SII-SWORD/CoKE huggingface dataset:
GYF domain 2 (GYF_2)
Type: Domain

This domain is found in bacteria, archaea and eukaryotes, and is approximately 50 amino acids in length. It contains an evolutionary conserved signature W-X-Y-X6-11-GPF-X4-M-X2-W-X3-GYF, the site of interaction with proline-rich peptides. Proteins containing this domain include RME-8 (Required for receptor-mediated endocytosis 8), a DNAJC13 protein. RME-8 was first identified as a protein that is required for endocytosis in Caenorhabditis elegans. It coordinates the activity of the WASH complex with the function of the retromer SNX dimer to control endosomal tubulation .
Domain of unknown function DUF4340 (DUF4340)
Type: Domain

This domain is found in the uncharacterised protein TP_0878 from Treponema pallidum; its function is not yet known.
Domain of unknown function DUF4342 (DUF4342)
Type: Domain

This function of this domain is not known. There is a single completely conserved residue P that may be functionally important.
ATP-grasp domain, R2K clade family 3 (R2K_3)
Type: Domain

Proteins containing this domain are a group of ATP-grasp enzymes belonging to the R2K clade, wherein one of the absolutely-conserved lysine residues has migrated to the RAGYNA domain which is a part of the core ATP-grasp module. This family is predicted to catalyse peptide ligation reactions on protein substrates in biological conflict contexts, probably between bacteriophages and their hosts .
Putative metallopeptidase (DUF4344)
Type: Family

This family of proteins is found in bacteria and archaea. Proteins in this family are typically between 247 and 291 amino acids in length. There is a conserved EED sequence motif. This is a putative metallopeptidase.
Domain of unknown function DUF4349 (DUF4349)
Type: Domain

This domain is functionally uncharacterised. There is a single completely conserved residue D that may be functionally important.
Domain of unknown function DUF4350 (DUF4350)
Type: Domain

This domain of unknown function is found in bacterial proteins, including the uncharacterised membrane protein Rv3691 from Mycobacterium tuberculosis, and in some archaeal sequences.
Putative component of 'biosynthetic module' (YceG_bac)
Type: Domain

This is a domain found 2-3 times in the YceG family of bacterial proteins. YceG is an additional gene-product encoded in the Ter operon and might thus be part of a 'biosynthetic module' encoding certain enzymes .
Protein of unknown function DUF4358 (DUF4358)
Type: Family

The function of these proteins is not known.
Protein of unknown function DUF4360 (DUF4360)
Type: Family

This family of proteins is functionally uncharacterised. There is a conserved GCP sequence motif near the N terminus.
Alkyldihydroxyacetonephosphate synthase (Alkyl-DHAP_Synthase)
Type: Family

Alkyl-dihydroxyacetonephosphate synthase is a peroxisomal enzyme that plays a key role in the biosynthesis of ether phospholipids .
Acyl-CoA thioesterase 2, C-terminal domain (TesB_C)
Type: Domain

Escherichia coli thioesterase 2 (TesB) adopts a 'double hot dog' configuration. It shows two structural repeats connected by a long loop. There is, however, no sequence similarity between the two halves of the molecule. This entry represents the C-terminal pseudo-domain, which is structurally similar to the recently described beta-hydroxydecanoyl thiol ester dehydrase .
Peroxisome biogenesis factor 2/10 (PEX2/10)
Type: Family

Peroxisome biogenesis factor 2 and 10, also known as peroxin-2/10 are involved in the formation of peroxisomes and matrix protein import. Tey form a retrotranslocation channel together with PEX12, which mediates the export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling . Each subunit contributes transmembrane segments that coassemble into an open channel. PEX2 is also involved in the response to reactive oxygen species (ROS) by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of PNPLA2/ATGL, thereby regulating lipolysis .
Peroxisomal membrane protein 14 (PEX14)
Type: Family

Peroxisomal membrane protein PEX14, or peroxin-14, is a core component of the peroxisomal translocation machinery or importomer . PEX14 is involved in the docking of PEX5-bound protein onto the peroxisomal membrane, and it may be involved in the translocation step into the peroxisome matrix . In addition to its role in protein docking, a role in transcriptional regulation has also been suggested for PEX14 .
RadC-like JAB domain (RadC_JAB)
Type: Domain

This domain is found in a family of proteins present widely across bacteria. This family was named initially with reference to the Escherichia coli radC102 mutation which suggested that RadC was involved in repair of DNA lesions . However, the relevant mutation has subsequently been shown to be in recG, where radC is in fact an allele of recG . In addition, all attempts to characterise a radiation-related function for RadC in Streptococcus pneumoniae failed, suggesting that it is not involved in repair of DNA lesions, in recombination during transformation, in gene conversion, nor in mismatch repair .

