SII-SWORD/CoKE huggingface dataset:
Forkhead box protein G1 (FOXG1)
Type: Family

This entry includes the transforming protein Qin from Avian sarcoma virus, which is homologue of the chicken orthologue of FOXG1, c-qin . It carries transforming activity of the virus.

The FOXG subfamily includes a winged helix transcription factor FOXG1, which is also called brain factor 1 (BF-1), brain factor 2 (BF-2), Forkhead box protein G1A, Forkhead box protein G1B, Forkhead box protein G1C, Forkhead-related protein FKHL1, Forkhead-related protein FKHL2, or Forkhead-related protein FKHL3. FOXG1 acts as a transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon. It is repetitively used in the sequential events of telencephalic development to control multi-steps of brain circuit formation ranging from cell cycle control to neuronal differentiation in a clade- and species-specific manner . Individuals with mutations in FOXG1 harbour "FOXG1-related encephalopathy", characterised by two clinical phenotypes/syndromes including microcephaly, developmental delay, severe cognitive disabilities, early-onset dyskinesia and hyperkinetic movements, stereotypies, epilepsy, and cerebral malformation for those with deletions or intragenic mutations of FOXG1 . FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.
Pyruvate oxidase POXB-like, pyrimidine-binding domain (TPP_PYR_POXB-like)
Type: Domain

This entry represents the PYR-binding domain of pyruvate oxidase (POXB) and similar proteins from bacteria and archaea .

The thiamine pyrophosphate (TPP) family has a thiamin diphosphate-binding fold consisting of two different functional modules, the pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules.

The PYR domain is found in many key metabolic enzymes which use TPP (also known as thiamine diphosphate) as a cofactor . TPP binds in the cleft formed by a PYR domain and a PP domain. The PYR domain, binds the aminopyrimidine ring of TPP, the PP domain binds the diphosphate residue. The PYR and PP domains have a common fold, but do not share strong sequence conservation . Most TPP-dependent enzymes have the PYR and PP domains on the same subunit although these domains can be alternatively arranged in the primary structure . TPP-dependent enzymes are multisubunit proteins, the smallest catalytic unit being a dimer-of-active sites. Lactobacillus plantarum POX is a homotetramer (dimer-of-homodimers), having two active sites per homodimer lying between PYR and PP domains of different subunits . POXB decarboxylates pyruvate, producing hydrogen peroxide and the energy-storage metabolite acetylphosphate . This entry also includes a closely homologous member, pyruvate dehydrogenase [ubiquinone] PoxB from Escherichia coli, a peripheral membrane protein that catalyses the oxidative decarboxylation of the central metabolite pyruvate to CO(2) and acetate. It has pyruvate oxidase as an alternate name .
Pyruvate oxidase/Pyruvate dehydrogenase [ubiquinone]-like (POXB-like)
Type: Family

This family includes a group of proteins from bacteria and archaea, which belong to the thiamine pyrophosphate (TPP family) , such as pyruvate oxidase (POXB) from Lactobacillus plantarum which decarboxylates pyruvate, producing hydrogen peroxide and the energy-storage metabolite acetylphosphate . This entry also includes a closely homologous member, pyruvate dehydrogenase [ubiquinone] PoxB from Escherichia coli, a peripheral membrane protein that catalyses the oxidative decarboxylation of the central metabolite pyruvate to CO(2) and acetate. It has pyruvate oxidase as an alternate name .
Pyruvate oxidase POXB-like, PP-binding domain (TPP_POXB-like)
Type: Domain

This entry represents the PP-binding module found in the C-terminal of pyruvate oxidase (POXB) and similar proteins from bacteria and archaea .

The thiamine pyrophosphate (TPP) family has a thiamin diphosphate-binding fold consisting of two different functional modules, the pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules.

