SII-SWORD/CoKE huggingface dataset:
Type III secretion system SsaH/EsaH (T3SS_SsaH/EsaH)
Type: Family

This family describes a small protein, always smaller than 100 amino acids, encoded in pathogenicity islands for bacterial type III secretion systems in various strains of Yersinia, Salmonella, and enteropathogenic Escherichia coli, as well as Chromobacterium violaceum and Citrobacter rodentium, which are part of the EscG/YscG/SsaH family of type III secretion system needle protein co-chaperones . In Edwardsiella piscicida, this protein is called EsaH and homologous to Salmonella SPI2 protein SsaH, which has been reported to be one of the chaperones of the Salmonella SPI2 needle protein SsaG . EsaH forms a complex with EscE, which is analogous to T3SS needle chaperones, and controls the
T3SS protein secretion by stabilizing EsaG whose secretion in turn leads to the secretion of the middle and late T3SS substrates .
Bor (Lambda_Bor)
Type: Family

This family consists of several Bacteriophage lambda Bor and Escherichia coli Iss proteins. Expression of bor significantly increases the survival of the E. coli host cell in animal serum. This property is a well known bacterial virulence determinant. Indeed, bor and its adjacent sequences are highly homologous to the iss serum resistance locus of the plasmid ColV2-K94, which confers virulence in animals. It has been suggested that lysogeny may generally have a role in bacterial survival in animal hosts, and perhaps in pathogenesis .

Bor and Iss have been shown to be present on the outer membrane of E. coli, where they may be recognised by the host's immune system .
MUN domain (MUN_dom)
Type: Domain

This entry corresponds to the MUN domain found in Munc13 proteins. These constitute a family of three highly homologous molecules (Munc13-1, Munc13-2 and Munc13-3) with homology to Caenorhabditis elegans unc-13p. Munc13 proteins contain a phorbol ester-binding C1 domain and two C2 domains, which are Ca2+/phospholipid binding domains. Sequence analyses have uncovered two regions called Munc13 homology domains 1 (MHD1) and 2 (MHD2) that are arranged between two flanking C2 domains. MHD1 and MHD2 domains are present in a wide variety of proteins from Arabidopsis thaliana, C. elegans, Drosophila melanogaster, mouse, rat and human, some of which may function in a Munc13-like manner to regulate membrane trafficking. Structural studies have defined MHD1 and MHD2 to be part of the larger MUN domain which forms an elongated structure composed of any pairs of α helices.
CH-like domain in sperm protein (CH_2)
Type: Domain

This entry represents a domain known as Spef, which is a region of sperm flagellar proteins. It probably exerts a role in spermatogenesis in that the protein is expressed predominantly in adult tissue. It is present in the tails of developing and epididymal sperm internal to the fibrous sheath and around the dense outer fibres of the sperm flagellum . The amino-terminal domain (residues 1-110) shows a possible calponin homology (CH) domain; however Spef does not bind actin directly under in vitro conditions, so the function of the amino-terminal calponin-like domain is unclear . Transcription aberrations leading to a truncated protein result in immotile sperm .
PET domain (PET_domain)
Type: Domain

The PET domain is a ~110 amino acid motif in the N-terminal part of LIM domain proteins. The domain was described in Drosophila proteins involved in cell differentiation and is named after Prickle, Espinas and Testin. PET domain proteins contain about three zinc-binding LIM domains (see

) and are found among metazoans. The PET domain has been suggested to play a role in protein-protein interactions with proteins involved in planar polarity signalling or organisation of the cytoskeleton . Some proteins known to contain a PET domain:

Mammalian testin protein (

), which may function as a tumour suppressor.

Mammalian LIM domain only protein 6 (LMO6/Prickle3,

).

Fruit fly prickle (

) and espinas (

) proteins encoded by the tissue polarity gene prickle (pk), involved in the control of orientation of bristles and hairs.

Mammalian prickle-like proteins 1 (

) and 2 (

).
Restriction endonuclease, type II, Tsp45I (Restrct_endonuc_II_Tsp45I)
Type: Family

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements , as summarised below:

Type I enzymes (

) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (

) activities.

Type II enzymes (

) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.

Type III enzymes (

) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (

).

Type IV enzymes target methylated DNA.

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .

This entry represents type II restriction endonucleases such as Tsp45I, which recognises the DNA sequence 5' GTSAC, cleaving prior to G-1 .
Bacteriophage lambda Kil (Phage_lambda_Kil)
Type: Family

This family consists of several Bacteriophage lambda Kil protein like sequences and prophages mainly found in proteobacteria. A cessation of division, followed by one or two fairly synchronous cell divisions in Escherichia coli is due to two genetically separable events: a temporary block of cell division and, at the same time, a block to the initiation of new rounds of DNA replication. The cell division block is a result of the transient expression of the lambda kil gene .

