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Conserved domains on  [gi|45361707|ref|NP_988991|]
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lys-63-specific deubiquitinase BRCC36-like [Mus musculus]

Protein Classification

MPN domain-containing protein( domain architecture ID 10169171)

MPN domain-containing protein contains the signature JAB1/MPN/Mov34 metalloenzyme (JAMM) motif, which is involved in zinc ion coordination; similar to components of the COP9 signalosome (CSN) complex that acts as a regulator of the ubiquitin conjugation pathway

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
MPN_BRCC36 cd08068
Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex; BRCC36 (BRCA1-A complex subunit ...
9-270 2.25e-150

Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex; BRCC36 (BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 36; BRCA1/BRCA2-containing complex subunit 3; BRCC3; BRISC complex subunit BRCC36; BRCC36 isopeptidase complex; Lys-63-specific deubiquitinase BRCC36) and BRCC36-like domains are members of JAMM/MPN+ deubiquitinases (DUBs), possibly with Zn2+-dependent ubiquitin isopeptidase activity. BRCC36 is part of the BRCA1/BRCA2/BARD1-containing nuclear complex that displays an E3 ubiquitin ligase activity. It is targeted to DNA damage foci after irradiation; RAP80 recruits the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA double strand breaks (DSBs) for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs. A new protein, MERIT40 (mediator of RAP80 interactions and targeting 40 kDa), also named NBA1 (new component of the BRCA1 A complex), exists in the same BRCA1-containing complex and is essential for the integrity of the complex. There are studies suggesting that MERIT40/NBA1 ties BRCA1 complex integrity, DSB recognition, and ubiquitin chain activities to the DNA damage response. It has also been shown that BRCA1-containing complex resembles the lid complex of the 26S proteasome.


:

Pssm-ID: 163699 [Multi-domain]  Cd Length: 244  Bit Score: 420.60  E-value: 2.25e-150
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707   9 VQAVYLESDAFLVCLNHALSTEKEEVMGLCIGQLNdhgrsdsrlayagaemctVAKKMEATRIVHIHSVIILRRSDKTKD 88
Cdd:cd08068   1 LSKVHLSADVYLVCLTHALSTEKEEVMGLLIGEIE------------------VSKKGEEVAIVHISAVIILRRSDKRKD 62
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707  89 RVEISPEQLSAASIEAERLAEQTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQSFVGLIFACFIEDKPTKIGRV 168
Cdd:cd08068  63 RVEISPEQLSAASTEAERLTEETGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDSGFVGLIFSCFNEDKSTKMGEV 142
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707 169 LYTCFQSVQASKSSEYERLEIPIHIVPRTTIGTVCLRSAIELPGILCQEEQEAYRRIHGLTHLDSVTKIHNGSVFTKHLC 248
Cdd:cd08068 143 QVTCFQSVQGNKAGQYERIEVPLEIVPTSTISEACLESLVELPEILYQEEEDAYNKALQSCDLDPLTKIHNGSVYTKSLC 222
                       250       260
                ....*....|....*....|..
gi 45361707 249 SQMSAVCGPLLQWLEDRLEQNQ 270
Cdd:cd08068 223 HILETISGPLLQLLEARLEQNK 244
 
Name Accession Description Interval E-value
MPN_BRCC36 cd08068
Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex; BRCC36 (BRCA1-A complex subunit ...
9-270 2.25e-150

Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex; BRCC36 (BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 36; BRCA1/BRCA2-containing complex subunit 3; BRCC3; BRISC complex subunit BRCC36; BRCC36 isopeptidase complex; Lys-63-specific deubiquitinase BRCC36) and BRCC36-like domains are members of JAMM/MPN+ deubiquitinases (DUBs), possibly with Zn2+-dependent ubiquitin isopeptidase activity. BRCC36 is part of the BRCA1/BRCA2/BARD1-containing nuclear complex that displays an E3 ubiquitin ligase activity. It is targeted to DNA damage foci after irradiation; RAP80 recruits the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA double strand breaks (DSBs) for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs. A new protein, MERIT40 (mediator of RAP80 interactions and targeting 40 kDa), also named NBA1 (new component of the BRCA1 A complex), exists in the same BRCA1-containing complex and is essential for the integrity of the complex. There are studies suggesting that MERIT40/NBA1 ties BRCA1 complex integrity, DSB recognition, and ubiquitin chain activities to the DNA damage response. It has also been shown that BRCA1-containing complex resembles the lid complex of the 26S proteasome.


