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Conserved domains on  [gi|6754724|ref|NP_034947|]
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26S proteasome non-ATPase regulatory subunit 7 [Mus musculus]

Protein Classification

26S proteasome regulatory subunit( domain architecture ID 10169140)

26S proteasome regulatory subunit acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins; belongs to the peptidase M67A family; similar to yeast 26S proteasome regulatory subunit RPN8

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MPN_RPN7_8 cd08062
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S ...
 7-285 0e+00

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: 520.22  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    7 QKVVVHPLVLLSVVDHFNRIGKvGNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDDSVWFLDHDYLENMYGMFKKVN 86
Cdd:cd08062   1 KKVVVHPLVLLSVVDHYNRVAK-GTSKRVVGVLLGSWKKGVLDVTNSFAVPFEEDEKDPSVWFLDHNYLENMYGMFKKVN 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724   87 ARERIVGWYHTGPKLHKNDIAINELMKRYCPNSVLVIIDVKPKDLGLPTEAYISVEEVHDDGTPTSKTFEHVTSEIGAEE 166
Cdd:cd08062  80 AKEKIVGWYSTGPKLRPNDLDINELFRRYCPNPVLVIIDVRPKDLGLPTEAYIAVEEVHDDGTPTSKTFVHVPSEIGAEE 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724  167 AEEVGVEHLLRDIKDTTVGTLSQRITNQVHGLKGLNSKLLDIRSYLEKVASGKLPINHQIIYQLQDVFNLLPDASLQEFV 246
Cdd:cd08062 160 AEEVGVEHLLRDIKDVTVSTLSTRVTNKLNSLKGLQSKLKEIKDYLQLVVEGKLPINHQIIYNLQDIFNLLPNLNLPELV 239

                       250       260       270
                ....*....|....*....|....*....|....*....
gi 6754724  247 KAFYLKTNDQMVVVYLASLIRSVVALHNLINNKIANRDA 285
Cdd:cd08062 240 KAFAVKTNDQMLVIYLSSLIRSVIALHNLINNKIANKEA 278
 
Name Accession Description Interval E-value
MPN_RPN7_8 cd08062
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S ...
 7-285 0e+00

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: 520.22  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    7 QKVVVHPLVLLSVVDHFNRIGKvGNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDDSVWFLDHDYLENMYGMFKKVN 86
Cdd:cd08062   1 KKVVVHPLVLLSVVDHYNRVAK-GTSKRVVGVLLGSWKKGVLDVTNSFAVPFEEDEKDPSVWFLDHNYLENMYGMFKKVN 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724   87 ARERIVGWYHTGPKLHKNDIAINELMKRYCPNSVLVIIDVKPKDLGLPTEAYISVEEVHDDGTPTSKTFEHVTSEIGAEE 166
Cdd:cd08062  80 AKEKIVGWYSTGPKLRPNDLDINELFRRYCPNPVLVIIDVRPKDLGLPTEAYIAVEEVHDDGTPTSKTFVHVPSEIGAEE 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724  167 AEEVGVEHLLRDIKDTTVGTLSQRITNQVHGLKGLNSKLLDIRSYLEKVASGKLPINHQIIYQLQDVFNLLPDASLQEFV 246
Cdd:cd08062 160 AEEVGVEHLLRDIKDVTVSTLSTRVTNKLNSLKGLQSKLKEIKDYLQLVVEGKLPINHQIIYNLQDIFNLLPNLNLPELV 239

                       250       260       270
                ....*....|....*....|....*....|....*....
gi 6754724  247 KAFYLKTNDQMVVVYLASLIRSVVALHNLINNKIANRDA 285
Cdd:cd08062 240 KAFAVKTNDQMLVIYLSSLIRSVIALHNLINNKIANKEA 278
PLN03246 PLN03246
26S proteasome regulatory subunit; Provisional
 6-284 5.79e-150

