NPL4 family; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear ...
161-467
6.76e-155
NPL4 family; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ER-associated degradation after ubiquitination of target proteins but before their recognition by the 26S proteasome. Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing.
The actual alignment was detected with superfamily member pfam05021:
Pssm-ID: 461524 Cd Length: 309 Bit Score: 444.02 E-value: 6.76e-155
NPL4 family, putative zinc binding region; The HRD4 gene was identical to NPL4, a gene ...
17-157
7.75e-93
NPL4 family, putative zinc binding region; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ER-associated degradation after ubiquitination of target proteins but before their recognition by the 26S proteasome. This region of the protein contains possibly two zinc binding motifs (Bateman A pers. obs.). Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing.
:
Pssm-ID: 461523 Cd Length: 145 Bit Score: 279.09 E-value: 7.75e-93
NPL4 family; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear ...
161-467
6.76e-155
NPL4 family; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ER-associated degradation after ubiquitination of target proteins but before their recognition by the 26S proteasome. Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing.
Pssm-ID: 461524 Cd Length: 309 Bit Score: 444.02 E-value: 6.76e-155
Mov34/MPN/PAD-1 family: nuclear protein localization-4 (Npl4) domain; Npl4p (nuclear protein ...
126-425
4.13e-147
Mov34/MPN/PAD-1 family: nuclear protein localization-4 (Npl4) domain; Npl4p (nuclear protein localization-4) is identical to Hmg-CoA reductase degradation 4 (HRD4) protein and contains a domain that is part of the pfam clan MPN/Mov34-like. Npl4 plays an intermediate role between endoplasmic reticulum-associated degradation (ERAD) substrate ubiquitylation and proteasomal degradation. Npl4p associates with Cdc48p (Cdc48 in yeast and p97 or valosin-containing protein (VCP) in higher eukaryotes), the highly conserved ATPase of the AAA family, via ubiquitin fusion degradation-1 protein (Ufd1p) to form a Cdc48p-Ufd1p-Npl4p complex which then functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation. This family of eukaryotic MPN-like domains lacks the key residues that coordinate a metal ion and therefore does not show catalytic isopeptidase activity.
Pssm-ID: 163692 Cd Length: 274 Bit Score: 422.54 E-value: 4.13e-147
NPL4 family, putative zinc binding region; The HRD4 gene was identical to NPL4, a gene ...
17-157
7.75e-93
NPL4 family, putative zinc binding region; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ER-associated degradation after ubiquitination of target proteins but before their recognition by the 26S proteasome. This region of the protein contains possibly two zinc binding motifs (Bateman A pers. obs.). Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing.
Pssm-ID: 461523 Cd Length: 145 Bit Score: 279.09 E-value: 7.75e-93
NPL4 family; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear ...
161-467
6.76e-155
NPL4 family; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ER-associated degradation after ubiquitination of target proteins but before their recognition by the 26S proteasome. Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing.
Pssm-ID: 461524 Cd Length: 309 Bit Score: 444.02 E-value: 6.76e-155
Mov34/MPN/PAD-1 family: nuclear protein localization-4 (Npl4) domain; Npl4p (nuclear protein ...
126-425
4.13e-147
Mov34/MPN/PAD-1 family: nuclear protein localization-4 (Npl4) domain; Npl4p (nuclear protein localization-4) is identical to Hmg-CoA reductase degradation 4 (HRD4) protein and contains a domain that is part of the pfam clan MPN/Mov34-like. Npl4 plays an intermediate role between endoplasmic reticulum-associated degradation (ERAD) substrate ubiquitylation and proteasomal degradation. Npl4p associates with Cdc48p (Cdc48 in yeast and p97 or valosin-containing protein (VCP) in higher eukaryotes), the highly conserved ATPase of the AAA family, via ubiquitin fusion degradation-1 protein (Ufd1p) to form a Cdc48p-Ufd1p-Npl4p complex which then functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation. This family of eukaryotic MPN-like domains lacks the key residues that coordinate a metal ion and therefore does not show catalytic isopeptidase activity.
Pssm-ID: 163692 Cd Length: 274 Bit Score: 422.54 E-value: 4.13e-147
NPL4 family, putative zinc binding region; The HRD4 gene was identical to NPL4, a gene ...
17-157
7.75e-93
NPL4 family, putative zinc binding region; The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ER-associated degradation after ubiquitination of target proteins but before their recognition by the 26S proteasome. This region of the protein contains possibly two zinc binding motifs (Bateman A pers. obs.). Npl4p physically associates with Cdc48p via Ufd1p to form a Cdc48p-Ufd1p-Npl4p complex. The Cdc48-Ufd1-Npl4 complex functions in the recognition of several polyubiquitin-tagged proteins and facilitates their presentation to the 26S proteasome for processive degradation or even more specific processing.
Pssm-ID: 461523 Cd Length: 145 Bit Score: 279.09 E-value: 7.75e-93
Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) ...
137-297
2.47e-21
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: 89.11 E-value: 2.47e-21
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.
of the residues that compose this conserved feature have been mapped to the query sequence.
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Functional characterization of the conserved domain architecture found on the query.
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if a domain or superfamily has been annotated with functional sites (conserved features),
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click on the bars or triangles to view your query sequence embedded in a multiple sequence alignment of the proteins used to develop the corresponding domain model.
The table lists conserved domains identified on the query sequence. Click on the plus sign (+) on the left to display full descriptions, alignments, and scores.
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Concise Display shows only the best scoring domain model, in each hit category listed below except non-specific hits, for each region on the query sequence.
(labeled illustration) Standard Display shows only the best scoring domain model from each source, in each hit category listed below for each region on the query sequence.
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Retrieve proteins that contain one or more of the domains present in the query sequence, using the Conserved Domain Architecture Retrieval Tool
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