SII-SWORD/CoKE huggingface dataset:
Sporadic carbohydrate cluster 2-oxoglutarate-Fe(II) oxygenase (SpoChClust_oxygenase)
Type: Family

This family, related to streptomycin biosynthesis protein StrG and to phytanoyl-CoA dioxygenase, belongs to the 2-oxoglutarate and Fe(II)-dependent oxygenase superfamily, which includes not just dioxygenases, but also some chlorinating enzymes involved in natural product biosynthesis. Most members of this family are adjacent to a member of

, and occur in a larger carbohydrate biosynthesis cluster found sporadically in genera Bradyrhizobium, Leptospira, Magnetospirillum, Oscillatoria, Prochlorococcus, etc.
Putative methyltransferase, LIC12133 family (Put_MTase_LIC12133)
Type: Family

Members of this family tend to occur next to glycosyltransferases and other characteristic enzymes of O-antigen biosynthetic regions. The founding member is LIC12133 (

) from Leptospira interrogans serovar Copenhageni. PSI-BLAST reveals distant homology to known SAM-dependent methyltransferases (

).
Surface carbohydrate biosynthesis protein LIC13510 (O_ant_LIC13510)
Type: Family

This uncharacterised, rare protein occurs in the highly variable O-antigen region of some strains of Leptospira, as well as strains of Desulfovibrio, and serves as a phylogenetic marker for the likely presence of six additional proteins, including an activated sugar-nucleotidyltransferase, an activated sugar epimerase and a dehydratase, an aldolase, and a DegT family aminotransferase. The patterns suggests a role in preparing a novel sugar for O-antigen incorporation.
Predicted outer membrane protein, Leptospiraceae (OMP_Lepto)
Type: Family

Members of this family are predicted outer membrane proteins, apparently restricted to the Leptospiraceae (Leptospira and Leptonema).
Putative TOMM peptide (TOMM_nitrile_2)
Type: Family

Members of this family of short peptides average about 110 amino acids in length, with greatest variability in the last thirty. The conserved region resembles the alpha subunit of nitrile hydratase, as with the NHLP leader peptide domain, and members usually are found near a cyclodehydratase (maturase) enzyme, marking these as like thiazole/oxazole-modified microcins (TOMM), but these precursor forms lack the GlyGly cleavage motif that marks the clear end of a leader peptide region. Genomes with this system include Streptomyces clavuligerus ATCC 27064, Verrucosispora maris AB-18-032, and Kitasatospora setae KM-6054.
CRISPR-associated protein Cas4, PREFRAN subtype (Cas4_PREFRAN)
Type: Family

Members of this family are the Cas4 protein of a novel CRISPR subtype, PREFRAN, found in Prevotella bryantii B14, Prevotella disiens FB035-09AN, Francisella tularensis subsp. novicida, Francisella philomiragia, Butyrivibrio proteoclasticus B316, Helcococcus kunzii ATCC 51366, etc.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes . CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids. CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).
CRISPR-associated endonuclease Cas1, PREFRAN subtype (Cas1_PREFRAN)
Type: Family

Members of this family are the Cas1 endonuclease of a novel CRISPR subtype, PREFRAN, found in Prevotella bryantii B14, Prevotella disiens FB035-09AN, Francisella tularensis subsp. novicida, Francisella philomiragia, Butyrivibrio proteoclasticus B316, Helcococcus kunzii ATCC 51366, etc.

CRISPR (clustered regularly interspaced short palindromic repeat), is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).

Cas1 acts as a dsDNA endonuclease that may be involved in the integration of spacer DNA into the CRISPR cassette.
Beta-propeller repeat, Msarc-type (Beta_prop_Msarc)
Type: Repeat

This entry describes a repeat region found mostly in cell surface proteins of various methanogens. Methanosarcina barkeri, for example, has twenty such proteins, often with either seven or fourteen repeats. These repeats resemble the β-propeller repeats of the TolB periplasmic protein of Gram-negative bacteria, part of a complex associated with various functions including biopolymer transport (see

).
C-S lyase, PatB-like (C-S_lyase_PatB-like)
Type: Family

This entry represents a group of bacterial C-S lyases from a family of pyridoxal phosphate-dependent enzymes, including PatB of Bacillus subtilis and MalY fom Escherichia coli . Other members of this family are: the virulence factor

from Treponema denticola, whose hemolysin activity may stem from H2S production ; and PatB from Staphylococcus hominis, a C-S lyase that is active on aliphatic cysteine-S-conjugates and that releases thioalcohol 3-methyl-3-sulfanylhexan-1-ol from the odourless precursor Cys-Gly-3M3SH secreted from human skin, which is a major contributor to body odour . Some member of this group occur next to examples of the enzyme 5-histidylcysteine sulfoxide synthase, from ovothiol A biosynthesis, and would be expected to perform a C-S cleavage of 5-histidylcysteine sulfoxide to leave 1-methyl-4-mercaptohistidine (ovothiol A) . Others are (mis)annotated as probable aminotransferases.
CRISPR-associated endonuclease Cas12a (Cas12a)
Type: Family

