Conserved Protein Domain Family

cd07767: MPN 
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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
View PSSM: cd07767
Aligned: 8 rows
Threshold Bit Score: 103.745
Threshold Setting Gi: 147898562
Created: 30-Sep-2008
Updated: 2-Oct-2020
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
1OI0_A        11 LKTILEAAksa--------hpdEFIALLSGskd-----------vmdELIFlpfvsgsvsavi-------------hldm 58  Archaeoglobus f...
2O95_A        17 LLSVVDHFnrigk----vgnqkRVVGVLLGswqkk-------vldvsNSFAvpfdeddkddsvwfldhdylenmygmfkk 85  human
2P87_A        48 LKKFITISdl----------rtQIAGFMYGvsppdnp----qvkeirCIVLvpqtgshqqvnlpt---------qlpdhe 104 nematode
1R5X_A        20 LKTILEAAksa--------hpdEFIALLSGskd-----------vmdELIFlpfvsgsvsavi-------------hldm 67  Archaeoglobus f...
NP_002802     16 LLSVVDHFnrigk----vgnqkRVVGVLLGswqkk-------vldvsNSFAvpfdeddkddsvwfldhdylenmygmfkk 84  human
2ZNR_A        18 CHKFLQLAesnt------vrgiETCGILCGklthn-------eftitHVIVpkqsagpdycdmenv-------eelfnvq 77  human
NP_998535     11 CKMLLHAAkyp---------hcAVNGLLVAekhkkkdnprdsvlcvdCVPLfhgalalapmleval-------tlidtwc 74  zebrafish
NP_001080427 227 NIMFENHTiadrfldfwrktgnQRIGYLYGrytehkd---iplglraEVAAiyeppqigtqnslqlldd-pkakvvdeia 302 African clawed ...
1OI0_A        59 lpigmkvFGTVHSHpsps---------------crpSEEDLSLFtrf-----------------gkYHIIVCypyd---- 102 Archaeoglobus f...
2O95_A        86 vnareriVGWYHTGpk-------------------lHKNDIAINelmkr------------ycpnsVLVIIDvkpkd--- 131 human
2P87_A       105 llrdfepLGWMHTQpnel---------------pqlSPQDVTTHaklltdni-------swdgektVMITCSftpg---- 158 nematode
1R5X_A        68 lpigmkvFGTVHSHpsps---------------crpSEEDLSLFtrf-----------------gkYHIIVCypyd---- 111 Archaeoglobus f...
NP_002802     85 vnareriVGWYHTGpk-------------------lHKNDIAINelmkr------------ycpnsVLVIIDvkpkd--- 130 human
2ZNR_A        78 dqhdlltLGWIHTHptqt---------------aflSSVDLHTHcsyql------------mlpeaIAIVCSpkh----- 125 human
NP_998535     75 kenkyviAGYYQANeri----------------ketRPNQVAEKvaaris----------enfseaAMIMMDnsrftmec 128 zebrafish
NP_001080427 303 aklglrkVGWIFTDlvsedtrkgtvrysrnkdtyflSAEECITAgyfqnkypnlcrlspdahfgskFVTVVAtggpdnqv 382 African clawed ...
1OI0_A       103 -------------ensWKCY 109 Archaeoglobus fulgidus
2O95_A       132 ------------lglpTEAY 139 human
2P87_A       159 -------------svsLTAY 165 nematode
1R5X_A       112 -------------ensWKCY 118 Archaeoglobus fulgidus DSM 4304
NP_002802    131 ------------lglpTEAY 138 human
2ZNR_A       126 --------------kdTGIF 131 human
NP_998535    129 fvp--vlfiydhhdnkWKCR 146 zebrafish
NP_001080427 383 hfegyqvsnqcmalvrDECL 402 African clawed frog
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