SII-SWORD/CoKE huggingface dataset:
Regulatory protein YycH (YycH)
Type: Domain

The YycFG two-component system is the only signal transduction system in Bacillus subtilis known to be essential for cell viability. This system is highly conserved in low-G+C Gram-positive bacteria, regulating important processes such as cell wall homeostasis, cell membrane integrity, and cell division. Four other genes, yycHIJK, are organised within the same operon with yycF and yycG in B. subtilis.

This entry represents a domain found in the YycH proteins. YycH plays a role in signal transduction and is found immediately downstream of the essential histidine kinase YycG. YycG forms a two component system together with its cognate response regulator YycF. PhoA fusion studies have shown that YycH is transported across the cytoplasmic protein. It is postulated that YycH functions as an antagonist to YycG . The molecule is made up of three domains, and has a novel three-dimensional structure. The N-terminal domain features a calcium binding site and the central domain contains two conserved loop regions .

YycI and YycH proteins interact to control the activity of the YycG kinase. Both YycI and YycH proteins are localized outside the cytoplasm and attached to the membrane by an N-terminal transmembrane sequence. Bacterial two-hybrid data showed that the YycH, YycI, and the kinase YycG form a ternary complex. The data suggest that YycH and YycI control the activity of YycG in the periplasm and that this control is crucial in regulating important cellular processes .
Movement protein R3 (MP_R3)
Type: Family

This family consists of several Geminiviridae R3 (or V3) proteins of around 90 residues in length. It may be involved in the viral transport within, and between cells .
YfaZ (YfaZ)
Type: Family

This family contains the precursor of the bacterial protein YfaZ (approximately 180 residues long). Many members of this family are hypothetical proteins.
Protein of unknown function DUF1514 (DUF1514)
Type: Family

This entry includes Bacteriophage phi PVL, Orf60. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This family consists of several Staphylococcus aureus and related bacteriophage proteins of around 65 residues in length. The function of this family is unknown.
Caerin 1 (Caerin_1)
Type: Domain

This entry consists of several caerin 1 proteins from Litoria species, Australian tree frogs. The caerin 1 peptides are among the most powerful of the broad-spectrum antibiotic amphibian peptides . These peptides are excreted from amphibian skin, and can interact with and disrupt bacterial membranes, leading to the permeabilisation of the cell membrane. Caerin 1.1 forms a helix-bend-helix structure, where both helices are required for activity, as well as the bend region for flexibility. This domain is found associated with the domain

, which contains a signal peptide .
SigmaK-factor processing regulatory BofA (BofA)
Type: Family

This family contains the sigmaK-factor processing regulatory protein BofA (Bypass-of-forespore protein A) (approximately 80 residues long). During sporulation in Bacillus subtilis, transcription is controlled in the developing sporangium by a cascade of sporulation-specific transcription factors (sigma factors). Following engulfment, processing of sigmaK is inhibited by BofA. It has been suggested that this effect is exerted by alteration of the level of the SpoIVFA protein .
Poneritoxin (Poneritoxin)
Type: Family

This family contains a number of Poneritoxin (also known as ponericin) peptides (approximately 30 residues long) from the venom of the predatory ant Pachycondyla goeldii (Ponerine ant). These peptides exhibit antibacterial and insecticidal properties, and may adopt an amphipathic α-helical structure in polar environments such as cell membranes .
HARP domain (HARP_dom)
Type: Domain

SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like1), also known as DNA-dependent ATPase A and HARP (Hep-A-related proteins), maintains genome integrity during DNA replication. SMARCAL1 has ATP-dependent annealing helicase activity, which helps to stabilise stalled replication forks and facilitate DNA repair during replication. Biochemically, SMARCAL1 can bind to DNA that contains single- and double-stranded regions such as forks and DNA hairpins. DNA binding activates its ATPase activity, and this activity promotes DNA single-stranded annealing .

