SII-SWORD/CoKE huggingface dataset:
Signal transduction histidine kinase, 5TM receptor LytS, transmembrane region (Sig_transdc_His_kinase_LytS_TM)
Type: Domain

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.

This entry represents the transmembrane region of the 5TM-Lyt (5TM Receptors of the LytS-YhcK type) histidine kinase . The two-component regulatory system LytS/LytT probably regulates genes involved in cell wall metabolism.
Metal-dependent phosphohydrolase, 7TM intracellular domain (Metal-dep_PHydrolase_7TM_intra)
Type: Domain

These bacterial 7TM receptor proteins have an intracellular domain

. This entry corresponds to the 7 helix transmembrane domain. These proteins also contain an N-terminal extracellular domain .
7TM-DISM receptor, extracellular domain, type 2 (7TMR_DISM_rcpt_extracell_dom2)
Type: Domain

This entry represents one of two distinct types of extracellular domain found in the 7TM-DISM (7TM Receptors with Diverse Intracellular Signalling Modules) bacterial transmembrane proteins . It is possible that this domain adopts a jelly roll fold and acts as a receptor for carbohydrates and their derivatives . It can also recognise Ca(II) (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1.
https://doi.org/10.1093/femsre/fuab043).
7TM-DISM receptor, extracellular domain, type 1 (7TMR_DISM_rcpt_extracell_dom1)
Type: Domain

This entry represents the transmembrane region of the 7TM-DISM (7TM Receptors with Diverse Intracellular Signalling Modules) .
Metal-dependent phosphohydrolase, 7TM extracellular domain (Metal-dep_PHydrolase_7TM_extra)
Type: Domain

This entry represents the extracellular domain of the 7TM-HD (7TM Receptors with HD hydrolase) protein family . These proteins are known or predicted, to posses metal-dependent phospohydrolase activity.
Alpha-2-macroglobulin, bait region domain (A2M_N_BRD)
Type: Domain

Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system . However, A2M-like proteins were identified in pathogenic invasive bacteria and species that colonize higher eukaryotes. In human A2Ms, this domain encompasses macroglobulin-like domain MG5 and 6 including bait region. In Salmonella enterica ser A2Ms, this domain encompasses MG7 and MG8 including the bait region . The bait region is cleaved by proteases, followed by a large conformational change that blocks the target protease within a cage-like complex. This model of protease entrapment is recognised as the Venus flytrap mechanism .
Alpha-macroglobulin-like, TED domain (Alpha-macroglobulin_TED)
Type: Domain

This entry corresponds to the TED domain of the complement components such as C3, C4 and C5 . This domain contains a short highly conserved region of proteinase-binding alpha-macro-globulins contains the cysteine and a glutamine of a thiol-ester bond that is cleaved at the moment of proteinase binding, and mediates the covalent binding of the alpha-macro-globulin to the proteinase. The GCGEQ motif is highly conserved .
Cleaved adhesin (Cleaved_adhesin)
Type: Domain

This conserved region is found in a group of haemagglutinins and peptidases, e.g.

, that, in Porphyromonas gingivalis (Bacteroides gingivalis), form components of the major extracellular virulence complex RgpA-Kgp - a mixture of proteinases and adhesins . These domains are cleaved from the original polyprotein and form part of the adhesins .
Zinc chaperone CobW-like, C-terminal (CobW-like_C)
Type: Domain

CobW proteins are generally found proximal to the trimeric cobaltochelatase subunit CobN, which is essential for vitamin B12 (cobalamin) biosynthesis . They contain a P-loop nucleotide-binding loop in the N-terminal domain and a histidine-rich region in the C-terminal portion suggesting a role in metal binding, possibly as an intermediary between the cobalt transport and chelation systems. CobW might be involved in cobalt reduction leading to cobalt(I) corrinoids.

This entry represents the C-terminal domain found in CobW, as well as in P47K (

), a Pseudomonas chlororaphis protein needed for nitrile hydratase expression .

