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Conserved domains on  [gi|2462520296|ref|XP_054222378|]
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AMSH-like protease isoform X1 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MPN_AMSH_like cd08066
Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM ...
 266-436 5.97e-117

Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM (signal-transducing adapter molecule, also known as STAMBP)) and AMSH-like proteins (AMSH-LP) are members of JAMM/MPN+ deubiquitinases (DUBs), with Zn2+-dependent ubiquitin isopeptidase activity. 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. AMSH and AMSH-LP are anchored on the early endosomal membrane via interaction with the clathrin coat. AMSH shares a common SH3-binding site with another endosomal DUB, UBPY (ubiquitin-specific protease Y; also known as USP8), the latter being a cysteine protease that does not discriminate between Lys48 and Lys63-linked ubiquitin. AMSH is involved in the degradation of EGF receptor (EGFR) and possibly other ubiquitinated endocytosed proteins. AMSH also interacts with CHMP1, CHMP2, and CHMP3 proteins, all of which are components of ESCRT-III, suggested to be required for EGFR down-regulation. The function of AMSH-LP has not been elucidated; however, it exhibits two fundamentally distinct features from AMSH: first, there is a substitution in the critical amino acid residue in the SH3-binding motif (SBM) in the human AMSH-LP, but not in its mouse ortholog, and lacks STAM-binding ability; second, AMSH-LP lacks the ability to interact with CHMP proteins. It is therefore likely that AMSH and AMSH-LP play different roles on early endosomes.


:

Pssm-ID: 163697  Cd Length: 173  Bit Score: 338.80  E-value: 5.97e-117
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 266 LRCVVLPEDLCHKFLQLAESNTVRGIETCGILCGKLTHNEFTITHVIVPKQSAGPDYCDMENVEELFNVQDQHDLLTLGW 345
Cdd:cd08066     1 LRQVVVPADLMDKFLQLAEPNTSRNLETCGILCGKLSNNAFFITHLIIPKQSGTSDSCQTTNEEELFDFQDQHDLITLGW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 346 IHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCSPKHKDTGIFRLT-NAGMLEVSACKKKGFHPHTKEPRLFSICKHVL 424
Cdd:cd08066    81 IHTHPTQTCFLSSVDLHTHCSYQLMLPEAIAIVCAPKYNEFGIFRLTdPPGLDEILNCKKTGFHPHPKDPPLYEDCGHVI 160

                         170
                  ....*....|...
gi 2462520296 425 VKD-IKIIVLDLR 436
Cdd:cd08066   161 WKDqLKVTVVDLR 173
USP8_dimer super family cl07540
USP8 dimerization domain; This domain is predominantly found in the amino terminal region of ...
 28-132 6.31e-19

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.


The actual alignment was detected with superfamily member pfam08969:

Pssm-ID: 462647  Cd Length: 113  Bit Score: 81.96  E-value: 6.31e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296  28 ERVRALSKLGCNITISEDITPRRYFRSGVEMERMASVYLEEGNLENAFVLYNKFITLFvEKLPNHRDYQQCAVPEKQDIM 107
Cdd:pfam08969  10 SSLEDLEKLTEKLEVDKNKSPKRYYRSALKLYKTAEEYRLEGDEENAYILYMKYFNLF-EKIRKHPDYKSVKATVRQMLG 88

                          90       100
                  ....*....|....*....|....*
gi 2462520296 108 KKLKEIAFPRTDELKNDLLKKYNVE 132
Cdd:pfam08969  89 KTKINEVLDELEKLKTSLLERYEEE 113
GBP_C super family cl46256
Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal ...
 120-198 4.23e-03

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.


