SII-SWORD/CoKE huggingface dataset:
Pfam PF18996: Family of unknown function (DUF5726) (family)
This family is found in various Platyhelminthes, with many of the sequences annotated as being the polyprotein of the transposon Ty3-I Gag-Pol. However, the genomic location of other members suggests that this region is not always found in a transposon. The family  members are characterised by a highly conserved DxDxDxCC motif. The function of this family is currently unknown.
Wikipedia: A domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. As of 2019, there are almost 4,000 DUF families within the Pfam database representing over 22% of known families. Some DUFs are not named using the nomenclature due to popular usage but are nevertheless DUFs.
Pfam PF12441: CopG antitoxin of type II toxin-antitoxin system (domain)
CopG antitoxin is a member of a type II toxin-antitoxin system family found in bacteria and archaea.  Most antitoxins encoded by the relBE and parDE loci belong to the MetJ/Arc/CopG family of dimeric proteins which bind DNA through N-terminal ribbon-helix-helix (RHH) motifs. The toxin for CopG proteins falls into the family BrnT_toxin, [pfam:PF04365].
Wikipedia: A toxin-antitoxin system consists of a "toxin" and a corresponding "antitoxin", usually encoded by closely linked genes. The toxin is usually a protein while the antitoxin can be a protein or an RNA. Toxin-antitoxin systems are widely distributed in prokaryotes, and organisms often have them in multiple copies. When these systems are contained on plasmids – transferable genetic elements – they ensure that only the daughter cells that inherit the plasmid survive after cell division. If the plasmid is absent in a daughter cell, the unstable antitoxin is degraded and the stable toxic protein kills the new cell; this is known as 'post-segregational killing' (PSK).
Pfam PF00618: RasGEF N-terminal motif (domain)
A subset of guanine nucleotide exchange factor for Ras-like small  GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.
Pfam PF02504: Fatty acid synthesis protein (family)
The plsX gene is part of the bacterial fab gene cluster which encodes several key fatty acid biosynthetic enzymes. The exact function of the plsX protein in fatty acid synthesis is unknown.
Pfam PF12563: Hemolytic toxin N terminal (family)
This domain family is found in bacteria, and is approximately 190 amino acids in length. The family is found in association with [pfam:PF07968], [pfam:PF00652]. This family is a bacterial virulence factor - hemolysin - which forms pores in erythrocytes and causes them to lyse.
Wikipedia: Hemolysins or haemolysins are lipids and proteins that cause lysis of red blood cells by disrupting the cell membrane. Although the lytic activity of some microbe-derived hemolysins on red blood cells may be of great importance for nutrient acquisition, many hemolysins produced by pathogens do not cause significant destruction of red blood cells during infection. However, hemolysins are often capable of lysing red blood cells in vitro.
Pfam PF21470: Minor structural protein 5-like, C-terminal domain (domain)
This domain is found at the C-terminal end of Minor structural protein 5 from Lactococcus phage Tuc2009 (BppU) and similar proteins from tailed bacteriophages and prophages found mostly in firmicutes. BppU is a viral baseplate component. This domain folds into a structure formed mostly by beta-strands.
Pfam PF22353: NAD(P)H:rubredoxin oxidoreductase, C-terminal domain (domain)
This domain is found at the C-terminal end of NAD(P)H:rubredoxin oxidoreductase from Pyrococcus furiosus (PF1197) and similar sequences mainly found in archaea. PF1197 catalyses the NADH -dependent reduction of rubredoxin (Rd), a small iron -containing redox protein. This domain, likely to be involved in dimerisation, is often found associated with [pfam:PF07992].
Pfam PF13417: Glutathione S-transferase, N-terminal domain (domain)
This entry represents the N-terminal domain of GST.
In eukaryotes, glutathione S-transferases (GSTs) participate in the detoxification of reactive electrophilic compounds by catalysing their conjugation to glutathione. The GST domain is also found in S-crystallins from squid, and proteins with no known GST activity, such as eukaryotic elongation factors 1-gamma and the HSP26 family of stress-related proteins, which include auxin-regulated proteins in plants and stringent starvation proteins in Escherichia coli. The major lens polypeptide of Cephalopoda is also a GST .

