SII-SWORD/CoKE huggingface dataset:
Beta-retroviral matrix protein (B_retro_matrix)
Type: Domain

Retroviral matrix proteins (or major core proteins) are components of envelope-associated capsids, which line the inner surface of virus envelopes and are associated with viral membranes . Matrix proteins are produced as part of Gag precursor polyproteins. During viral maturation, the Gag polyprotein is cleaved into major structural proteins by the viral protease, yielding the matrix (MA), capsid (CA), nucleocapsid (NC), and some smaller peptides. Gag-derived proteins govern the entire assembly and release of the virus particles, with matrix proteins playing key roles in Gag stability, capsid assembly, transport and budding. Although matrix proteins from different retroviruses appear to perform similar functions and can have similar structural folds which predominantly consist of four closely packed α-helices that are interconnected through loops, their primary sequences can be very different .

This entry represents matrix proteins from beta-retroviruses such as Mason-Pfizer monkey virus (MPMV) (Simian Mason-Pfizer virus) and Mouse mammary tumor virus (MMTV) . This entry also identifies matrix proteins from several eukaryotic endogenous retroviruses, which arise when one or more copies of the retroviral genome becomes integrated into the host genome .
TerD domain (TerD)
Type: Domain

The TerD domain is found in TerD family proteins that include the paralogous TerD, TerA, TerE, TerF and TerZ proteins . It is found in a stress response operon with TerB and TerC. TerD has a maximum of two calcium binding sites depending on the conservation of aspartates . It has various fusions to nuclease domains, RNA binding domains, ubiquitin related domains, and metal binding domains. The ter gene products lie at the centre of membrane-linked metal recognition complexes with regulatory ramifications encompassing phosphorylation-dependent signal transduction, RNA-dependent regulation, biosynthesis of nucleoside-like metabolites and DNA processing linked to novel pathways .

TerD domain is also found in cAMP binding protein, chemical-damaging agent resistance proteins and general stress proteins. The cellular Slime mould, Dictyostelium discoideum, contains a cAMP-binding protein, CABP1, which is composed of two subunits. The C-terminal half of these subunits contain this domain .
TRA-1 regulated (TRA-1_regulated)
Type: Family

This family of proteins represents the protein product of the gene R03H10.4 which is located near a sequence that matches the TRA-1 binding consensus. TRA-1 is a transcription factor which controls sexual differentiation in C.elegans. R03H10.4 shows male-enriched reporter gene expression and acts as a direct target of TRA-1 regulation .
Leucine zipper, Myc (Myc-LZ)
Type: Domain

This family consists of the leucine zipper dimerisation domain found in both cellular c-Myc proto-oncogenes and viral v-Myc oncogenes. Dimerisation via the leucine zipper motif with other basic helix-loop-helix-leucine zipper (b/HLH/lz) proteins is required for efficient DNA binding . The Myc-Max dimer is a transactivating complex activating expression of growth related genes promoting cell proliferation. The dimerisation is facilitated via interdigitating leucine residues every 7th position of the α helix. Like charge repulsion of adjacent residues in this region preturbs the formation of homodimers with heterodimers being promoted by opposing charge attractions. It has been demonstrated that in transgenic mice the balance between oncogene-induced proliferation and apoptosis in a given tissue can be a critical determinant in the initiation and maintenance of the tumor .
Acylneuraminate cytidylyltransferase (Cytidylyl_trans)
Type: Family

Synonym(s): CMP-N-acetylneuraminic acid synthetase

Acylneuraminate cytidylyltransferase (

) (CMP-NeuAc synthetase) catalyzes the reaction of CTP and NeuAc to form CMP-NeuAc, which is the nucleotide sugar donor used by sialyltransferases . The outer membrane lipooligosaccharides of some microorganisms contain terminal sialic acid attached to N-acetyllactosamine and so this modification may be important in pathogenesis.

