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

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 .

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 .
Neuregulin, C-terminal (Neuregulin_C)
Type: Domain

This entry represents the C-terminal, intracellular domain in NRG proteins found in animals.

The transmembrane forms of neuregulin 1 (NRG1) are present within synaptic vesicles, including those containing glutamate . After exocytosis, NRG1 is in the presynaptic membrane, where the ectodomain of NRG1 may be cleaved off. The ectodomain then migrates across the synaptic cleft and binds to and activates a member of the EGF-receptor family on the postsynaptic membrane. This has been shown to increase the expression of certain glutamate-receptor subunits. NRG1 appears to signal for glutamate-receptor subunit expression, localisation, and /or phosphorylation facilitating subsequent glutamate transmission. Membrane-anchored Nrg-1 isoforms consist of a variable N-terminal extracellular domain and a conserved transmembrane and C-terminal cytoplasmic domains .

Neuregulins (NRG) are a sub-family of EGF-like molecules that have been shown to play multiple essential roles in vertebrate embryogenesis including: cardiac development, Schwann cell and oligodendrocyte differentiation, some aspects of neuronal development, as well as the formation of neuromuscular synapses . Included in the family are heregulin; neu differentiation factor; acetylcholine receptor synthesis stimulator; glial growth factor; and sensory and motor-neuron derived factor . Multiple family members are generated by alternate splicing or by use of several cell type-specific transcription initiation sites. In general, they bind to and activate the erbB family of receptor tyrosine kinases (erbB2 (HER2), erbB3 (HER3), and erbB4 (HER4)), functioning both as heterodimers and homodimers.
Thiolase (Thiolase)
Type: Family

Thiolases are ubiquitous enzymes that catalyse the reversible thiolytic cleavage of 3-ketoacyl-CoA into acyl-CoA and acetyl-CoA, a 2-step reaction involving a covalent intermediate formed with a catalytic cysteine. They are found in prokaryotes and eukaryotes. Two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase (

) and 3-ketoacyl-CoA thiolase (

). 3-ketoacyl-CoA thiolase (also called thiolase I) has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase (also called thiolase II) is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis.

In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes.

There are two conserved cysteine residues important for thiolase activity. The first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate; the second located at the C-terminal extremity is the active site base involved in deprotonation in the condensation reaction .

Mammalian nonspecific lipid-transfer protein (nsL-TP) (also known as sterol carrier protein 2) is a protein which seems to exist in two different forms: a 14 Kd protein (SCP-2) and a larger 58 Kd protein (SCP-x). The former is found in the cytoplasm or the mitochondria and is involved in lipid transport; the latter is found in peroxisomes. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases .

The beta-ketothiolases from Haloferax mediterranei BktB and phaA have different substrate specificities and are involved in PHBV biosynthesis . Their catalytic residues have been identified .
Ribonuclease H domain (RNaseH_domain)
Type: Domain

This entry represents the RNase H type-I domain.

Ribonuclease H (RNase H) (

) is a member of the ribonuclease family, which recognises and cleaves the RNA strand of RNA-DNA heteroduplexes. The enzyme is widely present in all three kingdoms of living organisms, including bacteria, archaea, and eukaryotes, and their counterpart domains are also found in reverse transcriptases (RTs) from retroviruses and retroelements . RNases H are classified into two evolutionarily unrelated families, type-I and type-II RNase H, with common structural features of the catalytic domain but different range of substrates for enzymatic cleavage. There appears to be three evolutionarily distinct lineages of cellular Rnase H enzymes . Type-I or RNase HI domains have been found in all Eukarya, one Archaea, many Eubacteria, a few non-LTR retroposons and all LTR retrotransposons. Type II enzymes consist of RNase HII (rnhB) and HIII (rnhC), which are homologous enzymes. RNase HII can be found in Archaea, Eubacteria and all Eukarya, while RNase HIII appears only in some Eubacteria. In eukaryotes and all Archaea, RNase HII enzymes may constitute the bulk of all Rnase H activity, while the reverse is true in Eubacteria like E. coli where RNase HI is the major source of RNH activity . All LTR retrotransposons acquired an enzymatically weak RNase H domain that is missing an important catalytic residue found in all other RNase H enzymes. Vertebrate retroviruses appear to have reacquired their RNase H domains, which are catalytically more active, but their ancestral RNase H domains (found in other LTR retrotransposons) have degenerated to give rise to the tether domain unique to vertebrate retrovirus . Reverse transcriptase (RT) is a modular enzyme carrying polymerase and ribonuclease H (RNase H) activities in separable domains. Retroviral RNase H is synthesised as part of the POL polyprotein that contains an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins.
Cobalamin (vitamin B12)-binding protein (Cbl-bd_prot)
Type: Family

Cobalamin (Cbl or vitamin B12) is only accessible through diet in mammals. Absorption, plasma transport and cellular uptake of Cbl in mammals involves three Cbl-transporting proteins, which are listed below in order of increasing Cbl-specificity:

Haptocorrin (cobalophilin), which binds Cbl and Cbl-derivatives such as cobinamide; it may play a role in preventing the absorption of cobalamin analogues produced by bacteria.