The CRISPR-associated protein Cas12a (Cpf1) possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage . It is emerging as a powerful genome-editing tool .
Putative 7-cyano-7-deazaguanosine (preQ0) biosynthesis protein QueE (rSAM_QueE_gams)
Type: Family

Members of this radical SAM domain protein family appear to be a form of the queuosine biosynthesis protein QueE. QueE is involved in making preQ0 (7-cyano-7-deazaquanine), a precursor of both the bacterial/eukaryotic modified tRNA base queuosine and the archaeal modified base archaeosine. Members occur in preQ0 operons species that lack members of related protein family

.
Radical SAM/SPASM domain-containing Clo7bot peptide maturase (rSAM_Clo7bot)
Type: Family

In multiple strains of Clostridium botulinum, this single radical SAM domain protein occurs next to a tandem array of seven homologous Cys-rich small peptides (see

). Because this radical SAM enzyme contains the SPASM domain, associated with peptide modification, it is proposed to modify all seven C. botulinum targets, hence the name Clo7bot for this system. Suggested gene symbol is ctpM (Clostridial Tandem Peptide Maturase).
AmmeMemoRadiSam system protein A (AmmeMemoSam_A)
Type: Family

Members of this protein family belong to the same domain family as AMMECR1

, a mammalian protein whose deficit is involved in the association of Alport syndrome, midface hypoplasia, intellectual disability and elliptocytosis in humans . Members of the present family occur as part of a three gene system with a homologue of the mammalian protein Memo (Mediator of ErbB2-driven cell MOtility), and an uncharacterised radical SAM enzyme .
Thiazole/oxazole-forming peptide maturase, SagD family component (TOMM_cyclo_SagD)
Type: Family

Members of this protein family include enzymes related to SagD, previously referred to as a scaffold or docking protein, involved in the biosynthesis of streptolysin S in Streptococcus pyogenes from the protoxin polypeptide (product of the sagA gene). Newer evidence describes an enzymatic activity, an ATP-dependent cyclodehydration reaction, previously ascribed to the SagC component . This protein family serves as a marker for widely distributed prokaryotic systems for making a general class of heterocycle-containing bacteriocins .
Putative 4-mercaptohistidine N1-methyltranferase, OvoA C-terminal domain (OvoA_Cterm)
Type: Domain

Ovothiol A is an N1-methyl-4-mercaptohistidine. Ovothiols are efficient scavengers of radicals and peroxides with possible roles in the redox defense of a number of organisms . An ovothiol biosynthetic enzyme (OvoA) has been identified in Erwinia tasmaniensis and Trypanosoma cruzi, with homologous enzymes encoded in more than 80 genomes ranging from proteobacteria to animalia .

OvoA has 5-histidylcysteine sulfoxide synthase activity. In the absence of S-adenosylmethione, a methyl donor, the intermediate produced is 4-mercaptohistidine. The enzymes of Erwinia tasmaniensis, Trypanosoma cruzi and most homologues share an additional C-terminal methyltransferase domain. Thus OvoA may be a bifunctional enzyme with 5-histidylcysteine sulfoxide synthase and 4-mercaptohistidine N1-methyltranferase activity. This entry describes the C-terminal putative 4-mercaptohistidine N1-methyltranferase domain.
Pseudo-rSAM protein/SPASM domain protein (Pseudo_SAM_Halo)
Type: Family

Members of this family all have a C-terminal SPASM domain (

), a region usually found as a C-terminal second 4Fe-4S domain of radical SAM domain proteins. A majority of rSAM/SPASM proteins modify ribosomally produced peptides. In a few members of this family, the key Cys residues of the radical SAM domain have been lost, making this a pseudo-rSAM family. Members of this family are restricted so far to Haloarchaea, always occur next a member of family

, and are often accompanied by another rSAM/SPASM domain protein. The function of this two or three gene cassette is unknown.
Putative glycosyltransferase (Glycosyltransferase_put)
Type: Family

