SII-SWORD/CoKE huggingface dataset:
Medium-chain specific acyl-CoA dehydrogenase (MCAD)
Type: Family

Medium-chain specific acyl-CoA dehydrogenases (MCADs) are mitochondrial beta-oxidation enzymes, which catalyse the alpha,beta dehydrogenation of the corresponding medium chain acyl-CoA by FAD, which becomes reduced . The reduced form of MCAD 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. MCAD is a homotetramer . This protein contribute to PINK1-mediated regulation of fatty acid and amino acid metabolism, through a mechanism that is independent of its acyl-CoA dehydrogenase activity. Mutations in PINK1 are associated with Parkinson's disease .
Pre-mRNA-splicing factor Cwc2, RNA recognition motif (Cwc2_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of yeast protein Cwc2, also termed Cwf2, one of the components of the Prp19-associated complex [nineteen complex (NTC)]. that can bind to RNA. NTC is composed of the scaffold protein Prp19 and a number of associated splicing factors, and plays a crucial role in intron removal during premature mRNA splicing in eukaryotes. Cwc2 functions as an RNA-binding protein that can bind both small nuclear RNAs (snRNAs) and pre-mRNA in vitro. It interacts directly with the U6 snRNA to link the NTC to the spliceosome during pre-mRNA splicing .
Kexin/furin catalytic domain (Kexin/furin)
Type: Domain

This entry represents the catalytic domain of kexin, furin and related proteins . Protein convertases, whose members include furin (MEROPS identifier S08.071) and kexin (S08.070), are members of the peptidase S8 or subtilase family of peptidases . Kexins are involved in the activation of peptide hormones, growth factors, and viral proteins. Furin cleaves cell surface vasoactive peptides and proteins involved in cardiovascular tissue remodeling in the TGN, at cell surface, or in endosomes but rarely in the ER. Furin also plays a key role in blood pressure regulation though the activation of transforming growth factor (TGF)-beta. High specificity is seen for cleavage after dibasic (Lys-Arg or Arg-Arg) or multiple basic residues in protein convertases .

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 .
Isovaleryl-CoA dehydrogenase (IVD)
Type: Family

Isovaleryl-CoA dehydrogenase (IVD) is an acyl-CoA dehydrogenase, which catalyzes the third step in leucine catabolism, the conversion of isovaleryl-CoA (3-methylbutyryl-CoA) into 3-methylcrotonyl-CoA. IVD is a homotetramer and has the greatest affinity for small branched chain substrates .
Putative acyl-CoA dehydrogenase AidB (AidB)
Type: Family

AidB is one of several genes involved in the SOS adaptive response to DNA alkylation damage, whose expression is activated by the Ada protein . Its function has not been entirely elucidated; however, it is similar in sequence and function to acyl-CoA dehydrogenases . It has been proposed that aidB directly destroys DNA alkylating agents such as nitrosoguanidines (nitrosated amides) or their reaction intermediates .
Site-1 peptidase catalytic domain (Site-1_peptidase_cat_dom)
Type: Domain

Site-1 peptidase (also known as SKI-1 or type I membrane-bound subtilisin-kexin-isoenzyme; MEROPS identifier S08.063) is a secretory Ca
2+
-dependent serine endopeptidase and a member of the subtilisin family S8, subfamily S8A . It cleaves at nonbasic residues: Thr, Leu, and Lys. Site-1 peptidase plays a critical role in the regulation of the synthesis and metabolism of cholesterol and fatty acid metabolism .

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 .
Pin4-like, RNA recognition motif (PIN4-like_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) in Pin4, a novel phosphothreonine (pThr)-containing protein that specifically interacts with the pThr-binding site of the Rad53 FHA1 domain. Pin4 is involved in normal G2/M cell cycle progression in the absence of DNA damage and functions as a novel target of checkpoint-dependent cell cycle arrest pathways . It contains an N-terminal RRM, a nuclear localization signal, a coiled coil, and a total of 15 SQ/TQ motifs.

