SII-SWORD/CoKE huggingface dataset:
Sactipeptide maturase StsB (Sacti_mat_StsB)
Type: Family

Members of this family are radical SAM/SPASM enzymes that modify RiPP precursor peptides to introduce sulfur-to-alpha-carbon amino acid side chain crosslinks. Peptides modified in this way are often called sactipeptides, therefore, this family of proteins has been called radical SAM/SPASM domain sactipeptide maturase StsB based on the protein from Streptomyces sparsogenes. The enzyme crosslinks Cys residues to Gly residues in antiparallel peptide chain motifs of CxCxC to GxGxG in StsA, and CxC to GxG in related peptides . StsB shares higher full-length similarity with MftC (mycofactocin biosynthesis) than any other characterised enzyme. However, a comparative analysis of StsB to known rSAM proteins predicted that StsB would be distinct from MftC and instead form sactionine bonds .
Methanobactin export MATE transporter MbnM (Export_MbnM)
Type: Family

Members of this family of MATE type efflux transporter occur in methanobactin biosynthesis loci and are presumed to function in the export of methanobactin, a siderophore analog that is synthesized, exported so that it can bind copper ion with high affinity, and then reimported .
Methanobactin biosynthesis FAD monooxygenase MbnF (FAD_mono_MbnF)
Type: Family

This entry represents the methanobactin biosynthesis FAD monooxygenase MbnF, an NADPH-dependent flavin monooxygenase from Methylocystis sp. (

, ). Methanobactins (MBs) are ribosomally produced and post-translationally modified peptides (RiPPs) that are used by methanotrophs for copper acquisition. MbnF preferentially oxidises NADPH over NADH, supporting NAD(P)H-mediated flavin reduction, which is the initial step in the reaction cycle of several type A FMO enzymes. It is also shown that MbnF binds the precursor peptide for MB .
Gamma-glutamylputrescine synthetase (GGputSyn)
Type: Family

This family includes Gamma-glutamylputrescine synthetase from Haloferax mediterranei and related sequences from halobacteria. It is involved in the breakdown of putrescine via the biosynthesis of gamma-L-glutamylputrescine. It is not required for glutamine synthesis and it is not able to compensate for the loss of glutamine synthetase .
Type IV CRISPR-associated endonuclease Csf5 (Cas6_csf5)
Type: Family

This entry represents the type IV CRISPR-associated endonuclease Csf5 from Aromatoleum aromaticum (

) and similar bacterial sequences . Csf5 generates CRISPR RNAs (crRNAs) that are specifically incorporated into type IV CRISPR-ribonucleoprotein (crRNP) complexes.
ATP-dependent glucokinase, pyrobaculum-type (GK_pyrobaculum-type)
Type: Family

This small family of proteins includes glucokinase (also known as Pcal_1032) from Pyrobaculum calidifontis and related sequences from Thermoproteaceae. These proteins belong to the ROK family of sugar kinases and catalyse the phosphorylation of D-glucose to D-glucose 6-phosphate using ATP as the phosphate donor. It has a broad hexose specificity, and in addition to glucose, which shows the highest catalytic efficiency, it can also phosphorylate fructose, mannose, galactose and sorbitol. It can also use CTP, GTP or UTP as phosphoryl donor .
Sactipeptide RiPP StsA (StsA_sacti_RiPP)
Type: Family

Members of this small family are encoded next to the radical SAM enzyme StsB, and are average about 40 amino acids in length. Maturation involves the introduction of three sulfur-to-alpha carbon thioether (sactionine) crosslinks, from the Cys residues in the motif CxCxC to glycines in a nearby motif GxGxG that runs antiparallel in a hairpin structure .
Putative four-helix membrane protein (Four_helix_put)
Type: Family

This entry represents a group of uncharacterised proteins from Acinetobacter that are predicted to show four α-helices, the first of which is likely to be a signal peptide.
4-aminobenzoate N-oxygenase AurF (Diiron_AurF)
Type: Family

