SII-SWORD/CoKE huggingface dataset:
Lhr-like, DEAD/H associated domain (Lhr-like_DEAD/DEAH_assoc)
Type: Domain

This domain is found in Lhr DEAD-box RNA helicase and ATP-dependent helicases. This domain is associated with (

) and (

). It can be found C-terminal in some Lhr proteins.

Lhr is a DNA helicase that translocates in a 3'-to-5' direction on single-stranded DNA and is likely involved in DNA repair. It is most active on three- or four-stranded forked DNA structures, while flayed substrates and Holliday junctions are unwound with slightly less efficiency. Lhr can also unwind 3'-tailed duplexes, including RNA:DNA hybrids and double-stranded DNA with a 3'-single-stranded DNA overhang. However, it does not act on blunt-ended double-stranded DNA, and its activity on substrates with a 3'-single-stranded RNA tail, such as DNA:RNA or RNA:RNA, has not been tested. Lhr is probably involved in replication-coupled DNA repair, where it remodels forked DNA to generate single-stranded regions for ATP-dependent translocation .
FIST domain, N-terminal (FIST_domain_N)
Type: Domain

The FIST N domain is a novel sensory domain, which is present in signal transduction proteins from Bacteria, Archaea and Eukarya. Chromosomal proximity of FIST-encoding genes to those coding for proteins involved in amino acid metabolism and transport suggest that FIST domains bind small ligands, such as amino acids .
Peptidase S49, N-terminal proteobacteria (Peptidase_S49_N_proteobac)
Type: Domain

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This domain is found to the N terminus of bacterial signal peptidases that belong to the MEROPS peptidase family S49 (protease IV family, clan SK) (see also

) .
UPF0313, N-terminal (UPF0313_N)
Type: Domain

This domain tends to occur to the N terminus of

radical SAM domain in hypothetical bacterial proteins.

Proteins in this entry are radical SAM proteins, they catalyse diverse reactions, including unusual methylations, isomerization, sulphur insertion, ring formation, anaerobic oxidation and protein radical formation. Evidence exists that these proteins generate a radical species by reductive cleavage of S:-adenosylmethionine (SAM) through an unusual Fe-S centre .
Sterol methyltransferase C-terminal (Sterol_MeTrfase_C)
Type: Domain

This domain is found to the C terminus of a methyltransferase domain (

) in fungal and plant sterol methyltransferases .
PDE1, N-terminal domain (PDE1_N)
Type: Domain

This domain is found at the N terminus of PDE1 predominantly from vertebrates. This domain adopts an all α-helical structure. It is found next to the catalytic domain (

).

The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They are divided into 11 families. They regulate the localisation, duration and amplitude of cyclic nucleotide signalling within subcellular domains. PDEs are therefore important for signal transduction.

PDE enzymes are often targets for pharmacological inhibition due to their unique tissue distribution, structural properties, and functional properties. Inhibitors include: Roflumilast for chronic obstructive pulmonary disease and asthma , Sildenafil for erectile dysfunction and Cilostazol for peripheral arterial occlusive disease , amongst others.

Retinal 3',5'-cGMP phosphodiesterase is located in photoreceptor outer segments: it is light activated, playing a pivotal role in signal transduction . In rod cells, PDE is oligomeric, comprising an alpha-, a beta-and 2 gamma-subunits, while in cones, PDE is a homodimer of alpha chains, which are associated with several smaller subunits. Both rod and cone PDEs catalyse the hydrolysis of cAMP or cGMP to the corresponding nucleoside 5' monophosphates, both enzymes also binding cGMP with high affinity. The cGMP-binding sites are located in the N-terminal half of the protein sequence, while the catalytic core resides in the C-terminal portion.
Tombusvirus p33 (Tombusvirus_p33)
Type: Domain

Tombusviruses, which replicate in a wide range of plant hosts, replicate with the help of viral replicase protein including the overlapping p33 and p92 proteins which contain the domain described here .
Shikimate dehydrogenase substrate binding, N-terminal (Shikimate_DH-bd_N)
Type: Domain