Bacterial GSTs of known function often have a specific, growth-supporting role in biodegradative metabolism: epoxide ring opening and tetrachlorohydroquinone reductive dehalogenation are two examples of the reactions catalysed by these bacterial GSTs. Some regulatory proteins, like the stringent starvation proteins, also belong to the GST family . GST seems to be absent from Archaea in which gamma-glutamylcysteine substitute to glutathione as major thiol.

Soluble GSTs activate glutathione (GSH) to GS-. In many GSTs, this is accomplished by a Tyr at H-bonding distance from the sulphur of GSH. These enzymes catalyse nucleophilic attack by reduced glutathione (GSH) on nonpolar compounds that contain an electrophilic carbon, nitrogen, or sulphur atom .

Glutathione S-transferases form homodimers, but in eukaryotes can also form heterodimers of the A1 and A2 or YC1 and YC2 subunits. The homodimeric enzymes display a conserved structural fold, with each monomer composed of two distinct domains . The N-terminal domain forms a thioredoxin-like fold that binds the glutathione moiety, while the C-terminal domain contains several hydrophobic Î±-helices that specifically bind hydrophobic substrates.
Wikipedia: Glutathione S-transferases (GSTs), previously known as ligandins, are a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates for the purpose of detoxification. The GST family consists of three superfamilies: the cytosolic, mitochondrial, and microsomal—also known as MAPEG—proteins. Members of the GST superfamily are extremely diverse in amino acid sequence, and a large fraction of the sequences deposited in public databases are of unknown function. The Enzyme Function Initiative (EFI) is using GSTs as a model superfamily to identify new GST functions.
Pfam PF13596: PAS domain (domain)
This is a sensor domain that recognises O2, CO and NO (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
Wikipedia: A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life. Generally, the PAS domain acts as a molecular sensor, whereby small molecules and other proteins associate via binding of the PAS domain. Due to this sensing capability, the PAS domain has been shown as the key structural motif involved in protein-protein interactions of the circadian clock, and it is also a common motif found in signaling proteins, where it functions as a signaling sensor.
Pfam PF00185: Aspartate/ornithine carbamoyltransferase, Asp/Orn binding domain (domain)
This family contains two related enzymes:
 * Aspartate carbamoyltransferase (
2.1.3.2) (ATCase) catalyzes the conversion of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step in thede novo biosynthesis of pyrimidine nucleotides . In prokaryotes ATCase consists of two subunits: a catalytic chain (gene pyrB) and a regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi- functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals ) that also catalyzes other steps of the biosynthesis of pyrimidines.
 * Ornithine carbamoyltransferase (2.1.3.3) (OTCase) catalyzes the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme participates in the urea cycle  and is located in the mitochondrial matrix. In prokaryotes and eukaryotic microorganisms it is involved in the biosynthesis of arginine. In some bacterial species it is also involved in the degradation of arginine  (the arginine deaminase pathway).
It has been shown  that these two enzymes are evolutionary related. The predicted secondary structure of both enzymes are similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies , to be implicated in binding the phosphoryl group of carbamoyl phosphate and is described by IPR006132. The carboxyl-terminal, aspartate/ornithine-binding domain is connected to the amino-terminal domain by two Î±-helices, which comprise a hinge between domains .
Wikipedia: In molecular biology, the ATCase/OTCase family is a protein family which contains two related enzymes: aspartate carbamoyltransferase EC 2.1.3.2 and ornithine carbamoyltransferase EC 2.1.3.3. It has been shown that these enzymes are evolutionary related. The predicted secondary structure of both enzymes is similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies to be implicated in binding the phosphoryl group of carbamoyl phosphate and may also play a role in trimerisation of the molecules. The N-terminal domain is the carbamoyl phosphate binding domain. The C-terminal domain is an aspartate/ornithine-binding domain.
