SII-SWORD/CoKE huggingface dataset:
Dysbindin (Dysbindin)
Type: Family

Dysbindin is an evolutionary conserved 40kDa coiled-coil-containing protein that binds to alpha- and beta-dystrobrevin in muscle and brain. Dystrophin and alpha-dystrobrevin are co-immunoprecipitated with dysbindin, indicating that dysbindin is DPC-associated in muscle. Dysbindin co-localises with alpha-dystrobrevin at the sarcolemma and is up-regulated in dystrophin-deficient muscle. In the brain, dysbindin is found primarily in axon bundles and especially in certain axon terminals, notably mossy fibre synaptic terminals in the cerebellum and hippocampus. Dysbindin may have implications for the molecular pathology of Duchenne muscular dystrophy and may provide an alternative route for anchoring dystrobrevin and the DPC to the muscle membrane . Genetic variation in the human dysbindin gene is also thought to be associated with Schizophrenia .

.
Poxvirus early transcription factor, large subunit (Poxvirus_early-TF_lsu)
Type: Family

The poxvirus early transcription factor (VETF), in addition to the viral RNA polymerase, is required for efficient transcription of early genes
in vitro
. VETF is a heterodimeric protein that binds specifically to early gene promoters. The heterodimer is comprised of an 82kDa (this family) subunit and a 70kDa subunit.
Cytochrome c oxidase assembly protein CtaG/Cox11 (Cyt_c_oxidase_assmbl_CtaG)
Type: Family

Cytochrome c oxidase assembly protein is essential for the assembly of functional cytochrome oxidase protein. In eukaryotes it is an integral protein of the mitochondrial inner membrane. Cox11 is essential for the insertion of Cu(I) ions to form the CuB site. This is essential for the stability of other structures in subunit I, for example haems a and a3, and the magnesium/manganese centre. Cox11 is probably only required in sub-stoichiometric amounts relative to the structural units . The C-terminal region of the protein is known to form a dimer. Each monomer coordinates one Cu(I) ion via three conserved cysteine residues (111, 208 and 210) in Saccharomyces cerevisiae (

). Met 224 is also thought to play a role in copper transfer or stabilising the copper site .
Acyl-protein synthetase, LuxE (LuxE)
Type: Domain

LuxE is an acyl-protein synthetase found in bioluminescent bacteria. LuxE catalyses the formation of an acyl-protein thiolester from a fatty acid and a protein. This is the second step in the bioluminescent fatty acid reduction system, which converts tetradecanoic acid to the aldehyde substrate of the luciferase-catalysed bioluminescence reaction . A conserved cysteine found at position 364 in Photobacterium phosphoreum LuxE (

) is thought to be acylated during the transfer of the acyl group from the synthetase subunit to the reductase. The C-terminal of the synthetase is though to act as a flexible arm to transfer acyl groups between the sites of activation and reduction . A LuxE domain is also found in the Vibrio cholerae RBFN protein (

), which is involved in the biosynthesis of the O-antigen component 3-deoxy-L-glycero-tetronic acid.

This entry represents the LuxE domain, which is found in archaeal and bacterial proteins.
Catechol dioxygenase, N-terminal (Catechol_dOase_N)
Type: Domain

This domain is the N-terminal region of catechol, chlorocatechol or hydroxyquinol 1,2-dioxygenase proteins. This region is always found adjacent to the dioxygenase domain (

).

Dioxygenases catalyse the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms. Cleavage of aromatic rings is one of the most important functions of dioxygenases, which play key roles in the degradation of aromatic compounds. The substrates of ring-cleavage dioxygenases can be classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes use a non-haem Fe(III) to cleave the aromatic ring between two hydroxyl groups (ortho-cleavage), whereas extradiol enzymes (

) use a non-haem Fe(II) to cleave the aromatic ring between a hydroxylated carbon and an adjacent non-hydroxylated carbon (meta-cleavage) . These two subfamilies differ in sequence, structural fold, iron ligands, and the orientation of second sphere active site amino acid residues.