This domain is the substrate binding domain of shikimate dehydrogenase . Shikimate dehydrogenase catalyses the fourth step of the mycobacterial Shikimate pathway, which results in the biosynthesis of chorismate. Chorismate is a precursor of aromatic amino acids, naphthoquinones, menaquinones and mycobactins . This pathway is an important target for antibacterial agents, especially against Mycobacterium tuberculosis, since it does not occur in mammals.
2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain (2-isopropylmalate_synth_dimer)
Type: Domain

This is the C-terminal regulatory (R) domain of alpha-isopropylmalate synthase, which catalyses the first committed step in the leucine biosynthetic pathway . This domain, is an internally duplicated structure with a novel fold . It comprises two similar units that are arranged such that the two helices pack together in the centre, crossing at an angle of 34 degrees, sandwiched between the two three-stranded, antiparallel β-sheets. The overall domain is thus constructed as a β-α-β three-layer sandwich .
2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-acetyltransferase, N-terminal (DapH_N)
Type: Domain

This domain is found at the N terminus of t2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-acetyltransferase (DapH) which catalyses the acylation of L-2-amino-6-oxopimelate to 2-N-acetyl-6-oxopimelate in the meso-diaminopimelate/lysine biosynthetic pathway of bacteria, blue-green algae, and plants . The N-terminal domain as defined here contains three α-helices and two twisted hairpin loops .
Runx, C-terminal domain (RunxI_C_dom)
Type: Domain

This domain lies to the C terminus of Runx-related transcription factors and homologous proteins (AML, CBF-alpha, PEBP2). Its function might be to interact with functional cofactors .
Mitochondrial Myo2 receptor-related protein 1 (MMR1)
Type: Family

Myo2p, a class V myosin, is essential for mitochondrial distribution, class V being vital for organelle distribution in S. cerevisiae. The established mechanism for distribution of cellular components by class V myosins is that they interact with the cargo at the C-terminal tail domain and transport it along the actin cytoskeleton using the N-terminal motor domain. Cargo-specific myosin receptors act as the link between the myosin tail and cargo. Myo2 binds with MMR1 (mitochondrial Myo2p receptor-related protein 1), the receptor on cargo, via the C-terminal domain .
Exportin-2, central domain (XPO2_central)
Type: Domain

Exportin-2, also known as CAS, is an export receptor for importin-alpha . It binds strongly to importin alpha only in the presence of RanGTP, forming an importin alpha/CAS/RanGTP complex. Exportin-2 mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates have been released into the nucleoplasm .

This domain is found in exportin-2 and related proteins, such as exportin-7/8. This domain contains HEAT repeats.
Golgi apparatus membrane protein TVP15 (Golgi_TVP15)
Type: Family

Proteins in this family co-localise with COPI vesicle coat proteins . In yeast it is a Golgi membrane protein involved in vesicular trafficking, interacting with Tvp18 and Tvp23 .
Domain of unknown function DUF1746 (DUF1746)
Type: Domain

This is a fungal domain of unknown function. This domain can be found in DSC E3 ubiquitin ligase complex subunit 4 (Dsc4) from S. pombe. It is a component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. The complex plays also an important role in the multivesicular body (MVB) pathway and functions in a post-endoplasmic reticulum pathway for protein degradation . This domain is also found in GLD1 from S. cerevisiae, also a component of the DSC E3 ubiquitin ligase complex involved in the targeting of the DSC complex to the Golgi apparatus and endosome membranes via the AP3 pathway to ubiquitinate Golgi/endosome membrane proteins .
Adenylate cyclase G-alpha binding (Adenylate_cyclase_G-a-bd)
Type: Domain

Adenylate cyclase catalyses the conversion of ATP to 3',5'-cyclic AMP (cAMP) and pyrophosphate. It plays an essential role in the regulation of cellular metabolism by catalysing the synthesis of a second messenger, cAMP. G protein-mediated signalling is implicated in yeast and fungal cAMP pathways. The cAMP-PKA pathway consists of an extracellular ligand-sensitive G protein-coupled receptor, a G protein signal transmitter, and the effector adenylate cyclase. The product of adenylate cyclase, cAMP, acts as an intracellular second messenger .

