SII-SWORD/CoKE huggingface dataset:
Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase (Ser/Thr-sp_prot-phosphatase)
Type: Domain

Protein phosphorylation plays a central role in the regulation of cell functions , causing the activation or inhibition of many enzymes involved in various biochemical pathways . Kinases and phosphatases are the enzymes responsible for this, and may themselves be subject to control through the action of hormones and growth factors . Serine/threonine (S/T) phosphatases (

) catalyse the dephosphorylation of phosphoserine and phosphothreonine residues. In mammalian tissues four different types of PP have been identified and are known as PP1, PP2A, PP2B and PP2C. Except for PP2C, these enzymes are evolutionary related. The catalytic regions of the proteins are well conserved and have a slow mutation rate, suggesting that major changes in these regions are highly detrimental .

Protein phosphatase-1 (PP1) and protein phosphatase-2A (PP2A) have a broad specificity and there are two closely related isoforms of each, alpha and beta. PP2A is a trimeric enzyme that consists of a core composed of a catalytic subunit associated with a 65kDa regulatory subunit and a third variable subunit. Protein phosphatase-2B (PP2B or calcineurin), a calcium-dependent enzyme whose activity is stimulated by calmodulin, is composed of two subunits the catalytic A-subunit and the calcium-binding B-subunit. The specificity of PP2B is restricted. Other serine/threonine specific protein phosphatases that have been characterised include mammalian phosphatase-X (PP-X), and Drosophila phosphatase-V (PP-V), which are closely related but yet distinct from PP2A; yeast phosphatase PPH3, which is similar to PP2A, but with different enzymatic properties; and Drosophila phosphatase-Y (PP-Y), and yeast phosphatases Z1 and Z2 which are closely related but yet distinct from PP1.
Claudin (Claudin)
Type: Family

Claudins form the paracellular tight junction seal in epithelial tissues. In humans, 24 claudins (claudin 1-24) have been identified. Their ability to polymerise and form strands is affected by the cell types . They can also form heteropolymers with each other within and between tight junction strands . Most of the claudins (claudin-12 being the exception) have a C-terminal PDZ-binding motif that can interact with other PDZ domain proteins, such as scaffolding protein, ZO-1, -2 and -3 . They also interact with non-tight junction proteins, such as cell adhesion proteins EpCam and tetraspanins and the signaling proteins, ephrin A and B and their receptors, EphA and EphB .
CHASE domain (CHASE_dom)
Type: Domain

The CHASE domain is an extracellular domain of 200-230 amino acids, which is found in transmembrane receptors from bacteria, lower eukaryotes and plants. It has been named CHASE (Cyclases/Histidine Kinases Associated Sensory Extracellular) because of its presence in diverse receptor-like proteins with histidine kinase and nucleotide cyclase domains. It is found at the N-terminal in extracellular or periplasmic locations, followed by an intracellular tail housing diverse enzymatic signalling domains such as histidine kinase (

), adenyl cyclase, GGDEF-type nucleotide cyclase, and EAL-type phosphodiesterase domains, as well as non-enzymatic domains such as PAS (

), GAF (

), phosphohistidine, and response regulatory domains. This domain is predicted to bind diverse low molecular weight ligands, such as cytokinin-like adenine derivatives or peptides, and mediate signal transduction through the respective receptors . It has a predicted α+β fold, with two extended α helices on both boundaries and two central α helices separated by β sheets. The N-terminal and C-terminal regions are less conserved compared with the central part of the domain, which shows strongly conserved motifs.
Antifreeze-like/N-acetylneuraminic acid synthase, SAF domain (SAF_AFP_Neu5Ac)
Type: Domain

This entry represents the SAF domain at the C-terminal in AFPs.

