SII-SWORD/CoKE huggingface dataset:
Ephrin type-A receptor 8, ligand binding domain (EphA8_rcpt_lig-bd)
Type: Domain

This entry represents the ligand-binding domain found in ephrin type-A receptor 8 (EphA8), also known as EEK. EphA8 has been suggested to play a role in axonal pathfinding during nervous system development in mammals , as well as being implicated in cancer .

Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands .

Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) .
Laccase, first cupredoxin domain (CuRO_1_LCC)
Type: Domain

Laccase is a blue multicopper oxidase (MCO) which catalyzes the oxidation of a variety aromatic - notably phenolic and inorganic substances coupled to the reduction of molecular oxygen to water. Laccase has been implicated in a wide spectrum of biological activities and, in particular, plays a key role in morphogenesis, development and lignin metabolism. Plants usually express multiple laccase genes, but their precise physiological/biochemical roles remain largely unclear . In cotton (Gossypium spp.), laccases may be involved in fibre development .

MCOs are capable of oxidizing a vast range of substrates, varying from aromatic compounds to inorganic compounds such as metals. Although the members of this family have diverse functions, majority of them have three cupredoxin domain repeats. The copper ions are bound in several sites: Type 1, Type 2, and/or Type 3. The ensemble of types 2 and 3 copper is called a trinuclear cluster. MCOs oxidize their substrate by accepting electrons at a mononuclear copper centre and transferring them to the active site trinuclear copper centre. The cupredoxin domain 1 of 3-domain MCOs contains part the trinuclear copper binding site, which is located at the interface of domains 1 and 3 .
Laccase, third cupredoxin domain (CuRO_3_LCC)
Type: Domain

Laccase is a blue multicopper oxidase (MCO) which catalyzes the oxidation of a variety aromatic - notably phenolic and inorganic substances coupled to the reduction of molecular oxygen to water. Laccase has been implicated in a wide spectrum of biological activities and, in particular, plays a key role in morphogenesis, development and lignin metabolism. Plants usually express multiple laccase genes, but their precise physiological/biochemical roles remain largely unclear . In cotton (Gossypium spp.), laccases may be involved in fibre development .
Ephrin type-B receptor 4, ligand binding domain (EphB4_rcpt_lig-bd)
Type: Domain

This entry represents the ligand-binding domain found in ephrin type-B receptor 4 (EphB4). EphB4 has been implicated in a number of cancers . It has also been shown to play a role in osteoblast differentiation .

Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands .

Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) .
Thiamine phosphate synthase (TMP_synthase)
Type: Family

Thiamine phosphate synthase (TPS), also known as thiamin phosphate pyrophosphorylase (TMP-PPase), catalyzes the substitution of the pyrophosphate of 2-methyl-4-amino-5- hydroxymethylpyrimidine pyrophosphate by 4-methyl-5- (beta-hydroxyethyl)thiazole phosphate to yield thiamine phosphate in the thiamine biosynthesis pathway . This family includes the thiamine-phosphate pyrophosphorylase, ThiE, of a number of bacteria , and N-terminal domains of bifunctional thiamine proteins of Saccharomyces cerevisiae and Schizosaccharomyces pombe, in which the C-terminal domain corresponds to the bacterial hydroxyethylthiazole kinase ThiM . The plant enzyme is also bifunctional .
Aquaporin transporter (Aquaporin_transptr)
Type: Family

This entry represents the orthodox aquaporins.

Aquaporins are water channels, present in both higher and lower organisms, that belong to the major intrinsic protein family. Most aquaporins are highly selective for water, though some also facilitate the movement of small uncharged molecules such as glycerol . In higher eukaryotes these proteins play diverse roles in the maintenance of water homeostasis, indicating that membrane water permeability can be regulated independently of solute permeability. In microorganisms however, many of which do not contain aquaporins, they do not appear to play such a broad role. Instead, they assist specific microbial lifestyles within the environment, e.g. they confer protection against freeze-thaw stress and may help maintain water permeability at low temperatures . The regulation of aquaporins is complex, including transcriptional, post-translational, protein-trafficking and channel-gating mechanisms that are frequently distinct for each family member.

Structural studies show that aquaporins are present in the membrane as tetramers, though each monomer contains its own channel . The monomer has an overall "hourglass" structure made up of three structural elements: an external vestibule, an internal vestibule, and an extended pore which connects the two vestibules. Substrate selectivity is conferred by two mechanisms. Firstly, the diameter of the pore physically limits the size of molecules that can pass through the channel. Secondly, specific amino acids within the molecule regulate the preference for hydrophobic or hydrophilic substrates.

