SII-SWORD/CoKE huggingface dataset:
LanC-like protein, eukaryotic (LanC-like_prot_euk)
Type: Family

The LanC-like protein superfamily encompasses a highly divergent group of peptide-modifying enzymes, including the eukaryotic and bacterial lanthionine synthetase C-like proteins (LanC) ; subtilin biosynthesis protein SpaC from Bacillus subtilis ; epidermin biosynthesis protein EpiC from Staphylococcus epidermidis ; nisin biosynthesis protein NisC from Lactococcus lactis ; GCR2 from Arabidopsis thaliana (Mouse-ear cress) ; and many others.

The 3D structure of the lantibiotic cyclase from L. lactis has been determined by X-ray crystallography to 2.5A resolution . The globular structure is characterised by an all-α fold, in which an outer ring of helices envelops an inner toroid composed of 7 shorter, hydrophobic helices. This 7-fold hydrophobic periodicity has led several authors to claim various members of the family, including eukaryotic LanC-1 and GCR2, to be novel G protein-coupled receptors ; some of these claims have since been corrected .
Tumour necrosis factor receptor 10 (TNFR_10)
Type: Family

The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins. Family members are defined based on similarity in their extracellular domain - a region that contains many cysteine residues arranged in a specific repetitive pattern . The cysteines allow formation of an extended rod-like structure, responsible for ligand binding .

Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences . Activation of TNFRs can therefore induce a range of disparate effects, including cell proliferation, differentiation, survival, or apoptotic cell death, depending upon the receptor involved .

TNFRs are widely distributed and play important roles in many crucial biological processes, such as lymphoid and neuronal development, innate and adaptive immunity, and maintenance of cellular homeostasis . Drugs that manipulate their signalling have potential roles in the prevention and treatment of many diseases, such as viral infections, coronary heart disease, transplant rejection, and immune disease .
Interleukin-15, mammal (IL-15_mml)
Type: Family

Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells.

Interleukin-15 (IL-15) has a variety of biological functions, including stimulation and maintenance of cellular immune responses . It is required for division of CD8+ T cells of memory phenotype - a process that is increased by inhibition of IL-2 . The numbers of CD8+ memory T cells in animals may, therefore, be controlled by a balance between IL-15 and -2.

This entry represents interleukin-15 found in mammals.
Nisin biosynthesis protein, NisC (Nisin_biosynthesis_NisC)
Type: Family

The LanC-like protein superfamily encompasses a highly divergent group of peptide-modifying enzymes, including the eukaryotic and bacterial lanthionine synthetase C-like proteins (LanC) ; subtilin biosynthesis protein SpaC from Bacillus subtilis ; epidermin biosynthesis protein EpiC from Staphylococcus epidermidis ; nisin biosynthesis protein NisC from Lactococcus lactis ; GCR2 from Arabidopsis thaliana ; and many others.

The 3D structure of the lantibiotic cyclase from L. lactis has been determined by X-ray crystallography to 2.5A resolution . The globular structure is characterised by an all-α fold, in which an outer ring of helices envelops an inner toroid composed of 7 shorter, hydrophobic helices. This 7-fold hydrophobic periodicity has led several authors to claim various members of the family, including eukaryotic LanC-1 and GCR2, to be novel G protein-coupled receptors ; some of these claims have since been corrected .
Cytochrome P450, CYP2 family (Cyt_P450_CYP2_fam)
Type: Family

P450 enzymes constitute a superfamily of haem-thiolate proteins , widely distributed in bacteria, fungi, plants and animals. The enzymes are involved in metabolism of a plethora of both exogenous and endogenous compounds . Usually, they act as terminal oxidases in multi-component electron-transfer chains, called P450-containing monooxygenase systems.

On the basis of sequence similarity, all P450s can be categorised into 2 main classes , the so-called B- and E-classes: P450 proteins of prokaryotic 3-component systems and fungal P450nor (CYP55) belong to the B-class; all other known P450s from distinct systems are of the E-class. E-class P450s may be further divided into 5 subclasses (groups) according to protein sequence similarities. The data suggest that divergence of the P450 superfamily into B- and E-classes, and further divergence into stable P450 groups within the E-class, must be very ancient and had occurred before the appearance of eukaryotes.

