SII-SWORD/CoKE huggingface dataset:
Restriction endonuclease, type II, BpuJI, N-terminal (Restrct_endonuc_II_BpuJI_N)
Type: Domain

There are four classes of restriction endonucleases: types I, II,III and IV. All types of enzymes recognise specific short DNA sequences and carry out the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. They differ in their recognition sequence, subunit composition, cleavage position, and cofactor requirements , as summarised below:

Type I enzymes (

) cleave at sites remote from recognition site; require both ATP and S-adenosyl-L-methionine to function; multifunctional protein with both restriction and methylase (

) activities.

Type II enzymes (

) cleave within or at short specific distances from recognition site; most require magnesium; single function (restriction) enzymes independent of methylase.

Type III enzymes (

) cleave at sites a short distance from recognition site; require ATP (but doesn't hydrolyse it); S-adenosyl-L-methionine stimulates reaction but is not required; exists as part of a complex with a modification methylase methylase (

).

Type IV enzymes target methylated DNA.

Type II restriction endonucleases (

) are components of prokaryotic DNA restriction-modification mechanisms that protect the organism against invading foreign DNA. These site-specific deoxyribonucleases catalyse the endonucleolytic cleavage of DNA to give specific double-stranded fragments with terminal 5'-phosphates. Of the 3000 restriction endonucleases that have been characterised, most are homodimeric or tetrameric enzymes that cleave target DNA at sequence-specific sites close to the recognition site. For homodimeric enzymes, the recognition site is usually a palindromic sequence 4-8 bp in length. Most enzymes require magnesium ions as a cofactor for catalysis. Although they can vary in their mode of recognition, many restriction endonucleases share a similar structural core comprising four β-strands and one α-helix, as well as a similar mechanism of cleavage, suggesting a common ancestral origin . However, there is still considerable diversity amongst restriction endonucleases . The target site recognition process triggers large conformational changes of the enzyme and the target DNA, leading to the activation of the catalytic centres. Like other DNA binding proteins, restriction enzymes are capable of non-specific DNA binding as well, which is the prerequisite for efficient target site location by facilitated diffusion. Non-specific binding usually does not involve interactions with the bases but only with the DNA backbone .

BpuJI is a type II restriction endonuclease which recognises the asymmetric sequence 5'-CCCGT and cuts at multiple sites in the surrounding area of the target sequence. The BpuJI protein consists of two distinct modules; an N-terminal DNA recognition domain, and a C-terminal dimerisation and catalysis domain. The N-terminal domain is composed of two winged-helix subdomains and a disrupted linker subdomain. Target sequence recognition occurs through major groove contacts of amino acids in the winged-helix subdomains .
DNA replication/checkpoint protein (DNA_rep_checkpnt_protein)
Type: Family

Genome duplication is precisely regulated by cyclin-dependent kinases CDKs, which bring about the onset of S phase by activating replication origins and then prevent relicensing of origins until mitosis is completed. The optimum sequence motif for CDK phosphorylation is S/T-P-K/R-K/R, and Drc1-Sld2 is found to have at least 11 potential phosphorylation sites. Drc1 is required for DNA synthesis and S-M replication checkpoint control. Drc1 associates with Cdc2 and is phosphorylated at the onset of S phase when Cdc2 is activated. Thus Cdc2 promotes DNA replication by phosphorylating Drc1 and regulating its association with Cut5 . Sld2 and Sld3 represent the minimal set of S-CDK substrates required for DNA replication .

This entry also includes ATP-dependent DNA helicase Q4, which may be involved in chromosome segregation and has been associated with various diseases .
Hexameric tyrosine-coordinated heme protein (HTHP) (Hexamer_Tyr-coord_heme_pr_HTHP)
Type: Family

Hexameric tyrosine-coordinated heme protein (HTHP) is from the marine bacterium Silicibacter pomeroyi and has peroxidase and catalase activity. HTHP consists of six monomers which each binds a solvent accessible heme group and is stabilised by the interaction of three neighbouring monomers . The heme iron is penta-coordinated with a tyrosine residue as proximal ligand .
Group II intron-interrupted relaxase LtrB, C-terminal domain (LtrB_C)
Type: Domain

This entry represents the C-terminal helical domain hairpin of Group II intron-interrupted relaxase LtrB from Lactococcus lactis and similar sequences from Lactobacillales. LtrB mediates initiation of the conjugal transfer of the plasmid pRS01 possibly by introducing a single-stranded nick at the potential origin of transfer, to initiate single strand transfer from donor to recipient . Proteins found related to this domain have been previously misannotated as a lantibiotic immunity protein SrtI .
Acyl-ACP-thioesterase, N-terminal (Acyl-ACP-thioesterase_N)
Type: Domain