SMARCAL1 is a multifunctional protein. The ATPase domain, which lies in the C- terminal half of the protein, is split into two regions of primary amino acid sequence by a 115-amino-acid linker sequence. The N-terminal half of the protein contains a highly sequence conserved ssDNA-binding protein replication protein A (RPA)-binding domain, and one or two HARP domain(s). The evolutionarily conserved HARP domain determines the annealing helicase activity required for the in vivo and in vitro functions of SMARCAL1 .
Uncharacterised protein family Ycf66 (Uncharacterised_Ycf66)
Type: Family

This entry represents Ycf66, a protein that is restricted to the chloroplasts of simple plants and algae. It is also found in the cyanobacteria. The function is unknown. As the family is exclusively found in phototrophic organisms it may play a role in photosynthesis.
Formate hydrogenlyase maturation HycH (Formate_DH_maturation_HycH)
Type: Family

This family contains the bacterial formate hydrogenlyase maturation protein HycH, which is approximately 140 residues long. This may be required for the conversion of a precursor form of the large subunit of hydrogenlyase 3 into a mature form .
Bacteriophage P4, Psu, polarity suppression protein (Phage_P4_Psu)
Type: Family

This family contains a number of phage polarity suppression proteins (Psu) (approximately 190 residues long). The Psu protein of Bacteriophage P4
causes suppression of transcriptional polarity in Escherichia coli by overcoming Rho termination factor activity . It has the structure of a golf stick composed of seven helices. Psu is described to have a complicated knotted dimeric conformation. It binds to the hexameric capsomere on the P4 capsid to prevent DNA leakage .
SPAN-X family (SPAN-X_fam)
Type: Family

This entry represents SPAN-X (Sperm Protein Associated with the Nucleus on the X chromosome) family proteins, including N1, N2, N3 and N5. These human sperm proteins are associated with the nucleus and mapped to the X chromosome (SPAN-X) (approximately 100 residues long). SPAN-X proteins are cancer-testis antigens (CTAs), and thus represent potential targets for cancer immunotherapy because they are widely distributed in tumours but not in normal tissues, except testes. They are highly insoluble, acidic, and polymorphic .
Vibrio phage CTX, RstB (Vibrio_Phage_CTX_RstB)
Type: Family

This family contains a number of RstB proteins approximately 120 residues long, including RstB1 and RstB2, from the Vibrio cholerae phage CTX. Functional analyses indicate that rstB2 is required for integration of the CTXphi phage into the V. cholerae chromosome .
Apolipophorin-III (ApoLp-III)
Type: Family

This family consists of several insect apolipoprotein-III sequences. Exchangeable apolipoproteins constitute a functionally important family of proteins that play critical roles in lipid transport and lipoprotein metabolism. Apolipophorin III (apoLp-III) is a prototypical exchangeable apolipoprotein found in many insect species that functions in transport of diacylglycerol (DAG) from the fat body lipid storage depot to flight muscles in the adult life stage .
Photosystem I PsaM, reaction centre (PSI_PsaM)
Type: Family

Members of this protein family are PsaM, which is subunit XII of the photosystem I reaction centre. PsaM forms part of the photosystem I complex and its binding is stabilised by PsaI . This protein is found in both the Cyanobacteria and the chloroplasts of plants, but is absent from non-oxygenic photosynthetic bacteria such as Rhodobacter sphaeroides. Species that contain photosystem I also contain photosystem II, which splits water and releases molecular oxygen.
Nuclear receptor coactivator, DUF1518 (NCO_DUF1518)
Type: Domain

This conserved domain of unknown function is usually found tandemly repeated in the nuclear receptor coactivator family (NCOA1/2/3), also known as the SRC/p160 nuclear receptor coactivator family, which are ligand-dependent transcription factors .

NCOA1 directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion . It is involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs) . It is also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors . It plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors . It can be regulated by sumoylation and ubiquitination .
Spasmodic peptide gm9a (Toxin_11)
Type: Family

This family consists of several spasmodic peptide gm9a sequences. Conotoxin gm9a is a putative 27-residue polypeptide encoded by Conus gloriamaris and is known to be a homologue of the 'spasmodic peptide', tx9a, isolated from the venom of the mollusk-hunting cone shell Conus textile . Upon injection of this venom component, normal mice are converted into behavioural phenocopies of a well-known mutant, the spasmodic mouse .
Diphthamide synthesis DHP2 (DHP2)
Type: Family

DPH2, also known as diphthamide biosynthesis protein 2 or 2-(3-amino-3-carboxypropyl)histidine synthase subunit 2, has been shown in Saccharomyces cerevisiae (Baker's yeast) to be one of several required for the modification of a particular histidine residue of translation elongation factor 2 to diphthamide . This modified site can then become the target for ADP-ribosylation by diphtheria toxin . DPH proteins are highly conserved among eukaryotes .
5-oxoprolinase subunit B (PxpB)
Type: Family

