SII-SWORD/CoKE huggingface dataset:
Macro domain (Macro_dom)
Type: Domain

The Macro or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose (an NAD metabolite) or related ligands. Binding to ADP-ribose could be either covalent or non-covalent : in certain cases it is believed to bind non-covalently ; while in other cases (such as Aprataxin) it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein . The domain was described originally in association with ADP-ribose 1''-phosphate (Appr-1''-P) processing activity (A1pp) of the yeast YBR022W protein . The domain is also called Macro domain as it is the C-terminal domain of mammalian core histone macro-H2A . Macro domain proteins can be found in eukaryotes, in (mostly pathogenic) bacteria, in archaea and in ssRNA viruses, such as coronaviruses , Rubella and Hepatitis E viruses. In vertebrates the domain occurs e.g. in histone macroH2A, in predicted poly-ADP-ribose polymerases (PARPs) and in B aggressive lymphoma (BAL) protein. The macro domain can be associated with catalytic domains, such as PARP, or sirtuin. The Macro domain can recognise ADP-ribose or in some cases poly-ADP-ribose, which can be involved in ADP-ribosylation reactions that occur in important processes, such as chromatin biology, DNA repair and transcription regulation . The human macroH2A1.1 Macro domain binds an NAD metabolite O-acetyl-ADP-ribose . The Macro domain has been suggested to play a regulatory role in ADP-ribosylation, which is involved in inter- and intracellular signaling, transcriptional regulation, DNA repair pathways and maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis.

The 3D structure of the SARS-CoV Macro domain has a mixed α/β fold consisting of a central seven-stranded twisted mixed β-sheet sandwiched between two α-helices on one face, and three on the other. The final α-helix, located on the edge of the central β-sheet, forms the C terminus of the protein . The crystal structure of AF1521 (a Macro domain-only protein from Archaeoglobus fulgidus) has also been reported and compared with other Macro domain containing proteins. Several Macro domain only proteins are shorter than AF1521, and appear to lack either the first strand of the β-sheet or the C-terminal helix 5. Well conserved residues form a hydrophobic cleft and cluster around the AF1521-ADP-ribose binding site .
Type I phosphodiesterase/nucleotide pyrophosphatase/phosphate transferase (Phosphodiest/P_Trfase)
Type: Family

This family consists of phosphodiesterases, including human plasma-cell membrane glycoprotein PC-1/alkaline phosphodiesterase I/nucleotide pyrophosphatase (nppase). These enzymes catalyze the cleavage of phosphodiester and phosphosulphate bonds in NAD, deoxynucleotides and nucleotide sugars . Another member of this family is ATX an autotaxin, tumor cell motility-stimulating protein which exhibits type I phosphodiesterases activity . The alignment encompasses the active site . Also present within this family is 60kDa Ca2-ATPase from Myroides odoratus .

This entry also hits a number of ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis .

N-acetylglucosamine-6-O-sulfatase is another member of this family that catalyses the hydrolysis of the 6-sulfate groups of the N-acetyl-D-glucosamine 6-sulfate units and plays a key role in the persistence of the major human gut symbiont B.thetaiotaomicron in the gastrointestinal tract .
Outer capsid protein sigma-1, C-terminal domain (S1_C)
Type: Domain

This entry represents the C-terminal domain of Outer capsid protein sigma-1 from Reovirus type 1 (S1, also known as Cell attachment protein) and similar proteins from reovirales. This glycoprotein is a minor capsid protein and also determines the serotype-specific humoral immune response. Sigma 1 consist of a fibrous tail and a globular head. The head, a gobular domain that folds into a compact, eight-stranded β-barrel (this entry) has important roles in the cell attachment function of sigma 1 and determinant of the type-specific humoral immune response .
Domain of unknown function DX (DX)
Type: Domain

This domain has no known function. It is found in several Caenorhabditis proteins. The domain contains 6 conserved cysteines that probably form three disulphide bridges.
Glycoside hydrolase family 12 (GH12)
Type: Family

Glycoside hydrolase family 12

comprises enzymes with two known activities: Endo-β-1,4-glucanase (

) and Xyloglucan-specific endo-β-1,4-glucanase / endo-xyloglucanase (

). These enzymes were formerly known as cellulase family H.

