USP8 dimerization domain; This domain is predominantly found in the amino terminal region of Ubiquitin carboxyl-terminal hydrolase 8 (USP8). It forms a five helical bundle that dimerizes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577  28 ERVRALSKLGCNISINEDITPRRYFRSGVEMERMASVYLEEGNLENAFVLYNKFITLFvEKLPSHRDYQQCAVPEKQDIM 107
Cdd:pfam08969  10 SSLEDLEKLTEKLEVDKNKSPKRYYRSALKLYKTAEEYRLEGDEENAYILYMKYFNLF-EKIRKHPDYKSVKATVRQMLG 88

                          90       100
                  ....*....|....*....|....*
gi 1341395577 108 KKLKEIAFPRTDELKTDLLRKYNIE 132
Cdd:pfam08969  89 KTKINEVLDELEKLKTSLLERYEEE 113

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577 264 EGLRCVVLSRDLCHKFLLLADSNTVRGIETCGILCGKLTHNEFT-ITHVVVPKQSAGPDYCDVENVEELFNVQDQH---- 338
Cdd:pfam01398   1 SSVRTVIIHPLVLLKILDHANRGGKIGEEVMGVLLGKLEGDGTIeITNSFALPQEETEDDVNAVALDQEYMENMHEmlkk 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1341395577 339 ---GLLTLGWIHTHPTQtAFLSSVDLHTHCSYQLMLPE 373
Cdd:pfam01398  81 vnrKEEVVGWYHTHPGL-CWLSSVDVHTHALYQRMIPE 117

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577  269 VVLSRDLCHKFLLLADSNtvRGIETCGILCGKLTHNEFTITHVVVPKQSagPDYCDVENVEELFNV-------QDQHGLL 341
Cdd:smart00232   2 VKVHPLVPLNILKHAIRD--GPEEVCGVLLGKSNKDRPEVKEVFAVPNE--PQDDSVQEYDEDYSHlmdeelkKVNKDLE 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1341395577  342 TLGWIHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCSP---KHKD--TGIFRLTNA 394
Cdd:smart00232  78 IVGWYHSHPDESPFPSEVDVATHESYQAPWPISVVLIVDPiksFQGRlsLRAFRLTPE 135

Periplasmic chaperone for outer membrane proteins, Skp family [Cell wall/membrane/envelope biogenesis, Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1341395577 101 PEKQDIMKKLKEIAFPRTDELKTdLLRKYNIEYQEYLQSKNKYKAEILKKLEhQRLIEAER--QRIAQMRQQQLESEQ 176
Cdd:COG2825    39 PEGKAAQKKLEKEFKKRQAELQK-LEKELQALQEKLQKEAATLSEEERQKKE-RELQKKQQelQRKQQEAQQDLQKRQ 114

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577 134 QEYLQSKNKYKAEILK----KLEHQRLIEAERQRI-AQMRQQQLESEQFLFFEDQLKKQE 188
Cdd:cd16269   173 QEFLQSKEAEAEAILQadqaLTEKEKEIEAERAKAeAAEQERKLLEEQQRELEQKLEDQE 232

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577 274 DLCHKFLLLADSNTvrGIETCGILCGKLTHNEFTITHVVVPKQSAGPDYCDVENVEELFNVQDQHGLLTLGWIHTHPTQT 353
Cdd:cd08058     1 DALLKMLQHAESNT--GIEVMGLLCGELTHNEFTDKHVIVPKQSAGPDSCTGENVEELFNVQTGRPLLVVGWYHSHPTFT 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1341395577 354 AFLSSVDLHTHCSYQLMLPEAIAIVCSPKH--KDTGIFRLT 392
Cdd:cd08058    79 AWLSSVDIHTQASYQLMLPEAIAIVVSPKHrnKDTGIFRLT 119

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577 264 EGLRCVVLSRDLCHKFLLLADSNTVRGIETCGILCGKLTHNEFT-ITHVVVPKQSAGPDYCDVENVEELFNVQDQH---- 338
Cdd:pfam01398   1 SSVRTVIIHPLVLLKILDHANRGGKIGEEVMGVLLGKLEGDGTIeITNSFALPQEETEDDVNAVALDQEYMENMHEmlkk 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1341395577 339 ---GLLTLGWIHTHPTQtAFLSSVDLHTHCSYQLMLPE 373
Cdd:pfam01398  81 vnrKEEVVGWYHTHPGL-CWLSSVDVHTHALYQRMIPE 117