The actual alignment was detected with superfamily member cd16269:

Pssm-ID: 293879 [Multi-domain]  Cd Length: 291  Bit Score: 38.71  E-value: 4.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 120 ELKNDLLKKYNVE----------YQEYLQSKNKYKAEILK----KLEHQRLIEAERKRI-AQMRQQQLESEQflffedQL 184
Cdd:cd16269   149 EDREKLVEKYRQVprkgvkaeevLQEFLQSKEAEAEAILQadqaLTEKEKEIEAERAKAeAAEQERKLLEEQ------QR 222

                          90
                  ....*....|....
gi 2462520296 185 KKQELARGQMRSQQ 198
Cdd:cd16269   223 ELEQKLEDQERSYE 236
 
Name Accession Description Interval E-value
MPN_AMSH_like cd08066
Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM ...
 266-436 5.97e-117

Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM (signal-transducing adapter molecule, also known as STAMBP)) and AMSH-like proteins (AMSH-LP) are members of JAMM/MPN+ deubiquitinases (DUBs), with Zn2+-dependent ubiquitin isopeptidase activity. 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. AMSH and AMSH-LP are anchored on the early endosomal membrane via interaction with the clathrin coat. AMSH shares a common SH3-binding site with another endosomal DUB, UBPY (ubiquitin-specific protease Y; also known as USP8), the latter being a cysteine protease that does not discriminate between Lys48 and Lys63-linked ubiquitin. AMSH is involved in the degradation of EGF receptor (EGFR) and possibly other ubiquitinated endocytosed proteins. AMSH also interacts with CHMP1, CHMP2, and CHMP3 proteins, all of which are components of ESCRT-III, suggested to be required for EGFR down-regulation. The function of AMSH-LP has not been elucidated; however, it exhibits two fundamentally distinct features from AMSH: first, there is a substitution in the critical amino acid residue in the SH3-binding motif (SBM) in the human AMSH-LP, but not in its mouse ortholog, and lacks STAM-binding ability; second, AMSH-LP lacks the ability to interact with CHMP proteins. It is therefore likely that AMSH and AMSH-LP play different roles on early endosomes.


Pssm-ID: 163697  Cd Length: 173  Bit Score: 338.80  E-value: 5.97e-117
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 266 LRCVVLPEDLCHKFLQLAESNTVRGIETCGILCGKLTHNEFTITHVIVPKQSAGPDYCDMENVEELFNVQDQHDLLTLGW 345
Cdd:cd08066     1 LRQVVVPADLMDKFLQLAEPNTSRNLETCGILCGKLSNNAFFITHLIIPKQSGTSDSCQTTNEEELFDFQDQHDLITLGW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 346 IHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCSPKHKDTGIFRLT-NAGMLEVSACKKKGFHPHTKEPRLFSICKHVL 424
Cdd:cd08066    81 IHTHPTQTCFLSSVDLHTHCSYQLMLPEAIAIVCAPKYNEFGIFRLTdPPGLDEILNCKKTGFHPHPKDPPLYEDCGHVI 160

                         170
                  ....*....|...
gi 2462520296 425 VKD-IKIIVLDLR 436
Cdd:cd08066   161 WKDqLKVTVVDLR 173
JAB pfam01398
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ...
 264-373 1.74e-22

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.


Pssm-ID: 396120  Cd Length: 117  Bit Score: 92.02  E-value: 1.74e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 264 EGLRCVVLPEDLCHKFLQLAESNTVRGIETCGILCGKLTHNEFT-ITHVIVPKQSAGPDYCD--------MENVEELFNV 334
Cdd:pfam01398   1 SSVRTVIIHPLVLLKILDHANRGGKIGEEVMGVLLGKLEGDGTIeITNSFALPQEETEDDVNavaldqeyMENMHEMLKK 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462520296 335 QDQhDLLTLGWIHTHPTQtAFLSSVDLHTHCSYQLMLPE 373
Cdd:pfam01398  81 VNR-KEEVVGWYHTHPGL-CWLSSVDVHTHALYQRMIPE 117
USP8_dimer pfam08969
USP8 dimerization domain; This domain is predominantly found in the amino terminal region of ...
 28-132 6.31e-19

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.


Pssm-ID: 462647  Cd Length: 113  Bit Score: 81.96  E-value: 6.31e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296  28 ERVRALSKLGCNITISEDITPRRYFRSGVEMERMASVYLEEGNLENAFVLYNKFITLFvEKLPNHRDYQQCAVPEKQDIM 107
Cdd:pfam08969  10 SSLEDLEKLTEKLEVDKNKSPKRYYRSALKLYKTAEEYRLEGDEENAYILYMKYFNLF-EKIRKHPDYKSVKATVRQMLG 88

                          90       100
                  ....*....|....*....|....*
gi 2462520296 108 KKLKEIAFPRTDELKNDLLKKYNVE 132
Cdd:pfam08969  89 KTKINEVLDELEKLKTSLLERYEEE 113
JAB_MPN smart00232
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
 269-394 1.30e-12

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.


