SII-SWORD/CoKE huggingface dataset:
Signal transduction histidine kinase, subgroup 2, dimerisation and phosphoacceptor domain (Sig_transdc_His_kin_sub2_dim/P)
Type: Domain

This is the dimerisation and phosphoacceptor domain of a subfamily of histidine kinases. It shares sequence similarity with

and

. It is usually found adjacent to a C-terminal ATPase domain (

). This domain is found in a wide range of bacteria and also several archaea.

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .

Signal transducing histidine kinases are the key elements in two-component signal transduction systems, which control complex processes such as the initiation of development in microorganisms . Examples of histidine kinases are EnvZ, which plays a central role in osmoregulation , and CheA, which plays a central role in the chemotaxis system . Histidine kinases usually have an N-terminal ligand-binding domain and a C-terminal kinase domain, but other domains may also be present. The kinase domain is responsible for the autophosphorylation of the histidine with ATP, the phosphotransfer from the kinase to an aspartate of the response regulator, and (with bifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or to water . The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily.
Beta-N-acetylglucosaminidase, catalytic domain (O-GlcNAcase_cat)
Type: Domain

This entry represents the catalytic domain found at the N-terminal of the human protein O-GlcNAcase (OGA), O-GlcNAcase BT_4395 from Bacteroides thetaiotaomicron, Hyaluronoglucosaminidase from Clostridium perfringens (NagH) and similar sequences from eukaryotes and bacteria. OGA and BT_4395 cleave GlcNAc but not GalNAc from O-glycosylated proteins . NagH is involved in pathogenesis and is likely to act on connectivity tissue during gas gangrene . It catalyses the random hydrolysis of 1->4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate. This domain adopts an (β/α)8-barrel structure (eight-stranded parallel β-sheet core mainly surrounded by eight α-helices) .
Kelch repeat type 2 (Kelch_2)
Type: Repeat

Kelch is a 50-residue motif, named after the Drosophila mutant in which it was first identified . This sequence motif represents one β-sheet blade, and several of these repeats can associate to form a β-propeller. For instance, the motif appears 6 times in Drosophila egg-chamber regulatory protein (also known as ring canal kelch protein), creating a 6-bladed β-propeller. The motif is also found in mouse protein MIPP and in a number of poxviruses. In addition, kelch repeats have been recognised in alpha-and beta-scruin , and in galactose oxidase from the fungus Dactylium dendroides . The structure of galactose oxidase reveals that the repeated sequence corresponds to a 4-stranded antiparallel β-sheet motif that forms the repeat unit in a super-barrel structural fold .

The known functions of kelch-containing proteins are diverse: scruin is an actin cross-linking protein; galactose oxidase catalyses the oxidation of the hydroxyl group at the C6 position in D-galactose; and kelch may have a cytoskeletal function, as it is localised to the actin-rich ring canals that connect the 15 nurse cells to the developing oocyte in Drosophila . Nevertheless, based on the location of the kelch pattern in the catalytic unit in galactose oxidase, functionally important residues have been predicted in glyoxal oxidase .

This entry represents a type of kelch sequence motif that comprises one β-sheet blade.
Lipid A biosynthesis, N-terminal (Lipid_A_biosynth_N)
Type: Domain

This domain is found at the N terminus of a group of Chlamydial lipid A biosynthesis proteins. It is also found by itself in a family of proteins of unknown function.
GPCR, family 3, nine cysteines domain (GPCR_3_9-Cys_dom)
Type: Domain

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

GPCR family 3 receptors (also known as family C) are structurally similar to other GPCRs, but do not show any significant sequence similarity and thus represent a distinct group. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length . Family 3 members include the metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors . As these receptors regulate many important physiological processes they are potentially promising targets for drug development.

This entry represents a conserved sequence, found in the extracellular region, that contains several highly-conserved Cys residues that are predicted to form disulphide bridges.
Nucleolar complex-associated protein 3, N-terminal (Noc3_N)
Type: Domain

This entry represents the N-terminal domain of the nucleolar complex-associated protein (Noc3), which is conserved in eukaryotes and plays essential roles in replication and rRNA processing in Saccharomyces cerevisiae .
Nucleoporin Nup85-like (Nucleoporin_Nup85)
Type: Family

This is a family of nucleoporins conserved from yeast to human.