Given the rapid increase in numbers of P450s, Nelson introduced the concept of a higher-order classification of P450 families into clans based on sequence similarity. This is similar to the previous grouping into B- and E-classes; both classifications are still used. According to Nelsons system, clan 2 contains the CYP2 plus CYP1, 17, 18, 21 and 71 families, and corresponds to the E-class group I proteins . Members of the first 4 families are of vertebrate origin, while those from CYP71 derive from plants. CYP1 and CYP2 enzymes mainly metabolise exogenous substrates, whereas CYP17 and CYP21 are involved in metabolism of endogenous physiologically-active compounds.
Interleukin-13 (IL-13)
Type: Family

This entry represents interleukin-13 (IL-13), it is a pleiotropic cytokine which may be important in the regulation of the inflammatory and immune responses . IL-13 inhibits inflammatory cytokine production and synergises with IL-2 in regulating interferon-gamma synthesis. The sequences of IL-4 and IL-13 are distantly related.
Aldo-keto reductase (AKR)
Type: Family

In general, the aldo-keto reductase (AKR) protein superfamily members reduce carbonyl substrates such as: sugar aldehydes, keto-steroids, keto-prostaglandins, retinals, quinones, and lipid peroxidation by-products . However, there are some exceptions, such as the reduction of steroid double bonds catalysed by AKR1D enzymes (5beta-reductases); and the oxidation of proximate carcinogen trans-dihydrodiol polycyclic aromatic hydrocarbons; while the beta-subunits of potassium gated ion channels (AKR6 family) control Kv channel opening .

Structurally, they contain an (α/β)8-barrel motif, display large loops at the back of the barrel which govern substrate specificity, and have a conserved cofactor binding domain. The binding site is located in a large, deep, elliptical pocket in the C-terminal end of the β-sheet, the substrate being bound in an extended conformation. The hydrophobic nature of the pocket favours aromatic and apolar substrates over highly polar ones . They catalyse an ordered bi bi kinetic mechanism in which NAD(P)H cofactor binds first and leaves last . Binding of the NADPH coenzyme causes a massive conformational change, reorienting a loop, effectively locking the coenzyme in place. This binding is more similar to FAD- than to NAD(P)-binding oxidoreductases .
PAC1/LIS1-like, WD-40 repeat (WD40_PAC1)
Type: Repeat

This entry represents the WD-40 repeats in PAC1/LIS1 receptors, a class B G-protein-coupled receptor (GPCR) and similar GPCR related proteins. This entry also includes small ribosomal subunit proteins RACK1 and other scaffolding proteins such as CIAO1 and MDV1.

WD-40 repeats (also known as WD or beta-transducin repeats) are short ~40 amino acid motifs, often terminating in a Trp-Asp (W-D) dipeptide. WD40 repeats usually assume a 7-8 bladed β-propeller fold, but proteins have been found with 4 to 16 repeated units, which also form a circularised β-propeller structure. WD-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control and apoptosis. Repeated WD40 motifs act as a site for protein-protein or protein-DNA interaction, and proteins containing WD40 repeats are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins . The specificity of the proteins is determined by the sequences outside the repeats themselves. Examples of such complexes are G proteins (beta subunit is a β-propeller), TAFII transcription factor, and E3 ubiquitin ligase . In Arabidopsis spp., several WD40-containing proteins act as key regulators of plant-specific developmental events.
Endothelin (Endothelin)
Type: Family

Endothelins are small proteins that play an important role in the regulation of the cardiovascular system . They are the most potent vasoconstrictors known, they stimulate cardiac constriction, regulate release of vasoactive substances, and stimulate mitogenesis in blood vessels in primary culture. They also stimulate contraction in almost all other smooth muscles (e.g., uterus, bronchus, vas deferensa and stomach) and stimulate secretion in several tissues (e.g., kidney, liver and adrenals). Endothelin receptors have also been found in the brain, e.g. cerebral cortex, cerebellum and glial cells. Endothelins have been implicated in a variety of pathophysiological conditions associated with stress, including hypertension, myocardial infarction, subarachnoid haemorrhage and renal failure.

Endothelins are synthesised by proteolysis of large preproendothelins, which are cleaved to `big endothelins' before being processed to the mature peptide. Three distinct human endothelins encoded by separate genes have been identified: ET1, ET2 and ET3 are present in lung, kidney, adrenal gland, brain and other tissues. The sequences of the peptides contain 4 cysteine residues, which are involved in disulphide bond formation, and are highly similar to the SRTX family from snake venom.
NUDIX hydrolase (Nudix_hydrolase)
Type: Domain

Recently, the generic name 'NUDIX hydrolases' (NUcleoside DIphosphate linke to some other moeity X) has been coined for this domain family . The family can be divided into a number of subgroups, of which MutT anti-mutagenic activity represents only one type; most of the rest hydrolyse diverse nucleoside diphosphate derivatives (including ADP-ribose, GDP-mannose, TDP-glucose, NADH, UDP-sugars, dNTP and NTP).
Homeodomain, metazoa (HD_metazoa)
Type: Domain