GTP-bound RAS2 is required to elicit magnesium-dependent adenylyl cyclase activity in Saccharomyces cerevisiae. In Schizosaccharomyces pombe, however, the cyclase is probably not regulated by RAS proteins, but is activated by git1.

In S. pombe, Gpa2 Galpha binds an N-terminal domain of adenylate cyclase, comprising a moderately conserved sequence, which is within a region that is poorly related to other fungal adenylate cyclases. Adenylate cyclase is directly activated by a fungal G protein, which suggests a distinct activation mechanism from that of mammals .

This fungal domain interacts with the alpha subunit of heterotrimeric G proteins .
PIG-P (PIG-P)
Type: Domain

PIG-P (phosphatidylinositol N-acetylglucosaminyltransferase subunit P) is an enzyme involved in GPI anchor biosynthesis .
COQ9, C-terminal domain (COQ9_C)
Type: Domain

This entry represents the C-terminal region of the globular domain of COQ9 and similar sequences from bacteria and eukaryotes. This domain shows structural homology with the small molecule binding domain members of the TFR family of bacterial transcriptional regulators, adopting an α-helical configuration. It appears solvent exposed in the crystal structure, is very sensitive to mutations and is thought to be an important functional area of COQ9 .

Ubiquinone biosynthesis protein COQ9 is an protein that is required for the biosynthesis of coenzyme Q , which functions in the respiratory electron transport chain and serves as a lipophilic antioxidant. In Saccharomyces cerevisiae (Baker's yeast), Q biosynthesis requires nine Coq proteins (Coq1-Coq9), with the COQ9 product acting subsequent to the prenylation of 4-hydroxybenzoic acid.

COQ9 consists of an α-helical globular domain and an amphipathic C-terminal 10th α-helix responsible for membrane association .
Histone chaperone RTT106/FACT complex subunit SPT16-like, middle domain (RTT106/SPT16-like_middle_dom)
Type: Domain

This entry represents a domain found in the middle region of several eukaryotic proteins . It is present in various FACT (facilitates chromatin transactions) complex subunits, such as Spt16 and either Pob3 (yeast) or the related SSRP1 (higher eukaryotes). FACT is a general chromatin factor that acts to reorganise nucleosomes . In these proteins, the middle domain shows a double pleckstrin homology (PH) configuration and plays a role in DNA binding . This entry represents the second PH domain, which is also found in Rtt106p, a histone chaperone involved in heterochromatin-mediated silencing .
STAG (STAG)
Type: Domain

STAG domain proteins are subunits of cohesin complex - a protein complex required for sister chromatid cohesion in eukaryotes. The STAG domain is present in Schizosaccharomyces pombe (Fission yeast) mitotic cohesin Psc3, and the meiosis specific cohesin Rec11. Many organisms express a meiosis-specific STAG protein, for example, mice and humans have a meiosis specific variant called STAG3, although budding yeast does not have a meiosis specific version .
GIT, Spa2 homology (SHD) domain (GIT_SHD)
Type: Domain

This entry represents the Spa2 homology domain (SHD) domain found in the yeast Spa2/Sph1 protein and the mammalian GIT proteins.
DNA replication factor RFC1, C-terminal (DNA_replication_fac_RFC1_C)
Type: Domain

This is the C-terminal domain of replication factor C, RFC1. RFC complexes hydrolyse ATP and load sliding clamps such as PCNA (proliferating cell nuclear antigen) onto double-stranded DNA. RFC1 is essential for RFC function in vivo .
Mitofissin (Mitofissin)
Type: Family

This is a family of fungal proteins identified as mitochondrial fission factors (mitofissin, also referred to as Atg44) which are essential for mitophagy. Mitofissin directly binds to lipid membranes to drive mitochondrial fission required for mitophagy . This intermembrane space protein is essential for the completion of mitochondrial division .
Two-component sensor kinase, N-terminal (2CSK_N)
Type: Domain

This domain is found in bacterial two-component sensor kinases towards the N terminus. Proteins containing this domain includes sensor protein QseC, which is a member of a two-component regulatory system QseB/QseC . It recognises Autotinducer 3 (AI-3), epinephrine, norepinephrine and Fe(III) (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
BT_3987-like, N-terminal domain (BT_3987-like_N)
Type: Domain