This entry represents the N-terminal domain of acyl-ATP thioesterases from bacteria and eukaryotes. These proteins are typically between 120 and 131 amino acids in length. The plant acyl-acyl carrier protein (ACP) thioesterases (TEs) play an essential role in chain termination during de novo fatty acid synthesis .
Porin PorB/PorC (Porin_PorB/PorC)
Type: Family

This entry represents the putative cell wall channel-forming proteins porin B and porin C from Corynebacterium sp. Porin B from Corynebacterium glutamicum (Brevibacterium flavum) allows the exchange of material across the mycolic acid layer, which is the protective nonpolar barrier. Porin B has an α helical core structure consisting of four α-helices surrounding a nonpolar interior. There is a disulphide bridge between helices 1 and 4 to form a stable covalently bound ring . The channel of PorB is oligomeric .
Calcitonin/adrenomedullin (Calcitonin/adrenomedullin)
Type: Family

Calcitonin is a 32 amino acid polypeptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in the blood, by promoting the incorporation of these ions in the bones. This is the alpha type. Alternative splicing of the gene coding for calcitonin produces a distantly related peptide of 37 amino acids, called calcitonin gene-related peptide (CGRP), beta type. CGRP induces vasodilatation in a variety of vessels, including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role.

Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide (DAP), or amylin) is a peptide of 37 amino acids that selectively inhibits insulin-stimulated glucose utilisation and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. Structurally, IAPP is closely related to CGRP.

Calcitonin receptor-stimulating peptide 1 stimulates cAMP production via the calcitonin receptor.

Two conserved cysteines in the N-terminal of these peptides are known to be involved in a disulphide bond. The C-terminal residue of all three peptides is amidated.

xCxxxxxCxxxxxxxxxxxxxxxxxxxxxxxxxxxx-NH(2)
| | Amide group
+-----+

'C': conserved cysteine involved in a disulphide bond.

This entry represents procalcitonin (before cleavage into the calcitonin peptide) and adrenomedullin.
Calcitonin-like (Calcitonin-like)
Type: Family

Calcitonin is a 32 amino acid polypeptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in the blood, by promoting the incorporation of these ions in the bones. This is the alpha type. Alternative splicing of the gene coding for calcitonin produces a distantly related peptide of 37 amino acids, called calcitonin gene-related peptide (CGRP), beta type. CGRP induces vasodilatation in a variety of vessels, including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role.

Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide (DAP), or amylin) is a peptide of 37 amino acids that selectively inhibits insulin-stimulated glucose utilisation and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. Structurally, IAPP is closely related to CGRP.

Calcitonin receptor-stimulating peptide 1 stimulates cAMP production via the calcitonin receptor.

Two conserved cysteines in the N-terminal of these peptides are known to be involved in a disulphide bond. The C-terminal residue of all three peptides is amidated.

xCxxxxxCxxxxxxxxxxxxxxxxxxxxxxxxxxxx-NH(2)
| | Amide group
+-----+

'C': conserved cysteine involved in a disulphide bond.
Calcitonin (Calcitonin)
Type: Family

The calcitonin (CT) gene is alternatively expressed in a tissue-specific manner, producing either the calcium regulatory hormone CT in the thyroid, or the neuropeptide calcitonin gene related peptide (CGRP) in the brain . In medullary carcinoma of the thyroid, both peptides are produced . The calcitonin regulatory hormone is a peptide of 32 residues that causes a rapid but short-lived drop in calcium and phosphate levels in the blood by promoting the incorporation of these ions in the bones . The structure of Oncorhynchus keta (Chum salmon) calcitonin has been studied by 2D NMR in SDS micelles . The main conformational feature of the hormone is an α-helix from residues 6-22, which includes an amphipathic segment. Two cysteine residues (at positions 1 and 7) form an N-terminal loop, and a C-terminal decapeptide forms a loop that folds back towards the helix .
Poxvirus F1/C10 (Poxvirus_F1/C10)
Type: Family

This entry includes the poxvirus families F1 (also known as OPG045) and C10. C10 proteins are apoptosis regulators, which function to modulate the apoptotic cascades and thereby favour productive viral replication. One of these, M11L inhibits mitochondrial-dependent apoptosis by mimicking and competing with host proteins for the binding and blocking of Bak and Bax, two executioner proteins .
KduI/IolB isomerase (KduI/IolB_isomerase)
Type: Family

The KduI/IolB family of enzymes includes 5-keto 4-deoxyuronate isomerase (KduI) and 5-deoxy-glucuronate isomerase (IolB).
RNA ligase domain, REL/Rln2 (RNA_ligase_dom_REL/Rnl2)
Type: Domain

This entry represents the RNA ligase domain. RNA ligase enzyme repairs RNA strand breaks in nicked DNA:RNA and RNA:RNA but not in DNA:DNA duplexes . Members of this RNA ligase family include:

RNA editing ligase 1 (REL1), which is essential for RNA editing and may be active in U-deletion editing .