Pssm-ID: 214573  Cd Length: 135  Bit Score: 64.70  E-value: 1.30e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296  269 VVLPEDLCHKFLQLAESNtvRGIETCGILCGKLTHNEFTITHVI-VPKQSAGP-----DYCDMENVEELFnVQDQHDLLT 342
Cdd:smart00232   2 VKVHPLVPLNILKHAIRD--GPEEVCGVLLGKSNKDRPEVKEVFaVPNEPQDDsvqeyDEDYSHLMDEEL-KKVNKDLEI 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462520296  343 LGWIHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCSP---KHKD--TGIFRLTNA 394
Cdd:smart00232  79 VGWYHSHPDESPFPSEVDVATHESYQAPWPISVVLIVDPiksFQGRlsLRAFRLTPE 135
Rri1 COG1310
Proteasome lid subunit RPN8/RPN11, contains Jab1/MPN domain metalloenzyme (JAMM) motif ...
 269-393 3.01e-06

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


Pssm-ID: 440921  Cd Length: 127  Bit Score: 46.06  E-value: 3.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 269 VVLPEDLCHKFLQLAESNTVRgiETCGILCGKLThNEFTITHVIVpkqsagpdycdMENV------------EELFNVQ- 335
Cdd:COG1310     2 LVLPRELLDAILAHAEAAYPE--ECCGLLLGKGG-GDKRVTRVYP-----------ARNVaespetrfeidpEDLLAAEr 67

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462520296 336 --DQHDLLTLGWIHTHPTQTAFLSSVDLhTHCSYqlmlPEAIAIVCSPKHK--DTGIFRLTN 393
Cdd:COG1310    68 eaRERGLEIVGIYHSHPDGPAYPSETDR-AQAAW----PGLPYLIVSLPDGgpELRAWRLRD 124
GBP_C cd16269
Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal ...
 120-198 4.23e-03

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.


Pssm-ID: 293879 [Multi-domain]  Cd Length: 291  Bit Score: 38.71  E-value: 4.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 120 ELKNDLLKKYNVE----------YQEYLQSKNKYKAEILK----KLEHQRLIEAERKRI-AQMRQQQLESEQflffedQL 184
Cdd:cd16269   149 EDREKLVEKYRQVprkgvkaeevLQEFLQSKEAEAEAILQadqaLTEKEKEIEAERAKAeAAEQERKLLEEQ------QR 222

                          90
                  ....*....|....
gi 2462520296 185 KKQELARGQMRSQQ 198
Cdd:cd16269   223 ELEQKLEDQERSYE 236
 
Name Accession Description Interval E-value
MPN_AMSH_like cd08066
Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM ...
 266-436 5.97e-117

Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM (signal-transducing adapter molecule, also known as STAMBP)) and AMSH-like proteins (AMSH-LP) are members of JAMM/MPN+ deubiquitinases (DUBs), with Zn2+-dependent ubiquitin isopeptidase activity. 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. AMSH and AMSH-LP are anchored on the early endosomal membrane via interaction with the clathrin coat. AMSH shares a common SH3-binding site with another endosomal DUB, UBPY (ubiquitin-specific protease Y; also known as USP8), the latter being a cysteine protease that does not discriminate between Lys48 and Lys63-linked ubiquitin. AMSH is involved in the degradation of EGF receptor (EGFR) and possibly other ubiquitinated endocytosed proteins. AMSH also interacts with CHMP1, CHMP2, and CHMP3 proteins, all of which are components of ESCRT-III, suggested to be required for EGFR down-regulation. The function of AMSH-LP has not been elucidated; however, it exhibits two fundamentally distinct features from AMSH: first, there is a substitution in the critical amino acid residue in the SH3-binding motif (SBM) in the human AMSH-LP, but not in its mouse ortholog, and lacks STAM-binding ability; second, AMSH-LP lacks the ability to interact with CHMP proteins. It is therefore likely that AMSH and AMSH-LP play different roles on early endosomes.


