SII-SWORD/CoKE huggingface dataset:
Siphovirus Gp157 (Sipho_Gp157)
Type: Family

This family contains both viral and bacterial proteins which are related to the Gp157 protein of the Streptococcus thermophilus SFi bacteriophage. It is thought that bacteria possessing the gene coding for this protein have an increased resistance to the bacteriophage .
Siphovirus-type tail component, RIFT-related domain (Siphovirus-type_tail_N)
Type: Domain

This entry consists of several phage tail component proteins, including bacteriophage SPP1 distal tail protein Dit

(also known as Gp19.1 or Gp19) , as well as some bacterial proteins of unknown function. This entry represents the N-terminal domain.
Entomopoxvirus spheroidin (Spheroidin)
Type: Family

Entomopoxviruses (EPVs) are large (300-400 nm) oval-shaped viruses replicating in the cytoplasm of their insect host cells. At the end of their replicative cycle EPVs virions are occluded in a highly expressed protein called spheroidin. This protein forms large (5-20 mm long) oval-shaped occlusion bodies (OBs) called spherules. The infectious cycle of EPVs begins with the ingestion by the insect host of the spherules, their dissolution by the alkaline reducing conditions of the midgut fluid and the release of virions in the midgut lumen. The infective particles first replicate in midgut epithelial cells, then pass the gut barrier to colonise the internal tissues, mainly the fat body cells. Whilst spheroidin has been demonstrated to be non-essential for viral replication, it plays an essential role in the natural biological cycle of the virus in protecting virions from adverse environmental conditions (e.g. UV degradation) and thus improving transmission efficacy. In this respect, spheroidins are functionally similar to polyhedrins of baculoviruses or cypoviruses .
Spore germination GerAC-like (Spore_GerAC-like)
Type: Family

The GerAA, -AB, and -AC proteins of the Bacillus subtilis spore are required for the germination response to L-alanine as the sole germinant. Members of GerAC family are thought to be located in the inner spore membrane. Although the function of this family is unclear, they are likely to encode the components of the germination apparatus that respond directly to this germinant, mediating the spore's response .
Sporozoite P67 surface antigen (Sporozoite_P67)
Type: Family

This family consists of several Theileria P67 surface antigens. A stage specific surface antigen of Theileria parva, p67, is the basis for the development of an anti-sporozoite vaccine for the control of East Coast fever (ECF) in Bos taurus. The antigen has been shown to contain five distinct linear peptide sequences recognised by sporozoite-neutralising murine monoclonal antibodies .
Phenol-soluble modulin beta protein (PSMbeta)
Type: Family

This family consists of several different short Staphylococcal proteins known as the phenol-soluble modulin beta proteins, including SLUSH A, B and C proteins as well as haemolysin and gonococcal growth inhibitor . Some strains of the coagulase-negative Staphylococcus lugdunensis produce a synergistic hemolytic activity (SLUSH), phenotypically similar to the delta-hemolysin of S. aureus . Gonococcal growth inhibitor from Staphylococcus acts on the cytoplasmic membrane of the gonococcal cell causing cytoplasmic leakage and, eventually, death .
Suppressor of forked (Suf)
Type: Domain

This domain consists of several eukaryotic suppressor of forked (Suf) like proteins. The Drosophila melanogaster suppressor of forked [Su(f)] protein shares homology with the Saccharomyces cerevisiae RNA14 protein and the 77kDa subunit of Homo sapiens cleavage stimulation factor, which are proteins involved in mRNA 3' end formation. This suggests a role for Su(f) in mRNA 3' end formation in Drosophila. The su(f) gene produces three transcripts; two of them are polyadenylated at the end of the transcription unit, and one is a truncated transcript, polyadenylated in intron 4. It is thought that su(f) plays a role in the regulation of poly(A) site utilisation and the GU-rich sequence is important for this regulation to occur .
Plasmid regulator, Sulfolobaceae (Plasmid_regulator_arc)
Type: Family

This family consists of several plasmid regulatory proteins from the extreme thermophilic and acidophilic archaea Sulfolobus.
Synaphin (Synaphin)
Type: Family

This family consists of several eukaryotic synaphin 1 and 2 proteins. Synaphin/complexin is a cytosolic protein that preferentially binds to syntaxin within the SNARE complex. Synaphin promotes SNAREs to form precomplexes that oligomerise into higher order structures. A peptide from the central, syntaxin binding domain of synaphin competitively inhibits these two proteins from interacting and prevents SNARE complexes from oligomerising. It is thought that oligomerisation of SNARE complexes into a higher order structure creates a SNARE scaffold for efficient, regulated fusion of synaptic vesicles . Synaphin promotes neuronal exocytosis by promoting interaction between the complementary syntaxin and synaptobrevin transmembrane regions that reside in opposing membranes prior to fusion .
TEP1, N-terminal (TEP1_N)
Type: Repeat