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
African swine fever virus, MGF360 (ASFV_MGF360)
Type: Family

The multigene family 360 protein are found within the African swine fever virus (ASFV) genome which consist of dsDNA and has similar structural features to the poxviruses . The biological function of this family is not known , although

is a major structural protein .
Plasmid partition protein (Plasmid_parti)
Type: Family

This family consists of conserved hypothetical proteins from Borrelia burgdorferi (Lyme disease spirochete)
, some of which are putative plasmid partition proteins .
Herpesvirus major envelope glycoprotein (Herpes_env)
Type: Family

This family consists of probable major envelope glycoproteins from members of the herpesviridae including Human herpesvirus 1 (HHV-1), Human cytomegalovirus (HHV-5) and Human herpesvirus 3 (HHV-3). Members of the herpesviridae have a dsDNA genome and do not have an RNA stage during their replication.
Herpesvirus UL7-like (Herpes_UL7)
Type: Family

This family consists of various functionally undefined proteins from the herpesviridae and UL7 from Bovine herpesvirus 1 . UL7 is not essential for virus replication in cell culture, and is found localized in the cytoplasm of infected cells accumulated around the nucleus but could not be detected in purified virions . Members of the herpesviridae have a dsDNA genome and do not have a RNA stage during there replication.

This entry also includes cytoplasmic envelopment protein 1 (or UL103) which is important for the final step of tegumentation, envelope acquisition and egress of virus particles out of the cytoplasm .
C6 domain (C6_domain)
Type: Domain

This domain of unknown function is found at the C terminus in a number of sequences mainly from Caenorhabditis and related species. It may be an extracellular domain. Most copies of the domain contain six conserved cysteine residues. However some copies of the domain are missing cysteine residues 1 and 3 suggesting that these form a disulphide bridge.
Domain of unknown function DB (DB)
Type: Domain

This domain has no known function being found in several Caenorhabditis elegans proteins. The domain contains 12 conserved cysteines that probably form six disulphide bridges. This domain is found associated with Ig

and Fibronectin, type III

domains.
ET repeat (ET_repeat)
Type: Repeat

This repeat is found in proteins of unknown function, mainly from Caenorhabditis. Each repeat contains 8-10 conserved cysteines that probably form 4-5 disulphide bridges. By inspection of the conservation of cysteines it looks like cysteines 1, 2, 3, 4, 9 and 10 are always present and that sometimes the pair 5 and 8 or the pair 6 and 7 are missing. This suggests that cysteines 5/8 and 6/7 make disulphide bridges.
Adenovirus penton base protein (Adeno_Penton_B)
Type: Family

This family consists of various adenovirus penton base proteins (also known as Protein III) , from both the mastadenoviridae having mammalian hosts and the aviadenoviridae having avian hosts. The penton base is a major structural protein forming part of the penton which consists of a base and a fibre, the pentons hold a morphologically prominent position at the vertex capsomer in the adenovirus particle . In mammalian adenovirus there is only one tail on each base where as in avian adenovirus there are two .

The penton base proteins are also Involved in virus secondary attachment to host cell after initial attachment by the fibre protein .
Riboflavin kinase, bacterial (Riboflavin_kinase_bac)
Type: Family

Riboflavin is converted into catalytically active cofactors (FAD and FMN) by the actions of riboflavin kinase (

), which converts it into FMN, and FAD synthetase (

), which adenylates FMN to FAD. Eukaryotes usually have two separate enzymes, while most prokaryotes have a single bifunctional protein that can carry out both catalyses, although exceptions occur in both cases. While eukaryotic monofunctional riboflavin kinase is orthologous to the bifunctional prokaryotic enzyme , the monofunctional FAD synthetase differs from its prokaryotic counterpart, and is instead related to the PAPS-reductase family . The bacterial FAD synthetase that is part of the bifunctional enzyme has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases .

This entry represents the bacterial bifunctional form of riboflavin kinase.
Paramyxovirus non-structural protein C (Paramyxo_C)
Type: Family

This family consist of the C proteins (C', C, Y1, Y2) found in the Paramyxovirinae, e.g. Human parainfluenza virus 3, and Sendai virus. The C proteins effect viral RNA synthesis having both a positive and negative effect during the course of infection .
The paramyxovirinae have a negative-strand ssRNA genome of 15.3 kb from which six mRNAs are transcribed, five of these are monocistronic.
The P/C mRNA is polycistronic and has two overlapping open reading frames P and C, C encodes the nested C proteins C', C, Y1 and Y2 .
Peptidase S54, RHOMBOID-like (Peptidase_S54_rhomboid-like)
Type: Family

This group of proteins contain serine peptidases belonging to the MEROPS peptidase family S54 (Rhomboid, clan ST). They are integral membrane proteins related to the Drosophila melanogaster (Fruit fly) rhomboid protein

. Members of this family are found in bacteria, archaea, and eukaryotes, mainly plant and fungi.

Plant rhomboid-like proteins are rhomboid-type serine proteases that catalyse intramembrane proteolysis . This entry also includes some inactive homologues, such as Inactive RHOMBOID-like protein 8 from Arabidopsis (also known as KOM and KOMPEITO), which is essential for the meiosis stage-specific callose accumulation and pollen exine formation .
IstB-like ATP-binding domain (IstB_ATP-bd)
Type: Domain

Proteins in this entry contain an ATP/GTP binding P-loop motif, including the DNA replication protein DnaC and IS21 transposase regulator IstB, which are close paralogues . DnaC interacts with DnaB and form a primosome complex for DNA replication .
Adenovirus large t-antigen, E1B 55kDa protein (Adeno_E1B_55kDa)
Type: Family

This family consists of adenovirus E1B 55kDa protein or large t-antigen. E1B 55kDa binds p53 the tumor suppressor protein converting it from a transcriptional activator which responds to damaged DNA in to an unregulated repressor of genes with a p53 binding site . This protects the virus against p53 induced host antiviral responses and prevents apoptosis as induced by the adenovirus E1A protein .
The E1B region of adenovirus encodes two proteins E1B 55kDa, the large t-antigen as found in this family and E1B 19kDa

, the small t-antigen. Both of these proteins inhibit E1A induced apoptosis.
Inner layer core protein VP3, Orbivirus (Inner_layer_core_VP3_Orbivir)
Type: Family

This entry represents the inner layer core protein VP3 from Orbiviruses, a family of Reoviruses that have dsRNA genomes of 10-12 linear segments . Orbiviruses include Broadhaven virus (BRD), Epizootic hemorrhagic disease virus and Bluetongue virus (BTV) . The Orbivirus VP3 protein is part of the virus core and makes a 'subcore' shell made up of 120 copies of the 100K protein . VP3 particles can also bind RNA and are fundamental in the early stages of viral core formation . The structural core protein VP2 from BRD is similar to VP3 from BTV.
Photosystem I PsaJ, reaction centre subunit IX (PSI_PsaJ)
Type: Family

This family consists of the photosystem I reaction centre subunit IX or PsaJ from various organisms including Synechocystis sp. (strain PCC 6803), Pinus thunbergii (Japanese black pine) and Zea mays (Maize). PsaJ (

) is a small 4.4kDa, chloroplast encoded, hydrophobic subunit of the photosystem I reaction complex whose function is not yet fully understood . PsaJ can be cross-linked to PsaF (

) and has a single predicted transmembrane domain. It may help in the organization of the PsaE and PsaF subunits. It has a proposed role in maintaining PsaF in the correct orientation to allow for fast electron transfer from soluble donor proteins to P700+ .