Pssm-ID: 163699 [Multi-domain]  Cd Length: 244  Bit Score: 420.60  E-value: 2.25e-150
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707   9 VQAVYLESDAFLVCLNHALSTEKEEVMGLCIGQLNdhgrsdsrlayagaemctVAKKMEATRIVHIHSVIILRRSDKTKD 88
Cdd:cd08068   1 LSKVHLSADVYLVCLTHALSTEKEEVMGLLIGEIE------------------VSKKGEEVAIVHISAVIILRRSDKRKD 62
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707  89 RVEISPEQLSAASIEAERLAEQTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQSFVGLIFACFIEDKPTKIGRV 168
Cdd:cd08068  63 RVEISPEQLSAASTEAERLTEETGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDSGFVGLIFSCFNEDKSTKMGEV 142
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707 169 LYTCFQSVQASKSSEYERLEIPIHIVPRTTIGTVCLRSAIELPGILCQEEQEAYRRIHGLTHLDSVTKIHNGSVFTKHLC 248
Cdd:cd08068 143 QVTCFQSVQGNKAGQYERIEVPLEIVPTSTISEACLESLVELPEILYQEEEDAYNKALQSCDLDPLTKIHNGSVYTKSLC 222
                       250       260
                ....*....|....*....|..
gi 45361707 249 SQMSAVCGPLLQWLEDRLEQNQ 270
Cdd:cd08068 223 HILETISGPLLQLLEARLEQNK 244
BRCC36_C pfam18110
BRCC36 C-terminal helical domain; This is the C-terminal domain of BRCC36, a Zn2+ dependent ...
203-283 4.87e-35

BRCC36 C-terminal helical domain; This is the C-terminal domain of BRCC36, a Zn2+ dependent deubiquitinating enzyme, present in Camponotus floridanus. BRCC36 hydrolyzes lysine linked ubiquitin chains as part of macromolecular complexes that participate in either interferon signalling or DNA-damage recognition. The domain consists of 2 non canonical helices. The domain interacts hydrophobically with helices alpha 4 and alpha 5 of KIAA0157 in the form of a coiled coil helical bundle. This interaction helps establish the association of BRCC36 with KIAA0157, a pseudo-DUB MPN- protein that is essential for the activity of BRCC36.


Pssm-ID: 465654  Cd Length: 81  Bit Score: 121.27  E-value: 4.87e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707   203 CLRSAIELPGILCQEEQEAYRRIHGLTHLDSVTKIHNGSVFTKHLCSQMSAVCGPLLQWLEDRLEQNQQRLQELEQEKED 282
Cdd:pfam18110   1 CLESLTELPEILFQEEKEAYEKAKKSGSLDLLTKIHNGSVFTKSLCHITEAISGPLLQALEARLKLNKNRLAALKQEKEE 80

                  .
gi 45361707   283 L 283
Cdd:pfam18110  81 L 81
JAB_MPN smart00232
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
12-178 1.56e-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: 111.70  E-value: 1.56e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707     12 VYLESDAFLVCLNHALSTEKEEVMGLCIGQLNDHgrsdsrlayagaemctvakkmeatrIVHIHSVIILRRsDKTKDRVE 91
Cdd:smart00232   2 VKVHPLVPLNILKHAIRDGPEEVCGVLLGKSNKD-------------------------RPEVKEVFAVPN-EPQDDSVQ 55
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707     92 ISPEQLSAASIEAERlaeQTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQSFVGLIfacfIEDKPTKIGRVLYT 171
Cdd:smart00232  56 EYDEDYSHLMDEELK---KVNKDLEIVGWYHSHPDESPFPSEVDVATHESYQAPWPISVVLI----VDPIKSFQGRLSLR 128

                   ....*..
gi 45361707    172 CFQSVQA 178
Cdd:smart00232 129 AFRLTPE 135
Rri1 COG1310
Proteasome lid subunit RPN8/RPN11, contains Jab1/MPN domain metalloenzyme (JAMM) motif ...
82-137 2.45e-07