Antifreeze proteins (AFPs) are defined by their ability to bind ice and prevent it from growing. In this way they function in both freeze-resistance and freeze-tolerance strategies of organisms that live at sub-zero temperatures and require protection from ice growth. In fish, five AFP types have been described that are remarkably diverse in their 3D structures. They have completely dissimilar folds and no sequence homology. Type III AFPs found in eelpouts are 65-residue proteins with a compact globular fold formed from short β-strands, which presents a flat ice binding surface. These proteins are homologous to the C-terminal region of mammalian and prokaryotic sialic acid synthase (SAS; gene neuB), which has been called AFP-like domain . The similarity is greatest in the protein core and the flat ice-binding region. SAS is involved in the condensation of phosphoenolpyruvate with N-acetylmannosamine derivatives to generate N-acetylneuraminic acid, an intermediate used for the sialylation of glycoconjugates. The function of the AFP-like domain, which is a β-clip fold , in SAS is not known, but it has been proposed that it could be involved in sugar binding.
Glycine-tRNA synthetase, heterodimeric (Gly-tRNA-synth_heterodimer)
Type: Family

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

Glycyl-tRNA synthetase exhibits different oligomeric structures in different organisms (alpha2 beta2 and alpha2) . This entry represents the alpha and beta subunits of heterodimeric glycine-tRNA synthetases.
Aminoacyl-tRNA synthetase, class II (aa-tRNA-synth_II)
Type: Domain

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .

This entry recognises all class-II enzymes except for heterodimeric glycyl-tRNA synthetases

and alanyl-
tRNA synthetases.
RNA-binding domain, S1, IF1 type (RNA-binding_domain_S1_IF1)
Type: Domain

The S1 domain of around 70 amino acids, originally identified in ribosomal protein S1, is found in a large number of RNA-associated proteins. It has been shown that S1 proteins bind RNA through their S1 domains with some degree of sequence specificity. This type of S1 domain is found in translation initiation factor 1.

The solution structure of one S1 RNA-binding domain from Escherichia coli polynucleotide phosphorylase has been determined . It displays some similarity with the cold shock domain (CSD) (

). Both the S1 and the CSD domain consist of an antiparallel β barrel of the same topology with 5 β strands. This fold is also shared by many other proteins of unrelated function and is known as the OB fold. However, the S1 and CSD fold can be distinguished from the other OB folds by the presence of a short 3(10) helix at the end of strand 3. This unique feature is likely to form a part of the DNA/RNA-binding site.

This entry is specific for bacterial, chloroplastic and eukaryotic IF-1 type S1 domains.
Peptidase S24, LexA-like (Peptidase_S24_LexA)
Type: Family

This signature defines serine peptidases belong to MEROPS peptidase family S24 (LexA family, clan SF). They include:

LexA, the repressor of genes in the cellular SOS response to DNA damage

MucA and the related UmuD proteins, which are lesion-bypass DNA polymerases, induced in response to mitogenic DNA damage

RumA a plasmid encoded homologue of UmuD

RuvA, which is a component of the RuvABC resolvasome that catalyses the resolution of Holliday junctions that arise during genetic recombination and DNA repair

The LexA, UmuD and MucD proteins interact with RecA, which activates self cleavage either derepressing transcription in the case of LexA or activating the lesion-bypass polymerase in the case of UmuD and MucA. UmuD'2, is the homodimeric component of DNA pol V, which is produced from UmuD by RecA-facilitated self-cleavage. The first 24 N-terminal residues of UmuD are removed; UmuD'2 is a DNA lesion bypass polymerase . MucA , like UmuD, is a plasmid encoded a DNA polymerase (pol RI) which is converted into the active lesion-bypass polymerase by a self-cleavage reaction involving RecA .

