SII-SWORD/CoKE huggingface dataset:
Fervidolysin-like, N-terminal prodomain (Fervidolysin-like_N_prodom)
Type: Domain

This entry represents the N-terminal prodomain of Fervidolysin from Fervidobacterium pennivorans, an extracellular subtilisin-like serine protease able to degrade keratin into peptides . This domain folds into a globular α/β structure consisting of four-stranded antiparallel β-sheet and two α-helices packed on one side of it . The prodomain is proteolytically cleaved and removed from the proenzyme. Members of this group are found in bacteria.
Fervidolysin, second beta-sandwich domain (Fervidolysin_SD2)
Type: Domain

This entry represents the C-terminal second β-sandwich domain (SD2) present in Fervidolysin from Fervidobacterium pennivorans, a keratinolytic enzyme that allows this bacterium to grow on native feathers and similar sequences mainly found in Thermotogales. This domain shows a pair of four-stranded β-sheets .
Type IV pilin Tt1219-like, C-terminal (Tt1219-like_C)
Type: Domain

This entry is found at the C-terminal of the type IV pilin Tt1219 from Thermus thermophilus (

) and similar sequences. This protein is likely involved in the formation of polymers that extend from the surface of the bacterial cell and could mediate a wide variety of functions such as adhesion, motility and natural competence. This domain is closely related to type II secretion pseudopilins such as EpsJ, GspJ and XcpW. It consists of the canonical type IV pilin structural core comprising an α-helix packed against a four-stranded β-sheet and a variable lobe comprising a β-sheet that packs the helix on the side .
Type IV pilin Tt1218-like domain (Tt1218-like_dom)
Type: Domain

This entry represents a domain found in Tt1218 from Thermus thermophilus (

) and similar sequences from proteobacteria. Tt1218 is a type IV pilin likely involved in the formation of polymers that extend from the surface of the bacterial cell and could mediate a wide variety of functions such as adhesion, motility and natural competence. This domain is closely related to type II secretion pseudopilin EpsI. It consists of the canonical type IV pilin structural core comprising an α-helix packed against a four-stranded antiparallel β-sheet .
RNA-dependent RNA polymerase, palm domain, ribovirus (RdRp_palm_ribovirus)
Type: Domain

This entry represents the palm domain of RdRp from Riboviruses, such as Thosea asigna virus (TaV), an insect virus that has a positive-sense ssRNA genome encoding a replicase and capsid proteins. The replicase has a non-canonical arrangement in the palm sub-domain of the RNA-dependent RNA polymerase (RdRP), with a sequence permutation where the active site is anchored that is also found in Birnaviridae .
Elongation factor SelB, first winged-helix domain (SelB_WH1)
Type: Domain

This domain is found in Elongation factor SelB from Aquifex aeolicus(

) and similar prokaryotic proteins. SelB is a selenocysteine(Sec)-specific elongation factor that brings the selenocysteinyl-tRNA(Sec) to the ribosome. It consists of three EF-Tu-like domains (D1-3, where

is the first one), followed by four winged-helix domains (WHD1-4). This entry represents the first winged-helix domain (WHD1) .
Elongation factor SelB, second winged-helix domain (SelB_WH2)
Type: Domain

This domain is found in Elongation factor SelB from Aquifex aeolicus (

) and similar prokaryotic proteins. SelB is a selenocysteine(Sec)-specific elongation factor that brings the selenocysteinyl-tRNA(Sec) to the ribosome. It consists of three EF-Tu-like domains (D1-3, where

is the first one), followed by four winged-helix domains (WHD1-4). This entry represents the second winged-helix domain (WHD2) .
Mre11, accessory DNA binding capping domain (Mre11_acc_DNA_cap)
Type: Domain

This entry represents the accessory DNA binding capping domain found in Thermotoga maritima Mre11. Mre11, together with Rad50, form the MR protein complex involved in DNA double-strand break repair . This domain forms the nuclease module with the phosphodiesterase domain at the N-terminal .
Thiaminase I-like, N-terminal domain (Thiaminase_I-like_N)
Type: Domain

