SII-SWORD/CoKE huggingface dataset:
tRNA (guanine(6)-N2)-methyltransferase-like (Trm14-like)
Type: Family

This entry represents tRNA (guanine(6)-N2)-methyltransferase from Pyrococcus furiosus (Trm14) and similar proteins from Thermococcales. Trm14 is a S-adenosyl-L-methionine-dependent methyltransferase responsible for the methylation of guanosine nucleotides at position 6 in tRNA, specifically modifying tRNA(Phe) . Members of this family show an N-terminal THUMP domain (

), which is associated with RNA binding, and a C-terminal Rossmann-fold methyltransferase domain (

).
Cypemycin cysteine dehydrogenase (decarboxylating)-like (CypD-like)
Type: Family

This entry represents Cypemycin cysteine dehydrogenase (decarboxylating) from Streptomyces sp. (CypD) and similar sequences from actinobacteria. CypD, a Cys decarboxylase flavoprotein, oxidatively removes the carboxyl moiety from the C-terminal Cys residue of CypA, the precursor of the RiPP natural product cypemycin .
Indoleacetate decarboxylase-like (IAD-like)
Type: Family

This entry includes Indoleacetate decarboxylase (IAD) from Tractidigestivibacter scatoligenes and similar bacterial sequences.
IAD is a single subunit glycyl radical enzyme that depends on a cognate radical SAM enzyme for its activation. It performs the final step in the anaerobic fermentation of tryptophan to skatole, a malodorous volatile compound .
UTP--glucose-1-phosphate uridylyltransferase AglF-like (AglF-like)
Type: Family

This entry represents a family of proteins from halobacteria, including UTP--glucose-1-phosphate uridylyltransferase AglF	from Haloferax volcanii. AglF is involved in the assembly of a N-linked pentasaccharide that decorates the S-layer glycoprotein and flagellins. It is also involved in the biosynthesis of the hexuronic acid found at position 3 of the pentasaccharide .
Thc1, RRM domain (Thc1_RRM)
Type: Domain

The founder of this entry is a domain found in Thc1 protein from Schizosaccharomyces pombe. This protein is a subunit of sno(s)RNA-containing ribonucleoprotein complex and is involved in snRNA processing . This domain is predicted to adopt a typical RRM fold with a significant similarity to Poly (A)-specific ribonuclease PARN. Besides the global structural similarity, the residues involved in RNA-binding in PARN, are conserved within this entry. These residues define a semi-conserved IWx(2)DTx(5)F sequence motif.
Protein of unknown function DUF6959 (DUF6959)
Type: Family

This is a family of uncharacterised bacterial proteins. They contain conserved Pro-Gly-rich motif with a semi- conserved pattern PGRxFPGx3QGD.
Domain of unknown function DUF6950 (DUF6950)
Type: Domain

This domain is found in a group of uncharacterised proteins, mainly from proteobacteria. It is related to NlpC/P60 domains and it is likely to adopt similar structure as well as to possess an endopeptidase activity. All members of this family contain a conserved cysteine residue that is predicted to occupy equivalent spatial position as in the NlpC/P60 domains.
Protein of unknown function DUF6949 (DUF6949)
Type: Family

This is a family of uncharacterised proteins mainly found in proteobacteria. These proteins are enriched with hydrophobic residues and it is quite likely to be associated with the membrane.
Protein of unknown function DUF6960 (DUF6960)
Type: Family

This is a family of uncharacterised bacterial proteins. They are composed of two tandem domains with similarity to SH3 domains, in particular to YorP.
Bacteriophage N4 RNA polymerase, helical domain (N4_RNAP_helical)
Type: Domain

This is a helical domain, also known as 'Fingers subdomain', found in the bacteriophage N4 virion RNA polymerase . This domain possesses two essential functions of the RNAP: the N-terminal part plays a role in the nucleotide addition cycle, whereas the C-terminal part is involved in promoter recognition . A swing motion of the N-terminal part of the fingers is coupled with nucleotide addition, translocation of the DNA-RNA hybrid, and downstream double-strand DNA opening.
MTHFR, SAM-binding regulatory domain (MTHFR_C)
Type: Domain