Transcobalamin (TC), which transport Cbl from blood to cells.

Intrinsic factor (IF), which promotes Cbl absorption in the ileum by specific receptor-mediated endocytosis.

The structure of TC reveals a two-domain structure, an N-terminal α(6)-α(6) barrel, and a smaller C-terminal domain . Many interactions between Cbl and its binding site in the interface of the two domains are conserved among the other Cbl transporters. Specificity for Cbl between the different transporters may reside in a β-hairpin motif found in the smaller C-terminal domain .
CD36 family (CD36_fam)
Type: Family

This entry includes CD36 and CD36-like proteins, including SCARB1/2 from vertebrates and SNMP1/2 from flies.
Proteinase inhibitor I3, Kunitz legume (Prot_inh_Kunz-lg)
Type: Family

The Kunitz-type soybean trypsin inhibitor (STI) family consists mainly of proteinase inhibitors from Leguminosae seeds . They belong to MEROPS inhibitor family I3, clan IC. They exhibit proteinase inhibitory activity against serine proteinases; trypsin (MEROPS peptidase family S1,

) and subtilisin (MEROPS peptidase family S8,

), thiol proteinases (MEROPS peptidase family C1,

) and aspartic proteinases (MEROPS peptidase family A1,

) .

Inhibitors from cereals are active against subtilisin and endogenous alpha-amylases, while some also inhibit tissue plasminogen activator. The inhibitors are usually specific for either trypsin or chymotrypsin, and some are effective against both. They are thought to protect the seeds against consumption by animal predators, while at the same time existing as seed storage proteins themselves - all the actively inhibitory members contain 2 disulphide bridges. The existence of a member with no inhibitory activity, winged bean albumin 1, suggests that the inhibitors may have evolved from seed storage proteins.

Proteins from the Kunitz family contain from 170 to 200 amino acid residues and one or two intra-chain disulphide bonds. The best conserved region is found in their N-terminal section. The crystal structures of soybean trypsin inhibitor (STI), trypsin inhibitor DE-3 from the Kaffir tree Erythrina caffra (ETI) and the bifunctional proteinase K/alpha-amylase inhibitor from wheat (PK13) have been solved, showing them to share the same 12-stranded β-sheet structure as those of interleukin-1 and heparin-binding growth factors . The β-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel β-barrel. Despite the structural similarity, STI shows no interleukin-1 bioactivity, presumably as a result of their primary sequence disparities. The active inhibitory site containing the scissile bond is located in the loop between β-strands 4 and 5 in STI and ETI.

The STIs belong to a superfamily that also contains the interleukin-1 proteins, heparin binding growth factors (HBGF) and histactophilin, all of which have very similar structures, but share no sequence similarity with the STI family.
Pyridoxal 5'-phosphate synthase subunit PdxT/SNO (PdxT/SNO)
Type: Family

This entry represents a family of pyridoxal 5'-phosphate synthase subunit, also known as the pdxT/SNO family. This family belongs to a superfamily containing a triad glutamine aminotransferase fold,
characterised by a conserved Cys-His-Glu active site . Two regions are
highly conserved across all taxa, the PGGEST motif and the FHPE(LT) motif .
PdxT/SNO proteins are an α/β three-layer sandwich containing a seven-
stranded twisted mixed parallel β-sheet flanked by a six α-helices on
the N-terminal stretch of the sheet, four on one side and two on the other . They are involved in vitamin B6 biosynthesis.
Nucleosome assembly protein (NAP) (NAP_family)
Type: Family

It is thought that NAPs act as histone chaperones, shuttling both core and linker histones from their site of synthesis in the cytoplasm to the nucleus. The proteins may be involved in regulating gene expression and therefore cellular differentiation .

The centrosomal protein c-Nap1, also known as Cep250, has been implicated in the cell-cycle-regulated cohesion of microtubule-organising centres. This 281kDa protein consists mainly of domains predicted to form coiled coil structures. The C-terminal region defines a novel histone-binding domain that is responsible for targeting CNAP1, and possibly condensin, to mitotic chromosomes . During interphase, C-Nap1 localises to the proximal ends of both parental centrioles, but it dissociates from these structures at the onset of mitosis. Re-association with centrioles then occurs in late telophase or at the very beginning of G1 phase, when daughter cells are still connected by post-mitotic bridges. Electron microscopic studies performed on isolated centrosomes suggest that a proteinaceous linker connects parental centrioles, and C-Nap1 may be part of a linker structure that assures the cohesion of duplicated centrosomes during interphase, but that is dismantled upon centrosome separation at the onset of mitosis .
Plexin repeat (Plexin_repeat)
Type: Repeat

This is a cysteine rich repeat found in several different extracellular receptors. The function of the repeat is unknown. Three copies of the repeat are found in plexin (