This entry represents a domain found at the the N-terminal end of Thiaminase I from the amoeba Naegleria gruberi (

) and similar sequences from lower eukaryotes. This enzyme catalyse the elimination of the thiazole ring moiety from thiamin through substitution of the methylene group. This domain has thiaminase I activity by itself. It consists of a seven-stranded β-sheet surrounded by eight α-helices .
Amylopullulanase, X25 domain (X25_BaPul-like)
Type: Domain

X25 is a domain inserted in X45 domain of Bacillus acidopullulyticus pullulanase. This type of insertion is common in proteins containing X45-X25 pair. X25 domain itself is also found in tandem copies, such as in the highly modular amylopullulanase from Geobacillus stearothermophilus . It is likely that this domain is a carbohydrate-binding domain which targets mixed alpha-1,6/alpha-1,4 linked D-glucan polysaccharides such as pullulan.
ORF239-like (ORF239-like)
Type: Family

This entry represents a family of viral proteins, including ORF239 from Pyrobaculum Spherical Virus (

), which shows an all-α configuration .
BVU_2266-like (BVU_2266-like)
Type: Family

This family represents BVU_2266 from Phocaeicola vulgatus (

) and similar sequences from bacteroidetes. Members of this family show 16-stranded β-barrels resembling outer membrane porins. The interior of the barrels is mostly occupied by an insert with a partially helical structure.
GndA domain (GndA_dom)
Type: Domain

This domain covers the whole protein sequence in GndA from Escherichia coli, a small open reading frame (smORF)-encoded heat shock protein contained entirely within the 6-phosphogluconate dehydrogenase Gnd (

) that is predicted to form a transmembrane helix . It is also found in combination with other domains in other proteins from Enterobacterales.
LSO1/LSO2 (LSO1/2)
Type: Domain

This entry includes Protein LSO1 and LSO2 from Saccharomyces cerevisiae and similar sequences mainly found in fungi. LSO1 is likely to play a role in iron homeostasis. Its paralogue LSO2, which is constitutively expressed, is a ribosome-associated protein required for translational recovery after starvation from stationary phase. LSO2 is an orthologue of Coiled-coil domain containing 124 (Ccdc124, see

) .
Coiled-coil domain-containing protein 124/Oxs1, C-terminal (Ccdc124/Oxs1_C)
Type: Domain

This entry represents the C-terminal domain found in Coiled-coil domain-containing protein 124 (Ccdc124) from animals and Oxs1 from fission yeasts.

Oxs1 (oxidative stress transcription corepressor Oxs1) and Pap1 form a complex to regulate transcription when cells are exposed to diamide or Cd which causes disulfide stress. In fission yeast, such as S. pombe, heterologous Oxs1-like proteins can enhance diamide stress tolerance. Furthermore, human and arabidopsis Oxs1 can interchangeably bind Pap1 or Pap1 homologues from human (cJun) and arabidopsis (bZIP10), suggesting that Oxs1 may be a component of an evolutionarily conserved stress response pathway . Ccdc124 was identified as a novel component of the centrosome during interphase and G2/M transition and is involved in cytokinesis .
Sporulation protein 24 (SPO24)
Type: Family

This family includes Sporulation protein 24 from Saccharomyces cerevisiae (SPO24) and similar sequences from yeast. SPO24 is a 67-amino-acid protein required for efficient sporulation .
Glutathione S-transferase UstS-like , C-terminal domain (GST_UstS-like_C)
Type: Domain

This domain is found at the C-terminal end of a group of Glutathione transferases (GST) mainly found in fungi and bacteria, including Glutathione S-transferase-like protein ustS from Aspergillus flavus, Beta-etherase from Sphingobium sp. (LigE) and

from Phanerodontia chrysosporium (GTE1). UstS is part of the gene cluster that mediates the biosynthesis of the secondary metabolite ustiloxin B, an antimitotic tetrapeptide . LigE is able to degrade various dimeric lignin compounds . GTE1 is capable of binding nonsubstrate ligands derived from lignin degradation .
Secreted glycosylated protein U9-ORF (U9-ORF)
Type: Family