Proteasome lid subunit RPN8/RPN11, contains Jab1/MPN domain metalloenzyme (JAMM) motif [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440921  Cd Length: 127  Bit Score: 48.76  E-value: 2.45e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 45361707  82 RSDKTKDRVEISPEQLsaasIEAERLAEQTGrpMRVVGWYHSHPHITVWPSHVDVR 137
Cdd:COG1310  47 VAESPETRFEIDPEDL----LAAEREARERG--LEIVGIYHSHPDGPAYPSETDRA 96
 
Name Accession Description Interval E-value
MPN_BRCC36 cd08068
Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex; BRCC36 (BRCA1-A complex subunit ...
9-270 2.25e-150

Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex; BRCC36 (BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 36; BRCA1/BRCA2-containing complex subunit 3; BRCC3; BRISC complex subunit BRCC36; BRCC36 isopeptidase complex; Lys-63-specific deubiquitinase BRCC36) and BRCC36-like domains are members of JAMM/MPN+ deubiquitinases (DUBs), possibly with Zn2+-dependent ubiquitin isopeptidase activity. BRCC36 is part of the BRCA1/BRCA2/BARD1-containing nuclear complex that displays an E3 ubiquitin ligase activity. It is targeted to DNA damage foci after irradiation; RAP80 recruits the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA double strand breaks (DSBs) for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs. A new protein, MERIT40 (mediator of RAP80 interactions and targeting 40 kDa), also named NBA1 (new component of the BRCA1 A complex), exists in the same BRCA1-containing complex and is essential for the integrity of the complex. There are studies suggesting that MERIT40/NBA1 ties BRCA1 complex integrity, DSB recognition, and ubiquitin chain activities to the DNA damage response. It has also been shown that BRCA1-containing complex resembles the lid complex of the 26S proteasome.


Pssm-ID: 163699 [Multi-domain]  Cd Length: 244  Bit Score: 420.60  E-value: 2.25e-150
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707   9 VQAVYLESDAFLVCLNHALSTEKEEVMGLCIGQLNdhgrsdsrlayagaemctVAKKMEATRIVHIHSVIILRRSDKTKD 88
Cdd:cd08068   1 LSKVHLSADVYLVCLTHALSTEKEEVMGLLIGEIE------------------VSKKGEEVAIVHISAVIILRRSDKRKD 62
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707  89 RVEISPEQLSAASIEAERLAEQTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQSFVGLIFACFIEDKPTKIGRV 168
Cdd:cd08068  63 RVEISPEQLSAASTEAERLTEETGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDSGFVGLIFSCFNEDKSTKMGEV 142
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707 169 LYTCFQSVQASKSSEYERLEIPIHIVPRTTIGTVCLRSAIELPGILCQEEQEAYRRIHGLTHLDSVTKIHNGSVFTKHLC 248
Cdd:cd08068 143 QVTCFQSVQGNKAGQYERIEVPLEIVPTSTISEACLESLVELPEILYQEEEDAYNKALQSCDLDPLTKIHNGSVYTKSLC 222
                       250       260
                ....*....|....*....|..
gi 45361707 249 SQMSAVCGPLLQWLEDRLEQNQ 270
Cdd:cd08068 223 HILETISGPLLQLLEARLEQNK 244
MPN_euk_mb cd08058
Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); ...
17-171 1.25e-50

Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); eukaryotic; This family contains eukaryotic MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) domains found in proteins with a variety of functions, including AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM), H2A-DUB (histone H2A deubiquitinase), BRCC36 (BRCA1/BRCA2-containing complex subunit 36), as well as Rpn11 (regulatory particle number 11) and CSN5 (COP9 signalosome complex subunit 5). These domains contain the signature JAB1/MPN/Mov34 metalloenzyme (JAMM) motif, EXnHS/THX7SXXD, which is involved in zinc ion coordination and provides 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. CSN5 is critical for nuclear export and the degradation of several tumor suppressor proteins, including p53, p27, and Smad4. Over-expression of CSN5 has been implicated in cancer initiation and progression. AMSH specifically cleaves Lys 63 and not Lys48-linked polyubiquitin (poly-Ub) chains, thus facilitating the recycling and subsequent trafficking of receptors to the cell surface. It is involved in the degradation of EGF receptor (EGFR) and possibly other ubiquitinated endocytosed proteins. BRCC36 is part of the BRCA1/BRCA2/BARD1-containing nuclear complex that displays an E3 ubiquitin ligase activity; it is targeted to DNA damage foci after irradiation. 2A-DUB is specific for monoubiquitinated H2A (uH2A), regulating transcription by coordinating histone acetylation and deubiquitination, and destabilizing the association of linker histone H1 with nucleosomes. It is a positive regulator of androgen receptor (AR) transactivation activity on a reporter gene and serves as a marker in prostate tumors.


