SII-SWORD/CoKE huggingface dataset:
Remodelling complex subunit Rsc/polybromo (Rsc/polybromo)
Type: Family

There are two forms of the RSC remodelling complex in yeast, differing only in whether they contain the Rsc1 or Rsc2 subunits . Rsc1 and Rsc2 have similar structures including two bromodomains and a BAH (Bromo-adjacent homology) domain .

There is only a single orthologue of Rsc1/Rsc2 in human cells, a protein designated BAF180 (or Polybromo), which appears to be a fusion protein of Rsc1, Rsc2 and a third RSC protein, Rsc4. BAF180 contains six bromodomains, followed by two BAH domains and an HMG domain close to the C terminus . BAF180 is a subunit of the PBAF (or SWI/SNF-B) remodelling complex, which affects the transcription of many genes . Many human cancers have mutations in the gene encoding BAF180 .
Coiled-coil domain-containing protein 87 (CCDC87)
Type: Family

The function of this protein is not known.
Coiled-coil domain-containing protein 40 (CCDC40)
Type: Family

Coiled-coil domain containing protein 40 (CCDC40) plays an evolutionary conserved role in the assembly of motile cilia and establishment of the left-right axis . CCDC40 may serve as a part of the axoneme structural scaffold. It has been shown to be required for axonemal recruitment of CCDC39 . CCDC40 mutation is a cause of primary ciliary dyskinesia .
Pentatricopeptide repeat domain-containing protein 3 (PTCD3)
Type: Family

Pentatricopeptide repeat (PPR) domain proteins are involved in mitochondrial gene expression . PPR domain protein 3 (PTCD3, also known as Small ribosomal subunit protein mS39) is a RNA-binding protein that associates with the mitochondrial small ribosomal subunit and regulates translation of mitochondrial encoded proteins .
Kinetochore scaffold 1 (Blinkin)
Type: Family

The KMN network (for KNL1, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore that acts as a receptor for both microtubules and checkpoint proteins . Kinetochore scaffold 1, also known as Blinkin or KNL1, is a component of the KMN network. It is required to localize a subset of outer kinetochore proteins and is essential for chromosome segregation .
Outer dense fibre protein 1 (ODFP)
Type: Family

ODF1 is a component of the outer dense fibres (ODF), which are cytoskeletal structures specifically found in the sperm tails of vertebrates. ODF1 has been assigned to the heat shock protein family based on its overall structural features and especially on its conserved alpha-crystallin domain, and it is also known as HSPB10 . ODF1 is essential for tight linkage of sperm head to tail and is essential for male fertility .
Polyamine-modulated factor 1-binding protein 1 (PMF1-bd)
Type: Family

PMF-1 binding protein, also known as Stap (for sperm-tail-associated protein), is located mainly at the tail of elongated spermatids in the testis of adult fertile mice. It may affect fertility .
YfmP, Helix-Turn-Helix DNA binding domain (YfmP_HTH)
Type: Domain

This entry represents the N-terminal HTH (helix-turn-helix) domain of YfmP and related proteins. YfmP is a a transcription regulator that regulates the multidrug efflux protein, YfmO, and indirectly regulates the expression of the Bacillus subtilis copZA operon encoding a metallochaperone, CopZ, and a CPx-type ATPase efflux protein, CopA . These proteins belong to the MerR superfamily of transcription regulators that promote expression of several stress regulon genes by reconfiguring the spacer between the -35 and -10 promoter elements. Their conserved N-terminal domains contain predicted winged HTH motifs that mediate DNA binding, while the dissimilar C-terminal domains bind specific coactivator molecules .
Bud22/Serum response factor-binding protein 1 (Bud22/SRFB1)
Type: Family

Budding yeast Bud22 is required for rRNA maturation and ribosomal subunit biogenesis . Serum response factor-binding protein 1 (SRFB1) is Bud22 homologue in animals. SRFB1 may be involved in regulating transcriptional activation of cardiac genes during the aging process and may play a role in biosynthesis and/or processing of SLC2A4 in adipose cells .
Protein TBATA-like (TBATA-like)
Type: Family

