SII-SWORD/CoKE huggingface dataset:
ABC transporter, tyrosine-binding protein-like (ABC_transpt-TYRBP-like)
Type: Family

ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energize diverse biological systems. ABC transporters are minimally constituted of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These regions can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.

This family includes the tyrosine-binding protein from Clostridium difficile, which is probably part of an ABC transporter complex involved in tyrosine uptake and it may also import phenylalanine .
Protein of unknown function DUF535 (DUF535)
Type: Family

Family member Shigella flexneri VirK (

) is a virulence protein required for the expression, or correct membrane localisation of IcsA (VirG) on the bacterial cell surface . This family also includes Pasteurella haemolytica lapB (

), which is thought to be membrane-associated.
Regulator of chromosome segregation-like, C-terminal domain (RocS-like_C)
Type: Domain

This entry represents the C-terminal domain found in proteins predominantly from Firmicutes, including Regulator of chromosome segregation from Streptococcus pneumoniae (RocS). RocS is required for cell division and chromosome segregation. It binds to DNA and is involved in segregating the origin of replication (oriC) region to new daughter cells. When the nucleoid is not properly segregated, it is involved in blocking the cell division to protect the nucleoid against premature truncation by the newly forming septum, a function which is dependent on CpsD and its autophosphorylation level .

This region had previously been related with a theta-type replication mechanism .
Poxvirus B22 (Poxvirus_B22)
Type: Family

This entry represents B22 proteins of Poxviruses .
LytTR DNA-binding domain (LytTR_DNA-bd_dom)
Type: Domain

The LytTR domain is a DNA-binding, potential winged helix-turn-helix (wHTH) domain of about 100 amino acids, present in bacterial transcriptional regulators of the algR/agrA/lytR family. It is named after Bacillus subtilis LytT and Staphylococcus aureus lytR response regulators, involved in the regulation of cell autolysis .
Protein of unknown function DUF538 (DUF538)
Type: Family

This family consists of several plant proteins of unknown function.
Glutaredoxin 2, C-terminal (Glutaredoxin2_C)
Type: Domain

Glutaredoxins , also known as thioltransferases (disulphide reductases), are small proteins of approximately one hundred amino-acid residues which utilise glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system .

Glutaredoxin functions as an electron carrier in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Like thioredoxin (TRX), which functions in a similar way, glutaredoxin possesses an active centre disulphide bond . It exists in either a reduced or an oxidized form where the two cysteine residues are linked in an intramolecular disulphide bond. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH ->GSH reductase ->GSH ->GRX ->protein substrates . By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress.

Glutaredoxin has been sequenced in a variety of species. On the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is most probably a glutaredoxin. Finally, it must be noted that Bacteriophage T4 thioredoxin seems also to be evolutionary related. In position 5 of the pattern T4 thioredoxin has Val instead of Pro.

Unlike other glutaredoxins, glutaredoxin 2 (Grx2) cannot reduce ribonucleotide reductase . Grx2 has significantly higher catalytic activity in the reduction of mixed disulphides with glutathione (GSH) compared with other glutaredoxins. It adopts a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal α helical domain. The active site residues (Cys9-Pro10-Tyr11-Cys12, in Escherichia coli Grx2,

), which are found at the interface between the N- and C-terminal domains are identical to other glutaredoxins, but there is no other similarity between glutaredoxin 2 and other glutaredoxins. Grx2 is structurally similar to glutathione-S-transferases (GST), but there is no obvious sequence similarity . The inter-domain contacts are mainly hydrophobic, suggesting that the two domains are unlikely to be stable on their own. Both domains are needed for correct folding and activity of Grx2. It is thought that the primary function of Grx2 is to catalyse reversible glutathionylation of proteins with GSH in cellular redox regulation including the response to oxidative stress. The N-terminal domain is

.
(Na+)-NQR maturation factor NqrM (NqrM)
Type: Family

The NqrM gene is often found adjacent to the nqr operons that encode (Na+)-NQR subunits. NqrM is a maturation factor of bacterial Na+-translocating NADH:quinone oxidoreductase, presumably involved in the delivery of Fe to form the (Cys)4[Fe] centre between subunits NqrD and NqrE. The four conserved Cys residues found in NqrM are required for (Na+)-NQR maturation and may serve as ligands for a metal ion or metal cluster used to build up the (Na+)-NQR molecule .
Interleukin-1 receptor-associated kinase 1-binding protein 1/DUF541 (SIMPL/DUF541)
Type: Family

