SII-SWORD/CoKE huggingface dataset:
HRP1, RNA recognition motif 1 (Hrp1_RRM1)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of Hrp1p and similar proteins. Hrp1p is a sequence-specific trans-acting factor that is essential for mRNA 3'-end formation in yeast Saccharomyces cerevisiae. It can be UV cross-linked to RNA and specifically recognizes the (UA)6 RNA element required for both the cleavage and poly(A) addition steps. Moreover, Hrp1p can shuttle between the nucleus and the cytoplasm, and play an additional role in the export of mRNAs to the cytoplasm. Hrp1p also interacts with Rna15p and Rna14p, two components of CF1A . In addition, Hrp1p functions as a factor directly involved in modulating the activity of the nonsense-mediated mRNA decay (NMD) pathway; it binds specifically to a downstream sequence element (DSE)-containing RNA and interacts with Upf1p, a component of the surveillance complex, further triggering the NMD pathway .

Hrp1p contains two central RNA recognition motifs (RRMs) and an arginine-glycine-rich region harboruing repeats of the sequence RGGF/Y.
DNA topoisomerase 2, TOPRIM domain (TOPRIM_TopoII)
Type: Domain

This topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain is found in proteins of the type II family of DNA topoisomerases similar to Saccharomyces cerevisiae Topoisomerase II. TopoII enzymes cut both strands of the duplex DNA to remove (relax) both positive and negative supercoils in DNA. These enzymes covalently attach to the 5' ends of the cut DNA, separate the free ends of the cleaved strands, pass another region of the duplex through this gap, then rejoin the ends. These proteins also catenate/ decatenate duplex rings .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). This glutamate and two aspartates, cluster together to form a highly acid surface patch. The conserved glutamate may act as a general base in strand joining and as a general acid in strand cleavage by topisomerases. The DXD motif may co-ordinate Mg
2+
, a cofactor required for full catalytic function .
SF3B4, RNA recognition motif 1 (SF3B4_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of SF3B4, also termed pre-mRNA-splicing factor SF3b 49kDa (SF3b50), or spliceosome-associated protein 49 (SAP 49). SF3B4 is a component of the multiprotein complex splicing factor 3b (SF3B), an integral part of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP. SF3B is essential for the accurate excision of introns from pre-messenger RNA, and is involved in the recognition of the pre-mRNA's branch site within the major and minor spliceosomes . SF3B4 functions to tether U2 snRNP with pre-mRNA at the branch site during spliceosome assembly . It is an evolutionarily highly conserved protein with orthologues across diverse species.

SF3B4 contains two closely adjacent N-terminal RNA recognition motifs (RRMs). It binds directly to pre-mRNA and also interacts directly and highly specifically with another SF3B subunit called SAP 145 .

Mutations in the SF3B4 gene cause Nager syndrome, a form of acrofacial dysostosis which affects the development of the face, hands, and arms .
SF3B4, RNA recognition motif 2 (SF3B4_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of SF3B4, also termed pre-mRNA-splicing factor SF3b 49kDa (SF3b50), or spliceosome-associated protein 49 (SAP 49). SF3B4 is a component of the multiprotein complex splicing factor 3b (SF3B), an integral part of the U2 small nuclear ribonucleoprotein (snRNP) and the U11/U12 di-snRNP. SF3B is essential for the accurate excision of introns from pre-messenger RNA, and is involved in the recognition of the pre-mRNA's branch site within the major and minor spliceosomes . SF3B4 functions to tether U2 snRNP with pre-mRNA at the branch site during spliceosome assembly . It is an evolutionarily highly conserved protein with orthologues across diverse species.

SF3B4 contains two closely adjacent N-terminal RNA recognition motifs (RRMs). It binds directly to pre-mRNA and also interacts directly and highly specifically with another SF3B subunit called SAP 145 .

Mutations in the SF3B4 gene cause Nager syndrome, a form of acrofacial dysostosis which affects the development of the face, hands, and arms .