This family includes uncharacterised protein C4orf17 and TBATA, also known as Spatial or C4orf17-like. TBATA may be involved in spermatid differentiation .
GSK3B-interacting protein (GSKIP)
Type: Family

A-kinase anchoring protein GSKIP is a cytosolic scaffolding protein that binds GSK3B (glycogen synthase kinase 3-beta) and PKA (protein kinase A). Both interactions with GSK3B and PKA are required for the regulation of beta-catenin, and thus Wnt signaling .
FMN hydroxy acid dehydrogenase domain (FMN_HAD)
Type: Domain

A number of oxidoreductases that act on alpha-hydroxy acids and which are FMN-containing flavoproteins have been shown to be structurally related ; these enzymes are:

Lactate dehydrogenase (

), which consists of a dehydrogenase domain and a heme-binding domain called cytochrome b2 and which catalyzes the conversion of lactate into pyruvate.

Glycolate oxidase (

) ((S)-2-hydroxy-acid oxidase), a peroxisomal enzyme that catalyzes the conversion of glycolate and oxygen to glyoxylate and hydrogen peroxide.

Long chain alpha-hydroxy acid oxidase from rat (

), a peroxisomal enzyme.

Lactate 2-monooxygenase (

) (lactate oxidase) from Mycobacterium smegmatis, which catalyzes the conversion of lactate and oxygen to acetate, carbon dioxide and water.

(S)-mandelate dehydrogenase from Pseudomonas putida (gene mdlB), which catalyzes the reduction of (S)-mandelate to benzoylformate.

The first step in the reaction mechanism of these enzymes is the abstraction of the proton from the α-carbon of the substrate producing a carbanion which can subsequently attach to the N5 atom of FMN. A conserved histidine has been shown to be involved in the removal of the proton. Three-dimensional structures of FMN-dependent alpha-hydroxy acid dehydrogenases show a common fold with a TIM barrel structure.

This entry represents the FMN hydroxy acid dehydrogenase domain.
NAD(P)H oxidoreductase RTN4IP1, mitochondrial (RTN4IP1)
Type: Family

This entry describes mitochondrial NAD(P)H oxidoreductase RTN4IP1 proteins found in eukaryotes. In mammals, NAD(P)H oxidoreductase is involved in the ubiquinone biosynthetic pathway. Additionally, it is required for the O-methyltransferase activity of COQ3 . In mice, RTN4IP1 may also play a role in the regulation of retinal ganglion cell (RGC) neurite outgrowth and hence in the development of the inner retina and optic nerve . Caenorhabditis elegans ortolog, mitochondrial reticulon-4-interacting protein 1 (enconded by the rad-8 gene), plays a role in oxygen metabolism in the mitochondria by regulating the levels of reactive oxygen species (ROS), thereby conferring resistance to oxidative stress .
Glucan endo-1,3-beta-glucosidase (Glyco_hydro_64_fam)
Type: Family

Glucan endo-1,3-beta-glucosidase constitutes the glycoside hydrolase family 64. It has beta-1,3-glucanase activity .
Prostaglandin reductase 2 (PTGR2)
Type: Family

Prostaglandins and related eicosanoids are metabolized by the oxidation of the 15(S)-hydroxyl group of the NAD+-dependent (type I 15-PGDH) 15-prostaglandin dehydrogenase (15-PGDH) followed by reduction by NADPH/NADH-dependent (type II 15-PGDH) delta-13 15-prostaglandin reductase (13-PGR) to 15-keto-13,14-dihydroprostaglandins . Prostaglandin reductase 2 (also known as 15-oxoprostaglandin 13-reductase, 13-PGR) is a bifunctional enzyme, since it also has leukotriene B(4) 12-hydroxydehydrogenase activity . It belongs to the MDR/zinc-dependent alcohol dehydrogenase-like family.