26S proteasome regulatory subunit; Provisional


Pssm-ID: 215645 [Multi-domain]  Cd Length: 303  Bit Score: 423.00  E-value: 5.79e-150
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724     6 VQKVVVHPLVLLSVVDHFNRIGKvGNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDDSVWFLDHDYLENMYGMFKKV 85
Cdd:PLN03246   5 IEKVVVHPLVLLSIVDHYNRVAK-DTRKRVVGVLLGSSFRGRVDVTNSFAVPFEEDDKDPSIWFLDHNYLESMFGMFKRI 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    86 NARERIVGWYHTGPKLHKNDIAINELMKRYCPNSVLVIIDVKPKDLGLPTEAYISVEEVHDDGTPTS-KTFEHVTSEIGA 164
Cdd:PLN03246  84 NAKEHVVGWYSTGPKLRENDLDIHELFNDYVPNPVLVIIDVQPKELGIPTKAYYAVEEVKENATQKSqKVFVHVPSEIGA 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724   165 EEAEEVGVEHLLRDIKDTTVGTLSQRITNQVHGLKGLNSKLLDIRSYLEKVASGKLPINHQIIYQLQDVFNLLPDASLQE 244
Cdd:PLN03246 164 HEAEEIGVEHLLRDVKDTTVSTLATEVTGKLTALKGLDARLREIRSYLDLVVEGKLPLNHEILYHLQDVFNLLPNLNVEE 243

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 6754724   245 FVKAFYLKTNDQMVVVYLASLIRSVVALHNLINNKIANRD 284
Cdd:PLN03246 244 LVKAFAVKTNDMMLVIYLSSLIRSVIALHNLINNKILNKE 283
JAB pfam01398
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ...
 5-118 6.44e-43

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: 143.64  E-value: 6.44e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724      5 AVQKVVVHPLVLLSVVDHFNRIGKvgNQKRVVGVLLGSWQKK-VLDVSNSFAVPFDEDDKDDSVWFLDHDYLENMYGMFK 83
Cdd:pfam01398   2 SVRTVIIHPLVLLKILDHANRGGK--IGEEVMGVLLGKLEGDgTIEITNSFALPQEETEDDVNAVALDQEYMENMHEMLK 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 6754724     84 KVNARERIVGWYHTGPK---LHKNDIAINELMKRYCPN 118
Cdd:pfam01398  80 KVNRKEEVVGWYHTHPGlcwLSSVDVHTHALYQRMIPE 117
JAB_MPN smart00232
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
 8-143 3.06e-37

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: 129.80  E-value: 3.06e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724       8 KVVVHPLVLLSVVDHFNRIGkvgnQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDkdDSVWFLDHDYLENMYGMFKKVNA 87
Cdd:smart00232   1 EVKVHPLVPLNILKHAIRDG----PEEVCGVLLGKSNKDRPEVKEVFAVPNEPQD--DSVQEYDEDYSHLMDEELKKVNK 74

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6754724      88 RERIVGWYHTGP----KLHKNDIAINELMKRYCPNSVLVIID-VKPKDLGLPTEAYISVEE 143
Cdd:smart00232  75 DLEIVGWYHSHPdespFPSEVDVATHESYQAPWPISVVLIVDpIKSFQGRLSLRAFRLTPE 135
 
Name Accession Description Interval E-value
MPN_RPN7_8 cd08062
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in 19S ...
 7-285 0e+00

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: 520.22  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    7 QKVVVHPLVLLSVVDHFNRIGKvGNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDDSVWFLDHDYLENMYGMFKKVN 86
Cdd:cd08062   1 KKVVVHPLVLLSVVDHYNRVAK-GTSKRVVGVLLGSWKKGVLDVTNSFAVPFEEDEKDPSVWFLDHNYLENMYGMFKKVN 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724   87 ARERIVGWYHTGPKLHKNDIAINELMKRYCPNSVLVIIDVKPKDLGLPTEAYISVEEVHDDGTPTSKTFEHVTSEIGAEE 166
Cdd:cd08062  80 AKEKIVGWYSTGPKLRPNDLDINELFRRYCPNPVLVIIDVRPKDLGLPTEAYIAVEEVHDDGTPTSKTFVHVPSEIGAEE 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724  167 AEEVGVEHLLRDIKDTTVGTLSQRITNQVHGLKGLNSKLLDIRSYLEKVASGKLPINHQIIYQLQDVFNLLPDASLQEFV 246
Cdd:cd08062 160 AEEVGVEHLLRDIKDVTVSTLSTRVTNKLNSLKGLQSKLKEIKDYLQLVVEGKLPINHQIIYNLQDIFNLLPNLNLPELV 239

