SII-SWORD/CoKE huggingface dataset:
Nucleocapsid, N-terminal, Arenaviridae (Nucleocapsid_N_arenaviridae)
Type: Domain

Arenaviridae are single stranded RNA viruses. The arenaviridae S RNAs that have been characterised include conserved terminal sequences, an ambisense arrangement of the coding regions for the precursor glycoprotein (GPC) and nucleocapsid (N) proteins and an intergenic region capable of forming a base-paired "hairpin" structure. The mature glycoproteins that result are G1 and G2 and the N protein .

This entry represents the N-terminal domain found in nucleocapsid protein (that encapsulates the viral ssRNA) in arenaviridae. The domain folds into a novel structure with a deep cavity for binding the m7GpppN cap structure that is required for viral RNA transcription .
Nucleocapsid, C-terminal, Arenaviridae (Nucleocapsid_C_arenaviridae)
Type: Domain

Arenaviridae are single stranded RNA viruses. The arenaviridae S RNAs that have been characterised include conserved terminal sequences, an ambisense arrangement of the coding regions for the precursor glycoprotein (GPC) and nucleocapsid (N) proteins and an intergenic region capable of forming a base-paired "hairpin" structure. The mature glycoproteins that result are G1 and G2 and the N protein .

The C-terminal domain of the nucleocapsid protein (that encapsulates the viral ssRNA) in arenaviridae has an RNaseH-like fold. This domain contains 3'-5' exoribonuclease activity involved in suppressing interferon induction . It forms a typical α/β/α sandwich architecture and contains a CCHE zinc-binding site near the 3'-5' exonuclease active site.
Urocanase, Rossmann-like domain (Urocanase_Rossmann-like)
Type: Domain

This entry represents the central domain, with a rossmann-like fold, found in Urocanase. It is found also in S-methyl thiourocanate hydratase which cannot use urocanate or thiourocanate as substrate and catalyses the conversion of S-methyl thiourocanate, to S-methyl-thiohydantoin-5-propanoate .

Urocanase (also known as imidazolonepropionate hydrolase or urocanate hydratase) is the enzyme that catalyses the second step in the degradation of histidine, the hydration of urocanate into imidazolonepropionate:

urocanate + H
2
O = 4,5-dihydro-4-oxo-5-imidazolepropanoate

Urocanase is found in some bacteria (gene hutU) , in the liver of many vertebrates, and has also been found in the plant Trifolium repens (white clover). Urocanase is a protein of about 60 Kd, it binds tightly to NAD
+
and uses it as an electrophil cofactor. A conserved cysteine has been found to be important for the catalytic mechanism and could be involved in the binding of the NAD
+
.
D-glutamate N-acetyltransferase-like, C-terminal domain (DgcN-like_C)
Type: Domain

This entry represents a domain found at the C-terminal of a group of prokaryotic proteins that includes

from Tritonibacter scottomollicae (DgcN), an N-acetyltransferase responsible for N-acetylation of D-Glutamate, an essential component of bacterial peptidoglycans. DgcN consists of two distinct domains. This domain, which consists of four β-strands and five α-helices, shows a P-loop structure .
MatP, N-terminal (MatP_N)
Type: Domain

MatP organises the macrodomain Ter of the chromosome of bacteria such as E coli. In these bacteria, insulated macrodomains influence the segregation of sister chromatids and the mobility of chromosomal DNA. Organisation of the Terminus region (Ter) into a macrodomain relies on the presence of a 13 bp motif called matS repeated 23 times in the 800-kb-long domain. MatS sites are the main targets in the E. coli chromosome of YcbG or MatP (macrodomain Ter protein). MatP accumulates in the cell as a discrete focus that co-localises with the Ter macrodomain. The effects of MatP inactivation reveal its role as the main organiser of the Ter macrodomain: in the absence of MatP, DNA is less compacted, the mobility of markers is increased, and segregation of the Ter macrodomain occurs early in the cell cycle. A specific organisational system is required in the Terminus region for bacterial chromosome management during the cell cycle .

This entry represents the N-terminal domain of MatP.
Protective antigen, Ca-binding domain (PA_Ca-bd)
Type: Domain

This domain is a calcium-binding domain in the anthrax toxin protective antigen (PA).

