SII-SWORD/CoKE huggingface dataset:
Srp40, C-terminal (Srp40_C)
Type: Domain

This presumed domain is found at the C terminus of the budding yeast Srp40 and mammalian NOLC1 (also known as Nopp140) proteins. They are nucleolar proteins that contain a central domain consisting of ten repeats of acidic serine clusters alternating with lysine-, alanine- and proline-rich basic stretches . Srp40 may be involved in preribosome assembly or transport . Human NOLC1 interacts with casein kinase 2 (CK2), RNA polymerase I, p80 coilin , NAP57, and both major classes (box H/ACA and box C/D) of snoRNPs . It acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification .
Phytochelatin synthase, N-terminal catalytic domain (PCS_N)
Type: Domain

Phytochelatins are well known as the heavy metal-detoxifying peptides in higher plants, eukaryotic algae, fungi, nematode and cyanobacteria. Phytochelatin synthase (PCS, also known as glutathione gamma-glutamylcysteinyltransferase;

) is involved in the synthesis of phytochelatins (PC) and homophytochelatins (hPC). This enzyme is required for detoxification of heavy metals such as cadmium and arsenate. The N-terminal region of phytochelatin synthase contains the active site, as well as four highly conserved cysteine residues that appear to play an important role in heavy-metal-induced phytochelatin catalysis. The C-terminal region is rich in cysteines, and may act as a metal sensor, whereby the Cys residues bind cadmium ions to bring them into closer proximity and transferring them to the activation site in the N-terminal catalytic domain . The C-terminal region displays homology to the functional domains of metallothionein and metallochaperone.

This entry represents the N-terminal catalytic PCS domain, which belongs to the petidase family C83 of the papain superfamily of cysteine proteases, with a structurally conserved "catalytic triad" and oxyanion hole in the active site. It has an overall "crescent" shape with α/β fold containing eight α-helices and six β-strands .
Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q/GPI1 (PigQ/GPI1)
Type: Family

Glycosylphosphatidylinositol (GPI) represents an important anchoring molecule for cell surface proteins. The first step in its synthesis is the transfer of N-acetylglucosamine (GlcNAc) from UDP-N-acetylglucosamine to phosphatidylinositol (PI). This chemically simple step is genetically complex because three or four genes are required in both Saccharomyces cerevisiae (GPI1, GPI2 and GPI3) and mammals (GPI1, PIG A, PIG H and PIG C), respectively .

This entry includes the mammalian Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (PigQ), its homologue Phosphatidylinositol N-acetylglucosaminyltransferase subunit GPI1 (Gpi1) from yeast, and similar eukaryotic proteins. PigQ stabilises the complex of PIG-A, PIG-H, and PIG-C. It is important for the activity of this protein complex but not essential . A similar function has been suggested for the yeast Gpi1 .
D-ribose pyranase RbsD/L-fucose mutarotase FucU (RbsD_FucU)
Type: Family

RbsD is a component of the ribose operon. It was originally thought to be a high affinity ribose transport protein, but further analysis shows that it is a D-ribose pyranase

. It catalyses the interconversion of beta-pyran and beta-furan forms of D-ribose. It also catalyzes the conversion between beta-allofuranose and beta-allopyranose.

FucU is a component of the fucose operon and is a L-fucose mutarotase

, involved in the anomeric conversion of L-fucose. It also exhibits a pyranase activity for D-ribose .

Both have been classified in the RbsD/FucU family of proteins. Members of this family are ubiquitous having been found in organisms from eubacteria to mammals.
mRNA decapping protein 2, Box A domain (DCP2_BoxA)
Type: Domain

This presumed domain is always found to the N-terminal side of the NUDIX hydrolase domain

. This domain appears to be specific to mRNA decapping protein 2 (DCP2)

and its close homologues. This region has been termed Box A .
Poly(ADP-ribose) glycohydrolase (Poly_GlycHdrlase)
Type: Family

Poly(ADP-ribose) glycohydrolase (PARG) (

) is a ubiquitously expressed exo- and endoglycohydrolase which catalyses the hydrolysis of the O-glycosidic linkages of ADP-ribose polymers, reversing the effects of poly(ADP-ribose) . It generates mono-ADP-ribosylated proteins in cells, due to its ability of degrading poly(ADP-ribose) without cleaving the terminal protein-ribose bond . PARG is also involved in the synthesis of nuclear ATP, which is required for extensive chromatin remodeling events . This protein mediates oxidative and excitotoxic neuronal death .

Arabidopsis thaliana PARG1 is involved in abiotic stress responses and DNA repair .
Timeless, C-terminal (TIMELESS_C)
Type: Domain

This entry represents the C-terminal domain found in the Timeless (TIM) proteins. This domain can be found in TIM homologues mostly from animals. This domain found in hTIM has been shown to bind to the PARP-1 catalytic domain .

The timeless gene in Drosophila melanogasteris involved in circadian rhythm control . Drosophila contains two paralogs, dTIM and dTIM2, acting in clock/photoreception and chromosome integrity/photoreception respectively. The mammalian TIMELESS (TIM) protein, originally identified based on its similarity to Drosophila dTIM, interacts with the clock proteins dCRY and dPER and is essential for circadian rhythm generation and photo-entrainment in the fly . However, phylogenetic sequence analysis has demonstrated that dTIM2 is likely to be the orthologue of mammalian TIM and other widely conserved TIM-like proteins in eukaryotes . These proteins include Saccharomyces cerevisiae Tof1, Schizosaccharomyces pombe Swi1, and Caenorhabditis elegans TIM. These proteins are not involved in the core clock mechanism, but instead play important roles in chromosome integrity, efficient cell growth and/or development , with the exception of dTIM-2, that has an additional function in retinal photoreception .

Saccharomyces cerevisiae Tof1 is a subunit of a replication-pausing checkpoint complex (Tof1-Mrc1-Csm3) that acts at the stalled replication fork to promote sister chromatid cohesion after DNA damage, facilitating gap repair of damaged DNA . Schizosaccharomyces pombe Swi1 and Swi3 form the fork protection complex that coordinates leading- and lagging-strand synthesis and stabilizes stalled replication forks .
SS18, N-terminal (SS18_N)
Type: Domain

This entry represents the N-terminal domain of SS18 and related proteins.

SSXT (also known as SS18) appears to function synergistically with RBM14 as a transcriptional coactivator .

The SSXT protein is involved in synovial sarcoma in humans. A SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18) (p11;q11) is characteristic of synovial sarcomas. This translocation fuses the SSXT (SYT) gene from chromosome 18 to either of two homologous genes at Xp11, SSX1 or SSX2 .

The SS18 family also includes SS18-like proteins 1 and 2, and GRF1-interacting factors from plants . SS18-like protein 1 is a transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons .
Spo12 (Spo12)
Type: Family

This entry includes budding yeast Spo12 and its paralogue, Bns1, that arose from the whole genome duplication. Spo12 plays a regulatory role in two of the most fundamental processes of biology, mitosis and meiosis, and yet its biochemical function remains elusive . Spo12 is a nuclear protein . Spo12 is a component of the FEAR (Cdc fourteen early anaphase release) regulatory network, which promotes Cdc14 release from the nucleolus during early anaphase . The FEAR network is comprised of the polo kinase Cdc5, the separase Esp1, the kinetochore-associated protein Slk19, and Spo12 .
Pre-SET domain (Pre-SET_dom)
Type: Domain

This region is found in a number of histone lysine methyltransferases (HMTase), N-terminal to the SET domain; it is generally described as the pre-SET domain.