This group of proteins also contains proteins classified as non-peptidase homologues as they either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for catalytic activity.
LexA repressor, DNA-binding domain (LexA_DNA-bd_dom)
Type: Domain

The LexA SOS regulon repressor prevents the expression of DNA repair proteins in bacteria. This entry represents the DNA-binding domain, which contains a variant form of the helix-turn-helix DNA
binding motif .
Transcription regulator LexA (LexA)
Type: Family

LexA acts as a homodimer to repress a number of genes involved in the response to DNA damage (SOS response), including itself and RecA. RecA, in the presence of single-stranded DNA, acts as a co-protease to activate a latent autolytic protease activity (

) of LexA, where the active site Ser is part of LexA. The autolytic cleavage site is an Ala-Gly bond in LexA (at position 84-85 in E. coli LexA; this sequence is replaced by Gly-Gly in Synechocystis). The cleavage leads to derepression of the SOS regulon and eventually to DNA repair. LexA in Bacillus subtilis is called DinR. LexA is much less broadly distributed than RecA .
Neurotransmitter-gated ion-channel (Neur_channel)
Type: Family

The receptors are composed of varying numbers and types of subunit. Each subunit contains a large extracellular N-terminal ligand-binding region; 3 hydrophobic transmembrane domains; a large intracellular region; and a fourth hydrophobic domain. The GABA, acetylcholine, serotonin 5HT3 and glycine receptors share a degree of sequence similarity, but differ from the glutamate receptors - sequences of this family possess 2 Cys residues in the N-terminal domain, which, in nicotinic receptors, form a disulphide bond essential for correct folding of the structure .

This entry includes the subunits of the GABA-A, nicotinic, glycine, glutamate and 5HT3 receptors.

Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses . Five of these ion channel receptor families have been shown to form a sequence-related superfamily:

Nicotinic acetylcholine receptor (AchR), an excitatory cation channel in vertebrates and invertebrates; in vertebrate motor endplates it is composed of alpha, beta, gamma and delta/epsilon subunits; in neurons it is composed of alpha and non-alpha (or beta) subunits .

Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits .

Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known .

Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7) .

Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) .

These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence .
Neurotransmitter-gated ion-channel ligand-binding domain (Neur_chan_lig-bd)
Type: Domain

This entry presents the extracellular ligand binding domain of these ion channels. This domain forms a pentameric arrangement in the known structure.

Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses . Five of these ion channel receptor families have been shown to form a sequence-related superfamily:

Nicotinic acetylcholine receptor (AchR), an excitatory cation channel in vertebrates and invertebrates; in vertebrate motor endplates it is composed of alpha, beta, gamma and delta/epsilon subunits; in neurons it is composed of alpha and non-alpha (or beta) subunits .

Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits .

Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known .

Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7) .

Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) .

These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence .
GHMP kinase, ATP-binding, conserved site (GHMP_knse_ATP-bd_CS)
Type: Conserved_site

The galacto- (

), homoserine (

), mevalonate (

) and phosphomevalonate (

) kinases contain, in their N-terminal section, a conserved Gly/Ser-rich region which is probably involved in the binding of ATP . This group of kinases has been called 'GHMP' (from the first letter of their substrates).

This site is also found in some diphosphomevalonate decarboxylases, which are structurally related members of the GHMP superfamily , but do not possess kinase activity.
GHMP kinase N-terminal domain (GHMP_kinase_N_dom)
Type: Domain

The galacto- (

), homoserine (

), mevalonate (

) and phosphomevalonate (

) kinases contain, in their N-terminal section, a conserved domain with a Gly/Ser-rich region which is involved in the binding of ATP . This group of kinases has been called 'GHMP' (from the first letter of their substrates).
Mevalonate kinase (Mev_gal_kin)
Type: Family

Mevalonate kinase is well-characterised among eukaryotes, where it plays a role in the synthesis of isopentanyl pyrophosphate, a common intermediate for a number of pathways including cholesterol biosynthesis. It is also involved in mevalonate catabolism . Close homologues are found in archaea. Related bacterial proteins are also included in this entry.
Mevalonate/galactokinase (Mevalonate/galactokinase)
Type: Family