Pssm-ID: 163689  Cd Length: 119  Bit Score: 162.75  E-value: 1.25e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707  17 DAFLVCLNHALSTEKEEVMGLCIGQLNDHgrsdsrlayagaemctvakkmeatrivhihsviilRRSDKTKDRVEISPEQ 96
Cdd:cd08058   1 DALLKMLQHAESNTGIEVMGLLCGELTHN-----------------------------------EFTDKHVIVPKQSAGP 45
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 45361707  97 LSAASIE-AERLAEQTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQSFVGLIFACFIEDKPTkiGRVLYT 171
Cdd:cd08058  46 DSCTGENvEELFNVQTGRPLLVVGWYHSHPTFTAWLSSVDIHTQASYQLMLPEAIAIVVSPKHRNKDT--GIFRLT 119
BRCC36_C pfam18110
BRCC36 C-terminal helical domain; This is the C-terminal domain of BRCC36, a Zn2+ dependent ...
203-283 4.87e-35

BRCC36 C-terminal helical domain; This is the C-terminal domain of BRCC36, a Zn2+ dependent deubiquitinating enzyme, present in Camponotus floridanus. BRCC36 hydrolyzes lysine linked ubiquitin chains as part of macromolecular complexes that participate in either interferon signalling or DNA-damage recognition. The domain consists of 2 non canonical helices. The domain interacts hydrophobically with helices alpha 4 and alpha 5 of KIAA0157 in the form of a coiled coil helical bundle. This interaction helps establish the association of BRCC36 with KIAA0157, a pseudo-DUB MPN- protein that is essential for the activity of BRCC36.


Pssm-ID: 465654  Cd Length: 81  Bit Score: 121.27  E-value: 4.87e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707   203 CLRSAIELPGILCQEEQEAYRRIHGLTHLDSVTKIHNGSVFTKHLCSQMSAVCGPLLQWLEDRLEQNQQRLQELEQEKED 282
Cdd:pfam18110   1 CLESLTELPEILFQEEKEAYEKAKKSGSLDLLTKIHNGSVFTKSLCHITEAISGPLLQALEARLKLNKNRLAALKQEKEE 80

                  .
gi 45361707   283 L 283
Cdd:pfam18110  81 L 81
JAB_MPN smart00232
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
12-178 1.56e-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: 111.70  E-value: 1.56e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707     12 VYLESDAFLVCLNHALSTEKEEVMGLCIGQLNDHgrsdsrlayagaemctvakkmeatrIVHIHSVIILRRsDKTKDRVE 91
Cdd:smart00232   2 VKVHPLVPLNILKHAIRDGPEEVCGVLLGKSNKD-------------------------RPEVKEVFAVPN-EPQDDSVQ 55
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707     92 ISPEQLSAASIEAERlaeQTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQSFVGLIfacfIEDKPTKIGRVLYT 171
Cdd:smart00232  56 EYDEDYSHLMDEELK---KVNKDLEIVGWYHSHPDESPFPSEVDVATHESYQAPWPISVVLI----VDPIKSFQGRLSLR 128

                   ....*..
gi 45361707    172 CFQSVQA 178
Cdd:smart00232 129 AFRLTPE 135
JAB pfam01398
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ...
7-148 4.36e-29

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: 107.04  E-value: 4.36e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707     7 QGVQAVYLESDAFLVCLNHALSTEK--EEVMGLCIGQLNDHGRsdsrlayagaemctvakkmeatriVHIHSVIILRRSD 84
Cdd:pfam01398   1 SSVRTVIIHPLVLLKILDHANRGGKigEEVMGVLLGKLEGDGT------------------------IEITNSFALPQEE 56
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 45361707    85 KTKDRVEISPEQLSAASieAERLAEQTGRPMRVVGWYHSHPHItVWPSHVDVRTQAMYQMMDQS 148
Cdd:pfam01398  57 TEDDVNAVALDQEYMEN--MHEMLKKVNRKEEVVGWYHTHPGL-CWLSSVDVHTHALYQRMIPE 117
MPN_RPN11_CSN5 cd08069
Mov34/MPN/PAD-1 family: proteasomal regulatory protein Rpn11 and signalosome complex subunit ...
12-152 9.15e-14

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.


