SII-SWORD/CoKE huggingface dataset:
TRC8-like, N-terminal domain (TRC8_N_dom)
Type: Domain

This region is found at the N terminus of the TRC8 protein (

). TRC8 is an E3 ubiquitin-protein ligase also known as RNF139. This region contains 12 transmembrane domains and has been suggested to contain a sterol sensing domain . It has been found that TRC8 protein levels are sterol responsive and that it binds and stimulates ubiquitylation of the endoplasmic reticulum anchor protein INSIG .
Large ribosomal subunit protein uL4, C-terminal domain (Ribos_uL4_C_dom)
Type: Domain

This domain is found at the C terminus of the large ribosomal subunit protein uL4 from eukaryotes (also known as 60S ribosomal L4).
MYB-CC type transcription factor, LHEQLE-containing domain (Myb_CC_LHEQLE)
Type: Domain

This domain is found towards the C terminus of Myb-CC type transcription factors, and carries a highly conserved LHEQLE sequence motif.
Ternary complex factor MIP1, leucine-zipper (MIP1_Leuzipper)
Type: Domain

This leucine-zipper domain can be found in MIP1 proteins and in putative Rho GTPase-activating proteins. MIP1 proteins, here largely from plants, are subunits of the TORC2 (rictor-mTOR) protein complex controlling cell growth and proliferation . The leucine-zipper is likely to be the region that interacts with plant MADS-box factors ,
Fic/DOC N-terminal (Fic/DOC_N)
Type: Domain

This domain is found N-terminal to the fido domain (

) in proteins of the Fic/Doc family.
TRM3 (TRM3)
Type: Family

Trm3 is a 2'-O-ribose methyltransferase that catalyses the ribose methylation of the guanosine nucleotide at position 18 of tRNAs .
Fetuin-A-type cystatin domain (Cystatin_Fetuin_A)
Type: Domain

The cystatin superfamily consists of a large group of cystatin domain- containing proteins, most of which are reversible and tight-binding inhibitors of the papain (C1) and legumain (C13) families of cysteine proteases. Fetuins have been identified as main members of the cystatin superfamily and are composed of fetuin-A and fetuin-B. Fetuins are characterised by the presence of 2 N-terminally located cystatin-like repeats and a unique C-terminal domain which is not present in other proteins of the cystatin family .

Fetuin-A also called alpha-2-HS-glycoprotein, bone sialic acid- containing protein (BSP), countertrypin or PP63, is expressed in a tissue- and development-specific pattern which seems to be significantly different between species. A wide functional diversity of fetuin-A has been observed. It has been shown to function in many physiological aspects, such as fatty acid transport, regulation of insulin activity and hepatocyte-growth-factor activity, response to systemic inflammation, and inhibition of unwanted mineralization. It has been demonstrated that fetuin-A plays important roles during developmental processes, including osteogenesis, myotubule, fetal brain and nervous system development. Human fetuin is a heterodimer of chain A and B, which are derived by cleavage of a connecting peptide from a common precursor. Snake fetuin family proteins (antihemorrhagic proteins HSF, BJ46a and MSF and HLP-A and HLP-B) show a significant degree of sequence homology to fetuin-A .

The cystatin fold is formed by a five stranded anti-parallel β-sheet wrapped around a five-turn α-helix . Fetuin contains twelve conserved cysteines involved in six disulphide bonds. Eleven of the twelve invariant cysteines are located within the cystatin-like repeats. The 12th cysteine is located near the C terminus of the protein, separated by a region of variable length.
FFD box (FFD_box)
Type: Domain

Sm and Sm-like proteins of the RNA-binding Lsm (like Sm) domain family are found in all domains of life and are generally involved in important RNA- processing tasks. Lsm13-16 homologues share a domain organisation consisting of a divergent N-terminal Lsm domain and a central or C-terminal consensus motif DFDF-x(7)-F. In few other sequences, the DFDF box is replaced by a DYDF or EFDF box .

The FFD box and TFG box are two other strongly conserved sequence motifs(Y-x-K-x(3)-FFD-x-[IL]-S and [RKH]-x(2,5)-E-x(0-2)-[RK]-x(3,4)-[DE]-TFG respectively) contained in Lsm13-15, but not Lsm16, homologues. They succeed the DFDF-x(7)-F motif and are also predicted to be of helical nature .