TPP binds in the cleft formed by a PYR domain and a PP domain. The PYR domain (

), binds the aminopyrimidine ring of TPP, the PP domain binds the diphosphate residue. The PYR and PP domains have a common fold, but do not share strong sequence conservation . This entry represents the PP domain. Most TPP-dependent enzymes have the PYR and PP domains on the same subunit although these domains can be alternatively arranged in the primary structure . TPP-dependent enzymes are multisubunit proteins, the smallest catalytic unit being a dimer-of-active sites. Lactobacillus plantarum POX is a homotetramer (dimer-of-homodimers), having two active sites per homodimer lying between PYR and PP domains of different subunits . POXB decarboxylates pyruvate, producing hydrogen peroxide and the energy-storage metabolite acetylphosphate . This entry also includes a closely homologous member, pyruvate dehydrogenase [ubiquinone] PoxB from Escherichia coli, a peripheral membrane protein that catalyses the oxidative decarboxylation of the central metabolite pyruvate to CO(2) and acetate. It has pyruvate oxidase as an alternate name .
Pyruvate decarboxylase/indolepyruvate decarboxylase-like, pyrimidine-binding domain (TPP_PYR_PDC_IPDC-like)
Type: Domain

The thiamine pyrophosphate (TPP) family has a thiamin diphosphate-binding fold consisting of two different functional modules, the pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules. This entry represents the PYR-binding domain found at the N-terminal of pyruvate decarboxylase (PDC), indolepyruvate decarboxylase (IPDC) and related proteins .

The PYR domain is found in many key metabolic enzymes which use TPP (also known as thiamine diphosphate) as a cofactor . TPP binds in the cleft formed by a PYR domain and a PP domain. The PYR domain, binds the aminopyrimidine ring of TPP, the PP domain binds the diphosphate residue. The PYR and PP domains have a common fold, but do not share strong sequence conservation. Most TPP-dependent enzymes have the PYR and PP domains on the same subunit although these domains can be alternatively arranged in the primary structure. TPP-dependent enzymes are multisubunit proteins, the smallest catalytic unit being a dimer-of-active sites, for many the active sites lie between PP and PYR domains on different subunits.
Pyruvate decarboxylase/indolepyruvate decarboxylase-like, PP-binding domain (TPP_PDC_IPDC)
Type: Domain

The thiamine pyrophosphate (TPP) family has a thiamin diphosphate-binding fold consisting of two different functional modules, the pyridine-binding (Pyr) and pyrophosphate-binding (PP) modules. This entry represents the PP-binding module found at the C-terminal of pyruvate decarboxylase (PDC), indolepyruvate decarboxylase (IPDC) and related proteins from the thiamine pyrophosphate (TPP) family .

TPP binds in the cleft formed by a PYR domain (

) and a PP domain. The PYR domain, binds the aminopyrimidine ring of TPP, the PP domain binds the diphosphate residue. The PYR and PP domains have a common fold, but do not share strong sequence conservation. Most TPP-dependent enzymes have the PYR and PP domains on the same subunit although these domains can be alternatively arranged in the primary structure. TPP-dependent enzymes are multisubunit proteins, the smallest catalytic unit being a dimer-of-active sites, for many the active sites lie between PP and PYR domains on different subunits.
Galactose mutarotase-like (Galactose_mutarotase-like)
Type: Family

Galactose mutarotase (also known as aldose 1-epimerase) catalyses the conversion of beta-D-galactose to alpha-D-galactose . Beta-D-galactose is produced by the degradation of lactose, a disaccharide composed of beta-D-glucose and beta-D-galactose. This epimerization reaction is the first step in the four-step Leloir pathway, which converts galactose into metabolically important glucose . This epimerization step is followed by the phosphorylation of alpha-D-galactose by galactokinase, an enzyme which can only act on the alpha anomer. A glutamate and a histidine residue of the galactose mutarotase have been shown to be critical for catalysis, the glutamate serves as the active site base to initiate the reaction by removing the proton from the C-1 hydroxyl group of the sugar substrate, and the histidine as the active site acid to protonate the C-5 ring oxygen .

This entry includes the bifunctional protein GAL10 from yeasts, whose C-terminal domain has galactose mutarotase/aldose 1-epimerase activity . The uncharacterised isomerases YNR071C and YHR210C from Saccharomyces cerevisiae are also included in this entry, which are putative aldose 1-epimerases.
Putative endonuclease DUF559, bacteria (Endonuclease_DUF559_bact)
Type: Domain

This entry represents the DUF559 found mainly in bacteria, including the uncharacterised proteins HI_1162/HI_0925 from Haemophilus influenzae and YcjD from Escherichia coli. It is a putative endonuclease of unknown function, which belongs to a superfamily of nucleases including very short patch repair (Vsr) endonucleases, archaeal Holliday junction resolvases, MutH methyl-directed DNA mismatch-repair endonucleases, and catalytic domains of many restriction endonucleases, such as EcoRI, BamHI, and FokI.
Signal peptide peptidase A, N-terminal (S49_SppA_67K_type_N)
Type: Domain

This entry represents the N-terminal domain of the 67K type serine protease Signal peptide peptidase A (SppA) from Escherichia coli and similar proteins predominantly found in plants and bacteria.