Nup85 Nucleoporin is an essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance. As part of the NPC Nup107-160 subcomplex plays a role in RNA export and in tethering NUP98/Nup98 and NUP153 to the nucleus. The Nup107-160 complex seems to be required for spindle assembly during mitosis. NUP85 is required for membrane clustering of CCL2-activated CCR2. Seems to be involved in CCR2-mediated chemotaxis of monocytes and may link activated CCR2 to the phosphatidyl-inositol-3-kinase-Rac-lammellipodium protrusion cascade .

The Nup84 complex is composed of one copy each of Nup84, Nup85, Nup120, Nup133, Nup145C, Sec13, and Seh1. The structure of a complex of Nup85 and Seh1 was solved . The N terminus of Nup85 is inserted and forms a three-stranded blade that completes the Seh1 6-bladed β-propeller in trans. Following its N-terminal insertion blade, Nup85 forms a compact cuboid structure composed of 20 helices, with two distinct modules, referred to as crown and trunk .
Peptidase M26, C-terminal domain (Peptidase_M26_C_dom)
Type: Domain

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This entry represents the C-terminal domain of metallopeptidases belonging to MEROPS peptidase family M26. They are extracellular enzymes, which cleave mammalian IgA. They are only found in Gram-positive bacteria and are often found associated with an LPXTG-motif cell wall anchor, indicating that they may be attached to the cell wall. The family also includes the metallopeptidases ZmpB and ZmpC from Streptococcus pneumoniae. These metallopeptidases are thought to contribute to the inflammatory response to Streptococcal infection .
Planctomycete extracellular (Planctomycete_extracellular)
Type: Domain

This motif is conserved at the N terminus of several Rhodopirellula baltica proteins predicted to be extracellular.
RSD-2, N-terminal (RSD-2_N)
Type: Domain

This domain is found in three copies at the N terminus of the Caenorhabditis elegans RSD-2 protein. RSD-2 (RNAi spreading defective) is involved in systemic RNAi . Mutations in the rsd-2 gene do not affect somatic genes but only germline expressed genes .
RtxA toxin (RtxA_toxin)
Type: Repeat

This short repeat is found in the RtxA toxin family .
Non-structural maintenance of chromosomes element 1 (Nse1)
Type: Family

Saccharomyces cerevisiae Nse1 (

) forms part of a complex with SMC5-SMC6. This non-structural maintenance of chromosomes (SMC) complex plays an essential role in genomic stability, being involved in DNA repair and DNA metabolism . It is conserved in eukaryotes from yeast to human. Nse1 acts in a DNA repair pathway for removal of UV-induced DNA damage that is distinct from classical nucleotide excision repair and in repair of ionizing radiation damage. It also functions in homologous recombination repair of DNA double strand breaks and in recovery of stalled replication forks .
Secretin, N-terminal (Secretin_N_2)
Type: Domain

This is a short domain found in bacterial type II/III secretory system proteins. The architecture of these proteins suggests that this family may be functionally analogous to

.
Shugoshin, C-terminal (Shugoshin_C)
Type: Domain

This entry represents the C-terminal domain of Shugoshin (Sgo1) kinetochore-attachment proteins. Shugoshin has a conserved coiled-coil N-terminal domain and a highly conserved C-terminal basic region (

). Shugoshin is a crucial target of Bub1 kinase that plays a central role in chromosome cohesion during mitosis and meiosis divisions by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms . Shugoshin is thought to act by protecting Rec8 and Rad21 at the centromeres from separase degradation during anaphase I (during meiosis) so that sister chromatids remain tethered . Shugoshin also acts as a spindle checkpoint component required for sensing tension between sister chromatids during mitosis, its degradation when they separate preventing cell cycle arrest and chromosome loss in anaphase, a time when sister chromatids are no longer under tension. Human shugoshin is diffusible and mediates kinetochore-driven formation of kinetochore-microtubules during bipolar spindle assembly . Further, the primary role of shugoshin is to ensure bipolar attachment of kinetochores, and its role in protecting cohesion has co-developed to facilitate this process .
Shugoshin, N-terminal coiled-coil domain (Shugoshin_N)
Type: Domain

This entry represents the N-terminal domain of Shugoshin (Sgo1) kinetochore-attachment proteins. Shugoshin has this conserved coiled-coil N-terminal domain and a highly conserved C-terminal basic region (

).