Histone lysine methylation is part of the histone code that regulated chromatin function and epigenetic control of gene function. Histone lysine methyltransferases (HMTase) differ both in their substrate specificity for the various acceptor lysines as well as in their product specificity for the number of methyl groups (one, two, or three) they transfer. With just one exception , the HMTases belong to SET family that can be classified according to the sequences surrounding the SET domain . Structural studies on the human SET7/9, a mono-methylase, have revealed the molecular basis for the specificity of the enzyme for the histone-target and the roles of the invariant residues in the SET domain in determining the methylation specificities .
2-keto-3-deoxy-galactonokinase (DGOK)
Type: Family

2-keto-3-deoxy-galactonokinase

is a bacterial transferase that catalyses the second step in D-galactonate degradation.
ATP + 2-dehydro-3-deoxy-D-galactonate = ADP + 2-dehydro-3-deoxy-D-galactonate 6-phosphate
D-Galactonate is catabolized in saprophytic mycobacteria to give pyruvate and glyceraldehyde-3-phosphate by a pathway that involves galactonate dehydratase, 2-keto-3-deoxy-galactonate kinase, and 6-phospho-2-keto-3-deoxy-galactonate aldolase .
Sporulation-like domain (SPOR-like_dom)
Type: Domain

This 70 residue domain, known as SPOR domain, is composed of two 35 residue repeats that are found in bacterial proteins involved in sporulation and cell division, such as FtsN, CwlM and RlpA. The SPOR domains in the FtsN cell division proteins from Escherichia coli and Caulobacter crescentus have been shown to bind peptidoglycan. SPOR domains can localise to the division site by binding preferentially to septal peptidoglycan .

FtsN is an essential cell division protein with a simple bitopic topology: a short N-terminal cytoplasmic segment fused to a large carboxy periplasmic domain through a single transmembrane domain. The repeats lie at the periplasmic C terminus, which has an RNP-like fold . FtsN localises to the septum ring complex. The CwlM protein is a cell wall hydrolase, where the C-terminal region, including the repeats, determines substrate specificity . RlpA is a rare lipoprotein A protein that may be important for cell division. Its N-terminal cysteine may be attached to thioglyceride and N-fatty acyl residues .
Protein of unknown function DUF669 (DUF669)
Type: Family

Members of this family are found in various phages and bacteria.
Cytochrome b558 alpha-subunit (Cyt_b558_asu)
Type: Family

Flavocytochrome b558 is the catalytic core of the respiratory-burst oxidase, an enzyme complex that catalyzes the NADPH-dependent reduction of O2 into the superoxide anion O2 in phagocytic cells. Flavocytochrome b558 is anchored in the plasma membrane. It is a heterodimer that consists of a large glycoprotein gp91phox (phox forphagocyte oxidase) (beta subunit) and a small protein p22phox (alpha subunit). The other components of the respiratory-burst oxidase are water-soluble proteins of cytosolic origin, namely p67phox, p47phox, p40phox and Rac. Upon cell stimulation, they assemble with the membrane-bound flavocytochrome b558 which becomes activated and generates O2- .
Agouti (Agouti)
Type: Family

The agouti protein regulates pigmentation in the mouse hair follicle producing a black hair with a subapical yellow band. A highly homologous protein agouti signal protein (ASIP) is present in humans and is expressed at highest levels in adipose tissue where it may play a role in energy homeostasis and possibly human pigmentation . This family also includes the Agouti-related protein (Agrp), involved in energy balance, body weight regulation and metabolism. It interacts with melanocortin receptors MC3R, MC4R and MC5R .

This family also includes Toxin Tbo-IT2 from Oblong running crab spider, which contains an inhibitor cystine knot (ICK) fold with a spatial structure and very similar Cys distribution to agouti-signaling proteins (ASIP) and agouti-related proteins (AGRP) .
Heparan sulphate 2-O-sulfotransferase (Heparan_SO4_2-O-STrfase)
Type: Family

Heparan sulphate (HS) is a long unbranched polysaccharide found covalently attached to various proteins at the cell surface and in the extracellular matrix, where it acts as a co-receptor for a number of growth factors, morphogens, and adhesion proteins. HS-O-sulphotransferase (Hs2st) occupies a critical position in the succession of enzymes responsible for the biosynthesis of HS, catalysing the transfer of sulphate to the C2-position of selected hexuronic acid residues within the nascent HS chain. Mice that lack HS2ST undergo developmental failure after midgestation, the most dramatic effect being the complete failure of kidney development . This family is related to

.

