SII-SWORD/CoKE huggingface dataset:
Zinc finger, nanos-type (Znf_nanos-typ)
Type: Domain

Nanos is a highly conserved RNA-binding protein in higher eukaryotes and functions as a key regulatory protein in translational control using a 3'untranslated region during the development and maintenance of germ cells. Nanos comprises a non-conserved amino-terminus and highly conserved carboxy-terminal regions. The C-terminal region has two conserved Cys-Cys-His-Cys (CCHC)-type zinc-finger motifs that are indispensable for nanos function .

The structure of the nanos-type zinc finger is composed of two independent zinc-finger (ZF) lobes, the N-terminal ZF1 and the C-terminal ZF2, which are connected by a linker helix . These lobes create a large cleft. Zinc ions in ZF1 and ZF2 are bound to the CCHC motif by tetrahedral coordination.
Adaptor protein Cbl (Adaptor_Cbl)
Type: Family

Cbl (Casitas B-lineage lymphoma) is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface, including tyrosine kinases, cytokine receptors, and T-cell or B-cell receptors. There are three Cbl related proteins known to date: Cbl, CblB, and CblC/Cbl3 . Cbls function as ubiquitin E3 ligase proteins, accepting ubiquitin from specific E2 ubiquitin-conjugating enzymes and transferring it to substrates, promoting their degradation or endocytosis .
Aerotolerance regulator, N-terminal (Aerotolerance_reg_N)
Type: Domain

The Batl operon appears to be important in pathogenicity and aerotolerance. BatA (

) ensures bacterial survival in the early stages of the infection process, when the infected sites are aerobic, and is produced under conditions of oxidative stress . Proteins produced by the Batl operon share a highly-conserved sequence at their N terminus and the full length proteins carry multiple membrane-spanning domains .

This entry represents the conserved N-terminal domain, which is also found in some uncharacterised proteins.
KinB-signalling pathway activation protein (KinB-signalling_activ)
Type: Family

This entry represents a family of proteins involved in the activation of the KinB signaling pathway of sporulation .
Aminoglycoside 3-phosphotransferase (Kan/Strep_kinase)
Type: Family

Aminoglycoside antibiotics constitute an important class of clinically useful drugs, including gentamicin, tobramycin, and streptomycin, which are used in the treatment of a variety of bacterial infections . They work by targeting the bacterial ribosome and causing mistranslation of mRNA, leading to the production of defective proteins. In many cases these defective proteins insert into the cell membrane, causing a loss of membrane integrity and precipitating cell death. The most common cause of resistance to these antibiotics is their modification by acetylating, adenylating or phosphorylating enzymes.

This entry represents aminoglycoside 3'-phosphotransferases, one of the best characterised aminoglycoside-resistance enzyme families. These enzymes transfer a phophoryl group from ATP to the 3' position of the aminoglycoside molecule. Studies indicate that these enzymes are both structurally and functionally homologous to eukaryotic protein kinases . The enzyme contains two domains, an N-terminal domain composed mainly of an antiparallel β sheet, and a C-terminal domain which is largely α helical. The active site lies between these domains and comprises both the ATP binding site and the aminoglycoside binding site.
Ribosomal RNA assembly KRR1 (rRNA_assembly_KRR1)
Type: Family

This group represents ribosomal RNA assembly protein KRR1, required for 40S ribosome biogenesis. It is involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly in Saccharomyces cerevisiae . In Schizosaccharomyces pombe it is known as Mis3 .
Cytochrome c4-like (Cytochrome_c4-like)
Type: Family

This group represents cytochrome c4. It is a di-heme, high potential cytochrome c believed to be an intermediate electron donor in an anaerobic electron transport chain .
Catalase, SrpA-type, predicted (Catalase_SrpA-type_pred)
Type: Family

Catalase is a ubiquitous enzyme found in both prokaryotes and eukaryotes involved in the protection of cells from the toxic effects of peroxides. It catalyses the conversion of hydrogen peroxide to water and molecular oxygen. Several other related protein families share the catalase fold and bind to heme but do not necessarily have catalase activity. This entry contains uncharacterised proteins similar to the Synechococcus elongatus PCC 7942 periplasmic protein srpA, of mostly bacterial origin. The plasmid-encoded srpA is regulated by sulfate, but does not seem to function in its uptake or metabolism .
Serine-pyruvate aminotransferase/2-aminoethylphosphonate-pyruvate transaminase (SP_NH2Trfase/AEP_transaminase)
Type: Family

This entry represents a group of class-V pyridoxal-phosphate-dependent aminotransferases, and includes serine pyruvate aminotransferase and 2-aminoethylphosphonate-pyruvate transaminase .
Aminoglycoside N6-acetyltransferase (Aminoglycoside_N6-AcTrfrase)
Type: Family

Aminoglycoside N6'-acetyltransferase is a antibiotic resistance protein that catalyses the reaction:

acetyl-CoA + kanamycin-B = CoA + N(6')-acetylkanamycin-B
S-receptor-like serine/threonine-protein kinase (SRK-like_kinase)
Type: Family

Plant S-receptor kinase-like genes have diverse functions in cell signalling, development, stress responses and host-pathogen defence responses .

This entry contains receptor-like kinases, including S-locus receptor kinase (SRK). SRK is the female determinant of the self-incompatibility (SI) response in Brassica . Flowering plants apply a self-incompatibility mechanism to prevent inbreeding and thereby increase genetic diversity . In most flowering plants, SI systems are controlled by a single multi-allelic locus termed the S-locus. Other members of this group do not play a role in SI , and some members are from self-compatible plants such as Oryza sativa (Rice) and Arabidopsis thaliana (Mouse-ear cress), neither of which possess the SI response.

and

from Brassica oleracea (Wild cabbage), as well as

from A. thaliana, are reported to possibly have overlapping roles in both defence and development .

The proteins in this family contain an extracellular D-mannose-binding lectin domain (

), an S-locus glycoprotein family domain (

), a PAN domain, and an intracellular kinase domain (

).
Adenylyltransferase AadA/Aad9 (AadA/Aad9)
Type: Family

This family includes aminoglycoside (3'') (9) adenylyltransferase AadA and spectinomycin 9-adenylyltransferase Aad9. AadA mediates bacterial resistance to the antibiotics streptomycin and spectinomycin , while Aad9 mediates bacterial resistance to the antibiotic spectinomycin .
Phosphoesterase MJ0037-like (Pesterase_MJ0037-like)
Type: Family

This group of conserved proteins from bacteria and archaea contain one copy of the calcineurin-like phosphoesterase domain (

) and possess motifs characteristic of a variety of enzymatically active phosphoesterases , including acid and alkaline phosphatases, phosphoprotein phosphatases, 5'-nucleotidase, bis(5'-nucleosyl)-tetraphosphatase (symmetrical), sphingomyelin phosphodiesterase, 2',3'-cyclic-nucleotide 2'-phosphodiesterase, and 3',5'-nucleotide phosphodiesterase CpdA.
Hepatocyte growth factor/Macrophage stimulatory protein (HGF/MST1)
Type: Family

This entry includes hepatocyte growth factor (HGF; also called scatter factor) and HGF-like proteins (also known as macrophage stimulatory protein, MST1). Hepatocyte growth factor (HGF) is an activating ligand of the Met receptor tyrosine kinase, whose activity is essential for normal tissue development and organ regeneration . HGF is essential for placental, liver, and muscle development, whereas MST1 is not required for embryogenesis, fertility, or wound healing. Genes for HGF and its receptor, the Met tyrosine kinase, are close together on chromosome 7, so that polysomy of chromosome 7 may contribute to malignancy through overproduction of both molecules. MST1 and its receptor, the Ron tyrosine kinase, are close together on chromosome 3. HGF and MST1 are closely related to plasminogen, having similar domain architecture: signal sequence followed by a PAN (formerly apple) domain, four (rather than five) kringle domains, and a trypsin domain, which appears to lack any peptidase activity.
Peptidase S1A, complement C1r/C1S/mannan-binding (Pept_S1A_C1r/C1S/mannan-bd)
Type: Family

These proteins belong to MEROPS peptidase family S1 (chymotrypsin family, clan PA(S)), subfamily S1A.

