SII-SWORD/CoKE huggingface dataset:
Transient receptor potential channel, canonical 3 (TRPC3_channel)
Type: Family

Transient receptor potential (TRP) channels can be described as tetramers formed by subunits with six transmembrane domains and containing cation-selective pores, which in several cases show high calcium permeability. The molecular architecture of TRP channels is reminiscent of voltage-gated channels and comprises six putative transmembrane segments (S1-S6), intracellular N-and C-termini, and a pore-forming reentrant loop between S5 and S6 .

TRP channels represent a superfamily conserved from worms to humans that comprise seven subfamilies : TRPC (canonical), TRPV (vanilloid), TRPM (melastatin or long TRPs), TRPA (ankyrin, whose only member is Transient receptor potential cation channel subfamily A member 1, TrpA1), TRPP (polycystin), TRPML (mucolipin) and TRPN (Nomp-C homologues), which has a single member that can be found in worms, flies, and zebrafish. TRPs are classified essentially according to their primary amino acid sequence rather than selectivity or ligand affinity, due to their heterogeneous properties and complex regulation.

TRP channels are involved in many physiological functions, ranging from pure sensory functions, such as pheromone signalling, taste transduction, nociception, and temperature sensation, over homeostatic functions, such as Ca2+ and Mg2+ reabsorption and osmoregulation, to many other motile functions, such as muscle contraction and vaso-motor control .

The classical or canonical TRPC family (formerly short-TRPs, STRPs) encompasses channels presenting a large number of different activation modes. Some are store-operated, whereas others are receptor-operated channels activated by the production of diacylglicerol or redox processes. TRPC proteins also control growth cone guidance in both mammalian and amphibian model systems. All seven channels of this family share the common property of activation through phospholipase C (PLC)-coupled receptors . It is believed that functional TRPC channels are generated in situ by association of four TRPC proteins to form either homotetramers or heterotetramers .

On the basis of sequence similarity, TRPC channels can be subdivided into four subgroups group 1 (TRPC1), group 2 (TRPC2), group 3 (TRPC3, TRPC6 and TRPC7) and group 4 (TRPC4 and TRPC5) . While TRPC1 and TRPC2 are almost unique, TRPC4 and TRPC5 share approx. 65% identity. TRPC3, 6 and 7 form a structural and functional subfamily sharing 70-80% identity at the amino acid level and their common sensitivity towards diacylglycerol (DAG).

TRPC3, 6, and 7 interact physically and, upon coexpression, coassemble to form functional tetrameric channels .

TRPC3 is likely to be operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. It is activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C, and by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3 . High levels of TRPC3 mRNA have been related to elevated salt intake and increased blood pressure .
Transient receptor potential channel, canonical 4 (TRPC4_channel)
Type: Family

Transient receptor potential (TRP) channels can be described as tetramers formed by subunits with six transmembrane domains and containing cation-selective pores, which in several cases show high calcium permeability. The molecular architecture of TRP channels is reminiscent of voltage-gated channels and comprises six putative transmembrane segments (S1-S6), intracellular N-and C-termini, and a pore-forming reentrant loop between S5 and S6 .

TRP channels represent a superfamily conserved from worms to humans that comprise seven subfamilies : TRPC (canonical), TRPV (vanilloid), TRPM (melastatin or long TRPs), TRPA (ankyrin, whose only member is Transient receptor potential cation channel subfamily A member 1, TrpA1), TRPP (polycystin), TRPML (mucolipin) and TRPN (Nomp-C homologues), which has a single member that can be found in worms, flies, and zebrafish. TRPs are classified essentially according to their primary amino acid sequence rather than selectivity or ligand affinity, due to their heterogeneous properties and complex regulation.

TRP channels are involved in many physiological functions, ranging from pure sensory functions, such as pheromone signalling, taste transduction, nociception, and temperature sensation, over homeostatic functions, such as Ca2+ and Mg2+ reabsorption and osmoregulation, to many other motile functions, such as muscle contraction and vaso-motor control .

The classical or canonical TRPC family (formerly short-TRPs, STRPs) encompasses channels presenting a large number of different activation modes. Some are store-operated, whereas others are receptor-operated channels activated by the production of diacylglicerol or redox processes. TRPC proteins also control growth cone guidance in both mammalian and amphibian model systems. All seven channels of this family share the common property of activation through phospholipase C (PLC)-coupled receptors . It is believed that functional TRPC channels are generated in situ by association of four TRPC proteins to form either homotetramers or heterotetramers .

On the basis of sequence similarity, TRPC channels can be subdivided into four subgroups group 1 (TRPC1), group 2 (TRPC2), group 3 (TRPC3, TRPC6 and TRPC7) and group 4 (TRPC4 and TRPC5) . While TRPC1 and TRPC2 are almost unique, TRPC4 and TRPC5 share approx. 65% identity. TRPC3, 6 and 7 form a structural and functional subfamily sharing 70-80% identity at the amino acid level and their common sensitivity towards diacylglycerol (DAG).

