SII-SWORD/CoKE huggingface dataset:
Vinculin (Vinculin)
Type: Family

Vinculin is an actin filament (F-actin) binding protein involved in cell-matrix adhesion and cell-cell adhesion . In addition to actin, vinculin interacts with other structural proteins such as talin and alpha-actinins .

Vinculin is a large protein of 116kDa (about a 1000 residues). Structurally the protein consists of an acidic N-terminal domain of about 90kDa separated from a basic C-terminal domain of about 25kDa by a proline-rich region of about 50 residues. The central part of the N-terminal domain consists of a variable number (3 in vertebrates, 2 in Caenorhabditis elegans) of repeats of a 110 amino acids domain. Interestingly, vinculin exists in two conformations in the cell: an open, active form and a closed, auto-inhibited state in which the head domain forms extensive interactions with the tail .
Chaperone tailless complex polypeptide 1 (TCP-1) (Chaperone_TCP-1)
Type: Family

Protein folding is thought to be the sole result of properties inherent in polypeptide primary sequences. Sometimes, however, additional proteins are required to mediate correct folding and subsequent oligomer assembly . These `helpers', or chaperones, bind to specific protein surfaces, preventing incorrect folding and formation of non-functional structures .

The tailless complex polypeptide 1 (TCP-1) is a highly structurally conserved molecular chaperone located in the cytosol . The protein has also been shown to bind to Golgi membranes and to microtubules, this latter property suggesting a role in mitotic spindle formation in dividing cells (especially in sperm, where it is highly abundant) . TCP-1 forms a double ring structure, similar to the 10kDa and 60kDa chaperonins, with 6-8 subunits per ring. The amino acid sequence is significantly similar to the 60kDa chaperonin, and to TF55, a chaperone from the archaebacterium Sulfolobus shibatae .
Neurotransmitter-gated ion-channel, conserved site (Neurotransmitter_ion_chnl_CS)
Type: Conserved_site

This entry represents a conserved site based around two highly conserved cysteines in the N-terminal of AchR/GABA/5HT3/Gly receptors. The residues between these two cysteines are also well conserved. In AchR, these cysteine residues have been shown to form a disulphide bond essential to the tertiary structure of the receptor.

Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses . Five of these ion channel receptor families have been shown to form a sequence-related superfamily:

Nicotinic acetylcholine receptor (AchR), an excitatory cation channel in vertebrates and invertebrates; in vertebrate motor endplates it is composed of alpha, beta, gamma and delta/epsilon subunits; in neurons it is composed of alpha and non-alpha (or beta) subunits .

Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits .

Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known .

Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7) .

Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) .

These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence .
Herpesvirus UL45 (Herpes_UL45)
Type: Family

This family consists several UL45 proteins found in the herpes simplex virus family. The herpes simplex virus UL45 gene encodes an 18kDa virion envelope protein whose function remains unknown. It has been suggested that the 18kDa UL45 gene product is required for efficient growth in the central nervous system at low doses and may play an important role under the conditions of a naturally acquired infection .
Insecticidal toxin complex/plasmid virulence protein (Insecticidal_toxin/plasmid_vir)
Type: Family

This entry included insecticidal toxin complex proteins (TcaA, TccA, TcbA, TcdA) from Photorhabdus luminescens subsp. laumondii and Xenorhabdus nematophilus (Achromobacter nematophilus) , and virulence proteins from Salmonella typhimurium that are encoded on a 90kb plasmid.

P. luminescens and X. nematophilus are Gram-negative bacteria that form entomopathogenic symbioses with soil nematodes. The bacteria are found in the gut of entomopathogenic nematodes that invade and kill insects. When the nematode invades an insect host the bacteria are released into the insect haemocoel (the open circulatory system), both the bacteria and the nematode undergo multiple rounds of replication which kills the insect host. Mapping of the insecticidal toxin loci and studies on knockout mutants in P. luminescens showed that deletion of either tca or tcd loci dramatically reduced toxicity, while the double mutant tca/tcd abolished toxicity . However the biology of toxin action is unclear as is the species range of insects the toxins are active against.