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .
tRNA-guanine(15) transglycosylase-like (tRNA_ribo_trans-like)
Type: Domain

Queuine tRNA-ribosyltransferases, also known as tRNA-guanine transglycosylases (TGT)

, modify tRNAs for asparagine, aspartic acid, histidine and tyrosine with queuine at position 34 and with archaeosine at position 15 in archaeal tRNAs. In bacteria it catalyses the exchange of guanine-34 at the wobble position with 7-aminomethyl-7-deazaguanine (preQ1), and subsequently the addition of a cyclopentenediol moiety to 7-aminomethyl-7-deazaguanine-34 tRNA giving a hypermodified base queuine (Q) in the wobble position . In eukaryotes, TGT catalyses the irreversible exchange of guanine in the unmodified tRNA with free queuine. Eukaryotes cannot synthesize queuine
de novo
and must obtain it from the diet or gut flora .

The structure of TGT consists of an irregular (β/α)
8
barrel, represented by this entry, and a C-terminal zinc-containing subdomain .

This region is also found in DNA-guanine transglycosylase from Salmonella montevideo, which is involved in the insertion of 7-deazaguanine derivatives in DNA .
UDPGP family (UDPGP_fam)
Type: Family

This family contains UTP--glucose-1-phosphate uridylyltransferases (

), UDP-sugar pyrophosphorylases (

), UDP-N-acetylglucosamine pyrophosphorylases (

) and UDP-N-acetylhexosamine pyrophosphorylases, all of which catalyse the transfer of an uridylyl group.
Domain of unknown function CX (CX)
Type: Domain

This domain of unknown function is found in proteins from nematodes, including Uncharacterized protein C07A9.12 from Caenorhabditis elegans. The domain contains 6 conserved cysteines that probably form three disulphide bridges.
Geminivirus infecting protein (Gemini_mov)
Type: Family

This family consists of putative movement proteins from Maize streak virus and Wheat dwarf virus .
Transposase, Synechocystis PCC 6803 (Transposase_14)
Type: Domain

Transposase proteins are necessary for efficient DNA transposition.
This entry includes insertion sequences from Synechocystis sp. (strain PCC 6803) three of which are characterised as homologous to bacterial IS5- and IS4- and to several members of the IS630-Tc1-mariner superfamily .
Deoxynucleoside kinase (DCK/DGK)
Type: Family

This family consists of various deoxynucleoside kinases including cytidine (

), guanosine (

), adenosine (

) and thymidine kinase (

), which also phosphorylates deoxyuridine and deoxycytosine. These enzymes catalyse the production of deoxynucleotide 5'-monophosphate from a deoxynucleoside, using ATP and yielding ADP in the process.
Smr domain (Smr_dom)
Type: Domain

The Smr domain is an around 90-residue domain found in:

The C-terminal region of the MutS2 proteins from bacteria and plants, such as Endonuclease MutS2 from Bacillus thuringiensis.

The small MutS related (Smr) proteins from bacteria and eukaryotes, including Ribosome rescue factor SmrB from Escherichia coli.

Other Smr domain-containing animal and fungal proteins, including human NEDD4-binding protein 2, which has 5'-polynucleotide kinase and nicking endonuclease activity .

These proteins could be involved in mismatch repair (MMR) or/and chromosome crossing-over and segregation. It has been proposed that the Smr domain acts as a nicking endonuclease .
Photosystem II extrinsic protein O (PsbO)
Type: Family

In PSII, the oxygen-evolving complex (OEC) is responsible for catalysing the splitting of water to O(2) and 4H+. The OEC is composed of a cluster of manganese, calcium and chloride ions bound to extrinsic proteins. In cyanobacteria there are five extrinsic proteins in OEC (PsbO, PsbP-like, PsbQ-like, PsbU and PsbV), while in plants there are only three (PsbO, PsbP and PsbQ), PsbU and PsbV having been lost during the evolution of green plants .