TRPC4 and TRPC5 are thought to be receptor-operated, Ca2+-permeable, nonselective cation channels. It is likely that heteromultimers of TRPC1 and TRPC4 or TRPC5 form receptor-operated nonselective cation channels in central neurones, and that TRPC4 contributes to nonselective cation channels in intestinal smooth muscle .
Transient receptor potential channel, canonical 5 (TRPC5_channel)
Type: Family

Transient receptor potential (TRP) channels can be described as tetramers formed by subunits with six transmembrane domains and containing cation-selective pores, which in several cases show high calcium permeability. The molecular architecture of TRP channels is reminiscent of voltage-gated channels and comprises six putative transmembrane segments (S1-S6), intracellular N-and C-termini, and a pore-forming reentrant loop between S5 and S6 .

TRP channels represent a superfamily conserved from worms to humans that comprise seven subfamilies : TRPC (canonical), TRPV (vanilloid), TRPM (melastatin or long TRPs), TRPA (ankyrin, whose only member is Transient receptor potential cation channel subfamily A member 1, TrpA1), TRPP (polycystin), TRPML (mucolipin) and TRPN (Nomp-C homologues), which has a single member that can be found in worms, flies, and zebrafish. TRPs are classified essentially according to their primary amino acid sequence rather than selectivity or ligand affinity, due to their heterogeneous properties and complex regulation.

TRP channels are involved in many physiological functions, ranging from pure sensory functions, such as pheromone signalling, taste transduction, nociception, and temperature sensation, over homeostatic functions, such as Ca2+ and Mg2+ reabsorption and osmoregulation, to many other motile functions, such as muscle contraction and vaso-motor control .

The classical or canonical TRPC family (formerly short-TRPs, STRPs) encompasses channels presenting a large number of different activation modes. Some are store-operated, whereas others are receptor-operated channels activated by the production of diacylglicerol or redox processes. TRPC proteins also control growth cone guidance in both mammalian and amphibian model systems. All seven channels of this family share the common property of activation through phospholipase C (PLC)-coupled receptors . It is believed that functional TRPC channels are generated in situ by association of four TRPC proteins to form either homotetramers or heterotetramers .

On the basis of sequence similarity, TRPC channels can be subdivided into four subgroups group 1 (TRPC1), group 2 (TRPC2), group 3 (TRPC3, TRPC6 and TRPC7) and group 4 (TRPC4 and TRPC5) . While TRPC1 and TRPC2 are almost unique, TRPC4 and TRPC5 share approx. 65% identity. TRPC3, 6 and 7 form a structural and functional subfamily sharing 70-80% identity at the amino acid level and their common sensitivity towards diacylglycerol (DAG).

TRPC4 and TRPC5 are thought to be receptor-operated, Ca2+-permeable, nonselective cation channels. It is likely that heteromultimers of TRPC1 and TRPC4 or TRPC5 form receptor-operated nonselective cation channels in central neurones, and that TRPC4 contributes to nonselective cation channels in intestinal smooth muscle .
Transient receptor potential channel, canonical 6 (TRPC6_channel)
Type: Family

Transient receptor potential (TRP) channels can be described as tetramers formed by subunits with six transmembrane domains and containing cation-selective pores, which in several cases show high calcium permeability. The molecular architecture of TRP channels is reminiscent of voltage-gated channels and comprises six putative transmembrane segments (S1-S6), intracellular N-and C-termini, and a pore-forming reentrant loop between S5 and S6 .

TRP channels represent a superfamily conserved from worms to humans that comprise seven subfamilies : TRPC (canonical), TRPV (vanilloid), TRPM (melastatin or long TRPs), TRPA (ankyrin, whose only member is Transient receptor potential cation channel subfamily A member 1, TrpA1), TRPP (polycystin), TRPML (mucolipin) and TRPN (Nomp-C homologues), which has a single member that can be found in worms, flies, and zebrafish. TRPs are classified essentially according to their primary amino acid sequence rather than selectivity or ligand affinity, due to their heterogeneous properties and complex regulation.

TRP channels are involved in many physiological functions, ranging from pure sensory functions, such as pheromone signalling, taste transduction, nociception, and temperature sensation, over homeostatic functions, such as Ca2+ and Mg2+ reabsorption and osmoregulation, to many other motile functions, such as muscle contraction and vaso-motor control .

The classical or canonical TRPC family (formerly short-TRPs, STRPs) encompasses channels presenting a large number of different activation modes. Some are store-operated, whereas others are receptor-operated channels activated by the production of diacylglicerol or redox processes. TRPC proteins also control growth cone guidance in both mammalian and amphibian model systems. All seven channels of this family share the common property of activation through phospholipase C (PLC)-coupled receptors . It is believed that functional TRPC channels are generated in situ by association of four TRPC proteins to form either homotetramers or heterotetramers .