The lambda kil gene has been shown to be responsible for premature lysis on the addition of chloramphenicol between 15 and 20 min after thermal induction of a lambda prophage . Induction of a lambda prophage causes the death of the host cell even in the absence of phage replication and lytic functions due to expression of functions from the lambda p(L) operon. The kil gene causes cell death and filamentation .
Lipopolysaccharide assembly protein A domain (LapA_dom)
Type: Domain

This entry represents a domain found in lipopolysaccharide assembly protein A (LapA). LabA and LapB function together in the assembly of lipopolysaccharide (LPS) . This domain is also found in some uncharacterised proteins, such as Rv3760 from Mycobacterium tuberculosis.
Beta-1,4-N-acetylgalactosaminyltransferase (GalNAc_Trfase_b)
Type: Family

This family consists of several beta-1,4-N-acetylgalactosaminyltransferase proteins .
Herpesvirus IR6 (Herpes_IR6)
Type: Family

This family consists of several Herpesvirus IR6 proteins. The equine herpesvirus 1 (EHV-1) IR6 protein forms typical rod-like structures in infected cells, influences virus growth at elevated temperatures, and determines the virulence of EHV-1 Rac strains .
Torsin (Torsin)
Type: Family

Torsins are membrane-associated ATPases. They belong to the AAA+ (ATPase associated with a variety of cellular activities) superfamily of ATPases, but they lack conserved catalytic residues typically found in related ATPases. Accordingly, Torsins do not display ATPase activity unless they are engaged by their regulatory cofactors lamina-associated polypeptide 1 (LAP1) or luminal domain-like LAP1 (LULL1) , which are type II transmembrane proteins located in the nuclear envelope and endoplasmic reticulum (ER) . LAP1 and LULL1 integrate into the Torsin ring to produce the biologically active ATPase machine .

Torsion dystonia is an autosomal dominant movement disorder characterised by involuntary, repetitive muscle contractions and twisted postures. The most severe early-onset form of dystonia has been linked to mutations in the human DYT1 (TOR1A) gene encoding a protein termed torsinA. While causative genetic alterations have been identified, the function of torsin proteins and the molecular mechanism underlying dystonia remain unknown. It has been suggested that torsins play a role in effectively managing protein folding and that possible breakdown in a neuroprotective mechanism that is, in part, mediated by torsins may be responsible for the neuronal dysfunction associated with dystonia .
NUMB domain (Numb_domain)
Type: Domain

This entry represents a domain found in the cell-fate determinant Numb, and in related proteins. In Drosophila, two signalling pathways, one mediated by Numb and the other by Notch, play essential but antagonistic roles in enabling the two daughters to adopt different fates after a wide variety of asymmetric cell divisions . Numb acts to inhibit Notch signalling, this inhibition being critical for many cell fate decisions . Mammalian Numb (mNumb) has multiple functions and plays important roles in the regulation of neural development, including maintenance of neural progenitor cells and promotion of neuronal differentiation in the central nervous system (CNS) .
Neurexophilin (Nxph)
Type: Family

Neurexophilins (Nxphs) comprise a family of glycoproteins (Nxph1-4) that exhibit characteristics of secreted, preproprotein-derived molecules . The structure and characteristics of neurexophilins indicate that they function as neuropeptides that may signal via alpha-neurexins .

Nxph1 plays an instructive role in synaptic short-term plasticity and the configuration with GABA receptors . Nxph3 has been shown to support the survival of mouse induced pluripotent stem cell-derived (iPSC-derived) dopaminergic (DA) neurons in vitro and in vivo .
Acetoacetate decarboxylase (Acetoacetate_decarboxylase)
Type: Family

Acetoacetate decarboxylase (ADC) is involved in solventogenesis in certain bacteria, which occurs at the end of the exponential growth phase when there is a metabolic switch from classical sugar fermentation with the production of acetate and butyrate to the re-internalisation and oxidation of these acids to acetate and butanol . In Clostridium, SpoOA controls the switch from acid to solvent production. A SpoAO-binding motif occurs in the gene encoding ADC .