This entry represents 5-oxoprolinase subunit B from Bacillus subtilis (PxpB) and similar proteins widely spread among bacteria. PxpB was originally designated KipI, as it showed to be an inhibitor of B. subtilis sporulation kinase A (KinA) . It catalyses the cleavage of 5-oxoproline to form L-glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate. It folds into two α/β domains . Members of this family show a carboxyltransferase domain (

) covering its full length.
tRNA U34 carboxymethyltransferase (CmoB)
Type: Family

This family represents tRNA U34 carboxymethyltransferase CmoB.

CmoA and CmoB are important components of the cmo5U biosynthetic pathway. These enzymes are involved in the conversion of 5-hydroxyuridine (ho5U) to uridine-5-oxyacetic acid (cmo5U) at the wobble position (34) of tRNA . Uridine-5-oxyacetic acid at tRNA position 34 is apparently necessary for the efficient decoding of G-ending Pro, Ala, and Val codons in these organisms . cmo5U modification requires the previously unknown metabolite carboxy-S-adenosine-L-methionine (Cx-SAM), which is generated by CmoA. CmoB catalyzes carboxymethyl transfer from Cx-SAM to ho5U, converting ho5U into cmo5U at the wobble position of multiple tRNAs in Gram-negative bacteria .
Integral membrane protein, YccS (Integral_membrane_YccS)
Type: Family

This entry identifies a clade of sequences from gamma and beta proteobacteria. These proteins are more than 700 amino acids long and many have been annotated as putative membrane proteins. The gene from Salmonella has been annotated as a putative efflux transporter. The gene from Escherichia coli has been annotated as yccS.
Integral membrane protein, YccS/YhfK (Integral_membrane_YCCS_YHJK)
Type: Family

This entry identifies a clade of sequences from gamma and beta proteobacteria. These proteins are more than 700 amino acids long and many have been annotated as putative membrane proteins. The gene from Salmonella has been annotated as a putative efflux transporter. The gene from Escherichia coli has been annotated as yccS. The YccS hypothetical equivalog is found in beta and gamma proteobacteria, while the smaller YhfK group is only found in E. coli, Salmonella and Yersinia.
Phosphatidylglycerophosphate phosphatase (PGPP1/Gep4)
Type: Family

This group of proteins is a part of the IIIA subfamily of the haloacid dehalogenase (HAD) superfamily of hydrolases. All characterised members of this subfamily and most characterised members of the HAD superfamily are phosphatases. HAD superfamily phosphatases contain active site residues in several conserved catalytic motifs , all of which are found conserved here.

This family consists of sequences from fungi, plants, cyanobacteria, Gram-positive bacteria and Deinococcus. Proteins in this entry Includes phosphatidylglycerophosphatase Gep4 from budding yeasts and phosphatidylglycerophosphate phosphatase 1 (PGPP1) from plants. Gep4 is involved in the biosynthesis of cardiolipin and phosphatidylethanolamine for survival of prohibitin-deficient cells . Chloroplastic PGPP1 is involved in the biosynthesis of phosphatidylglycerol (PG), a phosphoglycerolipid present in chloroplastic thylakoid membranes and has a photosynthetic function .
Protein of unknown function XkdX (XkdX)
Type: Family

This entry identifies a family of small (about 50 amino acid) phage proteins, found in at least 12 different phage and prophage regions of Gram-positive bacteria. In a number of these phage, the gene for this protein is found near the holin and endolysin genes.
KdsC family (KdsC_fam)
Type: Family

This entry is a part of the haloacid dehalogenase (HAD) superfamily of hydrolases, mainly from beta, gamma and epsilon proteobacteria, Aquifex, Fusobacterium, Porphyromonas and Methanosarcina. All characterised members of the HAD-superfamily hydrolase, subfamily IIIA and most characterised members of the HAD superfamily are phosphatases. HAD superfamily phosphatases contain active site residues in several conserved catalytic motifs , all of which are found conserved in this family.