In S. pombe, Cip1 (Csx1-interacting protein 1) and Cip2 (Csx1-interacting protein 2) are novel cytoplasmic RRM-containing proteins that counteract Csx1 function during oxidative stress. They are not essential for viability in S. pombe . Both cip1 and cip2 contain one RRM. Like Pin4, Cip2 also possesses an R3H motif that may function in sequence-specific binding to single-stranded nucleic acids.
PoSI-like peptidase domain (Peptidases_S8_5)
Type: Domain

This domain is found predominantly in fungal members of the peptidase family S8 (subtilisin) . These proteins contain an additional domain inserted within the subtilisin domain known as a PA (protease-associated) domain. The only characterised member is the PoSI peptidase (MEROPS identifier S08.139) from the oyster mushroom (
Pleurotus ostreatus
). The peptidase is a two-chain, secreted glycoprotein probably involved in the activation of other peptidases secreted by the mushroom .

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 .
Broad-specificity linear acyl-CoA dehydrogenase FadE5-like (FadE5-like)
Type: Family

FadE5 is an acyl-CoA dehydrogenase that exhibits broad specificity for linear acyl-CoA substrates, with a preference for long-chain substrates .
MARF1, RNA recognition motif 1 (MARF1_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of MARF1 (also known as Limkain-b1).

MARF1 was first identified as a novel peroxisomal autoantigen that co-localizes with a subset of cytoplasmic microbodies marked by ABCD3 . Later, it was found to be an essential protein for controlling meiosis and retrotransposon surveillance in mouse oocytes. It may function both as an adaptor to recruit specific RNA targets and an effector to catalyse the specific cleavages of target RNAs . MARF1 contains an N-terminal NYN domain, two central RRMs, and C-terminal OST-HTH/LOTUS domains .
Subtilisin domain, cyanobacteria-type (Peptidase_S8_6)
Type: Domain

This domain is found in uncharacterised proteins that are homologues of the peptidase family S8 (subtilisins) . Examples are predominantly from Cyanobacteria, but also Actinobacteria and Archaea.

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 .
MARF1, RNA recognition motif 2 (MARF1_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of MARF1 (also known as Limkain-b1).

MARF1 was first identified as a novel peroxisomal autoantigen that co-localizes with a subset of cytoplasmic microbodies marked by ABCD3 . Later, it was found to be an essential protein for controlling meiosis and retrotransposon surveillance in mouse oocytes. It may function both as an adaptor to recruit specific RNA targets and an effector to catalyse the specific cleavages of target RNAs . MARF1 contains an N-terminal NYN domain, two central RRMs, and C-terminal OST-HTH/LOTUS domains .
SREK1, RNA recognition motif 2 (SREK1_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of SREK1 (also known as SRrp86). SREK1 belongs to a family of proteins containing regions rich in serine-arginine dipeptides (SR proteins family), which is involved in bridge-complex formation and splicing by mediating protein-protein interactions across either introns or exons. It may play a crucial role in determining tissue specific patterns of alternative splicing. SREK1 can alter splice site selection by both positively and negatively modulating the activity of other SR proteins. For instance, SREK1 can activate SRp20 and repress SC35 in a dose-dependent manner both in vitro and in vivo .

SREK1 contains two (some contain only one) RNA recognition motifs (RRMs), and two serine-arginine (SR)-rich domains (SR domains) separated by an unusual glutamic acid-lysine (EK) rich region. The RRM and SR domains are highly conserved among other members of the SR superfamily. However, the EK domain is unique to SREK1. It plays a modulatory role controlling SR domain function by involvement in the inhibition of both constitutive and alternative splicing and in the selection of splice-site .
Proteinase K-like catalytic domain (PCSK9_ProteinaseK-like)
Type: Domain

