Prokaryotic homologs of the JAB domain; These are metalloenzymes that function as the ubiquitin isopeptidase/ deubiquitinase in the ubiquitin-based signaling and protein turnover pathways in eukaryotes. Prokaryotic JAB domains are predicted to have a similar role in their cognates of the ubiquitin modification pathway. The domain is widely found in bacteria, archaea and phages where they are present in several gene contexts in addition to those that correspond to the prokaryotic cognates of the eukaryotic Ub pathway. Other contexts in which JAB domains are present include gene neighbor associations with ubiquitin fold domains in cysteine and siderophore biosynthesis, and phage tail morphogenesis, where they are shown or predicted to process the associated ubiquitin. A distinct family, the RadC-like JAB domains are widespread in bacteria and are predicted to function as nucleases. In halophilic archaea the JAB domain shows strong gene-neighborhood associations with a nucleotidyltransferase suggesting a role in nucleotide metabolism.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805378812    8 RDTLDFILEASRSMAPEEFAGLL-----QEQDGIITEVLILPG----TESSDSNAVLRLYMMPNVKAAGSVHSHPGPNRR 78
Cdd:pfam14464   2 APLLDAIVAHARAAHPLECCGILlgnelESQSVRVIPLVNPMRnrfeIDPGDSLRRVKAARERGLELVGIYHSHPGGPAY 81

                          90       100       110
                  ....*....|....*....|....*....|..
gi 805378812   79 PSKADLHLFSKTGNCHIIAGR-PYDRESWTCY 109
Cdd:pfam14464  82 PSETDRRDAAGPLPSYVIGGRaPPEIRSWRLV 113

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 805378812     6 IARDTLDFILEASRSMAPEEFAG-LLQEQDG---IITEVLILPGTESSDSNAVLRL---YMMPNVKAA--------GSVH 70
Cdd:smart00232   4 VHPLVPLNILKHAIRDGPEEVCGvLLGKSNKdrpEVKEVFAVPNEPQDDSVQEYDEdysHLMDEELKKvnkdleivGWYH 83

                           90
                   ....*....|....*
gi 805378812    71 SHPGPNRRPSKADLH 85
Cdd:smart00232  84 SHPDESPFPSEVDVA 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 805378812   9 DTLDFILEASRSMAPEEFAGLLQ-EQDGIITEVLILPGTESSDSNAVLRLYMMPNVKAAGSVHSHPGPNRRPSKADLHLF 87
Cdd:cd08059    1 DLLKTILVHAKDAHPDEFCGFLSgSKDNVMDELIFLPFVSGSVSAVIDLAALEIGMKVVGLVHSHPSGSCRPSEADLSLF 80

                         90       100
                 ....*....|....*....|..
gi 805378812  88 SKTGNCHIIAGRPYDrESWTCY 109
Cdd:cd08059   81 TRFGLYHVIVCYPYE-NSWKCY 101

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 805378812  14 ILEASRSMAPEEFAGLL----QEQDGIITEVLILPGTESSDSNAVLRLYMMPNVKA------AGSVHSHPGPNRRPSKAD 83
Cdd:cd07767    4 FLDAAKSINGKEVIGLLygskTKKVLDVDEVIAVPFDEGDKDDNVWFLMYLDFKKLnaglriVGWYHTHPKPSCFLSPND 83

                         90       100       110
                 ....*....|....*....|....*....|...
gi 805378812  84 LHLFSK-----TGNCHIIAGRPYDRE--SWTCY 109
Cdd:cd07767   84 LATHELfqryfPEKVMIIVDVKPKDLgnSWKCY 116

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 805378812     6 IARDTLDFILEASRSMAPEEFAG-LLQEQDG---IITEVLILPGTESSDSNAVLRL---YMMPNVKAA--------GSVH 70
Cdd:smart00232   4 VHPLVPLNILKHAIRDGPEEVCGvLLGKSNKdrpEVKEVFAVPNEPQDDSVQEYDEdysHLMDEELKKvnkdleivGWYH 83

                           90
                   ....*....|....*
gi 805378812    71 SHPGPNRRPSKADLH 85
Cdd:smart00232  84 SHPDESPFPSEVDVA 98