This is the C-terminal SAM-binding regulatory domain of 5,10-methylenetetrahydrofolate reductase (MTHFR) that follows the catalytic domain and is unique to eukaryotes. This domain provides the required interface for MTHFR homo-dimerization, thus positioning the N-terminal serine-rich phosphorylation region near the SAM-binding site. The core of this domain comprises two mixed β-sheets, one of which flanked with helices. This regulatory domain represents distinct architecture from the classical SAM-dependent methyltransferases and non-methyltransferases .
LppM domain (LppM)
Type: Domain

This domain is found in LppM, a bacterial effector implicated in the early steps of Mycobacterium tuberculosis infection. LppM is anchored to the mycobacterial cell wall by a C-terminal membrane domain. An isoform that lacks the latter is secreted. This domain has unusual fold consisting of a β-sandwich in which one of the β-sheets is extended with three β-strands packed with a α-helix . LppM is capable of binding phosphatidylinositol mannosides (PIM) derivatives .
Cell wall binding protein Cwp8, domain 2 (Cwp8_D2)
Type: Domain

Cwp8 is a member of the C. difficile cell wall protein (CWP) family. It consists of several domains. This entry represents domain 2 (D2) that is a part of the N-terminal elongated region of the molecule . This domain is composed of a three-stranded antiparallel β-sheet, an α-helix packed on it and a short β-hairpin located at the edge of the sheet.
Cell wall binding protein Cwp8, domain 3 (Cwp8_D3)
Type: Domain

This entry represents the third domain (D3) of cell wall protein Cwp8, found in C. difficile. This domain folds into an α/β structure consisting of a four-stranded antiparallel β-sheet packed on one side with α-helices . This domain is related to domain 1 (D1) of the cell wall protein Cwp2 from the same organism.
Protein of unknown function DUF6952 (DUF6952)
Type: Family

This is a family of uncharacterised bacterial proteins. They contain highly conserved acidic residues and G[S/A]ID motif at the C terminus.
2'-deoxycytidine 5'-triphosphate deaminase, C-terminal domain (DCD_C)
Type: Domain

This entry includes 2'-deoxycytidine 5'-triphosphate deaminase proteins (

) (DCD) from a set of mainly alphaproteobacteria, which consist of two dUTPase-like domains (

). This entry represents the C-terminal domain.
RNA polymerase sigma-70 ECF-like, HTH domain (HTH_Sigma70_ECF-like)
Type: Domain

This entry represents a HTH domain found in probable RNA polymerase sigma factors belonging to the extra-cytoplasmic function (ECF) subfamily . Sigma factors are able to regulate ECF . Eubacteria display considerable genetic diversity between ECF-sigma factors, but all retain two features: the ability to respond to extra-cytoplasmic functions; and regulation by anti-sigma and anti-anti-sigma factors .
CATSPERD, beta-propeller domain (CATSPERD_beta-prop)
Type: Domain

This entry represents the β-propeller domain of the delta subunit (CATSPERD) .

The CATSPER (cation channel of sperm) complex is a tetrameric complex consisting of CATSPER1, CATSPER2, CATSPER3 and CATSPER4, it functions as an alkalinisation-activated calcium channel. This complex is involved in sperm cell hyperactivation, a process needed for sperm motility, which is essential late in the preparation of sperm for fertilisation . This complex requires four auxiliary subunits (beta, gamma, delta and epsilon), which play a role in channel assembly . These are multidomain proteins which share a similar domain organisation.
CATSPERD/E, C-terminal domain (CATSPERD/E_C)
Type: Domain

This entry represents the C-terminal domain of delta and epsilon subunits, which covers the stem domain and the transmembrane helix, that are involved in the association with the channel domain .

The CATSPER (cation channel of sperm) complex is a tetrameric complex consisting of CATSPER1, CATSPER2, CATSPER3 and CATSPER4, it functions as an alkalinisation-activated calcium channel. This complex is involved in sperm cell hyperactivation, a process needed for sperm motility, which is essential late in the preparation of sperm for fertilisation . This complex requires four auxiliary subunits (beta, gamma, delta and epsilon), which play a role in channel assembly . These are multidomain proteins which share a similar domain organisation.
CATSPERE, Ig-like domain (CATSPERE_Ig-like)
Type: Domain

The CatSper (cation channel of sperm) complex is a tetrameric complex consisting of CATSPER1, CATSPER2, CATSPER3 and CATSPER4, it functions as an alkalinisation-activated calcium channel. This complex is involved in sperm cell hyperactivation, a process needed for sperm motility, which is essential late in the preparation of sperm for fertilisation . This complex requires four auxiliary subunits (beta, gamma, delta and epsilon), which play a role in channel assembly . These are multidomain proteins which share a similar domain organisation.