A large group of bacterial exotoxins are referred to as "A/B toxins", essentially because they are formed from two subunits . The "A" subunit possesses enzyme activity, and is transferred to the host cell following a conformational change in the membrane-bound transport "B" subunit. Clostridial species are one of the major causes of food poisoning/gastro-intestinal illnesses. They are Gram-positive, spore-forming rods that occur naturally in the soil . Among the toxins produced by certain Clostridium spp. are the binary exotoxins. These proteins consist of two independent polypeptides, which correspond to the A/B subunit moieties. The enzyme component (A) enters the cell through endosomes produced by the oligomeric binding/translocation protein (B), and prevents actin polymerisation through ADP-ribosylation of monomeric G-actin .

Members of the "B" binary toxin family also include the Bacillus anthracis protective antigen (PA) protein , most likely due to a common evolutionary ancestor. B. anthracis, a large Gram-positive spore-forming rod, is the causative agent of anthrax. Its two virulence factors are the poly-D-glutamate polypeptide capsule, and the actual anthrax exotoxin . The toxin comprises three factors: the protective antigen (PA); the oedema factor (EF); and the lethal factor (LF). Each is a thermolabile protein of ~80kDa. PA forms the "B" part of the exotoxin and allows passage of the "A" moiety (consisting of EF and LF) into target cells. PA protein forms the central part of the complete anthrax toxin, and translocates the B moiety into host cells after assembling as a heptamer in the membrane .
Tail sheath protein, subtilisin-like domain (Phage_sheath_subtilisin)
Type: Domain

This entry represents the second domain in a variety of phage tail sheath proteins, including Tail sheath protein from Bacteriophage T4 and Cis2 from Halogeometricum borinquense (Hbor_38820,

, ). According to ECOD this domain has a subtilisin-like structure.
Phosphorylase pyridoxal-phosphate attachment site (Pyridoxal_P_attach_site)
Type: Conserved_site

Phosphorylases (

) are important allosteric enzymes in carbohydrate metabolism. They catalyze the formation of glucose 1-phosphate from polyglucose such as glycogen, starch or maltodextrin. Enzymes from different sources differ in their regulatory mechanisms and their natural substrates. However, all known phosphorylases share catalytic and structural properties. They are pyridoxal-phosphate dependent enzymes; the pyridoxal-P group is attached to a lysine residue around which the sequence is highly conserved. This entry represents this conserved site that can be found in the glycosyl transferase family 35 members.
Gap junction alpha-1 protein (Cx43), alpha-helix domain superfamily (Alpha_helix_dom_sf)
Type: Homologous_superfamily

Gap junction alpha-1 protein (also called connexin43, or Cx43) is a connexin of 381 amino acid residues (human isoform) that is widely expressed in several organs and cell types and is the principal gap junction protein of the heart. Characterisation of genetically engineered mice that lack Cx43, and also of human patients that have spontaneously occurring mutations in the gene encoding it (GJA1) suggests Cx43 is essential for the development of normal cardiac architecture and ventricular conduction. Mice lacking Cx43 survive to term but die shortly after birth. They have cardiac malformations that lead to the obstruction of the pulmonary artery, leading to neonatal cyanosis and subsequent death. This phenotype is reminiscent of some forms of stenosis of the pulmonary artery. Human subjects with visceroatrial heterotaxia (a heart disorder characterised by arterial defects) have been found to have point mutations in the Cx43-encoding gene, as a result of which a potential phosphorylation site within the C-terminal is disrupted. Consequently, although these mutant Cx43 molecules still form functional gap junction channels, their response to protein kinase activation is impaired.

Regulation of cell-cell communication by the gap junction protein connexin43 can be modulated by a variety of connexin-associating proteins. In particular, c-Src can disrupt the connexin43 (Cx43)-zonula occludens-1 (ZO-1) interaction, leading to down-regulation of gap junction intercellular communication.
EV matrix protein, C-terminal (EV_matrix_protein_C)
Type: Homologous_superfamily

Ebola virus sp. are non-segmented, negative-strand RNA viruses that causes severe haemorrhagic fever in humans with high rates of mortality. The virus matrix protein VP40 is a major structural protein that plays a central role in virus assembly and budding at the plasma membrane of infected cells. VP40 proteins associate with cellular membranes, interact with the cytoplasmic tails of glycoproteins, and bind to the ribonucleoprotein complex. The VP40 monomer consists of two domains, the N-terminal oligomerization domain and the C-terminal membrane-binding domain, connected by a flexible linker. Both the N-and C-terminal domains fold into β sandwich structures of similar topology . Within the N-terminal domain are two overlapping L-domains with the sequences PTAP and PPEY at residues 7 to13, which are required for efficient budding . L-domains are thought to mediate their function in budding through their interaction with specific host cellular proteins, such as tsg101 and vps-4 .

