SII-SWORD/CoKE huggingface dataset:
Histone H1-like Hc1 (Hc1)
Type: Family

This entry represents a family that includes Histone H1-like protein HC1 from Chlamydia pneumoniae and similar proteins from bacteria and some archaeal species. The gene coding for HC1 is expressed only during the late stages of the chlamydial life cycle concomitant with the reorganisation of chlamydial reticulate bodies into elementary bodies, suggesting that the HC1 protein plays a role in the condensation of chlamydial chromatin during intracellular differentiation, in a role analogous to that of eukaryotic histone proteins .
CblD-like pilus biogenesis initiator (CblD)
Type: Family

This family consists of several minor pilin proteins including CblD from Burkholderia cepacia which is known to CblD be the initiator of pilus biogenesis . The family also contains a variety of Enterobacterial minor pilin proteins.
Protein of unknown function DUF1515 (DUF1515)
Type: Family

This family consists of several hypothetical bacterial proteins of around 130 residues in length. Members of this family seem to be found exclusively in Rhizobium species. The function of this family is unknown.
PriC (PriC)
Type: Family

This family contains the bacterial primosomal replication proteins PriC (approximately 180 residues long).

Replication restart protein PriC is involved in the reactivation of stalled replication forks by facilitating the reloading of the DnaB replicative helicase at sites other than the origin of replication . It recognises abandoned replication forks and remodels DNA single-stranded binding protein (SSB) bound to single-stranded DNA (ssDNA), thereby exposing a loading site for DnaB . PriC functions in multiple restart pathways: it is part of the minor PriC-Rep pathway, which exhibits distinct substrate specificity from the PriA-dependent pathway, and also contributes to the major replication restart pathway alongside PriA, PriB, DnaB, DnaT, and the DnaG primase. Notably, priB and priC have redundant roles in the cell. PriC has been shown to bind 7-9 nucleotides of ssDNA .
Secreted phosphoprotein 24 (Spp-24)
Type: Family

This entry represents a conserved region approximately 140 residues long within secreted phosphoprotein 24 (Spp-24), which seems to be restricted to vertebrates . This is a non-collagenous protein found in bone that is related in sequence to the cystatin family of thiol protease inhibitors. This suggests that Spp-24 could function to modulate the thiol protease activities known to be involved in bone turnover. It is also possible that the intact form of Spp-24 found in bone could be a precursor to a biologically active peptide that coordinates an aspect of bone turnover .
[NiFe]-hydrogenase maturation factor HyaE (NiFe-hyd_mat_HyaE)
Type: Family

This family contains bacterial hydrogenase-1 expression proteins approximately 120 residues long. This includes the Escherichia coli protein HyaE, and the homologous proteins HoxO of Ralstonia eutropha (Alcaligenes eutrophus) and HupG of Rhizobium leguminosarum. Deletion of the hoxO gene in R. eutropha led to complete loss of the uptake [NiFe] hydrogenase activity, suggesting that it has a critical role in hydrogenase assembly .
Stage V sporulation AD (SpoVAD)
Type: Family

This family contains the bacterial stage V sporulation protein AD (SpoVAD), which is approximately 340 residues long. This is one of six proteins encoded by the spoVA operon, which is transcribed exclusively in the forespore at about the time of dipicolinic acid (DPA) synthesis in the mother cell. The functions of the proteins encoded by the spoVA operon are unknown, but it has been suggested they are involved in DPA transport during sporulation .
CHRD (CHRD)
Type: Domain

CHRD (after SWISS-PROT abbreviation for chordin) is a novel domain identified in chordin, an inhibitor of bone morphogenetic proteins. This family includes bacterial homologues. It is anticipated to have an immunoglobulin-like β-barrel structure based on limited similarity to superoxide dismutases but, as yet, no clear functional prediction can be made .
Nuclease-associated modular DNA-binding 1 (NUMOD1)
Type: Domain

This helix-turn-helix-containing DNA-binding domain is found associated in homing nucleases .
Sporulation stage II, protein P (Spore_II_P)
Type: Family

This family contains the bacterial stage II sporulation protein P (SpoIIP) (approximately 350 residues long). It has been shown that a block in polar cytokinesis in Bacillus subtilis is mediated partly by transcription of spoIID, spoIIM and spoIIP. This inhibition of polar division is involved in the locking in of asymmetry after the formation of a polar septum during sporulation .