Pssm-ID: 163700 [Multi-domain]  Cd Length: 268  Bit Score: 69.59  E-value: 9.15e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707  12 VYLESDAFLVCLNHALSTEKEEVMGLCIGQLNDHgrsdsrlayagaemctvakkmeatrivhihSVIIlrrSD------- 84
Cdd:cd08069  12 VYISSLALLKMLKHARAGGPIEVMGLMLGKVDDY------------------------------TIIV---VDvfalpve 58
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 45361707  85 KTKDRVEISpeqlsAASIE---AERLAEQTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQSFVGL 152
Cdd:cd08069  59 GTETRVNAQ-----DEFQEymvQYEMLKQTGRPENVVGWYHSHPGYGCWLSGIDVNTQQLNQQLQDPFVAV 124
MPN_2A_DUB cd08067
Mov34/MPN/PAD-1 family: Histone H2A deubiquitinase; This family includes histone H2A ...
98-184 8.93e-11

Mov34/MPN/PAD-1 family: Histone H2A deubiquitinase; This family includes histone H2A deubiquitinase (Histone H2A DUB;MYSM1; myb-like, SWIRM and MPN domains 1; 2ADUB; 2A-DUB; KIAA19152ADUB, or KIAA1915/MYSM1), a member of JAMM/MPN+ deubiquitinases (DUBs), with possible Zn2+-dependent ubiquitin isopeptidase activity. It contains the SWIRM (Swi3p, Rsc8p and Moira), and SANT (SWI-SNF, ADA N-CoR, TFIIIB)/Myb domains; the SANT, but not the SWIRM, domain can bind directly to DNA. 2A-DUB is specific for monoubiquitinated H2A (uH2A), regulating transcription by coordinating histone acetylation and deubiquitination, and destabilizing the association of linker histone H1 with nucleosomes. 2A-DUB interacts with p/CAF (p300/CBP-associated factor) in a co-regulatory protein complex, where the status of acetylation of nucleosomal histones modulates its deubiquitinase activity. 2A-DUB is a positive regulator of androgen receptor (AR) transactivation activity on a reporter gene; it participates in transcriptional regulation events in androgen receptor-dependent gene activation. In prostate tumors, the levels of uH2A are dramatically decreased, thus 2A-DUB serving as a cancer-related marker.


Pssm-ID: 163698 [Multi-domain]  Cd Length: 187  Bit Score: 59.97  E-value: 8.93e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707  98 SAASIEAErLAEQ-TGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMM----DQS---FVGLIFACFIEDKPTKIGRVL 169
Cdd:cd08067  62 MDPVSETE-IRESlESRGLSVVGWYHSHPTFPPNPSLRDIDTQLDYQIMfkgsDSGyepCVGLICSPYDRRNSTPESQIT 140
                        90
                ....*....|....*
gi 45361707 170 YTCFQSVQASKSSEY 184
Cdd:cd08067 141 CFWVMPPPENRPNEY 155
Rri1 COG1310
Proteasome lid subunit RPN8/RPN11, contains Jab1/MPN domain metalloenzyme (JAMM) motif ...
82-137 2.45e-07

Proteasome lid subunit RPN8/RPN11, contains Jab1/MPN domain metalloenzyme (JAMM) motif [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 440921  Cd Length: 127  Bit Score: 48.76  E-value: 2.45e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 45361707  82 RSDKTKDRVEISPEQLsaasIEAERLAEQTGrpMRVVGWYHSHPHITVWPSHVDVR 137
Cdd:COG1310  47 VAESPETRFEIDPEDL----LAAEREARERG--LEIVGIYHSHPDGPAYPSETDRA 96
MPN_like cd08070
Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); ...
23-137 4.49e-06

Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); This family contains archaeal and bacterial MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+)-like domains. These domains contain the signature JAB1/MPN/Mov34 metalloenzyme (JAMM) motif, EXnHS/THX7SXXD, which is involved in zinc ion coordination and provides the active site for isopeptidase activity for the release of ubiquitin from ubiquitinated proteins (thus having deubiquitinating (DUB) activity) that are tagged for degradation. The JAMM proteins likely hydrolyze ubiquitin conjugates in a manner similar to thermolysin, in which the zinc-polarized aqua ligand serves as the nucleophile, compared with the classical DUBs that do so with a cysteine residue in the active site.