Enzymes that belong to the intradiol family include catechol 1,2-dioxygenase (1,2-CTD) (

); protocatechuate 3,4-dioxygenase (3,4-PCD) (

); and chlorocatechol 1,2-dioxygenase (

) .
Ribosomal RNA small subunit methyltransferase J (16SrRNA_methylTrfase_J)
Type: Family

Ribosomal RNA small subunit methyltransferase J specifically methylates the guanosine in position 1516 of 16S rRNA in Escherichia coli .
tRNAHis guanylyltransferase Thg1 (tRNAHis_GuaTrfase_Thg1)
Type: Family

tRNA His molecules are unusual in having an extra 5' GMP residue (G(-1)) that, in eukaryotes, is added after transcription and RNase P cleavage. Incorporation of this G(-1) residue is a rare example of nucleotide addition occurring at an RNA 5' end in a normal phosphodiester linkage. In Saccharomyces cerevisiae, YGR024c (Thg1p) protein is responsible for this guanylyltransferase reaction . It catalyses the guanylyltransferase step of G(-1) addition using a ppp-tRNA His substrate, and appears to catalyse the activation step using p-tRNA His and ATP. Thus, it catalyses phosphodiester bond formation at the 5' end of RNAs, formally in a 3'-5' direction .
dATP/dGTP diphosphohydrolase MazZ (dATP/dGTP_dipphydrolase_MazZ)
Type: Domain

This domain is found in phage proteins, such as

from Acinetobacter phage SH-Ab 15497 and

from cyanophage S-2L, which are associated with PurZ, an enzyme that catalyses the synthesis of diaminopurine (Z), a DNA modification that gives phages an advantage for evading host restriction enzymes activity . This domain has dATP and/or dGTP pyrophosphohydrolase activity; it catalyses the hydrolysis of dATP/dGTP to pyrophosphate and dAMP/dGMP, respectively, with little or no activities for NTPs and pyrimidine dNTPs. In SH-Ab 15497, it has both a dATPase and a dGTPase activities, while in S-2L it is only a dGTPase, suggesting some flexibility in the strategy of these phages to incorporate Z instead of A in their genome . Enzymes containing this domain supply dGMP as the substrate for PurZ, elevating dZTP level to promote Z incorporation .
Domain of unknown function DUF551 (DUF551)
Type: Domain

This entry represents the C terminus of a protein of unknown function, found in dsDNA viruses with no RNA stage, including bacteriophages lambda and P22, and also in some Escherichia coli prophages.
Fimbrial major subunit, CS1-type (Fimbrial_CS1-type)
Type: Family

Fimbriae, also known as pili, form filaments radiating from the surface of the bacterium to a length of 0.5-1.5 micrometres. They enable the cell to colonise host epithelia. This family constitutes the major subunits of CS1 like pili, including CS2 and CFA1 from Escherichia coli, and also the Cable type II pilin major subunit from Burkholderia cepacia . The major subunit of CS1 pili is called CooA. Periplasmic CooA is mostly complexed with the assembly protein CooB. In addition, a small pool of CooA multimers, and CooA-CooD complexes exists, but the functional significance is unknown . A member of this family has also been identified in Salmonella typhi and Salmonella enterica .
Uncharacterised protein family, basic secretory protein (Uncharacterised_BSP)
Type: Family

Proteins in this entry include basic secretory proteins (BSPs) believed to be part of the plants defence mechanism against pathogens . In plants, this group of proteins are known as PR-17 family, including At2g15120 from Arabidopsis, NtPRp27 from Nicotiana tabacum and StPRp27 from potatoes . This entry also includes uncharacterised proteins from bacteria and fungi.
Major capsid protein, C-terminal (MCP_C)
Type: Domain

The entry includes major capsid proteins (vp54 and vp72) found in Iridoviruses, Phycodnaviruses, Asfarviruses and Ascoviruses, which are all type II dsDNA viruses with no RNA stage. This is the most abundant structural protein and can account for up to 45% of virion protein . The structure of vp54 has been determined from Paramecium bursaria Chlorella virus 1 (PBCV-1), a very large icosahedral virus containing an internal membrane enclosed within a glycoprotein coat. The vp54 protein is a duplication consisting of two domains with a similar fold packed together like the nucleoplasmin subunits. The vp54 protein forms a trimer, where the domains are arranged around a pseudo 6-fold axis. The domains have a β-sandwich structure consisting of 8 strands in two sheets with a jelly-roll topology .
LptD, C-terminal (LptD_C)
Type: Domain

Lipopolysaccharide (LPS) is essential for most Gram-negative bacteria and has crucial roles in protection of the bacteria from harsh environments and toxic compounds, including antibiotics. LptD is an essential outer membrane protein that mediates the final transport of lipopolysaccharide (LPS) to outer leaflet. Structural analysis indicates that LptD forms a novel 26-stranded β-barrel. It interacts with LptE where LptE adopts a roll-like structure located inside the barrel of LptD. The LPS translocon LptD is unable to fold properly in the absence of LptE and the two proteins form a unique barrel and plug architecture for LPS transport and insertion . It has been suggested that LptD is a promising target for the development of effective vaccines and antibody-based therapies to control Vibrio infection .

