SII-SWORD/CoKE huggingface dataset:
GPCR, family 3, metabotropic glutamate receptor 7 (GPCR_3_mGluR7)
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.

GRM7 mRNA has a widespread distribution in many neuronal cells of the central nervous
system, with highest levels in the hippocampal formation, cerebral cortex
and cerebellum ; it is thus different from the more limitedly expressed
GRM4 or GRM6 mRNA . GRM7 and GRM4 are believed to correspond to the
putative L-2-amino-4-phosphonobutyrate receptor, which plays an important
role in modulation of glutamate transmission in the CNS .
Translation elongation factor IF5A-like (IF5A-like)
Type: Family

Eukaryotic eIF-5A was initially thought to function as a translation initiation factor, based on its ability to stimulate methionyl-puromycin synthesis. However, subsequent work revealed a role for eIF5A in translation elongation . Depletion or inactivation of eIF-5A in the yeast Saccharomyces cerevisiae (Baker's yeast) resulted in the accumulation of polysomes and an increase in ribosomal transit times. Addition of recombinant eIF-5A from yeast, but not a derivative lacking hypusine, enhanced the rate of tripeptide synthesis in vitro. Moreover, inactivation of eIF-5A mimicked the effects of the eEF2 inhibitor sordarin, indicating that eIF-5A might function together with eEF2 to promote ribosomal translocation. Finally, it was shown that eIF5A is specifically required to promote peptide-bond formation between consecutive proline residues. It has been proposed to stimulate the peptidyl-transferase activity of the ribosome and facilitate the reactivity of poor substrates like proline .

eIF-5A is a cofactor for the Rev and Rex transactivator proteins of human immunodeficiency virus-1 and T-cell leukaemia virus I, respectively . IF-5A is the sole protein in eukaryotes and archaea to contain the unusual amino acid hypusine (Ne-(4-amino-2-hydroxybutyl)lysine) that is an absolute functional requirement. The first step in the post-translational modification of lysine to hypusine is catalyzed by the enzyme deoxyhypusine synthase, the structure of which has been reported .

This family also includes the Woronin body major protein Hex1, whose sequence and structure are similar to eukaryotic initiation factor 5A (eIF5A), suggesting they share a common ancestor during evolution . Woronin bodies are important for stress resistance and virulence .
Lipoxygenase, mammalian (LipOase_mml)
Type: Family

Lipoxygenases ([ec:1.13.11.-]) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes . Sequence data is available for the following lipoxygenases:

Plant lipoxygenases (

). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme .

Mammalian arachidonate 5-lipoxygenase (

).

Mammalian arachidonate 12-lipoxygenase (

).

Mammalian arachidonate 15-lipoxygenase B (also known as erythroid cell-specific 15-lipoxygenase;

).

The iron atom in lipoxygenases is bound by four ligands, three of which are histidine residues . Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown to be important for the activity of lipoxygenases.

This entry represents mammalian lipoxygenases.
Barnase (Barnase)
Type: Family

Barnase is the extracellular ribonuclease of Bacillus amyloliquefaciens, and barstar its specific intracellular inhibitor . Expression of barstar is necessary to counter the lethal effect of expressed active barnase. Barnase hydrolyses phosphodiester bonds in RNA, poly- and oligo-ribonucleotides, resulting in 3'-nucleoside monophosphates via 2',3'-cyclo-phospate intermediates. It is a small single-chain protein that has neither disulphide bonds nor non-peptide components. The NMR structure contains 2 α-helices and a 5-stranded anti-parallel β-sheet. The protein core is formed by the packing of the first α-helix onto the β-sheet.
Transposase, type 1 (Transposase_1)
Type: Family

Autonomous mobile genetic elements such as transposon or insertion sequences (IS) encode an enzyme, transposase, that is required for excising and inserting the mobile element. Transposases have been grouped into various families . This family includes the mariner transposase .
Herpesvirus thymidine kinase (Herpes_TK)
Type: Family

The thymidine kinase from Herpesviridae catalyses the reaction:

ATP + THYMIDINE = ADP + THYMIDINE 5'-PHOSPHATE.

The enzyme is not subject to feedback inhibition by its product and the crystal structure of the enzyme from Human herpesvirus 1 (HHV-1) has been reported .
RNA-binding, CRM domain (RNA-binding_CRM)
Type: Domain

The CRM domain is an ~100-amino acid RNA-binding domain. The name chloroplast RNA splicing and ribosome maturation (CRM) has been suggested to reflect the functions established for the four characterised members of the family: Zea mays (Maize) CRS1 (

), CAF1 (

) and CAF2 (

) proteins and the Escherichia coli protein YhbY (

). The CRM domain is found in eubacteria, archaea, and plants. The CRM domain is represented as a stand-alone protein in archaea and bacteria, and in single-and multi-domain proteins in plants. It has been suggested that prokaryotic CRM proteins existed as ribosome-associated proteins prior to the divergence of archaea and bacteria, and that they were co-opted in the plant lineage as RNA binding modules by incorporation into diverse protein contexts. Plant CRM domains are predicted to reside not only in the chloroplast, but also in the mitochondrion and the nucleo/cytoplasmic compartment. The diversity of the CRM domain family in plants suggests a diverse set of RNA targets .