This entry represents the Ig-like domain of CATSPERE (epsilon subunit).
CATSPERE, beta-propeller domain (CATSPERE_beta-prop)
Type: Domain

The CatSper (cation channel of sperm) complex is a tetrameric complex consisting of CATSPER1, CATSPER2, CATSPER3 and CATSPER4, it functions as an alkalinisation-activated calcium channel. This complex is involved in sperm cell hyperactivation, a process needed for sperm motility, which is essential late in the preparation of sperm for fertilisation . This complex requires four auxiliary subunits (beta, gamma, delta and epsilon), which play a role in channel assembly . This entry includes CATSPERE, the auxiliary subunit epsilon of the CatSper complex. This is a multi-domain protein which has a similar domain organisation as the other auxiliary subunits, beta, gamma and delta.

The epsilon subunit has an additional N-terminal domain (NTD2) which is followed by a β-propeller domain, represented in this entry.
CATSPERE, second N-terminal domain (CATSPERE_NTD2)
Type: Domain

This entry includes CATSPERE, the auxiliary subunit epsilon of the CatSper complex, a complex involved in sperm cell hyperactivation. This process is needed for sperm motility, which is essential late in the preparation of sperm for fertilisation . This is a multi-domain protein which has a similar domain organisation as the other auxiliary subunits, beta, gamma and delta. The epsilon subunit has two N-terminal domains (NTD1/2); this entry represents the second one (NTD2) .
CATSPERE, first N-terminal domain (CATSPERE_NTD1)
Type: Domain

This entry includes CATSPERE, the auxiliary subunit epsilon of the CatSper complex, a complex involved in sperm cell hyperactivation. This process is needed for sperm motility, which is essential late in the preparation of sperm for fertilisation . This is a multi-domain protein which has a similar domain organisation as the other auxiliary subunits, beta, gamma and delta. The epsilon subunit has an additional N-terminal domain (NTD2). This entry represents the first N-terminal domain (NTD1) .
TEAD interacting region 3, omega loop (TEADIR3_omega_loop)
Type: Conserved_site

This entry represents the third TEAD interacting region (omega loop) present in YAP/TAZ, FAM181, and PERCC1 families . This conserved region is remotely related to the omega loop found in the Vestigial family (VGLL2 and VGLL3) .
MSL3 chromodomain-like (MSL3_chromo-like)
Type: Domain

This domain is found in Male-specific lethal-3 (MSL3) and other related proteins such as MRG1/2 transcription factors. MSL3 resides in the MSL (male-specific lethal) complex, which upregulates transcription by spreading the histone H4 Lys16 acetyl mark. The MSL3 chromo domain implicated in chromatin targeting and its deletion leads to the disruption of MSL targeting. This domain consists of a SH3-like β-barrel and a long α-helix .
Splicing regulator SDE2, ubiquitin domain (Sde2_Ubi)
Type: Domain

This entry represents the ubiquitin-fold domain found at the N-terminal of human SDE2 (Splicing regulator SDE2, also known as silencing defective 2) and similar proteins from vertebrates. SDE2 in a splicing regulator that supports splicing of selected pre-mRNAs in an intron-specific manner .
SDE2-like domain (SDE2-like_dom)
Type: Domain

SDE2 (silencing defective 2) is a ubiquitin-fold-containing splicing regulator that supports splicing of selected pre-mRNAs in an intron-specific manner in Schizosaccharomyces pombe. This splicing regulator is conserved among intron-rich eukaryotes up to humans, but is absent in intron-poor organisms such as S. cerevisiae. SDE2 is important in pre-mRNA splicing in mammalian cells . Human SDE2 is a regulatory component of the fork protection complex (FPC) at active and stalled replication forks .

SDE2 is translated as an inactive precursor harbouring an ubiquitin-fold at its N-terminal that is processed by deubiquitinating enzymes (DUBs, Ubp5 and Ubp15 in S.pombe) in a conserved GG-K motif to form activated K-Sde2-C , which is necessary to get incorporated into the spliceosome . SDE2 is both an RNA-binding protein and also a trans-acting adaptor protein that functions to regulate RNA splicing and ribosome biogenesis.

