SII-SWORD/CoKE huggingface dataset:
Large ribosomal subunit protein P1/P2, N-terminal domain (P1/P2_N_sf)
Type: Homologous_superfamily

This domain is found in the eukaryotic 60S ribosomal proteins P1 and P2, as well as in archaebacterial P1 (also known as 50S ribosomal protein L12). It is involved in dimerization . These proteins play an important role in the elongation step of protein synthesis .
Tc1-like transposase, DDE domain (Tc1-like_DDE_dom)
Type: Domain

This entry represents the DDE containing domain found in Tc1-like transposases . Tc1-like transposases are composed of three domains, the first two making up a bipartite DNA-binding domain, and the third a catalytic core domain containing a DDE motif . Transposases bind to the inverted terminal repeats (ITRs) of a transposon and catalyze the mobilization of the transposon to new location. Tc1 from C. elegans has been shown to serve as an endonuclease that produce a single strand nick at the 5'-end of the transposon .

Tc1 transposases are part of the DD[E/D]-transposase family that contain a characteristic motif of three acidic residues, two of which are aspartic acids and one is either glutamic or, in some cases, a third aspartic acid, a [D, D, (E or D)] motif. DD[E/D]-transposase family members have a common RNase H-like fold that brings three catalytic residues into close proximity for catalysis .
SNF2-like, N-terminal domain superfamily (SNF2-like_sf)
Type: Homologous_superfamily

This domain is found in proteins involved in a variety of processes including transcription regulation (e.g., SNF2, STH1, MOT1), DNA repair (e.g., RAD16, RAD5), DNA recombination (e.g., RAD54), and chromatin unwinding (e.g., ISWI) as well as a variety of other proteins with little functional information . SNF2 functions as the ATPase component of the SNF2/SWI multisubunit complex, which utilises energy derived from ATP hydrolysis to disrupt histone-DNA interactions, resulting in the increased accessibility of DNA to transcription factors.

Proteins that contain this domain appear to be distantly related to the
DEAX box helicases.
Phycobilisome, alpha/beta subunit superfamily (Phycobilisome_asu/bsu_sf)
Type: Homologous_superfamily

Cyanobacteria and red algae harvest light through water-soluble complexes, called phycobilisomes, which are attached to the outer face of the thylakoid membrane . These complexes are capable of transferring the absorbed energy to the photosynthetic reaction centre with greater than 95% efficiency. Phycobilisomes contain various photosynthetic light harvesting proteins known as biliproteins, and linker proteins which help assemble the structure. The two main structural elements of the complex are a core located near the photosynthetic reaction centre, and rods attached to this core. Allophycocyanin is the major component of the core, while the rods contain phycocyanins, phycoerythrins and linker proteins. The rod biliproteins harvest photons, with the excitation energy being passed through the rods into the allophycocyanin in the core. Other core biliproteins subsequently pass this energy to chlorophyll within the thylakoid membrane.

This entry represents the alpha and beta subunits found in biliproteins from cyanobacteria and red algae. Structural studies indicate that the basic structural unit of most biliproteins is a heterodimer composed of these alpha and beta subunits . The full protein is a ring-like trimer assembly of these heterodimers. Each subunit of the heterodimer has eight helices and binds chromophores through thioester bonds formed at particular cysteine residues. These chromophores, also known as bilins, are open-chain tetrapyrroles whose number and type vary with the particular biliprotein eg R-phyocerythrin binds five phycoerythrobilins per heterodimer, while allophycocyanin binds two phycocyanobilins per heterodimer.
YprB, ribonuclease H-like domain (YprB_RNase_H-like_dom)
Type: Domain

This entry represents the ribonuclease H-like domain found in a group of uncharacterised proteins, including YprB from Bacillus subtilis.
Transposase IS701-like, DDE domain (IS701-like_DDE_dom)
Type: Domain

This domain is a member of the DDE endonuclease superfamily, which contain 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.

This domain can be found in the transposase for insertion sequence IS701 from Microchaete diplosiphon .
Ner, winged helix-turn-helix DNA-binding domain (Ner_HTH_dom)
Type: Domain

This entry represent the winged helix-turn-helix DNA-binding found in Ner, a transcriptional regulator from Escherichia phage Mu . This domain can also be found in sugar fermentation stimulation protein B (sfsB), also known as Ner-like protein, from Escherichia coli .
ArnR1-like, winged helix-turn-helix domain (ArnR1-like_HTH)
Type: Domain

This domain is found in ArnR1 from Sulfolobus acidocaldarius. ArnR1 is involved in regulation of archaellar gene expression .