S. typhimurium contains a 90kb plasmid that is associated with virulence. This plasmid encodes at least 6 genes needed by the bacterium for invading host macrophages during infection. These include the 70kDa mkaA protein , a recognised virulence factor, and more recently described, four spv genes under the control of a regulator .

Deletion studies on the virulence plasmid have shown that an open reading frame encoding a 28kDa protein was needed for successful invasion of the host. This protein, designated mkfA , VRP4 or VirA by different groups, is utilised by the microbe upon entry into macrophages, although the exact mechanism is unclear.
KilA/APSES-type HTH, DNA-binding (KilA/APSES_HTH)
Type: Domain

The amino-terminal module of the poxvirus D6R/NIR proteins defines a novel conserved DNA-binding domain (the KilA-N domain) that is found in a wide range of proteins of large bacterial and eukaryotic DNA viruses . Putative proteins with homology to the KilA-N domain have also been identified in Maverick transposable elements of the parabasalid protozoa Trichomonas vaginalis . The KilA-N domain has been suggested to be homologous to the fungal DNA-binding APSES domain (see

). In all proteins shown to contain the KilA-N domain, it occurs at the extreme amino terminus accompanied by a wide range of distinct carboxy-terminal domains. These carboxy-terminal modules may be enzymes, such as the nuclease domains, or might mediate additional, specific interactions with nucleic acids or proteins, like the RING (see

) or CCCH fingers in the poxviruses . The KilA-N domain is predicted to adopt an α-β fold with four conserved strands and at least two conserved helices . Some proteins known to contain a KilA-N domain are listed below:

Cell pattern formation-associated protein stuA (

).

Host range factor p28 (

).

Bacteriophage P1 protein kilA (

).

Fowlpox virus (FPV) protein FPV236 (

).
Flagellar FliJ, proteobacteria (Flag_FliJ_proteobac)
Type: Family

Many flagellar proteins are exported by a flagellum-specific export pathway. Attempts have been made to characterise the apparatus responsible for this process, by designing assays to screen for mutants with export defects . Experiments involving filament removal from temperature-sensitive flagellar mutants of Salmonella typhimurium have shown that, while most mutants were able to regrow filaments, flhA, fliH, fliI and fliN mutants showed no or greatly reduced regrowth. This suggests that the corresponding gene products are involved in the process of flagellum-specific export. The sequences of fliH, fliI and the adjacent gene, fliJ, have been deduced. FliJ was shown to encode a protein of molecular mass 17,302 Da . It is a membrane-associated protein that affects chemotactic events, mutations in FliJ result in failure to respond to chemotactic stimuli.

This subgroup is dominated by FliJ proteins found in Proteobacteria.
Carbohydrate sulfotransferase 8-10 (Carb_sulfotrans_8-10)
Type: Family

This entry consists of a number of carbohydrate sulphotransferases that transfer sulphate to carbohydrate groups in glycoproteins and glycolipids. These include:

Carbohydrate sulphotransferases 8 and 9, which transfer sulphate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans . They function in the biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulphation of their carbohydrate structures.

Carbohydrate sulphotransferase 10, which transfers sulphate to position 3 of the terminal glucuronic acid in both protein- and lipid-linked oligosaccharides . It directs the biosynthesis of the HNK-1 carbohydrate structure, a sulphated glucuronyl-lactosaminyl residue carried by many neural recognition molecules, which is involved in cell interactions during ontogenetic development and in synaptic plasticity in the adult.

Carbohydrate sulphotransferases 11 - 13, which catalyze the transfer of sulphate to position 4 of the GalNAc residue of chondroitin . Chondroitin sulphate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Some, thought not all, of these enzymes also transfer sulphate to dermatan.