Pssm-ID: 163697  Cd Length: 173  Bit Score: 338.80  E-value: 5.97e-117
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 266 LRCVVLPEDLCHKFLQLAESNTVRGIETCGILCGKLTHNEFTITHVIVPKQSAGPDYCDMENVEELFNVQDQHDLLTLGW 345
Cdd:cd08066     1 LRQVVVPADLMDKFLQLAEPNTSRNLETCGILCGKLSNNAFFITHLIIPKQSGTSDSCQTTNEEELFDFQDQHDLITLGW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 346 IHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCSPKHKDTGIFRLT-NAGMLEVSACKKKGFHPHTKEPRLFSICKHVL 424
Cdd:cd08066    81 IHTHPTQTCFLSSVDLHTHCSYQLMLPEAIAIVCAPKYNEFGIFRLTdPPGLDEILNCKKTGFHPHPKDPPLYEDCGHVI 160

                         170
                  ....*....|...
gi 2462520296 425 VKD-IKIIVLDLR 436
Cdd:cd08066   161 WKDqLKVTVVDLR 173
MPN_euk_mb cd08058
Mpr1p, Pad1p N-terminal (MPN) domains with catalytic isopeptidase activity (metal-binding); ...
 274-392 9.01e-61

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  Cd Length: 119  Bit Score: 193.18  E-value: 9.01e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 274 DLCHKFLQLAESNTvrGIETCGILCGKLTHNEFTITHVIVPKQSAGPDYCDMENVEELFNVQDQHDLLTLGWIHTHPTQT 353
Cdd:cd08058     1 DALLKMLQHAESNT--GIEVMGLLCGELTHNEFTDKHVIVPKQSAGPDSCTGENVEELFNVQTGRPLLVVGWYHSHPTFT 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2462520296 354 AFLSSVDLHTHCSYQLMLPEAIAIVCSPKH--KDTGIFRLT 392
Cdd:cd08058    79 AWLSSVDIHTQASYQLMLPEAIAIVVSPKHrnKDTGIFRLT 119
MPN cd07767
Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) ...
 276-387 1.30e-43

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 [Multi-domain]  Cd Length: 116  Bit Score: 148.43  E-value: 1.30e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 276 CHKFLQLAESNtvRGIETCGILCGKLTHNEFTITHVIVPKQSAGPDYCDMENVEELFNVQDQHDLLTLGWIHTHPTQTAF 355
Cdd:cd07767     1 LKMFLDAAKSI--NGKEVIGLLYGSKTKKVLDVDEVIAVPFDEGDKDDNVWFLMYLDFKKLNAGLRIVGWYHTHPKPSCF 78

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2462520296 356 LSSVDLHTHCSYQLMLPEAIAIVCSPKHKDTG 387
Cdd:cd07767    79 LSPNDLATHELFQRYFPEKVMIIVDVKPKDLG 110
JAB pfam01398
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ...
 264-373 1.74e-22

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.


Pssm-ID: 396120  Cd Length: 117  Bit Score: 92.02  E-value: 1.74e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 264 EGLRCVVLPEDLCHKFLQLAESNTVRGIETCGILCGKLTHNEFT-ITHVIVPKQSAGPDYCD--------MENVEELFNV 334
Cdd:pfam01398   1 SSVRTVIIHPLVLLKILDHANRGGKIGEEVMGVLLGKLEGDGTIeITNSFALPQEETEDDVNavaldqeyMENMHEMLKK 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462520296 335 QDQhDLLTLGWIHTHPTQtAFLSSVDLHTHCSYQLMLPE 373
Cdd:pfam01398  81 VNR-KEEVVGWYHTHPGL-CWLSSVDVHTHALYQRMIPE 117
USP8_dimer pfam08969
USP8 dimerization domain; This domain is predominantly found in the amino terminal region of ...
 28-132 6.31e-19

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.


