRKGSGRR 288
MPN_euk_non_mb cd08057
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity (non ...
 38-196 1.43e-44

Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity (non metal-binding); eukaryotic; This family contains MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) domains variants lacking key residues in the JAB1/MPN/Mov34 metalloenzyme (JAMM) motif and are unable to coordinate a metal ion. Comparisons of key catalytic and metal binding residues explain why the MPN-containing proteins Rpn7/PSMD7, Rpn8/PSMD8, CSN6, Prp8p, and the translation initiation factor 3 subunits f and h do not show catalytic isopeptidase activity. It has been proposed that the MPN domain in these proteins has a primarily structural function. Rpn7 is known to be critical for the integrity of the 26S proteasome complex by establishing a correct lid structure. It is necessary for the incorporation/anchoring of Rpn3 and Rpn12 to the lid and essential for viability and normal mitosis. CSN6 is a highly conserved protein complex with diverse functions, including several important intracellular pathways such as the ubiquitin/proteasome system, DNA repair, cell cycle, developmental changes, and some aspects of immune responses. It cleaves ubiquitin-like protein Nedd8 (neural precursor cell expressed, developmentally downregulated 8)) in the cullin 1 in cells. EIF3f s a potent inhibitor of HIV-1 replication as well as an important negative regulator of cell growth and proliferation. EIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells.


Pssm-ID: 163688 [Multi-domain]  Cd Length: 157  Bit Score: 149.52  E-value: 1.43e-44
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  38 VALHPLVILNISDHWIRMRSQEGRpmqVIGALIGKQEGRNIEVMNSFELLSHTVEEKIIIDKEYYYTKEEQFKQVFKELE 117
Cdd:cd08057   1 VQLHPLVLLNISDHYTRRKYGIKR---VIGVLLGYVDGDKIEVTNSFELPFDEEEESIFIDTEYLEKRYNLHKKVYPQEK 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 118 FLGWYTTGGPPDP----SDIHVHKQVCEI-IESPLFLKLNPMTK--HTDLPVSVFESVIDIINGeatmlfAELTYTLATE 190
Cdd:cd08057  78 IVGWYSIGSNNSNeiskSDNSLHSQFSLIsEENPLILILDPSLQsdSEKLEISTFTSAQREENG------AEITYEIGTE 151


                ....*.
gi 33563284 191 EAERIG 196
Cdd:cd08057 152 ETERIA 157
MPN_RPN7_8 cd08062
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S ...
 37-294 2.22e-31

Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S proteasomal subunits Rpn7 and Rpn8; This family includes lid subunits of the 26 S proteasome regulatory particles, Rpn7 (PSMD7; proteasome 26S non-ATPase subunit 7; p44), and Rpn8 (PSMD8; proteasome 26S non-ATPase subunit 8; p40; Mov34). Rpn7 is known to be critical for the integrity of the 26 S proteasome complex by establishing a correct lid structure. It is necessary for the incorporation/anchoring of Rpn3 and Rpn12 to the lid and essential for viability and normal mitosis. Rpn7 and Rpn8 are ATP-independent components of the 19S regulator subunit, and contain the MPN structural motif on its N-terminal region. However, while they show a typical MPN metalloprotease fold, they lack the canonical JAMM motif, and therefore do not show catalytic isopeptidase activity. It is suggested that Rpn7 function is primarily structural.


Pssm-ID: 163693 [Multi-domain]  Cd Length: 280  Bit Score: 118.84  E-value: 2.22e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  37 SVALHPLVILNISDHWIRMRSQEGRpmQVIGALIGKQEGRNIEVMNSFELlshTVEEKI------IIDKEYYYTKEEQFK 110
Cdd:cd08062   2 KVVVHPLVLLSVVDHYNRVAKGTSK--RVVGVLLGSWKKGVLDVTNSFAV---PFEEDEkdpsvwFLDHNYLENMYGMFK 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 111 QVFKELEFLGWYTTGGPPDPSDIHVHKQVCEIIESPLFLKLNPMTKHTDLPVSVFESVIDII-NGEAT-MLFAELTYTLA 188
Cdd:cd08062  77 KVNAKEKIVGWYSTGPKLRPNDLDINELFRRYCPNPVLVIIDVRPKDLGLPTEAYIAVEEVHdDGTPTsKTFVHVPSEIG 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 189 TEEAERIGVDHVARMTATGSGenSTVAEHLIAQHSAIKMLHSRVKLILEYVKASEAGEVPFNHEILREAYALCHCLPVLS 268
Cdd:cd08062 157 AEEAEEVGVEHLLRDIKDVTV--STLSTRVTNKLNSLKGLQSKLKEIKDYLQLVVEGKLPINHQIIYNLQDIFNLLPNLN 234

                       250       260
                ....*....|....*....|....*.
gi 33563284 269 TDKFKTDFYDQCNDVGLMAYLGTITK 294
Cdd:cd08062 235 LPELVKAFAVKTNDQMLVIYLSSLIR 260
JAB_MPN smart00232
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
 38-168 8.49e-30

JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal subunits. Domain at Mpr1p and Pad1p N-termini. Domain of unknown function.