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 .
Nucleotide modification associated domain 1 (DUF1599)
Type: Domain

This entry represents an α helical domain with conserved polar residues suggestive of enzymatic function. The domain is associated with the 5-hydroxymethyl uridine synthase and is predicted to play a role in modified base biosynthesis pathways .
Protein of unknown function DUF1600 (DUF1600)
Type: Family

These proteins appear to be specific to Mycoplasma species. They are of unknown function.
Domain of unknown function DUF1601 (DUF1601)
Type: Domain

This domain of unknown function is found repeated in a number of proteins.
CARDB domain (CARDB)
Type: Domain

This entry represents a CARDB (cell adhesion related domain found in bacteria) domain.
Thiosulphate:quinone oxidoreductase small subunit DoxA (DoxA)
Type: Domain

Thiosulphate:quinone oxidoreductase (TQO) catalyses one of the early steps in elemental sulphur oxidation. A novel TQO enzyme was purified from the thermo-acidophilic archaeon Acidianus ambivalens and shown to consist of a large subunit (DoxD) and a smaller subunit (DoxA). The DoxD- and DoxA-like two subunits are fused together in a single polypeptide in

.
Sorbitol phosphotransferase enzyme II, C-terminal (PTS_EIIBC_GUT_C)
Type: Domain

The Gut family consists only of glucitol-specific permeases, but these occur both in Gram-negative and Gram-positive bacteria. Escherichia coli contains IIA protein, IIC protein and IIBC protein.

This entry represents the C-terminal conserved region of the IIBC component.
Type II methyltransferase M.TaqI-like domain (MethylTrfase_TaqI-like_dom)
Type: Domain

This entry contains restriction modification methylases, including Type II methyltransferase M.TaqI from Thermus aquaticus. This protein is a gamma subtype methylase that recognises the double-stranded sequence 5'-TCGA-3', methylates A-4 on both strands and protects the DNA from cleavage by the TaqI endonuclease .
Ferrous iron transport protein B, C-terminal (Fe2_transport_prot_B_C)
Type: Domain

Escherichia coli has an iron(II) transport system (feo) which may make an important contribution to the iron supply of the cell under anaerobic conditions . FeoB has been identified as part of this transport system. FeoB is a large 700-800 amino acid integral membrane protein. The N terminus has been previously erroneously described as being ATP-binding . Recent work shows that it is similar to eukaryotic G-proteins and that it is a GTPase .
Tyrosine-protein kinase ephrin type A/B receptor-like (Tyr-kin_ephrin_A/B_rcpt-like)
Type: Domain

This entry represents a domain found in various ephrin type A and B receptors, which have tyrosine kinase activity.

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups :

Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis . RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction .

Cytoplasmic/non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases .
Nucleoside transporter/FeoB GTPase, Gate domain (Gate_dom)
Type: Domain

This domain is responsible for determining nucleoside specificity in the human sodium/nucleoside cotransporter proteins CNT1 and CNT2 (e.g.

) . In the FeoB proteins (e.g.

), which are believed to be Fe
2+
transporters, it includes the membrane pore region, so the function of this domain is likely to be more general than just nucleoside specificity . It may represent the pore and gate, with a wide potential range of specificity. Hence its name - Gate.
High-CO2 inducible periplasmic protein (HCR1)
Type: Family

In Chlamydomonas reinhardtii, the gene encoding

is induced by iron deficiency . In green algae, this protein is periplasmic. The two paralogues FEA1 and FEA2 are the major proteins secreted by iron-deficient Chlamydomonas reinhardtii, and both are up-regulated in response to iron deficiency. FEA1 but not FEA2 is up-regulated by high CO2 concentration. Both FEA1 and FEA2 are secreted into the periplasmic space and genetic evidence confirms that their association with the cell is required for growth in low iron .
Heme NO-binding (Heme_NO-bd)
Type: Domain

