SII-SWORD/CoKE huggingface dataset:
Subtilisin SUB1-like catalytic domain (PfSUB1-like_cat_dom)
Type: Domain

This entry contains members of the peptidase family S8 (subtilisin) . Included in this entry are: PfSUB1 from the malaria parasite
Plasmodium
(MEROPS identifier S08.012), which activates the merozoite surface protein MSP1 allowing it to bind spectrin in the host erythrocyte membrane prior to egress ; perkinsin from the pathogenic marine protozoan
Perkinsus
(S08.041); and MCP-01 peptidase from the deep-sea bacterium
Pseudoalteromonas
(S08.130), which degrades insoluble collagen .

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 .
Nitrous-oxide reductase, C-terminal (N2OR_C)
Type: Domain

Nitrous-oxide reductase participates in nitrogen metabolism and catalyzes the last step in dissimilatory nitrate reduction, the two-electron reduction of N2O to N2. It contains copper ions as cofactors in the form of a binuclear CuA centre at the site of electron entry and a tetranuclear CuZ centre at the active site . The C terminus of Nitrous-oxide reductase is a cupredoxin domain .
RBM45, RNA recognition motif 2 (RBM45_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) 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.
RBM45, RNA recognition motif 3 (RBM45_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) 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.
RBM45, RNA recognition motif 4 (RBM45_RRM4)
Type: Domain

This entry represents the RNA recognition motif 4 (RRM4) 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.
PUF60, RNA recognition motif 1 (PUF60_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of PUF60 (also known as FIR). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65 . PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters . It has anti-inflammatory properties, playing a role in the host response . PUF60 contains two central RNA recognition motifs (RRMs) and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbours another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins .
Cytochrome c oxidase subunit 2, C-terminal (CcO_II_C)
Type: Domain

Cytochrome c Oxidase (CcO), the terminal oxidase in the respiratory chains of eukaryotes and most bacteria, is a multi-chain transmembrane protein located in the inner membrane of mitochondria and the cell membrane of prokaryotes. It catalyzes the reduction of O2 and simultaneously pumps protons across the membrane. The number of subunits varies from three to five in bacteria and up to 13 in mammalian mitochondria. Only subunits I and II are essential for function. Subunits I, II, and III of mammalian CcO are encoded within the mitochondrial genome and the remaining 10 subunits are encoded within the nuclear genome. Subunit II contains a copper-copper binuclear site called CuA, which is believed to be involved in electron transfer from cytochrome c to the binuclear centre (active site) in subunit I .
PUF60, RNA recognition motif 2 (PUF60_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of PUF60 (also known as FIR). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65 . PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters . It has anti-inflammatory properties, playing a role in the host response . PUF60 contains two central RNA recognition motifs (RRMs) and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbours another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins .
PUF60, RNA recognition motif 3 (PUF60_RRM3)
Type: Domain

This entry represents the RNA recognition motif 3 (RRM3) of PUF60 (also known as FIR). PUF60 is an essential splicing factor that functions as a poly-U RNA-binding protein required to reconstitute splicing in depleted nuclear extracts. Its function is enhanced through interaction with U2 auxiliary factor U2AF65 . PUF60 also controls human c-myc gene expression by binding and inhibiting the transcription factor far upstream sequence element (FUSE)-binding-protein (FBP), an activator of c-myc promoters . PUF60 contains two central RNA recognition motifs (RRMs) and a C-terminal U2AF (U2 auxiliary factor) homology motifs (UHM) that harbours another RRM and binds to tryptophan-containing linear peptide motifs (UHM ligand motifs, ULMs) in several nuclear proteins .
Vpr-like peptidase, catalytic domain (S8_Vpr-like)
Type: Domain

This entry represents a peptidase Vpr-like domain, found in a subgroup of proteins that belong to the peptidase family S8, subfamily S8A (subtilisin) . The maturation of the peptide antibiotic (lantibiotic) subtilin in Bacillus subtilis ATCC 6633 includes post-translational modifications of the propeptide and proteolytic cleavage of the leader peptide. Vpr (MEROPS identifier S08.114) was identified as one of the endopeptidases, along with WprA and AprE, that are capable of processing subtilin . Vpr is secreted and synthesized as an auto-processing precursor, and has been shown to be fibrinolytic . This entry also includes the FT peptidase from Bacillus sp. KSM-KP43 (S08.117) .

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 .
Ba3-like heme-copper oxidase subunit II, C-terminal (Ba3_CcO_II_C)
Type: Domain

The ba3 family of heme-copper oxidases are transmembrane protein complexes in the respiratory chains of prokaryotes and some archaea, which catalyze the reduction of O
2
and simultaneously pump protons across the membrane. It has been proposed that archaea acquired heme-copper oxidases through gene transfer from Gram-positive bacteria . The ba3 family contains oxidases that lack the conserved residues that form the D- and K-pathways in CcO and ubiquinol oxidase. Instead, they contain a potential alternative K-pathway. Additional proton channels have been proposed for this family of oxidases but none have been identified definitively .

The ba3-oxidase contains three subunits . This entry represents the C-terminal domain of subunit II.
RBM42, RNA recognition motif (RBM42_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of RBM42 which has been identified as a heterogeneous nuclear ribonucleoprotein K (hnRNP K)-binding protein. It also directly binds the 3' untranslated region of p21 mRNA that is one of the target mRNAs for hnRNP K. Both, hnRNP K and RBM42, are components of stress granules (SGs). Under nonstress conditions, RBM42 predominantly localizes within the nucleus and co-localizes with hnRNP K. Under stress conditions, hnRNP K and RBM42 form cytoplasmic foci where the SG marker TIAR localizes, and may play a role in the maintenance of cellular ATP level by protecting their target mRNAs. RBM42 contains an RNA recognition motif (RRM) .
C5a peptidase-like domain (C5a_Peptidase)
Type: Domain

Streptococcal cell-wall C5a peptidase (SCP; MEROPS identifier S08.020) is a highly specific endopeptidase and adhesin/invasin containing a subtilisin domain (peptidase family S8, subfamily S8A) . The peptidase cleaves complement component C5a . The subtilisin-like domain is located at the N-terminal and contains a PA (protease-associated) domain inserted into a loop (

). There are three fibronectin type III (Fn) domains at the C terminus. SCP binds to integrins with the help of Arg-Gly-Asp motifs, which are thought to stabilise conformational changes required for substrate binding . This domain is also found in other characterised peptidases, most of them also binding to the bacterial cell wall, including cell envelope peptidase A (S08.027) and PrtA (S08.064) from
Streptocccus
spp. which are virulence factors ; lactocepins (S08.019, S08.018, S08.118,S08.147) from Lactobacilli, which are multi-domain proteins ; collagenolytic endopeptidase from
Geobacillus
(S08.142) ; and SufA (S08.138) from
Finegoldia
which is fibrinolytic .

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 .
SART3, RNA recognition motif 1 (SART3_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of SART3.

SART3 (also known as Tip110) is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver . It is involved in the regulation of mRNA splicing probably via its complex formation with RNPS1 (an RNA-binding protein with a serine-rich domain), a pre-mRNA-splicing factor . SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication . In addition, SART3 is required for U6 snRNP targeting to Cajal bodies . It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro .

SART3 contains an N-terminal HAT (half-a-tetratricopeptide repeat)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs).
SART3, RNA recognition motif 2 (SART3_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of SART3 (also known as Tip110), which is an RNA-binding protein expressed in the nucleus of the majority of proliferating cells, including normal cells and malignant cells, but not in normal tissues except for the testes and fetal liver . It is involved in the regulation of mRNA splicing probably via its complex formation with RNPS1 (an RNA-binding protein with a serine-rich domain), a pre-mRNA-splicing factor . SART3 has also been identified as a nuclear Tat-interacting protein that regulates Tat transactivation activity through direct interaction and functions as an important cellular factor for HIV-1 gene expression and viral replication . In addition, SART3 is required for U6 snRNP targeting to Cajal bodies . It binds specifically and directly to the U6 snRNA, interacts transiently with the U6 and U4/U6 snRNPs, and promotes the reassembly of U4/U6 snRNPs after splicing in vitro .

SART3 contains a HAT (N-terminal half-a-tetratricopeptide repeat)-rich domain, a nuclearlocalization signal (NLS) domain, and two C-terminal RNA recognition motifs (RRMs).
ZCRB1, RNA recognition motif (ZCRB1_RRM)
Type: Domain

ZCRB1 is a novel multi-functional nuclear factor that may be involved in morphine dependence, cold/heat stress, and hepatocarcinoma. It is located in the nucleoplasm, but outside the nucleolus . ZCRB1 is one of the components of U11/U12 snRNPs that bind to U12-type pre-mRNAs and form a di-snRNP complex, simultaneously recognizing the 5' splice site and branchpoint sequence . ZCRB1 is characterised by an RNA recognition motif (RRM), and a CCHC-type zinc finger motif. In addition, it contains core nucleocapsid motifs, and Lys- and Glu-rich domains.

This entry represents the RNA recognition motif (RRM) of ZCRB1.
RBM34, RNA recognition motif 2 (RBM34_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of RBM34, a putative RNA-binding protein containing two RNA recognition motifs (RRMs). The function of RBM34 is not clear.
Carboxypeptidase D, carboxypeptidase-like domain 2 (M14_CPD_II)
Type: Domain

This entry represents the second carboxypeptidase (CP)-like domain of carboxypeptidase D (CPD; EC 3.4.17.22; MEROPS M14.016).

Carboxypeptidase D (CPD) differs from all other metallocarboxypeptidases in that it contains multiple CP-like domains . CPD belongs to the N/E-like subfamily (subfamily M14B) of the M14 family of metallocarboxypeptidases (MCPs) . CPD is a single-chain protein containing a signal peptide, three tandem repeats of CP-like domains separated by short bridge regions, followed by a transmembrane domain, and a C-terminal cytosolic tail. The first two CP-like domains of CPD contain all of the essential active site and substrate-binding residues, while the third CP-like domain lacks critical residues necessary for enzymatic activity and is inactive towards standard CP substrates. Domain I is optimally active at pH 6.3-7.5 and prefers substrates with C-terminal Arg, whereas domain II is active at pH 5.0-6.5 and prefers substrates with C-terminal Lys . CPD functions in the processing of proteins that transit the secretory pathway, and is present in all vertebrates as well as
Drosophila
. It is broadly distributed in all tissue types. Within cells, CPD is present in the trans-Golgi network and immature secretory vesicles, but is excluded from mature vesicles . It is thought to play a role in the processing of proteins that are initially processed by furin or related endopeptidases present in the trans-Golgi network, such as growth factors and receptors . CPD is implicated in the pathogenesis of lupus erythematosus (LE), it is regulated by TGF-beta in various cell types of murine and human origin and is significantly down-regulated in CD14 positive cells isolated from patients with LE. As down-regulation of CPD leads to down-modulation of TGF-beta, CPD may have a role in a positive feedback loop .

The carboxypeptidase A family can be divided into four subfamilies: M14A (carboxypeptidase A or digestive), M14B (carboxypeptidase H or regulatory), M14C (gamma-D-glutamyl-L-diamino acid peptidase I) and M14D (AGTPBP-1/Nna1-like proteins) . Members of subfamily M14B have longer C-termini than those of subfamily M14A , and carboxypeptidase M (a member of the H family) is bound to the membrane by a glycosylphosphatidylinositol anchor, unlike the majority of the M14 family, which are soluble . The zinc ligands have been determined as two histidines and a glutamate, and the catalytic residue has been identified as a C-terminal glutamate, but these do not form the characteristic metalloprotease HEXXH motif . Members of the carboxypeptidase A family are synthesised as inactive molecules with propeptides that must be cleaved to activate the enzyme. Structural studies of carboxypeptidases A and B reveal the propeptide to exist as a globular domain, followed by an extended α-helix; this shields the catalytic site, without specifically binding to it, while the substrate-binding site is blocked by making specific contacts .
Nop13/Rnp24, RNA recognition motif 1 (Nop13/Rnp24_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of Nop13p from Saccharomyces cerevisiae. It shares high sequence similarity with nucleolar protein 12 (Nop12p). Neither Nop12p nor Nop13p are essential for growth. However, unlike Nop12p that is localized to the nucleolus, Nop13p localizes primarily to the nucleolus but is also present in the nucleoplasm to a lesser extent. Nop13p contains two RNA recognition motifs (RRMs) . Proteins containing this domain include Rnp24 from S. pombe.
Nop13/Rnp24, RNA recognition motif 2 (Nop13/Rnp24_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RR2) of Nop13p from Saccharomyces cerevisiae. It shares high sequence similarity with nucleolar protein 12 (Nop12p). Neither Nop12p nor Nop13p are essential for growth. However, unlike Nop12p that is localized to the nucleolus, Nop13p localizes primarily to the nucleolus but is also present in the nucleoplasm to a lesser extent. Nop13p contains two RNA recognition motifs (RRMs) . Proteins containing this domain include Rnp24 from S. pombe.
Ubiquinol oxidase subunit 2, cupredoxin domain (CuRO_UO_II)
Type: Domain

The transfer of electrons to the terminal acceptor O
2
is catalyzed by a group of proteins in the heme-copper oxidases superfamily. This superfamily is divided into two distinct families: cytochrome c oxidases and ubiquinol oxidases, which have different electron donors. Ubiquinol oxidase, the terminal oxidase in the respiratory chains of aerobic bacteria, is a multi-chain transmembrane protein located in the cell membrane. It takes electrons from ubiquinol and catalyzes the reduction of O
2
, simultaneously pumping protons across the membrane. Subunit II of ubiquinol oxidase (known as CyoA in E. coli) lacks the binuclear CuA site found in cytochrome c oxidases, but the structure is conserved .

This entry represents the cupredoxin domain found in ubiquinol oxidase subunit II .
Nop6, RNA recognition motif (Nop6_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of Nop6, a component of 90S pre-ribosomal particles in S. cerevisiae. It is enriched in the nucleolus and is required for 40S ribosomal subunit biogenesis. Nop6 is a non-essential putative RNA-binding protein with two N-terminal putative nuclear localisation sequences (NLS-1 and NLS-2) and an RNA recognition motif (RRM). It binds to the pre-rRNA early during transcription and plays an essential role in pre-rRNA processing .
eIF4H, RNA recognition motif (eIF4H_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of eIF-4H, which, together with elf-4B/eIF-4G, serves as the accessory protein of RNA helicase eIF-4A . eIF-4H contains a well conserved RNA recognition motif (RRM). It stimulates protein synthesis by enhancing the helicase activity of eIF-4A in the initiation step of mRNA translation .
Nucleolin, RNA recognition motif 1 (Nucleolin_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of ubiquitously expressed protein nucleolin.

Nucleolin is a multifunctional major nucleolar phosphoprotein that has been implicated in various metabolic processes, such as ribosome biogenesis, cytokinesis, nucleogenesis, cell proliferation and growth, cytoplasmic-nucleolar transport of ribosomal components, transcriptional repression, replication, signal transduction, inducing chromatin decondensation, etc . Nucleolin exhibits intrinsic self-cleaving, DNA helicase, RNA helicase and DNA-dependent ATPase activities . It can be phosphorylated by many protein kinases, such as the major mitotic kinase Cdc2, casein kinase 2 (CK2), and protein kinase C-zeta .
Ephrin type-B receptor 1, ligand binding domain (EphB1_rcpt_lig-bd)
Type: Domain

This entry represents the ligand-binding domain found in ephrin type-B receptor 1 (EphB1). Using EphB1 knockout-mice, EphB1 has been shown to be essential to the development of long-term potentiation (LTP) , a cellular model of synaptic plasticity, learning and memory formation .

Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands .

Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) .