This entry also includes the orthologue from Schizosaccharomyces pombe Spliceosome-associated protein 49.
DNA gyrase subunit B, TOPRIM domain (TOPRIM_GyrB)
Type: Domain

This topoisomerase-primase (TOPRIM) nucleotidyl transferase/hydrolase domain of the kind found in proteins of the type IIA family of DNA topoisomerases is similar to the Escherichia coli GyrB subunit. TopoIIA enzymes cut both strands of the duplex DNA to remove (relax) both positive and negative supercoils in DNA. These enzymes covalently attach to the 5' ends of the cut DNA, separate the free ends of the cleaved strands, pass another region of the duplex through this gap, then rejoin the ends. These proteins also catenate/ decatenate duplex rings. DNA gyrase is more effective at relaxing supercoils than decatenating DNA. DNA gyrase in addition inserts negative supercoils in the presence of ATP .

The TOPRIM domain has two conserved motifs, one of which centres at a conserved glutamate and the other one at two conserved aspartates (DxD). The conserved glutamate may act as a general base in strand joining and as a general acid in strand cleavage by topisomerases. The DXD motif may co-ordinate Mg
2+
, a cofactor required for full catalytic function .
Pepsin-like domain, plant (Pepsin-like_plant)
Type: Domain

This entry represents a domain found in aspartic endopeptidases from plants including nepenthesin (MEROPS identifier A01.040), a digestive enzyme from the pitcher of the carnivorous pitcher plant Nepenthes ; CDR1 endopeptidase (=Constitutive Disease Resistance 1; MEROPS identifier A01.069) from the Arabidopsis apoplast involved in disease resistance signalling and which is not inhibited by pepstatin ; PCS1 peptidase (MEROPS identifier A01.074) which is important for protecting cells from apoptosis during embryo development ; and S5 peptidases (MEROPS identifier A01.086), which exist as homo- and hetero- dimers and formation of heterodimers leads to embryo-sac abortion resulting in sterility . Proteins containing this domain belong to the aspartic peptidase A1 family (peptidase family A1, subfamily A1B).

Aspartyl proteases (APs), also known as acid proteases, ([ec:3.4.23.-]) are a widely distributed family of proteolytic enzymes known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.

APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA.
Pepsin catalytic domain (Pepsin_A)
Type: Domain

Pepsins, well-known aspartic endopeptidases, are produced by gastric mucosa of chordates and are classified by MEROPS as members of peptidase family A1 (pepsin A, clan AA) . There are several genes encoding pepsin-like gastric endopeptidases in humans, including pepsins A (MEROPS identifier A01.001), A4 (A01.070) and A5 (A01.071), and chymosin (formerly known as rennin; A01.006). A pepsin-like protein is also secreted by the chicken embryo (embryonic pepsin, A01.028). The prosequence of the zymogens are self-cleaved under acidic pH. Pepsins play an integral role in the digestion process of vertebrates. Pepsins specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap .
Aspergillopepsin-like catalytic domain (Aspergillopepsin-like_cat_dom)
Type: Domain

This entry represents the peptidase domain found in a group of aspartic endopeptidases of fungal origin, including aspergillopepsin (MEROPS ientifier A01.016) , rhizopuspepsin (A01.012), endothiapepsin (A01.017) and penicillopepsin (A01.011) . Aspergillopepsin from A. fumigatus is involved in invasive aspergillosis owing to its elastolytic activity and aspergillopepsins from the mold A. saitoi are used in the fermentation industry . The members in this entry have an optimal acidic pH (5.5) and cleave protein substrates with similar specificity to that of porcine pepsin A, preferring hydrophobic residues at P1 and P1' in the cleavage site. This group of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA) .

Aspartyl proteases (APs), also known as acid proteases, ([ec:3.4.23.-]) are a widely distributed family of proteolytic enzymes known to exist in vertebrates, fungi, plants, retroviruses and some plant viruses. APs use an Asp dyad to hydrolyze peptide bonds.