LptD comprises a C-terminal β-barrel domain embedded in the outer membrane and an N-terminal domain that sits in the periplasm . This entry represents the C-terminal domain.
Type 1 encapsulin shell protein (ENCAP)
Type: Family

This protein family includes Type 1 encapsulin shell proteins found in prokaryotes. These proteins form nanocompartments within the bacterium which contain ferritin-like proteins or peroxidases, enzymes involved in oxidative-stress response. These enzymes are targeted to the interior of encapsulins via unique C-terminal extensions .
LOR/SDH bifunctional enzyme, conserved domain (LOR/SDH_bifunc_enz_cons_dom)
Type: Domain

Lysine-oxoglutarate reductase/Saccharopine dehydrogenase (LOR/SDH) is a bifunctional enzyme. This conserved region is commonly found immediately N-terminal to saccharopine dehydrogenase conserved region (

) in eukaryotes .

It is also found in Bifunctional arginine dihydrolase/ornithine cyclodeaminase ArgZ and ArgE involved in a cyanobacterial arginine utilization pathway that produces glutamate and enables cellular adaptation to nitrogen fluctuations .
Protein of unknown function DUF503 (DUF503)
Type: Family

This is a family of conserved hypothetical bacterial proteins, including TT1725 from Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579), which has a ferredoxin-like α+β-sandwich fold .
Uncharacterised protein family UPF0248 (UPF0248)
Type: Family

This is a family of uncharacterised archaeal proteins, which contain the MJ1316 RNA cyclic group end recognition domain (

).
Protein of unknown function DUF505 (DUF505)
Type: Family

This is a family of uncharacterised prokaryotic proteins.
Domain of unknown function DUF512 (DUF512)
Type: Domain

This entry represents a domain found in a group of putative radical SAM proteins mostly from bacteria. It is associated with the N-terminal domain [

].
Protein of unknown function DUF520 (DUF520)
Type: Family

This entry represents the UPF0234 family of uncharacterised proteins, which includes YajQ.

In Pseudomonas syringae, YajQ functions as a host protein involved in the temporal control of bacteriophage Phi6 gene transcription. It has been shown to bind to the phage's major structural core protein P1, most likely activating transcription by acting indirectly on the RNA polymerase. YajQ may remain bound to the phage particles throughout the infection period . Earlier, YajQ was characterised as a putative nucleic acid-binding protein based on the similarity of its (ferredoxin-like) three-dimensional topology with that of RNP-like RNA-binding domains .
2-thiouracil desulfurase (2-thiour_desulf)
Type: Family

This family of proteins, predominantly found in Bacteria, are involved in the desulfuration of 2-thiouracil into uracil in the 2-thiouridine degradation pathway. It has been demonstrated that these proteins contain a Fe-S cluster required for their activity .
CDP-glycerol glycerophosphotransferase (Glycerophosphate_synth)
Type: Family

Wall-associated teichoic acids are a heterogeneous class of phosphate-rich polymers that are covalently linked to the cell wall peptidoglycan of Gram-positive bacteria. They consist of a main chain of phosphodiester-linked polyols and/or sugar moieties attached to peptidoglycan via a linkage unit. CDP-glycerol:poly(glycerophosphate) glycerophosphotransferase TagF is responsible for the polymerisation of the main chain of the teichoic acid by sequential transfer of glycerol-phosphate units from CDP-glycerol to the linkage unit lipid . The TagF-like family of enzymes has been shown to be responsible for wall teichoic acid priming and polymerization events .
Protein of unknown function DUF499 (DUF499)
Type: Family

This is a family of uncharacterised hypothetical prokaryotic proteins.
Protein of unknown function DUF483 (DUF483)
Type: Family

This is a family of uncharacterised prokaryotic proteins.
PSP1, C-terminal (PSP1_C)
Type: Domain

The yeast polymerase suppressor 1 (PSP1) protein partially suppresses mutations in DNA polymerases alpha and delta . The C-terminal half of PSP1 contains a domain, which is also found in several hypothetical proteins from both eukaryotic and prokaryotic sources:

Crithidia fasciculata RBP45 and RBP33, subunits of the cycling sequence binding protein (CSBP) II. RBP45 and RBP33 proteins bind specifically to the cycling sequences present in several mRNAs that accumulate periodically during the cell cycle. RBP45 and RBP33 are phosphoproteins, which are phosphorylated differentially during progression through the cell cycle. Hypothetical proteins with high sequence similarity have been identified in other kinetoplastid organisms .