The CRM domain is a compact α/β domain consisting of a four-stranded β sheet and three α helices with an α-β-α-β-α-β-β topology. The β sheet face is basic, consistent with a role in RNA binding. Proximal to the basic β sheet face is another moiety that could contribute to nucleic acid recognition. Connecting strand beta1 and helix alpha2 is a loop with a six amino acid motif, GxxG flanked by large aliphatic residues, within which one 'x' is typically a basic residue .

Escherichia coli YhbY is associated with pre-50S ribosomal subunits, which implies a function in ribosome assembly. GFP fused to a single-domain CRM protein from maize localises to the nucleolus, suggesting that an analogous activity may have been retained in plants . A CRM domain containing protein in plant chloroplasts has been shown to function in group I and II intron splicing . In vitro experiments with an isolated maize CRM domain have shown it to have RNA binding activity. These and other results suggest that the CRM domain evolved in the context of ribosome function prior to the divergence of Archaea and Bacteria, that this function has been maintained in extant prokaryotes, and that the domain was recruited to serve as an RNA binding module during the evolution of plant genomes . YhbY has a fold similar to that of the C-terminal domain of translation initiation factor 3 (IF3C), which binds to 16S rRNA in the 30S ribosome .
Malic oxidoreductase (Malic_OxRdtase)
Type: Family

Malic enzymes (malate oxidoreductases) catalyse the oxidative decarboxylation of malate to form pyruvate, a reaction important in a number of metabolic pathways - e.g. carbon dioxide released from the reaction may be used in sugar production during the Calvin cycle of photosynthesis . There are 3 forms of the enzyme : an NAD-dependent form that decarboxylates oxaloacetate; an NAD-dependent form that does not decarboxylate oxalo-acetate; and an NADPH-dependent form. The malic enzyme from Bacillus stearothermophilus is NADPH-dependent, and also catalyses the decarboxylation of oxalacetate . Other proteins known to be similar to malic enzymes are the Escherichia coli scfA protein; an enzyme from Zea mays (Maize), formerly thought to be cinnamyl-alcohol dehydrogenase ; and the hypothetical Saccharomyces cerevisiae protein YKL029c.

Studies on the liver malic enzyme reveals that it can be alkylated by bromopyruvate, resulting in the loss of oxidative decarboxylation and the subsequent enhancement of pyruvate reductase activity . The alkylated form is able to bind NADPH but not L-malate, indicating impaired substrate-or divalent metal ion-binding in the active site . Sequence analysis has highlighted a cysteine residue as the point of alkylation, suggesting that it may play an important role in the activity of the enzyme , although it is absent in the sequences from some species.

There are three well conserved regions in the enzyme sequences. Two of them seem to be involved in the binding NAD or NADP. The significance of the third one, located in the central part of the enzymes, is not yet known.
Small ribosomal subunit protein uS13 (Ribosomal_uS13)
Type: Family

Small ribosomal subunit protein uS13, previously known as Ribosomal protein S13, is one of the proteins from the small ribosomal subunit. In Escherichia coli, it is known to be involved in binding fMet-tRNA and, hence, in the initiation of translation. It is a basic protein of 115 to 177 amino-acid residues that contains thee helices and a β-hairpin in the core of the protein, forming a helix-two turns-helix (H2TH) motif, and a non-globular C-terminal extension. This family of ribosomal proteins is present in prokaryotes, eukaryotes and archaea .

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 .
Cysteine-rich Golgi apparatus protein 1 repeat (Cys-rich_GLG1_repeat)
Type: Repeat

This cysteine rich repeat contains four cysteines. It is found in multiple copies in metazoan proteins, single copies occur in some bacterial species and is absent from the fungi.

The Golgi apparatus protein 1 (GLG1), which is located in Golgi cisterns of various cell types, can bind fibroblast growth factor and E-selectin. Sixteen cysteine-rich GLG1 repeats form the core of the protein and are located in the lumen. The C-terminal part of GLG1 is composed of a transmembrane region and a short cytoplasmic tail. The Cys-rich GLG1 repeat is a ~60 amino acid module that contains 4 Cys residues, which can form intrachain disulphide bridges . Homologues of the vertebrate GLG1/Golgi sialoglycoprotein MG-160 (Mg160)/E-selectin ligand 1 (ESL1)/cysteine-rich fibroblast growth factor receptor 1 (CFR1)/latent transforming growth factor-beta complex protein 1 (LTCP-1) have been found in insects and the nematode Caenorhabditis elegans .
Cathelicidin-like (Cathelicidin-like)
Type: Family

Cathelicidins are antimicrobial peptides and, together with defensins, form a large group of cationic peptides with amphipathic properties,
and are part of the innate immune system in many vertebrates. These peptides exert antimicrobial activity against a wide range of microorganisms such as bacteria, enveloped viruses and fungi. They were first described in bone marrow myeloid cells from mammals but they are also present in several organisms, as antimicrobial peptides are a conserved immune response in all organisms .