APs found in eukaryotic cells are α/β monomers composed of two asymmetric lobes ("bilobed"). Each of the lobes provides a catalytic Asp residue, positioned within the hallmark motif Asp-Thr/Ser-Gly, to the active site. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The enzymes specifically cleave bonds in peptides which have at least six residues in length with hydrophobic residues in both the P1 and P1' positions. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbour hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. Eukaryotic APs form peptidase family A1 of clan AA.
Pepsin-like domain (Pepsin-like_dom)
Type: Domain

This entry represents a domain found in a group of pepsin-like aspartic proteases. They are found in mammals, plants, fungi and bacteria and are classified by MEROPS as members of the peptidase family A1 (pepsin A, clan AA) . Proteins containing this domain also include the fungal enzymes mucorpepsin (A01.013) , polyporopepsin (A01.019) , CtsD peptidase from Aspergillus (A01.077) and CnAP1 peptidase from Cryptococcus neoformans (A01.078) ; plasmepsins from the malaria parasite Plasmodium (A01.021, A01.022, A01.023, A01.043, A01.059) and shewasin A from the bacterium Shewanella (A01.095) .
FeMo cofactor biosynthesis protein NifB, C-terminal (NifB_C)
Type: Domain

NifB belongs to a family of iron-molybdenum cluster-binding proteins that includes NifX, and NifY, all of which are involved in the synthesis of an iron-molybdenum cofactor (FeMo-co) that binds the active site of the dinitrogenase enzyme as part of nitrogen fixation in bacteria. This domain is sometimes found fused to a N-terminal domain (the Radical SAM domain) in nifB-like proteins .
Npl3, RNA recognition motif 1 (Npl3_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of Npl3p. Npl3p is a major yeast RNA-binding protein that competes with 3'-end processing factors, such as Rna15, for binding to the nascent RNA, protecting the transcript from premature termination and coordinating transcription termination and the packaging of the fully processed transcript for export. It specifically recognizes a class of G/U-rich RNAs . Npl3p is a multi-domain protein containing two central RNA recognition motifs (RRMs), separated by a short linker and a C-terminal domain rich in glycine, arginine and serine residues .
Nab3, RNA recognition motif (Nab3_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of Nab3p (also known as Hmd1p), an acidic nuclear polyadenylated RNA-binding protein that is essential for cell viability. Nab3p is predominantly localised within the nucleoplasm and essential for growth in budding yeast . It plays an important role in the maintenance of CLN3 mRNA levels . It is part of the Nrd1 complex (Nrd1p-Nab3p-Sen1p) that directs the termination and processing of short RNA polymerase II transcripts and regulates cellular response to nutrient availability .

This group of proteins also includes Uncharacterized RNA-binding protein C3H8.09c from Schizosaccharomyces pombe, the ortologous protein in fission yeast.
Peptidyl-prolyl cis-trans isomerase E, RNA recognition motif (PPIE_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of peptidyl-prolyl cis-trans isomerase E (PPIE, also known as Cyp33). PPIE is a nuclear RNA-binding cyclophilin with an N-terminal RNA recognition motif (RRM), and a C-terminal PPIase domain . Cyp33 possesses RNA-binding activity and preferentially binds to polyribonucleotide polyA and polyU, but hardly to polyG and polyC. It binds specifically to mRNA, which can stimulate its PPIase activity. Moreover, Cyp33 interacts with the third plant homeodomain (PHD3) zinc finger cassette of the mixed lineage leukemia (MLL) proto-oncoprotein and a poly-A RNA sequence through its RRM domain . It further mediates downregulation of the expression of MLL target genes HOXC8, HOXA9, CDKN1B, and C-MYC, in a proline isomerase-dependent manner . Cyp33 also possesses a PPIase activity that catalyzes cis-trans isomerization of the peptide bond preceding a proline, which has been implicated in the stimulation of folding and conformational changes in folded and unfolded proteins. The PPIase activity can be inhibited by the immunosuppressive drug cyclosporin A .
NifX-like domain (NifX-like)
Type: Domain