Carbohydrate sulphotransferase 14 (D4ST1), which transfers sulphate to position 4 of the GalNAc residue of dermatan sulphate .
Nucleoside-specific channel-forming protein, Tsx-like (Channel_Tsx-like)
Type: Family

The tsx gene of Escherichia coli encodes an outer membrane protein, Tsx, which constitutes the receptor for colicin K and Bacteriophage T6, and functions as a substrate-specific channel for nucleosides and deoxy-nucleosides . The protein contains 294 amino acids, the first 22 of which are characteristic of a bacterial signal sequence peptide. The putative mature form of Tsx contains 272 residues with a calculated Mr of 31418. The Tsx sequence shows an even distribution of charged residues and lacks extensive hydrophobic stretches . Tsx shows no significant similarities to the channel-forming proteins OmpC, OmpF, PhoE and LamB from the E. coli outer membrane.

This entry also contains related proteins of unknown function.
Nucleoside phosphorylase, conserved site (Nucleoside_phosphorylase_CS)
Type: Conserved_site

The following phosphorylases are in the same family:

Purine nucleoside phosphorylase (

) (PNP) from most bacteria (gene deoD), which catalyses the cleavage of guanosine or inosine to respective bases and sugar-1-phosphate molecules .

Uridine phosphorylase (

) (UdRPase) from bacteria (gene udp) and mammals, which catalyses the cleavage of uridine into uracil and ribose-1-phosphate, the products of the reaction are used either as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis .

5'-methylthioadenosine phosphorylase (

) (MTA phosphorylase) from Sulfolobus solfataricus .

It should be noted that mammalian and some bacterial PNP as well as eukaryotic MTA phosphorylase belong to a different family of phosphorylases.
Luteovirus Orf2 putative replicase 1 (Luteovirus_Orf2)
Type: Family

ORF2 of Potato leafroll virus (PLrV) encodes a polyprotein which is translated following a -1 frameshift. The polyprotein has a putative linear arrangement of membrane achor-VPg-peptidase-polmerase domains. The serine peptidase domain which is found in this group of sequences belongs to MEROPS peptidase family S39 (clan PA(S)), subfamily S39B. It is likely that the peptidase domain is involved in the cleavage of the polyprotein .

The nucleotide sequence for the RNA of PLrV has been determined . The sequence contains six large open reading frames (ORFs). The 5' coding region encodes two polypeptides of 28K and 70K, which overlap in different reading frames; it is suggested that the third ORF in the 5' block is translated by frameshift readthrough near the end of the 70K protein, yielding a 118K polypeptide . Segments of the predicted amino acid sequences of these ORFs resemble those of known viral RNA polymerases, ATP-binding proteins and viral genome-linked proteins. The nucleotide sequence of the genomic RNA of Beet western yellows virus (BWYV) has been determined . The sequence contains six long ORFs. A cluster of three of these ORFs, including the coat protein cistron, display extensive amino acid sequence similarity to corresponding ORFs of a second luteovirus: Barley yellow dwarf virus .
Oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase (OHCU_decarboxylase)
Type: Domain

The proteins in this entry are OHCU decarboxylase, an enzyme of the purine catabolism that catalyses the conversion of OHCU into S(+)-allantoin ; it is the third step of the conversion of uric acid (a purine derivative) to allantoin. Step one is catalysed by urate oxidase (

) and step two is catalysed by hydroxyisourate hydrolase (

).
IPP transferase (IPT)
Type: Family

This entry represents tRNA dimethylallyltransferase, also known as delta(2)-isopentenylpyrophosphate transferase, IPP transferral and 2-methylthio-N6-isopentyladenosine tRNA modification enzyme. This enzyme catalyses the first step in the modification of an adenosine near the anticodon to 2-methylthio-N6-isopentyladenosine .

Plants have two classes of isopentenyltransferases (IPTs): ATP/ADP isopentenyltransferases (IPT1, 3, 4-8) and tRNA IPTs (IPT2 and 9) . Both types are included in this family.
Ribosome maturation protein SBDS, conserved site (Ribosome_mat_SBDS_CS)
Type: Conserved_site

Proteins identified by this conserved site are involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes in eukaryotes. Together with the EF-2-like GTPase RIA1, they may trigger the GTP-dependent release of TIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating TIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export.
Cobalamin (vitamin B12) transport protein CbiM (CbiM)
Type: Family

Cobalamin (vitamin B12) is a structurally complex cofactor, consisting of a modified tetrapyrrole with a centrally chelated cobalt. Cobalamin is usually found in one of two biologically active forms: methylcobalamin and adocobalamin. Most prokaryotes, as well as animals, have cobalamin-dependent enzymes, whereas plants and fungi do not appear to use it. In bacteria and archaea, these include methionine synthase, ribonucleotide reductase, glutamate and methylmalonyl-CoA mutases, ethanolamine ammonia lyase, and diol dehydratase . In mammals, cobalamin is obtained through the diet, and is required for methionine synthase and methylmalonyl-CoA mutase .

This entry represents the integral membrane protein CbiM, which forms part of the energy-coupling factor (ECF) transporter complex CbiMNOQ that is involved in cobalt import , and plays a role in the cobalamin synthesis pathway.
2-hydroxycarboxylate transporter, proteobacteria/firmicutes (2-OHcarbox_trans_Prot/Firm)
Type: Family

The 2-hydroxycarboxylate transporter family is a family of secondary transporters found exclusively in the bacterial kingdom. They function in the metabolism of the di- and tricarboxylates malate and citrate, mostly in fermentative pathways involving decarboxylation of malate or oxaloacetate .

The majority of proteins in this family are known or predicted members of the citrate:cation symporter (CCS) family. They contain the predicted twelve-transmembrane helix motif common to many secondary transporters . Most of the characterised proteins in this entry are specific for citrate, with either Na+ of H+ as the contransported cation. However, one member is capable of cotransporting either citrate or malate with H+ , while another has been shown to be an Na+-dependent malate cotransporter .

This entry represents a subgroup of family members from proteobacteria and firmicutes.
DNA repair protein Rad4-like (DNA_repair_Rad4-like)
Type: Family

Mutations in the nucleotide excision repair (NER) pathway can cause the xeroderma pigmentosum skin cancer predisposition syndrome. NER lesions are limited to one DNA strand, but otherwise they are chemically and structurally diverse, being caused by a wide variety of genotoxic chemicals and ultraviolet radiation. The xeroderma pigmentosum C (XPC) protein has a central role in initiating global-genome NER by recognising the lesion and recruiting downstream factors.
Asn/Gln amidotransferase (Asn/Gln_amidotransferase)
Type: Domain

The GatB domain, the function of which is uncertain, is associated with aspartyl/glutamyl amidotransferase subunit B and glutamyl amidotransferase subunit E. These are involved in the formation of correctly charged Asn-tRNA(Asn) or Gln-tRNA(Gln) through the transamidation of misacylated Asp-tRNA(Asn) or Glu-tRNA(Gln) in organisms which lack either or both of asparaginyl-tRNA or glutaminyl-tRNA synthetases. The reaction takes place in the presence of glutamine and ATP through an activated phospho-Asp-tRNA(Asn) or phospho-Glu-tRNA(Gln).
Catalase, mono-functional, haem-containing (Catalase)
Type: Family

Catalases (

) are antioxidant enzymes that catalyse the conversion of hydrogen peroxide to water and molecular oxygen, serving to protect cells from its toxic effects . Hydrogen peroxide is produced as a consequence of oxidative cellular metabolism and can be converted to the highly reactive hydroxyl radical via transition metals, this radical being able to damage a wide variety of molecules within a cell, leading to oxidative stress and cell death. Catalases act to neutralise hydrogen peroxide toxicity, and are produced by all aerobic organisms ranging from bacteria to man. Most catalases are mono-functional, haem-containing enzymes, although there are also bifunctional haem-containing peroxidase/catalases (

) that are closely related to plant peroxidases, and non-haem, manganese-containing catalases (

) that are found in bacteria . Based on a phylogenetic analysis, catalases can be classified into clade 1, 2 and 3. Clade 1 contains small subunit catalases from plants and a subset of bacteria; clade 2 contains large subunit catalases from fungi and a second subset of bacteria; and clade 3 contains small subunit catalases from bacteria, fungi, protists, animals, and plants .

