SII-SWORD/CoKE huggingface dataset:
DNA-directed RNA polymerase III subunit RPC1 (RPC1)
Type: Family

This entry represents the DNA-directed RNA polymerase III subunit RPC1.

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.
Beta-2-Microglobulin (B2Microglobulin)
Type: Family

Beta-2-microglobulin (Beta2m) constitutes the 12kDa light chain of the class I major histocompatibility complex (MHC-I) on the surface of many cells, to which it is non-covalently associated. It is also found in the serum in a free form. Beta-2-microglobulin co-association with the MHC class I heavy chain is prerequisite for functional expression of the protein complex on the cell surface. Together these function in the presentation of nine amino acid peptides to the T-cell receptor of CD8-bearing T lymphocytes and killer inhibitory receptors on natural killer cells.

Beta2m contains a β-sandwich domain composed of two facing β-sheets (four stranded and three stranded), that is typical of the C-type immunoglobulin superfamily. This structure is stabilized by an intramolecular disulfide bridge connecting two Cys residues in the facing β-sheets .
DNA-directed RNA polymerase, subunit 2 (DNA-dir_RNA_pol_su2)
Type: Family

This entry represents the beta subunit (also referred to as subunit 2) from DNA-dependent RNA polymerases. RNA polymerases catalyse the DNA dependent polymerization of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). Each RNA polymerase complex contains two related members of this family, in each case they are the two largest subunits. The clamp is a mobile structure that grips DNA during elongation .

DNA-directed RNA polymerases

(also known as DNA-dependent RNA polymerases) are responsible for the polymerisation of ribonucleotides into a sequence complementary to the template DNA. In eukaryotes, there are three different forms of DNA-directed RNA polymerases transcribing different sets of genes. Most RNA polymerases are multimeric enzymes and are composed of a variable number of subunits. The core RNA polymerase complex consists of five subunits (two alpha, one beta, one beta-prime and one omega) and is sufficient for transcription elongation and termination but is unable to initiate transcription. Transcription initiation from promoter elements requires a sixth, dissociable subunit called a sigma factor, which reversibly associates with the core RNA polymerase complex to form a holoenzyme . The core RNA polymerase complex forms a "crab claw"-like structure with an internal channel running along the full length . The key functional sites of the enzyme, as defined by mutational and cross-linking analysis, are located on the inner wall of this channel.

RNA synthesis follows after the attachment of RNA polymerase to a specific site, the promoter, on the template DNA strand. The RNA synthesis process continues until a termination sequence is reached. The RNA product, which is synthesised in the 5' to 3' direction, is known as the primary transcript.

Eukaryotic nuclei contain three distinct types of RNA polymerases that differ in the RNA they synthesise:

RNA polymerase I: located in the nucleoli, synthesises precursors of most ribosomal RNAs.

RNA polymerase II: occurs in the nucleoplasm, synthesises mRNA precursors.

RNA polymerase III: also occurs in the nucleoplasm, synthesises the precursors of 5S ribosomal RNA, the tRNAs, and a variety of other small nuclear and cytosolic RNAs.

Eukaryotic cells are also known to contain separate mitochondrial and chloroplast RNA polymerases. Eukaryotic RNA polymerases, whose molecular masses vary in size from 500 to 700kDa, contain two non-identical large (>100kDa) subunits and an array of up to 12 different small (less than 50kDa) subunits.
Transmembrane emp24 domain-containing protein (Emp24-like)
Type: Family

This group of proteins consists of TMP21 (also known as transmembrane emp24 domain-containing protein 10) and related proteins, which are members of the p24 family. The p24 family is a widely conserved family of transmembrane proteins that plays a functional role in the initiation of assembly of COPI (Coat protein I) coated vesicles. COPI coated vesicles are involved in protein transport within the early secretory pathway .

p24 proteins are major membrane components of COPI- and COPII-coated vesicles and are implicated in cargo selectivity of ER to Golgi transport . Multiple members of the p24 family are found in all eukaryotes, from yeast to mammals. Members of the p24 family are type I membrane proteins with a signal peptide at the amino terminus, a lumenal coiled-coil (extracytosolic) domain, a single transmembrane domain with conserved amino acids, and a short cytoplasmic tail. They may be grouped into at least three subfamilies based on primary sequence . One subfamily comprises yeast Emp24p and mammalian p24A. Another subfamily comprises yeast Erv25p and mammalian Tmp21, and the third subfamily comprises mammalian gp25L proteins.
Myosin Light Chain Kinase 1, Kinase domain (MLCK1_kinase_dom)
Type: Domain

Smooth muscle myosin light chain kinase (also known as MLCK1) is a Ser/Thr protein kinase that phosphorylates phosphorylates the 20kDa myosin regulatory light chain (RLC) of smooth and nonmuscle myosin II in the presence of Ca2+ and calmodulin, which facilitates myosin interaction with actin filaments .

In mice, the mylk1 gene is a large gene spanning ~250 kb and comprising at least 31 exons. It encodes at least four protein products: two isoforms of the 220kDa MLCK (also known as endothelial, long, or nonmuscle MLCK), a 130kDa MLCK (also known as short or smooth muscle MLCK), and telokin (also known as kinase-related protein). Transcripts encoding these products are derived from four independent promoters within the gene. Each of the promoters within the mylk1 gene exhibits cell-specific differences in their activity . Both 130kDa and 220kDa MLCK contain a kinase (catalytic) domain, while telokin does not have a kinase domain.
Protein kinase C mu-related (Protein_Kinase_C_mu-related)
Type: Family

The protein kinase D family of enzymes consists of three isoforms: PKD1 (PKCmu), PKD2, and PKD3 (PKCnu). They all share a similar architecture with regulatory sub-domains that play specific roles in the activation, translocation and function of the enzymes. The PKD enzymes have recently been implicated in very diverse cellular functions, including Golgi organisation and plasma membrane directed transport, metastasis, immune responses, apoptosis and cell proliferation . Each isoform is differentially regulated through phosphorylation .

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .
Leucine-rich repeat-containing protein 37 (LRRC37)
Type: Family

This entry represents the leucine-rich repeat-containing protein 37. They are single-pass type I membrane proteins with unknown function.
Ral guanine nucleotide dissociation stimulator, RA domain (RalGDS_RA)
Type: Domain

RalGDS family members can act both as Ras effectors and as guanine nucleotide exchange factors (GEFs) for Ral. They act downstream of Ras and bind to the GTP-bound active form of Ras or Ras family members. They also promote the GDP to GTP exchange for Ral small GTPase, member of the Ras family . Due to their double action, the RalGDS proteins bridge Ras and Ral .

RalGDS belongs to the Ral GDP dissociation stimulator (RalGDS) family . It has been linked to cancer .

This entry represents the RA domain found at the C-terminal end of RalGDS. It has a β-grasp ubiquitin-like fold.
Translation initiation factor IF- 2 (TIF_IF2)
Type: Family

Initiation factor 2 (IF-2) is one of the three factors required for the initiation of protein biosynthesis in bacteria . IF-2 promotes the GTP-dependent binding of the initiator tRNA to the small subunit of the ribosome. IF-2 is a protein of about 70 to 95kDa that contains a central GTP-binding domain flanked by a highly variable N-terminal domain and a more conserved C-terminal domain. Some members of this group undergo protein self splicing that involves a post-translational excision of the intein followed by peptide ligation.

The function of IF-2 in facilitating the proper binding of initiator methionyl-tRNA to the ribosomal P site appears to be universally conserved .
Anti-muellerian hormone receptor, type II (Anti-muellerian_hrmn_rcpt_II)
Type: Family

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process.
Protein kinases fall into three broad classes, characterised with respect to substrate specificity :

Serine/threonine-protein kinases

Tyrosine-protein kinases

Dual specificity protein kinases (e.g. MEK -phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human . Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

Protein kinases are a group of enzymes that possess a catalytic subunit, which transfers the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues (such as serine, threonine, or tyrosine) in a substrate protein's side chain, resulting in a conformational change affecting protein function. Protein kinase function has been evolutionarily conserved from Escherichia coli to Homo sapiens (Human), where they play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation .

The catalytic subunits of protein kinases are highly conserved, and several structures have been solved , leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases .

Anti-Mullerian hormone (AMH), also called Mullerian inhibiting substance, is a member of the transforming growth factor beta (TGF-beta) family that represses the development and function of reproductive organs . Anti-Mullerian hormone is thought to exert its effects through two membrane-bound serine/threonine kinase receptors, type 2 and type 1. Upon ligand binding, these drive receptor-specific cytoplasmic substrates, the Smad molecules, into the nucleus where they act as transcription factors. A type 2 receptor specific for AMH was cloned through its homology with receptors of TGF-beta family members. Components of the AMH signalling pathway have been identified in gonads and gonadal cell lines. The AMH type II receptor is highly specific. In contrast, the identity of the AMH type I receptor is not clear.
Twist-related, basic helix-loop-helix domain (Twist-rel_bHLH)
Type: Domain

The bHLH (basic Helix-Loop-Helix) proteins contain the bHLH domain that is approximately 60 amino acids long and consists of a DNA-binding basic region followed by two α-helices separated by a variable loop region (HLH). The HLH domain promotes dimerisation, allowing the formation of homo- or heterodimeric complexes between different family members. Many bHLH proteins have been shown to act as transcriptional regulators .

Twist was first identified in Drosophila melanogaster as a gene crucial for proper gastrulation and mesoderm formation . Twist is a basic helix-loop-helix transcription factor that acts in a signalling cascade that initiates mesoderm development during gastrulation when it is involved in regulating the process of epithelial-mesenchymal transition (EMT) .

This entry represents the basic helix-loop-helix (bHLH) domain found in Twist and related proteins mainly from invertebrates.
Antimicrobial/protein inhibitor, gamma-crystallin-like (Antimic/Inh_G_crystallin-like)
Type: Homologous_superfamily

This structural domain is found in a family of proteins with a Greek key motif that are related in structure to the beta/gamma crystallins. This group of proteins includes:

Streptomyces killer toxin-like protein SKLP

Antifungal protein, AFP1

Plant antimicrobial protein, MIAMP1

Streptomyces metalloproteinase inhibitor, SMPI .

Note: SMPI belongs to MEROPS inhibitor I36, clan IU. It inhibits members of the thermolysin family, MEROPS peptidase family M4, (

) .
Kinesin light chain repeat (Kinesin_light_repeat)
Type: Repeat

Kinesin is a microtubule-associated force-producing molecular motor protein that transports numerous organelles along mirotubules. Kinesin is an oligomeric complex composed of two heavy chains and two identical light chains. The light chain has been proposed to function in the coupling of cargo to the heavy chain or in the modulation of its ATPase activity. The specificity of kinesin-cargo binding is thought to depend on the type of light chain that a kinesin molecule contains, where different isoforms of kinesin light chains are associated with different types of cargo, mitochondria and membranes of the Golgi complex .

The structure of Drosophila kinesin light chain was shown to have a core composed of a coiled-coil domain followed by five imperfect tandem repeats and a sixth shorter motif . These repeats are highly conserved across species. The N and C termini are more variable and alternative splicing is responsible for the production of isoforms that differ in those two regions.
Pyruvate kinase, barrel (Pyrv_Knase_brl)
Type: Domain

Pyruvate kinase (

) (PK) catalyses the final step in glycolysis , the conversion of phosphoenolpyruvate to pyruvate with concomitant phosphorylation of ADP to ATP:

ADP + phosphoenolpyruvate = ATP + pyruvate

The enzyme, which is found in all living organisms, requires both magnesium and potassium ions for its activity. In vertebrates, there are four tissue-specific isozymes: L (liver), R (red cells), M1 (muscle, heart and brain), and M2 (early foetal tissue). In plants, PK exists as cytoplasmic and plastid isozymes, while most bacteria and lower eukaryotes have one form, except in certain bacteria, such as Escherichia coli, that have two isozymes. All isozymes appear to be tetramers of identical subunits of ~500 residues.

PK helps control the rate of glycolysis, along with phosphofructokinase (

) and hexokinase (

). PK possesses allosteric sites for numerous effectors, yet the isozymes respond differently, in keeping with their different tissue distributions . The activity of L-type (liver) PK is increased by fructose-1,6-bisphosphate (F1,6BP) and lowered by ATP and alanine (gluconeogenic precursor), therefore when glucose levels are high, glycolysis is promoted, and when levels are low, gluconeogenesis is promoted. L-type PK is also hormonally regulated, being activated by insulin and inhibited by glucagon, which covalently modifies the PK enzyme. M1-type (muscle, brain) PK is inhibited by ATP, but F1,6BP and alanine have no effect, which correlates with the function of muscle and brain, as opposed to the liver.