This family also includes 8-amino-3,8-dideoxy-manno-octulosonate cytidylyltransferase found in the bacterial genus Shewanella, which is important in the development of the outer cell membrane and converts 3-deoxy-d-manno-octulosonic acid to 8-amino-3,8-dideoxy-d-manno-octulosonic acid (KDO8N) for incorporation into the lipopolysaccharide .
Major surface glycoprotein MSG (MSG)
Type: Family

The immunogenic major surface antigen (MSG) also termed glycoprotein A (gpA) is involved in the immunopathogenesis of Pneumocystis carinii. MSG from all P. carinii has conserved secondary structure, as well as function .
UDP-N-acetylglucosamine 2-epimerase domain (UDP_GlcNAc_Epimerase_2_dom)
Type: Domain

This entry represents a domain found in the bacterial UDP-N-acetylglucosamine 2-epimerase WecB, which is involved in the enterobacterial common antigen biosynthesis . It can also be found in the N-terminal region of the mammalian bifunctional protein GNE, which has both the UDP-N-acetylglucosamine 2-epimerase and the N-acetylmannosamine kinase functions. GNE catalyses the first two steps of sialic acid biosynthesis in the cytosol .
Decorin-binding protein (Decorin-bd)
Type: Family

Decorin is a proteoglycan that decorates collagen fibres. Borrelia burgdorferi causes lyme disease, a tick-borne infection that can develop into a chronic, multisystemic disorder. Decorin may mediate the adherence of B. burgdorferi to collagen fibres in skin and other tissues . B. burgdorferi decorin binding proteins A and B (DbpA/B) are responsible for decorin binding . DbpA of Borrelia burgdorferi mediates bacterial adhesion to heparin and dermatan sulfate associated with decorin .
Cyclopropane mycolic acid synthase (CMAS)
Type: Family

This entry represents cyclopropane mycolic acid synthases (CMAS) and related enzymes, including CmaA1, CmaA2 (cyclopropane mycolic acid synthase A1 and A2), MmaA1-4 (methoxymycolic acid synthase A1-4) and tuberculostearic acid methyltransferase UfaA1. All are thought to be S-adenosyl-L-methionine (SAM) utilising methyltransferases . This entry also includes S-adenosylmethionine-dependent methyltransferase UmaA from Mycobacterium tuberculosis, which is a methyltransferase that modifies short-chain fatty acids .

Mycolic acid cyclopropane synthase or cyclopropane-fatty-acyl-phospholipid synthase (CFA synthase)

catalyses the reaction:

S-adenosyl-L-methionine + phospholipid olefinic fatty acid ->S-adenosyl-L-homocysteine + phospholipid cyclopropane fatty acid.

The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain. Cyclopropanation may contribute to the structural integrity of the cell wall complex .
Trehalose-phosphatase (Trehalose_PPase)
Type: Family

Trehalose-phosphatases

catalyse the de-phosphorylation of trehalose-6-phosphate to trehalose and orthophosphate. Trehalose is a common disaccharide of bacteria, fungi and invertebrates that appears to play a major role in desiccation tolerance. A pathway for trehalose biosynthesis may also exist in plants . The trehalose-phosphatase signature is found in the C terminus of trehalose-6-phosphate synthase

adjacent to the trehalose-6-phosphate synthase domain (see

). It would appear that the two equivalent genes in the Escherichia coli otsBA operon: otsA, the trehalose-6-phosphate synthase and otsB, trehalose-phosphatase (this family) have undergone gene fusion in most eukaryotes . This entry includes sequences from plants and fly that does not possess catalytic activity .
CDC48, N-terminal subdomain (CDC4_N-term_subdom)
Type: Domain

This entry represents the amino-terminal subdomain.