Mevalonate kinase (

) and galactokinases (

) belong to this family. Mevalonate kinase may be a regulatory site in the cholesterol biosynthetic pathway. It is also involved in mevalonate catabolism. Galactokinase takes part in the first reaction of galactose metabolism by converting galactose to galactose-1-phosphate.
Cystine knot, C-terminal (Cys_knot_C)
Type: Domain

Four recent crystal structures of growth factors--nerve growth factor, transforming growth factor-beta, platelet-derived growth factor, and human chorionic gonadotropin--from four separate superfamilies revealed that these proteins are structurally related and share a common overall topology . These proteins have very little sequence homology, but they all have an unusual arrangement of six cysteines linked to form a "cystine-knot" conformation. The active forms of these proteins are dimers, either homo- or heterodimers . Because of their shape, there appears to be an intrinsic requirement for the cystine-knot growth factors to form dimers. This extra level of organisation increases the variety of structures built around this simple structural motif .
Glycoprotein hormone subunit beta (Glyco_hormone_CN)
Type: Domain

This domain is found at the C-terminal of glycoprotein hormones and various extracellular proteins. It is believed to be involved in disulphide-linked dimerisation .
Furin-like cysteine-rich domain (Furin-like_Cys-rich_dom)
Type: Domain

The furin-like cysteine rich region has been found in a variety of proteins from eukaryotes that are involved in the mechanism of signal transduction by receptor tyrosine kinases, which involves receptor aggregation .
Furin-like repeat (Furin_repeat)
Type: Repeat

The furin-like cysteine rich region has been found in a variety of proteins from eukaryotes that are involved in the mechanism of signal transduction by receptor tyrosine kinases, which involves receptor aggregation .
Bax inhibitor 1, conserved site (Bax_inhbtr1_CS)
Type: Conserved_site

Bax inhibitor-1 (BI-1) (gene TEGT) is a suppressor of apoptosis that interacts with BCL2 and BCL-X. These are proteins of about 25kDa which seem to contain seven transmembrane domains. Homologues are found in plants and bacteria.

This entry corresponds to a conserved region that starts with the beginning of the third transmembrane domain and ends in the middle of the fourth one.
Bax inhibitor 1-related (Bax_inhibitor_1-related)
Type: Family

This entry represents BI-1 and related sequences, including lifeguard proteins, which resemble BI-1 and also act as apoptotic regulators .

Bax inhibitor-1 (BI-1) is a suppressor of apoptosis that interacts with BCL2 and BCL-X. Human Bax BI-1 is an evolutionarily conserved integral membrane protein containing multiple membrane-spanning segments localised to the ER membrane. It has 6-7 membrane-spanning domains. The C termini of the mammalian BI-1 proteins are comprised of basic amino acids resembling some nuclear targeting sequences, but otherwise the predicted proteins lack motifs that suggest this function. BI-1 also regulates cell death triggered by ER stress . BI-1 appears to exert its effect through an interaction with calmodulin . Crystal structure of a bacterial member reveals that these proteins mediate a calcium leak across the membrane in a pH-dependent manner. Calcium homoeostasis balances passive calcium leak with active calcium uptake. The structure exists in a pore-closed and pore-open conformation, at pHs of 8 and 6 respectively .
Glycoside hydrolase, melibiase (Glyco_hydro_melibiase)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Families 27 (

) and 36 (

) encompasses alpha-galactosidases and alpha-N-acetylgalactosaminidases in which two conserved Asp residues may be involved in the catalytic mechanism. Alpha-galactosidase (melibiase) catalyses the hydrolysis of melibiose into galactose and glucose . In man, deficiency in the enzyme results in Fabry's disease (X-linked sphingolipidosis). Alpha-N-acetylgalactosaminidase catalyses the hydrolysis of terminal non-reducing N-acetyl-D-galactosamine residues in N-acetyl-alpha-D-galactosaminides . Deficiency in this enzyme results in Schindler and Kanzaki diseases.

This group identifies specifically melibiase.