SII-SWORD/CoKE huggingface dataset:
Melanin-concentrating hormone receptor (MCH_rcpt)
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 .

Melanin-concentrating hormone (MCH) is a cyclic peptide originally identified in teleost fish . In fish, MCH is released from the pituitary and causes lightening of skin pigment cells through pigment aggregation. In mammals, MCH is predominantly expressed in the hypothalamus, and functions as a neurotransmitter in the control of a range of functions. A major role of MCH is thought to be in the regulation of feeding: injection of MCH into rat brains stimulates feeding; expression of MCH is upregulated in the hypothalamus of obese and fasting mice; and mice lacking MCH are lean and eat less. MCH and alpha melanocyte-stimulating hormone (alpha-MSH) have antagonistic effects on a number of physiological functions. Alpha-MSH darkens pigmentation in fish and reduces feeding in mammals, whereas MCH increases feeding .

Two G protein-coupled receptors, MCH1 and MCH2, have recently been identified as receptors for the melanin-concentrating hormone.
Melanin-concentrating hormone receptor 2 (MCHR2)
Type: Family

This entry represents a group of proteins from vertebrates, including human Melanin-concentrating hormone receptor 2 (MCHR2 or MCH2).

Melanin-concentrating hormone (MCH) is a cyclic peptide originally identified in teleost fish . In fish, MCH is released from the pituitary and causes lightening of skin pigment cells through pigment aggregation. In mammals, MCH is predominantly expressed in the hypothalamus, and functions as a neurotransmitter in the control of a range of functions. A major role of MCH is thought to be in the regulation of feeding: injection of MCH into rat brains stimulates feeding; expression of MCH is upregulated in the hypothalamus of obese and fasting mice; and mice lacking MCH are lean and eat less. MCH and alpha melanocyte-stimulating hormone (alpha-MSH) have antagonistic effects on a number of physiological functions. Alpha-MSH darkens pigmentation in fish and reduces feeding in mammals, whereas MCH increases feeding .

Two G protein-coupled receptors, MCH1 and MCH2, have recently been identified as receptors for the melanin-concentrating hormone.

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 .

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 .
Paraoxonase1 (Paraoxonase1)
Type: Family

The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysis of the toxic metabolites of a variety of organophosphorus insecticides. The enzymes hydrolyse a broad spectrum of organophosphate substrates, including paraoxon and a number of aromatic carboxylic acid esters (e.g., phenyl acetate), and hence confer resistance to organophosphate toxicity .

Mammals have 3 distinct paraoxonase types, termed PON1-3 . In mice and humans, the PON genes are found on the same chromosome in close proximity. PON activity has been found in variety of tissues, with highest levels in liver and serum -the source of serum PON is thought to be the liver. Unlike mammals, fish and avian species lack paraoxonase activity.

Human and rabbit PONs appear to have two distinct Ca2+ binding sites, one required for stability and one required for catalytic activity. The Ca2+ dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as the electrophillic catalyst, like that proposed for phospholipase A2. The paraoxonase enzymes, PON1 and PON3, are high density lipoprotein (HDL)-associated proteins capable of preventing oxidative modification of low density lipoproteins (LPL) . Although PON2 has oxidative properties, the enzyme does not associate with HDL.

Within a given species, PON1, PON2 and PON3 share ~60% amino acid sequence identity, whereas between mammalian species particular PONs (1,2 or 3) share 79-90% identity at the amino acid level. Human PON1 and PON3 share numerous conserved phosphorylation and N-glycosylation sites; however, it is not known whether the PON proteins are modified at these sites, or whether modification at these sites is required for activity in vivo .