This entry represents a family of proteins from bacteria, archaea and animals, including Interleukin-1 receptor-associated kinase 1-binding protein 1 from mouse, which has been named SIMPL (signalling molecule that associates with mouse pelle-like kinase). SIMPL is a component of the IRAK1-dependent TNFRSF1A signaling pathway that leads to NF-kappa-B activation and is required for cell survival. It functions by enhancing RelA transcriptional activity . Separate experiments demonstrate that a mouse family member (named LaXp180) binds the Listeria monocytogenes surface protein ActA, which is a virulence factor that induces actin polymerisation. It may also bind stathmin, a protein involved in signal transduction and in the regulation of microtubule dynamics . In bacteria its function is unknown, but it is thought to be located in the periplasm or outer membrane.
Intermembrane transport protein PqiA-like (PqiA-like)
Type: Family

This family includes intermembrane transport proteins PqiA and YebS, which are components of transport pathways that contribute to membrane integrity . The promoter for the pqiA gene is inducible by paraquat, a superoxide radical-generating agent, and other known superoxide generators .
Essential recombination function protein (ERF_bacteria_virus)
Type: Family

The DNA single-strand annealing proteins (SSAPs), such as RecT, Red-beta, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. This family includes proteins related to ERF .
Protein of unknown function DUF531 (DUF531)
Type: Family

This is a family of hypothetical archaeal proteins.
Helicase-associated domain (Helicase-assoc_dom)
Type: Domain

This is the helicase associated domain (HA2) found as a diverse set of RNA helicases. It has an all α-helical fold that can be divided in two subdomains, an N-terminal degenerated winged helix (WH) and a C-terminal ratchet-like domain . This domain collaborates with the RecA domains at the N-terminal in the formation of a RNA binding channel to allow the helicases to keep a stable grip on the RNA.
Protein of unknown function DUF530 (DUF530)
Type: Family

This is a family of hypothetical archaeal proteins.
H/ACA ribonucleoprotein complex, subunit Gar1/Naf1 (H/ACA_rnp_Gar1/Naf1)
Type: Family

H/ACA ribonucleoprotein particles (RNPs) are a family of RNA pseudouridine synthases that specify modification sites through guide RNAs. The function of these H/ACA RNPs is essential for biogenesis of the ribosome, splicing of precursor mRNAs (pre-mRNAs), maintenance of telomeres and probably for additional cellular processes . All H/ACA RNPs contain a specific RNA component (snoRNA or scaRNA) and at least four proteins common to all such particles: Cbf5, Gar1, Nhp2 and Nop10. These proteins are highly conserved from yeast to mammals and homologues are also present in archaea . The H/ACA protein complex contains a stable core composed of Cbf5 and Nop10, to which Gar1 and Nhp2 subsequently bind .

Naf1 is an RNA-binding protein required for the maturation of box H/ACA snoRNPs complex and ribosome biogenesis. During assembly of the H/ACA snoRNPs complex, it associates with the complex, disappearing during maturation of the complex and being replaced by Gar1 to yield mature H/ACA snoRNPs complex. The core domain of Naf1 is homologous to the core domain of Gar1, suggesting that they share a common Cbf5 binding surface .
PD-(D/E)XK nuclease superfamily 7 (PDDEXK_7)
Type: Family

This domain has been identified as a member of the PD-(D/E)XK nuclease superfamily through transitive meta profile searches . The domain has two additional β-strands inserted to the core fold after the first core α-helix. It has been speculated that it could function as s methylation-dependent restriction . The domain has two additional β-strands inserted into the core fold after the first core α-helix. The PD-(D/E)XK signature is clearly conserved corresponding to an invariant PD (motif II) and DAK (motif III) motifs. There is also a conserved glutamic acid in motif I that is most likely to be involved in metal ion binding. The second core α-helix contains an invariant MHXYRD motif. It has been speculated that it could function as s methylation-dependent restriction enzyme .
Phosphomevalonate dehydratase large subunit-like domain (PMDh-L-like_dom)
Type: Domain

This entry represents a domain that covers the whole sequence in Phosphomevalonate dehydratase large subunit from Aeropyrum pernix (PMDh-L) and similar proteins mainly found in archaea, proteobacteria and fungi. PMDh-L is a component of a hydro-lyase that catalyses the dehydration of mevalonate 5-phosphate (MVA5P) to form trans-anhydromevalonate 5-phosphate (tAHMP) . It is involved in the archaeal mevalonate (MVA) pathway, which provides fundamental precursors for isoprenoid biosynthesis, such as isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) .

This domain is also found at the C-terminal end of Cis-3-hydroxy-L-proline dehydratase from Agrobacterium fabrum (LhpI), which catalyses the dehydration of cis-3-hydroxy-L-proline (c3LHyp) to Delta1-pyrroline-2-carboxylate (Pyr2C) .

