SII-SWORD/CoKE huggingface dataset:
G-protein, gamma subunit (G-protein_gamma)
Type: Family

This entry represents the G protein gamma subunit.

Guanine nucleotide binding proteins (G-proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha (

), beta (

) and gamma (

) . G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation . At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go on to activate distinct downstream effectors, such as adenylyl cyclase, phosphodiesterases, phospholipase C, and ion channels. These effectors in turn regulate the intracellular concentrations of secondary messengers, such as cAMP, diacylglycerol, sodium or calcium cations, which ultimately lead to a physiological response, usually via the downstream regulation of gene transcription. The cycle is completed by the hydrolysis of alpha subunit-bound GTP to GDP, resulting in the re-association of the alpha and beta/gamma subunits and their binding to the receptor, which terminates the signal . The length of the G protein signal is controlled by the duration of the GTP-bound alpha subunit, which can be regulated by RGS (regulator of G protein signalling) proteins or by covalent modifications .

G protein alpha subunits are 350-400 amino acids in length and have molecular weights in the range 40-45kDa. Seventeen distinct types of alpha subunit have been identified in mammals. These fall into 4 main groups on the basis of both sequence similarity and function: alpha-S (

), alpha-Q (

), alpha-I (

)and alpha-12(

) .

The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli . G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions.
Kinase associated domain 1 (KA1) (KA1_dom)
Type: Domain

Members of the KIN2/PAR-1/MARK kinase subfamily are conserved from yeast to human and share the same domain organisation: an N-terminal kinase domain (

) and a C-terminal kinase associated domain 1 (KA1). Some members of the KIN1/PAR-1/MARK family also contain an UBA domain (

). Members of this kinase subfamily are involved in various biological processes such as cell polarity, cell cycle control, intracellular signalling, microtubule stability and protein stability . The function of the KA1 domain is not yet known but several studies strongly suggest that it is involved in protein localisation. In addition, it has been reported that this C-terminal region acts as an autoinhibitory domain for the N-terminal kinase domain .

Some proteins known to contain a KA1 domain are listed below:

Mammalian MAP/microtubule affinity-regulating kinases (MARK 1,2,3). They regulate polarity in neuronal cell models and appear to function redundantly in phosphorylating MT-associated proteins and in regulating MT stability .

Mammalian maternal embryonic leucine zipper kinase (MELK). It phosphorylates ZNF622 and may contribute to its redirection to the nucleus. It may be involved in the inhibition of spliceosome assembly during mitosis.

Caenorhabditis elegans and drosophila PAR-1 protein. It is required for establishing polarity in embryos where it is asymmetrically distributed .

Fungal Kin1 and Kin2 protein kinases involved in regulation of exocytosis. They localise to the cytoplasmic face of the plasma membrane .

The KA1 domain comprises about 50 amino acid residues and end in the highly conserved Glu-Leu-Lys-Leu motif, termed the ELKL motif which forms a concave surface surrounded by positively charged residues, being important for the KA1 domain function. This domain adopts a compact α+β structure with a β-α-β-β-β-β-α topology .
Delta/Serrate/lag-2 (DSL) protein (DSL)
Type: Domain

Ligands of the Delta/Serrate/lag-2 (DSL) family and their receptors, members of the lin-12/Notch family, mediate cell-cell interactions that specify cell fate in invertebrates and vertebrates. In Caenorhabditis elegans, two DSL genes, lag-2 and apx-1, influence different cell fate decisions during development . Molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, has been shown and the same two EGF repeats of Notch may also constitute a Serrate binding domain .
GspD/PilQ family (GspD/PilQ)
Type: Family

The general (type II) secretion pathway (Gsp) within Gram-negative bacteria is a signal sequence-dependent process responsible for protein export . The process has two stages: exoproteins are first translocated across the inner membrane by the general signal-dependent export pathway (GEP), and then across the outer membrane by a species-specific accessory mechanism.

A number of proteins are involved in the Gsp; one of these is known as protein D (GspD protein), the most probable location of which is the outer membrane . This suggests that protein D constitutes the apparatus of the accessory mechanism, and is thus involved in transporting exoproteins from the periplasm, across the outer membrane, to the extracellular environment.