Structurally, these proteins consist of a highly conserved N-terminal "cathelin' domain including a signal sequence and a conserved region of about 100 residues that contains four cysteines involved in two disulphide bonds, and a highly divergent C-terminal section of variable size . It is in this C-terminal section that the antibacterial peptides are found; they are proteolytically processed from their precursor by enzymes such as elastase. This structure is shown in the following schematic representation:

+---+--------------------------------+--------------------+
|Sig| Propeptide C C C C | Antibacterial pep. |
+---+----------------|--|--|--|------+--------------------+
| | | |
+--+ +--+
'C': conserved cysteine involved in a disulphide bond.

Cathelicidins-related peptides from reptiles are also included in this family. They are potent antimicrobial peptides with low cytotoxicity, being interesting candidates as antimicrobial agents .
Ras guanine-nucleotide exchange factors catalytic domain (RASGEF_cat_dom)
Type: Domain

This entry represents the catalytic domain of the Ras guanine-nucleotide exchange factors.

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. The balance between the GTP bound (active) and GDP bound (inactive) states is regulated by the opposite action of proteins activating the GTPase activity and that of proteins which promote the loss of bound GDP and the uptake of fresh GTP . The latter proteins are known as guanine-nucleotide exchange (or releasing) factors (GEFs or GRFs) (or also as guanine-nucleotide dissociation stimulators (GDSs)). GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors .

The crystal structure of the GEF region of human Sos1 complexes with Ras has been solved . The structure consists of two distinct α helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. The N-terminal domain is likely to be important for the stability and correct placement of the hairpin structure.

Some proteins known to contain a Ras-GEF domain are listed below:

Cdc25 from yeast.

Scd25 from yeast.

Ste6 from fission yeast.

Son of sevenless (gene sos) from Drosophila and mammals.

p140-RAS GRF (cdc25Mm) from mammals. This protein possesses both a domain belonging to the CDC25 family and one belonging to the CDC24 family.

Bud5 from yeast, that may interact with the ras-like protein RSR1/BUD1.

Lte1 from yeast, whose target protein is not yet known.

ralGDS from mammals, which interacts with the ras-like proteins ralA and ralB .
Plant virus coat protein (Plant_vir_prot)
Type: Family

This family of membrane/coat proteins are found in a number of different ssRNA plant virus families that include Potexvirus, Hordeivirus and Carlavirus.
Porin, gammaproteobacterial (Porin_gammaproteobac)
Type: Family

Porins are found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts, where they form ion-selective channels for small hydrophilic molecules (up to ~600 D) . X-ray structure analyses of several bacterial porins have revealed a 16-stranded anti-parallel β-barrel structure enclosing the transmembrane pore, by contrast with all other integral membrane proteins described to date, which are α-helical. Three subunits form a trimer; the 3-fold axis is approximately parallel to the barrel axes and is assumed to be perpendicular to the membrane plane.

From the range of porins now known, similarities have been observed between porins from different species, and between porins of different specificity within the same species. But most porins cannot be related to each other on the basis of sequence alone, and this is reflected in the lengths of the known porin sequences, which range from 282-483 residues/monomer.

This entry is specific for porins in the gammaproteobacteria.
Solute carrier family 13 (SLC13A/DASS)
Type: Family

Integral membrane proteins that mediate the intake of a wide variety of molecules with the concomitant uptake of sodium ions (sodium symporters) can be grouped, on the basis of sequence and functional similarities into a number of distinct families. The SLC13 family consists mainly of dicarboxylate and sulfate transporters , and includes of the following proteins:

Mammalian sodium/sulphate cotransporter .

Mammalian renal sodium/dicarboxylate cotransporter , which transports succinate and citrate.

Mammalian sodium/citrate cotransporter , which mediates the entry of citrate into cells, which is a critical participant of biochemical pathways .

Mammalian intestinal sodium/dicarboxylate cotransporter.

Chlamydomonas reinhardtii putative sulphur deprivation response regulator SAC1 .

These transporters are proteins of from 430 to 620 amino acids which are highly hydrophobic and which probably contain about 12 transmembrane regions.
Ribonuclease II/R (RNase_II/R)
Type: Domain

This entry represents the catalytic domain of ribonuclease II . It includes characterised and related sequences to exoribonuclease II (RNase II) and ribonuclease R, a bacterial 3' --> 5' exoribonuclease homologous to RNase II .
Protein translocase complex, SecE/Sec61-gamma subunit (Translocase_SecE/Sec61-g)
Type: Family

Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them to the translocase component . From there, the mature proteins are either targeted to the outer membrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial chromosome.

The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integral membrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of the mature peptide into the periplasm (SecD and SecF) . The chaperone protein SecB is a highly acidic homotetrameric protein that exists as a "dimer of dimers" in the bacterial cytoplasm. SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membrane protein ATPase SecA for secretion . SecE, part of the main SecYEG translocase complex, is ~106 residues in length, and spans the inner membrane of the Gram-negative bacterial envelope. Together with SecY and SecG, SecE forms a multimeric channel through which preproteins are translocated, using both proton motive forces and ATP-driven secretion. The latter is mediated by SecA.