This domain, previously known as DUF1735, is found in a number of proteins mainly found in firmicutes, including
BT_3987 (

) and BT_3044 (

) from Bacteroides thetaiotaomicron. BT_3987 displays hydrolytic activity against Hy-type N-glycans, probably initiating the degradation of this type of glycan in the human gut . BT_3044 is a glycan binding enzyme that could degrade oligosaccharides or even large molecular size glycans . This domain adopts a β-sandwich fold.
Multiprotein bridging factor 1, N-terminal (MBF1_N)
Type: Domain

This domain is found in the multiprotein bridging factor 1 (MBF1) which forms a heterodimer with MBF2. It has been shown to make direct contact with the TATA-box binding protein (TBP) and interacts with Ftz-F1, stabilising the Ftz-F1-DNA complex . It is also found in the endothelial differentiation-related factor (EDF-1). Human EDF-1 is involved in the repression of endothelial differentiation, interacts with CaM and is phosphorylated by PKC . The domain is found in a wide range of eukaryotic proteins including metazoans, fungi and plants. A helix-turn-helix motif (

) is found to its C terminus.
Fyv7/TAP26 (Fyv7/TAP26)
Type: Family

This entry include proteins from the FYV7 and the TAP26 families .
Opacity-associated protein A-like, N-terminal (OapA_N)
Type: Domain

This domain is found in the Haemophilus influenzae opacity-associated protein (OapA) and related proteins. It is required for efficient nasopharyngeal mucosal colonisation, and its expression is associated with a distinctive transparent colony phenotype. OapA is thought to be a secreted protein, and its expression exhibits high-frequency phase variation . This motif occurs at the N terminus of these proteins. It contains a conserved histidine followed by a run of hydrophobic residues.
Protein-arginine deiminase (PAD), N-terminal (PAD_N)
Type: Domain

This entry represents the first immunoglobulin-like non-catalytic domain of protein-arginine deiminase.

Protein arginine deiminases (PADs) use a nucleophilic cysteine to hydrolyze guanidinium groups on arginine residues to form citrulline. This reaction, known as citrullination or deimination, results in the loss of positive charge, thereby affecting protein function and altering protein-protein and protein-nucleic acid interactions. Humans encode five PADs, designated PADs 1-4 and PAD6, which regulate numerous cellular processes. PADs are dysregulated in inflammatory diseases and cancer . PAD6 does not bind Ca2+ and is inactive in vitro assays against standard PADs substrate .

The PAD2 monomer consists of two immunoglobulin-like domains, IgG1 (residues 1-115) and IgG2 (residues 116-295), as well as a C-terminal catalytic domain (residues 296-665) .
Protein-arginine deiminase (PAD), central domain (Prot_Arg_deaminase_cen_dom)
Type: Domain

Peptidylarginine deiminase (PAD) enzymes catalyse the conversion of protein-bound arginine to citrulline. There are five types of PADs known in humans, PAD1-PAD4 and PAD6 . PAD6 does not bind Ca2+ and is inactive in vitro assays against standard PADs substrate . This entry represents the central non-catalytic domain of protein-arginine deiminase. This domain has an immunoglobulin-like fold .
Transcription factor Nrm1/Whi5 (TF_Nrm1/Whi5)
Type: Conserved_site

This is a short conserved sequence found in the Nrm1/Whi5 transcription factors. Nrm1 is a negative regulatory component of the MBF complex involved in cell-cycle-dependent transcription . Whi5 is a transcriptional repressor that negatively regulates G1-specific, SBF- and MBF-dependent transcription .
Transcription factor NusA, N-terminal (TF_NusA_N)
Type: Domain

This entry represents the N-terminal RNA polymerase-binding domain of bacterial transcription factors such as NusA (N-utilising substance A). NusA is involved in transcriptional pausing, termination and anti-termination. NusA from Thermotoga maritima contains an N-terminal domain and three RNA-binding domains (one S1 domain and two KH domains). The N-terminal domain consists of a bifurcated coiled β-sheet within an α/β(3)/α/β/α fold, which can be divided into two subdomains: a globular head and a helical body. The globular head subdomain may interact with RNA polymerase, while the helical body displays a similar structure to that of the helical domain in sigma70 .
Xaa-Pro dipeptidyl-peptidase, C-terminal (Xaa-Pro_dipept_C)
Type: Domain