RNA editing ligase 2 (REL2), which may be active in U-insertion editing .

RnlB RNA ligase 2 (or Rnl2), second RNA ligase of Enterobacteria phage T4 (Bacteriophage T4); unlike RNA ligase 1, RnlB prefers doule stranded substrates .

For the RNA-editing ligases Rel1 and Rel2 from Trypanosoma brucei brucei, Mg(2+) may play an important role both for nucleic acid binding and for activation of the nucleophile .
Type III secretion, needle-protein-like (T3SS_needle-like)
Type: Family

This entry represents bacterial type III secretion system needle-like proteins. Type III secretion systems are essential virulence determinants for many Gram-negative bacterial pathogens, acting to translocate proteins, usually virulence factors, out across both inner and outer membranes of bacteria and into the cytoplasm of the host cell .
CRISPR-associated protein, Cas5 (CRISPR-assoc_prot_Cas5)
Type: Family

This entry represents Cas5, which helps process or stabilize pre-crRNA into individual crRNA units. Cas5 and Cas6 are also required for optimal crRNA processing and/or stability .

The CRISPR-Cas system is a prokaryotic defence mechanism against foreign genetic elements. The key elements of this defence system are the Cas proteins and the CRISPR RNA.
Protein of unknown function DUF2127 (DUF2127)
Type: Family

There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. However, they are predicted to be integral membrane proteins (with several transmembrane segments).
Interferon gamma receptor, D2 domain, poxvirus/mammal (IFN_gamma_rc_D2_pox/mammal)
Type: Domain

Interferon (IFN)-gamma is a dimeric glycoprotein produced by activated T cells and natural killer cells. Although originally isolated based on its
antiviral activity, IFN-gamma also displays powerful anti-proliferative and immunomodulatory activities, which are essential for developing appropriate cellular defences against a variety of infectious agents. The first step in eliciting these responses is the specific high affinity interaction of IFN-gamma with its cell-surface receptor (IFN-gammaRalpha); the complex then interacts with at least one of a family of additional species-specific accessory factors (AF-1 or IFN-gammabeta), which convey different cellular responses. One such response is the association and phosphorylation of two protein tyrosine kinases (Jak-1 and Jak-2), which in turn stimulate nuclear transcription activators .

This entry includes:

The human IFN-gamma receptor 1 (IFN-gammaR1), a member of the hematopoietic cytokine receptor superfamily. It is expressed in a membrane-bound form in many cell types, and is over-expressed in tumour cells. It comprises an extracellular portion of 229 residues, a single transmembrane region, and a cytoplasmic domain of 221 residues. As with other members of its superfamily, the cytokine-binding sites are formed by a small set of closely-spaced surface loops that extend from a β-sheet core, much like antigen-binding sites on antibodies. The extracellular IFN-gammaR monomer comprises two domains (D1 and D2 domains), each resembling an Ig-like fold with fibronectin type III topology . The signalling complex comprises two IFN-gammaR1 chains and two IFN-gammaR2 chains, which dimerises in an IFN-gamma-driven fashion .

The vaccinia virus interferon (IFN)-gamma receptor (IFN-gammaR) is a 43kDa soluble glycoprotein that is secreted from infected cells early during infection. IFN-gammaR from vaccinia virus, cowpoxvirus and camelpox virus exist naturally as homodimers, whereas the cellular IFN-gammaR dimerizes only upon binding the homodimeric IFN-gamma. The existence of the virus protein as a dimer in the absence of ligand may provide an advantage to the virus in efficient binding and inhibition of IFN-gamma in solution .