Pfam PF16610: Unstructured region between two PDZ domains on Dlg5 (disordered)
dbPDZ_assoc is found on higher eukaryote Dlg5, Disks large homolog 5, proteins, lying between the second pair of PDZ domains. The sequence is natively unstructured but may just be long extensions of the PDZs on these sequences in this position. The function is not known.
Pfam PF01613: Flavin reductase like domain (domain)
This is a flavin reductase family consisting of enzymes known to be flavin reductases as well as various oxidoreductase and monooxygenase components. VlmR is a flavin reductase that functions in a two-component enzyme system to provide isobutylamine N-hydroxylase with reduced flavin and may be involved in the synthesis of valanimycin. SnaC is a flavin reductase that provides reduced flavin for the oxidation of pristinamycin IIB to pristinamycin IIA as catalysed by SnaA, SnaB heterodimer.  This flavin reductase region characterised by enzymes of the family is present in the C-terminus of potential FMN proteins from Synechocystis sp. suggesting it is a flavin reductase domain.
Pfam PF23768: Domain of unknown function (DUF7167) (domain)
This small phage protein forms a predicted strand swapped dimer using AlphaFold. It is composed of three beta strands and two alpha helices.There is also some weaker evidence for a tetramer. The function of these proteins is unknown.
Wikipedia: A domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. As of 2019, there are almost 4,000 DUF families within the Pfam database representing over 22% of known families. Some DUFs are not named using the nomenclature due to popular usage but are nevertheless DUFs.
Pfam PF11258: Protein of unknown function (DUF3048) N-terminal domain (domain)
Some members in this bacterial family of proteins are annotated as YerB. However currently no function is known. This entry represents the N-terminal domain.
Wikipedia: A domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. As of 2019, there are almost 4,000 DUF families within the Pfam database representing over 22% of known families. Some DUFs are not named using the nomenclature due to popular usage but are nevertheless DUFs.
Pfam PF04639: Baculoviral E56 protein, specific to ODV envelope (family)
This family represents the E56 protein, which is localises to the occlusion derived virus (ODV) envelope, but not to the budded virus (BV) envelope.
Pfam PF03888: MucB/RseB N-terminal domain (domain)
Members of this family are regulators of the anti-sigma E protein  RseD.
Pfam PF22888: FIMAH domain (domain)
This entry represents a small alpha helical bundle domain found in a large range of different domain architectures. The proteins containing these domains are extracellular enzymes often involved in cell wall processes. The domain is named for (Found In Many Architectures Helical). The precise function of this domain is unknown.  This domain is usually found at the C-terminus of the protein.
Pfam PF23280: Fungal tetratrico peptide repeats (repeat)
These predicted tetratrico peptide repeats (TPR) are found in E3 ubiquitin-protein ligase listerin from Neurospora crassa (Rkr-1) and similar fungal proteins. Rkr-1 component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation.
Pfam PF16768: Nucleoporin homology of Germinal-centre associated nuclear protein (family)
NupH_GANP is the nucleoporin-homology domain at the N-terminus of human GANP or germinal-centre associated nuclear proteins. GANP is part of the TREX-2 complex that links transcription with nuclear messenger RNA export, and it associates with the mRNP particle through the interaction of the NupH_GANP with NXF1, the export factor. This attachment mediates efficient delivery of mRNPs to nuclear pore complexes.
Pfam PF06968: Biotin and Thiamin Synthesis associated domain (domain)
Biotin synthase (BioB), [ec:2.8.1.6] , catalyses the last step of the biotin biosynthetic pathway.  The reaction consists in the introduction of a sulphur atom into dethiobiotin. BioB functions as a homodimer.  Thiamin synthesis if a complex process involving at least six gene products (ThiFSGH, ThiI and ThiJ). Two of the proteins required for the biosynthesis of the thiazole moiety of thiamine (vitamin B(1)) are ThiG and ThiH (this family) and form a heterodimer.  Both of these reactions are thought of involve the binding of co-factors, and both function as dimers. This domain therefore may be involved in co-factor binding or dimerisation (Finn, RD personal observation).