                       250       260       270
                ....*....|....*....|....*....|....*....
gi 6754724  247 KAFYLKTNDQMVVVYLASLIRSVVALHNLINNKIANRDA 285
Cdd:cd08062 240 KAFAVKTNDQMLVIYLSSLIRSVIALHNLINNKIANKEA 278
PLN03246 PLN03246
26S proteasome regulatory subunit; Provisional
 6-284 5.79e-150

26S proteasome regulatory subunit; Provisional


Pssm-ID: 215645 [Multi-domain]  Cd Length: 303  Bit Score: 423.00  E-value: 5.79e-150
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724     6 VQKVVVHPLVLLSVVDHFNRIGKvGNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDDSVWFLDHDYLENMYGMFKKV 85
Cdd:PLN03246   5 IEKVVVHPLVLLSIVDHYNRVAK-DTRKRVVGVLLGSSFRGRVDVTNSFAVPFEEDDKDPSIWFLDHNYLESMFGMFKRI 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    86 NARERIVGWYHTGPKLHKNDIAINELMKRYCPNSVLVIIDVKPKDLGLPTEAYISVEEVHDDGTPTS-KTFEHVTSEIGA 164
Cdd:PLN03246  84 NAKEHVVGWYSTGPKLRENDLDIHELFNDYVPNPVLVIIDVQPKELGIPTKAYYAVEEVKENATQKSqKVFVHVPSEIGA 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724   165 EEAEEVGVEHLLRDIKDTTVGTLSQRITNQVHGLKGLNSKLLDIRSYLEKVASGKLPINHQIIYQLQDVFNLLPDASLQE 244
Cdd:PLN03246 164 HEAEEIGVEHLLRDVKDTTVSTLATEVTGKLTALKGLDARLREIRSYLDLVVEGKLPLNHEILYHLQDVFNLLPNLNVEE 243

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 6754724   245 FVKAFYLKTNDQMVVVYLASLIRSVVALHNLINNKIANRD 284
Cdd:PLN03246 244 LVKAFAVKTNDMMLVIYLSSLIRSVIALHNLINNKILNKE 283
MPN_eIF3f cd08064
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF3f; ...
 9-273 5.54e-43

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: 148.89  E-value: 5.54e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    9 VVVHPLVLLSVVDHFNRigKVGNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDkdDSVwFLDHDYLENMYGMFKKVNAR 88
Cdd:cd08064   1 VRVHPVVLFSILDSYER--RNEGQERVIGTLLGTRSEGEVEITNCFAVPHNESE--DQV-AVDMEYHRTMYELHQKVNPK 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724   89 ERIVGWYHTGPKLHKNDIAINELMKRYC--PNSVLVIIDVKPKDLGLPTEAYISVeEVHDDGTPTSKTFEHVTSEIGAEE 166
Cdd:cd08064  76 EVIVGWYATGSEITEHSALIHDYYSRECtsYNPIHLTVDTSLDDGKMSIKAYVSS-PLGVPGKTLGSMFVPIPLELLYSE 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724  167 AEEVGVEHLLRDIKDTTVGTLSQRITNQVHG-LKGLNSKLLDIRSYLEKVASGKLPINHQIIYQLQDVFNLLPDASLQEF 245
Cdd:cd08064 155 AERVALDLLAKTLASPSRSAPLTSDLEQLEAsLEKLQEMLDRVLRYVEDVLAGKVKADNAIGRYLMDALTSVPKLDPEEF 234

                       250       260
                ....*....|....*....|....*...
gi 6754724  246 VKAFYLKTNDQMVVVYLASLIRSVVALH 273
Cdd:cd08064 235 EKMFNSSLQDLLMVTYLSNLTKTQLALA 262
JAB pfam01398
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ...
 5-118 6.44e-43