This entry represents 4-aminobenzoate N-oxygenase from Streptomyces thioluteus (AurF) are similar proteins. AurF is a di-iron oxygenase encoded in a polyketide synthase-type biosynthetic gene cluster that produce aureothin. It is a 4-aminobenzoate N-oxygenase (

) enzyme . This family is specific to Streptomyces.
Sterol transporter outer membrane protein BstC (BstC)
Type: Family

This entry represents a group of proteins from Methylococcales, including BstC from Methylococcus capsulatus (

). BstC has a predominantly hydrophilic exterior surface and shows four helical hairpins that resemble tetratricopeptide repeat (TPR) motifs .
Hydrolase HsaD (HsaD)
Type: Family

This entry represents 4,5:9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate hydrolasefrom	Mycobacterium tuberculosis (HsaD) and related proteins from actinomycetes. HsaD catalyses the hydrolysis of a carbon-carbon bond in 4,5: 9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oate to yield 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate (DOHNAA) and 2-hydroxy-hexa-2,4-dienoate. This enzyme has been implicated in the intracellular survival of the pathogen . This enzyme adopts α/β hydrolase fold
Lipid A 4'-phosphatase (LpxF)
Type: Family

This entry represents the Lipid A 4'-phosphatase from Francisella tularensis (LpxF) and related proteins. This enzyme removes the 4'-phosphate moiety from the tetraacylated precursor of lipid A and from pentaacylated lipid A, but not from hexaacylated lipid A which is found in E.coli. Its expression in E.coli confers resistance to the cationic antimicrobial peptide polymyxin B . It plays a critical role in the ability of the bacteria to avoid the host innate immune system .
Beta-carotene hydroxylase CrtR-like (CrtR-like)
Type: Family

This entry represents a group of proteins from cyanobacteria, including Beta-carotene hydroxylase from Synechocystis sp. (CrtR,

), which is involved both in zeaxanthin and myxoxanthophyll synthesis .
Beta-carotene ketolase CrtO-like (CrtO-like)
Type: Family

This entry represents a group of proteins from cyanobacteria, including Beta-carotene ketolase CrtO (all3744,

) from Anabaena sp. (Nostoc), which catalyse the conversion of beta-carotene to echinenone . This protein is not required for normal growth under standard or high light conditions .
Iron-dependent extradiol dioxygenase (HsaC)
Type: Family

This entry represents Iron-dependent extradiol dioxygenase from Mycobacterium tuberculosis (HsaC). and similar sequences specific to actinomycetes. This enzyme catalyses the meta-cleavage of 3,4-dihydroxy-9,10-seconandrost-1,3,5(10)-triene-9,17-dione to produce 4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-diene-4-oic acid. It plays a role in cholesterol catabolism which is central to the unusual ability to survive in macrophages .
Beta-carotene ketolase CrtW-like (CrtW-like)
Type: Family

This entry represents a group of proteins from cyanobacteria that contain the fatty acid desaturase domain (

), including beta-carotene ketolase CrtW (alr3189,

) from Nostoc, which catalyses the conversion of myxol 2'-fucoside to ketomyxol 2'-fucosid .
Flavin-dependent monooxygenase, reductase subunit HsaB (HsaB)
Type: Family

This entry represents Flavin-dependent monooxygenase, reductase subunit, known as HsaB. HsaB catalyses the reduction of free flavins (FMN or FAD) by NADH. Subsequently, the reduced flavins diffuse to the HsaA oxygenase subunit . Members of this family are found exclusively in Actinomycetes.
2'-O-glycosyltransferase CruG-like (CruG-like)
Type: Family

This entry represents a group of proteins from cyanobacteria, including 2'-O-glycosyltransferase CruG (

) from Picosynechococcus sp. .
Gamma-carotene 1'-hydroxylase CruF-like, cyanobacteria (CruF-like_cyanobact)
Type: Family