This entry describes the VP40 C-terminal domain.
Toxin-antitoxin system, RelE/ParE toxin domain superfamily (RelE/ParE_toxin_dom_sf)
Type: Homologous_superfamily

The RelE/ParE family encompasses several toxin components of toxin-antitoxin modules. RelE is a sequence-specific, ribosome-dependent mRNA endoribonuclease which inhibits translation during amino acid starvation . ParE is involved in plasmid partition. ParE acts by inhibiting DNA gyrase, converting supercoiled plasmid DNA into a singly cleaved linear form in an ATP-dependent fashion .

Toxin-antitoxin (TA) systems form a prokaryotic proteins ubiquitous class with functional roles in plasmid inheritance/environmental stress response/cell development. ParDE family TA systems are broadly conserved on plasmids/bacterial chromosomes. They have been well characterised as genetic elements that promote stable plasmid inheritance.
Histidine N-alpha-methyltransferase (EgtD)
Type: Family

This mostly bacterial family represents histidine N-alpha-methyltransferase EgtD.

Histidine-specific methyltransferase EgtD catalyses the methylations of histidine to form N-alpha, N-alpha ,N-alpha-trimethyl-L-histidine (also known as hercynine), part of the ergothioneine biosynthesis pathway .
Peptidase M29, N-terminal (M29_N-terminal)
Type: Homologous_superfamily

This superfamily represents a domain found in a group of metallopeptidases that belong to MEROPS peptidase family M29 (aminopeptidase T family, clan M-), and that includes AmpS and AmpT.

Staphylococcus aureus aminopeptidase S (AmpS) has been named for its predicted, but experimentally untested, aminopeptidase activity. The enzyme is homologous to biochemically characterised aminopeptidases. It is a dimeric protein with a very unusual, elongated shape and a large internal cavity .
Aminopeptidase T (AmpT) from Thermus thermophilus is a homologue of AmpS. AmpT, like AmpS, can be divided into an N-terminal domain and a C-terminal domain, with a flexible hinge between them . This entry represent the N-terminal domain.
YNR034W-A/EGO2 superfamily (YNR034W-A/EGO2_sf)
Type: Homologous_superfamily

This family of proteins is predominantly found in Saccharomycetales, including YNR034W-A (also known as EGO4) and YCR075W-A (EGO2) from Saccharomyces cerevisiae. EGO2 is a component of the yeast EGO complex (EGOC), which is responsible for the amino acid-dependent activation of the target of rapamycin complex 1 (TORC1), a central controller of cell growth, metabolism, proliferation, and differentiation in response to environmental cues. EGO2 adopts a Roadblock domain fold that consists of a central core β-sheet of five anti-parallel β-strands flanked by a long α-helix on the bottom side. EGO4 shows a similar αββαββ configuration. It interacts with the GTPase Gtr2, but its specific function remains unknown .
Anthrax toxin, edema factor, C-terminal (Anthrax_toxin_C-terminal)
Type: Homologous_superfamily

Anthrax toxin is a plasmid-encoded toxin complex produced by the Gram-positive, spore-forming bacteria, Bacillus anthracis. The toxin consists of three non-toxic proteins: the protective antigen (PA), the lethal factor (LF) and the edema factor (EF) . These component proteins self-assemble at the surface of host cell receptors, yielding a series of toxic complexes that can produce shock-like symptoms and death. Anthrax toxin is one of a large group of Bacillus and Clostridium exotoxins referred to as binary toxins, forming independent enzymatic (A moiety) and binding (B moiety) components. The LF and EF proteins are the enzymes (A moiety) that act on cytosolic substrates, while PA is a multi-functional protein (B moiety) that binds to cell surface receptors, mediates the assembly and internalisation of the complexes, and delivers them to the host cell endosome . Once PA is attached to the host receptor , it must then be cleaved by a host cell surface (furin family) protease before it is able to bind EF and LF. The cleavage of the N terminus of PA enables the C-terminal fragment to self-associate into a ring-shaped heptameric complex (prepore) that can bind LF or EF competitively. The PA-LF/EF complex is then internalised by endocytosis, and delivered to the endosome, where PA forms a pore in the endosomal membrane in order to translocate LF and EF to the cytosol. LF is a Zn-dependent metalloprotease that cleaves and inactivates mitogen-activated protein (MAP) kinases, kills macrophages, and causes death of the host by inhibiting cell proliferation . EF is a calcium-and calmodulin-dependent adenylyl cyclase that can cause edema (fluid-filled swelling) when associated with PA. EF is not toxic by itself, and is required for the survival of germinated Bacillus spores within macrophages at the early stages of infection. EF dramatically elevates the level of host intracellular cAMP, a ubiquitous messenger that integrates many processes of the cell; increases in cAMP can interfere with host intracellular signalling .