SpoIIP is one of the three genes (spoIID, spoIIM and spoIIP, ), under the control of sigma E, that have been shown to be essential for the engulfment of the forespore by the mother cell. Their products are involved in degradation of the septal peptidoglycan and mutations in spoIID, spoIIM or spoIIP block sporulation at morphological stage II, prior to the stage of engulfment. These three genes are absolutely conserved (sometimes even duplicated) in all endospore formers .
Heptaprenyl diphosphate synthase component I (Hpre_diP_synth_I)
Type: Family

This family contains component I of bacterial heptaprenyl diphosphate synthase (

) (approximately 170 residues long). This is one of the two dissociable subunits that form the enzyme, both of which are required for the catalysis of the biosynthesis of the side chain of menaquinone-7 .
Protein of unknown function UPF0344 (UPF0344)
Type: Family

This family contains a number of hypothetical bacterial proteins of unknown function approximately 120 residues long.
Nicotine adenine dinucleotide glycohydrolase, catalytic domain (NA_dinucl_GlycHdrlase_cat)
Type: Domain

This family consists of several bacterial nicotine adenine dinucleotide glycohydrolase (NGA) proteins which appear to be specific to Streptococcus pyogenes. NAD glycohydrolase (NADase) is a potential virulence factor. Streptococcal NADase may contribute to virulence by its ability to cleave beta-NAD at the ribose-nicotinamide bond, depleting intracellular NAD pools and producing the potent vasoactive compound nicotinamide .
Merozoite surface 1, C-terminal (MSP1_C)
Type: Domain

This entry represents the C-terminal region of merozoite surface protein 1 (MSP1), which is found in a number of Plasmodium species. MSP-1 is a 200kDa protein expressed on the surface of the Plasmodium vivax merozoite. MSP-1 of Plasmodium species is synthesised as a high-molecular-weight precursor and then processed into several fragments. At the time of red cell invasion by the merozoite, only the 19kDa C-terminal fragment (MSP-119), which contains two epidermal growth factor-like domains, remains on the surface. Antibodies against MSP-119 inhibit merozoite entry into red cells, and immunisation with MSP-119 protects monkeys from challenging infections. Hence, MSP-119 is considered a promising vaccine candidate .
NUMOD4 (NUMOD4)
Type: Domain

NUMOD4 is a putative DNA-binding motif found in homing endonucleases and related proteins .
Protein of unknown function DUF1517 (DUF1517)
Type: Family

This family consists of several hypothetical glycine rich plant and bacterial proteins of around 300 residues in length. This entry includes the Fluctuating-Light-Acclimation Protein 1 (FLAP1). FLAP1 is conserved in oxygenic phototrophs. FLAP1 is associated with chloroplast thylakoid and envelope membranes and is involved in plastidial pH control, but the molecular function of this family is unknown .
Glycosyl hydrolase, family 88 (Glyco_hydro_88)
Type: Family

Unsaturated glucuronyl hydrolase catalyses the hydrolytic release of unsaturated glucuronic acids from oligosaccharides produced by the reactions of polysaccharide lyases .
Bacteriophage lambda, Nu1, terminase small subunit (Phage_lambda_Nu1_terminase-ssu)
Type: Family

Terminase, the DNA packaging enzyme of bacteriophage lambda, is a heteromultimer composed of subunits Nu1 and A. The smaller Nu1 terminase subunit has a low-affinity ATPase stimulated by non-specific DNA .

This entry is representes Bacteriophage lambda Nu1 and related proteins. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Calcium-mediated lectin (Ca-mediated_lectin)
Type: Domain

This entry represents calcium-mediated lectins. Structures have been determined for both fucose-binding lectin II (PA-IIL) and mannose-specific lectin II (RS-IIL) . These proteins have homologous structures, their monomers consisting of a 9-stranded β sandwich with Greek-key topology. Each monomer contains two calcium ions that mediate an exceptionally high binding affinity to the monosaccharide ligand in a recognition mode unique among carbohydrate-protein interactions. In Pseudomonas aeruginosa, PA-IIL contributes to the pathogenic virulence of the bacterium, functioning as a tetramer when binding fucose . In the plant pathogen Ralstonia solanacearum (Pseudomonas solanacearum), RS-IIL recognises fucose, but displays much higher affinity to mannose and fructose, which is opposite to the preference of PA-IIL.
Longin domain (Longin_dom)
Type: Domain