This family contains the mammalian mannan-binding lectin-associated serine proteases 1 and 2 (MASP1 and MASP2) and complement components C1s and C1r. The C1 complex, containing C1q, C1s, and C1r, triggers the classical complement pathway. When C1q interacts with antibody, C1r becomes autocatalytically activated. Activated C1r in turn activates C1s, which then cleaves C2 and C4 in the classical pathway.

Mannose-binding lectin (MBL) complexes with MASP1, MASP2, and a smaller alternative splice product of the MASP2 gene. Binding of MBL to carbohydrates on the surface of microorganisms triggers activation of the associated MASPs. Then MASP1 activates C3 and C2, whereas MASP2 activates C4 and C2 . Based on the fact that the gene structures of MASP1, C1r, and C1s are similar except that C1r and C1s lack introns in the region encoding the trypsin domain, it has been proposed that the MASP proteins evolved earlier than C1r and C1s . The complement pathway is also involved in development .

These sequences typically contain a signal sequence, followed by a CUB domain, an EGF-like domain (which often is not detected), a second CUB domain, two sushi domains (sometimes only one is detected), and a trypsin domain.
Citrate synthase, bacterial-type (Citrate_synthase_bac-typ)
Type: Family

Citrate synthase

is a member of a small family of enzymes that can directly form a carbon-carbon bond without the presence of metal ion cofactors. It catalyses the first reaction in the Krebs' cycle, namely the conversion of oxaloacetate and acetyl-coenzyme A into citrate and coenzyme A. This reaction is important for energy generation and for carbon assimilation. The reaction proceeds via a non-covalently bound citryl-coenzyme A intermediate in a 2-step process (aldol-Claisen condensation followed by the hydrolysis of citryl-CoA).

This entry represents types I and II citrate synthase enzymes, as well as the related enzymes 2-methylcitrate synthase. 2-methylcitrate (

) synthase catalyses the conversion of oxaloacetate and propanoyl-CoA into (2R,3S)-2-hydroxybutane-1,2,3-tricarboxylate and coenzyme A (CoA). This enzyme is induced during bacterial growth on propionate, while type II hexameric citrate synthase is constitutive . This entry contains citrate synthases from bacteria and some eukaryotic (peroxisomal), and also an enzyme from Bacillus subtilis (citrate/2-methylcitrate synthase) that acts as both a citrate synthase and a methylcitrate synthase .
Biotin synthase (Biotin_synthase)
Type: Family

This family consists of biotin synthase B-like proteins.

Biotin synthase

works with flavodoxin, S-adenosylmethionine, and possibly cysteine to catalyze the last step of the biotin biosynthetic pathway. The reaction consists of the introduction of a sulphur atom into dethiobiotin, thus requiring activation of C-H bonds . Biotin (vitamin H) is a prosthetic group in enzymes catalysing carboxylation and transcarboxylation reactions .

Biotin synthase from Escherichia coli is a homodimer of 76kDa, with each polypeptide chain carrying an oxygen-sensitive (4Fe-4S) cluster, probably ligated by three cysteines of a CXXXCXXC box conserved among all known BioB sequences and a fourth still not identified ligand. BioB displays a pyridoxal phosphate-dependent cysteine desulphurase activity, which allows mobilisation of the sulphur atom from free cysteine .
Estrogen receptor/oestrogen-related receptor (Est_rcpt/est-rel_rcp)
Type: Family

Steroid or nuclear hormone receptors (NRs) constitute an important superfamily of transcription regulators that are involved in widely diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members of the superfamily include the steroid hormone receptors and receptors for thyroid hormone, retinoids, 1,25-dihydroxy-vitamin D3 and a variety of other ligands . The proteins function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner . In addition to C-terminal ligand-binding domains, these nuclear receptors contain a highly-conserved, N-terminal zinc-finger that mediates specific binding to target DNA sequences, termed ligand-responsive elements. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.

NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes, hormone resistance syndromes, etc. While several NRs act as ligand-inducible transcription factors, many do not yet have a defined ligand and are accordingly termed 'orphan' receptors. During the last decade, more than 300 NRs have been described, many of which are orphans, which cannot easily be named due to current nomenclature confusions in the literature. However, a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.

The oestrogen receptors (ERs) are steroid or nuclear hormone receptors that act as transcription regulators involved in diverse physiological functions. Oestrogen receptors function as dimeric molecules in nuclei to regulate the transcription of target genes in a ligand-responsive manner. The ER consists of three functional and structural domains: an N-terminal modulatory domain, a highly conserved DNA-binding domain that recognises specific sequences (

), and a C-terminal ligand-binding domain (

).

This entry represents oestrogen receptors and oestrogen-related receptors, which are members of the subfamily 3 of nuclear receptors . Oestrogen-related receptors (ERR-alpha, ERR-beta, and ERR-gamma) are orphan nuclear receptors whose physiological ligands have not yet been identified. Although ERRs are closely related to oestrogen receptors (ERs) they do not respond to oestrogens .
Bifunctional tetrapyrrole methylase/MazG NTP pyrophosphohydrolase, predicted (Tetrapyrrole_Mease/MazG_pred)
Type: Family

The proteins in this entry are uncharacterised but contain an N-terminal tetrapyrole methylase domain and a C-terminal MazG-type NTP pyrophosphohydrolase domain. On this basis they are predicted to be bifunctional tetrapyrole methylase/NTP pyrophosphohydrolases.
Chemotaxis response regulator CheV (Chemotax_regulator_CheV)
Type: Family

This group contains chemotaxis response regulator protein CheV. CheV is a two-domain protein with an N-terminal CheW-like (SH3-like) domain and a C-terminal CheY-like receiver domain. It is often regarded as a version of CheW, where the CheW-like domain is fused to the receiver domain.

In bacterial chemotaxis, cellular movement is directed in response to chemical gradients. Transmembrane chemoreceptors that sense the stimuli are coupled (via a coupling protein, CheW) with a signal transduction histidine kinase (CheA) . CheA phosphorylates response regulators CheB and CheY. The two cytoplasmic proteins, CheW and CheA, both contain homologous SH3-like domains that interact with transmembrane chemoreceptors, or methyl accepting chemotaxis proteins (MCPs). In CheA, a histidine protein kinase domain is fused to the amino-terminus of the SH3 region . CheV is a third type of protein with a CheW-like domain.

In Bacillus subtilis, CheW and CheV may be partially redundant in coupling the receptors to CheA; however, they are both necessary for efficient chemotaxis . CheV is phosphorylated in vitro on a conserved aspartate as a result of phosphoryl group transfer from phosphorylated CheA (CheA-P). This reaction is slower compared with the phospho-transfer reaction between CheA-P and one other response regulator of the system, CheB. It is part of a signal transduction pathway to facilitate adaptation to attractants . In Helicobacter pylori, CheV paralogues and CheW are not redundant and seem to have separate roles in chemotaxis and the CheV proteins play a role in the bacterial mobility .

For additional information please see .
Vaccinia virus A55R (Vaccinia_A55R)
Type: Family

This family includes ORF A55R from Vaccinia virus, which is characterised by having a BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain near the N terminus. The proteins are also characterised by kelch repeats C-terminal to the BTB domain. The function of these proteins are unknown.
RING finger protein Z, arenaviridae (RING_finger_Z_arenaviridae)
Type: Family

Arenaviridae produce four gene products: RNA-directed RNA polymerase, Z (zinc finger) protein, nucleocapsid protein (NP), and envelope glycoprotein precursor (which gives rise to mature proteins GP1 and GP2). The smallest protein is the Z protein (also called p11), which has molecular size of 11 kD. The Z protein has a zinc-binding RING-finger motif. It has been suggested that the Z-protein is a structural protein and is a component of the nucleocapsid. The arenavirus RING-finger Z protein is the main driving force of arenavirus budding, and myristoylation of its N terminus plays a key role . Z proteins also possess, near their C-termini, PPxY and/or P(T/S)AP motifs. These same motifs are found in the M proteins of Ebola (and other negative stranded RNA) viruses, as well as in Gag proteins of retroviruses. They are called "late budding domains" or "L domains" (despite their short length), and are essential for viral budding. Arenaviruses do not possess the M (or matrix) protein, but the Z protein plays the same important role .
Uncharacterised conserved protein UCP005637 (UCP005637)
Type: Family