Members or this group are distantly related to the Aconitase family of proteins by sequence similarity and secondary structure prediction .
3-deoxy-D-manno-octulosonic-acid transferase, N-terminal (Glycos_transf_N)
Type: Domain

This is a domain found in proteins that transfer activated sugars to a variety of substrates, including glycogen, fructose-6-phosphate and lipopolysaccharides. Proteins bearing this domain transfer UDP, ADP, GDP or CMP linked sugars. This region is flanked at the N terminus by a signal peptide and at the C terminus by a glycosyl transferase group 1 domain (

). The eukaryotic glycogen synthases may be distant members of this bacterial family .
D-aminoacyl-tRNA deacylase DtdA (DtdA)
Type: Family

D-aminoacyl-tRNA deacylases hydrolyse the ester bond between the polynucleotide and the D-amino acid, thereby preventing the accumulation of such mis-acylated and metabolically inactive tRNA molecules. Several aminoacyl-tRNA synthetases have the ability to transfer the D-isomer of their amino acid onto their cognate tRNA .
Protein of unknown function DUF515 (DUF515)
Type: Family

This is a family of hypothetical archaeal proteins.
Protein of unknown function DUF501 (DUF501)
Type: Family

This is a family of uncharacterised bacterial proteins.
MICOS complex subunit Mic10 (Mic10)
Type: Family

Mic10 (also known as MINOS1) is a component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane .
Small EDRK-rich factor-like, N-terminal (SERF-like_N)
Type: Domain

This entry represents the N-terminal domain of Small EDRK-rich factors (SERFs), including SERF1/2 from human. Proteins containing this domain are short proteins that are rich in aspartate, glutamate, lysine and arginine . SERF1/2 are positive regulators of amyloid protein aggregation and proteotoxicity; they induce conformational changes in amyloid proteins, driving them into compact formations preceding the formation of aggregates .
Mss4 (Mss4)
Type: Family

MSS4 (mammalian suppressor of Sec4) is an evolutionarily highly conserved protein, which is expressed in all mammalian tissues. Although it was first proposed to function as a guanine exchange factor (GEF) for Rab GTPases, it was soon described as a quite inefficient GEF and was thus suggested to function rather as a chaperone, protecting nucleotide free Rabs from degradation, than as a GEF .

The structure of MSS4 revealed a mostly β fold stabilized by a Zn(2+) ion coordinated by cysteine residues from two CxxC motifs. The fold of the MSS4 domain consists of a central β sheet (betaG-betaK) flanked by a β hairpin (betaB-betaC) on one side and a small variable sheet on the other. A single Zn(2+) ion, coordinated by the thiol groups of cysteine residues from two CxxC motifs located in the betaB-betaC and betaI-betaJ loops, appears to play an important structural role by reinforcing the hydrophobic core formed by the betaB-betaC hairpin, the betaG-betaH loop, and the central β sheet .
Coenzyme F420 hydrogenase/dehydrogenase beta subunit, N-terminal (Co_F420_Hydgase/DH_bsu_N)
Type: Domain

Coenzyme F420 hydrogenase (

) reduces the low-potential two-electron acceptor coenzyme F420. This entry contains the N termini of F420 hydrogenase and dehydrogenase beta subunits . The N terminus of Methanobacterium formicicum formate dehydrogenase beta chain (

,

) is also represented in this entry . This region is often found in association with the 4Fe-4S binding domain (

), and the C terminus

.
MINDY deubiquitinase (MINDY)
Type: Family

This entry represents a group of deubiquitinating (DUB) enzymes known as the MINDY family (MIU-containing novel DUB). Ubiquitin (Ub) is released one molecule at a time from the distal end of proteins with Lys48-linked polyubiquitin chains. Long polyubiquitin chains are preferred. The catalytic Cys and His residues have been identified by site-directed mutagenesis, as has the Gln that participates in formation of the oxyanion hole during catalysis. Despite the structural similarity to papain-like cysteine peptidases, a residue corresponding to the Asn that orientates the imidazolium ring of the catalytic His has not been identified. Members of the MINDY family of DUBs contain an MIU (motif interacting with Ub) motif, which is a helical motif that binds mono-Ub .
Bul1, N-terminal (Bul1_N)
Type: Domain

This domain is the N terminus of Saccharomyces cerevisiae (Baker's yeast) Bul1 and Bul2. Bul1 binds the ubiquitin ligase Rsp5, via an N-terminal PPSY motif (157-160 in

) . The complex containing Bul1 and Rsp5 is involved in intracellular trafficking of the general amino acid permease Gap1 , degradation of Rog1 in cooperation with Bul2 and GSK-3 , and mitochondrial inheritance . Bul2, which is homologous to Bul1, also interacts with Rsp5 .
Choline kinase, N-terminal (Choline_kin_N)
Type: Domain

This domain is found N-terminal to choline/ethanolamine kinase regions in some plant and fungal choline kinase enzymes (

). This region is only found in some members of the choline kinase family, and is therefore unlikely to contribute to catalysis.
CRISPR-associated protein TM1795 (CRISPR-assoc_prot_TM1795)
Type: Family

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.