This family also contains the fungal decarboxylase DEC1 encoded by the Tox1B locus, which along with the Tox1A gene product is required for the production of the polyketide T-toxin. The pathogenic fungus Cochliobolus heterostrophus (Drechslera maydis) requires the T-toxin for high virulence to maize with T-cytoplasm .
Isocitrate dehydrogenase kinasephosphatase (Isocitrate_DH_AceK)
Type: Family

This family consists of several bacterial isocitrate dehydrogenase kinase/phosphatase (ICDH kinase/phosphatase) proteins. The enzyme has no activating compound but is specific for its substrate. It is a bifunctional enzyme that catalyses the reversible phosphorylation of isocitrate dehydrogenase (IDH,

) on a seryl residue. It consequently belongs to the serine/threonine protein kinase family , and it acts in the Krebs cycle . The catalytic activities of ICDH kinase/phosphatase constitute a moiety conserved cycle, require ATP, and exhibit 'zero-order ultrasensitivity' .
RNA polymerase, arenaviral (RNA_pol_arenavir)
Type: Family

This family consists of several Arenavirus RNA polymerase proteins (

) .
Bacteriophage NinH (Phage_NinH)
Type: Family

This entry includes NinH from Bacteriophage 933W. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Bacteriophage 82, GpQ (Phage_82_GpQ)
Type: Family

This entry is represented by Bacteriophage 82, GpQ. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This family consists of several phage antitermination protein Q and related bacterial sequences. Phage 82 gene Q encodes a phage-specific positive regulator of late gene expression, thought, by analogy to the corresponding gene of phage lambda, to be a transcription antiterminator. GpQ positively regulates expression of the phage late gene operons. Bacterial host RNA polymerase modified by antitermination proteins transcribes through termination sites that otherwise prevent expression of the regulated genes .
Immunoglobulin C2-set-like, ligand-binding (IgC2-like_lig-bd)
Type: Domain

This entry represents a ligand-binding domain that displays similarity to C2-set immunoglobulin domains (antibody constant domain 2) . The two cysteine residues form a disulphide bridge.
Trichodiene synthase, ascomycetes (TRI5_ascomyc)
Type: Family

This family consists of several fungal trichodiene synthase proteins. TRI5 encodes the enzyme trichodiene synthase, which has been shown to catalyse the first step in the trichothecene pathways of Fusarium and Trichothecium species .
Competence protein ComK (ComK)
Type: Family

Competence is the ability of a cell to take up exogenous DNA from its environment, resulting in transformation. It is widespread among bacteria and is probably an important mechanism for the horizontal transfer of genes. DNA usually becomes available by the death and lysis of other cells. Competent bacteria use components of extracellular filaments called type 4 pili to create pores in their membranes and pull DNA through the pores into the cytoplasm. This process, including the development of competence and the expression of the uptake machinery, is regulated in response to cell-cell signalling and/or nutritional conditions .

This family consists of several bacterial ComK proteins. ComK of Bacillus subtilis is a positive autoregulatory protein occupying a central position in the competence-signal-transduction network. It positively regulates the transcription of late competence genes, which specify morphogenetic and structural proteins necessary for construction of the DNA-binding and uptake apparatus, as well as the transcription of comK itself . ComK specifically binds to the promoters of the genes that it affects. It has been found that ClpX plays an important role in the regulation of ComK at the post-transcriptional level .
Ectoine synthase (Ectoine_synth)
Type: Family

This family consists of several bacterial ectoine synthase proteins. The ectABC genes encode the diaminobutyric acid acetyltransferase (EctA), the diaminobutyric acid aminotransferase (EctB), and the ectoine synthase (EctC). Together these proteins constitute the ectoine biosynthetic pathway .

Ectoine synthase, also known as L-ectoine synthase or N-acetyldiaminobutyrate dehydratase (

) is a cupin-like bacterial protein that converts N'-acetyldiaminobutyric acid to ectoine, in the last step of the L-ectoine biosynthetic pathway, via a cyclo-condensation reaction and using iron as the cofactor .
Protein of unknown function DUF1057 (DUF1057)
Type: Family

This entry consists of proteins of unknown function which have an alpha/beta hydrolase fold.
DRF autoregulatory (Drf_DAD)
Type: Domain

This domain is found in Diaphanous-related formins (Drfs) from vertebrates and arthopods. It binds the N-terminal GTPase-binding domain; this link is broken when GTP-bound Rho binds to the GBD and activates the protein. The addition of diaphanous activating domains (DAD) to mammalian cells induces actin filament formation, stabilises microtubules, and activates serum-response mediated transcription .
Protein of unknown function DUF1058 (DUF1058)
Type: Family

SH3 (src Homology-3) domains are small protein modules containing approximately 50 amino acid residues . They are found in a great variety of intracellular or membrane-associated proteins for example, in a variety of proteins with enzymatic activity, in adaptor proteins, such as fodrin and yeast actin binding protein ABP-1.