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: 143.64  E-value: 6.44e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724      5 AVQKVVVHPLVLLSVVDHFNRIGKvgNQKRVVGVLLGSWQKK-VLDVSNSFAVPFDEDDKDDSVWFLDHDYLENMYGMFK 83
Cdd:pfam01398   2 SVRTVIIHPLVLLKILDHANRGGK--IGEEVMGVLLGKLEGDgTIEITNSFALPQEETEDDVNAVALDQEYMENMHEMLK 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 6754724     84 KVNARERIVGWYHTGPK---LHKNDIAINELMKRYCPN 118
Cdd:pfam01398  80 KVNRKEEVVGWYHTHPGlcwLSSVDVHTHALYQRMIPE 117
MPN_euk_non_mb cd08057
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity (non ...
 9-161 1.10e-38

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: 134.11  E-value: 1.10e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    9 VVVHPLVLLSVVDHFNRIGKvgNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDdsvWFLDHDYLENMYGMFKKVNAR 88
Cdd:cd08057   1 VQLHPLVLLNISDHYTRRKY--GIKRVIGVLLGYVDGDKIEVTNSFELPFDEEEES---IFIDTEYLEKRYNLHKKVYPQ 75

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6754724   89 ERIVGWYHTGPKLH----KNDIAINELMKRY-CPNSVLVIIDvkPKDLGLPTEAYISVEEVHDDGTPTSKTFEHVTSE 161
Cdd:cd08057  76 EKIVGWYSIGSNNSneisKSDNSLHSQFSLIsEENPLILILD--PSLQSDSEKLEISTFTSAQREENGAEITYEIGTE 151
MPN cd07767
Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) ...
 16-138 5.27e-38

Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) domains are found in the N-terminal termini of proteins with a variety of functions; they are components of the proteasome regulatory subunits, the signalosome (CSN), eukaryotic translation initiation factor 3 (eIF3) complexes, and regulators of transcription factors. These domains are isopeptidases that release ubiquitin from ubiquitinated proteins (thus having deubiquitinating (DUB) activity) that are tagged for degradation. Catalytically active MPN domains contain a metalloprotease signature known as the JAB1/MPN/Mov34 metalloenzyme (JAMM) motif. For example, Rpn11 (also known as POH1 or PSMD14), a subunit of the 19S proteasome lid is involved in the ATP-dependent degradation of ubiquitinated proteins, contains the conserved JAMM motif involved in zinc ion coordination. Poh1 is a regulator of c-Jun, an important regulator of cell proliferation, differentiation, survival and death. JAB1 is a component of the COP9 signalosome (CSN), a regulatory particle of the ubiquitin (Ub)/26S proteasome system occurring in all eukaryotic cells; it cleaves the ubiquitin-like protein NEDD8 from the cullin subunit of the SCF (Skp1, Cullins, F-box proteins) family of E3 ubiquitin ligases. AMSH (associated molecule with the SH3 domain of STAM, also known as STAMBP), a member of JAMM/MPN+ deubiquitinases (DUBs), specifically cleaves Lys 63-linked polyubiquitin (poly-Ub) chains, thus facilitating the recycling and subsequent trafficking of receptors to the cell surface. Similarly, BRCC36, part of the nuclear complex that includes BRCA1 protein and is targeted to DNA damage foci after irradiation, specifically disassembles K63-linked polyUb. BRCC36 is aberrantly expressed in sporadic breast tumors, indicative of a potential role in the pathogenesis of the disease. Some variants of the JAB1/MPN domains lack key residues in their JAMM motif and are unable to coordinate a metal ion. Comparisons of key catalytic and metal binding residues explain why the MPN-containing proteins Mov34/PSMD7, Rpn8, CSN6, Prp8p, and the translation initiation factor 3 subunits f (p47) and h (p40) do not show catalytic isopeptidase activity. It has been proposed that the MPN domain in these proteins has a primarily structural function.