Pssm-ID: 462647  Cd Length: 113  Bit Score: 81.96  E-value: 6.31e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296  28 ERVRALSKLGCNITISEDITPRRYFRSGVEMERMASVYLEEGNLENAFVLYNKFITLFvEKLPNHRDYQQCAVPEKQDIM 107
Cdd:pfam08969  10 SSLEDLEKLTEKLEVDKNKSPKRYYRSALKLYKTAEEYRLEGDEENAYILYMKYFNLF-EKIRKHPDYKSVKATVRQMLG 88

                          90       100
                  ....*....|....*....|....*
gi 2462520296 108 KKLKEIAFPRTDELKNDLLKKYNVE 132
Cdd:pfam08969  89 KTKINEVLDELEKLKTSLLERYEEE 113
JAB_MPN smart00232
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
 269-394 1.30e-12

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.


Pssm-ID: 214573  Cd Length: 135  Bit Score: 64.70  E-value: 1.30e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296  269 VVLPEDLCHKFLQLAESNtvRGIETCGILCGKLTHNEFTITHVI-VPKQSAGP-----DYCDMENVEELFnVQDQHDLLT 342
Cdd:smart00232   2 VKVHPLVPLNILKHAIRD--GPEEVCGVLLGKSNKDRPEVKEVFaVPNEPQDDsvqeyDEDYSHLMDEEL-KKVNKDLEI 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462520296  343 LGWIHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCSP---KHKD--TGIFRLTNA 394
Cdd:smart00232  79 VGWYHSHPDESPFPSEVDVATHESYQAPWPISVVLIVDPiksFQGRlsLRAFRLTPE 135
Rri1 COG1310
Proteasome lid subunit RPN8/RPN11, contains Jab1/MPN domain metalloenzyme (JAMM) motif ...
 269-393 3.01e-06

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


Pssm-ID: 440921  Cd Length: 127  Bit Score: 46.06  E-value: 3.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 269 VVLPEDLCHKFLQLAESNTVRgiETCGILCGKLThNEFTITHVIVpkqsagpdycdMENV------------EELFNVQ- 335
Cdd:COG1310     2 LVLPRELLDAILAHAEAAYPE--ECCGLLLGKGG-GDKRVTRVYP-----------ARNVaespetrfeidpEDLLAAEr 67

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462520296 336 --DQHDLLTLGWIHTHPTQTAFLSSVDLhTHCSYqlmlPEAIAIVCSPKHK--DTGIFRLTN 393
Cdd:COG1310    68 eaRERGLEIVGIYHSHPDGPAYPSETDR-AQAAW----PGLPYLIVSLPDGgpELRAWRLRD 124
MPN_PRP8 cd08056
Mpr1p, Pad1p N-terminal (MPN) domains without isopeptidase activity found in splicing factor ...
 239-364 6.71e-05

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.


Pssm-ID: 163687 [Multi-domain]  Cd Length: 252  Bit Score: 44.15  E-value: 6.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 239 ASHSPPVNRALTPAATLSAVQNL------VVEGLRCVVLPEDLCHKFLQLAEsntVRgIETCGILCGKLTHNEFTI---- 308
Cdd:cd08056     2 SSKTDWRVRAIAATNLHLRTKNIyvssddIKETGYTYILPKNLLKKFISISD---LR-TQIAGYLYGKSPPDNPQVkeir 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462520296 309 THVIVPkQSAGPDYCDMENveELFNVQDQHDLLTLGWIHTHPTQTAFLSSVDLHTH 364
Cdd:cd08056    78 CIVLVP-QLGTHQTVTLPQ--QLPQHEYLEDLEPLGWIHTQPNELPQLSPQDVTTH 130
MPN_RPN11_CSN5 cd08069
Mov34/MPN/PAD-1 family: proteasomal regulatory protein Rpn11 and signalosome complex subunit ...
 291-397 2.11e-04

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.