VAMPs (and its homologue synaptobrevins) define a group of SNARE proteins that contain a C-terminal coiled-coil/SNARE domain, in combination with variable N-terminal domains that are used to classify VAMPs: those containing longin N-terminal domains (~150 aa) are referred to as longins, while those with shorter N-termini are referred to as brevins . Longins are the only type of VAMP protein found in all eukaryotes, suggesting that their longin domain is essential. The longin domain is thought to exert a regulatory function. Longin domains have been shown to share the same structural fold, a profilin-like globular domain consisting of a five-stranded antiparallel β-sheet that is sandwiched by an α-helix on one side, and two α-helices on the other (β(2)-α-β(3)-α(2)).

This domain is also found in phytolongins, non-SNARE longin proteins involved in membrane-trafficking machinery.
PLAC (PLAC)
Type: Domain

The PLAC (protease and lacunin) domain is a six-cysteine region of about 40 residues that is present at or near the C-terminal of various enzymes and matrix proteins, including: mammalian PACE4 (paired basic amino acid cleaving enzyme 4), mammalian PCSK5 (proprotein convertase subtilisin/kexin type 5), mammalian metalloproteinases ADAMTS-2, -3, -10, -12, -14, -16, -17, and -19, and manduca Sexta matrix protein lacunin . The PLAC domain is often associated with other domains, such as the thrombospondin type I repeat (TSP1) (

), the Kunitz proteinase inhibitor domain (

), the Ig-like domain (

), the WAP domain (

), the subtilase domain (

), or the ADAM-type metalloprotease domain (

).
Nitrate/nitrite sensing protein, bacterial (Nitrate/nitrite_sensing_bac)
Type: Domain

The nitrate and nitrite-sensing (NIT) domain is a (~250 aa) sensor domain found in various receptor components of signal transduction pathways from different bacterial lineages . Proteins containing a NIT domain belong to one of four known classes of prokaryotic signal transduction proteins: intracellular transcription anti-termination regulators, sensor histidine kinases, methyl-accepting chemotaxis proteins, diguanylate cyclases/phosphodiesterases. NIT-containing receptors regulate cellular functions such as gene expression (transcription anti-terminators and histidine kinases), cell motility (chemotaxis receptors), and enzyme activity (diguanylate cyclases/phosphodiesterases), in response to changes in nitrate and/or nitrite concentrations. The NIT domain is found as both an extracellular and an intracellular sensor. The NIT domain can be found in combination with other signalling domains, such as ANTAR, HAMP (

), MCP, Hemerythrins (

), CHASE (

), GGDEF (

), PAS (

), EAL (

), HK (

), GAF, REC and Hpt (

).

This entry represents a subgroup found exclusively in bacteria.
Rab-binding domain (Rab_BD)
Type: Domain

This entry represents the Rab-binding domain.

Rab are small GTPases implicated in vesicle trafficking. Like the other small GTPases, Rab proteins act as molecular switches, with an active GTP-bound form that interacts with its target or effector protein and an inactive GDP-bound form. A subgroup of Rab effectors contain in their N-terminal part a conserved region of around 70 amino acid residues, the Rab-binding domain (RabBD). In some Rab effector domains an atypical FYVE-type zinc finger is inserted in the central part .

The crystal structure of the Rab effector domain of Rabphilin-3A in complex with Rab3A has been solved . The structure consists of two long helices separated by an atypical FYVE-type zinc finger which adopts a conformation similar to classical ones. The central zinc finger does not directly interact with Rab3A. The amino acids important for this interaction are located around a short C-terminal motif (SGAWFF) and an acidic cluster in the N-terminal area.
Spen paralogue/orthologue C-terminal, metazoa (SPOC_met)
Type: Domain

Spen (split end) proteins regulate the expression of key transcriptional effectors in diverse signalling pathways. They are large proteins characterised by N-terminal RNA-binding motifs and a highly conserved C-terminal SPOC (Spen paralog and ortholog C-terminal) domain. The function of the SPOC domain is unknown, but the SPOC domain of the SHARP Spen protein has been implicated in the interaction of SHARP with the SMRT/NcoR corepressor, where SHARP plays an essential role in the repressor complex .