This entry represents a group of proteins from cyanobacteria, including Gamma-carotene 1'-hydroxylase CruF (

) from Picosynechococcus sp. .
RCKP-type rubredoxin-like (Rubredox_RCKP)
Type: Family

This entry represents a group of bacterial uncharacterised sequences that contain a variant form of rubredoxin-like proteins that often covers its full-length, about 35 amino acids long. Of the five distinctive highly conserved Cys residues, the first two and last two are shared with typical rubredoxin-like domains, but the central Cys, in a well-conserved Arg-Cys-Lys-Pro, is distinctive.
GSU3473-like (GSU3473-like)
Type: Family

This entry represents the uncharacterised protein GSU3473 from Geobacter sulfurreducens (

) and similar sequences mainly from Thermodesulfobacteriota. Members of this family average about 70 amino acids in length. The function is unknown.
Two-CW domain (Two-CW_dom)
Type: Domain

The two-CW domain is a bacterial domain of up to 81-residues in its long form that shows strongly conserved motifs with six invariant Cys residues. A shorter form exists, with gaps at both sides of the motifs, that includes the third invariant Cys. The domain is named for CW dipeptides in the two strongest motifs, the N-terminal NCWEWxxCGREP and the central GRxCW. The domain may comprise the full length of a protein, or it may appear in much longer proteins. The function is unknown.
CD1247-like, N-terminal domain (CD1247_N)
Type: Domain

This entry represents the N-terminal domain of CD1247 from Clostridioides difficile (

) and similar proteins from in Gram-positive anaerobes. Most members share a C-terminal region with two CxxC motifs likely to have zinc-binding activity.
Lipid acquisition surface protein MG075-like (MG075-like)
Type: Family

This entry represents the uncharacterised protein MG075 homolog from Mycoplasma pneumoniae (MPN_213) and similar sequences from Mycoplasmatota. MG075, named P116, is an essential surface protein, shown to form a homodimer with a large hydrophobic cavity, and to play a role in obtaining lipids such as phosphatidylcholine, sphingomyelin, and cholesterol .
DNA polymerase I, 3'-5' exonuclease domain (DNA_polI_exonuclease)
Type: Domain

This entry represents a domain found in DNA polymerase I from Geobacillus stearothermophilus and similar sequences mainly from actinomycetes and firmicutes. In addition to polymerase activity, this enzyme has strand displacement and 5'-3' exonuclease activity, but lacks proofreading 3'-5' exonuclease activity . This domain is responsible for the 3'-5' exonuclease proofreading activity. It is one of the constituent domains of the Klenow fragment.
2-isopropylmalate synthase/homocitrate synthase, post-catalytic domain (LeuA/HCS_post-cat)
Type: Domain

This entry represents a domain found centrally in 2-isopropylmalate synthase from Neisseria meningitidis (LeuA) , homocitrate synthase from Sulfolobus acidocaldarius (HCS) and similar proteins found in all cellular organisms. This domain follows the catalytic domain and is required for the enzymatic activity.
2-isopropylmalate synthase-like, post-catalytic domain (LeuA-like_post-cat)
Type: Domain

This entry represents a domain found in 2-isopropylmalate synthase from Mycobacterium tuberculosis (LeuA, also known as alpha-isopropylmalate synthase, IPMS) and similar sequences from bacteria and fungi. LeuA catalyses the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (alpha-ketoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate) . This domain follows the catalytic domain and is required for the enzymatic activity .
Sensor histidine protein kinase/phosphatase WalK-like, HAMP domain (WalK-like_HAMP)
Type: Domain

This domain is found at the N-terminal of sensor histidine protein kinase/phosphatase WalK from Streptococcus pneumoniae, the histidine kinase SMU_1516 from Streptococcus mutans (CovS,

) and similar proteins mainly found in Lactobacillales.