This domain is found at the C terminus of cocaine esterase CocE, several glutaryl-7-ACA acylases, and the putative diester hydrolase NonD of Streptomyces griseus (all hydrolases). The domain, which is a β sandwich, is also found in serine peptidases belonging to MEROPS peptidase family S15: Xaa-Pro dipeptidyl-peptidases. Members of this entry, that are not characterised as peptidases, show extensive low-level similarity to the Xaa-Pro dipeptidyl-peptidases.
Bacterial alpha-L-rhamnosidase N-terminal (Bac_rhamnosid_N)
Type: Domain

This domain is found in bacterial rhamnosidase A and B enzymes and is probably involved in substrate recognition.
Beta-galactosidase trimerisation (Beta_galactosidase_Trimer)
Type: Domain

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

This is non catalytic domain B of beta-galactosidase enzymes belong to the glycosyl hydrolase 42 family. This domain is related to glutamine amidotransferase enzymes, but the catalytic residues are replaced by non functional amino acids. This domain is involved in trimerisation.
Beta-galactosidase C-terminal (Beta_galactosidase_C)
Type: Domain

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

This domain is found at the C terminus of beta-galactosidase enzymes that belong to the glycosyl hydrolase 42 family .
Redoxin (Redoxin)
Type: Domain

This redoxin domain is found in peroxiredoxin, thioredoxin and glutaredoxin proteins. Peroxiredoxins (Prxs) constitute a family of thiol peroxidases that reduce hydrogen peroxide, peroxinitrite, and hydroperoxides using a strictly conserved cysteine . Chloroplast thioredoxin systems in plants regulate the enzymes involved in photosynthetic carbon assimilation . It is thought that redoxins have a large role to play in anti-oxidant defence. Cadmium-sensitive proteins are also regulated via thioredoxin and glutaredoxin thiol redox systems .
Repressor KorB domain (KorB_domain)
Type: Domain

The korB gene is a major regulatory element in the replication and maintenance of broad host-range plasmid RK2. It negatively controls the replication gene trfA, the host-lethal determinants kilA and kilB, and the korA-korB operon . This domain found in KorB includes the DNA-binding HTH motif .
Whirly transcription factor (Whirly)
Type: Family

The whirly family members are plant transcription factors that bind to single-stranded DNA and regulate defense gene expression . They may contribute to plastid genome stability by protecting against illegitimate repeat-mediated recombination .
NBP1/CSA1 (NBP1/CSA1)
Type: Family

This family includes CDC5 pindle pole body anchor protein 1 (CSA1/YPR174C) and NAP1-binding protein (NBP1) from yeast, which are paralogues. Both proteins bind to the nuclear membrane. NBP1 has been shown in Saccharomyces cerevisiae to function in spindle pole body duplication and CSA1 is a specialised component of the nuclear membrane that may be involved in the connection of the spindle pole body (SPB) to the nuclear envelope . It recruits CDC5 to spindle pole bodies in metaphase .
Fusarinine C esterase SidJ (SidJ)
Type: Family

This entry includes fusarinine C esterase SidJ from the yeast
Neosartorya fumigata
. Fusarinine C is an intracellular siderophore (an iron-chelating compound that transports iron across membranes) that is crucial for virulence. The closely related siderophore triacetylfusarinine C is not hydrolysed by SidJ . Homologues of SidJ are found in plants and bacteria.
TORC2 component Bit61/PRR5 (Bit61/PRR5)
Type: Family

This entry includes PRR5 (also known as PROTOR1) from animals, Bit61 and its paralogue-Bit2 from budding yeasts . They are part of the Target Of Rapamycin Complex 2 (TORC2) complex, which plays an essential role in signal transduction . The mammalian TORC2 consists of mTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR . The budding yeast TORC2 is composed of Avo1, Avo2, Tsc11, Lst8, Bit61, Slm, Slm2 and Tor2 .