The SH3 domain has a characteristic fold which consists of five or six β-strands arranged as two tightly packed anti-parallel β-sheets. The linker regions may contain short helices. The surface of the SH3-domain bears a flat, hydrophobic ligand-binding pocket which consists of three shallow grooves defined by conservative aromatic residues in which the ligand adopts an extended left-handed helical arrangement. The ligand binds with low affinity but this may be enhanced by multiple interactions. The region bound by the SH3 domain is in all cases proline-rich and contains PXXP as a core-conserved binding motif. The function of the SH3 domain is not well understood but they may mediate many diverse processes such as increasing local concentration of proteins, altering their subcellular location and mediating the assembly of large multiprotein complexes .

This family consists of several hypothetical bacterial proteins of unknown function, but that contain an SH-3 region.
Hormone-sensitive lipase, N-terminal (HSL_N)
Type: Domain

This domain is found in several mammalian hormone-sensitive lipase (HSL) proteins. Hormone-sensitive lipase, a key enzyme in fatty acid mobilisation, overall energy homeostasis, and possibly steroidogenesis, is acutely controlled via reversible phosphorylation by catecholamines and insulin .
Beet necrotic yellow vein virus, movement protein TGB3 (BNYVV_TGB3)
Type: Family

This entry is represented by Beet necrotic yellow vein virus, movement protein TGB3 (also known as p15) which participates in the transport of viral RNA to the plasmodesmata .
Protein of unknown function DUF1068 (DUF1068)
Type: Family

This family consists of several hypothetical plant proteins from Arabidopsis thaliana and Oryza sativa. The function of this family is unknown.
Formin, FH3 domain (FH3_dom)
Type: Domain

Formin homology (FH) proteins play a crucial role in the reorganisation of the actin cytoskeleton, which mediates various functions of the cell cortex including motility, adhesion, and cytokinesis . Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins, although some formins have been assigned functions within the nucleus. Formins are characterised by the presence of three FH domains (FH1, FH2 and FH3), although members of the formin family do not necessarily contain all three domains . The proline-rich FH1 domain mediates interactions with a variety of proteins, including the actin-binding protein profilin, SH3 (Src homology 3) domain proteins, and WW domain proteins. The FH2 domain (

) is required to inhibit actin polymerisation. The FH3 domain is less well conserved and is required for directing formins to the correct intracellular location, such the mitotic spindle , or the projection tip during conjugation . In addition, some formins can contain a GTPase-binding domain (GBD) (

) required for binding to Rho small GTPases, and a C-terminal conserved Dia-autoregulatory domain (DAD).

This entry represents the FH3 domain.
Formin, GTPase-binding domain (GTPase-bd)
Type: Domain

Diaphanous-related formins (Drfs) are a family of formin homology (FH) proteins that act as effectors of Rho small GTPases during growth factor-induced cytoskeletal remodelling, stress fibre formation, and cell division . Drf proteins are characterised by a variety of shared domains: an N-terminal GTPase-binding domain (GBD), formin-homology domains FH1, FH2 (

) and FH3 (

), and a C-terminal conserved Dia-autoregulatory domain (DAD) that binds the GBD.

This entry represents the GBD, which is a bifunctional autoinhibitory domain that interacts with and is regulated by activated Rho family members. Mammalian Drf3 contains a CRIB-like motif within its GBD for binding to Cdc42, which is required for Cdc42 to activate and guide Drf3 towards the cell cortex where it remodels the actin skeleton .
AP-3 complex subunit delta domain, metazoa (AP3D_dom_metazoa)
Type: Domain

AP-3 complex subunit delta-1 (AP3D1) is part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. AP3D1 is required for efficient transport of VSV-G (vesicular stomatitis virus glycoprotein) from the trans-Golgi network to the cell surface .

This entry represents the AP-3 complex subunit delta domain found in metazoa.
Adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH_hormone)
Type: Family

This family consists of several insect adipokinetic hormone as well as the related crustacean red pigment concentrating hormone (RPCH) . Flight activity of insects comprises one of the most intense biochemical processes known in nature, and therefore provides an attractive model system to study the hormonal regulation of metabolism during physical exercise. In long-distance flying insects, such as the migratory locust, both carbohydrate and lipid reserves are utilised as fuels for sustained flight activity. The mobilisation of these energy stores in Locusta migratoria (Migratory locust) is mediated by three structurally related adipokinetic hormones (AKHs), which are all capable of stimulating the release of both carbohydrates and lipids from the fat body .