The RadC-like domain belongs to the JAB superfamily of metalloproteins . The domain shows fusions to an N-terminal Helix-hairpin-Helix (HhH) domain in most instances. Other domain combinations include fusions to the anti-restriction module ArdC, the DinG/RAD3-like superfamily II helicases and the DNAG-like primase. In some bacteria, closely related DinG/Rad3- like superfamily II helicases are fused to a 3'-5' exonuclease in the same position as the RadC-like JAB domain. These conserved domain associations lead to the hypothesis that the RadC-like JAB domains might function as a nuclease .
Cyclophilin TM1367-like domain (Cyclophilin_TM1367)
Type: Domain

This entry represent a TM1367-type cyclophilin-like domain. The crystal structure of protein TM1367 from Thermotoga maritima revealed an atypical cyclophilin (peptidylprolyl isomerase) fold . The catalytic site found in human cyclophilin is not conserved in this domain, suggesting a different function for this domain .
Tubby-like, C-terminal (Tubby-like_C)
Type: Homologous_superfamily

Tubby, an autosomal recessive mutation, mapping to mouse chromosome 7, was recently found to be the result of a splicing defect in a novel gene with unknown function. This mutation maps to the tub gene . The mouse tubby mutation is the cause of maturity-onset obesity, insulin resistance and sensory deficits. By contrast with the rapid juvenile-onset weight gain seen in diabetes (db) and obese (ob) mice, obesity in tubby mice develops gradually, and strongly resembles the late-onset obesity observed in the human population. Excessive deposition of adipose tissue culminates in a two-fold increase of body weight. Tubby mice also suffer retinal degeneration and neurosensory hearing loss. The tripartite character of the tubby phenotype is highly similar to human obesity syndromes, such as Alstrom and Bardet-Biedl. Although these phenotypes indicate a vital role for tubby proteins, no biochemical function has yet been ascribed to any family member , although it has been suggested that the phenotypic features of tubby mice may be the result of cellular apoptosis triggered by expression of the mutated tub gene. TUB is the founding-member of the tubby-like proteins, the TULPs. TULPs are found in multicellular organisms from both the plant and animal kingdoms. Ablation of members of this protein family cause disease phenotypes that are indicative of their importance in nervous-system function and development .

Mammalian TUB is a hydrophilic protein of ~500 residues. The N-terminal (

) portion of the protein is conserved neither in length nor sequence, but, in TUB, contains the nuclear localisation signal and may have transcriptional-activation activity. The C-terminal 250 residues are highly conserved. The C-terminal extremity contains a cysteine residue that might play an important role in the normal functioning of these proteins. The crystal structure of the C-terminal core domain from mouse tubby has been determined to 1.9A resolution. This domain is arranged as a 12-stranded, all anti-parallel, closed β-barrel that surrounds a central α helix, (which is at the extreme carboxyl terminus of the protein) that forms most of the hydrophobic core. Structural analyses suggest that TULPs constitute a unique family of bipartite transcription factors .

This superfamily represents the tubby C-terminal domain and the structurally related LURP1-like domain.
Cysteine peptidase, histidine active site (Pept_his_AS)
Type: Active_site

The sequences around the three active site residues are well conserved. This entry represents the histidine active site. The catalytic triad consists of this entry,

and

. This catalytic triad detects mainly proteases of the C1 family, including papain and several cathepsins.

Thiol (cysteine) proteases (EC 3.4.22.-) are a family of proteolytic enzymes which contain an active site cysteine. Catalysis proceeds through a thioester intermediate and is facilitated by a nearby histidine side chain; an asparagine completes the essential catalytic triad.

Cysteine peptidases have characteristic molecular topologies, which can be seen not only in their three-dimensional structures, but commonly also in the two-dimensional structures. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related), and further sub-divided into families, on the basis of the architecture of their catalytic dyad (cysteine-histidene) or triad .