This entry represents the homeodomain (HD), a protein domain of approximately 60 residues that usually binds DNA. It is encoded by the homeobox sequence , which was first identified in a number of Drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates . Proteins containing HDs are likely to play an important role in development - most are known to be sequence-specific DNA-binding transcription factors. This domain folds into a globular structure with three α-helices connected by two short loops that harbour a hydrophobic core. The second and third form a helix-turn-helix (HTH) motif, which make intimate contacts with the DNA: while the first helix of this motif helps to stabilise the structure, the second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA . One particularity of the HTH motif in some of these proteins arises from the stereo-chemical requirement for glycine in the turn (position 9 of the motif), which is needed to avoid steric interference of the β-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, while for many of the homeotic and other DNA-binding proteins the requirement is relaxed.
Intracellular proteinase inhibitor BsuPI (Intracell_prot_inh_BsuPI)
Type: Domain

This is a bacterial domain which has been named BsuPI in Bacillus subtilis. This domain is found in

, where it has been suggested to regulate the major intracellular proteinase (ISP-1) activity in vivo . The structure of proteins in this family adopt a β barrel topology.
Uncharacterised protein family YgbA (Uncharacterised_YgbA)
Type: Family

This entry contains proteins with no known function.
Protein of unknown function DUF5503 (DUF5503)
Type: Family

This is a family of unknown function found in Enterobacteriaceae. This family includes uncharacterised protein YedM.
Stationary phase protein 4 (Spg4)
Type: Family

Saccharomyces cerevisiae respond and cope to starvation by ceasing growth and entering a non-proliferating state referred to as stationary phase . Expression of SPG4 has been shown to be higher in stressed cells, and stationary phase cells compared to active cells. It is not required for growth on non-fermentable carbon sources .
Uncharacterised protein family YejG (Uncharacterised_YejG)
Type: Family

This entry contains proteins with no known function.
Uncharacterised protein family YaiZ (Uncharacterised_YaiZ)
Type: Family

This entry contains membrane proteins with no known function.
Biogenesis of lysosome-related organelles complex 1 subunit BLI1 (BLI1)
Type: Family

This entry represents biogenesis of lysosome-related organelles complex 1 subunit BLI1. The complex is found on tubular endosomes and plays an important role in the biogenesis of lysosome-related organelles, possibly by facilitating cargo sorting into tubular carriers .
Uncharacterised protein family HI0310 (Uncharacterised_HI0310)
Type: Family

This entry contains proteins with no known function.
Sigma-M inhibitor YhdK (YhdK)
Type: Family

Extracytoplasmic function (ECF) sigma factors are a diverse family of proteins within the class of the sigma 70 subunit of RNA polymerase. Most members are known to regulate gene expression in response to stress conditions. The Bacillus subtilis genome encodes at least 17 distinct sigma factors, seven of which are members of the ECF subfamily.
Protein of unknown function DUF5440 (DUF5440)
Type: Family

This is a family of unknown function found in Proteobacteria.
Anti-RecBCD protein 2, bacteriophage P22 (Phage_P22_anti-RecBCD_p2)
Type: Family

This phage protein modulates the activity of the host recBCD nuclease promoting phage growth and recombination and protects the linear double stranded DNA from exonuclease degradation .
Uncharacterised protein family AF1218 (Uncharacterised_AF1218)
Type: Family

This entry contains proteins with no known function.
Late transcription unit B (LtuB)
Type: Family

Chlamydiae possess an intracellular developmental cycle defined by the interconversion of infectious, metabolically inactive elementary bodies and noninfectious, dividing reticulate bodies. The predicted peptides encoded by late genes ltuA and ltuB do not resemble known proteins, and their function is not known. The transcription of at least some chlamydial late-stage genes is dependent on sigma 66, which is homologous to the major sigma factors of other eubacteria .
Uncharacterised protein family Rv2561 (Uncharacterised_Rv2561)
Type: Family

This entry contains proteins with no known function.
Protein of unknown function DUF5500 (DUF5500)
Type: Family

This is a family of unknown function found in Herpesvirus. The family includes uncharacterised protein UL19.
Protein of unknown function DUF5517 (DUF5517)
Type: Family

This is a family of unknown function found in Fuselloviridae. Structure analysis suggest a role in viral assembly.
SecA translation cis-regulator SecM, small type (SecM_small)
Type: Family

In E. coli, SecM encodes a presecretory protein that regulates secA expression at the translational level. SecM contains a C-terminal sequence motif that induces a transient translation arrest . SecM signal peptide plays an essential role in this regulatory process by acting as a molecular timer that coordinates secM membrane targeting with the synthesis of the arrest motif .
Uncharacterised protein family YnzE (Uncharacterised_YnzE)
Type: Family