Telomerase protein component 1 (TP1/TLP1) or TEP1 is a protein component of two ribonucleoprotein (RNP) complexes: vaults and telomerase. Vaults are large RNP particles with a barrel-like structure (

). The telomerase RNP replenishes incomplete chromosome termini due to DNA replication. Mammalian TEP1 is an RNA-binding protein and is required for the association of vault RNA with the vault particle . The N-terminal part of TEP1 contains 4 copies of the TEP1 N-terminal repeat in tandem. The repeat is composed of 30 amino acids and occurs in combination with the TROVE (

) and NACHT (

) domains and with WD-40 repeats (see

) in the C-terminal part.
Transcription initiation factor IIF, alpha subunit (TFIIF-alpha)
Type: Family

Transcription initiation factor IIF, alpha subunit (TFIIF-alpha) or RNA polymerase II-associating protein 74 (RAP74) is the large subunit of transcription factor IIF (TFIIF), which is essential for accurate initiation and stimulates elongation by RNA polymerase II .
TMEM9/TMEM9B (TMEM9/TMEM9B)
Type: Family

This entry includes human TMEM9/TMEM9B and their homologues. TMEM9 is a transmembrane protein that binds to and facilitates the assembly of lysosomal proton-transporting V-type ATPase (v-ATPase), resulting in enhanced lysosomal acidification and trafficking . It acts as a Wnt signaling amplifier that hyperactivates Wnt signaling for liver regeneration and tumorigenesis via lysosomal degradation of APC . TMEM9B has been shown to regulate the activity of inflammatory signaling pathways .
TPMT family (TPMT)
Type: Family

This family consists of thiopurine S-methyltransferase (

), thiol S-methyltransferase (

) and thiocyanate methyltransferase (

).

Thiopurine S-methyltransferase is a cytosolic enzyme that catalyses S-methylation of aromatic and heterocyclic sulphydryl compounds, including anticancer and immunosuppressive thiopurines . Thiopurine is commonly used to suppress the immune system in the case of autoimmune disease, inflammatory bowel disease and to prevent transplanted organ rejection . Thiopurine drugs can be toxic to cells but their effect can be mediated by the incorporation of thioguanine nucleotides into DNA .

Thiocyanate methyltransferase and thiol S-methyltransferase are involved in glucosinolate metabolism and defense against phytopathogens. Thiocyanate methyltransferase is highly reactive to thiocyanate (NCS-) derived from myrosinase-mediated hydrolysis of glucosinolates upon tissue damage .
Translocon-associated (TRAP-delta)
Type: Family

This family consists of several eukaryotic translocon-associated protein, delta subunit precursors (TRAP-delta or SSR-delta). The exact function of this protein is unknown .
Translocon-associated protein subunit beta (TRAP_beta)
Type: Family

This family consists of several eukaryotic translocon-associated protein beta (TRAPB) or signal sequence receptor beta subunit (SSR-beta) proteins. The normal translocation of nascent polypeptides into the lumen of the endoplasmic reticulum (ER) is thought to be aided in part by a translocon-associated protein (TRAP) complex consisting of 4 protein subunits. The association of mature proteins with the ER and Golgi, or other intracellular locales, such as lysosomes, depends on the initial targeting of the nascent polypeptide to the ER membrane. A similar scenario must also exist for proteins destined for secretion .
Thyrotropin-releasing hormone (TRH)
Type: Family

This family consists of several thyrotropin-releasing hormone (TRH) proteins. Thyrotropin-Releasing Hormone (TRH) is a tripeptide (pGlu-His-Pro-NH2) hormone that is primarily produced in the paraventricular nucleus of the hypothalamus and represents the most proximal member of the hypothalamic-pituitary-thyroid (HPT) axis. It plays an important role in maintaining the thyroid hormone (TH) homeostasis .
TROVE domain (TROVE_dom)
Type: Domain

The TROVE (Telomerase, Ro and Vault) domain is a module of ~300-500 residues that is found in TEP1 and Ro60 the protein components of three ribonucleoprotein particles. It is also found in bacterial ribonucleoproteins suggesting an ancient origin of these ribonucleoproteins. It can be found associated with other domains, such as the VWFA domain, the TEP1 N-terminal domain, the NACHT-NTPase domain, and WD-40 repeats. This domain may be involved in binding the RNA components of the three RNPs, which are telomerase RNA, Y RNA and vault RNA .