NifX belongs to a family of iron-molybdenum cluster-binding proteins that includes NifB, and NifY, all of which are involved in the synthesis of an iron-molybdenum cofactor (FeMo-co) that binds the active site of the dinitrogenase enzyme. The protein is part of the nitrogen fixation gene cluster in nitrogen-fixing bacteria and has sequence similarity to other members of the cluster . This domain is also found C-terminal in NifY, which is also part of the nif cluster .
Retropepsin-like catalytic domain (Retropepsin-like_cat_dom)
Type: Domain

This entry represents the peptidase domain found in a group of retropepsin-like aspartic endopeptidases from retroviruses, retrotransposons and retroelements. This group of aspartic peptidases is classified by MEROPS as the peptidase family A2 (retropepsin family, clan AA), subfamily A2A . Proteins containing this domain include retropepsins from human immunodeficiency viruses (MEROPS identifiers A02.001, A02.002) , Mason-Pfizer leukemia virus (A02.009), Rous sarcoma virus (A02.015), intracisternal A-particle (A02.016) , and "endogenous viruses" from human (A02.011) , rabbit (A02.024) and mouse (A02.060).
Peroxisomal acyl-coenzyme A oxidase (ACO)
Type: Family

Peroxisomal acyl-CoA oxidases (ACO) catalyze the first set in the peroxisomal fatty acid beta-oxidation, the alpha,beta dehydrogenation of the corresponding trans-enoyl-CoA by FAD, which becomes reduced. In a second oxidative half-reaction, the reduced FAD is reoxidized by molecular oxygen. ACO is generally a homodimer. There are several subtypes of AXO's, based on substrate specificity. Palmitoyl-CoA oxidase (ACOX1) acts on straight-chain fatty acids and prostanoids ; whereas, the closely related Trihydroxycoprostanoly-CoA oxidase (ACOX2) has the greatest activity for 2-methyl branched side chains of bile precursors . Pristanoyl-CoA oxidase (ACOX3), acts on 2-methyl branched fatty acids .
SHARP, RNA recognition motif 1 (SHARP_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of SHARP (also known as Msx2-interacting protein, or SPEN homologue).

SHARP is an estrogen-inducible transcriptional repressor that interacts directly with the nuclear receptor corepressor SMRT, histone deacetylases (HDACs) and components of the NuRD complex. SHARP recruits HDAC activity and binds to the steroid receptor RNA coactivator SRA through four conserved N-terminal RNA recognition motifs (RRMs), further suppressing SRA-potentiated steroid receptor transcription activity . Thus, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. SHARP also has been identified as a component of transcriptional repression complexes in Notch/RBP-Jkappa signaling pathways . In addition to the N-terminal RRMs, SHARP possesses a C-terminal SPOC domain (Spen paralog and ortholog C-terminal domain), which is highly conserved among Spen proteins .
SHARP, RNA recognition motif 2 (SHARP_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of SHARP (also known as Msx2-interacting protein, or SPEN homologue).

SHARP is an estrogen-inducible transcriptional repressor that interacts directly with the nuclear receptor corepressor SMRT, histone deacetylases (HDACs) and components of the NuRD complex. SHARP recruits HDAC activity and binds to the steroid receptor RNA coactivator SRA through four conserved N-terminal RNA recognition motifs (RRMs), further suppressing SRA-potentiated steroid receptor transcription activity . Thus, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. SHARP also has been identified as a component of transcriptional repression complexes in Notch/RBP-Jkappa signaling pathways . In addition to the N-terminal RRMs, SHARP possesses a C-terminal SPOC domain (Spen paralog and ortholog C-terminal domain), which is highly conserved among Spen proteins .
SHARP, RNA recognition motif 3 (SHARP_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of SHARP (also known as Msx2-interacting protein, or SPEN homologue).