Pssm-ID: 214573  Cd Length: 135  Bit Score: 110.54  E-value: 8.49e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284     38 VALHPLVILNISDHWIRMRsqegrPMQVIGALIGKQEGRNIEVMNSFELLSHTVEEKI-IIDKEYYYTKEEQFKQVFKEL 116
Cdd:smart00232   2 VKVHPLVPLNILKHAIRDG-----PEEVCGVLLGKSNKDRPEVKEVFAVPNEPQDDSVqEYDEDYSHLMDEELKKVNKDL 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 33563284    117 EFLGWYTTGG--PPDPS--DIHVHKQVCEIIESPLFLKLNPM-TKHTDLPVSVFESV 168
Cdd:smart00232  77 EIVGWYHSHPdeSPFPSevDVATHESYQAPWPISVVLIVDPIkSFQGRLSLRAFRLT 133
MPN_eIF3f cd08064
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF3f; ...
 38-295 1.15e-28

Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF3f; Eukaryotic translation initiation factor 3 (eIF3) subunit F (eIF3F; EIF3S5; eIF3-p47; eukaryotic translation initiation factor 3, subunit 5 epsilon, 47kDa; Mov34/MPN/PAD-1 family protein) is an evolutionarily non-conserved subunit of the functional core that comprises eIF3a, eIF3b, eIF3c, eIF3e, eIF3f, and eIF3h, and contains the MPN domain. However, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity. It has been shown that eIF3f mRNA expression is significantly decreased in many human tumors including pancreatic cancer and melanoma. EIF3f is a potent inhibitor of HIV-1 replication; it mediates restriction of HIV-1 expression through several factors including the serine/arginine-rich (SR) protein 9G8, and cyclin-dependent kinase 11 (CDK11). EIF3f phosphorylation by CDK11 is important in regulating its function in translation and apoptosis. It enhances its association with the core eIF3 subunits during apoptosis, suggesting that eIF3f may inhibit translation by increasing the binding to the eIF3 complex during apoptosis. Thus, eIF3f may be an important negative regulator of cell growth and proliferation.


Pssm-ID: 163695 [Multi-domain]  Cd Length: 265  Bit Score: 111.14  E-value: 1.15e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  38 VALHPLVILNISDHWirMRSQEGRPmQVIGALIGKQEGRNIEVMNSFELLSHTVEEKIIIDKEYYYTKEEQFKQVFKELE 117
Cdd:cd08064   1 VRVHPVVLFSILDSY--ERRNEGQE-RVIGTLLGTRSEGEVEITNCFAVPHNESEDQVAVDMEYHRTMYELHQKVNPKEV 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 118 FLGWYTTGGPPDPSDIHVH---KQVCEIIEsPLFLKLNPMTKHTDLPVSVFESVIDIINGEAT-MLFAELTYTLATEEAE 193
Cdd:cd08064  78 IVGWYATGSEITEHSALIHdyySRECTSYN-PIHLTVDTSLDDGKMSIKAYVSSPLGVPGKTLgSMFVPIPLELLYSEAE 156

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284 194 RIGVDHVARMTATGSGENSTVA--EHLIAqhsAIKMLHSRVKLILEYVKASEAGEVPFNHEILREAYALCHCLPVLSTDK 271
Cdd:cd08064 157 RVALDLLAKTLASPSRSAPLTSdlEQLEA---SLEKLQEMLDRVLRYVEDVLAGKVKADNAIGRYLMDALTSVPKLDPEE 233

                       250       260
                ....*....|....*....|....
gi 33563284 272 FKTDFYDQCNDVGLMAYLGTITKT 295
Cdd:cd08064 234 FEKMFNSSLQDLLMVTYLSNLTKT 257
JAB pfam01398
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ...
 33-145 2.61e-28

JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. This family is also known as the MPN domain and PAD-1-like domain, JABP1 domain or JAMM domain. These are metalloenzymes that function as the ubiquitin isopeptidase/ deubiquitinase in the ubiquitin-based signalling and protein turnover pathways in eukaryotes. Versions of the domain in prokaryotic cognates of the ubiquitin-modification pathway are shown to have a similar role, and the archael protein from Haloferax volcanii is found to cleave ubiquitin-like small archaeal modifier proteins (SAMP1/2) from protein conjugates.