The CDC48 N-terminal domain is a protein domain found in AAA ATPases including cell division protein 48 (CDC48), VCP-like ATPase (VAT) and N-ethylmaleimide sensitive fusion protein. It is a substrate recognition domain which binds polypeptides, prevents protein aggregation, and catalyses refolding of permissive substrates. It is composed of two equally sized subdomains. The amino-terminal subdomain forms a double-psi β-barrel whose pseudo-twofold symmetry is mirrored by an internal sequence repeat of 42 residues. The carboxy-terminal subdomain forms a novel six-stranded β-clamp fold . Together these subdomains form a kidney-shaped structure.
ABC/ECF transporter, transmembrane component (ABC/ECF_trnsptr_transmembrane)
Type: Family

ECF (energy-coupling factor) transporters are a subgroup of ABC (ATP-binding cassette) transporters involved in the uptake of vitamins and micronutrients in prokaryotes . ECF transporters are protein complexes consisting of a conserved module (two peripheral ATPases, known as the A and A' components, and the integral membrane protein EcfT) and a non-conserved integral membrane protein responsible for substrate specificity (S-component) . ECF transporters comprise a subgroup of ATP-binding cassette (ABC) transporters that do not make use of water-soluble substrate binding proteins or domains, but instead employ integral membrane proteins for substrate binding, the S component, in contrast to classical ABC importers.

This entry represents the transmembrane component (T component) of the ECF-type transporter, a transmembrane protein important for vitamin uptake in prokaryotes. The T component links the S component to the ATP-binding subcomplex .
B3 DNA binding domain (B3_DNA-bd)
Type: Domain

Two DNA binding proteins, RAV1 and RAV2 from Arabidopsis thaliana contain two distinct amino acid sequence domains found only in higher plant species. The N-terminal regions of RAV1 and RAV2 are homologous to the AP2 DNA-binding domain (see

) present in a family of transcription factors, while the C-terminal region exhibits homology to the highly conserved C-terminal domain, designated B3, of VP1/ABI3 transcription factors . The AP2 and B3-like domains of RAV1 bind autonomously to the CAACA and CACCTG motifs, respectively, and together achieve a high affinity and specificity of binding. It has been suggested that the AP2 and B3-like domains of RAV1 are connected by a highly flexible structure enabling the two domains to bind to the CAACA and CACCTG motifs in various spacings and orientations .

This entry represents the B3 DNA binding domain. Its DNA binding activity has been demonstrated . The B3 domain can be found in one or more copies.
Cysteine rich repeat, tripleX (Cys_rich_tripleX)
Type: Repeat

This signature describes a cysteine repeat C-X3-C-X3-C the function of which is unknown as is the function of the proteins in which they occur.
ArnT-like, N-terminal domain (ArnT-like_N)
Type: Domain

This entry represents the N-terminal domain found in glycosyltransferase family 39 members, including Undecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase (ArnT), Protein O-mannosyl-transferase 2	(pomt2) and Dolichyl-phosphate-mannose--protein mannosyltransferase proteins. This domain contains an all-helical fold.

Dolichyl-phosphate-mannose-protein mannosyltransferase proteins

belong to the glycosyltransferase family 39 (

) and are responsible for O-linked glycosylation of proteins. They catalyse the reaction:
Dolichyl phosphate D-mannose + protein ->dolichyl phosphate + O-D-mannosyl-protein.

The transfer of mannose to seryl and threonyl residues of secretory proteins is catalysed by a family of protein mannosyltransferases in Saccharomyces cerevisiae coded for by seven genes (PMT1-7). Protein O-glycosylation is essential for cell wall rigidity and cell integrity and this protein modification is vital for S. cerevisiae .

Undecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase proteins

belong to the glycosyltransferase family 83 (

). They catalyse the reaction:
4-amino-4-deoxy-alpha-L-arabinopyranosyl di-trans,octa-cis-undecaprenyl phosphate + lipid IV(A) = lipid II(A) + di-trans,octa-cis-undecaprenyl phosphate.

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.
Bacterial Ig-like domain, group 2 (Big_2)
Type: Domain

The Ig-like fold is part of proteins with important roles in different physiological processes . This entry represents the bacterial Ig-like domain (Big2). This domain is mainly found in a variety of bacterial and phage surface proteins such as intimins, but has also been found in several eukaryote proteins .

Intimin (Eae protein) is a bacterial cell-adhesion molecule that mediates the intimate bacterial host-cell interaction. It contains three domains; two immunoglobulin-like domains and a C-type lectin-like module implying that carbohydrate recognition may be important in intimin-mediated cell adhesion .