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577  269 VVLSRDLCHKFLLLADSNtvRGIETCGILCGKLTHNEFTITHVVVPKQSagPDYCDVENVEELFNV-------QDQHGLL 341
Cdd:smart00232   2 VKVHPLVPLNILKHAIRD--GPEEVCGVLLGKSNKDRPEVKEVFAVPNE--PQDDSVQEYDEDYSHlmdeelkKVNKDLE 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1341395577  342 TLGWIHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCSP---KHKD--TGIFRLTNA 394
Cdd:smart00232  78 IVGWYHSHPDESPFPSEVDVATHESYQAPWPISVVLIVDPiksFQGRlsLRAFRLTPE 135

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577 291 IETCGILCGKLTHNEFTITHVV----------VPKQSAGPDY-CDVENVEelfnvQDQHGLLTLGWIHTHPTQTAFLSSV 359
Cdd:cd08069    32 IEVMGLMLGKVDDYTIIVVDVFalpvegtetrVNAQDEFQEYmVQYEMLK-----QTGRPENVVGWYHSHPGYGCWLSGI 106

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1341395577 360 DLHTHCSYQLMLPEAIAIVCSPK------HKDTGIFRLTNAGML 397
Cdd:cd08069   107 DVNTQQLNQQLQDPFVAVVVDPIrslvkgKVVIGAFRTIPPGYK 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.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1341395577 343 LGWIHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCS 380
Cdd:cd08068    92 VGWYHSHPHITVWPSHVDVRTQAMYQMMDSGFVGLIFS 129

Mpr1p, Pad1p N-terminal (MPN) domains without isopeptidase activity found in splicing factor Prp8; Members of this family are found in pre-mRNA-processing factor 8 (Prp8) which is a critical splicing factor, interacting with several other spliceosomal proteins, snRNAs, and the pre-mRNA, thus organizing and stabilizing the spliceosome catalytic core. Prp8 is one of the largest and most highly conserved of nuclear proteins, occupying a central position in the catalytic core of the spliceosome. Its C-terminal domain exhibits a JAB1/MPN-like core similar to deubiquitinating enzymes, but does not show catalytic isopeptidase activity, possibly because the putative isopeptidase center is covered by insertions and terminal appendices that are grafted onto this core, thus impairing the metal binding site. It is proposed that this domain is a protein interaction domain instead of a Zn(2+)-dependent metalloenzyme as proposed for some MPN proteins. The DEAD-box protein Brr2 and the GTPase Snu114 bind to the Prp8 C-terminus, a region where mutations in human Prp8 (hPrp8) cause a severe form of the genetic disorder retinitis pigmentosa, RP13, which leads to progressive photoreceptor degeneration in the retina and eventual blindness. At the N-terminus of Prp8, there are several domains, including a highly variable nuclear localization signal (NLS) motif rich in prolines, a conserved RNA recognition motif (RRM), and U5 and U6 snRNA binding sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577 270 VLSRDLCHKFLLLADsntVRgIETCGILCGK-LTHNEFT--ITHVVVPkqsagPDYCDVENVEeLFNVQDQHGLLT---- 342
Cdd:cd08056    39 ILPKNLLKKFISISD---LR-TQIAGYLYGKsPPDNPQVkeIRCIVLV-----PQLGTHQTVT-LPQQLPQHEYLEdlep 108

                          90       100
                  ....*....|....*....|..
gi 1341395577 343 LGWIHTHPTQTAFLSSVDLHTH 364
Cdd:cd08056   109 LGWIHTQPNELPQLSPQDVTTH 130

Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal domain. Guanylate-binding proteins (GBPs) are synthesized after activation of the cell by interferons. The biochemical properties of GBPs are clearly different from those of Ras-like and heterotrimeric GTP-binding proteins. They bind guanine nucleotides with low affinity (micromolar range), are stable in their absence, and have a high turnover GTPase. In addition to binding GDP/GTP, they have the unique ability to bind GMP with equal affinity and hydrolyze GTP not only to GDP, but also to GMP. This C-terminal domain has been shown to mediate inhibition of endothelial cell proliferation by inflammatory cytokines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1341395577 134 QEYLQSKNKYKAEILK----KLEHQRLIEAERQRI-AQMRQQQLESEQFLFFEDQLKKQE 188
Cdd:cd16269   173 QEFLQSKEAEAEAILQadqaLTEKEKEIEAERAKAeAAEQERKLLEEQQRELEQKLEDQE 232