Pssm-ID: 163700 [Multi-domain]  Cd Length: 268  Bit Score: 43.01  E-value: 2.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 291 IETCGILCGKLTHNEFTITHVI----------VPKQSAGPDY-CDMENVEelfnvQDQHDLLTLGWIHTHPTQTAFLSSV 359
Cdd:cd08069    32 IEVMGLMLGKVDDYTIIVVDVFalpvegtetrVNAQDEFQEYmVQYEMLK-----QTGRPENVVGWYHSHPGYGCWLSGI 106

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2462520296 360 DLHTHCSYQLMLPEAIAIVCSPK------HKDTGIFRLTNAGML 397
Cdd:cd08069   107 DVNTQQLNQQLQDPFVAVVVDPIrslvkgKVVIGAFRTIPPGYK 150
MPN_BRCC36 cd08068
Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex; BRCC36 (BRCA1-A complex subunit ...
 343-380 3.27e-04

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.


Pssm-ID: 163699 [Multi-domain]  Cd Length: 244  Bit Score: 41.95  E-value: 3.27e-04
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2462520296 343 LGWIHTHPTQTAFLSSVDLHTHCSYQLMLPEAIAIVCS 380
Cdd:cd08068    92 VGWYHSHPHITVWPSHVDVRTQAMYQMMDSGFVGLIFS 129
PRP8 COG5178
U5 snRNP spliceosome subunit [RNA processing and modification];
187-380 9.96e-04

U5 snRNP spliceosome subunit [RNA processing and modification];


Pssm-ID: 227505 [Multi-domain]  Cd Length: 2365  Bit Score: 41.89  E-value: 9.96e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296  187 QELARGQMRSQQTSGLSEQIDGSALSCfSTHQNNSLLNVFADQPNKSDATNYASHSPP-----VNRALTPAATLSAVQNL 261
Cdd:COG5178   2043 FRISAPSGARQETAETEKQNSEKALSR-PTNVSTKTINGWGREYVVLDGMIYEGEKFSskeewRSEAIRTGPLELRTKNI 2121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296  262 VV-------EGLRCVVLPEDLCHKFLQLAESNtvrgIETCGILCGKLTHNEFTI----THVIVPKQSAgpdycdMENVEE 330
Cdd:COG5178   2122 YVtadeneeSIQQMYRLPLNLLEKFMRISDPH----VQVAGLVYGKSGSDNPQIkeilSFGLVPQLGS------LSGVQS 2191

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2462520296  331 LFNVQ----DQHDLLTLGWIHTHPTQTAFLSSVDLHTHcSYQLMLPEAIAIVCS 380
Cdd:COG5178   2192 SSFVPhdlpGDEDLEILGWIHTQDDELPYLEVAGVLTH-RKKIVDPEWDAVTLT 2244
MPN_2A_DUB cd08067
Mov34/MPN/PAD-1 family: Histone H2A deubiquitinase; This family includes histone H2A ...
 292-385 1.62e-03

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.


Pssm-ID: 163698 [Multi-domain]  Cd Length: 187  Bit Score: 39.56  E-value: 1.62e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 292 ETCGILCGKLTHN--EFTITHVIVPKQSAGPDYCDMENV--EELFNVQDQHDLLTLGWIHTHPTQTAFLSSVDLHTHCSY 367
Cdd:cd08067    27 EVIGYLGGTWDPNtqNLTILQAFPCRSRLTGLDCEMDPVseTEIRESLESRGLSVVGWYHSHPTFPPNPSLRDIDTQLDY 106

                          90       100
                  ....*....|....*....|....*
gi 2462520296 368 QLMLP-------EAIAIVCSPKHKD 385
Cdd:cd08067   107 QIMFKgsdsgyePCVGLICSPYDRR 131
GBP_C cd16269
Guanylate-binding protein, C-terminal domain; Guanylate-binding protein (GBP), C-terminal ...
 120-198 4.23e-03

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.


Pssm-ID: 293879 [Multi-domain]  Cd Length: 291  Bit Score: 38.71  E-value: 4.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462520296 120 ELKNDLLKKYNVE----------YQEYLQSKNKYKAEILK----KLEHQRLIEAERKRI-AQMRQQQLESEQflffedQL 184
Cdd:cd16269   149 EDREKLVEKYRQVprkgvkaeevLQEFLQSKEAEAEAILQadqaLTEKEKEIEAERAKAeAAEQERKLLEEQ------QR 222

                          90
                  ....*....|....
gi 2462520296 185 KKQELARGQMRSQQ 198
Cdd:cd16269   223 ELEQKLEDQERSYE 236
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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