Uronyl 2-sulfotransferase, a sulfotransferase that catalyses the transfer of sulfate to the position 2 of uronyl residues in glycosaminoglycan chains , is also included in this entry. It has mainly activity toward iduronyl residues in dermatan sulfate, and weaker activity toward glucuronyl residues of chondroitin sulfate and it has little to no activity toward desulfated N-resulfated heparin or N-sulfoheparosan .
Pecanex, C-terminal (Pecanex_C)
Type: Domain

This entry represents the C-terminal domain of pecanex protein. The pecanex protein is a maternal-effect neurogenic gene found in Drosophila .
Caleosin-related (Caleosin-related)
Type: Family

Caleosins are a family of lipid-associated proteins that are ubiquitous in plants and true fungi. In plants, caleosinss are Ca(2+)-binding oil-body surface proteins . Later, caleosin was identified as a putative peroxygenase, which is involved in oxylipin metabolism during biotic and abiotic stress responses in Arabidopsis . The calcium binding domain is probably related to the calcium-binding EF-hands motif

.
Mga helix-turn-helix domain (Mga_HTH)
Type: Domain

This domain is found in a group of positive transcriptional regulators, such as M regulator protein trans-acting positive regulator (Mga), a DNA-binding protein that activates the expression of several important virulence genes in group A streptococcus in response to changing environmental conditions . This domain is found in the centre of the Mga proteins. This domain is also found in a number of bacterial RofA transcriptional regulators that seem to be largely restricted to streptococci. These proteins have been shown to regulate the expression of important bacterial adhesins . This domain is also found in the transcriptional regulator MtlR from Bacillus subtilis which positively regulates the expression of the mtlAFD operon involved in the uptake and catabolism of mannitol . This is presumably a DNA-binding domain.
Rhamnan synthesis F (RgpF)
Type: Family

This family consists of a group of proteins which are related to the Streptococcal rhamnose-glucose polysaccharide assembly protein (RgpF). Rhamnan backbones are found in several O-polysaccharides found in phytopathogenic bacteria and are regarded as pathogenic factors .
Large ribosomal subunit protein mL49 (Ribosomal_mL49)
Type: Family

This entry represents the large ribosomal subunit protein mL49. This family of proteins has been identified as part of the mitochondrial large ribosomal subunit in Saccharomyces cerevisiae . In yeast , this protein was previously known as IMG2 and in mammals as MRPL49.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Ribosomal protein/NADH dehydrogenase domain (Ribosomal_mL43/mS25/NADH_DH)
Type: Domain

Proteins containing this domain are located in the mitochondrion and include large ribosomal subunit protein mL43 (known as MRPL51) and mL61 (MRP49), and small ribosomal subunit protein mS25 (S25). This domain is also found in mitochondrial NADH-ubiquinone oxidoreductase B8 subunit (CI-B8)

. It is not known whether all members of this family form part of the NADH-ubiquinone oxidoreductase and whether they are also all ribosomal proteins.
Periplasmic copper-binding protein NosD, beta helix domain (NosD_dom)
Type: Domain

This entry represents a parallel β helix domain found in several proteins, including NosD. NosD is a periplasmic protein which is thought to insert copper into the exported reductase apoenzyme (NosZ) .
Immunity-related GTPases-like (Immunity-related_GTPase-like)
Type: Family

This entry represents a group of immunity-related GTPase-like proteins, including interferon-inducible GTPase from mammals. It also includes some uncharacterised proteins from bacteria, fungi and invertebrates. These proteins adopt an α/β fold with a Ras-like topology .
Cytochrome c oxidase copper chaperone (Cyt_c_oxidase_Cu-chaperone)
Type: Family

Cox17p is essential for the assembly of functional cytochrome c oxidase (CCO). Binds and delivers two copper ions to the metallochaperone SCO1 which transports the copper ions to the Cu(A) site on the cytochrome c oxidase subunit II (MT-CO2/COX2) .
Broad mercury transporter MerE (MerE)
Type: Family

The prokaryotic MerE (or URF-1) protein is part of the mercury resistance operon often located on plasmids or transposons . It has been suggested that MerE is a broad mercury transporter mediating transport across the bacterial membrane .
Menin (Menin)
Type: Family

The tumour suppressor gene MEN1 is mutated in patients with a dominantly inherited tumour syndrome, multiple endocrine neoplasia type 1 (MEN1) . The MEN1 gene encodes a protein known as Menin, which is located predominantly in the nucleus. Menin has been shown to interact with the mixed lineage leukemia (MLL) protein, a histone H3 lysine 4 methyltransferase, and plays a critical role in hematopoiesis and leukemogenesis .
Autographa californica nuclear polyhedrosis virus (AcMNPV), Orf109 (AcMNPV_Orf109)
Type: Family

This entry includes protein AC109 from Autographa californica nuclear polyhedrosis virus (AcMNPV). The gene (Orf1090) is essential and transcribed late in virus assembly, and protein AC109 has been shown to be important for the transport of the budded virion to the host nucleus. In mutants lacking the AC109 gene, virions are unable to enter the nucleus and remain in the cytoplasm. Although addition of AC109 allowed virions to enter the nucleus, the occlusion bodies were empty, indicating that AC109 is also important for the production of infectious budded virus .
Protein of unknown function DUF677 (DUF677)
Type: Family

This entry contains proteins belonging to the UPF0496 family, found in plants. This family includes AT14A like proteins from Arabidopsis thaliana. At14a contains a small domain that has sequence similarities to integrins from fungi, insects and humans. Transcripts of At14a are found in all Arabidopsis tissues and the protein localises partly to the plasma membrane .
Protein of unknown function DUF674 (DUF674)
Type: Family

This family is found in Arabidopsis thaliana and contains uncharacterised proteins.
Domain of unknown function DUF676, lipase-like (DUF676_lipase-like)
Type: Domain

This domain, whose function is unknown, is found within a group of putative lipases. Proteins containing this domain include YOR059C (Lpl1) from budding yeasts. Lpl1 has been identified as a phospholipase B .
Virulence factor ActA (Virulence_actor_ActA)
Type: Family

The ActA family is found in Listeria and is associated with motility. ActA protein acts as a scaffold to assemble and activate host cell actin cytoskeletal factors at the bacterial surface, resulting in directional actin polymerisation and propulsion of the bacterium through the cytoplasm of the host cell .
Orbivirus VP4 core (Orbi_VP4)
Type: Family

Orbivirus are double stranded RNA retroviruses of which the Bluetongue virus (BTV) is a member. The core of BTV is a multienzyme complex composed of two major proteins (VP7 and VP3) and three minor proteins (VP1, VP4 and VP6) in addition to the viral genome. VP4 has been shown to perform all RNA capping activities and has both methyltransferase type 1 and type 2 activities associated with it .
N-acetylglucosaminyltransferase II (GlcNAc_II)
Type: Family

N-acetylglucosaminyltransferase II (

) is a Golgi resident enzyme that catalyzes an essential step in the biosynthetic pathway leading from high mannose to complex N-linked oligosaccharides . Mutations in the MGAT2 gene lead to a congenital disorder of glycosylation (CDG IIa). CDG IIa patients have an increased bleeding tendency, unrelated to coagulation factors .
Poxvirus A11 (Poxvirus_A11)
Type: Family

This entry represents Protein A11 from Vaccinia virus, also known as Protein OPG137, and similar sequences from poxvirus. A11 is required for viral crescent formation early during virus morphogenesis . A conserved region spans the entire protein in the majority of family members.
RICH domain (RICH)
Type: Domain

This domain is about 85 residues in length and very rich in charged residues, hence the name RICH (Rich In CHarged residues). It is found in secreted proteins such as PspC

, SpsA

and IgA FC receptor

from Streptococcus agalactiae. This domain could be involved in bacterial adherence or cell wall binding.