This entry represents the FFD box.
DFDF domain (DFDF)
Type: Domain

Sm and Sm-like proteins of the RNA-binding Lsm (like Sm) domain family are found in all domains of life and are generally involved in important RNA- processing tasks. Lsm13-16 homologs share a domain organisation consisting of a divergent N-terminal Lsm domain and a central or C-terminal consensus motif DFDF-x(7)-F closely preceded and followed by further phenylalanines and charged aspartates/glutamates and arginines/lysines/histidines. The variable seven-residue tract of this consensus motif usually contains an asparagine at the third or fourth position except of one sequence where the asparagine is replaced by a glycine. In few other sequences, the DFDF box is replaced by a DYDF or EFDF box . The DFDF domain is a heterodimerization domain, which adopts a helical conformation upon binding. It folds into two consecutive α helices that are preceded and connected by the FDF and a related FDK sequence .

Two other strongly conserved FFD box and TFG box sequence motifs Y-x-K-x(3)- FFD-x-[IL]-S and [RKH]-x(2,5)-E-x(0-2)-[RK]-x(3,4)-[DE]-TFG contained in Lsm13-15, but not Lsm16, homologs succeed the DFDF-x(7)-F motif and are also predicted to be of helical nature .

This entry represents the DFDF domain.
tRNA (guanine-N-7) methyltransferase catalytic subunit Trm8, eukaryote (Trm8_euk)
Type: Family

This entry represents the eukaryotic tRNA (guanine-N-7) methyltransferases catalytic subunit Trm8, and its homologue, such as METTL1 from humans .
Fetuin-B-type cystatin domain (Cystatin_Fetuin_B)
Type: Domain

The cystatin superfamily consists of a large group of cystatin domain- containing proteins, most of which are reversible and tight-binding inhibitors of the papain (C1) and legumain (C13) families of cysteine proteases. Fetuins have been identified as main members of the cystatin superfamily and are composed of fetuin-A and fetuin-B. Fetuins are characterised by the presence of 2 N-terminally located cystatin-like repeats and a unique C-terminal domain which is not present in other proteins of the cystatin family .

Fetuin-B has been suggested to be involved in systemic inflammation, as a tumor suppressor, and as a basic calcium phosphate precipitation inhibitor .

The cystatin fold is formed by a five stranded anti-parallel β-sheet wrapped around a five-turn α-helix . Fetuin contains twelve conserved cysteines involved in six disulphide bonds. Eleven of the twelve invariant cysteines are located within the cystatin-like repeats. The 12th cysteine is located near the C terminus of the protein, separated by a region of variable length.
ADD domain (ADD)
Type: Domain

One of the largest protein families in the human genome is the zinc finger family that contains members involved in the regulation of transcription processes. The zinc finger domains have been classified based on the order of cysteine (C) and histidine (H) residues. Zinc fingers are thought to mediate protein-DNA and protein-protein interactions. The ADD (ATRX, DNMT3, DNMT3L) domain is a cysteine-rich region that consists of a C2C2-type zinc finger and a closely located domain of an imperfect PHD-type zinc finger with C4C4. The region between the two subdomains has a constant length, and it contains identical and conserved amino acids . The ADD domain binds to the histone H3 tail that is unmethylated at lysine 4 .

The ADD domain is present in chromatin-associated proteins that play a role in establishing and/or maintaining a normal pattern of DNA methylation:

DNMT3A, DNMT3B, DNA methyltransferases.

DNMT3L, a DNMT3-like enzymatically inactive regulatory factor.

ATRX, a large nuclear protein predominantly localized to heterochromatin and nuclear PML bodies. At the C terminus is a helicase/ATPase domain, which characterises ATRX as a member of the SNF2 (SWI/SNF) family of chromatin-associated proteins.

The ADD domain is composed of three clearly distinguishable modules that pack together through extensive hydrophobic interactions to form a single globular domain. Packed against this GATA-like finger is a second subdomain, which binds two zinc ions and closely resembles the structure reported for several PHD fingers. Finally, there is a long C-terminal α-helix that runs out from the PHD finger and makes extensive hydrophobic contacts with the N- terminal GATA finger, bringing the N- and C-termini of the ADD domain close together. This combination of fused GATA-like and PHD fingers within a single domain is thus far unique .
TFG box (TFG_box)
Type: Domain

Sm and Sm-like proteins of the RNA-binding Lsm (like Sm) domain family are found in all domains of life and are generally involved in important RNA-
processing tasks. Lsm13-16 homologues share a domain organisation consisting of a divergent N-terminal Lsm domain and a central or C-terminal consensus motif DFDF-x(7)-F. In few other sequences, the DFDF box is replaced by a DYDF or EFDF box .