WalK functions as a sensor protein kinase which is autophosphorylated at a histidine residue and transfers its phosphate group to WalR , the other member of the two-component regulatory system WalK/WalR that regulates genes involved in cell wall metabolism. CovS plays a role in the regulation of acid production and tolerance conducive to dental caries, including proton expulsion. This protein has one transmembrane domain before a HAMP signal transducer domain (this entry), a PAS sensor domain (

), a DHp domain (

) and a CA domain (

). This domain shows two α-helices that form a parallel four-helical coiled-coil when the protein dimerises .
E3 ubiquitin-protein ligase parkin-like, IBR domain (Parkin-like_IBR)
Type: Domain

This entry represents an IBR (In Between Ring fingers) domain found in human E3 ubiquitin-protein ligase parkin and similar eukaryotic proteins. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalysing the covalent attachment of ubiquitin moieties onto substrate protein . This domain occurs between pair of ring fingers.
Pierisin-like domain (Pierisin-like_dom)
Type: Domain

This entry represents a domain found in a group of ADP-ribosyltransferases from bacteria and eukaryota, including Pierisin from the butterfly Pieris rapae and the smaller protein scabin (

), a novel DNA-targeting enzyme from the plant pathogen Streptomyces scabiei .
GTP-eEF1A, C-terminal domain (GTP-eEF1A_C)
Type: Domain

This entry represents a β-barrel domain that is found C-terminal in Elongation factor 1-alpha (eEF1A) and similar proteins from all cellular organisms. eEF1A promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis .
Nuclear pore complex interacting protein, N-terminal (NPIP_N)
Type: Domain

This entry includes a series of nuclear pore complex-interacting protein (NPIP) sequences from vertebrates. This entry represents helical segments that in some members constitute almost the full length of the sequence, while in others they are found at the N-terminal. In those cases, they are associated to a β-solenoid repeat (

).

NPIP are not considered one of the core structural nucleoporins that form the main scaffold of the nuclear pore complex (NPC), but it is classified as a nucleoporin-associated protein. This family is well conserved from African apes to humans .
Radical SAM (seleno)protein TrsS (rSAM_Se_TrsS)
Type: Family

This family represents TrsS (Third Radical SAM Selenoprotein) which joins two others radical SAM enzyme families of selenocysteine-containing family members. The other two are the arsenosugar biosynthesis radical SAM protein ArsS (

) and the CUAEP/CCAEP-tail radical SAM protein family. In all three cases, the Sec residue occurs where the Cys normally present is part of a novel motif, not the signature [4Fe-4S]-binding signature motif near the N-terminal of the radical SAM domain described

. TrsS shows its greatest sequence similarity, among characterised radical SAM proteins, to the molybdopterin cofactor biosynthesis protein MoaA, as found either in bacteria (

) or archaea (

), but is actually quite different, with novel additional domains both N-terminal and C-terminal to the shared radical SAM domain. Even so, TrsS may play a related role in the maturation of a molybdopterin (MPT) required by the molybdopterin-dependent aldehyde oxidoreductase that is nearly always found encoded nearby.
CUAEP/CCAEP-tail radical SAM protein (rSAM_CUAEP)
Type: Family

Members of this family are radical SAM enzymes with an N-terminal apparent B12-binding domain. Some members of the family have Cys-Cys motif about 10 amino acids before the C-terminal, but the majority of the family are selenoproteins with the second Cys replaced by selenocysteine, in a strongly conserved motif W[YF]C[CU]AEP. The proximity of the selenocysteine-encoding TGA codon to the C-terminal may have impeded recognition of this novel family of selenoproteins.
Methanethiol S-methyltransferase (MddA)
Type: Family

This family includes methanethiol S-methyltransferases which catalyse the methylation of methanethiol (MeSH) to yield dimethylsulphide (DMS) .
DVU0298-like (DVU0298-like)
Type: Family

Members of this family occur primarily in sulfate-reducing bacteria. They contain a HEAT repeat-region. DVU0298 (