Modification of the catalytic triad, especially of its first amino acid (cysteine), has been postulated as a suitable target for a chemical modulation of enzyme function. This is the case for silicateins, where the cysteine residue has been replaced by a serine . Silicateins represent a group of enzymes possessing bi-functional activity; in addition to the silica-condensing activity, they possess a proteolytic (cathepsin-like) activity .
Cysteine peptidase, asparagine active site (Pept_asp_AS)
Type: Active_site

The sequences around the three active site residues are well conserved. This entry represents the asparagine active site. The catalytic triad consists of this entry,

and

. This catalytic triad detects mainly proteases of the C1 family, including papain and several cathepsins.

Thiol (cysteine) proteases (EC 3.4.22.-) are a family of proteolytic enzymes which contain an active site cysteine. Catalysis proceeds through a thioester intermediate and is facilitated by a nearby histidine side chain; an asparagine completes the essential catalytic triad.

Cysteine peptidases have characteristic molecular topologies, which can be seen not only in their three-dimensional structures, but commonly also in the two-dimensional structures. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related), and further sub-divided into families, on the basis of the architecture of their catalytic dyad (cysteine-histidene) or triad .

Modification of the catalytic triad, especially of its first amino acid (cysteine), has been postulated as a suitable target for a chemical modulation of enzyme function. This is the case for silicateins, where the cysteine residue has been replaced by a serine . Silicateins represent a group of enzymes possessing bi-functional activity; in addition to the silica-condensing activity, they possess a proteolytic (cathepsin-like) activity .
Sigma-54 interaction domain, ATP-binding site 1 (Sigma_54_int_dom_ATP-bd_1)
Type: Binding_site

This entry represents a conserved site corresponding to the first ATP-binding motif located in the N-terminal section of the sigma-54 interaction domain.

Some bacterial regulatory proteins activate the expression of genes from promoters recognised by core RNA polymerase associated with the alternative sigma-54 factor. These have a conserved domain of about 230 residues involved in the ATP-dependent interaction with sigma-54. About half of the proteins in which this domain is found (algB, dcdT, flbD, hoxA, hupR1, hydG, ntrC, pgtA and pilR) belong to signal transduction two-component systems and possess a domain that can be phosphorylated by a sensor-kinase protein in their N-terminal section. Almost all of these proteins possess a helix-turn-helix DNA-binding domain in their C-terminal section.

The domain involved in interaction with the sigma-54 factor has an ATPase activity. This may be required to promote a conformational change necessary for the interaction . The domain contains an atypical ATP-binding motif A (P-loop) as well as a form of motif B.
A-kinase anchor protein 28kDa (AKAP_28)
Type: Family

28kDa AKAP (AKAP28) is highly enriched in human airway axonemes. The mRNA for AKAP28 is up-regulated as primary airway cells differentiate and is specifically expressed in tissues containing cilia and/or flagella . Homologs of AKAP28 are present in all animals.
Stage III sporulation protein AC/AD family (Spore_III_AC/AD)
Type: Family

This family consists of several bacterial stage III sporulation protein AC (SpoIIIAC) and SpoIIIAD sequences. The exact function of this family is unknown. SpoIIIAD is an uncharacterised protein which is part of the spoIIIA operon that acts at sporulation stage III as part of a cascade of events leading to endospore formation. The operon is regulated by sigmaG .
Outer membrane protein, beta-barrel domain 2 (Beta-barrel_OMP_2)
Type: Domain

This domain is found in a wide range of outer membrane proteins. This domain assumes a membrane bound β-barrel fold. It is part of a Pfam clan that includes other outer membrane protein β-barrel domains.
SprB repeat (SprB_repeat)
Type: Repeat

This repeat occurs several times in SprB, a cell surface protein involved in gliding motility in the bacterium Flavobacterium johnsoniae .
Transposase DDE domain (Tnp_DDE_dom)
Type: Domain

Transposase proteins are necessary for efficient DNA transposition. This domain is a member of the DDE superfamily, which contains three carboxylate residues that are believed to be responsible for coordinating metal ions needed for catalysis. The catalytic activity of this enzyme involves DNA cleavage at a specific site followed by a strand transfer reaction .
AAA domain (AAA_dom)
Type: Domain

This entry represents a wide variety of AAA domains, including some that have lost essential nucleotide binding residues in the P-loop.
Fox-1 C-terminal domain (Fox-1_C_dom)
Type: Domain

This domain is found in the C-terminal section of Fox-1 and its homologues, which regulate alternative splicing events by binding to 5'-UGCAUGU-3' elements .
Protein of unknown function with HXXEE motif (HXXEE)
Type: Family

This family of proteins contains an HXXEE motif, another conserved histidine and a YXPG motif. Its function is unknown.
Sigma factor regulator C-terminal domain (Sigma_reg_C_dom)
Type: Domain