On the basis of sequence similarity, TRPC channels can be subdivided into four subgroups group 1 (TRPC1), group 2 (TRPC2), group 3 (TRPC3, TRPC6 and TRPC7) and group 4 (TRPC4 and TRPC5) . While TRPC1 and TRPC2 are almost unique, TRPC4 and TRPC5 share approx. 65% identity. TRPC3, 6 and 7 form a structural and functional subfamily sharing 70-80% identity at the amino acid level and their common sensitivity towards diacylglycerol (DAG).

TRPC3, 6, and 7 interact physically and, upon coexpression, coassemble to form functional tetrameric channels .
Transient receptor potential channel, canonical 7 (TRPC7_channel)
Type: Family

Transient receptor potential (TRP) channels can be described as tetramers formed by subunits with six transmembrane domains and containing cation-selective pores, which in several cases show high calcium permeability. The molecular architecture of TRP channels is reminiscent of voltage-gated channels and comprises six putative transmembrane segments (S1-S6), intracellular N-and C-termini, and a pore-forming reentrant loop between S5 and S6 .

TRP channels represent a superfamily conserved from worms to humans that comprise seven subfamilies : TRPC (canonical), TRPV (vanilloid), TRPM (melastatin or long TRPs), TRPA (ankyrin, whose only member is Transient receptor potential cation channel subfamily A member 1, TrpA1), TRPP (polycystin), TRPML (mucolipin) and TRPN (Nomp-C homologues), which has a single member that can be found in worms, flies, and zebrafish. TRPs are classified essentially according to their primary amino acid sequence rather than selectivity or ligand affinity, due to their heterogeneous properties and complex regulation.

TRP channels are involved in many physiological functions, ranging from pure sensory functions, such as pheromone signalling, taste transduction, nociception, and temperature sensation, over homeostatic functions, such as Ca2+ and Mg2+ reabsorption and osmoregulation, to many other motile functions, such as muscle contraction and vaso-motor control .

The classical or canonical TRPC family (formerly short-TRPs, STRPs) encompasses channels presenting a large number of different activation modes. Some are store-operated, whereas others are receptor-operated channels activated by the production of diacylglicerol or redox processes. TRPC proteins also control growth cone guidance in both mammalian and amphibian model systems. All seven channels of this family share the common property of activation through phospholipase C (PLC)-coupled receptors . It is believed that functional TRPC channels are generated in situ by association of four TRPC proteins to form either homotetramers or heterotetramers .

On the basis of sequence similarity, TRPC channels can be subdivided into four subgroups group 1 (TRPC1), group 2 (TRPC2), group 3 (TRPC3, TRPC6 and TRPC7) and group 4 (TRPC4 and TRPC5) . While TRPC1 and TRPC2 are almost unique, TRPC4 and TRPC5 share approx. 65% identity. TRPC3, 6 and 7 form a structural and functional subfamily sharing 70-80% identity at the amino acid level and their common sensitivity towards diacylglycerol (DAG).

TRPC3, 6, and 7 interact physically and, upon coexpression, coassemble to form functional tetrameric channels .
Psychosine receptor (Psych_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 .

Psychosine is a glycosphingolipid implicated in the pathology of globoid cell leukodystrophy (GLD), a hereditary metabolic disorder that results from the absence of the enzyme galactosyl ceramide. This deficiency results in the accumulation of psychosine in the brain, leading to apoptosis of oligodendrocytes, progressive demyelination and the existence of large, multinuclear cells (globoid cells) derived from microglia .
P2Y14 purinoceptor (P2Y14_rcpt)
Type: Family

There are three distinct families of extracellular receptors for purine and pyrimidine nucleotides , known as P1, P2X and P2Y purinoceptors . These receptors induce a wide variety of biological effects and are involved in many different cellular functions . P2X receptors are ligand-gated ion channels, whereas P1 and P2Y receptors are rhodopsin-like G protein-coupled receptors . The families also differ by their method of activation: P1 receptors are preferentially activated by adenosine , P2X via ATP , whereas the P2Y receptors, in addition to being activated by ATP, are activated by different adenine and/or uridine nucleoside di- and triphosphates (ADP, UDP, UTP, UDP and UDP-glucose) .

The P2Y purinoceptors currently consist of eleven subtypes: P2Y1, P2Y2, P2Y3 P2Y4, P2Y6, P2Y8, P2Y10, P2Y11, P2Y12, P2Y13 and P2Y14 . P2Y3 has, as yet, only been found in birds , whilst the rest have been cloned in humans. The gaps in P2Y receptor numbering are due to the reclassification of some receptors that were initially associated with to the P2Y family. These include P2Y5 (now known as lysophosphatidic acid receptor 6), P2Y7 (now leukotriene B4 receptor) and P2Y9 (lysophosphatidic acid receptor 4) .