The SPOC domain is folded into a single compact domain consisting of a β-barrel with seven strands framed by six α helices. A number of deep grooves and clefts in the surface, plus two nonpolar loops, render the SPOC domain well suited to protein-protein interactions; most of the conserved residues occur on the protein surface rather than in the core. Other proteins containing a SPOC domain include Drosophila Split ends, which promotes sclerite development in the head and restricts it in the thorax, and mouse MINT (homologue of SHARP), which is involved in skeletal and neuronal development via its repression of Msx2.
RsgA GTPase domain (RsgA_GTPase_dom)
Type: Domain

GTPases function as crucial molecular switches in a broad variety of biochemical processes. The majority of GTPases form a vast class of evolutionarily related proteins within the broader class of P-loop-containing ATPases. The P-loop GTPases share a conserved amino acid sequence G1-G3-G4 motif pattern (G2 is less well conserved) present in the GTPase domain. The Escherichia coli protein EngC (also known as RsgA) represents a protein family whose members are broadly conserved in bacteria and are indispensable for growth. The GTPase domain of RsgA is very similar to several P-loop GTPases, but differs in having a circular permutation of the GTPase structure described by a G4-G1-G3 pattern . The RsgA-type GTPase domain is predominantly bacterial, with a probable acquisition by plants from chloroplasts .
Polyhydroxyalkanoate depolymerase (PHB_depoly_PhaZ)
Type: Family

This entry represents an intracellular depolymerase for polyhydroxyalkanoate (PHA), a carbon and energy storing polyester that accumulates in granules in many bacterial species when carbon sources are abundant but other nutrients are limiting.
TonB box, conserved site (TonB_box_CS)
Type: Conserved_site

This entry describes a short conserved region at the N terminus called the tonB-box , which is involved in the interaction of the protein with the TonB protein . In Escherichia coli the TonB protein interacts with outer membrane receptor proteins that carry out high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space. These substrates are either poorly permeable through the porin channels or are encountered at very low concentrations. In the absence of tonB these receptors bind their substrates but do not carry out active transport. The TonB protein also interacts with some colicins.
TonB-dependent receptor, conserved site (TonB_rcpt_CS)
Type: Conserved_site

This conserved site is found at the C terminus of outer membrane receptors which interact with the TonB . In Escherichia coli the TonB interacts with outer membrane receptor proteins that carry out high-affinity binding and energy-dependent uptake of specific substrates into the periplasmic space. These substrates are either poorly permeable through the porin channels or are encountered at very low concentrations. In the absence of TonB these receptors bind their substrates but do not carry out active transport. The TonB protein also interacts with some colicins.
PurM-like, C-terminal domain (PurM-like_C_dom)
Type: Domain

This domain is found in carbamoyl dehydratase HypE, which is involved in the maturation of NifE hydrogenase; AIR synthase (PurM) and FGAM synthase (PurL), which are involved in de novo purine biosynthesis; and selenide, water dikinase, an enzyme which synthesizes selenophosphate from selenide and ATP.

In PurM this domain, which has an α-β-type fold, is found at the C terminus of the protein .
SAND-like domain superfamily (SAND-like_dom_sf)
Type: Homologous_superfamily

The SAND domain (named after Sp100, AIRE-1, NucP41/75, DEAF-1) is a conserved ~80 residue region found in a number of nuclear proteins, many of which function in chromatin-dependent transcriptional control. These include proteins linked to various human diseases, such as the Sp100 (Speckled protein 100kDa), NUDR (Nuclear DEAF-1 related), GMEB (Glucocorticoid Modulatory Element Binding) proteins and AIRE-1 (Autoimmune regulator 1) proteins.

Proteins containing the SAND domain have a modular structure; the SAND domain can be associated with a number of other modules, including the bromodomain, the PHD finger and the MYND finger. Because no SAND domain has been found in yeast, it is thought that the SAND domain could be restricted to animal phyla. Many SAND domain-containing proteins, including NUDR, DEAF-1 (Deformed epidermal autoregulatory factor-1) and GMEB, have been shown to bind DNA sequences specifically. The SAND domain has been proposed to mediate the DNA binding activity of these proteins . Structurally, the SAND domain consists of a novel α/β fold, which has a core of three short helices packed against a barrel-like β-sheet; it is structurally similar to the SH3-like fold.