) was identified as candidate protein for involvement in carbon monoxide utilization as an electron donor during sulfate reduction .
Molybdopterin-dependent aldehyde oxidoreductase-related (Mop-rel)
Type: Family

This entry represents a family of bacterial proteins that occur regularly in the context of a molybdopterin-dependent aldehyde oxidoreductase (

). The N-terminal 200 amino acids are homologous to the molybdenum cofactor cytidylyltransferase MocA of Escherichia coli. The C-terminal 170 amino acid region contains an HDIG (or HD superfamily) phosphohydrolase-like domain. This family is likely to be involved biosynthesis of the molybdopterin cofactor used by the aldehyde oxidoreductase.
L-lactate dehydrogenase (quinone) large subunit LdhH-like (Quin_L_LdhH-like)
Type: Family

Members of this family, such as founding protein DVU3033 (

) from Desulfovibrio vulgaris Hildenborough, contain an N-terminal lactate utilization (LUD) domain (

) as found in lactate utilisation proteins LutB and LutC in Bacillus subtilis, but also a C-terminal GlpC-like domain . This enzyme differs from both NAD-dependent and cytochrome-dependent L-lactate dehydrogenases.
Molybdopterin-dependent aldehyde oxidoreductase (Mop)
Type: Family

Members of this family are molybdopterin-dependent enzymes that perform oxidative hydroxylation of aldehydes. Members are encoded in an eight-gene context that includes a radical SAM enzyme we designate TrsS, as it is the Third Radical SAM (Seleno)protein family discovered to have at least some members encoded with a selenocysteine (Sec, U) replacing an otherwise conserved Cys residue .
Methyltransferase double-selenoprotein MduS (MT_CxxU_and_UXX)
Type: Family

This entry represents a group of proteins from Thermodesulfobacteriota with an N-terminal SAM-dependent methyltransferase domain with two selenocysteine (U)-containing motifs in the C-terminal region, typically CDPU about 70 amino acids from the C-terminal, and UGX as the last three amino acids. The name MduS derives from the description 'Methyltransferase and Double U-containing region Selenoprotein'.
2,6-dihydroxypyridine 3-monooxygenase, substrate binding domain-like (DhpH_subs-bd)
Type: Domain

This domain is found in a number of FAD-binding enzymes from bacteria and eukaryotes including 2,6-dihydroxypyridine 3-monooxygenase from Paenarthrobacter nicotinovorans (DhpH), which catalyses the conversion of 2,6-dihydroxypyridine into 2,3,6-trihydroxypyridine in the nicotine degradation pathway . This protein is organised into three domains: an N-terminal FAD binding domain (

), an all-antiparallel β-sheet domain harbouring the substrate-binding site (represented by this entry) and a third forming connections between these domains .
Poly(A) RNA polymerase, mitochondrial-like, central palm domain (MTPAP-like_central)
Type: Domain

This domain is found centrally in human Poly(A) RNA polymerase, mitochondrial (MTPAP) and similar proteins from eukaryotes. MTPAP is a noncanonical polymerase that creates the 3' poly(A) tail of mitochondrial transcripts. It plays a role in the replication-dependent histone mRNA degradation. MTPAP may be involved in the terminal uridylation of mature histone mRNAs before their degradation is initiated and might be responsible for the creation of some UAA stop codons which are not encoded in mtDNA . This protein contains three domains: a N-terminal domain RL (

) and the canonical palm (represented by this entry) and fingers domains. This domain shows a five-stranded β-sheet with the three catalytic aspartic acid residues located on its surface , together with several α-helices, forming an α-β configuration.
Cilia- and flagella-associated protein 107 (CFAP107)
Type: Family

This family includes cilia and flagella associated protein 107 (CFAP107, also known as C1orf158 in human) and its homologues. CFAP107 is a microtubule inner protein (MIP) part of the doublet microtubules (DMTs) in cilia and sperm axoneme. CFAP107 belongs to the core MIPs and binds to protofilaments A10-A11 of the sperm DMTs .
Trichothecene 3-O-acetyltransferase-like, N-terminal (Tri101-like_N)
Type: Domain