This entry represents a domain found in the C-terminal region of a number of sigma factor regulator proteins. It may represent a sensory domain .
Protein of unknown function with PCYCGC motif (PCYCGC)
Type: Family

These proteins contain a PCYCGC motif and four other conserved cysteines. Their function is unknown.
Immunity protein Imm6 (Imm6)
Type: Family

This entry represents a predicted immunity protein, with an α+β fold (mostly α helices). The protein is present in polymorphic toxin systems as an immediate gene neighbour of the toxin gene .
Immunity protein Imm5 (Imm5)
Type: Domain

This entry represents a domain found in a predicted immunity protein, with an all-α fold, present in bacterial polymorphic toxin systems as an immediate neighbour of the toxin .
Clr5 domain (Clr5_dom)
Type: Domain

This domain is found at the N terminus of the Clr5 protein, which has been shown to be involved in silencing in fission yeast. This domain has been found to often be associated with proteins that contain ankyrin repeats and large regions of disordered sequence .
OST-HTH associated domain (OST-HTH-assoc_dom)
Type: Domain

This domain often occurs in association with the OST-HTH domain, which is predicted to be involved in RNA-binding .
Immunity protein Imm3 (Imm3)
Type: Family

This entry represents a predicted immunity protein, with a mostly all-alpha fold, present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene .
Immunity protein Imm2 (Imm2)
Type: Family

This entry represents a predicted immunity protein, with a mostly all-alpha fold, present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene .
Double-stranded DNA deaminase immunity protein DddI (DddI)
Type: Family

DddI is an immunity protein component of a toxin-immunity protein module, which functions as a cellular contact-dependent growth inhibition (CDI) system .
Phage phiEco32-like COOH-NH2 ligase-type 2 (COOH-NH2_lig)
Type: Family

This entry represents a family of COOH-NH2 ligases/GCS superfamily found in the neighbourhood of YheC/D-like ATP-grasp and the CotE family of proteins in the firmicutes. Contextual analysis suggests that it might be involved in cell wall modification and spore coat biosynthesis .
CpXC domain (CpXC_dom)
Type: Domain

This presumed domain is functionally uncharacterised. This domain is found in bacterial and archaeal proteins, and is typically between 122 and 134 amino acids in length. It contains four conserved cysteines forming two CpXC motifs.
Protein beta (Protein_beta)
Type: Family

This family includes protein beta from Bacteriophage T4 (

). Protein beta prevents the gop protein (

) from killing the bacterial host cell .
Gliding motility protein SprA N-terminal domain (SprA_N_dom)
Type: Domain

This domain is found repeated three times in the N-terminal half of the gliding motility-related SprA proteins. The role of this domain in motility is uncertain . It is also found in proteins required for secretion .
YoaP-like domain (YoaP-like_dom)
Type: Domain

The YoaP-like domain is found at the C terminus of the Bacillus subtilis YoaP protein (

) and other bacterial and archaeal proteins, and is approximately 40 amino acids in length. There is a single completely conserved residue A that may be functionally important.
Glucosyl transferase II (Glucos_trans_II)
Type: Family

This family includes glucosyl transferase II from the Shigella phage SfII (

), which mediates seroconversion of Shigella flexneri when the phage is integrated into the host chromosome .
C4-type zinc-finger of DNA polymerase delta (Znf-C4pol)
Type: Domain

In fission yeast, this zinc-finger domain appears is the region of Pol3 that binds directly to the B-subunit, Cdc1 . Pol delta is a hetero-tetrameric enzyme comprising four evolutionarily well-conserved proteins: the catalytic subunit Pol3 and three smaller subunits Cdc1, Cdc27 and Cdm1 .
PGDYG protein (PGDYG_prot)
Type: Family

This family of proteins is functionally uncharacterised. Proteins in this family are approximately 150 amino acids in length. There is a conserved PGDYG motif.
Sporulation protein YtrH (Spore_YtrH)
Type: Family

This family of proteins is involved in sporulation. It may contribute to the formation and stability of the thick peptidoglycan layer between the two membranes of the spore, known as the cortex . In Bacillus subtilis its expression is regulated by sigma-E .
Methyltransferase, putative (Methyltransf_put)
Type: Family

The structure of the proteins in this family suggest that they might function as methyltransferases.
GspL periplasmic domain (GspL_pp_dom)
Type: Domain