Other proteins display domains that are structurally similar to the SAND domain. One such example is the SMAD4-binding domain of the oncoprotein Ski, which is stabilised by a bound zinc atom, and resembles a SAND domain, in which the corresponding I loop is responsible for DNA binding. Ski is able to disrupt the formation of a functional complex between the Co- and R-SMADs, leading to the repression of TGF-beta, Activin and BMP responses, resulting in the repression of TGF-signalling .
LSM domain superfamily (LSM_dom_sf)
Type: Homologous_superfamily

This domain superfamily is found as the core structure in Lsm (like-Sm) proteins and bacterial Lsm-related Hfq proteins, and as the middle domain of the mechanosensitive channel protein MscS. In each case, the domain adopts a core structure consisting of an open β-barrel with an SH3-like topology.

Lsm proteins have diverse functions, and are thought to be important modulators of RNA biogenesis and function . The Sm proteins form part of specific small nuclear ribonucleoproteins (snRNPs) that are involved in the processing of pre-mRNAs to mature mRNAs, and are a major component of the eukaryotic spliceosome. These snRNPs consist of seven Sm proteins (B/B', D1, D2, D3, E, F and G), plus a small nuclear RNA (snRNA) (either U1, U2, U5 or U4/6) . Other snRNPs, such as U7 snRNP, can contain different Lsm proteins. Lsm proteins are also found in archaebacteria, which do not have any splicing apparatus suggesting a more general role for Lsm proteins.

The pleiotropic translational regulator Hfq (host factor Q) is a bacterial Lsm-like protein, which modulates the structure of numerous RNA molecules by binding preferentially to A/U-rich sequences in RNA . Hfq forms an Lsm-like fold, however, unlike the heptameric Sm proteins, Hfq forms a homo-hexameric ring.

The middle domain of the mechanosensitive channel of small conductance protein (MscS or YggB) structurally resembles an Lsm protein. MscS is a mechanosensitive channel present in the membrane of bacteria, archaea and eukarya that responds both to stretching of the cell membrane and to membrane depolarisation . MscS folds as a homo-heptamer with a cylindrical shape, and can be divided into transmembrane and extramembrane regions: an N-terminal periplasmic region, a transmembrane region, and a C-terminal cytoplasmic region. The C-terminal cytoplasmic region can be further divided into middle and C-terminal domains, which together create a framework that connects to the cytoplasm through distinct openings. The middle domain exhibits an Lsm-like structure, consisting of five β-strands that pack together with those of other subunits to form a barrel-like sheet extending around the entire protein.
Trp repressor/replication initiator (Trp_repressor/repl_initiator)
Type: Homologous_superfamily

The Trp repressor (TrpR) binds to at least five operators in the Escherichia coli genome, repressing gene expression. The operators at which it binds vary considerably in DNA sequence and location within the promoter; when bound to the Trp operon it recognises the sequence 5'-ACTAGT-3' and acts to prevent the initiation of transcription. The TrpR controls the trpEDCBA (trpO) operon and the genes for trpR, aroH, mtr and aroL, which are involved in the biosynthesis and uptake of the amino acid tryptophan . The repressor binds to the operators only in the presence of L-tryptophan, thereby controlling the intracellular level of its effector; the complex also regulates Trp repressor biosynthesis by binding to its own regulatory region. TrpR acts as a dimer that is composed of identical 6-helical subunits, where four of the helices form the core of the protein and intertwine with the corresponding helices from the other subunit.

The bacterial chromosomal replication initiation factor DnaA is a monomeric protein that shows structural similarity to the TrpR, except that it contains additional N-terminal helices. DnaA is a member of the AAA+ family of ATPases, and forms a large, oligomeric assembly at the replication origin site (oriC); the oligomeric complex of DnaA recognises and processes specific origin sequences in order to initiate replication in bacteria .
tRNA threonylcarbamoyladenosine biosynthesis protein SUA5 (T(6)A37_SUA5)
Type: Family

The yeast SUA5 protein is part of the YrdC/SUA5 family is required for the formation of threonylcarbamoyladenosine in tRNA . SUA5 has been shown to be required for translational regulation and telomere recombination and replication in yeast.

Members of this group contain two domains: a YrdC-like domain and the C-terminal SUA5-like domain. The YrdC-like domain has been implicated in RNA-binding, which correlates with its proposed role as a translation factor . There is a prediction for the RNA-binding site in the depression on the surface of the protein based on the structural features . The C-terminal SUA5-type domain has been shown to be essential for the regulatory function of SUA5 protein .