SII-SWORD/CoKE huggingface dataset:
Type II/III secretion system, secretin-like domain (T2SS/T3SS_dom)
Type: Domain

This family includes: protein D that is involved in the general (type II) secretion pathway (GSP) within Gram-negative bacteria, a signal sequence-dependent process responsible for protein export and protein G from the type III secretion system.

A number of proteins are involved in the GSP; one of these is known as protein D (GSPD protein), the most probable location of which is the outer membrane . This suggests that protein D constitutes the apparatus of the accessory mechanism, and is thus involved in transporting exoproteins from the periplasm, across the outer membrane, to the extracellular environment.

The type III secretion system is of great interest, as it is used to transport virulence factors from the pathogen directly into the host cell and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis. However, while the latter forms a ring structure to allow secretion of flagellin and is an integral part of the flagellum itself , type III subunits in the outer membrane translocate secreted proteins through a channel-like structure. Protein G aids in the structural assembly of the invasion complex .
Na(+)/H(+) antiporter subunit E1 (Antiport_suE1)
Type: Family

The Mnh complex is a Na+/H+ antiporter that is involved in Na+ excretion. This entry represents Mnh complex subunit E1. It is encoded by one of the seven ORFs of the mnh operon of Staphylococcus aureus. The seven open reading frames (ORFs) are necessary for Na+/H+ antiporter function as demonstrated by functional complementation in Escherichia coli and detection of Na+/H+antiport activity in membrane vesicles prepared from E. coli cells expressing the mnh operon components .
African swine fever virus, family 110 (ASFV_fam_110)
Type: Family

This entry represents a family of proteins specific to the African swine fever virus (ASFV) known as the 110 family . Proteins in this group are responsible for the redistribution of lumenal ER protein to an enlarged ERGIC compartment . They contain a central cysteine rich region with eight conserved cysteines. Some proteins in this entry contain two copies of the cysteine rich region (e.g.

).
6-phosphogluconate dehydrogenase, YqeC-type (6DGDH_YqeC)
Type: Family

Bacillus subtilis contains three classes of 6-phosphogluconate dehydrogenases (6PGD), including Gnd (YqjI), GntZ and YqeC. This entry represent the YqeC class, which in B. subtilis is a truncated 6PGD that possesses a NAD+-dependent activity .
NtA (N-terminal agrin) domain (NtA_dom)
Type: Domain

Agrin is a multidomain heparan sulphate proteoglycan, that is a key organiser for the induction of postsynaptic specializations at the neuromuscular junction. Binding of agrin to basement membranes requires the amino terminal (NtA) domain . This region mediates high affinity interaction with the coiled-coil domain of laminins. The binding of agrin to laminins via the NtA domain is subject to tissue-specific regulation. The NtA domain-containing form of agrin is expressed in non-neuronal cells or in neurons that project to non-neuronal cell such as motor neurons. The NtA domain forms the most N-terminal part, followed by 9 Kazal-like domains and 2 LE domains. The C-terminal part consists of a SEA domain, 4 EGF-like domains and 3 Laminin G domains, responsible for the clustering of acetylcholine receptors .

Tertiairy structures show that the NtA domain folds as a β-barrel core flanked by N-and C-terminal helical regions. The core of the domain consists of 5 β-strands that form 2 β-sheets. The structure belongs to the OB fold family and shows similarity with the protease inhibition domain of TIMP-1, suggesting alternative functions for agrin in addition to synaptogenic activity . Residues Leu 117 and Val 124 in helix 3 of the NtA domain are essential for binding to the laminin gamma1 chain .
Di-haem cytochrome c peroxidase (Di-haem_cyt_c_peroxidsae)
Type: Domain

This is a group of distinct cytochrome c peroxidases (CCPs) that contain two haem groups. Similar to other cytochrome c peroxidases, they reduce hydrogen peroxide to water using c-type haem as an oxidizable substrate. However, since they possess two, instead of one, haem prosthetic groups, bacterial CCPs reduce hydrogen peroxide without the need to generate semi-stable free radicals. The two haem groups have significantly different redox potentials. The high potential (+320 mV) haem feeds electrons from electron shuttle proteins to the low potential (-330 mV) haem, where peroxide is reduced (indeed, the low potential site is known as the peroxidatic site) . The CCP protein itself is structured into two domains, each containing one c-type haem group, with a calcium-binding site at the domain interface. This family also includes MauG proteins, whose similarity to di-haem CCP was previously recognised .
Sugar phosphate transporter domain (Sugar_P_trans_dom)
Type: Domain

This domain is found in a number of sugar phosphate transporters, including those with a specificity for triose phosphate .
Ubiquitin fusion degradation protein Ufd1-like (Ufd1-like)
Type: Family

This entry includes Ubiquitin fusion degradation protein Ufd1 from fungi and Ufd1-like proteins from animals and plants.