Rabbit and human serum PON1 also hydrolyse a variety of lactones and cyclic carbonate esters, including naturally occurring lactones and pharmacological agents . Humans have 2 common PON1 allozymes, determined by the presence of either arginine or glutamine at position 191. The A-type allozyme (glutamine at position 191) causes low paraoxonase activity ; this polymorphism is associated with variations in cholesterol and lipoprotein levels.
Paraoxonase2 (Paraoxonase2)
Type: Family

The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysis of the toxic metabolites of a variety of organophosphorus insecticides. The enzymes hydrolyse a broad spectrum of organophosphate substrates, including paraoxon and a number of aromatic carboxylic acid esters (e.g., phenyl acetate), and hence confer resistance to organophosphate toxicity .

Mammals have 3 distinct paraoxonase types, termed PON1-3 . In mice and humans, the PON genes are found on the same chromosome in close proximity. PON activity has been found in variety of tissues, with highest levels in liver and serum -the source of serum PON is thought to be the liver. Unlike mammals, fish and avian species lack paraoxonase activity.

Human and rabbit PONs appear to have two distinct Ca2+ binding sites, one required for stability and one required for catalytic activity. The Ca2+ dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as the electrophillic catalyst, like that proposed for phospholipase A2. The paraoxonase enzymes, PON1 and PON3, are high density lipoprotein (HDL)-associated proteins capable of preventing oxidative modification of low density lipoproteins (LPL) . Although PON2 has oxidative properties, the enzyme does not associate with HDL.

Within a given species, PON1, PON2 and PON3 share ~60% amino acid sequence identity, whereas between mammalian species particular PONs (1,2 or 3) share 79-90% identity at the amino acid level. Human PON1 and PON3 share numerous conserved phosphorylation and N-glycosylation sites; however, it is not known whether the PON proteins are modified at these sites, or whether modification at these sites is required for activity in vivo .
Prostanoid receptor (Prostanoid_rcpt)
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 .

Prostanoids (prostaglandins (PG) and thromboxanes (TX)) mediate a wide variety of actions and play important physiological roles in the cardiovascular and immune systems, and in pain sensation in peripheral systems. PGI2 and TXA2 have opposing actions, involving regulation of the interaction of platelets with the vascular endothelium, while PGE2, PGI2 and PGD2 are powerful vasodilators and potentiate the action of various autocoids to induce plasma extravasation and pain sensation. To date, evidence for at least 5 classes of prostanoid receptor has been obtained. However, identification of subtypes and their distribution is hampered by expression of more than one receptor within a tissue, coupled with poor selectivity of available agonists and antagonists.
Nuclear factor of activated T cells (NFAT) (NFAT)
Type: Family

Antigenic stimulation of T lymphocytes initiates a complex series of intracellular signal transduction pathways that leads to the expression of a panel of immunoregulatory genes, whose function is critical to the initiation and coordination of the immune response. The multi-subunit nuclear factor of activated T cells (NFAT) transcription factor family plays a pivotal role in this process and is involved in the expression of a number of immunologically important genes. These include the cytokines IL-2, IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, and tumour necrosis factor-alpha, as well as several cell-surface molecules, such as CD40L and FasL. Although originally described in T cells, it is now apparent that NFAT proteins are also expressed in other immune system cells, including B cells, mast cells, basophils and natural killer cells, as well as in a variety of non-immune cell types and tissues, such as skeletal muscle, neurons, heart and adipocytes. However, although NFAT acts as a calcium-dependent transcription factor and serves to couple gene expression to changes in intracellular calcium levels in most cases, NFAT target genes have not been identified in these latter cell types.

NFAT proteins appear to be regulated primarily at the level of their subcellular localisation . They are found exclusively in the cytoplasm of resting T cells, and consist of 2 components: a pre-existing cytoplasmic component that translocates into the nucleus on calcium mobilisation, and an inducible nuclear component comprising members of the activating protein-1 (AP-1) family of transcription factors. In response to antigen receptor signalling, the calcium-regulated phosphatase calcineurin acts directly to dephosphorylate NFAT proteins, causing their rapid translocation from the cytoplasm to the nucleus, where they cooperatively bind their target.
Regucalcin (Regucalcin)
Type: Family

Regucalcin, also known as senesence marker protein-30 (SMP30), was discovered in 1978 as a Ca
2+
binding protein that does not contain EF-hand motifs, suggesting a novel class of Ca
2+
binding protein. It is primarily localised to the liver and kidney cortex of animals. Expression of its mRNA in the liver and renal cortex of rats is stimulated by an increase in cellular Ca
2+
levels .