Signal peptide peptidase A is involved in the cleavage of signal peptides after their removal from the precursor proteins by signal peptidases. Members in this entry contain an N-terminal domain in addition to the C-terminal protease domain that is conserved in all the S49 family members (sometimes referred to as 67K type), as found in E. coli and Arabidopsis thaliana SppA peptidases .

Unlike the eukaryotic functional homologues that are proposed to be aspartic proteases, site-directed mutagenesis and sequence analysis have shown that members in this subfamily, mostly bacterial, are serine proteases. The predicted active site serine for members in this entry occurs in a transmembrane domain. Mutagenesis studies also suggest that the catalytic centre comprises a Ser-Lys dyad (both residues absolutely conserved within bacteria, chloroplast and mitochondrial signal peptidase family members) and not the usual Ser-His-Asp catalytic triad found in the majority of serine proteases. Interestingly, the single membrane spanning E. coli SppA carries out catalysis using a Ser-Lys dyad with the serine located in the C-terminal protease domain and the lysine in the N-terminal domain. The N- and C-terminal halves of SppA in E. coli are tandem repeats .
Uncharacterized sodium-dependent transporter YocR/YhdH-like (YocR/YhdH-like)
Type: Family

This family includes a group of prokaryotic proteins that belong to the sodium:neurotransmitter symporter family, including Uncharacterized sodium-dependent transporter YocR and YhdH from Bacillus subtilis. Member of this entry appear to contain 11 transmembrane (TM) helices .
Histone-lysine N-methyltransferase 2A/2B, SET domain (KMT2A_2B_SET)
Type: Domain

This entry represents the SET domain of Histone-lysine N-methyltransferase 2A/B (KMT2A/B) and KMT2B. Both act as histone methyltransferases that methylate 'Lys-4' of histone H3 (H3K4me), which represents a specific tag for epigenetic transcriptional activation. Abnormal expression of KMT2B has been associated with early-onset generalized dystonia . The homologue of KMT2A in Drosophila melanogaster is also named Histone-lysine N-methyltransferase trithorax.
HTH-type transcriptional activator RhaR/RhaS, N-terminal domain (RhaR_RhaS-like_N)
Type: Domain

This entry represents the N-terminal cupin domain found in the HTH-type transcription activators RhaS and RhaRan similar sequences predominantly found in Proteobacteria. RhaS and RhaR respond to the availability of L-rhamnose and activate transcription of the operons in the Escherichia coli L-rhamnose catabolic regulon. The E. coli RhaR protein activates expression of the rhaSR operon in the presence of its effector, L-rhamnose. The resulting RhaS protein (plus L-rhamnose) activates expression of the L-rhamnose catabolic operon rhaBAD as well as the transport operon rhaT. These proteins bind DNA as dimers, via their HTH motifs in the C-terminal domain (

). Proteins in this family belong to the cupin superfamily with a conserved "jelly roll-like" β-barrel fold capable of homodimerisation .
Circadian clock protein kinase KaiC, N-terminal domain (KaiC_N)
Type: Domain

KaiC is a circadian clock protein, most studied in cyanobacteria. KaiC, an autokinase, autophosphatase, and ATPase, is part of the core oscillator, composed of three proteins: KaiA, KaiB, and KaiC. The circadian oscillation is regulated via KaiC phosphorylation .
Circadian clock protein kinase KaiC, C-terminal domain (KaiC_C)
Type: Domain

KaiC is a circadian clock protein, most studied in cyanobacteria. KaiC, an autokinase, autophosphatase, and ATPase, is part of the core oscillator, composed of three proteins: KaiA, KaiB, and KaiC. The circadian oscillation is regulated via KaiC phosphorylation .