The structure of several pyruvate kinases from various organisms have been determined . The protein comprises three-four domains: a small N-terminal helical domain (absent in bacterial PK), a β/α-barrel domain, a β-barrel domain (inserted within the β/α-barrel domain), and a 3-layer α/β/α sandwich domain.

This entry represents the two barrel domains, the β/α-barrel, and the β-barrel inserted within it.
Pyruvate kinase, C-terminal (Pyrv_Knase_C)
Type: Domain

Pyruvate kinase (

) (PK) catalyses the final step in glycolysis , the conversion of phosphoenolpyruvate to pyruvate with concomitant phosphorylation of ADP to ATP:

ADP + phosphoenolpyruvate = ATP + pyruvate

The enzyme, which is found in all living organisms, requires both magnesium and potassium ions for its activity. In vertebrates, there are four tissue-specific isozymes: L (liver), R (red cells), M1 (muscle, heart and brain), and M2 (early foetal tissue). In plants, PK exists as cytoplasmic and plastid isozymes, while most bacteria and lower eukaryotes have one form, except in certain bacteria, such as Escherichia coli, that have two isozymes. All isozymes appear to be tetramers of identical subunits of ~500 residues.

PK helps control the rate of glycolysis, along with phosphofructokinase (

) and hexokinase (

). PK possesses allosteric sites for numerous effectors, yet the isozymes respond differently, in keeping with their different tissue distributions . The activity of L-type (liver) PK is increased by fructose-1,6-bisphosphate (F1,6BP) and lowered by ATP and alanine (gluconeogenic precursor), therefore when glucose levels are high, glycolysis is promoted, and when levels are low, gluconeogenesis is promoted. L-type PK is also hormonally regulated, being activated by insulin and inhibited by glucagon, which covalently modifies the PK enzyme. M1-type (muscle, brain) PK is inhibited by ATP, but F1,6BP and alanine have no effect, which correlates with the function of muscle and brain, as opposed to the liver.

The structure of several pyruvate kinases from various organisms have been determined . The protein comprises three-four domains: a small N-terminal helical domain (absent in bacterial PK), a β/α-barrel domain, a β-barrel domain (inserted within the β/α-barrel domain), and a 3-layer α/β/α sandwich domain.

This entry represents the 3-layer α/β/α sandwich domain which contains the FBP (fructose 1,6-bisphosphate) binding site . This domain has a similar topology to the archaeal hypothetical protein, MTH1675 from Methanobacterium thermoautotrophicum.
Impact YigZ-like (Impact_YigZ-like)
Type: Family

The Impact protein is a translational regulator that ensures constant high levels of translation under amino acid starvation. It acts by interacting with Gcn1/Gcn1L1, thereby preventing activation of Gcn2 protein kinases (EIF2AK1 to 4) and subsequent down-regulation of protein synthesis. It is evolutionary conserved from eukaryotes to archaea .

This entry represents Impact family members found mostly in bacteria, though there are also some archaeal sequences as well. Crystallography of the Escherichia coli protein YigZ shows a two-domain stucture, where the C-terminal domain is suggested to bind nucleic acids. The function of this proteins is unknown .
NUDIX hydrolase-like domain superfamily (NUDIX_hydrolase-like_dom_sf)
Type: Homologous_superfamily

MutT is a small bacterial protein (~12-15Kd) involved in the GO system responsible for removing an oxidatively damaged form of guanine (8-hydroxy-guanine or 7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool. 8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with near equal efficiency, leading to A-T to G-C transversions. MutT specifically degrades 8-oxo-dGTP to the monophosphate, with the concomitant release of pyrophosphate. A short conserved N-terminal region of mutT (designated the MutT domain) is also found in a variety of other prokaryotic, viral and eukaryotic proteins .

The generic name 'NUDIX hydrolases' (NUcleoside DIphosphate linked to some other moiety X) has been coined for this domain superfamily . The superfamily can be divided into a number of subgroups, of which MutT anti-mutagenic activity represents only one type; most of the rest hydrolyse diverse nucleoside diphosphate derivatives (including ADP-ribose, GDP-mannose, TDP-glucose, NADH, UDP-sugars, dNTP and NTP).