This family represents the secreted glycosylated protein U9-ORF from Mus musculus and similar sequences from vertebrates. U9-ORF is a 118-residues protein encoded by U90926, a long non-coding RNAs (lncRNAs) that has been associated with the proliferation of herpes simplex virus 1 (HSV-1) in retinal photoreceptor cells . U9-ORF is secreted by activated myeloid cells. Its expression has been associated with protection during endotoxic shock and with the proliferation of herpes simplex virus 1 (HSV-1) in murine retinal photoreceptor cells .
Aminodeoxyfutalosine deaminase/Imidazolonepropionase-like, composite domain, N-terminal (MQNX/HUTI_composite_N)
Type: Domain

This entry represents the N-terminal segment of the composite domain usually found in metal-dependent hydrolases, including Imidazolonepropionase from Paracoccus denitrificans (HUTI) and Aminodeoxyfutalosine deaminase from Deinococcus radiodurans (MQNX). HUTI catalyses the hydrolytic cleavage of the carbon-nitrogen bond in imidazolone-5-propanoate to yield N-formimidoyl-L-glutamat and MQNX the deamination of aminodeoxyfutalosine (AFL) into futalosine (FL) .
The composite domain is interrupted by the catalytic α/β barrel domain (

). It has a pseudo-barrel fold.
NSF, AAA+ ATPase lid domain (NSF_ATPase_lid)
Type: Domain

This entry represents the ATPase lid domain of the second AAA+ ATP-binding domain (also known as D2) of animal NSF proteins , which is found at the C terminus. NFS proteins are responsible for essential membrane fusion events. They play the role of a chaperone by activating the SNAP receptor proteins (SNAREs) so that they can participate in membrane fusion .
RAE1/2 domain I, C-terminal region (RAE1_2_domI_C)
Type: Domain

This entry represents the C-terminal region of domain I from Rab escort proteins 1/2 (RAE1/2, also known as Rab proteins geranylgeranyltransferase component A 1/2) which are the substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) complex . These proteins bind unprenylated Rab proteins and presents the substrate peptide to the catalytic component B, remaining bound to it after the geranylgeranyl transfer reaction.Members of this entry are mainly found in vertebrates and some species of arthropods.
McpB, second HAMP domain (McpB_HAMP_2nd)
Type: Domain

This entry represents the second HAMP domain found in Methyl-accepting chemotaxis protein McpB from Pseudomonas aeruginosa and similar sequences from proteobacteria. McpB, also known as Aerotaxis transducer Aer2, is a chemoreceptor that plays a critical role in the virulence and pathogenesis of the bacteria. This domain folds into a unique four-helix bundle that comparatively differs from the first and third HAMP domains of the same protein .
Tetracyclin repressor-like HI_0893, C-terminal domain (TetR-like_HI_0893_C)
Type: Domain

This entry represents the C-terminal domain of some HTH-type transcriptional repressors, such as HI_0893 from Haemophilus influenzae.
Replitron, C-terminal domain (Replitron_C)
Type: Domain

This entry represents a presumed domain found adjacent to the HUH endonuclease domain (

) of the eukaryotic transposase encoded by Replitron, a fourth independent group of DNA transposons encoding HUH endonuclease that are found in genomes of green algae and plants, diverse stramenopiles including brown seaweeds and likely also cryptophytes and haptophytes, which suggests an ancient origin and broad eukaryotic distribution. According to structure predictions from AlphaFold DB, and structural similarities with related Rep HUH endonucleases (

), this may be an oligomerisation domain.
Replitron, HUH endonuclease domain (Replitron_HUH)
Type: Domain