Shugoshin is a crucial target of Bub1 kinase that plays a central role in chromosome cohesion during mitosis and meiosis divisions by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms . Shugoshin is thought to act by protecting Rec8 and Rad21 at the centromeres from separase degradation during anaphase I (during meiosis) so that sister chromatids remain tethered . Shugoshin also acts as a spindle checkpoint component required for sensing tension between sister chromatids during mitosis, its degradation when they separate preventing cell cycle arrest and chromosome loss in anaphase, a time when sister chromatids are no longer under tension. Human shugoshin is diffusible and mediates kinetochore-driven formation of kinetochore-microtubules during bipolar spindle assembly . Further, the primary role of shugoshin is to ensure bipolar attachment of kinetochores, and its role in protecting cohesion has co-developed to facilitate this process .
RNA polymerase sigma-70 ECF-like (RNA_pol_sigma70_ECF-like)
Type: Family

This entry represents a group of sigma factors that are able to regulate extra cellular function (ECF) . Eubacteria display considerable genetic diversity between ECF-sigma factors, but all retain two features: the ability to respond to extra-cytoplasmic functions; and regulation by anti-sigma and anti-anti-sigma factors . This family show sequence similarity to

and

.

The bacterial core RNA polymerase complex, which consists of five subunits, is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . RNA polymerase recruits alternative sigma factors as a means of switching on specific regulons. Most bacteria express a multiplicity of sigma factors. Two of these factors, sigma-70 (gene rpoD), generally known as the major or primary sigma factor, and sigma-54 (gene rpoN or ntrA) direct the transcription of a wide variety of genes. The other sigma factors, known as alternative sigma factors, are required for the transcription of specific subsets of genes.

With regard to sequence similarity, sigma factors can be grouped into two classes, the sigma-54 and sigma-70 families. Sequence alignments of the sigma70 family members reveal four conserved regions that can be further divided into subregions eg. sub-region 2.2, which may be involved in the binding of the sigma factor to the core RNA polymerase; and sub-region 4.2, which seems to harbor a DNA-binding 'helix-turn-helix' motif involved in binding the conserved -35 region of promoters recognised by the major sigma factors .

The plastids of higher plants originating from an ancestral cyanobacterial endosymbiont also contain sigma factors that are encoded by a small family of nuclear genes. All plastid sigma factors belong to the superfamily of sigmaA/sigma70 and have sequences homologous to the conserved regions 1.2, 2, 3, and 4 of bacterial sigma factors .
Transposase, Rhodopirellula-type (Transposase_36)
Type: Family

These transposases are found in the planctomycete Rhodopirellula baltica, the cyanobacterium Nostoc, and the Gram-positive bacterium Streptomyces.
ASPIC/UnbV (UnbV_ASPIC)
Type: Domain

This conserved sequence is found associated with

in many bacterial proteins, including

from Rhodopirellula baltica. It is also found associated with

in several eukaryotic integrin-like proteins (e.g. human ASPIC

) and in several other bacterial proteins (e.g.

) .
Vestigial family (Vg_fam)
Type: Family

The mammalian TEF and the Drosophila scalloped genes belong to a conserved family of transcriptional factors that possesses a TEA/ATTS DNA-binding domain. Transcriptional activation by these proteins likely requires interactions with specific coactivators.

In Drosophila, Vestigial (Vg) has a short 25 aa motif necessary and sufficient to interact with Scalloped (Sd) to form a complex. This motif is also present in four mammalian proteins, which are named Vestigial-like proteins (Vgl1-4) .

In Drosophila, the Vg-Sd complex binds DNA through the Sd TEA/ATTS domain. The Sd-Vg heterodimer is a key regulator of wing development, which directly controls several target genes and is able to induce wing outgrowth when ectopically expressed. This short conserved region is needed for interaction with Sd .