The FFD box and TFG box are two other strongly conserved sequence motifs(Y-x-K-x(3)-FFD-x-[IL]-S and [RKH]-x(2,5)-E-x(0-2)-[RK]-x(3,4)-[DE]-TFG respectively) contained in Lsm13-15, but not Lsm16, homologues. They succeed the DFDF-x(7)-F motif and are also predicted to be of helical nature .

This entry represents the TGF box.
Protein-S-isoprenylcysteine O-methyltransferase (PPMT_MeTrfase)
Type: Family

Protein-S-isoprenylcysteine O-methyltransferase catalyses the post-translational methylation of isoprenylated C-terminal cysteine residues .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Phosphoethanolamine N-methyltransferase (Phosphoethanolamine_N-MeTrfase)
Type: Family

Phosphoethanolamine N-methyltransferase catalyses N-methylation of phosphoethanolamine, phosphomonomethylethanolamine and phosphodimethylethanolamine, the three methylation steps required to convert phosphoethanolamine to phosphocholine.
Arterivirus papain-like cysteine protease beta (PCPbeta) domain (AV_PCPbeta)
Type: Domain

Arteriviruses are enveloped, positive-stranded RNA viruses and include pathogens of major economic concern to the swine- and horse-breeding industries:

Equine arteritis virus (EAV).

Porcine reproductive and respiratory syndrome virus (PRRSV).

Mice actate dehydrogenase-elevating virus.

Simian hemorrhagic fever virus.

The arterivirus replicase gene is composed of two open reading frames (ORFs). ORF1a is translated directly from the genomic RNA, whereas ORF1b can be expressed only by ribosomal frameshifting, yelding a 1ab fusion protein. Both replicase gene products are multidomain precursor proteins which are proteolytically processed into functional nonstructural proteins (nsps) by a complex proteolytic cascade that is directed by four (PRRSV/LDV) or three (EAV) proteinase domains encoded in ORF1a. The arterivirus replicase processing scheme involves the rapid autoproteolytic release of two or three N-terminal nsps (nsp1 (or nsp1alpha/1beta) and nsp2) and the subsequent processing of the remaining polyproteins by the "main protease" residing in nsp4, together resulting in a set of 13 or 14 individual nsps. The arterivirus nsp1 region contains a tandem of papain-like cysteine autoprotease domains (PCPalpha and PCPbeta), but in EAV PCPalpha has lost its enzymatic activity, resulting in the 'merge' of nsp1alpha and nsp1beta into a single nsp1 subunit. Thus, instead of three self-cleaving N-terminal subunits, EAV has two: nsp1 and nsp2. The PCPalpha and PCPbeta domains mediate the nsp1alpha|1beta and nsp1beta|2 cleavages, respectively. The catalytic dyad of PCPalpha and PCPbeta domains is composed of Cys and His residues. In EAV, a Lys residue is found in place of the catalytic Cys residue, which explains the proteolytic deficiency of the EAV PCPalpha domain . The PCPalpha and PCPbeta domains form respectively peptidase families C31 and C32.

The PCPalpha and PCPbeta domains have a typical papain fold, which consists of a compact global region containing sequentially connected left (L) and right (R) parts in a so-called standard orientation. The L subdomain of PCPalpha consists of four α-helices, while the R subdomain is formed by three antiparallel β strands . The L subdomain of the PCBbeta consists of three α-helices, while the R subdomain is formed by four antiparallel β-strands . The Cys and His residues face each other at the L-R interface and form the catalytic centre of the PCPalpha and PCPbeta domains .

This entry represents the PCPbeta domain (peptidase C32).
Picrinine-N-methytransferase-like (PiNMT-like)
Type: Family

This entry represents a subgroup of the class I SAM-dependent methyltransferases, including Picrinine, Ajmaline, Norajmaline methyltransferases, 2-methyl-6-phytyl-1,4-hydroquinone methyltransferase and plant plastid tocopherol O-methyltransferase (also known as g-TMT (gamma-tocopherol methyltransferase)). Tocopherol O-methyltransferase is involved in the synthesis of tocopherol (vitamin E). It methylates gamma- and delta-tocopherol to form beta- and alpha-tocopherol, respectively .
This family also includes 3-hydroxy-16-methoxy-2,3-dihydrotabersonine N-methyltransferase, a homologue of tocopherol methyltransferases involved in vindoline biosynthesis .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Birnavirus VP4 protease domain (Birna_VP4_Prtase_dom)
Type: Domain

Viruses of the Birnaviridae family infect animal species belonging to vertebrates, molluscs, insects and rotifers and are characterised by their bi- segmented double-stranded RNA genome (segments A and B). Segment A encodes two overlapping reading frames and the larger open reading frame encodes a polyprotein (NH2-pVP2-VP4-VP3-COOH). The polyprotein is processed through the proteolytic activity of VP4 to generate pVP2 and VP3. During virus assembly pVP2 is further processed by VP4 to generate the capsid protein VP2 and structural peptides. Evolutionarily, the VP4 protease of the Birnaviridae family belongs to clan SJ and family S50 .