This winged helix-turn-helix domain contains an extended C-terminal α helix which is responsible for dimerisation of this domain .
Regulatory protein RepA, RSF1010-type (RepA)
Type: Family

RepA is a hexameric replicative helicase encoded by a plasmid, which is found in bacteria. RepA is a 5'-3' DNA helicase which can utilize ATP, GTP and CTP to a lesser extent .
General stress protein, FMN-binding split barrel domain (YdaG_split_barrel_FMN-bd)
Type: Domain

This domain, approximately 140 residues in length, is mainly found in general stress proteins in various Xanthomonas species. It is composed of a six-stranded antiparallel β-barrel flanked by five α-helices and can bind to FMN and FAD, suggesting that it may help the bacteria to react against the oxidative stress induced by the defense mechanisms of the plant . Proteins containing this domain also include some fungal proteins, such as bli-3 from Neurospora crassa. Bli-3 is induced by blue-light and osmotic stress .
PD-(D/E)XK endonuclease-like domain, AddAB-type (PDDEXK_AddAB-type)
Type: Domain

This entry represent a PD-(D/E)XK endonuclease-like domain . PD-(D/E)XK nucleases constitute a large and highly diverse superfamily of enzymes that display little sequence similarity. However, they share a common core fold and a few critical active site residues . This domain can be found at the C terminus of nuclease/helicase AddA, AddB, and RecB.

There are two classes of helicase-nuclease complex involved in the initiation step for recombinational repair. AddAB-type enzymes (also called RexAB) are found mainly in Gram-positive bacteria, whereas heterotrimeric RecBCD-type enzymes are found mainly in Gram-negative bacteria . The RecBCD holoenzyme has a single nuclease domain found in RecB .
NadR/Ttd14, AAA domain (NadR/Ttd14_AAA_dom)
Type: Domain

This entry represents the AAA domain found in a group of proteins, including NadR from Escherichia coli and Ttd14 from Drosophila melanogaster. NadR has three activities: DNA binding, nicotinamide mononucleotide (NMN) adenylyltransferase and ribosylnicotinamide (RN) kinase . Ttd14 is a GTP-binding protein that regulates trafficking of the TRPL ion channel in Drosophila photoreceptor cells .

AAA ATPases belong to the AAA+ superfamily of ringshaped P-loop NTPases, which exert their activity through the energy-dependent unfolding of macromolecules .
Uncharacterized membrane protein YkvI-like (YkvI-like)
Type: Family

This entry includes a group of uncharacterised membrane proteins, including YkvI from Bacillus subtilis and YyaD.
Rad50/SbcC-type AAA domain (Rad50/SbcC_AAA)
Type: Domain

This entry represents the AAA domain found in some DNA repair proteins, such as Rad50, SbcC, RecF, RecN and structural maintenance of chromosomes proteins 5 and 6 (Smc5-Smc6) .

The proteins in this superfamily are characterised by the structural conservation of a central ATPase domain of about 250 amino acids called the AAA module. Typically, the AAA domain can be divided into two structural subdomains, an N-terminal P-loop NTPase α-β-α subdomain that is connected to a smaller C-terminal all-α subdomain. The α-β-α subdomain adopts a Rossman fold and contains several motifs involved in ATP binding and hydrolysis, including classical motifs Walker A and Walker B . The all-α subdomain , is much less conserved across AAA proteins.

The AAA+ superfamily of ATPases is found in all kingdoms of living organisms where they participate in diverse cellular processes including membrane fusion, proteolysis and DNA replication. Although the terms AAA+ and AAA are often used loosely and interchangeably, the classical AAA family members are distinguished by their possession of the SRH region in the AAA module. Many AAA+ proteins are involved in similar processes to those of AAA proteins (facilitation of protein folding and unfolding, assembly or disassembly of proteins complexes, protein transport and degradation), but others function in replication, recombination, repair and transcription. For a review see .
Hydrogenase-4 component E-like (HyfE-like)
Type: Family

HyfE is a probable component of hydrogenase 4 . This entry also includes some uncharacterised proteins.
Glycosyltransferase RgtA/B/C/D-like (RgtA/B/C-like)
Type: Domain

This entry represents a group of glycosyltransferases, including RgtA/B/C/D from Rhizobium leguminosarum bv. viciae. RgtA/B/C/D are involved in the modification of the lipopolysaccharide (LPS) inner core .
FAD-dependent urate hydroxylase HpyO/Asp monooxygenase CreE-like, FAD/NAD(P)-binding domain (HpyO/CreE_NAD-binding)
Type: Domain

