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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987  772 NEQPFTIDVSSNTMIVMDIHSHISSTEVIGMLGGKFNPDTNHITILLAIPCNSISSDIQCDMDPNSQIAAKEMVNSIGLD 851
Cdd:cd08067    1 KIQPFKVTVSSNALLLMDFHCHLTTSEVIGYLGGTWDPNTQNLTILQAFPCRSRLTGLDCEMDPVSETEIRESLESRGLS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987  852 IVGWYHSHPNFEPIPSLRDIETQTSFQNLFATSSnnnnnnnkSMIEPFIGFIVNPYH--KNGLISNFNCITITKQMD-ET 928
Cdd:cd08067   81 VVGWYHSHPTFPPNPSLRDIDTQLDYQIMFKGSD--------SGYEPCVGLICSPYDrrNSTPESQITCFWVMPPPEnRP 152

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 66815987  929 NQYRIPYQLSTSYTPSLN-NQYLYQQIDNLFEKYK 962
Cdd:cd08067  153 NEYGVPMLMSYTVSQDEFlTQDVLKELRWLVEFYR 187

'SWI3, ADA2, N-CoR and TFIIIB' DNA-binding domains. Tandem copies of the domain bind telomeric DNA tandem repeatsas part of the capping complex. Binding is sequence dependent for repeats which contain the G/C rich motif [C2-3 A (CA)1-6]. The domain is also found in regulatory transcriptional repressor complexes where it also binds DNA.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 66815987  231 PWSNEEHELFLKAIEKYGRGNWKLISTLIKSRNTLQIKNHARIYF 275
Cdd:cd00167    1 PWTEEEDELLLEAVKKYGKNNWEKIAKELPGRTPKQCRERWRNLL 45

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987  772 NEQPFTIDVSSNTMIVMDIHSHISSTEVIGMLGGKFNPDTNHITILLAIPCNSISSDIQCDMDPNSQIAAKEMVNSIGLD 851
Cdd:cd08067    1 KIQPFKVTVSSNALLLMDFHCHLTTSEVIGYLGGTWDPNTQNLTILQAFPCRSRLTGLDCEMDPVSETEIRESLESRGLS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987  852 IVGWYHSHPNFEPIPSLRDIETQTSFQNLFATSSnnnnnnnkSMIEPFIGFIVNPYH--KNGLISNFNCITITKQMD-ET 928
Cdd:cd08067   81 VVGWYHSHPTFPPNPSLRDIDTQLDYQIMFKGSD--------SGYEPCVGLICSPYDrrNSTPESQITCFWVMPPPEnRP 152

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 66815987  929 NQYRIPYQLSTSYTPSLN-NQYLYQQIDNLFEKYK 962
Cdd:cd08067  153 NEYGVPMLMSYTVSQDEFlTQDVLKELRWLVEFYR 187

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 66815987     787 VMDIHSHISSTEVIGMLGGKFNPDTNHITILLAIPCNSISSDIQC-DMDPNSQIAAKEMVNSIGLDIVGWYHSHPNFEPI 865
Cdd:smart00232   12 ILKHAIRDGPEEVCGVLLGKSNKDRPEVKEVFAVPNEPQDDSVQEyDEDYSHLMDEELKKVNKDLEIVGWYHSHPDESPF 91

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|..
gi 66815987     866 PSLRDIETQTSFQnlfatssnnnnnnnkSMIEPFIGFIVNPY 907
Cdd:smart00232   92 PSEVDVATHESYQ---------------APWPISVVLIVDPI 118

'SWI3, ADA2, N-CoR and TFIIIB' DNA-binding domains. Tandem copies of the domain bind telomeric DNA tandem repeatsas part of the capping complex. Binding is sequence dependent for repeats which contain the G/C rich motif [C2-3 A (CA)1-6]. The domain is also found in regulatory transcriptional repressor complexes where it also binds DNA.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 66815987  231 PWSNEEHELFLKAIEKYGRGNWKLISTLIKSRNTLQIKNHARIYF 275
Cdd:cd00167    1 PWTEEEDELLLEAVKKYGKNNWEKIAKELPGRTPKQCRERWRNLL 45

Myb-like DNA-binding domain; This family contains the DNA binding domains from Myb proteins, as well as the SANT domain family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 66815987    231 PWSNEEHELFLKAIEKYGrGNWKLISTLIKSRNTLQIKNHARIYF 275
Cdd:pfam00249    3 PWTPEEDELLLEAVEKLG-NRWKKIAKLLPGRTDNQCKNRWQNYL 46

SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 66815987     150 RSSWTKEEERLFVEAYKLYDKDN-KKIQEHVKTKTILQVRSHAQKF 194
Cdd:smart00717    1 KGEWTEEEDELLIELVKKYGKNNwEKIAKELPGRTAEQCRERWRNL 46

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 66815987    795 SSTEVIGMLGGKFNPDTN-HITILLAIPCNSISSDIQC-DMDPNSQIAAKEMVNSIGLD--IVGWYHSHPNFePIPSLRD 870
Cdd:pfam01398   26 IGEEVMGVLLGKLEGDGTiEITNSFALPQEETEDDVNAvALDQEYMENMHEMLKKVNRKeeVVGWYHTHPGL-CWLSSVD 104

                   ....*...
gi 66815987    871 IETQTSFQ 878
Cdd:pfam01398  105 VHTHALYQ 112

myb-like DNA-binding domain, SHAQKYF class; This model describes a DNA-binding domain restricted to (but common in) plant proteins, many of which also contain a response regulator domain. The domain appears related to the Myb-like DNA-binding domain described by pfam00249. It is distinguished in part by a well-conserved motif SH[AL]QKY[RF] at the C-terminal end of the motif.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 66815987    150 RSSWTKEEERLFVEAYKLYDKDN----KKIQEHVKTK--TILQVRSHAQKFALKL 198
Cdd:TIGR01557    3 RVVWTEDLHDRFLQAVQKLGGPDwatpKRILELMVVDglTRDQVASHLQKYRLKQ 57

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987  772 NEQPFTIDVSSNTMIVMDIHSHISSTEVIGMLGGKFNPDTNHITILLAIPCNSISSDIQCDMDPNSQIAAKEMVNSIGLD 851
Cdd:cd08067    1 KIQPFKVTVSSNALLLMDFHCHLTTSEVIGYLGGTWDPNTQNLTILQAFPCRSRLTGLDCEMDPVSETEIRESLESRGLS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987  852 IVGWYHSHPNFEPIPSLRDIETQTSFQNLFATSSnnnnnnnkSMIEPFIGFIVNPYH--KNGLISNFNCITITKQMD-ET 928
Cdd:cd08067   81 VVGWYHSHPTFPPNPSLRDIDTQLDYQIMFKGSD--------SGYEPCVGLICSPYDrrNSTPESQITCFWVMPPPEnRP 152

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 66815987  929 NQYRIPYQLSTSYTPSLN-NQYLYQQIDNLFEKYK 962
Cdd:cd08067  153 NEYGVPMLMSYTVSQDEFlTQDVLKELRWLVEFYR 187

SWIRM domain; This SWIRM domain is a small alpha-helical domain of about 85 amino acid residues found in chromosomal proteins. It contains a helix-turn helix motif and binds to DNA.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987    535 DLNIITQEEMMGCKEYFTGqISKTPDRYIKIRDKIIRQWDSFKPNYLSKTFSRNQIKdcgSDINSIGRVHQFLESIGVIN 614
Cdd:pfam04433    2 DPDKLHPIEKRLLPEFFNG-KSKTPEVYLEIRNFILNLWRENPKEYLTKTDARRALK---GDVNLISRIHEFLERWGLIN 77

                   .
gi 66815987    615 F 615
Cdd:pfam04433   78 F 78

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987  785 MIVMD------IHSHISST---EVIGMLGGKFNPDTnhiTILLAIPCNSISSDIQC--DMDPNSQIAA-KEMVNSiGLDI 852
Cdd:COG1310    1 MLVLPrelldaILAHAEAAypeECCGLLLGKGGGDK---RVTRVYPARNVAESPETrfEIDPEDLLAAeREARER-GLEI 76

                         90       100
                 ....*....|....*....|
gi 66815987  853 VGWYHSHPNFEPIPSLRDIE 872
Cdd:COG1310   77 VGIYHSHPDGPAYPSETDRA 96

SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 66815987     230 TPWSNEEHELFLKAIEKYGRGNWKLISTLIKSRNTLQIKNHARIYFDK 277
Cdd:smart00717    2 GEWTEEEDELLIELVKKYGKNNWEKIAKELPGRTAEQCRERWRNLLKP 49