This entry represents a C-terminal region in the edema factor, the calmodulin-activated adenylate cyclase component of anthrax toxin, as well as in adenylyl cyclases from other bacterial toxins. The C-terminal region contains the calmodulin-dependent activation domain and the catalytic site .
Transcription elongation factor, IIS-type (TF_IIS-typ)
Type: Family

This group represents transcription elongation factor IIS (TFIIS) and transcription factor S-II homologues from viruses. TFIIS is a component of RNA polymerase II preinitiation complexes, and is required for preinitiation complex assembly and stability . TFIIS binds to RNA polymerase Pol II, and in stalled and arrested elongation complexes it stimulates the cleavage of the nascent transcript at the 3' end. It enhances the excision of mis-incorporated nucleotides by RNA polymerase II, providing an mRNA proof-reading mechanism during transcription elongation . Three distinct TFIIS isoforms exist in vertebrates .
Phosphomevalonate kinase (Phosphomevalonate_kinase)
Type: Family

This entry includes phosphomevalonate kinases from bacteria, fungi, plants and archaea. The eukaryote enzyme is phosphomevalonate kinase Erg8 . The phosphomevalonate kinase from
Sulfolobus solfataricus
catalyses the phosphorylation of (R)-mevalonate 5-phosphate to (R)-mevalonate 5-diphosphate and is important in the pathway for the biosynthesis of archaeal membrane lipids .
Ribosomal protein S1-like (Ribosomal_protein_S1-like)
Type: Family

This entry includes small ribosomal subunit protein bS1 (RPS1) and related proteins, such as 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (IspH) and general stress protein 13 (YugI) from
Bacillus subtilis
, which has an S1 domain and a conserved RNA binding surface .

The bacterial RPS1 consists of 4-6 tandem S1 domains . In some bacteria, the tandem S1 array is located C-terminal to a 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HMBPP reductase) domain. While RPS1 is found primarily in bacteria, proteins with tandem RPS1-like domains have been identified in plants and humans, however these lack the N-terminal HMBPP reductase domain.
Deoxycytidylate deaminase domain (Deoxycytidylate_deaminase_dom)
Type: Domain

This entry represents a domain found in a group of deoxycytidylate deaminases.

Deoxycytidylate deaminase (

) (dCMP deaminase) hydrolyzes deoxycytidylate mono phosphate (dCMP) into deoxyuridine mono phosphate (dUMP), thus providing the nucleotide substrate for thymidylate synthase. The enzyme requires zinc for catalytic activity which is regulated by the ratio of dCTP to dTTP, both the end products of the pyrimidine salvage pathway . It contains a cytidine and deoxycytidylate deaminase domain.

This domain can also be found in cytidine and dCMP deaminase domain-containing protein 1 (CDADC1), which may play an important role in testicular development and spermatogenesis .
Spastin, chordate (Spastin_chordate)
Type: Family

Spastin is an ATP-dependent microtubule severing protein. Microtubule severing may promote reorganisation of cellular microtubule arrays and the release of microtubules from the microtubule organising centre following nucleation .

This entry represents Spastin specific to chordates.
tRNA thiolation protein, TtcA/Ctu1 type (tRNA_thiolation_TtcA_Ctu1)
Type: Family

This entry represents a group of tRNA thiolation proteins. It includes the tRNA-cytidine(32) 2-sulfurtransferase (

), and Cytoplasmic tRNA 2-thiolation protein 1 (

).

tRNA-cytidine(32) 2-sulfurtransferase (also known as 2-thiocytidine tRNA biosynthesis protein TtcA) is required for the thiolation of cytidine in position 32 of tRNA, to form 2-thiocytidine (s(2)C32). The modified nucleoside 2-thiocytidine (s(2)C) has so far been found in tRNA from archaea and bacteria. The TtcA protein family is characterised by the existence of both a PP-loop and a Cys-X(1)-X(2)-Cys motif in the central region of the protein but can be divided into two distinct groups based on the presence and location of additional Cys-X(1)-X(2)-Cys motifs in terminal regions of the sequence. Mutant analysis showed that both cysteines in this central conserved Cys-X(1)-X(2)-Cys motif are required for the formation of s(2)C .