This entry represents the C-terminal domain of KaiC and similar bacterial proteins.
Carbonic anhydrase, gamma-class, LbH domain (CA_gamma_LbH)
Type: Domain

Carbonic anhydrases (CA) are zinc-containing enzymes that catalyse the reversible hydration of carbon dioxide in a two-step mechanism, involving the nucleophilic attack of a zinc-bound hydroxide ion on carbon dioxide, followed by the regeneration of the active site by ionization of the zinc-bound water molecule and removal of a proton from the active site. They are ubiquitous enzymes involved in fundamental processes like photosynthesis, respiration, pH homeostasis and ion transport. There are three distinct groups of carbonic anhydrases: alpha, beta and gamma, which show no significant sequence identity or structural similarity .

CAs are homotrimeric enzymes, with each subunit containing a left-handed parallel β-helix (LbH) structural domain, which is represented in this entry . It is found at the N-terminal the cyanobacterial Carboxysome assembly protein CcmM, while the archaeal Carbonic anhydrase (CAH) only has this domain.
Fatty acid synthase subunit alpha-like, C-terminal (FAS_alpha_su_C)
Type: Domain

This entry represents the C-terminal domain found in fatty acid synthase subunit alpha and similar sequences from fungi and bacteria. These "elongating" condensing enzymes are a subclass of decarboxylating condensing enzymes characterised by the utilisation of acyl carrier protein (ACP) thioesters as primer substrates, as well as the nature of their active site residues .
GRAF, PH domain (PH_GRAF)
Type: Domain

This entry represents the PH domain of GRAF family of proteins.

Graf is an essential component of the CLIC (clathrin-independent carrier)/GEEC (GPI-anchored protein-enriched early endocytic compartment) endocytic pathway . It plays a critical role during development; it is essential for normal mushroom body (MB) development and, therefore, the formation of olfactory long-term memories . During embryo cellularization, it is required for maintaining and regulating the rate of actomyosin ring constriction .

OPHN1 is a RhoGAP involved in X-linked mental disabilities, epilepsy, rostral ventricular enlargement, and cerebellar hypoplasia. Affected individuals have morphological abnormalities of their brain with enlargement of the cerebral ventricles and cerebellar hypoplasia. OPHN1 negatively regulates RhoA, Cdc42, and Rac1 in neuronal and non-neuronal cells . GRAF1 sculpts the endocytic membranes of the CLIC/GEEC (clathrin-independent carriers/GPI-enriched early endosomal compartments) endocytic pathway. It strongly interacts with dynamin and inhibition of dynamin abolishes CLIC/GEEC endocytosis . Its mutations are linked to leukaemia. GRAF2, GRAF3 and oligophrenin are likely to play similar roles during clathrin-independent endocytic events .
RNA-binding protein MEX-3, second type I KH domain (KH-I_MEX3_rpt2)
Type: Domain

This entry represents the second type I KH domain of MEX3 proteins.

The MEX-3 protein family includes four members, MEX3A/RKHD4, MEX3B/RKHD3/RNF195, MEX3C/ RKHD2/RNF194, and MEX3D/RKHD1/RNF193/TINO . They are homologous of Caenorhabditis elegans MEX-3 protein, a translational regulator that specifies the posterior blastomere identity in the early embryo and contributes to the maintenance of the germline totipotency . MEX-3 proteins are RNA-binding phosphoproteins involved in post-transcriptional regulatory mechanisms . It has been shown that these proteins are deregulated in several cancers and affects apoptosis regulation, antigen processing, and presentation, which, therefore, contribute to the immune evasion of tumour cells .

They are characterised by containing two K-homology (KH) RNA-binding domains and a C-terminal RING finger . They bind RNA through their KH domains and shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway .
RNA-binding protein MEX3 (MEX3)
Type: Family

The MEX-3 protein family includes four members, MEX3A/RKHD4, MEX3B/RKHD3/RNF195, MEX3C/ RKHD2/RNF194, and MEX3D/RKHD1/RNF193/TINO . They are homologous of Caenorhabditis elegans MEX-3 protein, a translational regulator that specifies the posterior blastomere identity in the early embryo and contributes to the maintenance of the germline totipotency . MEX-3 proteins are RNA-binding phosphoproteins involved in post-transcriptional regulatory mechanisms . It has been shown that these proteins are deregulated in several cancers and affects apoptosis regulation, antigen processing, and presentation, which, therefore, contribute to the immune evasion of tumour cells .

They are characterised by containing two K-homology (KH) RNA-binding domains and a C-terminal RING finger . They bind RNA through their KH domains and shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway .
RNA-binding protein MEX-3, first type I KH domain (KH-I_MEX3_rpt1)
Type: Domain

This entry represents the first type I KH domain of MEX3 proteins.