Pssm-ID: 163686 [Multi-domain]  Cd Length: 116  Bit Score: 131.09  E-value: 5.27e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724   16 LLSVVDHFNRIgkvgNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDDSVWFLdhdylenMYGMFKKVNARERIVGWY 95
Cdd:cd07767   1 LKMFLDAAKSI----NGKEVIGLLYGSKTKKVLDVDEVIAVPFDEGDKDDNVWFL-------MYLDFKKLNAGLRIVGWY 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 6754724   96 HTGPK----LHKNDIAINELMKRYCPNSVLVIIDVKPKDLGLPTEAY 138
Cdd:cd07767  70 HTHPKpscfLSPNDLATHELFQRYFPEKVMIIVDVKPKDLGNSWKCY 116
JAB_MPN smart00232
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
 8-143 3.06e-37

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: 129.80  E-value: 3.06e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724       8 KVVVHPLVLLSVVDHFNRIGkvgnQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDkdDSVWFLDHDYLENMYGMFKKVNA 87
Cdd:smart00232   1 EVKVHPLVPLNILKHAIRDG----PEEVCGVLLGKSNKDRPEVKEVFAVPNEPQD--DSVQEYDEDYSHLMDEELKKVNK 74

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6754724      88 RERIVGWYHTGP----KLHKNDIAINELMKRYCPNSVLVIID-VKPKDLGLPTEAYISVEE 143
Cdd:smart00232  75 DLEIVGWYHSHPdespFPSEVDVATHESYQAPWPISVVLIVDpIKSFQGRLSLRAFRLTPE 135
MPN_CSN6 cd08063
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in COP9 ...
 8-277 4.69e-28

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: 110.03  E-value: 4.69e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    8 KVVVHPLVLLSVVDHFNRIgKVGNQK---RVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDDSVwfLDHDYLENMYGMFKK 84
Cdd:cd08063   2 SVKLHPLVILNISDHITRH-RAQSQSeppRVVGALLGQQDGREIEIENSFELKYDTNEDGEIV--LDKEFLETRLEQFKQ 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724   85 VNARERIVGWYHTGPK--------LHKNDIAINElmkrycpNSVLVIIDVKPKDLG--LPTEAYISVEEVhDDGTPTSKt 154
Cdd:cd08063  79 VFKDLDFVGWYTTGPGgptesdlpIHKQILEINE-------SPVLLLLDPEANASGkdLPVTIYESVLEL-VDGEATLR- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724  155 FEHVTSEIGAEEAEEVGVEHLLR--DIKDTTVGTLSQRITNQVHGLKGLNSKLLDIRSYLEKVASGKLPINHQIIYQLQD 232
Cdd:cd08063 150 FRELPYTIETGEAERIGVDHVARggASGSSEKSTVAAHLQAQHNAIKMLNSRVELILEYLKAVPVGEVPPDHSILRSISA 229

                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 6754724  233 VFNLLPDASLQEFVKAFYLKTNDQMVVVYLASLIRSVVALHNLIN 277
Cdd:cd08063 230 LCSRLPVLKSEAFREELLAEYNDVLLVAYLATLTKGCNTLNELVD 274
MitMem_reg pfam13012
Maintenance of mitochondrial structure and function; This is C-terminal to the Mov24 region of ...
 174-236 5.39e-14

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: 65.98  E-value: 5.39e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6754724    174 HLLRdikdTTVGTLSQRITNQVHGLKGLNSKLLDIRSYLEKVASGKLPINHQIIYQLQDVFNL 236
Cdd:pfam13012   9 HLAR----PDIKSLSSDLERQYYSLKMLQDRLDLILKYVEDVLDGELPPDHAIGRYLQDLLAL 67
MPN_eIF3h cd08065
Mpr1p, Pad1p N-terminal (MPN) domains without catalytic isopeptidase activity, found in eIF2h; ...
 8-97 2.70e-06

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: 48.03  E-value: 2.70e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6754724    8 KVVVHPLVLLSVVDHfnriGKVGNQKRVVGVLLGSWQKKVLDVSNSFAVPFDEDDKDDSVWFLDHDYLENMYGMFKKVNA 87
Cdd:cd08065   2 SVQIDGLVVLKIIKH----CKEELPELVQGQLLGLDVGGTLEVTNCFPFPKSEEDDSDRADEDIADYQLEMMRLLREVNV 77

                        90
                ....*....|
gi 6754724   88 RERIVGWYHT 97
Cdd:cd08065  78 DHNHVGWYQS 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.
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