PRP8 family protein similar to Homo sapiens pre-mRNA-processing-splicing factor 8 that plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes, both of the predominant U2-type spliceosome and the minor U12-type spliceosome
Ribonuclease-like Prp8 domain IV core; This family contains Prp8 domain IV, which adopts a ...
1790-2040
3.23e-173
Ribonuclease-like Prp8 domain IV core; This family contains Prp8 domain IV, which adopts a RNase H like fold within its core structure but with little sequence similarity. Prp8, a spliceosome protein, interacts directly with the splice sites and branch regions of precursor-mRNAs and spliceosomal RNAs associated with catalysis of the two steps of splicing. Catalysis of RNA cleavage by RNase H-like proteins involves a two-metal mechanism in which adjacently-bound divalent magnesium ions promote hydrolysis by activation of a water nucleophile and stabilization of the transition-state. However, the Prp8 domain IV contains only one of the canonical metal-binding sites and the coordinating side chains are spatially conserved with respect to Mg2+-coordinating residues within the RNase H fold.
Pssm-ID: 260013 Cd Length: 251 Bit Score: 530.00 E-value: 3.23e-173
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
2124-2260
3.99e-34
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: 128.65 E-value: 3.99e-34
Ribonuclease-like Prp8 domain IV core; This family contains Prp8 domain IV, which adopts a ...
1790-2040
3.23e-173
Ribonuclease-like Prp8 domain IV core; This family contains Prp8 domain IV, which adopts a RNase H like fold within its core structure but with little sequence similarity. Prp8, a spliceosome protein, interacts directly with the splice sites and branch regions of precursor-mRNAs and spliceosomal RNAs associated with catalysis of the two steps of splicing. Catalysis of RNA cleavage by RNase H-like proteins involves a two-metal mechanism in which adjacently-bound divalent magnesium ions promote hydrolysis by activation of a water nucleophile and stabilization of the transition-state. However, the Prp8 domain IV contains only one of the canonical metal-binding sites and the coordinating side chains are spatially conserved with respect to Mg2+-coordinating residues within the RNase H fold.
Pssm-ID: 260013 Cd Length: 251 Bit Score: 530.00 E-value: 3.23e-173
PRP8 domain IV core; This domain is found in eukaryotes, and is about 20 amino acids in length. ...
1784-2013
2.37e-153
PRP8 domain IV core; This domain is found in eukaryotes, and is about 20 amino acids in length. It is found associated with pfam10597, pfam10596, pfam10598, pfam08083, pfam08082, pfam01398, pfam08084. There is a conserved LILR sequence motif. The domain is a selenomethionine domain in a subunit of the spliceosome. The function of PRP8 domain IV is believed to be interaction with the splicosomal core.
Pssm-ID: 432353 Cd Length: 230 Bit Score: 473.39 E-value: 2.37e-153
Mpr1p, Pad1p N-terminal (MPN) domains without isopeptidase activity found in splicing factor ...
2091-2345
1.42e-140
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: 438.21 E-value: 1.42e-140
PRO8NT (NUC069), PrP8 N-terminal domain; The PRO8NT domain is found at the N-terminus of ...
79-229
3.85e-105
PRO8NT (NUC069), PrP8 N-terminal domain; The PRO8NT domain is found at the N-terminus of pre-mRNA splicing factors of PRO8 family. The NLS or nuclear localization signal for these spliceosome proteins begins at the start and runs for 60 residues. N-terminal to this domain is a highly variable proline-rich region.
Pssm-ID: 462361 [Multi-domain] Cd Length: 152 Bit Score: 332.33 E-value: 3.85e-105
U6-snRNA interacting domain of PrP8; This domain incorporates the interacting site for the ...
1466-1624
1.39e-103
U6-snRNA interacting domain of PrP8; This domain incorporates the interacting site for the U6-snRNA as part of the U4/U6.U5 tri-snRNPs complex of the spliceosome, and is the prime candidate for the role of cofactor for the spliceosome's RNA core. The essential spliceosomal protein Prp8 interacts with U5 and U6 snRNAs and with specific pre-mRNA sequences that participate in catalysis. This close association with crucial RNA sequences, together with extensive genetic evidence, suggests that Prp8 could directly affect the function of the catalytic core, perhaps acting as a splicing cofactor.
Pssm-ID: 431383 Cd Length: 159 Bit Score: 328.29 E-value: 1.39e-103
U5-snRNA binding site 2 of PrP8; The essential spliceosomal protein Prp8 interacts with U5 and ...
1234-1367
6.89e-87
U5-snRNA binding site 2 of PrP8; The essential spliceosomal protein Prp8 interacts with U5 and U6 snRNAs and with specific pre-mRNA sequences that participate in catalysis. This close association with crucial RNA sequences, together with extensive genetic evidence, suggests that Prp8 could directly affect the function of the catalytic core, perhaps acting as a splicing cofactor.
Pssm-ID: 402297 Cd Length: 134 Bit Score: 279.26 E-value: 6.89e-87
RNA recognition motif of the spliceosomal PrP8; The large RNA-protein complex of the ...
1009-1099
5.91e-45
RNA recognition motif of the spliceosomal PrP8; The large RNA-protein complex of the spliceosome catalyzes pre-mRNA splicing. One of the most conserved core proteins is PrP8 which occupies a central position in the catalytic core of the spliceosome, and has been implicated in several crucial molecular rearrangements that occur there, and has recently come under the spotlight for its role in the inherited human disease, Retinitis Pigmentosa. The RNA-recognition motif of PrP8 is highly conserved and provides a possible RNA binding centre for the 5-prime SS, BP, or 3-prime SS of pre-mRNA which are known to contact with Prp8. The most conserved regions of an RRM are defined as the RNP1 and RNP2 sequences. Recognition of RNA targets can also be modulated by a number of other factors, most notably the two loops beta1-alpha1, beta2-beta3 and the amino acid residues C-terminal to the RNP2 domain.
Pssm-ID: 463163 Cd Length: 92 Bit Score: 157.79 E-value: 5.91e-45
JAB/MPN domain; Domain in Jun kinase activation domain binding protein and proteasomal ...
2124-2260
3.99e-34
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: 128.65 E-value: 3.99e-34
Mpr1p, Pad1p N-terminal (MPN) domains; MPN (also known as Mov34, PAD-1, JAMM, JAB, MPN+) ...
2136-2252
3.78e-16
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: 76.40 E-value: 3.78e-16
JAB1/Mov34/MPN/PAD-1 ubiquitin protease; Members of this family are found in proteasome ...
2124-2233
3.73e-09
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: 56.58 E-value: 3.73e-09
Mov34/MPN/PAD-1 family; AMSH (associated molecule with the Src homology 3 domain (SH3) of STAM ...
2198-2224
7.81e-04
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: 42.58 E-value: 7.81e-04
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: 39.10 E-value: 4.53e-03
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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