The MEX-3 protein family includes four members, MEX3A/RKHD4, MEX3B/RKHD3/RNF195, MEX3C/ RKHD2/RNF194, and MEX3D/RKHD1/RNF193/TINO . They are homologous of Caenorhabditis elegans MEX-3 protein, a translational regulator that specifies the posterior blastomere identity in the early embryo and contributes to the maintenance of the germline totipotency . MEX-3 proteins are RNA-binding phosphoproteins involved in post-transcriptional regulatory mechanisms . It has been shown that these proteins are deregulated in several cancers and affects apoptosis regulation, antigen processing, and presentation, which, therefore, contribute to the immune evasion of tumour cells .

They are characterised by containing two K-homology (KH) RNA-binding domains and a C-terminal RING finger . They bind RNA through their KH domains and shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway .
Nuclear factor interleukin-3-regulated protein-like (NFIL3-like)
Type: Family

This entry represents a group of proteins from animals that belong to the bZIP family of transcription factors, including NFIL3 . This protein family also includes the orthologue of human NFIL3 in Caenorhabditis elegans transcription factor atf-2 .

Nuclear factor interleukin-3-regulated protein (NFIL3, also known as E4BP4) was first identified as a transcriptional repressor capable of binding an activating transcription factor (ATF) DNA consensus sequence site in the adenovirus E4 promoter . Later, it was independently identified as a transactivator of the IL3 promoter in human T cells .

E4BP4 is involved in a several biological processes, including transcriptional control of the circadian clock, neuron growth and survival, osteoblast function, and regulation of ovulation . It is essential for the development of NK cells and CD8alpha(+) conventional dendritic cells, and is also involved in macrophage activation, polarisation of CD4(+) T cell responses and B cell class switching to IgE .
Circadian locomoter output cycles protein kaput-like (CLOCK-like)
Type: Family

This entry represents a group of animal proteins related to core components of the circadian clock, including the human proteins circadian locomoter output cycles protein kaput (CLOCK), neuronal PAS domain-containing protein 2 (NPAS2) and the circadian clock protein PASD1.

CLOCK and NPAS2 are core clock components. CLOCK is a transcriptional activator that also has an intrinsic acetyltransferase activity, which enables circadian chromatin remodelling by acetylating histones and nonhistone proteins, including its own partner BMAL1 . NPAS2 mediates the diurnal variation in the expression of GABARA1 receptor in the brain and contributes to the regulation of anxiety-like behaviors and GABAergic neurotransmission in the ventral striatum .

PASD1 functions as a nuclear repressor of the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock components, acting as a suppressor of the biological clock that drives the daily circadian rhythms of cells throughout the body .
Histone-lysine N-methyltransferase SETDB1/2-like, methyl-CpG binding domains (SETDB1/2-like_MBD)
Type: Domain

This entry represents the methyl-CpG binding domains (MBD) of SETDB1/2 and similar animal proteins. This group of proteins also includes the SETDB1 homologues Histone-lysine N-methyltransferase eggless from Drosophila melanogaster , and Histone-lysine N-methyltransferase met-2 Caenorhabditis elegans .

SETDB1 is a member of the histone-lysine N-methyltransferase Suvar3-9 subfamily. Members of this subfamily trimethylate 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones . This enzyme mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. It probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation .

SETDB2 is a histone methyltransferase involved in left-right axis specification in early development and mitosis. It specifically trimethylates 'Lys-9' of histone H3 (H3K9me3), a specific tag for epigenetic transcriptional repression that recruits HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. SETDB2 contributes to H3K9me3 in both the interspersed repetitive elements and centromere-associated repeats. This protein plays a role in chromosome condensation and segregation during mitosis .
Ureidoglycolate amidohydrolase, cupin domain (UAH_cupin)
Type: Domain

This entry represents the cupin domain of ureidoglycolate amidohydrolase and related proteins predominantly found in fungi and bacteria.

Ureidoglycolate lyase (

) is involved in the degradation of ureidoglycolate, an intermediate of purine degradation. It breaks down (S)-ureidoglycolate to produce glyoxylate and urea . This family of ureidoglycolate lyases were initially annotated as ureidoglycolate hydrolases, but this has since been corrected .