Aquaporins are classified into two subgroups: the aquaporins (also known as orthodox aquaporins), which transport only water, and the aquaglyceroporins, which transport glycerol, urea, and other small solutes in addition to water .
NADP transhydrogenase beta-like domain (PNTB-like)
Type: Domain

NAD(P) transhydrogenase catalyses the transfer of reducing equivalents between NAD(H) and NADP(H), coupled to the translocation of protons across a membrane . It is an integral membrane protein found in most organisms except for yeasts, plants and some bacterial species. In bacterial species it is located in the cytoplasmic membrane, while in mitochondria it is located in the inner membrane. Under most physiological conditions this enzyme synthesises NADPH, driven by consumption of the proton electrochemical gradient. The resulting NADPH is subsequently used for biosynthetic reactions or the reduction of glutathione.

Bacterial NADP(H) transhydrogenases consist of two subunits, an alpha subunit with an NAD(H)-binding domain and a beta subunit with an NADP(H)-binding domain . This entry corresponds to the beta subunit of NADP transhydrogenase in prokaryotes, and either the protein N- or C-terminal domain in eukaryotes.
Protein Wnt-8A/8C (Protein_Wnt-8A/8C)
Type: Family

Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) . It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals . Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease .

Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the frizzled family; the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in development . Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other .

Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins: a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.

This entry represents proteins Wnt-8A, Wnt-8C and similar sequences from vertebrates.
S-100 (S-100_dom)
Type: Domain

This entry represents the S-100 domain. Proteins containing this domain are belonging to the largest family within the superfamily of proteins carrying the Ca-binding EF-hand motif. S100 proteins are expressed exclusively in vertebrates, and are implicated in intracellular and extracellular regulatory activities. Intracellularly, S100 proteins act as Ca-signaling or Ca-buffering proteins . Many S100 proteins have been found to bind transition metals, such as Zn2+ and Cu2+ .
ROD1, RNA recognition motif 1 (ROD1_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 of ROD1 (also known as polypyrimidine tract-binding protein 3, PTBP3), which is an RNA-binding protein highly expressed in hematopoietic cells . It is a functional homologue of fission yeast Nrd1 and may be involved in differentiation control . It also plays a role in nonsense-mediated mRNA decay (NMD) . Several ROD1 isoforms can be generated by alternative splicing and translation initiation . Rod1 contains four repeats of RNA recognition motifs (RRM).
Glutathione S-transferases, class Zeta , C-terminal (GST_Zeta_C)
Type: Domain

This entry represents the C-terminal domain of the glutathione S-transferase (GST) class Zeta subfamily members.

GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal α helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain .
Uracil phosphoribosyltransferase, archaea (Upp_A)
Type: Family

The enzyme uracil phosphoribosyltransferase (UPRT,

) catalyzes conversion of uracil to uridine 5'-monophosphate utilizing 5'-phosphoribosyl--1-pyrophosphate (PRPP).

UMP + diphosphate = uracil + 5-phospho-alpha-D-ribose 1-diphosphate

This entry includes uracil phosphoribosyltransferase from archaea. In archaea this enzyme is activated by GTP and inhibited by CTP .
Uracil phosphoribosyltransferase, bacterial-type (Upp_B)
Type: Family

The enzyme uracil phosphoribosyltransferase (UPRT,

) catalyzes conversion of uracil to uridine 5'-monophosphate utilizing 5'-phosphoribosyl--1-pyrophosphate (PRPP).

UMP + diphosphate = uracil + 5-phospho-alpha-D-ribose 1-diphosphate

This entry contains uracil phosphoribosyltransferase mainly from bacteria.
Glutathione S-transferases, class Zeta , N-terminal (GST_Zeta_N)
Type: Domain

GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal α helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain .

This entry represents the N-terminal domain of the the glutathione S-transferase (GST) class Zeta subfamily members.
Prostaglandin E synthase 2 (PGES2)
Type: Family

Prostaglandin E synthase 2 is an isomerase that catalyzes the conversion of prostaglandin H2 (PGH2) into the more stable prostaglandin E2 (PGE2) .
Prostaglandin E synthase 2, C-terminal (PGES2_C)
Type: Domain

This entry represents the C-terminal domain of prostaglandin E synthase 2 (also known as membrane-associated prostaglandin E synthase-2, or mPGES2). mPGES2 is a membrane-anchored dimeric protein containing a CXXC motif which catalyzes the isomerization of PGH2 to PGE2. Unlike cytosolic PGE synthase (cPGES) and microsomal PGES Type 1 (mPGES1), mPGES2 does not require glutathione (GSH) for its activity, although its catalytic rate is increased two- to four-fold in the presence of DTT, GSH, or other thiol compounds . PGE2 is widely distributed in various tissues and is implicated in the sleep/wake cycle, relaxation/contraction of smooth muscle, excretion of sodium ions, maintenance of body temperature, and mediation of inflammation .

mPGES2 contains an N-terminal hydrophobic domain which is membrane associated and a C-terminal soluble domain with a GST-like structure. The C-terminal GST-like domain contains two structural domains, an N-terminal thioredoxin-fold domain and a C-terminal α helical domain. The GST active site is located in a cleft between the two structural domains.
Ganglioside-induced differentiation-associated protein 1, C-terminal domain (GST_C_GDAP1)
Type: Domain

GDAP1 belongs to a subfamily of the glutathione S-transferase (GST) family. Mutations of the GDAP1 gene cause Charcot-Marie-Tooth disease (CMT), one of the most frequent inherited peripheral neuropathy in humans . GDAP1 is an integral, tail-anchored protein of the mitochondrial outer membrane (MOM) and the peroxisomal membrane, predominantly expressed in neural cells. The recombinant human GDAP1 has been shown to have specific GSH-conjugating activity in vitro, this activity is regulated by its hydrophobic domain 1 (HD1) . This entry also includes GDAP1L1 (ganglioside-induced differentiation-associated protein 1-like 1), which is a paralogue of GDAP1 . GDAP1L1 is capable of substituting for the loss of GDAP1 in the central nervous system of GDAP1-deficient mice .

Proteins in this entry contains the GST-N and the GST-C domains, and an extended interdomain linker which may adopt two additional α-helices . This is the C-terminal domain of GDAP1.
Glutathione S-transferases, subfamily 4, C-terminal (GST_4_C)
Type: Domain

Glutathione S-transferases (GSTs) are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal α helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain .

This entry represents the C-terminal α helical domain found in subfamily 4 of GST. This subfamily represents a group of mostly uncharacterised bacterial proteins with similarity to GSTs, including YfcF from Escherichia coli. YfcF is reported to have GSH-conjugating activity toward 1-chloro-2,4-dinitorobenzene and GSH-dependent peroxidase activity toward cumene hydroperoxide. It is believe to be important for defense against oxidative stress .
Stringent starvation protein A, N-terminal (SspA_N)
Type: Domain

Stringent starvation protein A (SspA) is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation . SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal α helical domain, but it does not bind glutathione (GSH) and lacks GST activity . SspA is highly conserved among Gram-negative bacteria. Related proteins found in Neisseria (called RegF) , Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis .

This entry represents the N-terminal GST-like thioredoxin (TRX) fold domain of the SspA (stringent starvation protein A) protein.
Stringent starvation protein A, C-terminal (SspA_C)
Type: Domain

This entry represents the C-terminal GST-like α helical domain of the SspA (stringent starvation protein A) protein.

Stringent starvation protein A (SspA) is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation . SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal α helical domain, but it does not bind glutathione (GSH) and lacks GST activity . SspA is highly conserved among Gram-negative bacteria. Related proteins found in Neisseria (called RegF) , Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis .
Gtt2-like, N-terminal (Gtt2-like_N)
Type: Domain

This entry represents the N-terminal GST-like TRX-fold domain found in the budding yeast Gtt2 protein. Gtt2 is a glutathione S-transferase involved in the glutaredoxin-mediated antioxidant activity . Proteins containing this domain also include some bacterial GST-like proteins.
Gtt2-like, C-terminal (Gtt2-like_C)
Type: Domain

This entry represents the C-terminal GST-like α helical domain found in the budding yeast Gtt2 protein. Gtt2 is a glutathione S-transferase involved in the glutaredoxin-mediated antioxidant activity . Proteins containing this domain also include some bacterial GST-like proteins.
Glutathione S-transferases Phi, C-terminal (GST_Phi_C)
Type: Domain

This entry represents the C-terminal α helical domain found in the Phi subfamily (also known as GSTF) of the glutathione S-transferase (GST) family. GSTF had long been regarded as plant specific but has also been found in basidiomycete fungi .

GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal α helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain .
RLI, domain 1 (RLI_dom_1)
Type: Domain

This entry represents an N-terminal domain of the ABC ATPase, RNase L inhibitor (RLI). RLI is also known as ABCE1, which contains two nucleotide-binding domains (NBDs) typical of the ABC transporter protein superfamily ; however, it lacks the transmembrane domains required for membrane transport functions .

RLI is a key enzyme in ribosomal biogenesis, formation of translation pre-initiation complexes, and assembly of HIV capsids . RLI1 was first identified as an endoribonuclease inhibitor that interacts directly with RNase L to prevent it from binding 2-5A (5'-phosphorylated 2',5'-linked oligo- adenylates) . Structurally, RLIs have an N-terminal Fe-S domain and two nucleotide binding domains which are arranged to form two composite active sites in their interface cleft . RLI is one of the most conserved enzymes between archaea and eukaryotes with a sequence identity more than 48%. The high degree of evolutionary conservation suggests that RLI performs a central role in archaeal and eukaryotic physiology.
NUCL, RNA recognition motif 1 (NUCL_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of a group of plant nucleolin-like proteins, including nucleolin 1 (also termed protein nucleolin like 1) and nucleolin 2 (also termed protein nucleolin like 2, or protein parallel like 1). They play roles in the regulation of ribosome synthesis and in the growth and development of plants . Like yeast nucleolin, nucleolin-like proteins possess two RNA recognition motifs (RRMs).
NUCL, RNA recognition motif 2 (NUCL_RRM2)
Type: Domain

This entry represents the RNA recognition motif 2 (RRM2) of a group of plant nucleolin-like proteins, including nucleolin 1 (also termed protein nucleolin like 1) and nucleolin 2 (also termed protein nucleolin like 2, or protein parallel like 1). They play roles in the regulation of ribosome synthesis and in the growth and development of plants . Like yeast nucleolin, nucleolin-like proteins possess two RNA recognition motifs (RRMs).
Nrp1, RNA recognition motif (Nrp1_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of Nrp1 , which contains an RNA recognition motif (RRM), two Ran-binding protein zinc fingers (Znf-RanBP), and an asparagine-rich region. The function of Nrp1 is not clear. It may be involved in ribosome biogenesis .
Rim4/Msa1, RNA recognition motif 1 (Rim4_RRM1)
Type: Domain

This entry represents the RNA recognition motif 1 (RRM1) of Rim4, a putative RNA binding protein that is expressed at elevated levels early in meiosis . It functions as a meiotic activator required for both the IME1- and IME2-dependent pathways of meiotic gene expression, as well as early events of meiosis, such as meiotic division and recombination . RIM4 contains two RNA recognition motifs (RRMs).

Proteins containing this domain also includes Msa1 from Schizosaccharomyces pombe. It may be involved in the inhibition of sexual differentiation by controlling the expression of Ste11-regulated genes, possibly through the pheromone-signaling pathway . Like Rim4, Msa1 also contains two RRMs, both of which are essential for the function of Msa1.
ABT1/ESF2, RNA recognition motif (ABT1/ESF2_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of a novel nuclear protein termed ABT1 and its homologous counterpart, pre-rRNA-processing protein Esf2 (eighteen S factor 2), from yeast.

ABT1 associates with the TATA-binding protein (TBP) and enhances basal transcription activity of class II promoters. Meanwhile, ABT1 could be a transcription cofactor that can bind to DNA in a sequence-independent manner .
Slt11, RNA recognition motif (Slt11_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) of Slt11 (also known as Ecm2), a splicing factor required for spliceosome assembly in yeast. It contains a conserved RNA recognition motif (RRM). Slt11 can facilitate the cooperative formation of U2/U6 helix II in association with stem II in the yeast spliceosome by utilizing its RNA-annealing and -binding activities .
Yra1/Mlo3, RNA recognition motif (Yra1/Mlo3_RRM)
Type: Domain

This entry represents the RNA recognition motifs (RRM) Yra1 and Mlo3 found in budding yeast and fission yeast, respectively.
Vip1, RNA recognition motif (Vip1_RRM)
Type: Domain

This entry represents the RNA recognition motif (RRM) found in Vip1 from Schizosaccharomyces pombe. Its biological role remains unclear. Vip1 contains an N-terminal RNA recognition motif (RRM).