The MDR/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH . MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR) . The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a β-α form and an N-terminal catalytic domain with distant homology to GroES .
Malonate utilization transcriptional regulator, PBP2 domain (MdcR_PBP2)
Type: Domain

This entry represents the C-terminal substrate binding domain of LysR-type transcriptional regulator (LTTR) MdcR that controls the expression of the malonate decarboxylase (mdc) genes . Like other members of the LTTRs, MdcR is a positive regulatory protein for its target promoter and composed of two functional domains joined by a linker helix involved in oligomerization: an N-terminal HTH (helix-turn-helix) domain, which is responsible for the DNA-binding specificity, and a C-terminal substrate-binding domain, which is structurally homologous to the type 2 periplasmic binding proteins (PBP2) .

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .
SnoaL-like domain (SnoaL-like)
Type: Domain

This entry represents a SnoaL-like domain that is found in a large number of other sequences. SnoaL is a polyketide cyclase that adopts a distorted α-β barrel fold .
HTH-type transcriptional regulator YidZ, PBP2 domain (YidZ_PBP2)
Type: Domain

This entry represents the C-terminal substrate binding domain of LysR-type transcriptional regulator YidZ, which is involved in anaerobic NO protection . This substrate-binding domain shows significant homology to the type 2 periplasmic binding proteins (PBP2).

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .
HTH-type transcriptional regulator CynR, PBP2 domain (CynR_PBP2)
Type: Domain

CynR is a LysR-like transcriptional regulator of the cyn operon, which encodes genes that allow cyanate to be used as a sole source of nitrogen. The operon includes three genes in the following order: cynT (cyanate permease), cynS (cyanase), and cynX (a protein of unknown function) . CynR negatively regulates its own expression independently of cyanate. CynR binds to DNA and induces bending of DNA in the presence or absence of cyanate, but the amount of bending is decreased by cyanate. CynR, as other LysR-type transcriptional regulators, is composed of two functional domains joined by a linker helix involved in oligomerization: an N-terminal HTH (helix-turn-helix) domain, which is responsible for the DNA-binding specificity, and a C-terminal substrate-binding domain, which is structurally homologous to the type 2 periplasmic binding proteins (PBP2) .

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .
HTH-type transcriptional activator IlvY, PBP2 domain (IlvY_PBP2)
Type: Domain

In Escherichia coli, IlvY is required for the regulation of ilvC gene expression that encodes acetohydroxy acid isomeroreductase (AHIR), a key enzyme in the biosynthesis of branched-chain amino acids (isoleucine, valine, and leucine). The ilvGMEDA operon genes encode remaining enzyme activities required for the biosynthesis of these amino acids . Activation of ilvC transcription by IlvY requires the additional binding of a co-inducer molecule (either alpha-acetolactate or alpha-acetohydoxybutyrate, the substrates for AHIR) to a preformed complex of IlvY protein-DNA . Like many other LysR-family members, IlvY negatively auto-regulates the transcription of its own divergently transcribed ilvY gene in an inducer-independent manner . This substrate-binding domain has significant homology to the type 2 periplasmic binding proteins (PBP2).

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .
HTH-type transcriptional regulator GbpR, PBP2 domain (GbpR_PBP2)
Type: Domain

Galactose-binding protein regulator (GbpR), a member of the LysR family of bacterial transcriptional regulators, regulates the expression of chromosomal virulence gene chvE . The chvE gene is involved in the uptake of specific sugars, in chemotaxis to these sugars, and in the VirA-VirG two-component signal transduction system. In the presence of an inducing sugar such as L-arabinose, D-fucose, or D-galactose, GbpR activates chvE expression, while in the absence of an inducing sugar, GbpR represses expression . The topology of this substrate-binding domain is most similar to that of the type 2 periplasmic binding proteins (PBP2).