The structure of this domain was also described in the Tail tube protein of phage lambda (TTP). This protein assembles in hexameric rings that stack on top of each others .

Nuclear pore membrane glycoprotein 210 from humans (POM210) also belongs to this group of proteins. This nucleoporin is essential for nuclear pore assembly and fusion, nuclear pore spacing, as well as structural integrity .
Big-1 (bacterial Ig-like domain 1) domain (Big_1_dom)
Type: Domain

The bacterial immunoglobulin-like (Ig) domain 1 or Big-1 domain is a domain of ~95 amino acids present in bacterial adhesion molecules of the intimin/invasin family, involved in pathogenicity, and YeeJ, a inverse autotransporter adhesin. The domain is named after the 3D structure of the domain in enteropathogenic Escherichia coli intimin and in Yersinia pseudotuberculosis invasin, which are both adhesins with a tandem repeat of the Big-1 domain. The 3D structure of the Big-1 domain is a β-sheet sandwich with a topology similar to eukaryotic members of the immunoglobulin superfamily. In most intimin/invasin proteins the Big-1 domain occurs in a tandem, N-terminal to a different Ig-like domain, followed by a C-terminal C-type lectin-like domain. Big-1 can also occur in combination with the lysM domain or in a tandem repeat of several copies.

Big-1 proteins are surface-expressed proteins that mediate mammalian host cell invasion or attachment. The tandem of Ig-like domains appears to form a rod to link the bacterial outer membrane anchor to the C-terminal lectin-like domain to interact with their receptors in the host cell membrane .
M protein repeat (M_repeat)
Type: Repeat

This short repeat is found in multiple copies in bacterial M proteins. The M proteins bind to IgA and are closely associated with virulence.
The M protein has been postulated to be a major group A streptococcal (GAS) virulence factor because of its contribution to the bacterial resistance to opsonophagocytosis .
Transposase IS116/IS110/IS902, C-terminal (Transposase_20)
Type: Domain

Transposases are needed for efficient transposition of the insertion sequence or transposon DNA. This entry represents the C-terminal domain of region of the pilin gene inverting protein (PIVML) and transposases IS116, IS110 and IS902 .
JmjC domain (JmjC_dom)
Type: Domain

The JmjN and JmjC domains are two non-adjacent domains which have been identified in the jumonji family of transcription factors. Although it was originally suggested that the JmjN and JmjC domains always co-occur and might form a single functional unit within the folded protein, the JmjC domain was later found without the JmjN domain in organisms from bacteria to human .

Proteins containing JmjC domain are predicted to be metalloenzymes that adopt the cupin fold and are candidates for enzymes that regulate chromatin remodelling . The cupin fold is a flattened β-barrel structure containing two sheets of five antiparallel β-strands that form the walls of a zinc-binding cleft. Based on the crystal structure of JmjC domain containing protein FIH and JHDM3A/JMJD2A, the JmjC domain forms an enzymatically active pocket that coordinates Fe(III) and alphaKG. Three amino-acid residues within the JmjC domain bind to the Fe(II) cofactor and two additional residues bind to alphaKG .

JmjC domains were identified in numerous eukaryotic proteins containing domains typical of transcription factors, such as PHD, C2H2, ARID/BRIGHT and zinc fingers . The JmjC has been shown to function in a histone demethylation mechanism that is conserved from yeast to human . JmjC domain proteins may be protein hydroxylases that catalyse a novel histone modification . The human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation .
JmjN domain (JmjN)
Type: Domain

This entry represents the JmjN domain.

The JmjN and JmjC domains are two non-adjacent domains which have been identified in the jumonji family of transcription factors. Although it was
originally suggested that the JmjN and JmjC domains always co-occur and might form a single functional unit within the folded protein, the JmjC domain was later found without the JmjN domain in organisms from bacteria to human .