) . Two copies of the repeat are found in mahogany protein. A related Caenorhabditis elegans protein (

) contains four copies of the repeat, while the Met receptor contains a single copy of the repeat.
RNA dependent RNA polymerase, hepatitis C virus (RNA_pol_HCV)
Type: Family

The RNA dependent RNA polymerase is also known as non-structural protein NS5B. NS5B is a 65kDa protein that resembles other viral RNA polymerases. Hepatitis C virus (HCV) replication is thought to occur in membrane bound replication complexes. These complexes transcribe the positive strand and the resulting minus strand is used as a template for the synthesis of genomic RNA. There are two viral proteins involved in the reaction, NS3 and NS5B .
Solute carrier family 25 member 16-like (GDC-like)
Type: Family

This family includes a variety of substrate carrier proteins that are involved in energy transfer
are found in the inner mitochondrial membrane . Such proteins include:
ADP, ATP carrier protein (ADP/ATP translocase); 2-oxoglutarate/malate carrier
protein; phosphate carrier protein; tricarboxylate transport protein (or
citrate transport protein); Solute carrier family 25 member 16 (SLC25A16, also known as Graves disease carrier protein, GDC); yeast
mitochondrial proteins MRS3 and MRS4; yeast mitochondrial FAD carrier protein;
and many others.

GDC, which belongs to the mitochondrial metabolite carrier family , is required for the accumulation of coenzyme A in the mitochondrial matrix . The protein is recognised by IgG
from patients with active Graves disease. It is an integral membrane protein thought to reside in the inner
mitochondrial membrane. The predicted amino acid sequence of 348 residues
comprises three similar domains.
Lipase, GDXG, putative histidine active site (Lipase_GDXG_HIS_AS)
Type: Active_site

The following lipolytic enzymes are evolutionary related:

Mammalian hormone sensitive lipase (HSL). In adipose tissue and heart, HSL primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production.

Mammalian arylacetamide deacetylase (DAC).

Moraxella strain TA144 lipase 2 (gene lip2), an enzyme active at a low temperature.

Acinetobacter calcoaceticus esterase which seems to be active on simple triglycerides such as triacetin.

Streptomyces hygroscopicus acetyl-hydrolase (gene bah), which removes the N-acetyl group from the antibiotic bialaphos.

Escherichia coli acetyl esterase.

These enzymes contain a Ser-centred consensus sequence and a conserved His-Gly dipeptide found in most lipase N-terminal domains. These sequences are involved in the lipase active site conformation since substitution of the conserved Ser or His residues by Ala and Gln, respectively, results in the loss of both lipase and esterase activities .

This entry represents a conserved region containing the putative His active site.
Peptidase M9A/M9B, collagenase, bacterial (Peptidase_M9A/M9B)
Type: Family

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This entry represents sequences belonging to peptidase family M9, subfamilies M9A and M9B (microbial collagenase, clan MA(E)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the metal ligands and active site residues for members of this family and thermolysin occur in the motif HEXXH .

Microbial collagenases have been identified from bacteria of both the Vibrio and Clostridium genera. Collagenase is used during bacterial attack to degrade the collagen barrier of the host during invasion. Vibrio bacteria are non-pathogenic, and are sometimes used in hospitals to remove dead tissue from burns and ulcers. Clostridium histolyticum is a pathogen that causes gas gangrene; nevertheless, the isolated collagenase has been used to treat bed sores. Collagen cleavage occurs within the Gly-Xaa-Yaa repeats at Xaa+Gly in Vibrio and at Yaa+Gly bonds in Clostridium collagenase.

Analysis of the primary structure of the gene product from Clostridium perfringens has revealed that the enzyme is produced with a stretch of 86 residues that contain a putative signal sequence . Within this stretch is found PLGP, an amino acid sequence typical of collagenase substrates. This sequence may thus be implicated in self-processing of the collagenase .
Large ribosomal subunit protein uL2 (Ribosomal_uL2)
Type: Family

This entry represents the large ribosomal subunit protein uL2 family found in archaea, bacteria and eukaryotes including eukaryotic organelles such as chloroplast and mitochondria.

Ribosomal protein uL2 is one of the proteins from the large ribosomal subunit. The best conserved region is located in the C-terminal section of these proteins. In Escherichia coli, uL2 is known to bind to the 23S rRNA and to have peptidyltransferase activity. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities , groups:

Eubacterial uL2 (old name L2).

Algal and plant chloroplast uL2 (old name L2).

Cyanelle uL2 (old name L2).

Archaebacterial uL2 (old name L2).

Plant uL2 (old name L2).

Slime mold uL2 (old name L2).

Marchantia polymorpha mitochondrial uL2m (old name L2).

Paramecium tetraurelia mitochondrial uL2m (old name L2).

Fission yeast K5, K37 and KD4.

Yeast YL6.

Vertebrate uL2 (old name L8).

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 .