This entry represents GspD and close homologues, including the type IV pilus outer membrane secretin PilQ. It also includes virion export protein, which is thought to form a channel across the host outer membrane for the purposes of extruding the bacteriophage.
Large ribosomal subunit protein eL33 (Ribosomal_eL33)
Type: Family

The ribosomal eL33 eukaryotic and archaebacterial ribosomal proteins, previously known as L35A, can be grouped on the basis of sequence similarities. One of these families consists of:

Vertebrate eL33 (old name L35A).

Caenorhabditis elegans eL33 (old name L35A (F10E7.7)).

Saccharomyces cerevisiae eL33A/eL33B (old name L37A/L37B (Rp47)).

Plant eL33 (old name L35A).

Pyrococcus woesei eL33 (old name L35A) homologue .

These proteins have 87 to 110 amino-acid residues.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Flagellar P-ring protein (Flag_FlgI)
Type: Family

The flgH, flgI and fliF genes of Salmonella typhimurium encode the major proteins for the L, P and M rings of the flagellar basal body . In fact, the basal body consists of four rings (L,P,S and M) surrounding the flagellar rod, which is believed to transmit motor rotation to the filament . The M ring is integral to the inner membrane of the cell, and may be connected to the rod via the S (supramembrane) ring, which lies just distal to it. The L and P rings reside in the outer membrane and periplasmic space, respectively.

The sequences of the FlgH, FlgI and FliF gene products have been determined . FlgH and FlgI, which are exported across the cell membrane to their destinations in the outer membrane and periplasmic space, have typical N-terminal cleaved signal-peptide sequences . FlgH is predicted to have an extensive β-sheet structure, in keeping with other outer membrane proteins, and FlgI is thought to have even more β-structure content . Several aspects of the DNA sequence of these genes and their surrounds suggest complex regulation of the flagellar gene system.
Bunyavirus nucleocapsid (N) protein (Bunya_nucleocap)
Type: Family

Orthobunyavirus are enveloped viruses with a genome consisting of 3 ssRNA segments (called L, M and S). The nucleocapsid protein (also known as nucleoprotein) is encoded on the small (S) genomic RNA. The N protein is the major component of the nucleocapsids. This protein is thought to interact with the L protein, virus RNA and/or other N proteins .
GPCR, family 3, metabotropic glutamate receptor 4 (GPCR_3_mGluR4)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

GPCR family 3 receptors (also known as family C) are structurally similar to other GPCRs, but do not show any significant sequence similarity and thus represent a distinct group. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length . Family 3 members include the metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors . As these receptors regulate many important physiological processes they are potentially promising targets for drug development.

The metabotropic glutamate receptors are functionally and pharmacologically distinct from the ionotropic glutamate receptors. They are coupled to G-proteins and stimulate the inositol phosphate/Ca
2+
intracellular signalling pathway . At least eight sub-types of metabotropic receptor (GRM1-8) have been identified in cloning studies. The sub-types differ in their agonist pharmacology and signal transduction pathways.

GRM4 is brain-specific, showing a distinct distribution (excluding the cerebellum), being expressed
in the thalamus, hypothalamus and caudate nucleus . In rat, the strongest
MRM4 mRNA signal is found in the cerebellar granule cells . The principal
difference from rat brain is the presence in human brain of MGR4 mRNA in
the caudate nucleus and putamen . MGR4 inhibits adenylyl cyclase through
a pertussis-toxin-sensitive G-protein, probably of the Gi/Go class.
Large ribosomal subunit protein bL21 (Ribosomal_bL21)
Type: Family

This entry represents the Large ribosomal subunit protein bL21 found in bacteria and eukaryotic organelles such as chloroplast and mitochondria. In Escherichia coli, bL21 is known to bind to the 23S rRNA in the presence of bL20. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups:

Bacterial bL21 (old name L21).

Marchantia polymorpha, chloroplast bL21 (old name L21).

Dictyostelium discoideum, mitochondrial bL21m (old name L21).

Plant, chloroplast bL21c (old name L21, nuclear-encoded) and mitochondrial bL21m (old name L21).