The HNOB (Haem NO Binding) domain is a predominantly α-helical domain and binds heme via a covalent linkage to histidine . This domain is found in soluble guanylate cyclases, which are nitric oxide-responsive signaling proteins. It is predicted to function as a haem-dependent sensor for gaseous ligands and to transduce diverse downstream signals in both bacteria and animals. In Clostridium botulinum displays femtomolar affinity for nitrous oxide (NO) .
Haem NO binding associated (HNOB_dom_associated)
Type: Domain

The HNOBA (Haem NO Binding) domain is found associated with the HNOB domain and

in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a haem-dependent sensor for gaseous ligands, and transduce diverse downstream signals in both bacteria and animals.
KAP family P-loop domain (KAP_P-loop)
Type: Domain

The KAP (after Kidins220/ARMS and PifA) family of predicted NTPases are sporadically distributed across a wide phylogenetic range in bacteria and in animals. Many of the prokaryotic KAP NTPases are encoded in plasmids and tend to undergo disruption to form pseudogenes. A unique feature of all eukaryotic and certain bacterial KAP NTPases is the presence of two or four transmembrane helices inserted into the P-loop NTPase domain. These transmembrane helices anchor KAP NTPases in the membrane such that the P-loop domain is located on the intracellular side .
Circadian clock oscillator protein KaiA (Circadian_clock_KaiA)
Type: Family

KaiA is a component of the the KaiABC oscillator complex, which constitutes the main circadian regulator in cyanobacteria . The kaiABC complex may act as a promoter-nonspecific transcription regulator that represses transcription, possibly by acting on the state of chromosome compaction. In the complex, KaiA enhances the phosphorylation status of kaiC. In contrast, the presence of kaiB in the complex decreases the phosphorylation status of kaiC, suggesting that kaiB acts by antagonising the interaction between kaiA and kaiC. The activity of KaiA activates kaiBC expression, while KaiC represses it . The overall fold of the KaiA monomer is that of a four-helix bundle, which forms a dimer in the known structure . KaiA functions as a homodimer. Each monomer is composed of three functional domains: the N-terminal amplitude-amplifier domain, the central period-adjuster domain and the C-termianl clock-oscillator domain. The N-terminal domain of KaiA, from cyanobacteria, acts as a psuedo-receiver domain, but lacks the conserved aspartyl residue required for phosphotransfer in response regulators . The C-terminal domain is responsible for dimer formation, binding to KaiC, enhancing KaiC phosphorylation and generating the circadian oscillations .
KaiB domain (KaiB_domain)
Type: Domain

The cyanobacterial clock proteins KaiA, KaiB and SasA are proposed as regulators of the circadian rhythm in cyanobacteria . Mutations in both proteins have been reported to alter or abolish circadian rhythmicity. KaiB adopts an α-β meander motif and is found to be a dimer . KaiB was originally discovered from the cyanobacterium Synechococcus as part of the circadian clock gene cluster, kaiABC. KaiB attenuates KaiA-enhanced KaiC autokinase activity by interacting with KaiA-KaiC complexes in a circadian fashion . KaiB is membrane-associated as well as cytosolic. The amount of membrane-associated protein peaks in the evening (at circadian time (CT) 12-16) while the cytosolic form peaks later (at CT 20). The rhythmic localisation of KaiB may function in regulating the formation of Kai complexes. SasA is a sensory histidine kinase which associates with KaiC . Although it is not an essential oscillator component, it is important in enhancing kaiABC expression and is important in metabolic growth control under day/night cycle conditions. SasA contains an N-terminal sensory domain with a TRX fold which is involved in the SasA-KaiC interaction . This domain shows high sequence similarity with KaiB . However, the KaiB structure does not show a classical TRX fold. The N-terminal half of KaiB shares the same β-α-β topology as TRX, but the topology of its C-terminal half diverges.
Peptidase M20, dimerisation domain (Peptidase_M20_dimer)
Type: Domain