SHARP is an estrogen-inducible transcriptional repressor that interacts directly with the nuclear receptor corepressor SMRT, histone deacetylases (HDACs) and components of the NuRD complex. SHARP recruits HDAC activity and binds to the steroid receptor RNA coactivator SRA through four conserved N-terminal RNA recognition motifs (RRMs), further suppressing SRA-potentiated steroid receptor transcription activity . Thus, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. SHARP also has been identified as a component of transcriptional repression complexes in Notch/RBP-Jkappa signaling pathways . In addition to the N-terminal RRMs, SHARP possesses a C-terminal SPOC domain (Spen paralog and ortholog C-terminal domain), which is highly conserved among Spen proteins .
SHARP, RNA recognition motif 4 (SHARP_RRM4)
Type: Domain

This entry represents the RNA recognition motif 4 (RRM4) of SHARP (also known as Msx2-interacting protein, or SPEN homologue).

SHARP is an estrogen-inducible transcriptional repressor that interacts directly with the nuclear receptor corepressor SMRT, histone deacetylases (HDACs) and components of the NuRD complex. SHARP recruits HDAC activity and binds to the steroid receptor RNA coactivator SRA through four conserved N-terminal RNA recognition motifs (RRMs), further suppressing SRA-potentiated steroid receptor transcription activity . Thus, SHARP has the capacity to modulate both liganded and nonliganded nuclear receptors. SHARP also has been identified as a component of transcriptional repression complexes in Notch/RBP-Jkappa signaling pathways . In addition to the N-terminal RRMs, SHARP possesses a C-terminal SPOC domain (Spen paralog and ortholog C-terminal domain), which is highly conserved among Spen proteins .
Peptidase MprA-like catalytic domain (Peptidases_S8_13)
Type: Domain

This entry represents a peptidase MprA-like domain, found in the bacterial members of the peptidase family S8 (subtilase serine endo- and exo-peptidases) , including peptidase MprA from Burkholderia (MEROPS identifier S08.107) which degrades host immunoglobulins, transferrin and myosin ; apr (S08.023, S08.040, S08.067) and bpr peptidases (S08.022) from Dichelobacter, which break down collagen in sheep hooves (ovine foot-rot) ; StmPr1 peptidase from Stenotrophomonas (S08.110) which is a keratinase. These enzymes are stabilized by calcium ions, and because of sensitivity to EDTA were erronerously considered to be metallopeptidases .

The subtilisin family is one of the largest serine peptidase families characterised to date. Over 200 subtilisins are presently known, more than 170 of which have their complete amino acid sequence . It is widespread, being found in eubacteria, archaebacteria, eukaryotes and viruses . The vast majority of the family are endopeptidases, although there is an exopeptidase, tripeptidyl peptidase . Structures have been determined for several members of the subtilisin family: they exploit the same catalytic triad as the chymotrypsins, although the residues occur in a different order (HDS in chymotrypsin and DHS in subtilisin), but the structures show no other similarity . Some subtilisins are mosaic proteins, while others contain N- and C-terminal extensions that show no sequence similarity to any other known protein .
PPARGC1B, RNA recognition motif (PPARGC1B_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of PPARGC1B (also known as PGC-1beta or PERC), which is one of the members of the PGC-1 transcriptional coactivators family, including PGC-1alpha and PGC-1-related coactivator (PRC). PGC-1beta is a tissue-specifically expressed coactivator of selective nuclear receptors and plays a nonredundant role in controlling mitochondrial oxidative energy metabolism and affects both insulin sensitivity and mitochondrial biogenesis, and functions in a number of oxidative tissues .
Isobutyryl-CoA dehydrogenase (IBD)
Type: Family

Isobutyryl-CoA dehydrogenase (IBD) catalyses the alpha, beta-dehydrogenation of short branched chain acyl-CoA intermediates in valine catabolism. It is predicted to be a homotetramer .
Long-chain specific acyl-CoA dehydrogenase (LCAD)
Type: Family

LCAD is an acyl-CoA dehydrogenases (ACAD), which is found in the mitochondria of eukaryotes and in some prokaryotes. It catalyzes the alpha, beta dehydrogenation of the corresponding trans-enoyl-CoA by FAD, which becomes reduced. The reduced form of LCAD is reoxidized in the oxidative half-reaction by electron-transferring flavoprotein (ETF), from which the electrons are transferred to the mitochondrial respiratory chain coupled with ATP synthesis. LCAD acts as a homodimer .