Cytoplasmic tRNA 2-thiolation protein 1 (also known as Ncs6/Tuc1 in budding yeasts) is responsible for 2-thiolation of mcm5S2U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln) . It directly binds tRNAs and probably acts by catalysing adenylation of tRNAs, an intermediate required for 2-thiolation. Its fission yeast homologue, Ctu1 forms a complex with Ctu2 (Ncs2/Tuc2 homologue) and serves as a putative enzyme for the formation of 2-thiouridine . This family also includes tRNA-5-methyluridine(54) 2-sulfurtransferase, which catalyses the 2-thiolation of 5-methyluridine residue at position 54 in the T loop of tRNAs, leading to 5-methyl-2-thiouridine .
Ancylostoma-associated secreted protein related (ASPR)
Type: Family

This family includes members encoded by ASP-related genes which are distant homologues to ASPs (Ancylostoma-associated secreted proteins). ASPRs are predicted to be secreted, with one ASPR in Heligmosomoides bakeri shown to be secreted by parasitic adults. Thus, like ASPs, ASPRs are suggested to comprise an important element of hookworm infection in vivo .
HCMV protein UL42 (UL42)
Type: Family

Members of this family include UL42 proteins found in Human cytomegalovirus (HCMV). UL42 has two Pro-Pro-X-Tyr (PPxY) sequences, a hydrophobic region at the C terminus and no N-terminal signal peptide. These features are shared with herpes simplex virus (HSV) UL56. UL42 has a putative C-terminal trans-membrane region. HCMV UL42 interacts with Itch, a member of the Nedd4 family of ubiquitin E3 ligases, through its PY motifs as observed in HSV UL56, suggestive of a regulatory function .
Protein of unknown function DUF5516 (DUF5516)
Type: Family

This is a family of unknown function found mostly in Autographiviridae phages.
Viral unique long protein 21a (UL21a)
Type: Family

Members of this family include UL21a, found in Human cytomegalovirus (HCMV). UL21a is required for HCMV to establish efficient productive infection. It is a short-lived cytoplasmic protein that facilitates HCMV replication . It has also been shown to be responsible for APC1, APC4 and APC5 degradation .
Protein 14, SARS-like (Protein_14_SARS-like)
Type: Family

This is a family of unknown function found in SARS and SARS-like coronaviruses. It includes uncharacterised protein 14 from SARS coronavirus 2 (SARS-CoV-2), Human SARS coronavirus (SARS-CoV) and Bat coronavirus Rp3/2004 (SARS-like coronavirus Rp3) . In SARS-CoV, Orf14 is completely contained within the ORF encoding the nucleocapsid protein (N) . In SARS-CoV-2 uncharacterised protein 14 is predicted to contain one transmembrane helix.
Gene product 67 (GP67)
Type: Family

This is a family of unknown function found in Myoviridae such as Enterobacteria phages. Family members include Gp67, a prohead core (scaffold) protein .
Protein of unknown function DUF5514 (DUF5514)
Type: Family

This is a family of unknown function found in Bacillus.
Protein of unknown function DUF5510 (DUF5510)
Type: Family

This is a family of unknown function found in Rickettsia. Family members are predicted to have 2 or 3 trans-membrane regions.
Inclusion membrane protein D (IncD)
Type: Family

The chlamydial inclusion membrane is extensively modified by the insertion of type III secreted effector proteins . These inclusion membrane proteins (Incs) have two major characteristics: an N-terminal type III secretion signal that is necessary for their secretion out of the bacterium and a hydrophobic region consisting of at least two trans-membrane helices that allows insertion into the inclusion membrane. Generally, both the N- and C-terminal regions of the Inc are exposed to the host cell cytosol .

This family has members such as the IncD proteins found in Chlamydia trachomatis. This C. trachomatis effector protein IncD has been shown to recruit the lipid transfer protein CERT to the inclusion membrane by directly interacting with CERT PH domain, which mediates the FFAT motif-dependent recruitment of the ER-resident protein VAPB (vesicle-associated membrane protein-associated protein) to the inclusion .