This domain consists of 4 β-strands and two α-helices which make up the dimerisation surface of members of the MEROPS peptidase family M20 . This family includes a range of zinc exopeptidases: carboxypeptidases, dipeptidases and specialised aminopeptidases .
Notch ligand, N-terminal domain (Notch_ligand_N)
Type: Domain

This entry represents a region of conserved sequence at the N terminus of several Notch ligand proteins, including Delta-like protein 1 (DLL1), 4 (DLL4) and Protein jagged-1. It plays a role in lipid binding .
MORN variant (MORN_2)
Type: Repeat

This entry represents an apparent variant of the

repeat.
Lipoprotein protein 35 (Lipoprotein_p35)
Type: Family

This group of paralogous proteins identified in Mycoplasma penetrans includes homologues of lipoprotein p35 .
M penetrans paralogue 26 (MpPF26)
Type: Family

These proteins include those ascribed to M penetrans paralogue family 26 in .
Notch, NODP domain (Notch_NODP_dom)
Type: Domain

NOTCH signalling plays a fundamental role during a great number of developmental processes in multicellular animals . NOD and NODP represent a region present in many NOTCH proteins and NOTCH homologues in multiple species such as NOTCH2 and NOTCH3, LIN12, SC1 and TAN1. The role of the NOD and NODP domains remains to be elucidated.
Concentrative nucleoside transporter C-terminal domain (CNT_C_dom)
Type: Domain

The concentrative nucleoside transporter (CNT) (TC 2.A.41) family includes

, which is a purine-specific Na
+
-nucleoside cotransporter localised to the bile canalicular membrane . It also includes

, a Na
+
-dependent nucleoside transporter selective for pyrimidine nucleosides and adenosine, which also transports the anti-viral nucleoside analogues AZT and ddC .

This entry covers the C terminus of this family of transporters.
PA14 domain (PA14_dom)
Type: Domain

The PA14 domain forms an insert in bacterial beta-glucosidases, other glycosidases, glycosyltransferases, proteases, amidases, yeast adhesins and bacterial toxins, including anthrax protective antigen (PA). The domain also occurs in a Dictyostelium pre-spore cell-inducing factor Psi and in fibrocystin, the mammalian protein whose mutation leads to polycystic kidney and hepatic disease. The crystal structure of PA shows that this domain (named PA14 after its location in the PA20 pro-peptide) has a β-barrel structure. The PA14 domain sequence suggests a binding function, rather than a catalytic role. The PA14 domain distribution is compatible with carbohydrate binding .
WD40-like beta-propeller (PD40)
Type: Repeat

This region appears to be related to the

repeat. This model is likely to miss copies within a sequence.

WD-40 repeats (also known as WD or beta-transducin repeats) are short ~40 amino acid motifs, often terminating in a Trp-Asp (W-D) dipeptide. WD40 repeats usually assume a 7-8 bladed β-propeller fold, but proteins have been found with 4 to 16 repeated units, which also form a circularised β-propeller structure. WD-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control and apoptosis. Repeated WD40 motifs act as a site for protein-protein or protein-DNA interaction, and proteins containing WD40 repeats are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins . The specificity of the proteins is determined by the sequences outside the repeats themselves. Examples of such complexes are G proteins (beta subunit is a β-propeller), TAFII transcription factor, and E3 ubiquitin ligase . In Arabidopsis spp., several WD40-containing proteins act as key regulators of plant-specific developmental events.
Antitoxin VapB-like (VapB-like)
Type: Family

This entry includes a group of antitoxins, including vapB from Mycobacterium smegmatis. VapB is an antitoxin component of a type II toxin-antitoxin (TA) module that controls growth via inhibition of translation .
Sulphur oxygenase reductase (S_Oase_red)
Type: Family

The crystal structure of the sulphur oxygenase/reductase (SOR) of the thermo-acidophilic archaeon Acidianus ambivalens has been determined to 1.7-A resolution . Twenty-four monomers form a large hollow sphere enclosing a positively charged nanocompartment. Apolar channels provide access for linear sulphur species. A cysteine persulphide and a low-potential mononuclear non-heme iron site ligated by a 2-His-1-carboxylate facial triad in a pocket of each subunit constitute the active sites, accessible from the inside of the sphere. The iron is likely the site of both sulphur oxidation and sulphur reduction.