This domain is found in some members of peptidase family S8 (subtilisins) , such as PCSK9 (proprotein convertase subtilisin/kexin type 9; MEROPS identifier S08.039), proteinase K (S08.054), proteinase T (S08.061) from the fungus
Tritirachium album
Limber , and other subtilisin-like serine endopeptidases. PCSK9 post-translationally regulates hepatic low-density lipoprotein receptors (LDLRs) by binding to LDLRs on the cell surface, leading to their degradation, and is a target for drugs for hypercholesterolaemia. The binding site of PCSK9 has been localised to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR . Characterised proteinases K are secreted endopeptidases that are not substrate-specific and function in a wide variety of species in different pathways. It can hydrolyse keratin and other proteins with subtilisin-like specificity . The number of calcium-binding motifs found in these differs .

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 .
Mrn1, RNA recognition motif 1 (Mrn1_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) in Mrn1. Proteins containing this motif also include S. pombe Nrd1 (also known as Msa2), which inhibits sexual differentiation .

Mrn1 is an RNA binding protein that localizes both to the nucleus and cytoplasm. It may be involved in the mRNA processing pathway . Mrn1 contains four copies of a conserved RNA recognition motif (RRM).
CELF1/2, RNA recognition motif 1 (CELF1/2_RRM1)
Type: Domain

The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 1 (RRM1) of CELF-1 and CELF-2 protein.

CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) .

The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase . It preferentially targets UGU-rich mRNA elements . CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene . CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein.

Proteins containing this motif also include Drosophila melanogaster Bruno protein, which plays a central role in regulation of Oskar (Osk) expression in flies. It mediates repression by binding to regulatory Bruno response elements (BREs) in the Osk mRNA 3' UTR . The full-length Bruno protein contains three RRMs, two located in the N-terminal half of the protein and the third near the C terminus, separated by a linker region.
Cucumisin-like catalytic domain (Peptidases_S8_3)
Type: Domain

This entry represents a peptidase cucumisin-like domain, found in a subgroup of proteins that belong to the members of the peptidases S8 (subtilisins), predominantly from plants. This peptidase domain has a protease-associated (PA) domain nested within it. Some members, such as cucumisin, have an extra C-terminal fibronectin-III-like domain. Cucumisin (MEROPS identifier S08.092) is an extracellular glycoprotein that is a major allergen from melon . It is synthesized as a precursor with the C-terminal of the propeptide binding to the active site cleft in a substrate-like manner . Other proteins included in this entry are the ALE1 peptidase (abnormal leaf shape 1; S08.014) from
Arabidopsis
which is expressed in the developing embryo and absence of which leads to a defective cuticle ; and phytaspase (S08.150) which have a caspase-like specificity and play a similar role in programmed cell death .

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 .
CELF1/2, RNA recognition motif 2 (CELF1/2_RRM2)
Type: Domain

The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 2 (RRM2) of CELF-1 and CELF-2 protein.

CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) .

The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase . It preferentially targets UGU-rich mRNA elements . CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene . CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein.
CELF1/2, RNA recognition motif 3 (CELF1/2_RRM3)
Type: Domain

The human CELF family has six members, which can be divided into two subfamilies based on their phylogeny: CELF1-2 and CELF3-6. This entry represents the RNA recognition motif 3 (RRM3) of CELF-1 and CELF-2 protein.

CELF-1 and CELF-2 belong to the CELF (CUGBP and ETR-3 Like Factor)/Bruno-like protein family, whose members play important roles in the regulation of alternative splicing and translation. CELF-1 and CELF-2 share sequence similarity to the Drosophila Bruno protein and binds to the Bruno response elements (cis-acting sequences in the 3'-untranslated region (UTR) ofoskar mRNA) .

The human CELF-1 (also known as CUG-BP or BRUNOL-2) binds to RNA substrates and recruits PARN deadenylase . It preferentially targets UGU-rich mRNA elements . CELF-1 has been implicated in onset of type 1 myotonic dystrophy (DM1), a neuromuscular disease associated with an unstable CUG triplet expansion in the 3'-UTR (3'-untranslated region) of the DMPK (myotonic dystrophy protein kinase) gene . CELF-1 contain three highly conserved RNA recognition motifs (RRMs): two consecutive RRMs (RRM1 and RRM2) situated in the N-terminal region followed by a linker region and the third RRM (RRM3) close to the C terminus of the protein.
RDM1, RNA recognition motif (RDM1_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of RDM1, also termed RAD52 homologue B, a novel factor involved in the cellular response to the anti-cancer drug cisplatin in vertebrates . RDM1 contains a small RD motif that is shared with the recombination and repair protein RAD52, and an RNA recognition motif (RRM). The RD motif is responsible for the acidic pH-dependent DNA-binding properties of RDM1. It interacts with ss- and dsDNA, and may act as a DNA-damage recognition factor by recognizing the distortions of the double helix caused by cisplatin-DNA adducts in vitro. In addition, due to the presence of RRM, RDM1 can bind to RNA as well as DNA .
RNPS1, RNA recognition motif (RNPS1_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of RNPS1 and its eukaryotic homologues. RNPS1 was originally characterised as a general pre-mRNA splicing activator, which activates both constitutive and alternative splicing of pre-mRNA in vitro . It has been identified as a protein component of the splicing-dependent mRNP complex, or exon-exon junction complex (EJC), and is directly involved in mRNA surveillance . Furthermore, RNPS1 is a splicing regulator whose activator function is controlled in part by CK2 (casein kinase II) protein kinase phosphorylation . It can also function as a squamous-cell carcinoma antigen recognized by T cells-3 (SART3)-binding protein, and is involved in the regulation of mRNA splicing . RNPS1 contains an N-terminal serine-rich (S) domain, a central RNA recognition motif (RRM), and the C-terminal arginine/serine/proline-rich (R/S/P) domain.
Subtilisin Carlsberg-like catalytic domain (Subtilisin_Carlsberg-like)
Type: Domain

This entry includes prokaryote proteins with a subtilisin-like domain. Subtilisin is a serine endopeptidase in peptidase family S8, subfamily S8A . Characterised peptidases in this entry include subtilisin Carlsberg (S08.001), TK-subtilisin (S08.129), subtilisin PB92 (S08.003) and subtilisin BPN' (S08.034). TK-subtilisin is secreted from the hyperthermophilic archaeon Thermococcus kodakaraensis as an inactive precursor. TK-subtilisin matures from pro-TK-subtilisin upon autoprocessing and degradation of the propeptide. Unlike other subtilisins, the folding of the unprocessed form of pro-TK-subtilisin is induced by Ca
2+
binding, which is almost completed prior to autoprocessing. Ca
2+
is required for activity, unlike the bacterial subtilisins. The propeptide is not required for folding of the mature domain, unlike the bacterial subtilases, because of the stability produced from Ca
2+
binding . Subtilisin BPN'/Novo is extremely similar in structure to subtilisin Carlsberg, though it has a 30% difference in amino acid sequence. The substrate binding regions are also similar, and two possible Ca
2+
binding sites have been identified . Subtilisin Carlsberg possesses the highest commercial importance as a proteolytic additive for detergents . Subtilisin Pb92, the serine protease from the alkalophilic Bacillus strain PB92, also contains two calcium ions and the overall folding of the polypeptide chain closely resembles that of the subtilisins .

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 .
RBM45, RNA recognition motif 1 (RBM45_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of RBM45, also termed developmentally-regulated RNA-binding protein 1 (DRB1), a member of RNA recognition motif (RRM)-type neural RNA-binding proteins, which is expressed under spatiotemporal control. It is encoded by gene drb1 that is expressed in neurons, not in glial cells. RBM45 predominantly localizes in the cytoplasm of cultured cells and specifically binds to poly(C) RNA. It could play an important role during neurogenesis . RBM45 carries four RRMs.