This entry represents the Rep HUH endonuclease domain of the eukaryotic transposase encoded by replitrons, a fourth independent group of DNA transposons found in genomes of green algae and plants, diverse stramenopiles including brown seaweeds and likely also cryptophytes and haptophytes, which suggests an ancient origin and broad eukaryotic distribution. This domain contains motif I (SUTU), motif II (HUQ) and motif III (YxxK), the latter including the catalytic tyrosine residue. There is also a conserved Glu upstream of motif II, which may represent the third metal-binding ligand, analogous to those in the Reps of CRESS-DNA virus PCV2 or Helraiser Helitron . Members of this group are mainly found in plants.
Cdc6/ORC1-like, ATPase lid domain (Cdc6_ORC1-like_ATPase_lid)
Type: Domain

This entry represents the AAA+ ATPase lid domain of eukaryotic Cdc6/ORC proteins and its homologues from archaea . Cdc6 is involved in the initiation of DNA replication. It also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
TOTE conflict systems, S1/CSD-like domain 1 (S1CSD-TOTE-1)
Type: Domain

This entry represents a presumed ribonucleoprotein complex-forming domain of the TOTE systems, potentially binding ssRNAs derived from hybrid duplexes bound by the systems. It is typically found in a two-domain tandem repeat arrangement, this is the first domain .
TOTE conflict systems, S1/CSD-like domain 2 (S1CSD-TOTE-2)
Type: Domain

This entry represents a presumed ribonucleoprotein complex-forming domain of the TOTE ((TPR, OB, TBP, Effector) conflict systems, potentially binding ssRNAs derived from hybrid duplexes bound by the systems. It is typically found in a two-domain tandem repeat arrangement, this is the second domain .
TMADH/DMDH/HD, second alpha/beta domain (TMADH/DMDH/HD_second_a-b)
Type: Domain

This domain is found in a group of diverse dehydrogenases from the old yellow enzyme (OYE) superfamily, such as histamine dehydrogenase (HD) from Nocardioides simplex, dimethylamine dehydrogenases (DMDH), trimethylamine dehydrogenase (TMADH) from Methylophilus methylotrophus (sp. W(3)A(1)) , in which it has been described as a small, second α/β domain . Members of this group are mainly found in proteobacteria and some actinobacterial species.

TMADH is an iron-sulfur flavoprotein that catalyses the oxidative demethylation of trimethylamine to form dimethylamine and formaldehyde. The protein forms a symmetrical dimer with each subunit containing one 4Fe-4S cluster and one FMN cofactor . It contains a unique flavin, in the form of a 6-S-cysteinyl FMN which is bent by ~25 degrees along the N5-N10 axis of the flavin isoalloxazine ring. The closely related histamine dehydrogenase catalyses oxidative deamination of histamine .
Muscleblind-like, CCCH zinc finger (Znf-CCCH_Muscleblind-like)
Type: Domain

This is the CCCH-type zinc finger domain found in muscleblind (MBL) from Drosophila and its homologues.

MBL is required for terminal differentiation of photoreceptor cells and it is vital for embryonic development . Mammalian MBL-like proteins (MBL1-4) mediate pre-mRNA alternative splicing regulation . They act either as activator or repressor of splicing on specific pre-mRNA targets. They can inhibit cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. MBL0like proteins antagonize the alternative splicing activity pattern of CELF proteins. These are RNA-binding proteins that bind to 5-'ACACCC-3' core sequence, termed zipcode, within the 3'UTR of ITGA3. They bind to CUG triplet repeat expansion in myotonic dystrophy muscle cells by sequestering the target RNAs. Together with RNA binding proteins RBPMS and RBFOX2, they activate vascular smooth muscle cells alternative splicing events .
Baseplate wedge protein gp10, domain 3 (Gp10_D3)
Type: Domain

This domain is found in the central region of Baseplate wedge protein gp10 and related viral proteins. This domain folds into a β-sandwich.
RNA-dependent RNA polymerase, thumb domain, ribovirus (RdRp_thumb_ribovirus)
Type: Domain