This is the D2 domain, which is involved in forming receptor-receptor contacts .
CRISPR-associated endonuclease Cas2 (CRISPR_associated_Cas2)
Type: Family

This entry represents members of the family of Cas2, one of the first four protein families found to mark prokaryotic genomes that contain multiple CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) elements. CRISPR systems protect against invasive nucleic acid sequences, including phage. Cas2 proteins have been characterised as either endoribonuclease (for ssRNA) or endodeoxyribonuclease (for dsDNA), depending on the system to which the Cas2 belongs . CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats . The cas genes usually are found near the repeats. It's worth noting that there is a distinct branch of the Cas2 family

showing a very low level of sequence identity .
Phosphoribosyl-ATP pyrophosphohydrolase-like (PRib-ATP_PPHydrolase-like)
Type: Family

Phosphoribosyl-ATP pyrophosphatase,

catalyses the second step in the histidine biosynthetic pathway:

5-phosphoribosyl-ATP + H2O = 5-phosphoribosyl-AMP + PPi

The Neurospora crassa enzyme also catalyzes the reactions of histidinol dehydrogenase (

) and phosphoribosyl-AMP cyclohydrolase (

).

This entry also includes the Bacillus subtilis Cof proteins, which catalyze the hydrolysis of 4-amino-2-methyl-5-hydroxymethylpyrimidine pyrophosphate to 4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate .
Large ribosomal subunit protein uL15/eL18 (Ribosomal_uL15/eL18)
Type: Domain

This entry represents a domain conserved both in large ribosomal subunit proteins uL15 and eL18, which share a common structure consisting mainly of parallel β sheets (β-α-β units) with a core of three turns of irregular (β-β-α)n superhelix . This entry includes uL15 proteins that were known as L15 from bacteria, L28 from yeast, and L27A from higher eukaryotes, fungal mitochondrial uL15m (previously L10), mitochondrial uL15m (MRLP15), and eL18 proteins from archaea and eukaryotes.

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 .
Large ribosomal subunit protein eL18, conserved site (Ribosomal_eL18/eL18-A/B/_CS)
Type: Conserved_site

This signature covers a stretch of about 13 residues in the first third of teh members of the large ribosomal subunit protein eL18 family.

Members of this family are large subunit ribosomal proteins which are found in eukaryotes and archaea . These proteins have 115 to 187 amino-acid residues. The family consists of:

Vertebrate eL18 (known as L14 in Xenopus)

Plant eL18

Yeast eL18 (Rp28)

Haloarcula marismortui (Halobacterium marismortui) HL29

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 .
HEAT, type 2 (HEAT_type_2)
Type: Repeat

The HEAT repeat is a tandemly repeated, 37-47 amino acid long module occurring in a number of cytoplasmic proteins, including the four name-giving proteins huntingtin, elongation factor 3 (EF3), the 65 kDa alpha regulatory subunit of protein phosphatase 2A (PP2A) and the yeast PI3-kinase TOR1 . Arrays of HEAT repeats consists of 3 to 36 units forming a rod-like helical structure and appear to function as protein-protein interaction surfaces. It has been noted that many HEAT repeat-containing proteins are involved in intracellular transport processes.

In the crystal structure of PP2A PR65/A , the HEAT repeats consist of pairs of antiparallel α-helices .
Bestrophin-like (Bestrophin-like)
Type: Family

This entry represents animal bestrophin homologues.

Bestrophin is a 68kDa basolateral plasma membrane protein expressed in retinal pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated in Best macular dystrophy, a disease characterised by a depressed light peak in the electrooculogram . VMD2 encodes a 585-amino acid protein with an approximate mass of 68kDa which has been designated bestrophin. Bestrophin shares homology with the Caenorhabditis elegans RFP gene family, named for the presence of a conserved arginine (R), phenylalanine (F), proline (P), amino acid sequence motif. Bestrophin is a plasma membrane protein, localised to the basolateral surface of RPE cells consistent with a role for bestrophin in the generation or regulation of the EOG light peak.

Bestrophin and other RFP family members represent a new class of calcium-activated chloride channels (CaCC) , indicating a direct role for bestrophin in generating the light peak . Bestrophins are also permeable to other monovalent anions including bicarbonate, bromine, iodine, thiocyanate an nitrate . Structural analysis revealed that N-terminal region of the proteins is highly conserved and sufficient for its CaCC activity. The C-terminal region has low sequence identity. The VMD2 gene underlying Best disease was shown to represent the first human member of the RFP-TM protein family. More than 97% of the disease-causing mutations are located in the N-terminal domain altering the electrophysiological properties of the channel .

The bestrophins are four-pass transmembrane chloride-channel proteins , and the RFP-TM or bestrophin domain extends from the N terminus through approximately 350 amino acids and contains all of the TM domains as well as nearly all reported disease causing mutations . Interestingly, the RFP motif is not conserved evolutionarily back beyond Metazoa, neither is it in plant members.