There are currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function.
5-formyltetrahydrofolate cyclo-ligase-like domain superfamily (FTHF_cligase-like_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in 5-formyltetrahydrofolate cyclo-ligase, also known as 5,10-methenyltetrahydrofolate synthetase. This enzyme is involved in folate metabolism. It is a single-domain alpha/beta protein. The central core of the protein is a four-stranded parallel β-strand flanked by three helices on one side and a single helix on the other side . This domain is also found in LutC/YkgG. The Escherichia coli ykgEFG operon is a clear homologue of the Bacillus subtilis lutABC operon. This operon is involved in lactate catabolism in B. subtilis, though its role in E. coli is not clear. LutB and LutC probably act as electron transporters during oxidation of L-lactate .
Signal transduction response regulator, heterocyst pattern formation, PatA (Sig_transdc_resp-reg_PatA)
Type: Family

This group contains response regulators involved in the control of heterocyst pattern formation. Heterocysts are microaerobic, N
2
-fixing cells that form in a patterned array within O
2
-producing filamentous cyanobacteria . PatA plays a role in controlling the differentiation process that produces heterocysts . PatA and HetR are believed to be components of the same environment-sensing regulatory circuit in species of
Anabaena
.

Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver (phosphoacceptor) domain and a C-terminal output (usually DNA-binding) domain. Members of this group, however, have the receiver domain in the C-terminal region, and the exact function of the N-terminal domain is not clear yet. In two-component signal transduction systems, in response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator . Phosphorylation of the receiver domain induces conformational changes that activate an associated output domain, which in turn triggers the response. Phosphorylation-induced conformational changes in response regulator molecules have been demonstrated in direct structural studies .
Signal transduction response regulator, citrate/malate metabolism (Sig_transdc_resp-reg_cit/mal)
Type: Family

Members of this group are response regulators containing CheY-like receiver and HTH (helix-turn-helix) DNA-binding domains. Several members of this group have been characterised as response regulators controlling the genes involved in metabolism of citrate or C4-dicarboxylates (aspartate, fumarate, malate, and succinate). In Klebsiella pneumoniae, the phosphorylation of CitB, subsequent conformational changes and increase of apparent DNA-binding affinity (10 to 100-fold), and specific binding to the two sites in the citC-citS intergenic region have been shown experimentally . The DcuS/R system in Escherichia coli is involved in C4-dicarboxylate-stimulated regulation of the genes encoding the anaerobic fumarate respiratory system . The DpiB/A system (synonyms: CriR, CitB, but note that the name CitB can also be used for unrelated proteins) is involved in transcriptional regulation of the cit operon (citrate-specific fermentation genes) and of genes involved in plasmid inheritance .

Response regulators of the microbial two-component signal transduction systems typically consist of an N-terminal CheY-like receiver domain and a C-terminal output (usually DNA-binding) domain . In response to an environmental stimulus, a phosphoryl group is transferred from the His residue of sensor histidine kinase to an Asp residue in the CheY-like receiver domain of the cognate response regulator. Phosphorylation of the CheY-like receiver domain induces conformational changes that activate an associated output domain. Phosphorylation-induced conformational changes in the response regulator molecule have been demonstrated in direct structural studies . In members of this group, these conformational changes affect the binding of the associated HTH domains to their recognition sites on the chromosomal DNA.

HTH domains are very diverse with respect to their sequence, as well as the specific binding sites that they recognise . There have been several attempts to classify them . A detailed sequence analysis of response regulator proteins has been hampered by the remarkable sequence conservation of their N-terminal CheY-like receiver domain, which largely masked (dis)similarities of the DNA-binding domains of various response regulators.

For additional information please see .