This putative glycosyltransferase is found in marine bacteria such as Marinobacter and soil bacteria such as Anaeromyxobacter, but does not seem to occur in known pathogenic bacteria.
Conjugal transfer/type IV secretion protein DotA/TraY (DotA_TraY)
Type: Family

Members of this protein family include transfer protein TraY of IncI1 plasmid R64 and DotA (defect in organelle trafficking A) of Legionella pneumophila .
Putative protein phosphatase DevT-like (DevT-like)
Type: Family

DevT (Alr4674) is a putative protein phosphatase from Nostoc PCC 7120 (Anabaena PCC 7120) . DevT mutants form mature heterocysts, but they are unable to fix N(2) and must be supplied with a source of combined nitrogen in order to survive. Anabaena DevT shows homology to phosphatases of the PPP family and displays a Mn(2+)-dependent phosphatase activity. DevT is constitutively expressed in both vegetative cells and heterocysts, and is not regulated by NtcA. The heterocyst regulator HetR may exert a certain inhibition on the expression of devT. Under diazotrophic growth conditions, DevT protein accumulates specifically in mature heterocysts. The role that DevT plays in a late essential step of heterocyst differentiation is still unknown.
Monomeric [FeFe] hydrogenase (Mono_FeFe_hydrog)
Type: Family

This family of iron-only hydrogenases is encoded in a single polypeptide chain, and termed monomeric, including [FeFe] hydrogenases from group B1/B3 .
Type 2 lantibiotic, A2 family (Lant_2_A2)
Type: Family

This entry represents a number of type 2 lantibiotic-type bacteriocins, related to but distinct from the family that includes lichenicidin and mersacidin . Sequence similarity among members consists largely of a 20-residue block of conserved sequence that covers most of the leader peptide region, absent from the mature lantibiotic. This is followed by a region with characteristic composition for lantibiotic precursor regions, rich in Ser and Thr and including a near-invariant Cys near or at the C terminus, involved in cyclization. Members of this family typically are shorter than 70 amino acids.
Putative heme D1 biosynthesis radical SAM protein NirJ2 (rSAM_NirJ2)
Type: Family

Members of this radical SAM protein subfamily, designated NirJ2, occur in genomic contexts with a paralogue NirJ1 and with other nitrite reductase operon genes associated with heme D1 biosynthesis, as in Heliobacillus mobilis and Heliophilum fasciatum. NirJ2 is presumed by bioinformatics analysis to be a heme D1 biosynthesis protein by context.
Type 2 lantibiotic, leader peptide domain (Lantibiotic2_lead_pep_dom)
Type: Domain

This entry represents the leader peptide region of a number of type 2 lantibiotic-type bacteriocins, including mersacidin and lichenicidin. They are often are found as gene pairs encoding two-chain bacteriocins . Maturation is accomplished, at least in part, by a LanM-type enzyme (

).
Glucan-binding repeat (Glucan-bd_rpt)
Type: Repeat

This entry describes a region of about 63 amino acids that is composed of three repeats of a more broadly distributed family of shorter repeats represented by

. While the shorter repeats are often associated with choline binding (and therefore with cell wall binding), the longer repeat described here represents a subgroup of repeat sequences associated with glucan binding, as found in a number glycosylhydrolases. A repeat consensus, WYYFDANGKAVTGAQTINGQTLYFDQDGKQVKG, has been described that corresponds to half of the repeat as modeled here and one and a half copies of the repeat as modeled by

.
ComB, archaeal (ComB_archaeal)
Type: Family

2-phosphosulpholactate phosphatase (ComB;

) is a magnesium-dependent acid phosphatase that catalyzes the second step in coenzyme M (CoM; 2-mercaptoethanesulphonic acid) biosynthesis, namely, the hydrolysis of (2R)-2-phospho-3-sulpholactate to yield (2R)-3-sulpholactate and phosphate. CoM is an essential cofactor that acts as the terminal methyl carrier in methanogenesis . CoM has also a role in the bacterial pathway of aliphatic epoxide carboxylation . Homologues of ComB have been identified in all available cyanobacterial genome sequences and in genomes from phylogenetically diverse bacteria and archaea. However, many of these organisms lack homologues of other CoM biosynthetic genes.

ComB has a complex α/β topology. The monomer is composed of two domains thought to be related by a common ancestral gene, plus a C-terminal helical and β-hairpin region .

This entry represents ComB, archaeal type.
Kinesin-like protein (Kinesin-like_fam)
Type: Family

This entry includes kinesin heavy chain and kinesin-like proteins, which are members of the kinesin superfamily (also known as KIFs). KIFs constitute 15 kinesin families . They are important molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs .

Kinesin is a microtubule-associated force-producing protein that play a role in organelle transport. The kinesin motor activity is directed toward the microtubule's plus end. Kinesin is an oligomeric complex composed of two heavy chains and two light chains. The maintenance of the quaternary structure does not require interchain disulphide bonds.
Formin-like family, plant (Formin-like_plant)
Type: Family

Formins (formin homology proteins) proteins play a crucial role in the reorganisation of the actin cytoskeleton and associate with the fast-growing end (barbed end) of actin filaments . This entry represents the formin homologues from plants. Seed plants have two formin clades with numerous paralogues . They can be classified as class I and class II formins. Class I formins includes a N-terminal membrane insertion signal, a predicted extracytoplasmic Pro-rich stretch, a transmembrane region, and C-terminal FH1 and FH2 domains . Though class II formins usually contain a N-terminal PTEN domain related to the human PTEN protein (implied in pathogenesis of the Parkinson disease) , the N-termini of type-II plant formins do not contain any recognisable domain that can provide a clue to their biological function.
Pre-mRNA-processing-splicing factor 8 (PRP8)
Type: Family

Pre-mRNA-processing-splicing factor 8 (Prp8) is a central component of the spliceosome, which may play a role in aligning the pre-mRNA 5'- and 3'-exons for ligation. It interacts with U5 snRNA, and with pre-mRNA 5'-splice sites in B spliceosomes and 3'-splice sites in C spliceosomes. It is part of the U5 snRNP complex, and of U5.4/6 and U5.U4atac/U6atac snRNP complexes in U2- and U12-dependent spliceosomes, respectively. It is also found in a mRNA splicing-dependent exon junction complex (EJC) with SRRM1 where it interacts with U5 snRNP proteins SNRP116 and WDR57/SPF38 .

Mutations of human Prp8 cause retinitis pigmentosa 13, a retinal dystrophy belonging to the group of pigmentary retinopathies .
Beta-sarcoglycan (Sgcb)
Type: Family

Beta-sarcoglycan is a component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix .

The sarcoglycan (SG) complex consists of four subunits, the transmembrane proteins sarcoglycan alpha, beta gamma and delta. Defects in the subunits of the SG complex are responsible for several muscular dystrophies .
P2Y purinoceptor 8 (P2Y8_rcpt)
Type: Family

This entry represents the P2Y8 receptor. It was originally identified in Xenopus and found to be activated equipotently by all naturally occurring nucleoside triphosphates (ATP, CTP, GTP, ITP and UTP) but not by inorganic polyphosphates .

P2RY8 is a G protein-coupled receptor for S-geranylgeranyl-glutathione (GGG), an endogenous metabolite present in lymphoid tissues. It couples the binding of GGG to the activation of GNA13 and downstream repression of AKT activation in lymphocytes defining their positioning and growth within lymphoid organs . In lymphoid follicles, confines B cells and follicular helper T cells in germinal centers (GCs) in response to GGG local gradients established by GGT5 (via GGG catabolism) and ABCC1 (via extracellular transport) with lower concentrations of GGG found in the follicular dendritic cell network region around which germinal centers are formed . In the bone marrow, also in response to GGG gradients established by GGT5 and ABCC1, it restricts chemotactic transmigration of B cells, T cells and NK cells from blood vessels to the bone marrow parenchyma .

There are three distinct families of extracellular receptors for purine and pyrimidine nucleotides , known as P1, P2X and P2Y purinoceptors . These receptors induce a wide variety of biological effects and are involved in many different cellular functions . P2X receptors are ligand-gated ion channels, whereas P1 and P2Y receptors are rhodopsin-like G protein-coupled receptors . The families also differ by their method of activation: P1 receptors are preferentially activated by adenosine , P2X via ATP , whereas the P2Y receptors, in addition to being activated by ATP, are activated by different adenine and/or uridine nucleoside di- and triphosphates (ADP, UDP, UTP, UDP and UDP-glucose) .

The P2Y purinoceptors currently consist of eleven subtypes: P2Y1, P2Y2, P2Y3 P2Y4, P2Y6, P2Y8, P2Y10, P2Y11, P2Y12, P2Y13 and P2Y14 . P2Y3 has, as yet, only been found in birds , whilst the rest have been cloned in humans. The gaps in P2Y receptor numbering are due to the reclassification of some receptors that were initially associated with to the P2Y family. These include P2Y5 (now known as lysophosphatidic acid receptor 6), P2Y7 (now leukotriene B4 receptor) and P2Y9 (lysophosphatidic acid receptor 4) .
P2Y purinoceptor 11 (P2Y11_rcpt)
Type: Family

There are three distinct families of extracellular receptors for purine and pyrimidine nucleotides , known as P1, P2X and P2Y purinoceptors . These receptors induce a wide variety of biological effects and are involved in many different cellular functions . P2X receptors are ligand-gated ion channels, whereas P1 and P2Y receptors are rhodopsin-like G protein-coupled receptors . The families also differ by their method of activation: P1 receptors are preferentially activated by adenosine , P2X via ATP , whereas the P2Y receptors, in addition to being activated by ATP, are activated by different adenine and/or uridine nucleoside di- and triphosphates (ADP, UDP, UTP, UDP and UDP-glucose) .

The P2Y purinoceptors currently consist of eleven subtypes: P2Y1, P2Y2, P2Y3 P2Y4, P2Y6, P2Y8, P2Y10, P2Y11, P2Y12, P2Y13 and P2Y14 . P2Y3 has, as yet, only been found in birds , whilst the rest have been cloned in humans. The gaps in P2Y receptor numbering are due to the reclassification of some receptors that were initially associated with to the P2Y family. These include P2Y5 (now known as lysophosphatidic acid receptor 6), P2Y7 (now leukotriene B4 receptor) and P2Y9 (lysophosphatidic acid receptor 4) .

This entry represents the P2Y11 receptor, which is the only P2Y receptor that is selective for ATP. It is not activated by UTP or UDP . It couples to both Gs and Gq/11 and activates the phospholipase C and adenylate cyclase signalling cascades.
I-BAR domain containing protein IRSp53/IRTKS/Pinkbar (IRSp53/IRTKS/Pinkbar)
Type: Family

This entry represents a group of I-BAR (Bin/amphipysin/Rvs) domain containing proteins, including IRSp53, IRTKS, Pinkbar. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. The BAR domain containing proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature . Proteins in this family also contain an additional C-terminal SH3 domain.
Tubulin-specific chaperone C (TBCC)
Type: Family

The tubulin heterodimer consists of one alpha- and one beta-tubulin polypeptide. In humans, five tubulin-specific chaperones termed TBCA/B/C/D/E are essential for bring the alpha- and beta-tubulin subunits together into a tightly associated heterodimer. Following the generation of quasi-native beta- and alpha-tubulin polypeptides (via multiple rounds of ATP-dependent interaction with the cytosolic chaperonin), TBCA and TBCB bind to and stabilise newly synthesised beta- and alpha-tubulin, respectively. The exchange of beta-tubulin between TBCA and TBCD, and of alpha-tubulin between TBCB and TBCE, resulting in the formation of TBCD/beta and TBCE/alpha. These two complexes then interact with each other and form a supercomplex (TBCE/alpha/TBCD/beta). Interaction of the supercomplex with TBCC causes the disassembly of the supercomplex and the release of E-site GDP-bound alpha/beta tubulin heterodimer, which becomes polymerization competent following spontaneous exchange with GTP .

This entry represents tubulin-specific chaperone C (TBCC, also known as tubulin-folding cofactor C), which is involved in the final step of the tubulin folding pathway . In Arabidopsis thaliana, it is required for continuous microtubule cytoskeleton organisation, mitotic division, cytokinesis, and to couple cell cycle progression to cell division in embryos and endosperms .
Syncoilin (Syncoilin)
Type: Family

Syncoilin belongs to the intermediate filament family and is highly expressed in skeletal and cardiac muscle . It co-localises with alpha-dystrobrevin (DTNA) and desmin (DES). The dysfunction or absence of syncoilin may result in the disruption of the intermediate filament network, leading to muscle necrosis .
Flotillin family (Flotillin_fam)
Type: Family

Flotillin proteins are membrane-bound chaperones that localize to lipid rafts, where they may recruit the proteins that need to be localized in lipid rafts to be active and facilitate their interaction and oligomerization. Proteins in this entry include flotillin-1 (also known as reggie-2), flotillin-2 (also known as reggie-1) and their homologues. Flotillin-1 and flotillin-2 associate with membrane microdomains known as rafts . They play a role in various cellular processes such as insulin signaling, T cell activation, membrane trafficking, phagocytosis, and epidermal growth factor receptor signaling .

This entry also include bacterial homologues of Flotillin-1. These bacterial proteins are found in membrane microdomains that may be equivalent to eukaryotic membrane rafts . Similarly to eukaryotic flotillin proteins, flotillins in bacteria play an essential role in organizing and maintaining the correct architecture of the functional membrane microdomains .