Pssm-ID: 396120  Cd Length: 117  Bit Score: 105.89  E-value: 2.61e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284    33 TGSVSVALHPLVILNISDHWIRMRSQEGRpmqVIGALIGKQEGR-NIEVMNSFELLSHTVEEK---IIIDKEYYYTKEEQ 108
Cdd:pfam01398   1 SSVRTVIIHPLVLLKILDHANRGGKIGEE---VMGVLLGKLEGDgTIEITNSFALPQEETEDDvnaVALDQEYMENMHEM 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 33563284   109 FKQVFKELEFLGWYTTGGP---PDPSDIHVHKQVCEIIES 145
Cdd:pfam01398  78 LKKVNRKEEVVGWYHTHPGlcwLSSVDVHTHALYQRMIPE 117
PLN03246 PLN03246
26S proteasome regulatory subunit; Provisional
 38-304 2.60e-26

26S proteasome regulatory subunit; Provisional


Pssm-ID: 215645 [Multi-domain]  Cd Length: 303  Bit Score: 105.59  E-value: 2.60e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284   38 VALHPLVILNISDHWIRMrsQEGRPMQVIGALIGKQEGRNIEVMNSFELlshTVEEKI------IIDKEYYYTKEEQFKQ 111
Cdd:PLN03246   8 VVVHPLVLLSIVDHYNRV--AKDTRKRVVGVLLGSSFRGRVDVTNSFAV---PFEEDDkdpsiwFLDHNYLESMFGMFKR 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  112 VFKELEFLGWYTTGGPPDPSDIHVHKQVCEIIESPLFLKLNPMTKHTDLPVSVFESVIDI-ING--EATMLFAELTYTLA 188
Cdd:PLN03246  83 INAKEHVVGWYSTGPKLRENDLDIHELFNDYVPNPVLVIIDVQPKELGIPTKAYYAVEEVkENAtqKSQKVFVHVPSEIG 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  189 TEEAERIGVDHVAR--MTATgsgeNSTVAEHLIAQHSAIKMLHSRVKLILEYVKASEAGEVPFNHEILREAYALCHCLPV 266
Cdd:PLN03246 163 AHEAEEIGVEHLLRdvKDTT----VSTLATEVTGKLTALKGLDARLREIRSYLDLVVEGKLPLNHEILYHLQDVFNLLPN 238

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 33563284  267 LSTDKFKTDFYDQCNDVGLMAYLGTITKTCNTMNQFVN 304
Cdd:PLN03246 239 LNVEELVKAFAVKTNDMMLVIYLSSLIRSVIALHNLIN 276
MitMem_reg pfam13012
Maintenance of mitochondrial structure and function; This is C-terminal to the Mov24 region of ...
 191-261 1.28e-21

Maintenance of mitochondrial structure and function; This is C-terminal to the Mov24 region of the yeast proteasomal subunit Rpn11 and seems likely to regulate the mitochondrial fission and tubulation processes, ie the outer mitochondrial membrane proteins. This function appears to be unrelated to the proteasome activity of the N-terminal region.


Pssm-ID: 463772 [Multi-domain]  Cd Length: 72  Bit Score: 86.78  E-value: 1.28e-21
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 33563284   191 EAERIGVDHVARMTATgsgensTVAEHLIAQHSAIKMLHSRVKLILEYVKASEAGEVPFNHEILREAYALC 261
Cdd:pfam13012   1 EAERIGVDHLARPDIK------SLSSDLERQYYSLKMLQDRLDLILKYVEDVLDGELPPDHAIGRYLQDLL 65
MPN_eIF3h cd08065
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; ...
 37-124 7.23e-05

Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; Eukaryotic translation initiation factor 3 (eIF3) subunit h (eIF3h; eIF3 subunit 3; eIF3S3; eIF3-gamma; eIF3-p40) is an evolutionarily non-conserved subunit of the functional core that comprises eIF3a, eIF3b, eIF3c, eIF3e, eIF3f, and eIF3h, and contains the MPN domain. However, it lacks the canonical JAMM motif, and therefore does not show catalytic isopeptidase activity.Together with eIF3e and eIF3f, eIF3h stabilizes the eIF3 complex. Results suggest that eIF3h regulates cell growth and viability, and that over-expression of the gene may provide growth advantage to prostate, breast, and liver cancer cells. For example, EIF3h gene amplification is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease. It has been shown that coamplification of MYC, a well characterized oncogene involved in cell growth, differentiation, and apoptosis, and EIF3h in patients with non-small cell lung cancer (NSCLC) improves survival if treated with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), Gefitinib. Plant eIF3h is implicated in translation of specific mRNAs.


Pssm-ID: 163696 [Multi-domain]  Cd Length: 266  Bit Score: 43.79  E-value: 7.23e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33563284  37 SVALHPLVILNISDHwirmrSQEGRPMQVIGALIGKQEGRNIEVMNSFELLSHTVEEKIIIDKE---YYYTKEEQFKQVF 113
Cdd:cd08065   2 SVQIDGLVVLKIIKH-----CKEELPELVQGQLLGLDVGGTLEVTNCFPFPKSEEDDSDRADEDiadYQLEMMRLLREVN 76

                        90
                ....*....|.
gi 33563284 114 KELEFLGWYTT 124
Cdd:cd08065  77 VDHNHVGWYQS 87
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH