SII-SWORD/CoKE huggingface dataset:
Rubella virus (RUBV) nonstructural (NS) protease domain (RUBV_NS_PRO)
Type: Domain

Rubella virus (RUBV) is the etiological agent of a disease known as rubella or German measles. RUBV, a positive sense, single-strand RNA virus, is the sole member of the Rubivirus genus in the Togaviridae family of animal viruses. The RUBV genome contains two open reading frames (ORFs) encoding five proteins after postranslational proteolytic processing; two proteins (P150 and P90) involved in viral replication are translated from the nonstructural protein ORF (NSP-ORF) and the three structural proteins that form the virus particle are translated from the structural protein ORF (ST-ORF). A cysteine protease domain situated at the C terminus of P150 and immediately upstream from the cleavage site within the NS-ORF precursor (P200) is responsible for self-cleavage of P200 into P150 and P90. This protease domain, termed the NS protease domain, is a papain-like protease with catalytic dyad of Cys and His. The NS protease domain contains an EF-hand Ca+2 binding motif, which plays a structural role in stabilising the protease at physiological temperatures, as well as a structural Zn+2 binding site coordinated by four cysteines, which is necessary for protease activity. The RUBV NS protease domain forms the MEROPS peptidase family C27 of clan CA .
Kelch-like protein 2 , BTB/POZ domain (KLHL2_BTB/POZ)
Type: Domain

KLHL2, also called actin-binding protein Mayven, is a novel actin-binding protein predominantly expressed in the brain. It plays a role in the reorganisation of the actin cytoskeleton, and promotes growth of cell projections in oligodendrocyte precursors . KLHL2 is a component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, leading most often to their proteasomal degradation . It contains a BTB domain and kelch repeat domains, characteristics of a kelch family protein.

This entry represents the BTB/POZ domain, which is a common protein-protein interaction motif of about 100 amino acids.
Formyltetrahydrofolate deformylase, ACT domain (PurU_ACT)
Type: Domain

An Escherichia coli gene designated purU has been identified and characterised. The gene codes for a 280-amino-acid protein, PurU (

,

). PurU is an enzyme that catalyses the hydrolysis of 10-formyltetrahydrofolate (formyl-FH4) to FH4 and formate
.

10-formyltetrahydrofolate + H(2)O = formate +tetrahydrofolate

Formyl-FH4 hydrolase generates the formate that is used by purT-encoded 5'-phosphoribosylglycinamide transformylase for step three of de novo purine nucleotide synthesis. Formyl-FH4 hydrolase, a hexamer of 32kDa subunits, is activated by methionine and inhibited by glycine. Heterotropic cooperativity is observed for activation by methionine in the presence of glycine and for inhibition by glycine in the presence of methionine. These results suggest that formyl-FH4 hydrolase is a regulatory enzyme whose main function is to balance the pools of FH4 and C1-FH4 in response to changing growth conditions. The enzyme uses methionine and glycine to sense the pools of C1-FH4 and FH4, respectively.

This entry also includes PurU from Arabidopsis, which is involved in photorespiration. It prevents the excessive accumulation of 5-formyl tetrahydrofolate (THF), a potent inhibitor of the Gly decarboxylase/Ser hydroxymethyltransferase complex .

This entry represents the N-terminal ACT domain of formyltetrahydrofolate deformylase.
PRKCBP1, PHD finger (PRKCBP1_PHD)
Type: Domain

PRKCBP1, also known as ZMYND8, is a chromatin reader that recognises dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) . It was first identified as a receptor for activated C-kinase (RACK)-like protein involved in PKC signaling cascade . It also has been identified as a formin homology-2-domain containing protein 1 (FHOD1)-binding protein that may be involved in FHOD1-regulated actin polymerisation and transcription . It acts as a transcriptional corepressor for KDM5D and EZH2 . ZMYND8 recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination . Moreover, PRKCBP1 may function as a REST co-repressor 2 (RCOR2) interacting factor; the RCOR2/ZMYND8 complex which might be involved in the regulation of neural differentiation . PRKCBP1 contains a plant homeodomain (PHD) finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

This entry represents the PHD finger domain.
Large ribosomal subunit protein P2, eukaryotes (Ribosomal_P2)
Type: Family

This entry represents the eukaryotic large ribosomal protein P2.

Eukaryotic P1 and P2 are functionally equivalent to the bacterial protein L7/L12, but are not homologous to L7/L12. P2 is located in the L12 stalk, with proteins P1, P0, L11, and 28S rRNA. P1 and P2 are the only proteins in the ribosome to occur as multimers, always appearing as sets of heterodimers. Eukaryotes have four copies (two heterodimers), while most archaeal species contain six copies of L12p (three homodimers). Bacteria may have four or six copies of L7/L12 (two or three homodimers) depending on the species . Experiments using S. cerevisiae P1 and P2 indicate that P1 proteins are positioned more internally with limited reactivity in the C-terminal domains, while P2 proteins seem to be more externally located and are more likely to interact with other cellular components . In lower eukaryotes, P1 and P2 are further subdivided into P1A, P1B, P2A, and P2B, which form P1A/P2B and P1B/P2A heterodimers . Some plants have a third P-protein, called P3, which is not homologous to P1 and P 2 .

In humans, P1 and P2 are strongly autoimmunogenic. They play a significant role in the etiology and pathogenesis of systemic lupus erythema (SLE). In addition, the ribosome-inactivating protein trichosanthin (TCS) interacts with human P0, P1, and P2, with its primary binding site in the C-terminal region of P2. TCS inactivates the ribosome by depurinating a specific adenine in the sarcin-ricin loop of 28S rRNA .
Amylosucrase, catalytic domain (Amylosucrase)
Type: Domain

Amylosucrase is a glucosyltransferase that catalyses the transfer of a D-glucopyranosyl moiety from sucrose onto an acceptor molecule. When the acceptor is another saccharide, only alpha-1,4 linkages are produced. Unlike most amylopolysaccharide synthases, it does not require any alpha-D-glucosyl nucleoside diphosphate substrate. In the presence of glycogen it catalyses the transfer of a D-glucose moiety onto a glycogen branch, but in its absence, it hydrolyses sucrose and synthesises polymers, smaller maltosaccharides, and sucrose isoforms .

The Alpha-amylase family comprises the largest family of glycoside hydrolases (GH), with the majority of enzymes acting on starch, glycogen, and related oligo- and polysaccharides. These proteins catalyse the transformation of alpha-1,4 and alpha-1,6 glucosidic linkages with retention of the anomeric centre. The protein is described as having 3 domains: A, B, C. A is a (β/α) 8-barrel; B is a loop between the β3 strand and α3 helix of A; C is the C-terminal extension characterised by a Greek key. The majority of the enzymes have an active site cleft found between domains A and B where a triad of catalytic residues (Asp, Glu and Asp) performs catalysis. Other members of this family have lost the catalytic activity as in the case of the human 4F2hc, or only have 2 residues that serve as the catalytic nucleophile and the acid/base, such as Thermus A4 beta-galactosidase with 2 Glu residues (GH42) and human alpha-galactosidase with 2 Asp residues (GH31) .
Mot1, ATP-binding domain (Mot1_ATP-bd)
Type: Domain

The TATA-binding protein (TBP) is a major target for transcriptional regulation. Mot1, a Swi2/Snf2-related ATPase, dissociates TBP from DNA in an ATP dependent process . The N-terminal domain of Mot1 has been shown to bind TBP, NC2 and DNA. Its ATPase domain is at the C terminus .

This domain contains the ATP-binding region found in Mot1.
TBCE, ubiquitin-like (Ubl) domain (Ubl_TBCE)
Type: Domain

Tubulin proteostasis is regulated by a group of molecular chaperones termed tubulin cofactors (TBC). This entry represents TBCE (tubulin-specific chaperone E), which is involved in the second step of the tubulin folding pathway through cooperating in tubulin heterodimer dissociation both in vivo and in vitro. It may also be implicated in the maintenance of the neuronal microtubule network . Mutations in TBCE gene cause hypoparathyroidism, mental retardation and facial dysmorphism . TBCE contains an N-terminal cytoskeleton-associated protein with glycine-rich segment (CAP-Gly) domain, a leucine-rich repeat protein-protein interaction domain followed by leucine-rich repeat (LRR) domains, and a C-terminal ubiquitin-like (Ubl) domain .

This entry represents the Ubl domain.
MDM2, modified RING finger, HC subclass (MDM2_mRING-HC-C2H2C4)
Type: Domain

MDM2 is an E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome . p53 acts as an important defense mechanism against cancer, and is negatively regulated by interaction with the oncoprotein MDM2 . MDM2 overexpression correlates with metastasis and advanced forms of several cancers and may be used as a cancer drug target . In addition, MDM2 has important roles in the cell independent of p53. It interacts with several proteins such as Rb/E2F-1 complex , the DNA methyltransferase DNMT3A , p107 , MTBP and the cyclin kinase inhibitor p21 . MDM2 also affects cell apoptosis .

MDM2 contains an N-terminal p53-binding domain, and a C-terminal modified C2H2C4-type RING-HC finger conferring E3 ligase activity that is required for ubiquitination and nuclear export of p53. It is also responsible for the hetero-oligomerization of MDM2, which is crucial for the suppression of P53 activity during embryonic development, and the recruitment of E2 ubiquitin-conjugating enzymes . MDM2 also harbours a RanBP2-type zinc finger (Znf-RanBP2) domain, as well as a nuclear localisation signal (NLS) and a nuclear export signal (NES), near the central acidic region. The Znf-RanBP2 domain plays an important role in mediating MDM2 binding to ribosomal proteins and thus is involved in MDM2-mediated p53 suppression.

This entry represents the C-terminal modified C2H2C4-type RING-HC finger.
Domain of unknown function DUF5776 (DUF5776)
Type: Domain

This entry represents a presumed stalk domain found in bacterial surface proteins forming tandem repeats with high sequence identity. This domain is also associated with other known bacterial surface protein stalks and adhesive domains.

This domain can also be found in Endolysin and L-alanyl-D-glutamate peptidase from phage.
SpaK/NisK-like, Histidine kinase-like ATPase domain (SpaK_NisK-like_HATPase)
Type: Domain

This domain is a histidine kinase-like ATPase (HATPase) domain of two-component sensor histidine kinases similar to Bacillus subtilis SpaK and Lactococcus lactis NisK. SpaK is the histidine kinase (HK) of the SpaK-SpaR two-component regulatory system (TCS), which is involved in the regulation of the biosynthesis of lantibiotic subtilin . NisK is the HK of the NisK-NisR TCS, which is involved in the regulation of the biosynthesis of lantibiotic nisin . SpaK and NisK may function as membrane-associated protein kinases that phosphorylate SpaR and NisR, respectively, in response to environmental signals.
(R)-stereoselective amidase RamA-like (RamA-like)
Type: Domain

This entry represents a domain found in RamA (also known as MCI3434), which is a R-amidase that hydrolyses (R,S)-piperazine-2-tert-butylcarboxamide to form (R)-piperazine-2-carboxylic acid. It does so with strict R-stereoselectively. Its preferred substrates are carboxamide compounds which have the amino or imino group connected to their β- or γ-carbon .

RamA belongs to a larger nitrilase superfamily comprised of nitrile- or amide-hydrolysing enzymes and amide-condensing enzymes, which depend on a Glu-Lys-Cys catalytic triad . Members of the nitrilase superfamily generally form homomeric complexes, the basic building block of which is a homodimer .
AvModA-like, substrate binding domain (AvModA-like_subst-bd)
Type: Domain

In general, ModA serves as initial receptors in the ABC transport of molybdate in eubacteria and archaea. Bacteria and archaea import molybdenum and tungsten from the environment in the form of the oxyanions molybdate (MoO(4) (2-)) and tungstate (WO(4) (2-)). After binding molybdate with high affinity, they interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis .

In contrast to the structure of the two ModA homologues from Escherichia coli and Azotobacter vinelandii, where the oxygen atoms are tetrahedrally arranged around the metal centre, the structure of Pyrococcus furiosus ModA/WtpA (PfModA) has shown that a binding site for molybdate and tungstate is where the central metal atom is in a hexacoordinate configuration. This octahedral geometry was rather unexpected .

The ModA proteins belong to the PBP2 superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap .

This entry represents a domain found in the ModA protein from Azotobacter vinelandii and its homologues.
D-galactose-binding periplasmic protein MglB-like, PBP domain (MglB-like_PBP1)
Type: Domain

This entry represents the PBP (periplasmic binding protein) domain found in a group of glucose/galactose-binding proteins, including MglB (a D-galactose-binding periplasmic protein) from E. coli . They belong to the periplasmic binding protein superfamily which consists of two α/β globular domains connected by a three-stranded hinge. This Venus flytrap-like domain undergoes transition from an open to a closed conformational state upon ligand binding . Moreover, this group of proteins are homologous to the ligand-binding domain of eukaryotic receptors such as glutamate receptor (GluR) and DNA-binding transcriptional repressors such as LacI and GalR .
Aldehyde dehydrogenase LUC3-like (LUC3-like)
Type: Domain

This entry represents the aldehyde dehydrogenase domain found in FUS7 and LUC3 proteins. FUS7 is part of the gene cluster that mediates the biosynthesis of the mycotoxin fusarin C . LUC3 is part of the gene cluster that mediates the biosynthesis of the mycotoxin lucilactaene and the lucilactaene-related compound NG-391 that act as cell cycle inhibitors with potent growth inhibitory activity against malarial parasites and moderate growth inhibitory activity against cancer cells. They have no activity against bacteria and fungi . LUC3 is important for lucilactaene biosynthesis and performs the oxidation of the C-20 alcoholic analogue prelucilactaene G into a carboxylic derivative that has still to be identified .
2-hydroxychromene-2-carboxylate isomerase NahD-like (NahD-like)
Type: Family

NahD is a 2-hydroxychromene-2-carboxylate isomerase (also known as HCCA isomerase) converts HCCA, a hemiketal formed spontaneously after ring cleavage of 1,2-dihydroxynaphthalene by a dioxygenase, into cis-o-hydroxybenzylidenepyruvate (cHBPA). This is the fourth reaction in a six-step pathway that converts naphthalene into salicylate . HCCA isomerase is unique to bacteria that degrade polycyclic aromatic compounds. It is closely related to the eukaryotic protein, GSH transferase kappa (GSTK) .
Glutathione S-transferase kappa (GSTK)
Type: Family

GSTK is a member of the GST family of enzymes which catalyses the transfer of the thiol of GSH to electrophilic substrates . It is specifically located in the mitochondria and peroxisomes, unlike other members of the canonical GST family, which are mainly cytosolic . The biological substrates of GSTK are not yet known. It is presumed to have a protective role during respiration when large amounts of reactive oxygen species are generated. GSTK has the same general fold as DsbA, consisting of a thioredoxin domain interrupted by an α-helical domain and its biological unit is a homodimer . GSTK is closely related to the bacterial enzyme, 2-hydroxychromene-2-carboxylate (HCCA) isomerase. It shows little sequence similarity to the other members of the GST family .
Magnesium transporter Alr1-like (Alr1-like)
Type: Family

This eukaryotic subfamily belongs to the Thermotoga maritima CorA (TmCorA)-family of the MIT superfamily of essential membrane proteins involved in transporting divalent cations (uptake or efflux) across membranes. This subfamily includes three Saccharomyces cerevisiae members: two plasma membrane proteins, the Mg2 transporter Alr1 and the putative Mg2 transporter, Alr2, and the vacuole membrane protein Mnr2, a putative Mg2 transporter .

Thermotoga maritima CorA forms funnel-shaped homopentamers, the tip of the funnel is formed from two C-terminal transmembrane (TM) helices from each monomer, and the large opening of the funnel from the N-terminal cytoplasmic domains. The GMN signature motif of the MIT superfamily occurs just after TM1, mutation within this motif is known to abolish Mg2 transport by Alr1. Natural variants in this signature sequence may be associated with the transport of different divalent cations. The functional diversity of the MIT superfamily may also be due to minor structural differences regulating gating, substrate selection, and transport .
Nei2, N-terminal (Nei2_N)
Type: Domain

This entry represents the N-terminal domain of the actinomycetal protein Nei2, which is a homologue of Endonuclease 8 (also known as Nei) from E. coli. Nei is a bacterial enzyme with DNA N-glycosylase and abasic site lyase (AP1 lyase) activities, participates in base excision repair of oxidatively generated DNA damage. Nei removes oxidatively damaged pyrimidines from substrate DNA and serves as a back-up for endonuclease III .

Similar to Nei, Mycobacterium tuberculosis Nei2 (MtuNei2) is functionally active in vivo and recognises both guanine and cytosine oxidation products .
Nei, N-terminal (EcNei-like_N)
Type: Domain

This entry represents the N-terminal domain of Nei (also known as Endonuclease 8) from E. coli. Nei is a bacterial enzyme with DNA N-glycosylase and abasic site lyase (AP1 lyase) activities, participates in base excision repair of oxidatively generated DNA damage. Nei removes oxidatively damaged pyrimidines from substrate DNA and serves as a back-up for endonuclease III . It belongs to the FPG family and contains 1 FPG-type zinc finger .
Serine/threonine-protein PRP4, catalytic domain (STKc_PRP4)
Type: Domain

PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyse pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation . In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing . It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores .

This entry represents the catalytic domain of PRP4.
Cyclin-dependent kinase 10, catalytic domain (STKc_CDK10)
Type: Domain

Cyclin-dependent kinases (cdks) are the catalytic subunits of a large family of serine/threonine protein kinases (STKs). They are key regulators of eukaryotic cell cycle progression. CDK10 (also known as PISSLRE) is a cdc2-related kinase that contains the canonical regulatory Tyr and Thr residues present in all protein kinases and a PSTAIRE-like motif named PISSLRE . CDK10 is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle . CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen .
AtsA-like, MBL-fold (AtsA-like_MBL-fold)
Type: Domain

Pseudoalteromonas carrageenovora arylsulfatase AtsA may function as a glycosulfohydrolase involved with desulfation of sulfated polysaccharides, which catalyses hydrolysis of the arylsulfate ester bond, producing the aryl compounds and inorganic sulfate . Proteins containing this domain also include some sequences annotated as Ribonuclease Z.
ADCK2-like dom (ADCK2_dom)
Type: Domain

Proteins containing this domain include aarF domain containing kinase 2 (ADCK2) from humans, YPL109C from budding yeasts and SPBC21C3.03 from fission yeasts. Eukaryotes contain at least three ABC1-like proteins; in humans, these are ADCK3 and the putative protein kinases named ADCK1 and ADCK2 . YPL109C and SPBC21C3.03 are uncharacterised mitochondrial proteins.
Isoamylase 2, catalytic domain (AmyAc_plant_ISA2)
Type: Domain

This entry represents the catalytic domain found in plant Isoamylase 2 (ISA2), which is a Isoamylase-type debranching enzyme (ISA

) that plays a major role in amylopectin synthesis. Arabidopsis contains three isoamylase-like proteins (AtISA1, AtISA2 and AtISA3) together with one LDA protein (AtLDA) . In potato tubers, it has been shown that isoamylase is heteromultimeric and that two isoamylase proteins, ISA1 and ISA2, associate with each other to form a single isoamylase enzyme in vivo. The heteromultimeric isoamylase may function during starch synthesis to suppress the initiation of glucan molecules .
Alkyl/aryl-sulfatase Bds1/ SdsA1 , MBL-fold (Bds1/SdsA1_MBL-fold)
Type: Domain

This entry represents a group of arylsulfatases, including Bds1 from budding yeasts, SdsA1

from Pseudomonas aeruginosa and YjcS from E. coli. SdsA1 is a secreted SDS hydrolase that allows the bacterium to use primary sulfates such as the detergent SDS common in commercial personal hygiene products as a sole carbon or sulfur source . SdsA1 also contributes to the in vivo virulence of P. aeruginosa by playing a central role in the degradation of mucin . YjcS is also able to cleave SDS . Bds1, also known as bacterially-derived sulfatase, is required for use of alkyl- and aryl-sulfates as sulfur sources .
STAMBP/STALP-like, MPN domain (STAMBP/STALP-like_MPN)
Type: Domain

This domain is known as the MPN domain , PAD-1-like domain , JABP1 domain or JAMM domain . Proteins with this domain include proteasome regulatory subunits, eukaryotic initiation factor 3 (eIF3) subunits and regulators of transcription factors. They are metalloenzymes that function as the ubiquitin isopeptidase/deubiquitinase in the ubiquitin-based signaling and protein turnover pathways in eukaryotes . Versions of the domain in prokaryotic cognates of the ubiquitin-modification pathway are predicted to have a similar role .

This entry represents the MPN domain found in human STAMBP (also known as AMSH) and STALP (also known as
AMSH-LP) proteins. They are Zn-dependent deubiquitinating enzymes (DUBs) that regulate receptor trafficking by specifically cleaving Lys 63-linked polyubiquitin chains from internalised receptors . Mutations in the STAMBP gene cause microcephaly-capillary malformation syndrome .