This family represents the PSII OEC protein PsbO, which appears to be the most important extrinsic protein for oxygen evolution. PsbO lies closest to the Mn cluster where water oxidation occurs, and has a stabilising effect on the Mn cluster. As a result, PsbO is often referred to as the Mn-stabilising protein (MSP), although none of its amino acids are likely ligands for Mn. Calcium ions were found to modify the conformation of PsbO in solution .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .
Cobalamin-independent methionine synthase MetE, C-terminal/archaeal (Met_Synth_C/arc)
Type: Domain

Methionine synthases catalyse the the final step of methionine biosynthesis. Two apparently unrelated families of proteins catalyse this step: cobalamin-dependent methionine synthase, which catalyses the transfer of a methyl group from N5-methyltetrahydrofolate to L-homocysteine and requires cobalamin as a cofactor (MetH; 5-methyltetrahydrofolate:L-homocysteine S-methyltransferase;

) and cobalamin-independent methionine synthase, which catalyses the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine without using an intermediate methyl carrier (MetE; 5-methyltetrahydropteroyltri-L-glutamate:L-homocysteine S-methyltransferase;

). These enzymes display no detectable sequence homology between them, but both require zinc for activation and binding to L-homocysteine. Organisms that cannot obtain cobalamin (vitamin B12) encode only the cobalamin-independent enzyme. Escherichia coli and many other bacteria express both enzymes . Mammals utilise only cobalamin-dependent methionine synthase, while plants and yeasts utilise only the cobalamin-independent enzyme.

The N-terminal half and C-terminal half of MetE in E. coli show some sequence similarity, indicating that the metE gene has evolved from an ancestral metE gene by duplication . This entry represents a the C-terminal domain of cobalamin-independent methionine synthase (MetE) from bacteria and plants, which contains the zinc ion responsible for binding and activating homocysteine . It also includes archaeal proteins where this domain corresponds to the entire length of the protein .
Orbivirus non-structural protein NS1/hydrophobic tubular protein (Orbi_NS1)
Type: Family

This family consists of orbivirus non-structural protein NS1, or hydrophobic tubular protein. NS1 has no specific function in virus replication, it is however thought to play a role in transport of mature virus particles from virus inclusion bodies to the cell membrane . Orbivirus are part of the larger reoviridae which have a dsRNA genome of at least 10 segments encoding at least 10 viral proteins ; orbivirus found in this family include Bluetongue virus, and African horsesickness virus.
Plasmid replication protein, origin binding domain (Plasmid_rep_OBD)
Type: Domain

This entry represents the N-terminal origin binding domain (OBD) of various bacterial plasmid replication (Rep) proteins. Rep is a rolling-circle replication (RCR) initiation protein and provides endonuclease activity. It is generally found as hexamer, in contrast to other RCR proteins that are purified as monomers or dimers. These proteins are essential for replication of plasmids, the Rep proteins are topoisomerases that nick the positive stand at the plus origin of replication and also at the single-strand conversion sequence .

Crystal structure of RepB revealed that the DNA-binding capability as well as the nuclease and strand-transfer activities reside in its N-terminal origin binding domain (OBD), which belongs to the replication (Rep) class of the HUH endonuclease superfamily. The C-terminal oligomerization domain of the protein form a rigid cylindrical scaffold to which the N-terminal DNA-binding/catalytic domains are attached as highly flexible appendages, featuring multiple orientations .
Bacteriocin, class IIa (Bacteriocin_IIa)
Type: Family

Many Gram-positive bacteria produce ribosomally synthesized antimicrobial peptides, often termed bacteriocins. One important and well studied class of bacteriocins is the class IIa or pediocin-like bacteriocins produced by lactic acid bacteria. All class IIa bacteriocins are produced by food-associated strains, isolated from a variety of food products of industrial and natural origins, including meat products, dairy products and vegetables. Class IIa bacteriocins are all cationic, display anti-Listeria activity, and kill target cells by permeabilizing the cell membrane .
BolA protein (BolA)
Type: Family

This family consist of the morpho-protein BolA from Escherichia coli and its various homologues. In E. coli, over-expression of this protein causes round morphology and may be involved in switching the cell between elongation and septation systems during cell division . The expression of BolA is growth rate regulated and is induced during the transition into the the stationary phase . BolA is also induced by stress during early stages of growth and may have a general role in stress response. It has also been suggested that BolA can induce the transcription of penicillin binding proteins 6 and 5 . IbaG is a BolA homologue involved in acid resistance .