Conserved Protein Domain Family

cd08058: MPN_euk_mb 
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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
Aligned: 5 rows
Threshold Bit Score: 171.223
Created: 30-Nov-2009
Updated: 2-Oct-2020
Aligned Rows:
MPN+ (JAMM)Zinc-binding
Conserved site includes 5 residues -Click on image for an interactive view with Cn3D
Feature 1:MPN+ (JAMM) motif
  • Comment:Based on literature and mutation studies

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
Feature 1                       #                                                             
2ZNR_A     16 DLCHKFLQLAEsntvrgiETCGILCGKlthn-----------------------------------eftiTHVIVpkqsa 60  human
Q5VVJ2    582 EALLIMDLHAHvs---maEVIGLLGGRyse--------------------------------------vdKVVEVcaaep 620 human
2ZNV_A     16 DLCHKFLQLAEsntvrgiATCGILCGKlthn-----------------------------------eftiTHVIVpkqsa 60  human
AAH21313   17 DAFLVCLNHALste--keEVMGLCIGElnddirsdskftytgtemrtvqekmdtirivhihsviilrrsdKRKDRveisp 94  house mouse
O00487     36 LALLKMLKHGRagv--pmEVMGLMLGEfv---------------------------------------ddYTVRVidvfa 74  horse
Feature 1                                           # #       #  #                            
2ZNR_A     61 gpdycdmen----------veelfnvqdqhdllTLGWIHTHPtqtaFLSSVDLHTHCSYQlm----lpEAIAIVCSPkh- 125 human
Q5VVJ2    621 cnslstglqcemd---pvsqtqasetlavrgfsVIGWYHSHPafdpNPSLRDIDTQAKYQsyfsrggaKFIGMIVSPynr 697 human
2ZNV_A     61 gpdycdmen----------veelfnvqdqhdllTLGWIHTHPtqtaFLSSVDLHTHCSYQlm----lpEAIAIVCSPkh- 125 human
AAH21313   95 eqlsaaste-----------aerlaeltgrpmrVVGWYHSHPhitvWPSHVDVRTQAMYQmm----dqGFVGLIFSCfie 159 house mouse
O00487     75 mpqsgtgvsveavdpvfqakmldmlkqtgrpemVVGWYHSHPgfgcWLSGVDINTQQSFEal----seRAVAVVVDPiqs 150 horse
Feature 1                  
2ZNR_A    126 ----kdTGIFRLT 134 human
Q5VVJ2    698 ---nnpLPYSQIT 707 human
2ZNV_A    126 ----kdTGIFRLT 134 human
AAH21313  160 d-kntkTGRVLYT 171 house mouse
O00487    151 vkgkvvIDAFRLI 163 horse

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