Myb-like DNA-binding domain; This family contains the DNA binding domains from Myb proteins, as well as the SANT domain family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 66815987    231 PWSNEEHELFLKAIEKYGrGNWKLISTLIKSRNTLQIKNHARIYF 275
Cdd:pfam00249    3 PWTPEEDELLLEAVEKLG-NRWKKIAKLLPGRTDNQCKNRWQNYL 46

SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 66815987     150 RSSWTKEEERLFVEAYKLYDKDN-KKIQEHVKTKTILQVRSHAQKF 194
Cdd:smart00717    1 KGEWTEEEDELLIELVKKYGKNNwEKIAKELPGRTAEQCRERWRNL 46

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66815987  787 VMDIHSHISSTEVIGMLGGKFNPDTNHITILLAIPcnSISSDIQCDMDPNSQIAAKEMvnSIGLDIVGWYHSHPNFEPIP 866
Cdd:cd07767    4 FLDAAKSINGKEVIGLLYGSKTKKVLDVDEVIAVP--FDEGDKDDNVWFLMYLDFKKL--NAGLRIVGWYHTHPKPSCFL 79

                         90
                 ....*....|....*
gi 66815987  867 SLRDIETQTSFQNLF 881
Cdd:cd07767   80 SPNDLATHELFQRYF 94

myb-like DNA-binding domain, SHAQKYF class; This model describes a DNA-binding domain restricted to (but common in) plant proteins, many of which also contain a response regulator domain. The domain appears related to the Myb-like DNA-binding domain described by pfam00249. It is distinguished in part by a well-conserved motif SH[AL]QKY[RF] at the C-terminal end of the motif.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 66815987    231 PWSNEEHELFLKAIEKYGRGNW---KLISTLIK-SRNTL-QIKNHARIYFDK 277
Cdd:TIGR01557    5 VWTEDLHDRFLQAVQKLGGPDWatpKRILELMVvDGLTRdQVASHLQKYRLK 56

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 66815987  798 EVIGMLGGKFNPDTNHITILLAIP-------CNSIssdiqcdMDPNSQIAAKEMVNSIG--LDIVGWYHSHPNFEPIPSL 868
Cdd:cd08069   33 EVMGLMLGKVDDYTIIVVDVFALPvegtetrVNAQ-------DEFQEYMVQYEMLKQTGrpENVVGWYHSHPGYGCWLSG 105

                         90
                 ....*....|..
gi 66815987  869 RDIETQTSFQNL 880
Cdd:cd08069  106 IDVNTQQLNQQL 117

Telomere repeat binding factor-like DNA-binding domains of the SANT/myb-like family; Human telomere repeat binding factors, TRF1 and TRF2, function as part of the 6 component shelterin complex. TRF2 binds DNA and recruits RAP1 (via binding to the RAP1 protein c-terminal (RCT)) and TIN2 in the protection of telomeres from DNA repair machinery. Metazoan shelterin consists of 3 DNA binding proteins (TRF2, TRF1, and POT1) and 3 recruited proteins that bind to one or more of these DNA-binding proteins (RAP1, TIN2, TPP1). Schizosaccharomyces pombe TAZ1 is an orthlog and binds RAP1. Human TRF1 and TRF2 bind double-stranded DNA. hTRF2 consists of a basic N-terminus, a TRF homology domain, the RAP1 binding motif (RBM), the TIN2 binding motif (TBM) and a myb-like DNA binding domain, SANT, named after 'SWI3, ADA2, N-CoR and TFIIIB', several factors that share this domain. Tandem copies of the domain bind telomeric DNA tandem repeats as part of the capping complex. The single myb-like domain of TRF-type proteins is similar to the tandem myb_like domains found in yeast RAP1.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 66815987  231 PWSNEEHELFLKAIEKYGRGNWKLI---STLIKSRNTLQIKNHAR 272
Cdd:cd11660    2 KWTDEEDEALVEGVEKYGVGNWAKIlkdYFFVNNRTSVDLKDKWR 46

Mov34/MPN/PAD-1 family: archaeal JAB1/MPN/Mov34 metalloenzyme; This family contains only archaeal 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 66815987  798 EVIGMLGGKfnpdTNHITILLAIP---CNSISSDIQCDMDPnsqiaakemvnsIGLDIVGWYHSHPNFEPIPSLRDI 871
Cdd:cd08072   20 EFAALLRGK----DGVITELLILPgteSGEVSAVFPLLMLP------------LDMSIVGSVHSHPSGSPRPSDADL 80