This entry represents the N-terminal domain of trichothecene 3-O-acetyltransferase from Gibberella zeae (Tri101,

) and similar fungal sequences. Some members of this entry consist of N- and C-terminal domains arranged in a doughnut-form. The active site lies in the doughnut-hole formed by the interface between these domains .
eIF3a, PCI domain, TPR-like region (eIF3a_PCI_TPR-like)
Type: Domain

This entry represents the TPR-like region of the PCI domain of the Eukaryotic translation initiation factor 3 subunit A from Saccharomyces cerevisiae (eIF3a) and similar eukaryotic sequences. eIF3a is the RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome, and specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation . This region folds into flatly arranged helical repeats .
CRISPR-associated nuclease/helicase Cas3 domain (Cas3-like_dom)
Type: Domain

This entry represents a domain of CRISPR-associated nuclease/helicase Cas3 subtype I-F/YPEST from Pseudomonas aeruginosa (Cas3) and similar prokaryotic sequences. Cas3 is a DNA-degradation enzyme that forms part of the CRISPR-Cas bacterial immune system. Cas3 contains a Cas2 domain, an HD nuclease domain (

), RecA1, RecA2, a long linker region, and a C-terminal domain (this entry). This domain contains two α-helices and two six-stranded β-blades .
GMIP/FCHO2-like, FCH domain (GMIP/FCHO2-like_FCH)
Type: Domain

This entry represents the FCH (FER-CIP4 homology) domain (part of the F-BAR domain) found at the N-terminal of GEM-interacting protein from humans (GMIP) and F-BAR domain only proteins 1 and 2 (FCHO1/2) . This domain is also found in Rho GTPase-activating protein 29 and 45. This domain mediates dimerisation and acts as a membrane recruitment module that affects membrane curvature .

GMIP interacts with Gem, a Ras-related protein, through its N-terminal half and stimulates the GTPase activity of RhoA through its C-terminal domain (

).
GPR158/179, extracellular domain (GPR158_179_extracellular)
Type: Domain

This entry represents the extracellular domain of GPR158 (also known as metabotropic glycine receptor, mGlyR), GRP179 and similar animal sequences. GPR158 is a metabotropic receptor for glycine that controls synapse formation and function in the brain . It functions in cognition, stress-induced mood control, and synaptic development. GRP179 is an orphan receptor involved in vision that is required for signal transduction through retinal depolarizing bipolar cells .

This domain has a Cache-like fold which participates in ligand recognition and also mediates dimerisation and stability of the dimer .
Digeranylgeranylglycerophospholipid reductase, catalytic domain (GGR_cat)
Type: Domain

This entry represents the catalytic domain of a group of geranylgeranyl reductases (GGR) mainly found in prokaryotes, including Digeranylgeranylglycerophospholipid reductase from from Sulfolobus acidocaldarius . This domain contains the PxxYxWxFP sequence motif, which defines a specificity pocket in the structure, providing a structural basis for the substrate specificity of GGRs .
Soluble Rieske-type ferredoxin domain (Sol_Rieske_ferrdox_dom)
Type: Domain

This entry represents a Rieske-type ferredoxin domain from soluble animal, plant and fungi sequences, referred to as MRF and HRF for the mouse and human proteins, respectively, whose function is not yet known .
Internalin J, immunoglobulin-like domain (InlJ_Ig-like)
Type: Domain

This entry represents an immunoglobulin-like domain present in the Internalin J (InlJ) protein from Listeria monocytogenes . Members of this group are mainly found in Listeria species.
YhfS-like, C-terminal domain (YhfS-like_C)
Type: Domain

This entry represents the C-terminal domain of the uncharacterised protein YhfS from E.coli and similar bacterial sequences. This is an α/β domain commonly found in PLP-dependent enzymes.