This entry represents P2Y14 receptor (previously known as GPR105 or UDP-glucose receptor) . It is activated exclusively by sugar nucleotides, such as UDP-glucose, UDP-galactose, UDP-glucuronic acid and UDP-N-acetylglucosamine, but not by uracil or adenine nucleotides . It inhibits adenylate cyclase and stimulates phospholipase C . The P2Y14 receptor is widely distributed in the human body, with moderate to high levels observed in placenta, adipose tissue, stomach, intestine, spleen, lung, heart, bone marrow, thymus, and selected brain regions .
Histidine kinase domain (His_kinase_dom)
Type: Domain

The entry represents the histidine kinase core.

Most prokaryotic signal-transduction systems and a few eukaryotic pathways use phosphotransfer schemes involving two conserved components, a histidine protein kinase (HK) and a response regulator protein (RR). The HK, which is regulated by environmental stimuli, autophosphorylates at a histidine residue, creating a high-energy phosphoryl group that is subsequently transferred to an aspartate residue in the RR domain. Phosphorylation induces a conformational change in RR that results in activation of an associated domain that effects the response.

Both prokaryotic and eukaryotic HKs contain the same basic signalling components, namely a diverse sensing domain and a highly conserved kinase core that has a unique fold, distinct from that of the Ser/Thr/Tyr kinase superfamily. The overall activity of the kinase is modulated by input signals to the sensing domain. HKs undergo an ATP-dependent autophosphorylation at a conserved His residue in the kinase core. Autophosphorylation is a bimolecular reaction between homodimers, in which one HK monomer catalyses the phosphorylation of the conserved His residue in the second monomer.

The sensing domains are variable in sequence, reflective of the many different environmental signals to which HKs are responsive, whereas the about 250-residue kinase core is more conserved. The kinase core is composed of a dimerisation domain and an ATP/ADP-binding phosphotransfer or catalytic domain and can be identified by five conserved primary sequence motifs present in both eukaryotic and prokaryotic HKs. These motifs have been termed the H, N, G1, F and G2 boxes. The conserved His substrate is the central feature in the H box, whereas the N, G1, F and G2 boxes define the nucleotide binding cleft. In most HKs, the H box is part of the dimerisation domain. However, for some proteins, like CheA, the conserved His is located at the far N terminus of the protein in a separate HPt domain. The N, G1, F and G2 boxes are usually contiguous, but the spacing between these motifs is somewhat varied. The catalytic core forms an α-β sandwich consisting of five antiparallel β-strands and three α-helices .
Avidin/streptavidin (Avidin/str)
Type: Family

This entry includes avidin and streptavidin, and their homologs such as afifavidin , hoefavidin and fibropellin .

Avidin is a minor constituent of egg white in several groups of oviparous vertebrates. Avidin, which was discovered in the 1920's, takes its name from the avidity with which it binds biotin. These two molecules bind so strongly that is extremely difficult to separate them. Streptavidin is a protein produced by Streptomyces avidinii which also binds biotin and whose sequence is evolutionary related to that of avidin.

Avidin and streptavidin both form homotetrameric complexes of noncovalently associated chains. Each chain forms a very strong and specific non-covalent complex with one molecule of biotin. The three-dimensional structures of both streptavidin and avidin have been determined and revealed them to share a common fold: an eight stranded anti-parallel β-barrel with a repeated +1 topology enclosing an internal ligand binding site.

Fibropellins I and III are proteins that form the apical lamina of the sea urchin embryo, a component of the extracellular matrix. These two proteins have a modular structure composed of a CUB domain (see

), followed by a variable number of EGF repeats and a C-terminal avidin-like domain.
Avidin (Avidin)
Type: Family

Avidin is a minor constituent of egg white in several groups of oviparous vertebrates. Avidin, which was discovered in the 1920's, takes its name from the avidity with which it binds biotin. These two molecules bind so strongly that is extremely difficult to separate them. Streptavidin is a protein produced by Streptomyces avidinii which also binds biotin and whose sequence is evolutionary related to that of avidin.

Avidin and streptavidin both form homotetrameric complexes of noncovalently associated chains. Each chain forms a very strong and specific non-covalent complex with one molecule of biotin. The three-dimensional structures of both streptavidin and avidin have been determined and revealed them to share a common fold: an eight stranded anti-parallel β-barrel with a repeated +1 topology enclosing an internal ligand binding site.

Fibropellins I and III are proteins that form the apical lamina of the sea urchin embryo, a component of the extracellular matrix. These two proteins have a modular structure composed of a CUB domain (see

), followed by a variable number of EGF repeats and a C-terminal avidin-like domain.