The TROVE domain contains a few absolutely conserved residues. As none of these conserved residues are the polar type of amino acids found in active sites, it seems unlikely that this region has an enzymatic function .
Thrombospondin, C-terminal (Thrombospondin_C)
Type: Domain

Thrombospondins are multimeric multidomain glycoproteins that function at cell surfaces and in the extracellular matrix milieu. They act as regulators of cell interactions in vertebrates. They are divided into two subfamilies, A and B, according to their overall molecular organisation. The subgroup A proteins TSP-1 and -2 contain an N-terminal domain, a VWFC domain, three TSP1 repeats, three EGF-like domains, TSP3 repeats and a C-terminal domain. They are assembled as trimer. The subgroup B thrombospondins, designated TSP-3, -4, and COMP (cartilage oligomeric matrix protein, also designated TSP-5) are distinct in that they contain unique N-terminal regions, lack the VWFC domain and TSP1 repeats, contain four copies of EGF-like domains, and are assembled as pentamers . EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.

The globular C-terminal domain is a β sandwich of two curved antiparallel β-sheets . The fold is an elaboration of the jelly role topology, with strand B3-B7, B11 and B14-B15 forming the eight-stranded jelly roll motif. The function of the C-terminal domain is not yet known.
Taeniidae antigen (Taeniidae_ag)
Type: Family

This family consists of several antigen proteins found in flatworms.
Phage Tail Protein X-like (GpX-like)
Type: Family

This entry includes GpX protein from Bacteriophage P2. GpX is a phage tail protein . Sequence analysis suggests that they are related to

which suggests a general peptidoglycan binding function.

This entry also includes uncharacterised bacterial proteins.
T-complex 11 (Tcp11)
Type: Family

This family consists of several eukaryotic T-complex protein 11 (Tcp11) related sequences. Tcp11 is only expressed in fertile adult mammalian testes and is thought to be important in sperm function and fertility. The family also contains the Saccharomyces cerevisiae Sok1 protein which is known to suppress cyclic AMP-dependent protein kinase mutants .
Toxic anion resistance (Toxic_anion-R_TelA)
Type: Family

This family consists of several prokaryotic TelA like proteins. TelA and KlA are associated with tellurite resistance and plasmid fertility inhibition .
Nucleocapsid, Tenuivirus (Nucleocapsid_Tenuivirus)
Type: Family

This family consists of several Tenuivirus nucleocapsid proteins .
DNA replication terminus site-binding protein (DNA_replication_term_site-bd)
Type: Family

This entry contains several bacterial DNA replication terminus site-binding proteins (also known as Tus or Ter-binding proteins). They are required for the termination of DNA replication and function by binding to DNA replication terminator sequences, thus preventing the passage of replication forks . The termination efficiency is affected by the affinity of a particular protein for the terminator sequence.
Bacteriophage lambda, GpA-like (Phage_lambda_GpA-like)
Type: Family

This entry consists of several phage terminase large subunit proteins, including GpA (also known as TerL) from Bacteriophage lambda and from Enterobacteria phage P21, as well as related sequences from several bacterial species. The DNA packaging enzyme of Bacteriophage lambda, terminase, is a heteromultimer composed of a small subunit, gpNu1 involved in DNA recognition, and a large subunit, gpA involved in late stages of packaging, products of the Nu1 and A genes, respectively. Terminase is involved in the site-specific binding and cutting of the DNA in the initial stages of packaging. This large subunit is an ATPase required for viral DNA translocation into empty capsids and also acts as an endonuclease that cuts the viral genome from the concetamer to initiate and to end the packaging reaction .
Thiazole synthase (ThiG)
Type: Family

Thiazole synthase (ThiG) is the tetrameric enzyme involved in the formation of the thiazole moiety of thiamin pyrophosphate, an essential ubiquitous cofactor that plays an important role in carbohydrate and amino acid metabolism. ThiG catalyzes the formation of thiazole from 1-deoxy-D-xylulose 5-phosphate (DXP) and dehydroglycine, with the help of the sulfur carrier protein ThiS that carries the sulfur needed for thiazole assembly on its carboxy terminus (ThiS-COSH) .
Bacterial TniB (TniB)
Type: Family

This family consists of several bacterial TniB NTP-binding proteins. TniB is a probable ATP-binding protein which is involved in Tn5053 mercury resistance transposition .
Toluene tolerance Ttg2/phospholipid-binding protein MlaC (MlaC/ttg2D)
Type: Family

This family includes toluene tolerance protein Ttg2 and intermembrane phospholipid transport system binding protein MlaC. Proteins in this family show similarity to ABC transporters .

Toluene tolerance is mediated by increased cell membrane rigidity resulting from changes in fatty acid and phospholipid compositions, exclusion of toluene from the cell membrane, and removal of intracellular toluene by degradation . Ttg2 is one of the many proteins involved in these processes .

MlaC actively prevents phospholipid accumulation at the cell surface. It probably maintains lipid asymmetry in the outer membrane by retrograde trafficking of phospholipids from the outer membrane to the inner membrane. It may transfer phospholipid across the periplasmic space and deliver it to the mlaFEDB complex at the inner membrane .
Totivirus coat (Totivirus_coat)
Type: Family

This family of proteins contain the coat proteins of the Totiviruses.
Insecticidal crystal toxin (Toxin_P42)
Type: Domain

This entry represents a domain found in insecticidal crystal toxins. Strains of Bacillus that have this insecticidal activity use a binary toxin comprised of two proteins, P51 and P42 (this entry) . This domain is also found in Binary larvicide subunit BinA, a component of a binary toxin active against Culex and some Aedes mosquito larvae . Members of this entry are highly conserved between strains of different serotypes and phage groups .
TraA (TraA)
Type: Family

Conjugative transfer of a bacteriocin plasmid, pPD1, of Enterococcus faecalis is induced in response to a peptide sex pheromone, cPD1, secreted from plasmid-free recipient cells. cPD1 is taken up by a pPD1 donor cell and binds to an intracellular receptor, TraA. Once a recipient cell acquires pPD1, it starts to produce an inhibitor of cPD1, termed iPD1, which functions as a TraA antagonist and blocks self-induction in donor cells. TraA transduces the signal of cPD1 to the mating response .
Enterobacterial TraT complement resistance (TraT_complement-R)
Type: Family

The traT gene is one of the F factor transfer genes and encodes an outer membrane protein which is involved in interactions between Escherichia coli and its surroundings . The protein plays a role in preventing unproductive conjugation between bacteria carrying like plasmids.
TraX (TraX)
Type: Family

This family consists of several bacterial TraX proteins. TraX is responsible for the N-terminal acetylation of F-pilin subunits .
Relaxosome protein TraY (TraY)
Type: Family

TraY is part of the relaxosome, a complex of DNA-processing proteins required for the initiation of conjugative DNA transfer. It facilitates a site- and strand-specific cut in the origin of transfer by TraI, at the nic site .
Transposase IS66, Orf2 (Transposase_IS66_Orf2)
Type: Family

This entry represents a group of bacterial proteins found in insertion sequences related to IS66. The function of these proteins is uncertain, but they are probably essential for transposition.

The IS66 family insertion sequence element encodes a DDE transposase TnpC, and two accessory proteins, TnpA and TnpB. It has been assumed that the TnpA, TnpB, and TnpC proteins are produced independently in appropriate amounts and form a complex, which acts as a transposase to promote the transposition of an IS66 family element.TnpB, as the term is used for proteins encoded by IS66 family insertion elements, is considered an accessory protein, since TnpC, encoded by a neighbouring gene, is a DDE family transposase. .
Coat protein, trichovirus/vitivirus (Coat_protein_tricho/vitivirus)
Type: Family

This family consists of several coat proteins which are specific to the ssRNA positive-strand, no DNA stage viruses such as the Trichoviruses and Vitiviruses .
Trigger factor, C-terminal (Trigger_fac_C)
Type: Domain

In the Escherichia coli cytosol, a fraction of the newly synthesised proteins requires the activity of molecular chaperones for folding to the native state. The major chaperones implicated in this folding process are the ribosome-associated Trigger Factor (TF), and the DnaK and GroEL chaperones with their respective co-chaperones. Trigger Factor is an ATP-independent chaperone and displays chaperone and peptidyl-prolyl-cis-trans-isomerase (PPIase) activities
in vitro
. It is composed of three domains, an N-terminal ribosome-binding domain (RBD) which mediates association with the large ribosomal subunit, a central PPIase domain with homology to FKBP proteins, and a C-terminal substrate-binding domain (SBD) which forms the central body of the protein and has two helical arms that create a cavity . The association between its N-terminal domain with the ribosomal protein L23 located next to the peptide tunnel exit is essential for the interaction with nascent polypeptides and its in vivo function .