Lipopolysaccharides of Gram-negative bacteria consist of a heteropolysaccharide component (O-antigen) and a hydrophobic component (lipid A). Linking the two portions is 3-Deoxy-D-manno-octulosonate (KDO), an 8-carbon sugar. Biosynthesis of KDO linked to lipid A proceeds via five steps, one of which involves removal of a phosphate from KDO 8-P via the action of KDO 8-P phosphatase (

) . This entry includes two homologues with divergent functions: 2-keto-3-deoxy-d-manno-octulosonate 8-phosphate phosphohydrolase (KDO8P phosphatase, KDO8PP, KdsC) and 2-keto-3-deoxy-9-O-phosphonononic acid phosphohydrolase (KDN9P phosphatase, KDN9PP). KDO8PP and KDN9PP catalyze the final step in the synthesis of KDO and the 9-carbon derivative KDN, respectively .

One member of this family, the YrbI protein from Haemophilus influenzae has been cloned, expressed, purified and found to be an active phosphatase. Furthermore, its crystal structure has been determined . The sequence from Methanosarcina acetivorans,

, is distinctive in that it is linked to an N-terminal cytidylyltransferase domain (

) and is annotated as acylneuraminate cytidylyltransferase.
Conserved hypothetical protein CHP1671 (CHP16711)
Type: Family

This entry represents an uncharacterised, well-conserved family of proteins found in bacteriophage and prophage regions of mainly Gram-positive bacteria.
HAD-superfamily phosphatase, subfamily IIIB, AphA (HAD-SF_ppase_IIIB_AphA)
Type: Family

This family of proteins is a member of the IIIB subfamily (

) of the haloacid dehalogenase (HAD) superfamily of hydrolases. All characterised members of subfamily III and most characterised members of the HAD superfamily are phosphatases. HAD superfamily phosphatases contain active site residues in several conserved catalytic motifs , all of which are found conserved in this family.

AphA is a periplasmic acid phosphatase of Escherichia coli belonging to class B bacterial phosphatases , which is part of the DDDD superfamily of phosphohydrolases. The crystal structure of AphA has been determined at 2.2A and its resolution extended to 1.7A. Despite the lack of sequence homology, the AphA structure reveals a haloacid dehalogenase-like fold. This finding suggests that this fold could be conserved among members of the DDDD superfamily of phosphohydrolases. The active enzyme is a homotetramer built by using an extended N-terminal arm intertwining the four monomers. The active site of the native enzyme hosts a magnesium ion, which can be replaced by other metal ions. The structure explains the non-specific behaviour of AphA towards substrates, while a structure-based alignment with other phosphatases provides clues about the catalytic mechanism .
Phage holin, LL-H family (Phage_holin_LL-H)
Type: Family

This entry represents a family of putative phage holins from a number of phage and prophage regions of Gram-positive bacteria. Like other holins, it is small (about 100 amino acids) with stretches of hydrophobic sequence and is encoded adjacent to lytic enzymes.
Tail assembly protein G (Tail_assembly_G)
Type: Domain

This entry represents a domain found in the tail assembly protein G from lambda-like viruses and their prophage.

In bacteriophage lambda, the overlapping open reading frames G and T are expressed by a programmed translational frameshift to produce the tail assembly proteins G and GT . Tail assembly protein GT shares it's N-terminal residues with tail assembly protein G, followed by residues of unique sequence . An analogous frameshift is widely conserved among other dsDNA tailed phages in their corresponding 'G' and 'GT' tail genes even in the absence of detectable sequence homology . The lambda tail assembly protein G and frameshift product GT are produced in a molar ratio of approximately 30:1. The correct molar ratio of these two related proteins, normally determined by the efficiency of the frameshift, is crucial for efficient assembly of functional tails . Although tail assembly proteins G and GT are both required for assembly of functional tails, neither is present in mature tails .
Acid phosphatase, plant (Acid_phosphatase_pln)
Type: Family

This entry represents a family of acid phosphatase from plants which are closely related to the class B non-specific acid phosphatase OlpA (

, which is believed to be a 5'-nucleotide phosphatase) and somewhat more distantly to another class B phosphatase, AphA (

). Together these three clades define a subfamily of Acid phosphatase (Class B), which corresponds to the IIIB subfamily of the haloacid dehalogenase (HAD) superfamily of aspartate nucleophile hydrolases. It has been reported that the best substrates were purine 5'-nucleoside phosphates . This is in concordance with the assignment of the Haemophilus influenzae hel protein (from