Pfam PF17436: Family of unknown function (DUF5415) (family)
This is a family of unknown function found in Enterococcus.
Wikipedia: A domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. As of 2019, there are almost 4,000 DUF families within the Pfam database representing over 22% of known families. Some DUFs are not named using the nomenclature due to popular usage but are nevertheless DUFs.
Pfam PF04192: Utp21 specific WD40 associated putative domain (domain)
Utp21 is a subunit of U3 snoRNP, which is essential for synthesis of 18S rRNA.
Pfam PF06559: 2'-deoxycytidine 5'-triphosphate deaminase (DCD) N-terminal domain (domain)
This entry includes several bacterial 2'-deoxycytidine 5'-triphosphate deaminase proteins ([ec:3.5.4.13]) (DCD) which consist of two dUTPase-like domains (PDBe:2r9q). This entry represents the N-terminal catalytic domain, which contains the active site residues Arg115 and Glu138, important for its activity.
Pfam PF11919: Proteasome activator complex subunit 4-like, C-terminal (domain)
This domain is found at the C-terminal end of human Proteasome activator complex subunit 4 (PSME4) and similar sequences from eukaryotes. PSME4 is an associated component of the proteasome that specifically recognises acetylated histones and promotes ATP- and ubiquitin -independent degradation of core histones during spermatogenesis and DNA damage response. This protein adopts a dome-like structure composed of HEAT repeat-like modules and a C-terminal domain that contains a hydrophobic -tyrosine-other motif (this entry). This domain, which adopts an all-alpha structure, is responsible for the interaction with the alpha-ring surface of the 20S.
Pfam PF00030: Beta/Gamma crystallin (domain)
The alignment comprises two Greek key motifs since the similarity between them is very low.
Wikipedia: In anatomy, a crystallin is a water-soluble structural protein found in the lens and the cornea of the eye accounting for the transparency of the structure. It has also been identified in other places such as the heart, and in aggressive breast cancer tumors.
The physical origins of eye lens transparency and its relationship to cataract are an active area of research. Since it has been shown that lens injury may promote nerve regeneration,
crystallin has been an area of neural research. So far, it has been demonstrated that crystallin β b2 (crybb2) may be a neurite-promoting factor.
Pfam PF17208: RNA binding Region (family)
This entry represents the RNA-binding region of human SCML2/4, also found in other Polycomb-group proteins from the Scm (Sex comb on midleg) subfamily. Members of this group are found in vertebrates.
Sex comb on midleg-like protein 2 (SCML2) is a mammalian Polycomb-group protein, which associates with the Polycomb repressive complex-1 (PRC1) that is essential for the epigenetic regulation of gene expression. Isoform SCML2A has been shown to bind to PRC1 via its SPM domain and to interact with ncRNAs through a novel RNA-binding region (RBR). The RBR is necessary for targeting of SCML2A to chromatin and PRC1 recruitment, suggesting a role for ncRNAs in regulating SCML2 function .
Sex comb on midleg-like protein 4 (SCML4), which is thought to have a similar function, has been associated with coronary artery disease .
Pfam PF21596: Lactoylglutathione lyase, putative-like, N-terminal (domain)
This domain is found at the N-terminal end of Putative lactoylglutathione lyase from Bdellovibrio bacteriovorus (Bd2520) and similar sequences predominantly found in prokaryotes. It shows a three-stranded beta-sheet and one alpha-helix.
Pfam PF19278: Hydantoinase/oxoprolinase C-terminal domain (domain)
This domain is found at the C-terminus of acetophenone carboxylase alpha subunit. According to ECOD this domain adopts a reverse ferredoxin fold. This domain is found at the C-terminus of a wide range of related enzymes subunits.
Pfam PF04213: Htaa (family)
This domain is found in HtaA, a secreted protein implicated in iron acquisition and transport.
Pfam PF03467: Smg-4/UPF3 family (family)
This family contains proteins that are involved in nonsense mediated mRNA decay. A process that is triggered by premature stop codons in mRNA. The family includes Smg-4 and UPF3.