This entry contains membrane proteins with no known function.
Poly-beta-1,6-N-acetyl-D-glucosamine synthesis protein IcaD (IcaD)
Type: Family

IcaD is essential for the synthesis of poly-beta-1,6-N-acetyl-D-glucosamine (PNAG, also known as PIA), a biofilm adhesin polysaccharide. IcaD is required for full IcaA N-acetylglucosaminyltransferase activity .
Uncharacterised protein family HI0941 (Uncharacterised_HI0941)
Type: Family

This entry contains proteins with no known function.
Uncharacterised protein family, inner membrane YaiY (Uncharacterised_IM_YaiY)
Type: Family

This entry contains membrane proteins with no known function.
Uncharacterised protein family YxcD (Uncharacterised_YxcD)
Type: Family

This entry contains proteins with no known function.
Transcription regulator PrtN (Tscrpt_reg_PrtN)
Type: Family

PrtN is a transcriptional activator for pyocin synthesis genes , and probably acts by binding to the sequences conserved in their 5' non-coding regions (P box) .
Divergent protein kinase domain 2A/B (DIPK2A/B)
Type: Family

DIPK2A, also known as DIA1 (deleted in autism protein 1), may play a role in cardiomyocyte proliferation through paracrine signaling and activation of the PPI3K-AKT-CDK7 signaling cascade . This entry also includes DIPK2B, whose function is not clear.
Large ribosomal subunit protein cL38 (Ribosomal_cL38)
Type: Family

The spinach plastid 50S subunit comprises 33 proteins, of which 31 are orthologues of Escherichia coli ribosomal proteins and two are plastid-specific ribosomal proteins (PSRP-5 and PSRP-6) having no homologues in other types of ribosomes . This entry represents Large ribosomal subunit protein cL38 (PSRP-6, also known as 50S ribosomal protein 6, chloroplastic ) and similar sequences from plants.

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 .
UL17, Cytomegalovirus (UL17_Cytomegalovir)
Type: Family

This family consists of UL17 proteins from Cytomegalovirus, mainly from Human cytomegalovirus (HCMV), also known as Human herpesvirus 5 (HHV-5). Its function is not known .
Origin recognition complex, subunit 6, metazoa/plant (ORC6_met/pln)
Type: Family

The Origin Recognition Complex (ORC) is a six-subunit ATP-dependent DNA-binding complex encoded by ORC1-6 . ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle . ORC directs DNA replication throughout the genome and is required for its initiation . ORC bound at replication origins serves as the foundation for assembly of the pre-replicative complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2-7 complex . Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase . Cell cycle-regulated phosphorylation of ORC2, ORC6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2/M phase .

In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR) . ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers .
Cycloeucalenol cycloisomerase (Cycloeucalenol_cycloisomerase)
Type: Family

This entry represents the enzyme cycloeucalenol cycloisomerase (

) and is involved in the synthesis of plant sterols, by converting pentacyclic cyclopropyl sterols to tetracyclic sterols .

In Arabidopsis thaliana (Mouse-ear cress), cycloeucalenol cycloisomerase functions during and just after division and supports gravitropism by establishing polar PIN2 (auxin transporter) localisation, it is also required for endocytosis of PIN2 .
Developmental regulator, ULTRAPETALA (Developmental_reg_ULTRAPETALA)
Type: Family

This entry represents a developmental regulator that acts as a key negative regulator of cell accumulation in shoot and floral meristems. Negatively regulates the size of the WUSCHEL (WUS)-expressing organising centre in inflorescence meristems. May act by down-regulating expression of WUS and can compensate for mutant ULT1 protein when over expressed .
Uncharacterised protein family YqxA (Uncharacterised_YqxA)
Type: Family

This entry contains proteins with no known function.
Thil, AANH domain (ThiI_AANH)
Type: Domain

This entry represents the AANH domain.

Three domains of ThiI are essential for the thiolation of tRNA: a THUMP domain that binds tRNA (see

) , an AANH domain (

) that activates the uridine residue by adenylylation , and a rhodanese-like domain (

) that transfers sulfur to the activated uridine residue . Neither the THUMP nor the AANH domain of ThiI are essential for thiamine synthesis, only the rhodanese domain is necessary for synthesis of the thiazole moiety of thiamine .

tRNA sulfurtransferase ThiI catalyses the ATP-dependent transfer of a sulfur to tRNA to produce 4-thiouridine in position 8 of tRNAs, which functions as a near-UV photosensor . In some bacteria, ThiI is a bifunctional enzyme required for the synthesis of both the 4-thiouridine modification in tRNA and the thiazole moiety in the thiamine biosynthesis pathway .