) as a 5'-nucleotidase, however there is presently no other evidence to support this specific function for this family of plant phosphatases. Many genes from this family have been annotated as vegetative storage proteins (VSPs) due to their close homology with these earlier-characterised gene products which are highly expressed in leaves. There are significant differences however, including expression levels and distribution . The most important difference is the lack in authentic VSPs of the nucleophilic aspartate residue, which is instead replaced by serine, glycine or asparagine. Thus these proteins can not be expected to be active phosphatases. This issue was confused by the publication in 1992 of an article claiming activity for the Glycine max (Soybean) VSP . In 1994 this assertion was refuted by the separation of the activity from the VSP. This entry explicitly excludes the VSPs which lack the nucleophilic aspartate. The possibility exists, however, that some members of this family may, while containing all of the conserved HAD-superfamily catalytic residues, lack activity and have a function related to the function of the VSPs rather than the acid phosphatases.
Galactonolactone dehydrogenase (GL_DH)
Type: Family

This entry identifies L-galactono-gamma-lactone dehydrogenase

. This enzyme performs the final step in ascorbic acid biosynthesis in higher plants. The protein is homologous to ascorbic acid biosynthesis enzymes of other species: L-gulono-gamma-lactone oxidase in rat and L-galactono-gamma-lactone oxidase in yeast. All three covalently bind the cofactor FAD.
L-gulonolactone oxidase, plant (GULO_Plant)
Type: Family

This entry represents a family of L-gulonolactone oxidases. At least seven distinct members are found in Arabidopsis thaliana (Mouse-ear cress). This group of proteins may be involved in the biosynthesis of ascorbic acid .
L-gulonolactone/D-arabinono-1,4-lactone oxidase-like (FAD_lactone_oxidase-like)
Type: Family

This entry identifies a family of at least two different sugar 1,4 lactone oxidases, both involved in synthesising ascorbic acid or a derivative. These include L-gulono-1,4-lactone dehydrogenase from bacteria ([ec:1.1.2.-]), L-gulonolactone oxidase (

) from mammals and D-arabinono-1,4-lactone oxidase Alo1 (

) from yeasts. Members are proposed to have the cofactor FAD covalently bound at a site specified by

.
HAD-superfamily phosphatase, subfamily IIIC (HAD_SF_ppase_IIIC)
Type: Domain

This entry represents the IIIC subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate nucleophile hydrolases. Subfamily III, which includes subfamily IIIA (

) and subfamily IIIB (

) contains sequences which do not contain either of the insert domains between the 1st and 2nd conserved catalytic motifs, subfamily I (

,

,

, and

), or between the 2nd and 3rd, subfamily II (

, and

). Subfamily IIIC contains five relatively distantly related clades: a family of viral proteins (

), a family of eukaryotic proteins called MDP-1 and a family of archaeal proteins most closely related to MDP-1 (

), a family of bacteria including the Streptomyces FkbH protein (

), and a small clade including the Pasteurella multocida BcbF and EcbF proteins. The overall lack of species overlap among these clades may indicate a conserved function, but the degree of divergence between the clades and the differences in architecture outside of the domain in some clades warns against such a conclusion.
No member of this subfamily is characterised with respect to function, however the MDP-1 protein is a characterised phosphatase. All of the characterised enzymes within subfamily III are phosphatases, and all of the active site residues characteristic of HAD-superfamily phosphatases are present in subfamily IIIC.
ThiS, thiamine-biosynthesis (Thi_S)
Type: Family

This entry identifies the ThiS family, which are thiamine-biosynthesis proteins related to MoaD. MoaD is a molybdenum cofactor biosynthesis protein. Both ThiS and MoaD proteins are involved in sulphur transfer.
Magnesium-dependent phosphatase-1, eukaryotic/archaeal-type (MDP_1_eu_arc)
Type: Family

This entry represents two closely related clades of sequences from eukaryotes and archaea, however, some uncharacterised bacterial sequences are also included in this family. The mouse enzyme has been characterised as a phosphatase and has been positively identified as a member of the haloacid dehalogenase (HAD) superfamily by site-directed mutagenesis of the active site residues . Its structure is similar to other HAD members but MDP-1 appears to be equally able to dephosphorylate phosphotyrosine and closed-ring phosphosugars .