This helical bundle domain, known as the thumb domain, is found in the RNA-dependent RNA polymerase (RdRp) of Riboviruses, such as Thosea asigna virus (TaV), C-terminal to the palm domain (

). This domain is larger than the thumb domains of other viral ssRNA RdRPs .
Argonaute, middle domain, bacteria (Ago_MID_bact)
Type: Domain

This entry represents the middle domain of bacterial argonaute (Ago) . Ago binds small RNA or DNA guides, which provide base-pairing specificity for the recognition and cleavage of complementary nucleic acid targets. Bacterial Ago adopts a bilobed structure; an N-terminal and a PAZ domain constitute one lobe, the second one consists of a middle (MID) domain and the catalytic PIWI domain. This domain mediates the recognition of the 5' end of the guide .
Argonaute, PAZ domain, methanocaldococcus (Ago_PAZ_methanocaldococcus)
Type: Domain

This entry represents the PAZ domain of Protein argonaute from Methanocaldococcus jannaschii (Ago, ) and similar sequences. Ago is a DNA-guided ssDNA endonuclease that may play a role in defence against invading genetic elements that uses short ssDNA sequences as guides (gDNA) to bind complementary target strands resulting in slicing of the target DNA (tDNA) .
PspA-associated domain (PspA-assoc_dom)
Type: Domain

This entry represents a trihelical domain (α+β) with highly conserved R and D, which occurs as a two-gene cluster with PspA in prokariotic sequences. This domain covers the whole length of the protein in most sequences, but is occasionally found fused to an N-terminal PspA in actinobacteria and chloroflexi .
Structural cement protein E217 gp24/Pam3 gp6 (Struct_cement_gp24/gp6)
Type: Family

E217 is a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa . Gp24 is a trimeric structural protein and component of the E217 icosahedral head. Gp24 adopts a beta-tulip fold similar to the gp87 protein found in the thermophilic phage P74-26. Each gp24 subunit consists of two anti-parallel beta-sheets, that form a tulip-like structure. Gp24 structural protein probably stabilises the E217 capsid. This entry includes the cement protein gp6 of cyanophage Pam3 . It consists of an N-terminal β-tulip domain followed by a C-terminal domain of seven antiparallel beta-strands. Gp6 trimers sit at the icosahedral threefold and quasi-threefold axes, stabilising the capsid shell.
Tail fiber protein gp32-like (Gp32-like)
Type: Family

This entry represents a family of proteins from tailed bacteriophages and bacterial prophages, including Gp32 from E217, a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa. Stacked hexamers of the tail tube protein gp32 form the central tube of the E217 tail. The tail tube protein is structurally conserved and homologous to the tail tube protein gp32 found in non-contractile tails, bacterial pyocins, and type VI secretion systems. Gp32 consists of a classical β-sandwich that contains two four-stranded sheets facing each other and surrounded by a long α-helix and an extended β-turn .
Collar protein gp28-like (Gp28-like)
Type: Family

This entry represents a family of proteins from tailed bacteriophages and proteobacterial prophages, including Gp28 from E217, a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa. The collar protein gp28 is located at the neck of the E217 virion. Gp28 consists of a small β-barrel decorated by an α-helix and two wing-like lateral extensions. Six collar proteins pack under the head-to-tail dodecamer with Gp28 N-helix positioned orthogonal to two Gp27 subunits. On the opposite side of the Gp28 barrel, the wing-like extensions contact two gateway subunits .
E217 Baseplate component gp38-like (E217_Gp38-like)
Type: Family

This entry represents a family of proteins from tailed bacteriophages, including Gp38 from E217, a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa. Gp38 is a baseplate cap component that forms a heterodimeric complex with Gp37. These proteins adopt a similar fold, consisting of two orthogonally packed β-sheets that coil into a barrel shape .
Glycan binding protein Y3-like domain (Y3-like_dom)
Type: Domain