Pfam PF09238: Interleukin-4 receptor alpha chain, N-terminal (domain)
Members of this family are related in overall topology to fibronectin type III modules and fold into a sandwich comprising seven antiparallel beta sheets arranged in a three-strand and a four-strand beta-pleated sheet. They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of a Th2-dominated early immune response.
Wikipedia: The interleukin 4 receptor is a type I cytokine receptor. It is a heterodimer, that is, composed of two subunits. IL4R is the human gene coding for IL-4Rα, the subunit which combines with either common gamma chain or with IL-13Rα1.
Pfam PF05539: Pneumovirinae attachment membrane glycoprotein G (family)
This family of proteins contain the major surface glycoprotein of turkey rhinotracheitis virus (TRTV), avian pneumovirus (APV), the aetiological agent of turkey rhinotracheitis (TRT), and other Metapneumoviruses. The major surface glycoprotein is the attachment (G) protein, which, by analogy with other respiratory syncytial viruses (RSV), has been proposed to be responsible for virus binding to its cell receptor. The APV G gene and its predicted protein have several features in common with their RSV counterparts. Both G proteins are type II glycoproteins and both the RSV G and APV G proteins are heavily O-glycosylated. In both RSV and APV, the G protein is the most variable protein and is a major target for neutralizing antibodies .
Pfam PF18456: Diiron non-heme beta-hydroxylase N-terminal domain (domain)
This is the N-terminal domain found in Diiron non-heme beta-hydroxylase (CmlA). CmlA catalyzes beta-hydroxylation of the precursor molecule l-p-aminophenylalanine (l-PAPA) to form l-p-aminophenylserine. Structural analysis indicate that the N-terminal domain facilitates dimerization and has a mixed alpha-beta topology. Furthermore, a projecting 'dimerization arm' (residues 108-146) from the N-terminal domain of CmlA mediates the interaction between the monomers.
Pfam PF14473: RD3 protein (family)
RD3 is a human protein that is found preferentially expressed in the retina.  Mutations in RD3 causes Leber Congenital Amaurosis type 12.
Pfam PF15955: Cuticle protein (family)
Adult cuticle protein 1 (Acp1) from Drosophila may be involved in some specialised function such as thickening of the adult cuticle .
Pfam PF12994: Domain of unknown function, E. rectale Gene description (DUF3878) (family)
Based on Eubacterium rectale gene EUBREC_0973. As seen in gene expression experiments (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE14737). it appears to be upregulated in the presence of Bacteroides thetaiotaomicron vs when isolated in culture.
Wikipedia: A domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. As of 2019, there are almost 4,000 DUF families within the Pfam database representing over 22% of known families. Some DUFs are not named using the nomenclature due to popular usage but are nevertheless DUFs.
Pfam PF02092: Glycyl-tRNA synthetase beta subunit (family)
This entry represents the beta subunit of glycine-tRNA ligase.
The aminoacyl-tRNA synthetases (6.1.1) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction. These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold and are mostly monomeric, while class II aminoacyl-tRNA synthetases share an anti-parallel Î²-sheet formation, flanked by Î±-helices , and are mostly dimeric or multimeric. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic aci, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan and valine belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, lysine, phenylalanine, proline, serine, and threonine belong to class-II synthetases.

The 10 class I synthetases are considered to have in common the catalytic domain structure based on the Rossmann fold, which is totally different from the class II catalytic domain structure. The class I synthetases are further divided into three subclasses, a, b and c, according to sequence homology. No conserved structural features for tRNA recognition by class I synthetases have been established.
Pfam PF20797: HepT-like protein (domain)
This family of proteins are related to the HepT toxin-antitoxin system proteins [pfam:PF01934]. This suggests that these proteins are ribonuclease toxins.
Pfam PF22683: Nab2-like CCCH zinc finger (domain)
This entry represents the C-terminal zinc CCCH finger of Nab2-like proteins from fungi. Nab2 is a nuclear polyadenylated RNA-binding protein.