The birnavirus VP4 protease domain displays a catalytic serine/lysine dyad in its active site. The birnavirus VP4 protease domain has an α/β fold .
Histone-lysine N-methyltransferase SUVR4/SUVR1/SUVR2 (SUVR4/1/2)
Type: Family

This entry represents a family of plant proteins that includes histone-lysine N-methyltransferase SUVR4 and related proteins SUVR1 and SUVR2. SUVR4 is an active histone methyltransferase with a preference for H3K9me1 . SUVR2 has no histone methyltransferase activity and is involved in transcriptional gene silencing . SUVR2 forms a complex with SUVR1 and associates with the SNF2-related chromatin-remodeling proteins. No histone methyltransferase activity has been detected for SUVR1 neither .
GMP synthetase ATP pyrophosphatase domain (GMPS_ATP_PPase_dom)
Type: Domain

Guanosine 5'-monophosphate synthetase (GMPS) is a widespread enzyme seen in all domains of life. GMPS is required for the final step of the de novo synthesis of guanine nucleotides, converting xanthosine 5'-monophosphate (XMP) into guanosine 5'-monophosphate (GMP), a precursor of DNA and RNA. GMPS consists of two catalytic units, glutamine amidotransferase (GATase) and ATP pyrophosphatase (ATP-PPase). GATase hydrolyzes glutamine to yield glutamate and ammonia, while ATP-PPase utilises ammonia to convert adenyl xanthosine 5'-monophosphate (adenyl-XMP) into GMP. The two catalytic units are either encoded by a single gene (two-domain type) in eucaryotes, bacteria, and some archaea, or encoded by two separate genes (two-subunit type) in other archaea. In two-domain-type GMPS, the GATase domain is located in the N-terminal half, and the ATP-PPase domain is located in the C-terminal half; in two-subunit-type GMPS, these two units exist as separate polypeptides. ATP-PPase consists of two domains (N-domain and C-domain). The N-domain contains an ATP-binding platform called P-loop, whereas the C-domain contains the XMP-binding site and also contributes to homodimerisation .

The GMP synthetase ATP-PPase ATP-binding domain is a twisted, five-stranded parallel β-sheet sandwiched between helical layers. It contains a glycine rich ATP-binding motif called the "P-loop motif" located after the first β-strand .
Histone-lysine N-methyltransferase, plant (Hist-Lys_N-MeTrfase_plant)
Type: Family

Members of this family are polycomb group (PcG) proteins from plants. They act as the catalytic subunit of some PcG multiprotein complex, which methylates 'Lys-27' of histone H3, leading to transcriptional repression of the affected target genes. These enzymes are also required to regulate floral development by repressing the AGAMOUS homeotic gene in leaves, inflorescence stems and flowers. They regulate the antero-posterior organisation of the endosperm, as well as the division and elongation rates of leaf cells. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Methionine S-methyltransferase (Met_S-MeTrfase)
Type: Family

This entry represents the methionine S-methyltransferase (

) family, which catalyse the S-methylmethionine (SMM) biosynthesis from adenosyl-L-homocysteine (AdoMet) and methionine . All flowering plants produce S-methylmethionine (SMM) from Met and have a separate mechanism to convert SMM back to Met. The functions of SMM and the reasons for its interconversion with Met are unknown .

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Histone-lysine N-methyltransferase ATX (Hist-Lys_N-MeTrfase_ATX)
Type: Family

This entry represents a group of predictive histone-lysine N-methyltransferases from plants that includes ATX3, ATX4 and ATX5.

Methyltransferases (EC [ec:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Histone-lysine N-methyltransferase Set9, fungi (Set9_fungi)
Type: Family

This entry represents fungal histone-lysine N-methyltransferase Set9 that belongs to the Suv4-20 family. This enzyme catalyzes mono-, di-, and trimethylation of H4K20. It participates in DNA damage response by giving a 'histone mark' required for the recruitment of the checkpoint protein Crb2 to sites of DNA damage .
Protein N-terminal and lysine N-methyltransferase EFM7 (EFM7)
Type: Family

This entry includes N-terminal and lysine N-methyltransferase EFM7 that trimethylates the N-terminal glycine of elongation factor 1-alpha (TEF1 and TEF2) and then the adjacent lysine . It may be involved in rDNA silencing and in lifespan determination .