Bacillus subtilis YaaT protein (also known as RicT), which was first thought to play a significant role in phosphorelay during initiation of sporulation . However, YaaT/RicT belongs to a iron-sulfur containing regulatory complex that is conserved also in many non-sporulating species, together with homologs of YmcA (RicA) and YlbF (RicF) .

The actual biological significance of the PSP1 C-terminal domain has not yet been clearly established.
Restriction endonuclease type IV, Mrr (Restrct_endonuc_IV_Mrr)
Type: Domain

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements , as summarised below:

Type I enzymes (

) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (

) activities.

Type II enzymes (

) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.

Type III enzymes (

) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (

).

Type IV enzymes target methylated DNA.

This entry represents Mrr, a type IV restriction endonuclease involved in the acceptance of modified foreign DNA, restricting both adenine- and cytosine-methylated DNA. Plasmids carrying HincII, HpaI, and TaqI R and M genes are severely restricted in Escherichia coli strains that are Mrr+ . Mrr appears to be the final effector of the bacterial SOS response, which is not only a vital reply to DNA damage but also constitutes an essential mechanism for the generation of genetic variability that in turn fuels adaptation and resistance development in bacterial populations . Mrr possesses a cleavage domain that is similar to that found in type II restriction enzymes, however it has an unusual glutamine residue at the central position of the (D/E)-(D/E)XK hallmark of the active site .
Cell division protein SepF/SepF-related (Cell_div_SepF/SepF-rel)
Type: Family

This entry represents a cell division protein, designated SepF, which is conserved in Gram-positive bacteria. SepF accumulates at the cell division site in an FtsZ-dependent manner and is required for proper septum formation . This protein uses an amphipathic helix for membrane binding and polymerises into large rings that bundle FtsZ filaments . Mutants are viable but the formation of the septum is much slower and occurs with a very abnormal morphology. This entry also includes archaeal related proteins, such as SepF from Haloferax volcanii .
Transglutaminase-like domain (Transglutaminase-like_domain)
Type: Domain

This entry represents a transglutaminase-like domain found in a family of uncharacterised archaeal proteins that had previously been called DUF553 and UPF0252.
Protein of unknown function DUF554 (DUF554)
Type: Family

This is a family of uncharacterised prokaryotic proteins. Multiple predicted transmembrane regions suggest that the protein is membrane associated.
Uncharacterised protein family UPF0212 (UPF0212)
Type: Family

This is a family of uncharacterised, hypothetical archaeal proteins.
(5-formylfuran-3-yl)methyl phosphate synthase (4HFCP_synth)
Type: Family

This entry represents the (5-formylfuran-3-yl)methyl phosphate synthase (also known as 4-HFC-P synthase or MfnB), which has a classical TIM-barrel structure whose biological unit is a homohexamer. It is involved in the production of methanofuran. MfnB from Methanocaldococcus jannaschii catalyzed at least 10 separate chemical reactions in converting two molecules of glyceraldehyde-3-P (GA-3-P) to 4-(hydroxymethyl)-2-furancarboxaldehyde-P (4-HFC-P), the first discrete intermediate in the biosynthetic pathway to the furan moiety of the coenzyme methanofuran .

This family also includes putative (5-formylfuran-3-yl)methyl phosphate synthases from bacteria.
Phosphoenolpyruvate carboxylase, archaeal-type (PEP_COase_arc-type)
Type: Family

Phosphoenolpyruvate carboxylase (PEPCase), an enzyme found in all multicellular plants, catalyses the formation of oxaloacetate from phosphoenolpyruvate (PEP) and a hydrocarbonate ion . This reaction is harnessed by C4 plants to capture and concentrate carbon dioxide into the photosynthetic bundle sheath cells. It also plays a key role in the nitrogen fixation pathway in legume root nodules: here it functions in concert with glutamine, glutamate and asparagine synthetases and aspartate amido transferase, to synthesise aspartate and asparagine, the major nitrogen transport compounds in various amine-transporting plant species .

This entry represents the archaeal-type family.
Mid2 domain (Mid2_dom)
Type: Domain

This domain is found near the C terminus of Mid2, which contains a transmembrane region. The remainder of the protein sequence is serine-rich and of low complexity, and is therefore impossible to align accurately. Mid2 is thought to act as a mechanosensor of cell wall stress. The C-terminal cytoplasmic region of Mid2 is known to interact with Rom2, a guanine nucleotide exchange factor (GEF) for Rho1, which is part of the cell wall integrity signalling pathway .
RTA-like protein (RTA1)
Type: Family

This family is comprised of fungal proteins with multiple transmembrane regions. RTA1 (

) is involved in resistance to 7-aminocholesterol , while RTM1 (

) confers resistance to an unknown toxic chemical in molasses . RSB1 is also a member of this family; it is sphingoid long-chain base transporter .
Domain of unknown function DUF559 (DUF559)
Type: Domain

This entry represents a domain of unknown function found in Type II nicking enzyme V.HpaIIP from Haemophilus parainfluenzae, an endonuclease that may nick HpaII sequences that contain GT mismatches resulting from m5C-deamination and play a role in the very short patch (VSP) repair process, counteracting mutations . GT mismatches can lead to C-to-T transition mutations if not repaired. VSR repairs the mismatches in favour of the G-containing strand. In Escherichia coli, this endonuclease nicks double-stranded DNA within the sequence CT(AT)GN or NT(AT)GG next to the thymidine residue, which is mismatched to 2'-deoxyguanosine . The incision is mismatch-dependent and strand specific. The structure of VSR is similar to the core structure of restriction endonucleases, which have a 3-layer α/β/α topology . Several catalytic residues from VSR endonucleases are conserved in this domain and form the composite sequence motif EDxHD .

This domain can also be found in some uncharacterised proteins, such as HI_0925 from Haemophilus influenzae.
Uncharacterised protein family Ycf23 (Uncharacterised_Ycf23)
Type: Family

Protein in this entry are of unknown function and are found in cyanobacteria and the chloroplasts of algae. As the family is exclusively found in phototrophic organisms it may play a role in photosynthesis.
Uncharacterised protein family Ycf20 (Uncharacterised_Ycf20)
Type: Family

This family represents Ycf20, it is found in cyanobacteria and is also encoded in plant and algal chloroplasts; its function is unknown. As the family is exclusively found in phototrophic organisms it may therefore play a role in photosynthesis.
QWRF family (QWRF)
Type: Family

The plant augmin complex is involved in assembly of microtubules (MT) arrays during mitosis and contains eight subunits (AUG1 -AUG8). Among them, AUG1 to AUG6 share similarity with their animal counterparts, but AUG7 and AUG8 share homology only with proteins of plant origin . AUG8 belongs to the plant QWRF motif-containing protein family, which also includes microtubule-associated protein ENDOSPERM DEFECTIVE 1 and SNOWY COTYLEDON 3 . AUG8 binds the microtubule and participates in the reorientation of microtubules in hypocotyls (the stem of a germinating seedling) .
Phycobilisome degradation protein NblA (NblA)
Type: Family

In the cyanobacterium Synechococcus species PCC 7942 (

), nblA triggers degradation of light-harvesting phycobiliproteins in response to deprivation nutrients including nitrogen, phosphorus and sulphur. The mechanism of nblA function is not known, but it has been hypothesised that nblA may act by disrupting phycobilisome structure, activating a protease or tagging phycobiliproteins for proteolysis. Members of this family have also been identified in the chloroplasts of some red algae.
SchA/CurD-like domain (SchA_CurD-like)
Type: Domain

Proteins having this domain have been identified mainly in species of the Streptomyces genus. Two of them are known to be part of gene clusters involved in the synthesis of polyketide-based spore pigments, homologous to clusters involved in the synthesis of polyketide antibiotics. Their function is unknown, but they has been speculated to contain a NAD(P) binding site . Many of these proteins contain two copies of the domain.
CITED (CITED)
Type: Family

CITED, CBP/p300-interacting transactivator with ED-rich tail, is characterised by a conserved 32-amino acid sequence at the C terminus. CITED protein does not bind DNA directly and is thought to function as a transcriptional co-activator .
Glycosyltransferase, DXD sugar-binding motif (GlycoTrfase_DXD_sugar-bd_CS)
Type: Conserved_site

This entry represents those sugar-binding regions of glycosyltransferases that contain a DXD motif. The DXD motif is a short conserved motif found in many families of glycosyltransferases, which add a range of different sugars to other sugars, phosphates and proteins. DXD-containing glycosyltransferases all use nucleoside diphosphate sugars as donors and require divalent cations, usually manganese. The DXD motif is expected to play a carbohydrate binding role in sugar-nucleoside diphosphate and manganese dependent glycosyltransferases .