This domain is the periplasmic domain of the GspL/EpsL family proteins. These proteins are involved in type II secretion systems.
Mechanosensitive ion channel inner membrane domain 1 (MscS_IM_dom1)
Type: Domain

The small mechanosensitive channel, MscS, is a part of the turgor-driven solute efflux system that protects bacteria from lysis in the event of osmotic shock . The MscS protein alone is sufficient to form a functional mechanosensitive channel gated directly by tension in the lipid bilayer. The MscS proteins are heptamers of three transmembrane subunits with seven converging M3 domains , and this domain is one of the inner membrane domains.
Glycine-zipper-containing OmpA-like membrane domain (Gly-zipper_OmpA-like_dom)
Type: Domain

This entry represents a glycine-zipper-containing OmpA-like membrane domain. The domain is found in a number of experimentally uncharacterised transmembrane proteins.
Mitochondrial splicing apparatus component MNE1 (MNE1)
Type: Family

MNE1 is a novel component of the mitochondrial splicing apparatus responsible for the processing of a COX1 group I intron in yeast . Yeast cells lacking MNE1 are deficient in intron splicing in the gene encoding the Cox1 subunit of cytochrome oxidase but do contain wild-type levels of the bc1 complex.
DoxX-like family (DoxX-like)
Type: Family

This family of uncharacterised proteins appear to be related to DoxD (

).
Exosome RNA helicase MTR4-like, beta-barrel domain (Beta-barrel_MTR4)
Type: Domain

This entry represents the β-barrel of MTR4 and related Ski2-like helicases. Ski2 from yeast has an overall similar structure to MTR4 proteins. However, it does not have the KOW motif and it is not included in this entry.

Exosome RNA helicase Mtr4 is a essential RNA helicase, and is an exosome-activating cofactor. It functions together with the nuclear exosome being involved in processing of structured RNAs, including snRNAs and snoRNAs. It also plays a role in nuclear RNA surveillance pathways involving the so-called TRAMP complex . It contains an arch domain, required for proper 5.8S rRNA processing, and appears to function independently of canonical helicase activity . The arch domain comprises an helical stalk/elbow that flanks a KOW module which adopts a β-barrel fold .
CLU domain (CLU_dom)
Type: Domain

The CLU domain (CLUstered mitochondria) is a eukaryotic domain found in highly conserved eukaryotic proteins required for correct mitochondrial dispersal . The exact function of the domain is unknown .
2TM domain (2TM_dom)
Type: Domain

This domain is comprised of two transmembrane α helices that are found associated with a wide range of other domains. This domain may be involved in cell lysis or peptidoglycan turnover.
ABC-2 membrane transporter-like (ABC2_memb-like)
Type: Family

This family is related to the ABC-2 membrane transporter family .
L-lysine 6-monooxygenase/L-ornithine 5-monooxygenase (Lys/Orn_oxygenase)
Type: Family

This is a family of Rossmann fold oxidoreductases that catalyse NADPH-dependent hydroxylation and are involved in siderophore biosynthesis. This family includes L-ornithine 5-monooxygenase, which catalyses the hydroxylation of L-ornithine at the N5 position , and L-lysine 6-monooxygenase, which catalyses the hydroxylation of lysine at the N6 position . This entry also includes Putrescine N-hydroxylase, an homologous of L-ornithine 5-monooxygenase and L-lysine 6-monooxygenase , involved in the biosynthesis of the siderophore putrebactin .
Ubiquitin-conjugating enzyme, E2, family E (UBQ-conjugat_E2_E)
Type: Family

This entry represents the family E of the E2/UBC superfamily of proteins found in diverse bacteria. Analysis of the active site residues suggest that members of this family are inactive as they lack the characteristic catalytic residues of the E2 enzymes . They are usually fused to or in the neighbourhood of a multi/poly ubiquitin domain protein. Other proteins of the ubiquitin modification pathway such as the E1 and JAB proteins are also found in its gene neighbourhood along with a distinct predicted metal-binding protein.
Aliphatic aldoxime/phenylacetaldoxime dehydratase (OXD)
Type: Family

This family includes aldoxime dehydratase (

). This is a haem-containing enzyme, which catalyses the dehydration of aldoximes to their corresponding nitrile . The family also includes phenylacetaldoxime dehydratase (

). This haem-containing enzyme catalyses the dehydration of Z-phenylacetaldoxime to phenylacetonitrile . The enzyme forms an elliptic β barrel, composed of eight β-strands, flanked by α-helices .