This entry represents the mono-functional, haem-containing catalases.
Fimbrial membrane usher, conserved site (Fimbrial_membr_usher_CS)
Type: Conserved_site

In Gram-negative bacteria the biogenesis of fimbriae (or pili) requires a two- component assembly and transport system which is composed of a periplasmic chaperone (see

) and an outer membrane protein which has been termed a molecular 'usher' .
D-aminoacyl-tRNA deacylase, archaea (Deacylase_DtdA_archaea)
Type: Family

D-aminoacyl-tRNA deacylases hydrolyse the ester bond between the polynucleotide and the D-amino acid, thereby preventing the accumulation of such mis-acylated and metabolically inactive tRNA molecules. Several aminoacyl-tRNA synthetases have the ability to transfer the D-isomer of their amino acid onto their cognate tRNA .

This entry represents a group of Archaeal D-aminoacyl-tRNA deacylases (also known as d-Tyr- tRNA(Tyr) deacylases) that shares homology with plant D-aminoacyl-tRNA deacylase. The expression of plant D-aminoacyl-tRNA deacylase is capable of functionally compensating in E. coli for the absence of endogeneous d-Tyr- tRNA(Tyr) deacylase .
KRR1 interacting protein 1 (Kri1)
Type: Family

The budding yeast KRR1-interacting protein 1 (Kri1) is an essential nucleolar protein required for 40S ribosome biogenesis . This entry also includes Kri1 homologues from animals and plants. Their function is not clear.
Flagellar assembly protein FliH/Type III secretion system HrpE (Flagellar_FliH/T3SS_HrpE)
Type: Domain

This entry represents a region found in the flagellar assembly protein FliH, as well as in type III secretion system protein HrpE.

Many flagellar proteins are exported by a flagellum-specific export pathway. Attempts have been made to characterise the apparatus responsible for this process, by designing assays to screen for mutants with export defects.
Experiments involving filament removal from temperature-sensitive flagellar mutants of Salmonella typhimurium have shown that, while most mutants were able to regrow filaments, flhA, fliH, fliI and fliN mutants showed no or greatly reduced regrowth. This suggests that the corresponding gene products are involved in the process of flagellum-specific export . The sequence of fliH has been deduced and shown to encode a protein of molecular mass of 25,782 Da.

Bacterial HrpE proteins are belived to function on the type III secretion system, specifically the secretion of HrpZ (harpinPss) .
Protein of unknown function DUF429, subgroup (DUF429_subgr)
Type: Family

This is a family of uncharacterised proteins.
Nitrogen fixation protein FixH, Proteobacterial (FixH_proteobacterial)
Type: Family

This family consists of several Rhizobium FixH like proteins. It has been suggested that the four proteins FixG, FixH, FixI, and FixS may participate in a membrane-bound complex coupling the FixI cation pump with a redox process catalysed by FixG .

This entry represents a proteobacterial subgroup of FixH.
Large ribosomal subunit protein uL30, conserved site (Ribosomal_uL30_CS)
Type: Conserved_site

Ribosomal protein uL30 is one of the proteins from the large ribosomal subunit. uL30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups bacteria and archaea uL30 (known as L30), yeast mitochondrial uL30m (known as L33), and Drosophila melanogaster, Dictyostelium discoideum (Slime mold), fungal and mammalian uL30 (known as L7) ribosomal proteins. uL30 from bacteria are small proteins of about 60 residues, those from archaea are proteins of about 150 residues, and eukaryotic uL30 (L7) are proteins of about 250 to 270 residues.

This entry represents a conserved site of prokaryotic uL30 and eukaryotic uL30 (L7) ribosomal proteins. It is also found in ribosome biogenesis protein RLP7, a nucleolar protein that plays a critical role in processing of precursors to the large ribosomal subunit RNAs .