This entry represents the domain present in the glycan-binding protein Y3 from Coprinus comatus (

) and related proteins from fungi. The structure of this domain consists of an α-β-α sandwich motif, which includes three α-helices and a five-stranded β-sheet. This domain is characterised by the presence of four intramolecular disulfide bridges .
YoaL-like (YoaL-like)
Type: Family

This protein family includes YoaL from Escherichia coli, the product of a small open reading frame (smORF), which may serve a regulatory role in the expression of its downstream gene . Members of this group are specific to Enterobacterales.
T3SS, peptide-binding chaperone domain (T3SS_chaperone_dom)
Type: Domain

This domain is observed in proteins from bacterial host systems predicted to counter viral ribosylating toxins. They are predicted to function as peptide-binding chaperone domains that target proteins modified by ADPr and potentially misfolded as a consequence .
CIMIP3-like (CIMIP3-like)
Type: Family

This family represents human CIMIP3 and similar sequences mainly found in vertebrates. CIMIP3 is thought to be a microtubule inner protein (MIP) part of the doublet microtubules (DMTs) in the sperm axoneme .
Gateway protein gp29-like (Gp29-like)
Type: Family

This entry represents a family of proteins from tailed bacteriophages and bacterial prophages, including Gp29 from E217, a Pseudomonas phage used in an experimental cocktail to eradicate cystic fibrosis-associated Pseudomonas aeruginosa. The gateway protein gp29 is a neck factor of the E217 virion that connects the neck to the sheath lattice .
Helix-turn-helix domain, putative, ascomycetes (HTH_put_ascomycetes)
Type: Domain

This entry represents a putative helix-turn-helix domain found C-terminal in a group of uncharacterised proteins from actinomycetes. It may be involved in DNA binding.
Nonstructural protein, WIV domain (WIV_dom)
Type: Domain

This domain is found in Nonstructural protein from Lake Sinai virus and similar sequences from arthropod-infecting viruses and lower eukaryotes. It has been named 'Widespread, Intriguing, Versatile' (WIV) domain. This region is likely to play a role in viral infection of arthropods.
TIL-like domain (TIL-like_dom)
Type: Domain

This entry represents a small cysteine rich domain that is related to the Trypsin Inhibitor like cysteine rich domain found in

. Members of this group are found in nematodes.
RhopH3, C-terminal domain (RhopH3_C)
Type: Domain

This entry represents a domain found towards the C terminus in homologues of High molecular weight rhoptry protein 3 from Plasmodium falciparum (RhopH3) and similar sequences specific to Plasmodium species. RhopH3 is a component of the RhopH complex that is essential for the pathogen erythrocyte invasion and for remodelling its host cells to achieve tissue adherence and nutrient acquisition .
Minimal SLOG domain (mSLOG_dom)
Type: Domain

This entry represents a domain predicted to be an active, minimal version of the SLOG domain. It is found N-terminally fused to the DUF4326 domain (

). It may play a role in base cleavage, potentially forming abasic sites acted on by the DuOB domain (

) . Members of this group are found in proteobacteria.
PssL-like (PssL-like)
Type: Family

This family includes Protein PssL from Escherichia coli, the product of a small open reading frame (smORF), which may serve a regulatory role in expression of downstream gene . Members of this group are found in Enterobacterales.
NGO_1070-like (NGO_1070-like)
Type: Family

This protein family includes the uncharacterised protein NGO_1070 from Neisseria gonorrhoeae (

) and similar proteins mainly found in proteobacteria. NGO_1070 adopts a β-barrel fold. Its function is unknown.
TraH, VirB8-like domain (TraH_VirB8-like_dom)
Type: Domain

This entry represents the VirB8-like domain present in TraH from Enterococcus faecalis (

) and similar sequences from Bacilli. TraH is part of the type IV secretion system (T4SS) . This domain shows structural similarity to the VirB8 domain (

).