This entry represents the C-terminal domain of bacterial TF proteins, which has a multi-helical structure consisting of an irregular array of long and short helices. This domain is structurally similar to the peptide-binding domain of the bacterial porin chaperone SurA .
Trigger factor, ribosome-binding, bacterial (Trigger_fac_ribosome-bd_bac)
Type: Domain

In the Escherichia coli cytosol, a fraction of the newly synthesised proteins requires the activity of molecular chaperones for folding to the native state. The major chaperones implicated in this folding process are the ribosome-associated Trigger Factor (TF), and the DnaK and GroEL chaperones with their respective co-chaperones. Trigger Factor is an ATP-independent chaperone and displays chaperone and peptidyl-prolyl-cis-trans-isomerase (PPIase) activities
in vitro
. It is composed of at least three domains, an N-terminal domain which mediates association with the large ribosomal subunit, a central substrate binding and PPIase domain with homology to FKBP proteins, and a C-terminal domain of unknown function. The positioning of TF at the peptide exit channel, together with its ability to interact with nascent chains as short as 57 residues renders TF a prime candidate for being the first chaperone that binds to the nascent polypeptide chains . This group of sequences contain the ribosomal subunit association domain.
Procyclic acidic repetitive (Trypano_PARP)
Type: Family

This family consists of several Trypanosoma brucei procyclic acidic repetitive protein (PARP) like sequences. The procyclic acidic repetitive protein (parp) genes of T. brucei encode a small family of abundant surface proteins whose expression is restricted to the procyclic form of the parasite. They are found at two unlinked loci, parpA and parpB; transcription of both loci is developmentally regulated .
Ubiquitin E2 variant, N-terminal (UEV_N)
Type: Domain

The N-terminal ubiquitin E2 variant (UEV) domain is ~145 amino acid residues in length and shows significant sequence similarity to E2 ubiquitin ligases but is unable to catalyze ubiquitin transfer as it lacks the active site cysteine that forms the transient thioester bond with the C terminus of ubiquitin (Ub). Nevertheless, at least some UEVs have retained the ability to bind Ub, and appear to act either as cofactors in ubiquitylation reactions, or as ubiquitin sensors. UEV domains also frequently contain other protein recognition motifs, and may generally serve to couple protein and Ub binding functions to facilitate the formation of multiprotein complexes .

The UEV domain is found in the eukaryotic tumour susceptibility gene 101 protein (TSG101). Altered transcripts of this gene have been detected in sporadic breast cancers and many other Homo sapiens malignancies. However, the involvement of this gene in neoplastic transformation and tumourigenesis is still elusive. TSG101 is required for normal cell function of embryonic and adult tissues but this gene is not a tumour suppressor for sporadic forms of breast cancer .
Macrocin-O-methyltransferase (TylF_MeTrfase)
Type: Family

This family consists of bacterial macrocin O-methyltransferase (TylF) proteins. TylF is responsible for the methylation of macrocin to produce tylosin. Tylosin is a macrolide antibiotic used in veterinary medicine to treat infections caused by Gram-positive bacteria and as an animal growth promoter in the Sus scrofa (Pig) industry. It is produced by several Streptomyces species. As with other macrolides, the antibiotic activity of tylosin is due to the inhibition of protein biosynthesis by a mechanism that involves the binding of tylosin to the ribosome, preventing the formation of the mRNA-aminoacyl-tRNA-ribosome complex .
Uncharacterised protein family UPF0227/Esterase YqiA (UPF0227/Esterase_YqiA)
Type: Family

Despite being classed as uncharacterised proteins, the members of this family are almost certainly enzymes in that contain a domain distantly related to

. One of the members of this family YqiA has been shown to be a esterase . Other members, which include the Escherichia coli (strain K12) YcfP protein, are uncharacterised.
Uncharacterised protein family UPF0228 (UPF0228)
Type: Family

This small family of proteins is currently restricted to Methanosarcina species. Members of this family are about 200 residues in length, except for

that has two copies of this region. Although the function of this region is unknown the pattern of conservation suggests that this may be an enzyme, including multiple conserved aspartate and glutamate residues. The most conserved motif in these proteins is NEL/MEXNE/D, where X can be any amino acid, and is found at the C terminus of these proteins.
Ustilago B locus mating-type (Ustilago_mating)
Type: Domain

This domain consists of several Ustilago mating-type proteins. The b locus of the phytopathogenic fungus Ustilago maydis encodes a multiallelic recognition function that controls the ability of the fungus to form a dikaryon and complete the sexual stage of the life cycle. The b locus has at least 25 alleles and any combination of two different alleles, brought together by mating between haploid cells, allows the fungus to cause disease and undergo sexual development within the plant .