This entry represents the SDE2 domain, a coiled-coil domain required for the interaction of SDE2 with TIMELESS (TIM), which promotes stable association of the FPC at active replication forks .
CLIC, N-terminal domain (CLIC_N)
Type: Domain

This entry represents the N-terminal domain of chloride ion channels CLIC and related sequences.

The chloride intracellular channel (CLICs) belong to the glutathione-S-transferase (GSTs) superfamily, highly conserved in vertebrates which usually possess six distinct paralogues (CLIC1-CLIC6) . They are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division and apoptosis. CLIC proteins can exist as both soluble globular proteins and integral membrane proteins with ion channel function . Membrane insertion is redox-regulated and has a strong pH dependence ; the N-terminal domain of CLIC1 undergoes a structural change to form a non-covalent dimer stabilized by the formation of an intramolecular disulfide bond between two cysteines that are far apart in the reduced form. This redox-controlled structural rearrangement exposes a large hydrophobic surface that may represent the docking interface of CLIC1 in its membrane-bound state . The two cysteines in CLIC1 that form the disulfide bond in oxidizing conditions are essential for dimerization and chloride channel activity.
Protein of unknown function DUF7010 (DUF7010)
Type: Family

This entry represents a family of uncharacterised bacterial proteins. They are predicted to adopt α-helical structure composed of six up-and-down α-helices. It is likely that these proteins are associated with the membrane.
Protein of unknown function DUF7009 (DUF7009)
Type: Family

This is a family of uncharacterised proteins found in bacteria. It is predicted to adopt a globular structure consisting of two nearly orthogonal β-sheets and two α-helices that connect them. Toward the C terminus, these proteins contain a highly conserved region enriched with negatively charged residues, having nearly invariant EKDFxC sequence motif.
WD repeat-containing protein 75 (WDR75)
Type: Family

This entry includes WD repeat-containing protein 75 (WDR75) from animals and its orthologues, Nan1/Utp17 (NET1-associated nuclear protein 1) from yeast. These proteins are involved in ribosome biogenesis, specifically as factors within the small subunit (SSU) processome, which is the initial precursor to the small eukaryotic ribosomal subunit . These proteins are essential for various stages of pre-rRNA processing, including RNA folding, modification, rearrangement, and cleavage. They also contribute to the targeted degradation of pre-ribosomal RNA by the RNA exosome. Additionally, they play a crucial role in the nucleolar processing of pre-18S ribosomal RNA and are necessary for the optimal transcription of pre-ribosomal RNA by RNA polymerase I .
Baseplate structural protein Gp10, C-terminal domain (Gp10_C)
Type: Domain

This entry represents the C-terminal domain (CTD) of baseplate structural protein Gp10 that assembles into trimeric structures. The core structure and assembly of Gp10 has structural similarity to that of the head domain of Gp11 and the receptor binding domain of Gp12 . The monomeric CTD of Gp10 consists of an α-helix followed by a three-stranded, antiparallel β-sheet, which is almost perpendicular to the helix. The three symmetry related β-sheets interact with their first β-strands in the trimer, thus creating a flower-like arrangement with the α-helices being the flower stem and the three β-sheets being the petals.

Interestingly, this domain is also identified in proteins found in Trichomonas.
Putative 5'-nucleotidase, C-terminal domain (Nucleosidase_C)
Type: Domain

This is the C-terminal domain of a family of putative Zn2-dependent 5'-nucleotidases including a nucleotidase from Candida albicans (

) and a secreted protein ARB_01864 (

) from Arthroderma benhamiae. This domain adopts a four-layered structure with a five-stranded β-sheet forming the structural core

.
XLF-like, coiled-coil region (XLF-like_CC)
Type: Domain

This entry represents the coiled-coil region of Xrcc4-like factor 1 from Schizosaccharomyces pombe (XLF) and similar sequences from animals and fungi.