Bacterial bL21 is a protein of about 100 amino-acid residues, the mature form of the spinach chloroplast L21 has 200 residues.
RNA-dependent RNA polymerase, alsuviricetes (RNA-dep_RNA_pol_alsuvir)
Type: Domain

This entry represents the C-terminal domain of RNA dependent RNA polymerases found in Alsuviricetes class of positive-strand RNA viruses that infect eukaryotes , including those with a tripartite genome (RNA1, RNA2 and RNA3) and an encapsidated subgenomic RNA (RNA4) from which the coat protein is expressed, such as Cucumber mosaic virus (strain NT9) (CMV). This entry contains the following proteins:

Viral RNA-directed RNA polymerase 2A (protein 2A) .

Replicase large subunit (also known as RNA-directed RNA polymerase) from Tobacco mosaic virus .

Polyprotein P1234 (also known as Non structural polyprotein) from Alphavirus .

In alphavirus, this region comprises the RdRp domain, which adopts the characteristic right-hand fold of viral RdRps, where fingers-palm-thumb subdomains are sequentially arranged from the amino-to-carboxylic ends .
Signal transduction response regulator, receiver domain (Sig_transdc_resp-reg_receiver)
Type: Domain

The response regulators act as phosphorylation-activated switches to affect a cellular response, usually by transcriptional regulation. Most of these proteins consist of two domains, an N-terminal response regulator receiver domain, and a variable C-terminal effector domain with DNA-binding activity. This entry represents the response regulator receiver domain, which belongs to the CheY family, and receives the signal from the sensor partner in the two-component system.

Bipartite response regulator proteins are involved in a two-component signal transduction system in bacteria, and certain eukaryotes like protozoa, that functions to detect and respond to environmental changes . These systems have been detected during host invasion, drug resistance, motility, phosphate uptake, osmoregulation, and nitrogen fixation, amongst others . The two-component system consists of a histidine protein kinase environmental sensor that phosphorylates the receiver domain of a response regulator protein; phosphorylation induces a conformational change in the response regulator, which activates the effector domain, triggering the cellular response . The domains of the two-component proteins are highly modular, but the core structures and activities are maintained.

Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions . Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk . These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more . Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) . The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.

A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response .
Large ribosomal subunit protein uL10 (Ribosomal_uL10)
Type: Family

This entry represents the large ribosomal subunit protein uL10 family, with includes ribosomal proteins found in bacteria, archaea and eukaryotes as well as in eukaryotic organelles such as chloroplast and mitochondria.

On the basis of sequence similarities the following prokaryotic and eukaryotic ribosomal proteins can be grouped:

Bacterial 50S ribosomal protein uL10 (old name L10);

Archaebacterial acidic ribosomal protein uL10 (old name P0 homologue (L10E));

Eukaryotic 60S ribosomal protein uL10 (old name P0 (L10E)).

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Acylphosphatase-like domain (Acylphosphatase-like_dom)
Type: Domain

Acylphosphatase (

) is an enzyme of approximately 98 amino acid residues that specifically catalyses the hydrolysis of the carboxyl-phosphate bond of acylphosphates , its substrates including 1,3-diphosphoglycerate and carbamyl phosphate . The enzyme has a mainly β-sheet structure with 2 short α-helical segments. It is distributed in a tissue-specific manner in a wide variety of species, although its physiological role is as yet unknown : it may, however, play a part in the regulation of the glycolytic pathway and pyrimidine biosynthesis . There are two known isozymes. One seems to be specific to muscular tissues, the other, called 'organ-common type', is found in many different tissues. A number of bacterial and archebacterial hypothetical proteins are highly similar to that enzyme and that probably possess the same activity.

An acylphosphatase-like domain is also found in some prokaryotic hydrogenase maturation HypF carbamoyltransferases .
Retinal pigment epithelium GPCR (RPE_GPCR)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices .

Retinal pigment epithelium (RPE) hosts a putative GPCR. The RPE-retinal GPCR (RGR) covalently binds all-trans- and 11-cis-retinal after reduction by sodium borohydride . All-trans-retinal is bound preferentially over the 11-cis isomer. The human sequence is 86% identical to that of bovine RGR , and a lysine residue, analogous to the retinaldehyde attachment site of rhodopsin, is conserved in TM domain 7 . The human gene, whose structure is distinct from that of the visual pigment genes, spans 14.8 kb and is split into 7 exons . This suggests that the rgr gene represents the earliest independent branch of the vertebrate opsin gene family . Since the RGR gene product preferentially binds all-trans-retinal, it is thought that one of its functions may be to catalyse isomerisation of the chromophore by a retinochrome-like mechanism .