SII-SWORD/CoKE huggingface dataset:
MepK (MepK)
Type: Family

This entry (ex DUF882) represents MepK and related proteins in bacteria. Some MepK proteins contain the TAT conserved site (

). These proteins contain a similar fold to the zinc-binding motif in bacterial D-alanyl-D-alanine carboxypeptidases (DD-peptidases).

Peptidoglycan L,D-endopeptidase MepK cleaves meso-diaminopimelic acid (mDAP)-mDAP cross-links in peptidoglycan. It acts in conjunction with other elongation-specific D, D-endopeptidases to create space for the efficient incorporation of nascent peptidoglycan strands into the sacculus, thereby enabling cell wall expansion . In vitro, MepK can cleave mDAP cross-links in both soluble muropeptides and intact peptidoglycan sacculi. It also displays weak D, D-endopeptidase activity .
Allatostatin (Allatostatin)
Type: Family

This family consists of allatostatins, bombystatins, helicostatins, cydiastatins and schistostatin from several insect species. Allatostatins (ASTs) of the Tyr/Phe-Xaa-Phe-Gly Leu/Ile-NH2 family are a group of insect neuropeptides that inhibit juvenile hormone biosynthesis by the corpora allata .
Varicellovirus Gp2, glycoprotein (Varicellovirus_Gp2_glycop)
Type: Family

This entry consists of a number of glycoprotein Gp2 sequences mainly found from equine herpesviruses .
Inner membrane protein YqjD/ElaB (YqjD/ElaB)
Type: Family

This family consists of several bacterial proteins and includes the Escherichia coli genes for ElaB, YgaM and YqjD.

YqjD is an inner membrane and ribosome binding protein expressed during the stationary growth phase. It is possible that YqjD inactivates ribosomes by localizing a part of the ribosome to the membrane during the stationary phase . Its expression is regulated by stress response sigma factor RpoS. The two paralogues of YqjD, ElaB and YgaM, are expressed and bind to ribosomes in a similar manner to YqjD . These proteins may have important cellular roles during the stress response. ElaB has been shown to protect cells against oxidative and heat shock stress .
(Uracil-5)-methyltransferase family (U5_MeTrfase_fam)
Type: Family

This family consists of (uracil-5-)-methyltransferases

from bacteria, archaea and eukaryotes. They are class I-like SAM-binding methyltransferases.

Methyltransferases (MTs) (EC 2.1.1.-) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as nitrogen, oxygen, sulfur or carbon leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids. MTs are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing .

More than 230 different enzymatic reactions of MTs have been described so far, of which more than 220 use SAM as the methyl donor. A review published in 2003 divides all MTs into 5 classes based on the structure of their catalytic domain (fold):

class I: Rossmann-like α/β

class II: TIM β/α-barrel α/β

class III: tetrapyrrole methylase α/β

class IV: SPOUT α/β

class V: SET domain all β

A more recent paper based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds:

class VI: transmembrane all α

class VII: DNA/RNA-binding 3-helical bundle all α

class VIII: SSo0622-like α+β

class IX: thymidylate synthetase α+β

The vast majority of MTs belong to the Rossmann-like fold (Class I) which consists in a seven-stranded β-sheet adjoined by α-helices. The β-sheet contains a central topological switch-point resulting in a deep cleft in which SAM binds. Class I MTs display two conserved positions, the first one is a GxGxG motif (or at least a GxG motif) at the end of the first β-strand which is characteristic of a nucleotide-binding site and is hence used to bind the adenosyl part of SAM, the second conserved position is an acidic residue at the end of the second β-strand that forms one hydrogen bond to each hydroxyl of the SAM ribose part. The core of these enzymes is composed by about 150 amino acids that show very strong spatial conservation. Catechol O-MT (EC 2.1.1.6) is the canonical Class I MT considering that it consists in the exact consensus structural core with no extra domain .
Protein of unknown function DUF885 (DUF885)
Type: Family

This family consists of hypothetical bacterial proteins.
Uncharacterised protein family HutD/Ves (Uncharacterised_HutD/Ves)
Type: Family

This entry contains proteins of unknown function, which include HutD from Pseudomonas fluorescens and Ves from Escherichia coli K12.

HutD from P. fluorescens is a component of the histidine uptake and utilisation operon. HutD is operonic with the well characterised repressor protein HutC. Genetic analysis using transcriptional fusions (lacZ) and deletion mutants shows that hutD is necessary to maintain fitness in environments replete with histidine. HutD probably sets an upper bound on the level of hut operon transcription . The mechanistic basis is unknown, but in silico molecular docking studies based on the crystal structure of HutD from Pseudomonas aeruginosa show that urocanate (the first breakdown product of histidine) docks with the active site of HutD.
Photosystem II reaction center protein Ycf12 (PSII_Ycf12_core-subunit)
Type: Family

This family represents Ycf12, also known as Photosystem II reaction center protein Psb30, a core subunit of photosystem II. Its function is unknown . Members of this entry are predominantly found in cyanobacteria and plants.
DNA helicase Pif1-like, DEAD-box helicase domain (DNA_helicase_pif1-like_DEAD)
Type: Domain

This entry represents the DEAD-box helicase domain, which includes the ATP-binding region, of a group of DNA helicases, including Pif1 and Rrm3 from budding yeasts and Pfh1 from fusion yeast. This entry also includes Pif1 like proteins from prokaryotes and eukaryotes including plants.

Pif1 is a DNA helicase conserved from bacteria to humans . It suppresses both G-quadruplex-associated DNA damage and telomere lengthening. In budding yeast, it exists in two forms, nuclear form and mitochondrial form. Its nuclear form inhibits telomerase, while its mitochondrial form is involved in repair and recombination of mitochondrial DNA .
METTL16/RlmF family (METTL16/RlmF)
Type: Family

This family includes ribosomal RNA large subunit methyltransferase F (RlmF), and related proteins, including methyltransferase-like protein 16 (METTL16). METTL16 is a conserved RNA methyltransferase which interacts specifically with the MALAT1 triple helix. METTL16 shows nuclear localisation . Another functional study indicates that METTL16 regulates expression of human MAT2A, which encodes the SAM synthetase expressed in most cells. Furthermore, results indicate that METTL16 is the long-unknown methyltransferase for the U6 spliceosomal small nuclear RNA (snRNA) and it has evolved an additional function in vertebrates to control SAM homeostasis by post-transcriptionally regulating SAM synthetase gene expression .

RlmF methylates the adenine in position 1618 of 23S rRNA . This family also includes psilocybin synthase (PsiM), which is a methyltransferase involved in the biosynthesis of the psychotropic agent psilocybin from the mushroom Psilocybe cubensis .
Protein of unknown function DUF892, YciF-like (DUF892_YciF-like)
Type: Family

This protein family is found in bacteria, including Protein YciF from Escherichia coli. This protein is produced by bacteria in response to stress conditions. It adopts a dimeric configuration in which each monomer shows five α-helices. Its function is still unknown .
Bacterial ABC transporter EcsB (EcsB_ABC)
Type: Family

The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions . Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette . More than 50 subfamilies have been described based on a phylogenetic and functional classification .

This family consists of several bacterial ABC transporter proteins which are homologous to the EcsB protein of Bacillus subtilis. EcsB is thought to encode a hydrophobic protein with six membrane-spanning helices in a pattern found in other hydrophobic components of ABC transporters .
Transmembrane secretion effector (TM_effector)
Type: Family

This is a family of transport proteins. Members of this family include a protein responsible for the secretion of the ferric chelator, enterobactin , and a protein involved in antibiotic resistance .
Ion channel regulatory protein, UNC-93 (Ion_channel_UNC-93)
Type: Family

This family represents UNC-93 from Caenorhabditis elegans, protein unc-93 homologue A (UNC93A) and UNC93-like protein MFSD11 (also called major facilitator superfamily domain-containing protein 11 or protein ET) from mammals, and similar eukaryotic proteins. UNC-93 colocalises with SUP-10 and SUP-9 within muscle cells. UNC-93 acts as a regulatory subunit of a multi-subunit potassium channel complex that may function in coordinating muscle contraction in C. elegans . MFSD11 is ubiquitously expressed in the periphery and the central nervous system of mice, where it is expressed in excitatory and inhibitory mouse brain neurons .
Uncharacterised protein family CreA (Uncharacterised_CreA)
Type: Family

This family consists of several bacterial CreA proteins, the function of which is unknown.
Na+-dependent bicarbonate transporter superfamily (Sbt_1)
Type: Family

This is a family of bacterial proteins that are likely to be part of the Na(+)-dependent bicarbonate transporter (sbt) family. Members carry 10TMS in a 5+5 duplicated structure. The loop between helices 5 and 6 in Synechocystis PCC6803 is likely to be the location for regulatory mechanisms governing the activation of the transporter .
ADAMTS/ADAMTS-like, Spacer 1 (ADAMTS_spacer1)
Type: Domain

This entry represents the Spacer-1 domain found in ADAM-TS and ADAM-TS-like proteins.

Proteolysis of the extracellular matrix plays a critical role in establishing tissue architecture during development and in tissue degradation in diseases such as cancer, arthritis, Alzheimer's disease and a variety of inflammatory conditions . The proteolytic enzymes responsible for this process are members of diverse protease families, including the secreted zinc metalloproteases (MPs) .

ADAM-TS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) is closely related to the ADAM family (A Disintegrin and Metalloproteinase) and is a subfamily of the MP family, consists of at least 20 members sharing a high degree of sequence similarity and conserved domain organisation . The defining domains of the ADAM-TS family are (from N- to C-termini) a pre-pro metalloprotease domain of the reprolysin type, a snake venom disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-rich region, and a cysteine-free (spacer) domain . Domain organisation following the spacer domain C terminus shows some variability in certain ADAM-TS members, principally in the number of additional TS domains. These enzymes have a wide-spectrum role in vascular biology and cardiovascular pathophysiology .

Members of the ADAM-TS family have been implicated in a range of diseases . For instance, members of this family have been found to participate directly in processes in the central nervous system (CNS) such as the regulation of brain plasticity . ADAM-TS1 is reported to be involved in inflammation and cancer cachexia , whilst recessively inherited ADAM-TS2 mutations cause Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by severe skin fragility . ADAM-TS4 is an aggrecanase involved in arthritic destruction of cartilage .

ADAM-TS-like proteins lack a metalloprotease domain. They resides in the ECM and have regulatory roles . Examples of ADAM-TS-like proteins are papilin and punctin .
Protein of unknown function DUF898 (DUF898)
Type: Family

This family consists of several bacterial proteins of unknown function. Some of the family, including YjgN, are putative transmembrane proteins.

These proteins have a βααβα hairpin structure that is repeated.
Protein of unknown function DUF899, thioredoxin-like (DUF899_thioredox)
Type: Family

This family consists of uncharacterised bacterial proteins of unknown function which are thioredoxin-like.
Protein of unknown function DUF900, hydrolase-like (DUF900_hydrolase)
Type: Family

This domain is associated with proteins of unknown function, which are hydrolase-like.
NYN/PIN ribonuclease, YacP-like (YacP-like)
Type: Family

This family includes YacP from Bacillus subtilis (also known as Rae1,

) and similar proteins from bacteria and plants. YacP is a translation-dependent endoribonuclease that belongs to the NYN subfamily of PIN domain enzymes. Its optimal cleavage site appears to be immediately upstream of a lysine codon. Its crystal structure reveal an N-terminal NYN/PIN domain with an exposed active site and a flexible putative C-terminal RNA binding domain that consists of two α-helices .
Cysteine dioxygenase type I (CDO_1)
Type: Family

Cysteine dioxygenase (CDO) plays an important role in the homeostatic regulation of steady-state cysteine levels and provides important oxidized metabolites of cysteine such as sulfate and taurine. It converts cysteine to cysteinesulphinic acid and is the rate-limiting step in sulphate production .

This entry also includes a cysteine dioxygenase homologue from Pseudomonas aeruginosa known as p3MDO. It functions as a 3-mercaptopropionate dioxygenase that catalyses the dioxygenation of 3-MPA to 3-sulfinopropionic acid (3-SPA) . 3-Mercaptopropionic acid (3-MPA) is a structural analogue of cysteine.
Ribosomal RNA processing protein 1 (RRP1)
Type: Family

This entry represents Ribosomal RNA-processing protein 1 (RPP1) from yeast and its homologues, such as RRP1A/B from mammals and RRP1L from Drosophila. In Saccharomyces cerevisiae, RPP1 is required for 27S rRNA processing to 25S and 5.8S. In humans, RRP1A (also known as) Nop52 is believed to be involved in the generation of 28S rRNA .
UL27-like protein, herpesvirus (UL27-like_protein_herpesevirus)
Type: Family

This entry represents a family of herpesvirus proteins that includes UL27, U5 and U7. UL27 promotes a cell cycle arrest in G0/G1 by inducing the proteasomal degradation of host histone acetyltransferase KAT5/Tip60 .
CREB-binding protein/p300, atypical RING domain (RING_CBP-p300)
Type: Domain

CBP (CREB-binding protein) and p300 (also known as CREBBP or KAT3A and EP300 or KAT3B, respectively) are two histone acetyltransferases (HATs) that associate with and acetylate transcriptional regulators and chromatin. The catalytic core of animal CBP-p300 contains a bromodomain, a CH2 region containing a discontinuous PHD domain interrupted by this RING domain, and a HAT domain. Bromodomain-RING-PHD forms a compact module in which the RING domain is juxtaposed with the HAT substrate-binding site. This ring domain contains only a single zinc ion-binding cluster instead of two; instead of a second zinc atom, a network of hydrophobic interactions stabilizes the domain. The RING domain has an inhibitory role. Disease mutations that disrupt RING attachment lead to upregulation of HAT activity. HAT regulation may require repositioning of the RING domain to facilitate access to an otherwise partially occluded HAT active site. Plant CBP-p300 type HATs lack a bromodomain whose role in the animal animal CBP-p300's is to bind acetylated histones; it has been suggested that these plant proteins may utilize a different domain or another bromodomain protein to perform this function . This RING domain has also been referred to as DUF902.
Survival motor neuron, Tudor domain (SMN_Tudor)
Type: Domain

This entry represents the Tudor domain of eukaryotic survival motor neuron (SMN) and survival of motor neuron-related-splicing factor 30 (SPF30) proteins. The Survival of Motor Neurons (SMN) protein, the product of the spinal muscular atrophy-determining gene, is part of a large macromolecular complex (SMN complex) that functions in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs). The SMN complex functions as a specificity factor essential for the efficient assembly of Sm proteins on U snRNAs and likely protects cells from illicit, and potentially deleterious, non-specific binding of Sm proteins to RNAs . SMN has three highly conserved domains: a short N-terminal segment responsible for binding with high affinity to Gemin2 (a protein involved in snRNP assembly), therefore, called Gemin2-binding domain (G2-BD), a central Tudor domain and a C-terminal YG-box domain. This domain covers the Tudor domain of SMN and SPF30, in which an aromatic cage mediates symmetric dimethylarginine modifications recognition by electrostatic stabilization through cation-pi interactions in a number of proteins involved in RNA processing .
Lipoprotein YgdI/YgdR-like (YgdI/YgdR-like)
Type: Family

This family consists of several small bacterial lipoproteins, including YgdI and YgdR from E. coli. The function of this family is unknown.
Alpha-D-ribose 1-methylphosphonate 5-phosphate C-P-lyase (PhnJ)
Type: Family

The cleavage of the C-P bond in PRPn to form a-D-ribose-1,2-cyclic-phosphate-5-phosphate (PRcP) is assumed to involve a radical mechanism and PhnJ is a protein that, belonging to the Radical SAM superfamily can perform such a reaction. This enzyme appears to function through the formation of a glycyl radical by the 5'-Ado radical, this radical is then passed onto a conserved cysteine residue. The cysteine radical then forms a covalent bond with the phosphate in the substrate. The glycyl radical is recycled, ready for another reaction to occur .
.
Laminin domain II (Laminin_dom_II)
Type: Domain

It has been suggested that the domains I and II from laminin A, B1 and B2 may come together to form a triple helical coiled-coil structure .
TRP, C-terminal (TRP_C)
Type: Domain

This entry represents the C-terminal domain of transient receptor potential channel-like proteins. The family includes several fungal flavin carrier proteins, which may be responsible for the transport of FAD into the endoplasmatic reticulum lumen, where it is required for oxidative protein folding . The family also includes the TRP-like ion channel pkd2, which acts as a key signaling component in the regulation of cell shape and cell wall synthesis through interaction with GTPase Rho1 .
E3 ubiquitin ligase, domain of unknown function DUF908 (E3_Ub_ligase_DUF908)
Type: Domain

This is a domain of unknown function found at the N terminus of a family of E3 ubiquitin protein ligases, including yeast TOM1, many of which appear to play a role in mRNA transcription and processing. This domain is found in association with and immediately N-terminal to another domain of unknown function:

.
Type VII secretion system ESAT-6-like (T7SS_ESAT-6-like)
Type: Family

Members of this protein family include secretion targets for type main variants of type VII secretion systems (T7SS), one found in the Actinobacteria, one found in the Firmicutes. Members of this family usually are ~100 amino acids in length but occasionally have long C-terminal extension .

The best characterised member of this family is ESAT-6. This is a small protein that appears to be of fundamental importance in virulence and protective immunity in Mycobacterium tuberculosis. Homologues have been detected in other Gram-positive bacterial species. It may represent a novel secretion system potentially driven by the

domains in the YukA-like proteins .
Reovirus core-spike lambda-2 (Reovirus_L2)
Type: Family

This family consists of several Reovirus core-spike protein lambda-2 (L2) sequences. The reovirus L2 genome segment encodes the core spike protein lambda-2, which mediates enzymatic reactions in 5' capping of the viral plus-strand transcripts .
Global transcriptional regulator CodY, N-terminal (Transc_reg_CodY_N)
Type: Domain

This entry represents N-terminal domain of several bacterial Global transcriptional regulator CodY proteins. CodY has been found to repress the dipeptide transport operon (dpp) of Bacillus subtilis in nutrient-rich conditions . The CodY protein also has a repressor effect on many genes in Lactococcus lactis during growth in milk .
Glycine N-acyltransferase (Glycine_N-acyltransferase)
Type: Family

This entry represents glycine N-acyltransferase (also called aralkyl acyl-CoA:amino acid N-acyltransferase;

). Mitochondrial acyltransferases catalyse the transfer of an acyl group from acyl-CoA to the N terminus of glycine to produce N-acylglycine. These enzymes can conjugate a multitude of substrates to form a variety of N-acylglycines. The CoA derivatives of a number of aliphatic and aromatic acids, but not phenylacetyl-CoA or (indol-3-yl)acetyl-CoA, can act as donor .
E3 ubiquitin ligase, domain of unknown function DUF913 (E3_Ub_ligase_DUF913)
Type: Domain

This is a domain of unknown function found towards the N terminus of a family of E3 ubiquitin protein ligases, including yeast TOM1, many of which appear to play a role in mRNA transcription and processing. This domain is found in association with and immediately C-terminal to another domain of unknown function:

.
Protein of unknown function DUF915, hydrolase-like (DUF915_hydro-like)
Type: Family

This family consists of bacterial hydrolase-like proteins of unknown function.
DNA-3-methyladenine glycosylase AlkA, N-terminal (AlkA_N)
Type: Domain

AlkA (DNA-3-methyladenine glycosylase II) is a base excision repair glycosylase from Escherichia coli. It removes a variety of alkylated bases from DNA, primarily by removing alkylation damage from duplex and single stranded DNA. AlkA is similar in fold and active site location to the bifunctional glycosylase/lyase endonuclease III. This suggests that the two may use similar mechanisms for base excision . The structural analysis of the AlkA and AlkA-hypoxanthine structures indicate that free hypoxanthine binding in the active site may inhibit glycosylase activity .

The AlkA protein consists of three domains: an N-terminal mixed α-β structure, a central seven-helix bundle, and a C-terminal domain of four a helices . This entry represents the N-terminal domain.
WxL Interacting Protein, peptidoglycan binding domain (WxLIP_PGBD)
Type: Domain

This domain is found in WxL interacting proteins (WxLIP) which play a role in virulence and are widely distributed in firmicutes. The WxL proteins usually occur within a gene cluster that contains two WxL proteins and a WxL interacting protein composed of three domains: peptidoglycan binding domain (PGBD), host binding domain (HBD), and transmembrane helix (TMH). The domain represented by this entry, previously known as DUF916, is involved in binding to peptidoglycan and to WxL, and anchoring the protein cluster onto the bacterial surface. This PGBD domain is frequently found in combination with HBD domain (

) and both were shown to function synergistically as a single unit that binds to the peptidoglycan and interacts with the eukaryotic host . The PGBD domain is predicted to adopt a β-sandwich with an Ig-like topology.
S-Me-THD, N-terminal domain (S-Me-THD_N)
Type: Domain

This entry represents a domain found N-terminal of S-methyl thiohydantoin desulfurase from Variovorax sp. (S-Me-THD) and similar sequences mainly found in bacteria and fungi. S-Me-THD catalyses the hydrolysis of S-methyl-thiohydantoin-5-propanoate into hydantoin-5-propanoate and methanethiol, the third step in S-methyl ergothioneine degradation .

This domain is also found in the hypothetical protein from Chromobacterium violaceum

and related hypothetical bacterial, archaeal and eukaryotic proteins of unknown function. This domain adopts a globular 3-layer(aba) structure consisting os a central mixed β-sheet and α-helices packed on both sides of it

.