Pssm-ID: 163701  Cd Length: 128  Bit Score: 44.94  E-value: 4.49e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 45361707  23 LNHALSTEKEEVMGLCIGqlndHGRSDSRLAYAGAEMCTVAkkmeatrivhihsviilrrsDKTKDRVEISPEQLsaasI 102
Cdd:cd08070   8 LAHAEAEYPEECCGLLLG----KGGGVTAIVTEVYPVRNVA--------------------ESPRRRFEIDPAEQ----L 59
                        90       100       110
                ....*....|....*....|....*....|....*
gi 45361707 103 EAERLAEQTGrpMRVVGWYHSHPHITVWPSHVDVR 137
Cdd:cd08070  60 AAQREARERG--LEVVGIYHSHPDGPARPSETDLR 92
MPN cd07767
Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) ...
115-165 4.66e-04

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: 39.03  E-value: 4.66e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 45361707 115 MRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQSFVGLI--FACFIEDKPTKI 165
Cdd:cd07767  63 LRIVGWYHTHPKPSCFLSPNDLATHELFQRYFPEKVMIIvdVKPKDLGNSWKC 115
MPN_prok_mb cd08059
Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); ...
88-139 2.25e-03

Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); prokaryotic; This family contains bacterial and archaeal MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+)-like domains. These catalytically active domains contain the signature JAB1/MPN/Mov34 metalloenzyme (JAMM) motif, EXnHS/THX7SXXD, which is involved in zinc ion coordination and provides the active site for isopeptidase activity for the release of ubiquitin from ubiquitinated proteins (thus having deubiquitinating (DUB) activity) that are tagged for degradation. The JAMM proteins likely hydrolyze ubiquitin conjugates in a manner similar to thermolysin, in which the zinc-polarized aqua ligand serves as the nucleophile, compared with the classical DUBs that do so with a cysteine residue in the active site.


Pssm-ID: 163690  Cd Length: 101  Bit Score: 36.77  E-value: 2.25e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 45361707  88 DRVEISPEQLSAASIEAERLAEQTGrpMRVVGWYHSHPHITVWPSHVDVRTQ 139
Cdd:cd08059  31 DELIFLPFVSGSVSAVIDLAALEIG--MKVVGLVHSHPSGSCRPSEADLSLF 80
MPN_AMSH_like cd08066
Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM ...
103-145 3.96e-03

Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM (signal-transducing adapter molecule, also known as STAMBP)) and AMSH-like proteins (AMSH-LP) are members of JAMM/MPN+ deubiquitinases (DUBs), with Zn2+-dependent ubiquitin isopeptidase activity. AMSH specifically cleaves Lys 63 and not Lys48-linked polyubiquitin (poly-Ub) chains, thus facilitating the recycling and subsequent trafficking of receptors to the cell surface. AMSH and AMSH-LP are anchored on the early endosomal membrane via interaction with the clathrin coat. AMSH shares a common SH3-binding site with another endosomal DUB, UBPY (ubiquitin-specific protease Y; also known as USP8), the latter being a cysteine protease that does not discriminate between Lys48 and Lys63-linked ubiquitin. AMSH is involved in the degradation of EGF receptor (EGFR) and possibly other ubiquitinated endocytosed proteins. AMSH also interacts with CHMP1, CHMP2, and CHMP3 proteins, all of which are components of ESCRT-III, suggested to be required for EGFR down-regulation. The function of AMSH-LP has not been elucidated; however, it exhibits two fundamentally distinct features from AMSH: first, there is a substitution in the critical amino acid residue in the SH3-binding motif (SBM) in the human AMSH-LP, but not in its mouse ortholog, and lacks STAM-binding ability; second, AMSH-LP lacks the ability to interact with CHMP proteins. It is therefore likely that AMSH and AMSH-LP play different roles on early endosomes.


Pssm-ID: 163697  Cd Length: 173  Bit Score: 37.19  E-value: 3.96e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 45361707 103 EAERLAEQTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMM 145
Cdd:cd08066  63 EEELFDFQDQHDLITLGWIHTHPTQTCFLSSVDLHTHCSYQLM 105
 
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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