This entry represents the N-terminal region from a family of Cas proteins that includes TM1795 from Thermotoga maritima. The N-terminal half of these proteins is the region with the strongest level of conservation.
NDUFAF3/Mth938 domain-containing protein (NDUFAF3/AAMDC)
Type: Family

This entry includes NDUFAF3, an essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) , and the Mth938 domain-containing protein . The crystal structure of NDUFAF3 revealed a 3-layer β+α/β/α topology .
Pectate lyase, N-terminal (Pec_lyase_N)
Type: Domain

This region is found N-terminal to the pectate lyase domain (

) in some plant pectate lyase enzymes.
Coenzyme F420 hydrogenase/dehydrogenase beta subunit, C-terminal (FrhB_FdhB_C)
Type: Domain

Coenzyme F420 hydrogenase (

) reduces the low-potential two-electron acceptor coenzyme F420. This family contains the C-termini of F420 hydrogenase and dehydrogenase beta subunits . The C terminus of Methanobacterium formicicum formate dehydrogenase beta chain (

,

) is also represented in this entry . This region is often found in association with the 4Fe-4S binding domain (

), and the N terminus

.
SWIRM domain (SWIRM)
Type: Domain

The SWIRM domain is a small α-helical domain of about 85 amino acid residues found in eukaryotic chromosomal proteins. It is named after the proteins SWI3, RSC8 and MOIRA in which it was first recognised. This domain mediates protein-protein interactions in the assembly of chromatin-protein complexes . The yeast SWI3 SWIRM structure revealed that it forms a four-helix globular domain containing a helix-turn-helix motif .

The SWIRM domain can be linked to different domains, such as the ZZ-type zinc finger (

), the Myb DNA-binding domain (

), the HORMA domain (

), the amino-oxidase domain, the chromo domain (

), and the JAB1/PAD1 domain.
Zinc finger, SWIM-type (Znf_SWIM)
Type: Domain

This entry represents the SWIM (SWI2/SNF2 and MuDR) zinc-binding domain, which is found in a variety of prokaryotic and eukaryotic proteins, such as mitogen-activated protein kinase kinase kinase 1 (or MEKK1). It is also found in the related protein MEX (MEKK1-related protein X), a testis-expressed protein that acts as an E3 ubiquitin ligase through the action of E2 ubiquitin-conjugating enzymes in the proteasome degradation pathway; the SWIM domain is critical for MEX ubiquitination . SWIM domains are also found in the homologous recombination protein Sws1 , as well as in several hypothetical proteins.

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.
RINT-1/Tip20 (RINT1_Tip20)
Type: Family

This entry includes RINT-1 from animals, Tip20 from yeasts and MAIGO2 (Mag2) from plants. They play a role in anterograde transport from the endoplasmic reticulum (ER) to the Golgi and/or retrograde transport from the Golgi to the ER share sequence similarity . They are part of the CATCHR (complexes associated with tethering containing helical rods) family which comprises the exocyst, COG, GARP, and DSL1 complexes and share a similar structure organisation with an N-terminal coiled-coil and a C-terminal α-helical bundle, which might be a protein-protein interaction module necessary for the formation of functional complexes.

RINT-1 interacts with Rad50 only during late S and G2/M phases and participates in radiation induced checkpoint control . RINT-1 also functions in membrane trafficking from the endoplasmic reticulum (ER) to the Golgi complex in interphase cells .

Tip20 is involved in the retrograde transport from the Golgi to the ER .

Arabidopsis Mag2 functions in the transport of storage protein precursors between the ER and Golgi complex in plants .
Zinc finger, HIT-type (Znf_HIT)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents the HIT-type zinc finger, which contains 7 conserved cysteines and one histidine that can potentially coordinate two zinc atoms. It has been named after the first protein that originally defined the domain: the yeast HIT1 protein (

) . The HIT-type zinc finger displays some sequence similarities to the MYND-type zinc finger. The function of this domain is unknown but it is mainly found in nuclear proteins involved in gene regulation and chromatin remodeling. This domain is also found in the thyroid receptor interacting protein 3 (TRIP-3)

, that specifically interacts with the ligand binding domain of the thyroid receptor.
Aminoglycoside 6-adenylyltransferase (Aminoglycoside_adenylylTfrase)
Type: Family

Also known as aminoglycoside 6-adenylyltransferase (

), this protein confers resistance to aminoglycoside antibiotics.