At 85 degrees C
in vitro
, elemental sulphur is oxidised to sulphite, thiosulphate and hydrogen sulphide with no external cofactors needed. The proposed equation is: 4S + O
2
+ 4 H
2
O ---> 2 HSO3- + 2 H2S + 2 H
+
.
Secretin/TonB, short N-terminal domain (Secretin/TonB_short_N)
Type: Domain

This is a short domain found at the N terminus of the Secretins of the bacterial type II/III secretory system, as well as the TonB-dependent receptor proteins. These proteins are involved in TonB-dependent active uptake of selective substrates.
UbiC transcription regulator-associated (UTRA)
Type: Domain

The UbiC transcription regulator-associated (UTRA) domain is a conserved ligand-binding domain that has a similar fold to

. It is believed to modulate activity of bacterial transcription factors in response to binding small molecules (sugar phosphates and urocanate, . Proteins containing this domain include the histidine utilisation repressor (expressed from the hutC gene in Pseudomonas putida), which binds to the hutP region in the histidine utilisation (hut) operon and blocks the expression of all the hut genes in the absence of inducer .
Abortive infection system protein AbiD/AbiF-like (Abi_system_AbiD/AbiF-like)
Type: Family

Bacteria have numerous mechanisms to resist bacteriophage infection. While most are based on preventing infection in the first place, the abortive infection (Abi) systems provide protection by the abortion of an existing phage infection . Typically, these Abi systems target a crucial step of phage multiplication such as replication, transcription or translation, and lead to the death of the infected cell.

These protein sequences, found in various bacterial species, are similar to those of the AbiD and AbiF proteins from Lactococcus species . The proteins are thought to have helix-turn-helix motifs, found in many DNA-binding proteins, allowing them to perform their function .
Brf1, TBP-binding domain (BRF1_TBP-bd_dom)
Type: Domain

In budding yeasts, Brf1 forms the TFIIIB complex with TATA-binding protein (TBP) and Bdp1 . The TFIIIB complex can be recruited to the Pol III promoters and form an exceptionally kinetically stable TFIIIB-DNA complex, which then recruits the Pol III enzymatic complex and helps maintain it for multiple transcription cycles in a process called facilitated recycling .

This entry represents the TATA binding protein (TBP) binding domain of Brf1 that covers both the Brf homology II and III regions .
G patch domain-containing protein, N-terminal (DUF1604)
Type: Domain

This domain is found at the N terminus of several eukaryotic RNA processing proteins, including Arabidopsis TGH, which is involved in microRNA (miRNA) and small interfering RNA (siRNA) biogenesis .
Uncharacterised protein family UPF0329 (UPF0329)
Type: Family

This region is found in a number of hypothetical proteins thought to be expressed by the eukaryote Encephalitozoon cuniculi, an obligate intracellular microsporidial parasite. The proteins are approximately 200 residues long.
Small zinc finger protein HVO_2753-like, zinc-binding pocket (HVO_2753-like_ZBP)
Type: Domain

This domain is present in a group of archaeal proteins, including HVO_2753 (also known as Small CPxCG-related zinc finger protein) from Haloferax volcanii . NMR 3D structure analysis revealed the content of four C(P)XCG motifs, suggesting the presence of two zinc-binding pockets (ZBPs). However, only C(P)XCG motifs 2 and 4 (comprising Cys-32 to Cys-35 and Cys-50 to Cys-53) form a ZBP and binds one zinc atom, while C(P)XCG motifs 1 and 3 (comprising Cys-12 to Cys-15 and Cys-39 to Cys-42) form a four-Cys cluster that do not bind zinc. The four C(P)XCG motifs are critical for protein stability, folding and functionality .