This entry represents the FAD/NAD(P)-binding domain found in a group of proteins, including HpyO from Xanthomonas campestris pv. campestris (FAD-dependent urate hydroxylase) and L-aspartate N-monooxygenase CreE from Streptomyces cremeus. HpyO catalyses the hydroxylation of urate to 5-hydroxyisourate (HIU) . CreE is involved in the biosynthesis of cremeomycin, a light-sensitive o-diazoquinone with antibacterial and antiproliferative effects. It catalyses the iterative oxidation of L-aspartic acid to nitrosuccinic acid (2-nitrobutanedioate) .
Predicted DNA-binding protein, ribbon-helix-helix domain (Predicted_DNA_bind_prot_RHH)
Type: Domain

This entry represents the ribbon-helix-helix domain found in a group of predicted DNA-binding proteins.
YhaN, AAA domain (YhaN_AAA)
Type: Domain

This AAA domain is found in a group of uncharacterised proteins, including YhaN from Bacillus subtilis and DNA double-strand break repair Rad50 ATPase from Archaeoglobus fulgidus.

AAA ATPases belong to the AAA+ superfamily of ringshaped P-loop NTPases, which exert their activity through the energy-dependent unfolding of macromolecules .
MSMEG_1276-like, nucleoside triphosphate pyrophosphohydrolase domain (MSMEG_1276-like_NTP-PPase_dom)
Type: Domain

The domain can be found in some uncharacterised hypothetical proteins from archaea and bacteria. Although their biological roles remain unclear, the family members show significant sequence similarity to the dimeric 2-deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTP pyrophosphatase or dUTPase) and NTP-PPase MazG proteins. However, unlike typical tandem-domain MazG proteins, this group of proteins contain a single MazG-like domain .
Splicing factor 3B subunit 1-like (SF3b_su1-like)
Type: Family

This entry includes animal splicing factor 3B subunit 1 (SF3B1, also known as
SAP 155) and its homologues such as Hsh155 from budding yeasts and Prp10 from fission yeasts . SF3B1 is a component of the splicing factor SF3B complex, which is important for anchoring the spliceosome to precursor mRNA. SF3B1 binds to pre-mRNA on both sides of the intron branch site region . This subunit is required for 'A' splicing complex assembly (formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA) and 'E' splicing complex assembly .
Nedd8-like ubiquitin (Nedd8-like)
Type: Domain

Nedd8 (also known as Rub1) has a single conserved ubiquitin-like domain that is part of a protein modification pathway similar to that of ubiquitin . Nedd8 modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis . This entry also includes Nedd8-like proteins from fungi and plants.
Armadillo-type fold containing protein ARMC8/Vid28 (ARMC8/Vid28)
Type: Family

Proteins in this family contain the armadillo-type fold, such as ARMC8 from humans and Vid28 from budding yeasts. Vid28 is a subunit of the GID Complex, a multisubunit ubiquitin ligase, involved in catabolite-induced degradation of gluconeogenic enzymes . ARMC8 plays an important role in regulating cell migration and proliferation, but its exact function is not clear .
BioF2-like, acetyltransferase domain (BioF2-like_GNAT_dom)
Type: Domain

This entry represents the acetyltransferase domain found in a group of proteins, including BioF2 from Mycobacterium tuberculosis. BioF2 is a putative 8-amino-7-oxononanoate synthase.
AP-5 complex subunit beta-1 (AP5B1)
Type: Family

AP5B1 is part of the AP-5 adaptor protein complex, which may be involved in endosomal transport .
FRS2, PTB domain (FRS2_PTB)
Type: Domain

FRS2 (also called Suc1-associated neurotrophic factor (SNT)-induced tyrosine-phosphorylated target) proteins are membrane-anchored adaptor proteins. They are composed of an N-terminal myristoylation site followed by a phosphotyrosine binding (PTB) domain, which has a PH-like fold, and a C-terminal effector domain containing multiple tyrosine and serine/threonine phosphorylation site. The FRS2/SNT proteins show increased tyrosine phosphorylation by activated receptors, such as fibroblast growth factor receptor (FGFR) and TrkA, recruit SH2 domain containing proteins such as Grb2, and mediate signals from activated receptors to a variety of downstream pathways. The PTB domains of the SNT proteins directly interact with the canonical NPXpY motif of TrkA in a phosphorylation dependent manner, they directly bind to the juxtamembrane region of FGFR in a phosphorylation-independent manner . This domain can also be found in FRS3 .
YjgH-like (YjgH-like)
Type: Family

YjgH belongs to a large family of YjgF/YER057c/UK114-like proteins present in bacteria, archaea, and eukaryotes with no definitive function. The conserved domain is similar in structure to chorismate mutase but there is no sequence similarity and no functional connection. Members of this family have been implicated in isoleucine (Yeo7, Ibm1, aldR) and purine (YjgF) biosynthesis, as well as threonine anaerobic degradation (tdcF) and mitochondrial DNA maintenance (Ibm1) .
Hri1, N-terminal (Hri1_N)
Type: Domain

Saccharomyces cerevisiae Hri1 (Hrr25-interacting protein 1, YLR301w) is a non-essential gene product named for its interaction with the yeast protein kinase Hrr25. It has also been characterised as an interaction partner for Sec72p, but does not seem to be required for protein translocation into the ER. It may be a cytosolic protein. Hri1p contains a tandem repeat of a structural unit that forms a β-barrel with structural similarity to nitrobindin. This N-terminal repeat is involved in homodimerization and may contain a ligand binding site .
AT4G37440-like (AT4G37440-like)
Type: Domain

This domain contains an extensive protein sequence fragment that appears conserved in a number of plant proteins, including the gene product of Arabidopsis thaliana locus AT4G37440. The homologue from white cabbage cultivars has been identified in transcriptional profiling as expressed at different levels .
Alpha-tubulin N-acetyltransferase (Atat)
Type: Family

Alpha-tubulin N-acetyltransferase was originally known as mechanosensory abnormality protein 17 (Mec-17), as it is the protein product of one of the 18 genes required for the development and function of the touch receptor neuron for gentle touch . Mec-17 specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules . It is inefficient, and its activity is enhanced when tubulin is incorporated in microtubules . It may affect microtubule stability and regulate microtubule dynamics. It can function as an enzymatic timer for microtubule lifetimes .
Stannin (Stannin)
Type: Family

Stannin (SNN) is a mitochondrial membrane protein that plays a role in the toxic effects of organotins . TMT (trimethyltin), an organotin compound extensive used in industry and agriculture, can cause injury to specific regions of the brain. Stannin is expressed in the TMT-damaged neuronal cells and may be involved in mitochondria-mediated apoptosis in these cells . The structure of stannin is composed of three domains: a single transmembrane helix, a linker and a distorted cytoplasmic helix .
GINS complex protein Sld5, alpha-helical domain (Sld5_GINS_A)
Type: Domain

Sld5 is a component of GINS tetrameric protein complex, and within the complex Sld5 interacts with Psf1 via its N-terminal A-domain, and with Psf2 through a combination of the A and B domains . Sld5 in Drosophila is required for normal cell cycle progression and the maintenance of genomic integrity . GINS is a complex of four subunits (Sld5, Psf1, Psf2 and Psf3) that is involved in both initiation and elongation stages of eukaryotic chromosome replication . Besides being essential for the maintenance of genomic integrity, GINS plays a central role in coordinating DNA replication with cell cycle checkpoints and is involved in cell growth. The eukaryotic GINS subunits are homologous and homologues are also found in the archaea; the complex is not found in bacteria. The four subunits of the complex consist of two domains each, termed the α-helical (A) and β-strand (B) domains. The A and B domains of Sld5/Psf1 are permuted with respect to Psf1/Psf3 .
Uncharacterized protein YczE/YyaS-like (YczE/YyaS-like)
Type: Family

This entry includes a group of uncharacterised proteins, including YyaS, HI_0522 and YczE from Bacillus subtilis.
INTS8 (INTS8)
Type: Family

Integrator complex subunit 8 (INTS8) is a component of the multiprotein complex Integrator, which is responsible for the endonucleolytic cleavage in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing .

The Integrator is an RNA polymerase II complex which contains at least 12 novel subunits and core RNAPII subunits. Two of the Integrator subunits share similarity with subunits of the cleavage and polyadenylation specificity factor (CPSF) complex. Integrator has been shown to be recruited to the U1 and U2 snRNA genes, and to mediate the snRNAs' 3' end processing. The Integrator complex is evolutionarily conserved in metazoans, and directly interacts with the C-terminal domain of the RNA polymerase II largest subunit .
IQ domain-containing protein H (IQCH)
Type: Family

This family comprises eukaryotic and prokaryotic proteins. It includes mammalian IQ domain-containing protein H, also known as NYD-SP5, which has a potential role in testis development and spermatogenesis .
NF-kappa-B inhibitor-like protein 1 (NFKBIL1)
Type: Family

NF-kappa-B inhibitor-like protein 1 (NFKBIL1, also known as IKBL) is a member of the nuclear IkB family. Classical IkB proteins retain NF-kB dimers in the cytoplasm; IkBL belongs to the atypical or nuclear IkB proteins . It inhibits LPS-induced NF-kB activation and transcription of TNF-alpha and IL-6 .
Testis-expressed basic protein 1 (TSBP1)
Type: Family

This is a family of uncharacterised proteins from mammals.
CheY-P phosphatase CheX-like (CheX-like)
Type: Family

CheX is responsible for modulating the bacterial swimming behaviour in the presence of external chemicals (nutrients and repellents) . CheX is very closely related to the CheC chemotaxis phosphatase, but it dimerises in a different way, via a continuous β sheet between the subunits. CheC and CheX both dephosphorylate CheY, which controls the sense of flagella rotation and thereby determines swimming behaviour. The structures of CheX and CheC have been solved .
Bombesin receptor-activated protein (BRAP)
Type: Family

Bombesin receptor-activated protein (BRAP, C6orf89) is an important regulator of immune and inflammatory responses in the human airway epithelium . BRAP interacts with the orphan G protein-coupled bombesin receptor subtype 3 . BRAP is widely expressed in human airway epithelial cells and vascular endothelial cells. It regulates NF-kB activity by enhancing histone deacetylase (HDAC) activity .
HSPRO1/HSPRO2 (HSPRO1/HSPRO2)
Type: Family

This entry includes a group of resistance proteins from plants, including HSPRO1 and HSPRO2. HSPRO1 is believed to confer resistance to nematodes . HSPRO2 is involved in basal resistance to the bacterial pathogen Pseudomonas syringae .
Photosystem II PsbY, plant (PsbY_plant)
Type: Family

This entry represents photosystem II core complex protein psbY from plants. In higher plants, two related PsbY proteins exist, PsbY-1 and PsbY-2, which appear to function as a heterodimer. In spinach and Arabidopsis, these two proteins arise from a single-copy nuclear gene that is processed in the chloroplast. PsbY has two low manganese-dependent activities: a catalase-like activity and an L-arginine metabolising activity that converts L-arginine into ornithine and urea .
Antibiotic biosynthesis monooxygenase, predicted (ABM_predict)
Type: Family

This entry includes a group of predicted antibiotic biosynthesis monooxygenase.
DHH phosphoesterase superfamily (DHH_sf)
Type: Homologous_superfamily

DHH phosphoesterase superfamily includes manganese-dependent inorganic pyrophosphatase (family II), Drosophila prune protein and bacterial RecJ exonuclease . Typically, its members consist of two non-similar domains:
domain 1 with parallel sheet of 6 strands and domain 2 with mixed sheet of 5 strands.
GNAT family N-acetyltransferase, predicted (GNAT_N_AcTrfase_prd)
Type: Family

This entry represents a subgroup of the GNAT N-acetyltransferase family. The function of the proteins is not clear.
Papain-like cysteine peptidase superfamily (Papain-like_cys_pep_sf)
Type: Homologous_superfamily

This entry represents the papain-like cysteine peptidase superfamily. Its members typically consist of one α-helix and 4 strands of antiparallel β-sheet and contain the catalytic triad Cys-His-Asn.
Membrane component of ABC transporter, predicted (Membrane_comp_ABC_pdt)
Type: Family

This entry represents a group of bacterial membrane proteins that may be part of the ABC transporter, including the uncharacterised YbbP from Escherichia coli. Rv0987 from Mycobacterium tuberculosis, also included in this entry, is likely part of an ABC transporter complex involved in host cell binding either through secretion of an adherence factor or through maintaining the architecture and integrity of the mycobacterial cell envelope . It could be required for host endothelial-cell invasion and/or intracellular survival .
PF0610-like transcription regulator (PF0610-like)
Type: Family

This entry represents PF0610 protein from Pyrococcus furiosus (

) and related putative transcription regulators in prokaryotes. This protein has a Zn-ribbon embedded in a winged HTH fold. The N-terminal wHTH fold is represented by

. The Zn-ribbon embedded fold is represented by

. This family also represents arsenical resistance operon repressor (ArsR)

and similar metal-regulated homodimeric repressors, which also accquires a winged helix topology in the N-terminal .

The function of PF0610 has not been fully chracterized. wHTH domains containing proteins are believed to serve as DNA- or RNA-binding domains

. A large number of wHTH proteins are transcriptional regulators, while others are involved in chromosome packing. Because of its apparent sequence-independent interaction with DNA, PF0610 could be a part of the chromatin system of P. furiosus. The numerous basic residues in PF0610 ensure strong DNA interactions. The Zn ribbon motif could help improve the structural stability of the protein at a high temperature. Another possibility is that PF0610 is a metal-dependent transcription factor. This is based on DNA microarray data. However, further research is needed to conclude if PF0610 is an iron-containing protein