Mammalian Vgl-1 may promote cancer progression . Vgl-2 interacts with TEF-1 and MEF2 to promote skeletal muscle differentiation . Vgl-4, is the only member of the Vestigial-like family expressed in the heart .
YTV (YTV)
Type: Repeat

This entry represents several repeats of a sequence whose core contains the residues YTV which are found in hypothetical proteins from Planctomycetes.
Thiamin/hydroxymethyl pyrimidine-binding YkoF, putative (Thiamin/HMP-bd_put_YkoF)
Type: Domain

This entry represents YkoF-related proteins. YkoF is involved in the hydroxymethyl pyrimidine (HMP) salvage pathway . The domain is found in pairs in these proteins.
SARAH domain (SARAH_dom)
Type: Domain

The SARAH (Sav/Rassf/Hpo) domain is found at the C terminus in three classes of eukaryotic tumour suppressors that give the domain its name. In the Sav (Salvador) and Hpo (Hippo) families, the SARAH domain mediates signal transduction from Hpo via the Sav scaffolding protein to the downstream component Wts (Warts); the phosphorylation of Wts by Hpo triggers cell cycle arrest and apoptosis by down-regulating cyclin E, Diap 1 and other targets . The SARAH domain is also involved in dimerisation, as in the human Hpo orthologue, Mst1, which homodimerises via its C-terminal SARAH domain. The SARAH domain is found associated with other domains, such as protein kinase domains, WW/rsp5/WWP domain (

), C1 domain (

), LIM domain (

), or the Ras-associating (RA) domain (

).
ABC transporter type 1, transmembrane domain (ABC1_TM_dom)
Type: Domain

This entry represents the transmembrane domain in cases where the TMD and ABC region are found in the same protein, and corresponds to ABC type 1 from
Transporter Classification Database
.

ABC transporters minimally contain two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). In certain bacterial transporters, these regions are found on different polypeptides. The function of the integral inner-membrane protein is to translocate the substrate across the membrane, as well as in substrate recognition .

ABC transporters belong to the ATP-Binding Cassette (ABC) superfamily, which uses the hydrolysis of ATP to energise diverse biological systems. ABC transporters minimally consist of two conserved regions: a highly conserved ATP binding cassette (ABC) and a less conserved transmembrane domain (TMD). These can be found on the same protein or on two different ones. Most ABC transporters function as a dimer and therefore are constituted of four domains, two ABC modules and two TMDs.

ABC transporters are involved in the export or import of a wide variety of substrates ranging from small ions to macromolecules. The major function of ABC import systems is to provide essential nutrients to bacteria. They are found only in prokaryotes and their four constitutive domains are usually encoded by independent polypeptides (two ABC proteins and two TMD proteins). Prokaryotic importers require additional extracytoplasmic binding proteins (one or more per systems) for function. In contrast, export systems are involved in the extrusion of noxious substances, the export of extracellular toxins and the targeting of membrane components. They are found in all living organisms and in general the TMD is fused to the ABC module in a variety of combinations. Some eukaryotic exporters encode the four domains on the same polypeptide chain .

The ATP-Binding Cassette (ABC) superfamily forms one of the largest of all protein families with a diversity of physiological functions . Several studies have shown that there is a correlation between the functional characterisation and the phylogenetic classification of the ABC cassette . More than 50 subfamilies have been described based on a phylogenetic and functional classification ; (for further information see
Transporter Classification Database
).
Nuclease-related domain, NERD (NERD)
Type: Domain

The nuclease-related domain (NERD) is found in a broad range of bacterial, as well as single archaeal and plant proteins. Most NERD-containing proteins have a single domain, sometimes with additional (predicted) transmembrane helices. In a few instances, proteins containing NERD domains have additional domains (mostly involved in DNA processing), such as the HRDC, the UvrD/REP helicase, the DNA-binding C4 zinc finger, or the serine/threonine and tyrosine protein kinases. In all cases in which a NERD domain is present in multidomain proteins, it is found at the N terminus. The NERD domain is predicted to function in DNA processing, and may have a nuclease function .
Glutamate 5-kinase (Glu_5kinase)
Type: Family

L-glutamate 5-phosphotransferase, (gamma-glutamyl kinase, proB,

), catalyzes the first step in proline biosynthesis

ATP + L-glutamate = ADP + L-glutamate 5-phosphate.

the product of which rapidly cyclizes to 5-oxoproline and phosphate.