JmJC domains are predicted to be metalloenzymes that adopt the cupin fold, and are candidates for enzymes that regulate chromatin remodelling. The cupin fold is a flattened β-barrel structure containing two sheets of five antiparallel β-strands that form the walls of a zinc-binding cleft. JmjC domains were identified in numerous eukaryotic proteins containing domains typical of transcription factors, such as PHD, C2H2, ARID/BRIGHT and zinc fingers . The JmjC has been shown to function in a histone demethylation mechanism that is conserved from yeast to human .
CUT domain (CUT_dom)
Type: Domain

The CUT domain is a DNA-binding motif which can bind independently or in cooperation with the homeodomain, often found downstream of the CUT domain. Multiple copies of the CUT domain can exist in one protein.
Dishevelled protein domain (Dishevelled_protein_dom)
Type: Domain

This domain is specific to the signalling protein dishevelled. Dishevelled (Dsh/Dvl) is a highly conserved protein family that plays an important role in mediating Wnt signaling. Wnt signal transduction pathways control a variety of developmental and homeostatic events. Dishevelled is involved in both the canonical and non-canonical (B-catenin-independent) pathways .

This domain is found adjacent to the PDZ domain (

), often in conjunction with DEP (

) and DIX (

).
Phosphotransferase system, EIIC (PTS_EIIC)
Type: Domain

The bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) is a multi-protein system involved in the regulation of a variety of metabolic and transcriptional processes. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease which consists of at least three structurally distinct domains (IIA, IIB, and IIC) which can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII). The IIC domain catalyzes the transfer of a phosphoryl group from IIB to the sugar substrate.

PTS systems commonly occur in bacteria. An archaeal version has also been discovered . This entry identifies both the bacterial family members and archaeal homologues.
Phosphotransferase system, fructose-specific IIB subunit (PTS_IIB_fruc)
Type: Domain

The bacterial phosphoenolpyruvate: sugar phosphotransferase system (PTS) is a multi-protein system involved in the regulation of a variety of metabolic and transcriptional processes. The PTS catalyzes the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane. The general mechanism of the PTS is the following: a phosphoryl group from phosphoenolpyruvate (PEP) is transferred to enzyme-I (EI) of PTS which in turn transfers it to a phosphoryl carrier protein (HPr). Phospho-HPr then transfers the phosphoryl group to a sugar-specific permease which consists of at least three structurally distinct domains (IIA, IIB, and IIC) which can either be fused together in a single polypeptide chain or exist as two or three interactive chains, formerly called enzymes II (EII) and III (EIII). IIB (

) is is phosphorylated by phospho-IIA, before the phosphoryl group is transferred to the sugar substrate.

Several PTS permease families are currently recognised, namely, the (i) glucose (including glucoside), (ii) fructose (including mannitol), (iii) lactose (including N,N-diacetylchitobiose), (iv) galactitol, (v) glucitol, (vi) mannose, and (vii) l-ascorbate families .

This entry represents the component EIIB of fructose-specific PTS systems.
Small/middle T-antigen (Papo_T_antigen)
Type: Domain

This domain represents a conserved region in papovavirus small and middle T-antigens. It is found as the N-terminal domain in the small T-antigen, and is centrally located in the middle T-antigen .
DNA methylase, adenine-specific (DNA_methylase_A-5)
Type: Domain

This domain is found in N-6 adenine-specific DNA methylases (

) mainly from prokaryotes.
These enzymes are responsible for the methylation of specific DNA sequences in order to prevent the host from digesting its own genome via its restriction enzymes. These methylases have the same sequence specificity as their corresponding restriction enzymes. The type I restriction and modification system is composed of three polypeptides R, M and S. The M and S subunits together form a methyltransferase that methylates two adenine residues in complementary strands of a bipartite DNA recognition sequence. In the presence of the R subunit, the complex can also act as an endonuclease, binding to the same target sequence but cutting the DNA some distance from this site. Whether the DNA is cut or modified depends on the methylation state of the target sequence. When the target site is unmodified, the DNA is cut. When the target site is hemimethylated, the complex acts as a maintenance methyltransferase, modifying the DNA so that both strands become methylated.