XLF (also called Cernunnos) is involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. XLF and XRCC4 form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair . It directly interacts with the XRCC4-Ligase IV complex and siRNA-mediated downregulation of XLF in human cell lines leads to radio-sensitivity and impaired DNA non-homologous end-joining . XLF is the human orthologue of fission yeast Xrcc4-like factor 1 .
Domain of unknown function DUF6922 (DUF6922)
Type: Domain

This domain is found in bacterial proteins either as a standalone domain or in combination with an HTH domain that resembles lambda C1 repressor DNA-binding domain. This domain has a partial sequence similarity to the RAP1 C-terminal (RCT) domain.
SOGP, N-terminal domain (SOGP_N)
Type: Domain

This entry represents the N-terminal domain of 1,2-beta oligoglucan phosphorylase (SOGP) and related bacterial proteins. This enzyme catalyses the phosphorolysis of beta-1,2-glucooligosaccharides (sophorooligosaccharides, Sops) with degrees of polymerization (DP) of 3 or more. It consists of four domains: two β-sandwich domains, an (α/α)6 catalytic domain and a β-sheet domain. The N-terminal domain adopts a supersandwich fold in which 18 β-strands define two β-sheets .
Domain of unknown function DUF6924 (DUF6924)
Type: Domain

This domain of unknown function is found in bacterial and fungal proteins, either standalone or in combination with other domains. It is probably remotely related to the anticodon binding domain observed in histidyl, glycyl, threonyl and prolyl tRNA synthetases.
Small archaeal modifier protein 2 (SAMP2)
Type: Family

The ubiquitin-like small archaeal modifer protein 2 (SAMP2) is involved in sulfur transfer during molybdenum cofactor biosynthesis. SAMP2 has been demonstrated to form covalent conjugates with substrate proteins through an isopeptide linkage via C-terminal di-glycine motif in a streamlined archaeal E1-dependent pathway. SAMP2 also forms homo-conjugates through the intermolecular isopeptide bond between the C-terminal glycine and the Lys58 side chain, a feature that likely resembles polyubiquitination. This protein adopt a typical ubiquitin-like fold.
Ubiquitin-like small modifier protein 2, halobacteria (SAMP2_halobacteria)
Type: Family

This family of proteins is involved in post-translational modification of substrate proteins through a process known as sampylation . Members of this family function by covalently attaching to lysine residues on target proteins via an isopeptide bond formed with the C-terminal glycine carboxylate of the modifier protein. Additionally, these proteins act as sulfur carriers during the thiolation of tRNA. They are capable of forming polymeric chains through a specific lysine residue, which is a characteristic reminiscent of ubiquitin and other ubiquitin-like modifiers. This modification can serve as a signal for proteolytic degradation, targeting proteins to the proteasome.
Set1/Ash2 histone methyltransferase complex subunit ASH2-like, winged-helix (ASH2L-like_WH)
Type: Domain

This domain is found in Set1/Ash2 histone methyltransferase complex subunit ASH2 from humans (ASH2L, named after 'Absent, small, homeotic disks-2-like') and similar animal proteins. ASH2L is a non-catalytic component of the Set1/Ash2 histone methyltransferase (HMT) complex. Aberrant expression and recurrent recurrent mutations in components of this complex have been related to different diseases. This entry represents the winged-helix (WH) domain, which is found N-terminal to the SPRY domain (

) in ASH2L. It binds directly to DNA and shows a compact α/β structure consisting of three α-helices and a curved three-stranded β-sheet .
Nuclear-export cofactor Arc1-like, N-terminal domain (Arc1-like_N)
Type: Domain

This entry represents a domain found N-terminal in the nuclear-export cofactor Arc1 (Arc1-N) from yeast and related proteins. Arc1-N and GluRS-N are known to be necessary and sufficient for formation of the yeast aaRS complex in vivo and in vitro. They are likely to form a stable complex with each other. Arc1-N adopts a fold similar to the C-terminal domain of glutathione S-transferase (GST-C) .

This domain is also found at the C-terminal of the Arc1 homologue AIMP3/p18, a human translation elongation factor 1 which is associated with the multi-tRNA synthetase complex via its specific interaction with methionyl-tRNA synthetase, and also works as a tumor suppressor by interacting with ATM, the upstream kinase of p53 .

This domain was also identified in bifunctional glutamate/proline--tRNA ligase, a multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex .
AIMP3/p18, C-terminal domain (AIMP3/p18_C)
Type: Domain

AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal α-helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging .
Protein of unknown function DUF6925 (DUF6925)
Type: Family

This is a family of uncharacterised bacterial proteins. They are probably distantly related to heme-binding proteins PhuS, ChuS, HmuS.
Domain of unknown function DUF6926 (DUF6926)
Type: Domain

This domain of unknown function is found in bacterial proteins. It is probably distantly related to dodecin. It is predicted to adopt a simple fold consisting of a core of 3 β-strands, forming a curved β-sheet, and two short α-helices.