Regucalin, as a regulatory protein of Ca
2+
, has a pivotal role in the control of many cell functions. The protein has a reversible effect on Ca
2+
-induced activation and inhibition of many enzymes in both the liver and renal cortex cells . It has also been shown to inhibit various protein kinases (including Ca
2+
/calmodulin-dependent protein kinase , protein kinase C and tyrosine kinase) and protein phosphatases, indicating a regulatory role in signal transduction within the cell. In addition, regucalcin regulates intracellular Ca
2+
homeostasis by enhancing Ca2+-pumping activity in the plasma membrane through activation of the pump enzymes . Moreover, it can inhibit RNA synthesis in the nuclei of normal and regenerating rat livers in vitro .

Hydropathy profiles indicate hydrophobic domains in both N-and C-terminal regions of the regucalcin molecule; the protein also exhibits hydrophilic characteristics . Human and rodent regucalcins share 89% sequence identity, the high degree of conservation between species suggesting that the complete structure is required for physiological function.
Voltage-dependent calcium channel, gamma subunit (VDCC_gsu)
Type: Family

Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins . The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.

Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.

The voltage-dependent calcium channel gamma (VDCCG) subunit family consists of at least 8 members, which share a number of common structural features . Each member is predicted to possess 4 transmembrane domains, with intracellular N-and C-termini. The first extracellular loop contains a highly conserved N-glycosylation site and a pair of conserved cysteine residues. The C-terminal 7 residues of VDCCG-2, -3, -4 and -8 are also conserved and contain a consensus site for phosphorylation by cAMP and cGMP-dependent protein kinases, and a target site for binding by PDZ domain proteins .
Voltage-dependent calcium channel, gamma-5 subunit (VDCC_g5su)
Type: Family

Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins . The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.

Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.

The voltage-dependent calcium channel gamma (VDCCG) subunit family consists of at least 8 members, which share a number of common structural features . Each member is predicted to possess 4 transmembrane domains, with intracellular N-and C-termini. The first extracellular loop contains a highly conserved N-glycosylation site and a pair of conserved cysteine residues. The C-terminal 7 residues of VDCCG-2, -3, -4 and -8 are also conserved and contain a consensus site for phosphorylation by cAMP and cGMP-dependent protein kinases, and a target site for binding by PDZ domain proteins .

The VDCCG-5 subunit was identified by genomic database searching, pursuing sequences similar to VDCCG-1 and -2. Mouse, human and rat isoforms have been cloned. VDCCG-5 is expressed in a range of tissues, including brain, kidney and testis .
Voltage-dependent calcium channel, gamma-6 subunit (VDCC_g6su)
Type: Family

Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins . The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.

Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.

The voltage-dependent calcium channel gamma (VDCCG) subunit family consists of at least 8 members, which share a number of common structural features . Each member is predicted to possess 4 transmembrane domains, with intracellular N-and C-termini. The first extracellular loop contains a highly conserved N-glycosylation site and a pair of conserved cysteine residues. The C-terminal 7 residues of VDCCG-2, -3, -4 and -8 are also conserved and contain a consensus site for phosphorylation by cAMP and cGMP-dependent protein kinases, and a target site for binding by PDZ domain proteins .

The VDCCG-6 subunit was identified by high throughput genomic sequence database searching, pursuing sequences similar to VDCCG-1 to -5 . Mouse, human and rat isoforms have been cloned. VDCCG-6 is expressed in a range of tissues including brain, kidney, lung, skeletal muscle, prostate and testis .