Ufd1 is part of the Ufd1-Npl4 complex that functions as the substrate-recruiting cofactor for Cdc48 segregase. The Cdc48-Ufd1-Npl4 complex is involved in degradation of misfolded ER proteins . The Ufd1-Npl4 complex has been found to recruit Cdc48 to ubiquitylated CMG (Cdc45-MCM-GINS) helicase at the end of chromosome replication, thereby driving the disassembly reaction .

In humans, Npl4-Ufd1 acts as a cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I (a viral RNA sensor) .
Transcription factor IIA, alpha/beta subunit (TFIIA_asu/bsu)
Type: Family

Transcription factor IIA (TFIIA) is one of several factors that form part of a transcription pre-initiation complex along with RNA polymerase II, the TATA-box-binding protein (TBP) and TBP-associated factors, on the TATA-box sequence upstream of the initiation start site. After initiation, some components of the pre-initiation complex (including TFIIA) remain attached and re-initiate a subsequent round of transcription. TFIIA binds to TBP to stabilise TBP binding to the TATA element. TFIIA also inhibits the cytokine HMGB1 (high mobility group 1 protein) binding to TBP , and can dissociate HMGB1 already bound to TBP/TATA-box.

Human and Drosophila TFIIA have three subunits: two large subunits, LN/alpha and LC/beta, derived from the same gene, and a small subunit, S/gamma. Yeast TFIIA has two subunits: a large TOA1 subunit that shows sequence similarity to the N-terminal of LN/alpha and the C-terminal of LC/beta, and a small subunit, TOA2 that is highly homologous with S/gamma. The conserved regions of the large and small subunits of TFIIA combine to form two domains: a four-helix bundle (helical domain) composed of two helices from each of the N-terminal regions of TOA1 and TOA2 in yeast; and a β-barrel (β-barrel domain) composed of β-sheets from the C-terminal regions of TOA1 and TOA2 .

This entry represents the precursor that yields both the alpha and beta subunits of TFIIA. The TFIIA heterotrimer is an essential general transcription initiation factor for the expression of genes transcribed by RNA polymerase II .
Glycosyl transferase, ALG6/ALG8 (Glyco_trans_ALG6/ALG8)
Type: Family

N-linked (asparagine-linked) glycosylation of proteins is mediated by a highly conserved pathway in eukaryotes, in which a lipid (dolichol phosphate)-linked oligosaccharide is assembled at the endoplasmic reticulum membrane prior to the transfer of the oligosaccharide moiety to the target asparagine residues. This oligosaccharide is composed of Glc(3)Man(9)GlcNAc(2). The addition of the three glucose residues is the final series of steps in the synthesis of the oligosaccharide precursor. Alg6 transfers the first glucose residue, and Alg8 transfers the second one . In the human alg6 gene, a C-T transition, which causes Ala333 to be replaced with Val, has been identified as the cause of a congenital disorder of glycosylation, designated as type Ic .
Multigene family 505 (MGF_505)
Type: Family

This entry represents multigene family 505 proteins from African swine fever virus (ASFV) viruses. Members have been have been connected with ASFV host range specificity, blocking of the host innate response, and virus virulence .
Xrn1, N-terminal (Xrn1_N)
Type: Domain

This is the N-terminal domain of 5'-3' exoribonuclease 1/2 (Xrn1/2)

, which may be necessary for 5'-3' exonuclease function.
Homing endonuclease, LAGLIDADG domain (LAGLIDADG_dom)
Type: Domain

Homing endonucleases (HEnases) form a large and highly diverse class of proteins encoded by introns and inteins that confer mobility to their host genetic elements. LAGLIDADG HEnases are structured into two tandemly repeated homing endonuclease-like domains . This entry represents the homing endonuclease LAGLIDADG domain .
Atypical dual-specificity phosphatase Siw14-like (Siw14-like)
Type: Family

This group of atypical dual-specificity phosphatases are predominantly from fungi, plants and bacteria. This entry includes budding yeast Siw14 (also known as Oca3) and related proteins. Siw14 is a inositol pyrophosphate phosphatase that modulates inositol pyrophosphate metabolism by dephosphorylating the IP7 isoform 5PP-IP5to IP6 . This entry also includes budding yeast Oca1/2/4/6 and Arabidopsis DSP1/2/3/4/5. All DSPs tested (AtPFA-DSP1, -2, -3, and -5) displayed phosphatase activity toward PI(3,5)P2, with AtPFA-DSP2 showing a higher activity . Oca1/2/4/6 are putative phosphatases associated with the caffeine-sensitivity stress pathway in S. cerevisiae . It also includes dual specificity protein phosphatase TpbA that regulates diverse phenotypes in P.aeruginosa via regulation of the concentration of cellular c-di-GMP . This phosphatase acts by dephosphorylating the membrane-anchored diguanylate cyclase TpbB at tyrosine and serine/threonine sites, leading to inactivation of TpbB and reduced c-di-GMP production .
Late embryogenesis abundant protein, LEA_2 subgroup (LEA_2)
Type: Domain

This entry represents a region found in the subgroup of LEA proteins LEA_2 (LEA14, D-95) . The structure of Arabidopsis LEA14 has been revealed .

LEA (late embryogenesis abundant) proteins were first identified in land plants. Plant LEA proteins have been found to accumulate to high levels during the last stage of seed formation (when a natural desiccation of the seed tissues takes place) and during periods of water deficit in vegetative organs. Later, LEA homologues have also been found in various species . They have been classified into several subgroups in Pfam and according to Bray and Dure .
HSR domain (HSR_dom)
Type: Domain

The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerisation domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region) . This domain can also be found in Vertebrate AutoImmune REgulator (AIRE) protein, a transcription regulator predominantly expressed in thymus medullary epithelial cells which also localises to nuclear dots .
Chitobiase/beta-hexosaminidases, N-terminal domain (CHB/HEX_N_dom)
Type: Domain

This domain is found in the N terminus of chitobiases and beta-hexosaminidases. It is composed of a β sandwich structure that is similar in structure to the cellulose binding domain of cellulase from Cellulomonas fimi , suggesting that it may function as a carbohydrate-binding domain.
Chitobiase C-terminal domain (CHB_C_dom)
Type: Domain

E or "early" set domains are associated with the catalytic domain of chitobiase and beta-hexosaminidases (

) at the C terminus. Chitobiase digests the beta, 1-4 glycosidic bonds of the N-acetylglucosamine (NAG) oligomers found in chitin, an important structural element of fungal cell wall and arthropod exoskeletons. It is thought to proceed through an acid-base reaction mechanism, in which one protein carboxylate acts as the catalytic acid, while the nucleophile is the polar acetamido group of the sugar in a substrate-assisted reaction with retention of the anomeric configuration . The C terminus of chitobiase is composed of a β sandwich structure and may be related to the immunoglobulin and/or fibronectin type III superfamilies. E set domains are associated with different types of catalytic domains at either the N-terminal or C-terminal end and may be involved in homodimeric/tetrameric/dodecameric interactions.
DNA-directed DNA polymerase, family B, mitochondria/virus (DNA-dir_DNA_pol_B_mt/vir)
Type: Domain

This entry is found in DNA polymerase type B proteins. Proteins in this entry are found in plant and fungal mitochondria, and in viruses.
Membrane transport protein MMPL domain (MMPL_dom)
Type: Domain

This entry represents a domain found in the MmpL family of membrane transport proteins. Many of the proteins contain two copies of this aligned region. Some members have been characterised, for instance, Mycobacterium tuberculosis MMPL10 is required for the biosynthesis of polyacyltrehalose (PAT) and the transport of diacyltrehalose (DAT) and possibly PAT to the cell surface , while MMPL4 is a part of an export system required for biosynthesis and secretion of siderophores .
Nucleoporin, Nup155-like (Nucleoporin_Nup155)
Type: Family

This is a family of nucleoporin proteins (Nups). Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells, and mediate bidirectional nucleocytoplasmic transport, especially of mRNA and proteins. Two subsets of nucleoporins that contain peptide repeats have been identified: one is characterised by the FG (Phe-Gly) repeat; the other, which is included in this family, contain WD (Trp-Asp) repeats. WD repeat Nups (Nup37, Nup43, Seh1, ALADIN, RAE, and Sec13) are thought to be involved in the assembly of structural domains of the nuclear pore complex .
Cleavage/polyadenylation specificity factor, A subunit, C-terminal (Cleavage/polyA-sp_fac_asu_C)
Type: Domain

This family includes a region that lies towards the C terminus of the cleavage and polyadenylation specificity factor (CPSF) A (160kDa) subunit. CPSF is involved in mRNA polyadenylation and binds the AAUAAA conserved sequence in pre-mRNA. CPSF has also been found to be necessary for splicing of single-intron pre-mRNAs . The function of the aligned region is unknown but may be involved in RNA/DNA binding.
Lipoprotein NlpA family (Lipoprotein_NlpA)
Type: Family

This entry represents bacterial lipoproteins that belong to the NlpA family . It contains several antigenic members, that may be involved in bacterial virulence. This entry includes the D-methionine binding lipoprotein MetQ, which is the substrate-binding component of a D-methionine permease, a binding protein-dependent, ATP-driven transport system . Other members of this family, such as NlpA, have been identified as putative substrate-binding components of ABC transporters. NlpA, is an inner-membrane-anchored lipoprotein that has been shown to have a minor role in methionine import .
BURP domain (BURP_dom)
Type: Domain

The BURP domain was named after the proteins in which it was first identified: BNM2, USP, RD22, and PG1beta. It is found in the C terminus of a number of plant cell wall proteins, which are defined not only by the BURP domain, but also by the overall similarity in their modular construction. The BURP domain-containing proteins consists of either three or four modules: (i) an N-terminal hydrophobic domain - a presumptive transit peptide, joined to (ii) a short conserved segment or other short segment, (iii) an optional segment consisting of repeated units which is unique to each member, and (iv) the C-terminal BURP domain. Although the BURP domain proteins share primary structural features, their expression patterns and the conditions under which they are expressed differ. The presence of the conserved BURP domain in diverse plant proteins suggests an important and fundamental functional role for this domain . It is possible that the BURP domain represents a general motif for localization of proteins within the cell wall matrix. The other structural domains associated with the BURP domain may specify other target sites for intermolecular interactions .

Some proteins known to contain a BURP domain are listed below :

Brassica protein BNM2, which is expressed during the induction of microspore embryogenesis.

Field bean USPs, abundant non-storage seed proteins with unknown function.

Soybean USP-like proteins ADR6 (or SALI5-4A), an auxin-repressible, aluminium-inducible protein and SALI3-2, a protein that is up-regulated by aluminium.

Soybean seed coat BURP-domain protein 1 (SCB1). It might play a role in the differentiation of the seed coat parenchyma cells.

Arabidopsis RD22 drought induced protein.

Maize ZRP2, a protein of unknown function in cortex parenchyma.

Tomato PG1beta, the beta-subunit of polygalacturonase isozyme 1 (PG1), which is expressed in ripening fruits.

Cereal RAFTIN. It is essential specifically for the maturation phase of pollen development.
DDE superfamily endonuclease domain (DDE_SF_endonuclease_dom)
Type: Domain

Proteins containing this domain are probably endonucleases of the DDE superfamily. This domain contains 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. Proteins containing this domain include tigger transposable element derived proteins from mammals and protein Pdc2 from budding yeasts . Interestingly, proteins conatining this domain also includes the Centromere Protein B (CENP-B) protein, which appears to have lost the metal binding residues in this domain and is unlikely to have endonuclease activity. CENP-B is a an inner kinetochore protein that binds to a specific centromere sequence .
Corona nucleocapsid I (Corona_nucI)
Type: Family

Members of this family are Coronavirus proteins that are located in the nucleocapsid .
Otopetrin (Otopetrin)
Type: Family

The otopetrins are a group of proteins evolutionarily conserved among metazoan . In most vertebrates there are three Otopetrin genes that encode three proteins, OTOP1, OTOP2, and OTOP3. All form proton-selective ion channels that allow influx of protons into cells
. The structure of otopetrin-1 (

) shows it to have 12 transmembrane domains, with three conserved sub-domains (OD-1 to OD-III) . Otopetrins were initially thought to modulate calcium homeostasis and influx of calcium in response to extracellular ATP but were subsequently shown to form proton-selective ion channels .
Spermatogenesis-associated protein 20-like, TRX domain (Ssp411-like_TRX)
Type: Domain

This entry represents the TRX domain found in highly conserved proteins present in eukaryotes, bacteria and archaea, about 600-800 amino acids in length. This domain contains a redox active CXXC motif. The human/rat protein, called Spermatogenesis-associated protein 20 (SSP411), is specifically expressed in the testis in an age-dependent manner. The SSP411 mRNA is increased during spermiogenesis and is localized in round and elongated spermatids, suggesting a function in fertility regulation .
Ribosome biogenesis GTPase RsgA (Ribosome_biogen_GTPase_RsgA)
Type: Family

This entry contains Escherichia coli (strain K12) RsgA, which plays a role in the late maturation steps of the functional core of the 30S ribosomal subunit. It removes RbfA from mature, but not immature, 30S ribosomes in a GTP-dependent manner , and binds the 30S subunit making contact with the head, platform and rRNA helix 44 . RsgA (sometimes known as YjeQ or EngC) is an unusual circulary permuted GTPase that catalyzes rapid hydrolysis of GTP with a slow catalytic turnover. It is dispensible for viability, but important for overall fitness. The intrinsic GTPase activity is stimulated by the presence of 30S (160-fold increase in
k
cat
) or 70S (96 fold increase in
k
cat
) ribosomes . The GTPase is inhibited by aminoglycoside antibiotics such as neomycin and paromycin streptomycin and spectinomycin . This inhibition is not due to competition for binding sites on the 30S or 70S ribosome .
Luc7-related (Luc7-rel)
Type: Family

This family consists of several Luc7 protein homologues that are restricted to eukaryotes. In budding yeast, Luc7 is an essential subunit of the yeast U1 snRNP, which forms the spliceosomal commitment complex with other proteins that targets pre-mRNA to the splicing pathway . Its N-terminal zinc finger has been found to bind pre-mRNA . This entry also contains human and mouse Luc7 like (LUC7L) proteins .
Lateral organ boundaries, LOB (LOB)
Type: Domain

The lateral organ boundaries (LOB) gene is expressed at the adaxial base of initiating lateral organs and encodes a plant-specific protein of unknown function. The N-terminal one half of the LOB protein contains a conserved approximately 100-amino acid domain (the LOB domain) that is present in 42 other Arabidopsis thaliana proteins and in proteins from a variety of other plant species. Genes encoding LOB domain (LBD) proteins are expressed in a variety of temporal- and tissue-specific patterns, suggesting that they may function in diverse processes
The LOB domain contains conserved blocks of amino acids that identify the LBD gene family. In particular, a conserved C-x(2)-C-x(6)-C-x(3)-C motif, which is defining feature of the LOB domain, is present in all LBD proteins. It is possible that this motif forms a new zinc finger .
Protein of unknown function DUF261 (DUF261)
Type: Family

This is a group of proteins of unknown function.
Protein of unknown function FRD2 (FRD2)
Type: Family

This is group of bacteriophage proteins has no known function.
Glucanosyltransferase (Glucanosyltransferase)
Type: Family

This is a family of yeast glycosylphosphatidylinositol-anchored beta(1-3)glucanosyltransferases . It includes Candida albicans pH-regulated protein PHR1, which is required for apical growth and plays a role in morphogenesis and Saccharomyces cerevisiae glycolipid anchored surface protein Gas1-5 .

Gas1 is a beta-1,3-glucanosyltransferase that was initially characterised at the cell wall where it remodels chains of beta-1,3-glucan. Later, it was found to be involved in transcriptional silencing and DNA damage response .
Glutathione synthase, substrate-binding domain (GSH_synth_subst-bd)
Type: Domain

This entry represents the substrate-binding domain of glutathione synthetase (

) (GSS), a homodimeric enzyme that catalyses the conversion of gamma-L-glutamyl-L-cysteine and glycine to phosphate and glutathione in the presence of ATP. This is the second step in glutathione biosynthesis, the first step being catalysed by gamma-glutamylcysteine synthetase . In humans, defects in GSS are inherited in an autosomal recessive way and are the cause of severe metabolic acidosis, 5-oxoprolinuria, and increased rate of haemolysis and defective function of the central nervous system. The substrate-binding domain has a 3-layer α/β/α structure .