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .
HTH-type transcriptional regulator MetR, PBP2 domain (MetR_PBP2)
Type: Domain

MetR, a member of the LysR family, is a positive regulator for the metA, metE, metF, and metH genes . The sulfur-containing amino acid methionine is the universal initiator of protein synthesis in all known organisms and its derivative S-adenosylmethionine (SAM) and autoinducer-2 (AI-2) are involved in various cellular processes. SAM plays a central role as methyl donor in methylation reactions, which are essential for the biosynthesis of phospholipids, proteins, DNA and RNA. The interspecies signaling molecule AI-2 is involved in cell-cell communication process (quorum sensing) and gene regulation in bacteria. Although methionine biosynthetic enzymes and metabolic pathways are well conserved in bacteria, the regulation of methionine biosynthesis involves various regulatory mechanisms. In Escherichia coli and Salmonella enterica serovar Typhimurium, MetJ and MetR regulate the expression of methionine biosynthetic genes . The MetJ repressor negatively regulates the E. coli met genes, except for metH . Several of these genes are also under the positive control of MetR with homocysteine as a co-inducer. In Bacillus subtilis, the met genes are controlled by S-box termination-antitermination system. This substrate-binding domain shows significant homology to the type 2 periplasmic binding proteins (PBP2).

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .
MbtH-like protein (MLP_fam)
Type: Family

MbtH-like proteins (MLPs) are small, bacterial proteins that are nearly always encoded within a nonribosomal peptide biosynthetic gene cluster. MLPs are essential for solubility and/or activity of the nonribosomal peptide synthetases encoded in these gene clusters . MbtH, which gives the name to this family, is the eighth gene in the mycobactin biosynthesis gene cluster in Mycobacterium tuberculosis .
HTH-type transcriptional regulator cbl, PBP2 domain (Cbl_PBP2)
Type: Domain

Cbl is a member of the LysR transcriptional regulators that comprise the largest family of prokaryotic transcription factor. Cbl shows high sequence similarity to CysB, the LysR-type transcriptional activator of genes involved in sulfate and thiosulfate transport, sulfate reduction, and cysteine synthesis . In Escherichia coli, the function of Cbl is required for expression of sulfate starvation-inducible (ssi) genes, coupled with the biosynthesis of cysteine from the organic sulfur sources (sulfonates). The ssi genes include the ssuEADCB and tauABCD operons encoding uptake systems for organosulfur compounds, aliphatic sulfonates, and taurine . The genes in these operons encode an ABC-type transport system required for uptake of aliphatic sulfonates and a desulfonation enzyme. Both Cbl and CysB require expression of the tau and ssu genes. Like many other members of the LTTR family, the Cbl is composed of two functional domains joined by a linker helix involved in oligomerization: an N-terminal HTH (helix-turn-helix) domain, which is responsible for the DNA-binding specificity, and a C-terminal substrate-binding domain, which is structurally homologous to the type 2 periplasmic binding proteins. As also observed in the periplasmic binding proteins, the C-terminal domain of the bacterial transcriptional repressor undergoes a conformational change upon substrate binding which in turn changes the DNA binding affinity of the repressor . The structural topology of this substrate-binding domain is most similar to that of the type 2 periplasmic binding proteins (PBP2).

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .
HTH-type transcriptional regulator XapR, PBP2 domain (XapR_PBP2)
Type: Domain

In Escherichia coli, XapR is a positive regulator for the expression of xapA gene, encoding xanthosine phosphorylase, and xapB gene, encoding a polypeptide similar to the nucleotide transport protein NupG. As an operon, the expression of both xapA and xapB is fully dependent on the presence of both XapR and the inducer xanthosine. Expression of the xapR is constitutive but not auto-regulated, unlike many other LysR family proteins . This substrate-binding domain shows significant homology to the type 2 periplasmic binding proteins (PBP2).

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .
HTH-type transcriptional regulator BudR, PBP2 domain (BudR_PBP2)
Type: Domain

This entry represents the substrate binding domain of BudR regulator, which is responsible for induction of the butanediol formation pathway under fermentative growth conditions. Three enzymes are involved in the production of 1 mol of 2,3 butanediol from the condensation of 2 mol of pyruvate with acetolactate and acetoin as intermediates: acetolactate synthetase, acetolactate decarboxylase, and acetoin reductase. In Klebsiella terrigena, BudR regulates the expression of the budABC operon genes, encoding these three enzymes of the butanediol pathway . In many bacterial species, the use of this pathway can prevent intracellular acidification by diverting metabolism from acid production to the formation of neutral compounds (acetoin and butanediol). This substrate-binding domain has significant homology to the type 2 periplasmic binding proteins (PBP2).

The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction .