SII-SWORD/CoKE huggingface dataset:
Large ribosomal subunit protein uL18 (Ribosomal_L18)
Type: Family

This entry describes the family large subunit ribosomal protein uL18 found in eukaryotes and prokaryotes.

The large ribosomal subunit protein uL18 is an essential component of the large subunit LSU, which is required in its formation and stabilisation. The LSU contains the ribosomal catalytic site termed the peptidyl transferase centre (PTC), which catalyses the formation of peptide bonds, thereby polymerising the amino acids delivered by tRNAs into a polypeptide chain. Additionally, uL18 is essential for binding and coordinating 5S rRNA into the ribosome, a key step in ribosome biogenesis and assembly .

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 .
Uncharacterized protein YcgB-like (Ycgb-like)
Type: Family

This entry represents a group of proteins mainly found in proteobacteria, including YcgB, an uncharacterised protein first described in Escherichia coli (strain K12) [

] . YcgB has been suggested to be part of a conserved signalling pathway with YeaH and YeaG. This pathway may be involved in nitrogen metabolism (see Supplementary note 5 in )
YagK/YfjJ, C-terminal domain (YagK_YfjJ_C)
Type: Domain

This domain is found at the C-terminal end of a group of uncharacterised proteins from bacteria, such as YagK and YfjJ from E.coli. This domain is structurally similar to viral Rep proteins and bacterial relaxases based on structure predictions and comparison, containing also the conserved HXH motif typically found in those proteins.
Piwi domain, nematodes (Piwi_nem)
Type: Domain

This entry describes the Piwi domain mainly found in nematodes. This domain corresponds to the C-terminal portion of Argonaute proteins, which are involved in RNA silencing. The Piwi domain consists of two subdomains, one of which provides the 5' anchoring of the guide RNA and the other, the catalytic site for slicing. Additionally, this domain is believed to perform a crucial role in germline cells via a similar mechanism .

RNA silencing refers to a group of related gene-silencing mechanisms mediated by short RNA molecules, including siRNAs, miRNAs, and heterochromatin-related guide RNAs. The central component of the RNA-induced silencing complex (RISC) and related complexes is Argonaute.
Ddi1/2, HDD domain (Ddi1/2_HDD)
Type: Domain

This domain is found in the human DNA-damage-inducible homologs 1 and 2 (hDdi1, hDdi2) and related proteins. hDdi2 is a member of the Ddi1-like protein family, which is intricately connected to the UBQ-proteasome. The better-studied yeast homologue Ddi1 (yDdi1) has been implicated in cell cycle regulation, DNA damage response, and exocytosis. There are significant functional differences between hDdi2 and yDdi1 . The domain represented by this entry is located centrally in the hDdi2, between the UBL and aspartic protease-like RVP domain. It is named HDD after "the helical domain of Ddi." It is composed of four α-helices that are arranged in a helical bundle . This domain may act as an interaction platform for an RVP substrate.
Crescentin, N-terminal domain (CreS_N)
Type: Domain

This entry represents the short N-terminal domain of intermediate filament-like cell shape determinant crescentin
(CreS) found in caulobacterales. According to structure predictions, this domain adopts an α-helical configuration.

CreS is the bacterial equivalent to Intermediate Filament (IF) proteins from eukaryotes. Its cytoskeletal function is required for the vibrioid and helical shapes of Caulobacter crescentus in which it was seen that without CreS, the cells adopt a straight-rod morphology. This protein, similarly to IF proteins, can assemble itself into filaments in vitro with no need of energy or additional cofactors. In vivo, it forms a helical structure that colocalises with the inner cell curvatures beneath the cytoplasmic membrane . CreS possesses the typical tripartite IF-like domain architecture found in IF proteins, which contains a coiled-coil rod domain with short head (N-terminal) and tail (C-terminal) domains .
GLAA-B, beta-barrel domain I (Beta-barrel_GLAA-B_I)
Type: Domain

This entry represents the first β-barrel domain found towards the N terminus of Alpha-1,3-galactosidase A-B (GLAA-B) from bacteria. These proteins share a domain architecture consisting of a core β-helix surrounded by two small β-barrel domains (domains I and II), which are involved in protein dimerisation . GLAA-B are α-galactosidases grouped in the GH110 subfamily by its narrow subtract specificity. These proteins remove branched alpha-1,3-linked galactose residues present in blood group B antigens .
Thermus phage P23-45 gp39, N-terminal (P23-45_gp39_N)
Type: Domain

This domain is found at the N-terminal in the protein gp35 from Thermus phage P23-45 and similar sequences from tailed bacteriophages. This protein binds the host's DNA-dependent RNA polymerase (RNAP), inhibiting host gene transcription while allowing transcription of phage genes. Structural studies show this core domain of the protein binds to the RNA beta-flap domain. It consists of a central β sheet and an N-terminal helix .
Secreted LysM effector LysM, C-terminal domain (LysM_C)
Type: Domain

This domain is found at the C-terminal end of Secreted LysM effector LysM3, 6, 9 and 14 from Penicillium expansum, which might have a role in sequestration of chitin oligosaccharides to dampen host defence . This domain is predicted to have a mainly β configuration.
MGAT4, conserved region (MGAT4)
Type: Domain

This entry represents the conserved region found in N-acetylglucosaminyltransferase IV (MGAT4, also known as GnT-IV) and related proteins. N-acetylglucosaminyltransferases (GnTs) take part in the formation of branches in the biosynthesis of complex-type sugar chains. In vertebrates, six GnTs, designated as GnT-I to -VI, which catalyse the transfer of GlcNAc to the core mannose residues of Asn-linked sugar chains, have been identified. GnT-IV (

) catalyses the transfer of GlcNAc from UDP-GlcNAc to the GlcNAc1-2Man1-3 arm of core oligosaccharide [Gn2(22)core oligosaccharide] and forms GlcNAc1-4(GlcNAc1-2)Man1-3 structure on the core oligosaccharide (Gn3(2,4,2)core oligosaccharide). In some members, the conserved region occupies all but the very N-terminal, where there is a signal sequence on all members. For other members, the conserved region does not occupy the entire protein but is still to the N-terminal of the protein .
REST-like, C2H2-type zinc finger (Zfn-C2H2_REST)
Type: Domain

This entry represents a C2H2-type zinc finger found in human RE1-silencing transcription factor (REST) and similar sequences from vertebrates. REST is a transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells .
RETREG1-3/ARL6IP-like, N-terminal reticulon-homology domain (RETREG1-3-like_RHD)
Type: Domain

This entry represents the N-terminal reticulon-homology domain (RHD) of Reticulophagy regulator 1-3 (RETREG1-3), ARL-6 -interacting protein 1 (ARL6IP) and similar animal sequences. These proteins are regulators involved in endoplasmic reticulum tubulation that have been associated with diverse neurological diseases .
RGF3, winged helix domain (RGF3_WH)
Type: Domain

This entry represents a winged helix domain found in Rho1 guanine nucleotide exchange factors RGF3 and TUS1 from fission and baker's yeast and related proteins. Both RGF3 and TUS1 stimulate the exchange of Rho1 GDP-bound form into GTP-bound form . RGF3 was found to regulate the beta-1,3-glucan biosynthesis and cell wall integrity during septation whereas TUS1 contributes to cell wall integrity-mediated modulation of RHO1 activity . This domain has a weak sequence similarity to known winged helix domains and it is predicted to adopt similar structure.
Rho GTPase-activating protein 35-like, FF domain (FF_RHG35_4th)
Type: Domain

This domain is found in Rho GTPase-activating protein 35 from Rattus norvegicus (RHG35) and similar animal sequences. RHG35 is involved in cell differentiation, cell adhesion and migration, retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis . This domain is predicted to adopt an all α-helical structure.
RNA cytosine-C(5)-methyltransferase NSUN2-like, pre-PUA domain (Pre-PUA_NSUN2)
Type: Domain

This domain is found in RNA cytosine C(5)-methyltransferase NSUN2 from animals, multisite-specific tRNA:(cytosine-C(5))- methyltransferase (Trm4) from yeast and related eukaryotic proteins. This domain has detectable similarity to known pre-PUA domains and it is predicted to adopt similar structure.

NSUN2 is an RNA cytosine C5-methyltransferase that methylates cytosine to 5-methylcytosine in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs .

The yeast Trm4 is capable of methylating cytosine to m5C at several positions in different yeast tRNAs and pre-tRNAs containing intron .
RNA cytosine-C(5)-methyltransferase NSUN2-like, PUA domain (PUA_NSUN2)
Type: Domain

This domain is found in RNA cytosine C(5)-methyltransferase NSUN2 from animals, multisite-specific tRNA:(cytosine-C(5))- methyltransferase (Trm4) from yeast and related eukaryotic proteins. NSUN2 is an RNA cytosine C5-methyltransferase that methylates cytosine to 5-methylcytosine in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs . Trm4 is capable of methylating cytosine to m5C at several positions in different yeast tRNAs and pre-tRNAs containing intron . This domain has a detectable similarity to known PUA domains and it is predicted to adopt similar structure.
Nodulin homeobox, N-terminal domain (Ndx_N)
Type: Domain

This domain is found at the N-terminal end of Nodulin homeobox (Ndx) from Arabidopsis thaliana and related plant proteins. Ndx regulates COOLAIR, a set of antisense transcripts originating from the 3' end of FLOWERING LOCUS C . It associates with single-stranded DNA that is part of an RNA-DNA hybrid, or R-loop, that covers the COOLAIR promoter . This domain is predicted to contain an array of α-helices.
PLEKHM2, PH domain-like (PH_PLEKHM2)
Type: Domain

This entry represents one or two PH domains found in the PLEKHM2 and related proteins. This domain does not appear to be found in the PLEKHM1 proteins.
Rab1/Ypt1 (Rab1/Ypt1)
Type: Family

This entry represents Rab1 and its yeast homologue Ypt1. Rab1 is found in eukaryotes and is a key regulatory component for the transport of vesicles from the ER to the Golgi apparatus . Studies on mutations of Ypt1 showed that this protein is necessary for the budding of vesicles of the ER as well as for their transport to, and fusion with, the Golgi apparatus .
Cation/H(+) antiporter, C-terminal domain (CHX17_C)
Type: Domain

This domain is found at the C-terminal end of the CHX family of plant Cation/H(+) antiporters, including Cation/H(+) antiporter 17 from Arabidopsis thaliana (CHX17).

Plant Cation/H+ antiporters, also known as CHX-type antiporters, are involved in exchanging K+ or Na+ ions with protons (H+) across membranes. These transporters play crucial roles in various physiological processes, including ion homeostasis, pH regulation, and plant stress responses . These transporters belong to the monovalent cation proton antiporter (CPA) superfamily.

CHX17 functions as a K+/H+ antiporter that controls K+ acquisition and homeostasis . This protein has a highly hydrophobic N-terminal domain (

) and a C-terminal region predicted to be non cytoplasmic that is organised into two domains thought to have a similar α-β configuration.
Cation/H(+) antiporter, central domain (CHX17_2nd)
Type: Domain

This entry represents the first domain of the C-terminal region of Cation/H(+) antiporter 17 from Arabidopsis thaliana (CHX17) and similar plant sequences.

Plant Cation/H+ antiporters, also known as CHX-type antiporters, are involved in exchanging K+ or Na+ ions with protons (H+) across membranes. These transporters play crucial roles in various physiological processes, including ion homeostasis, pH regulation, and plant stress responses . These transporters belong to the monovalent cation proton antiporter (CPA) superfamily.

CHX17 functions as a K+/H+ antiporter that controls K+ acquisition and homeostasis . This protein has a highly hydrophobic N-terminal domain (

) and a C-terminal region predicted to be non cytoplasmic that is organised into two domains thought to have a similar α-β configuration.
Serine/threonine-protein kinase 11-interacting protein, PH domain (PH_S11IP)
Type: Domain

This entry represents a pleckstrin homology (PH) domain found in Serine/threonine-protein kinase 11-interacting proteins (S11IP). The domain is found C-terminal to the LIP1 domain (

). Some members of this group also contain LRR (leucine-rich repeat) domains. The S11IP protein is found in vertebrates and arthropods.
Ribonuclease R, second OB domain (RNR_OB2)
Type: Domain

This entry represents the second OB domain found in ribonuclease R (RNR) from bacteria. The function of this domain is unknown.

Ribonuclease R proteins are 3'-5' exoribonucleases that release 5'-nucleoside monophosphates and are involved in maturation of structured RNAs .
Unkempt, zinc finger domain 4 (UNK_Znf_4)
Type: Domain

This entry represents the fourth CCCH-type zinc finger found in RING finger protein Unkempt (UNK).

Unkempt is an evolutionary conserved RNA-binding protein that regulates translation of its target genes and is required for the establishment of the early bipolar neuronal morphology . It carries six CCCH zinc fingers (Znfs) forming two compact clusters, Znf1-3 and Znf4-6, that recognize distinct trinucleotide RNA substrates. These clusters, recognize an unexpectedly short stretch of RNA sequence-only three consecutive ribonucleotides-with a varying degree of specificity. Znf1-3 binds to the UUA motif of RNA substrates .
Unkempt, zinc finger domain 5 (UNK_Znf_5)
Type: Domain

This entry represents the fifth CCCH-type zinc finger found in RING finger protein Unkempt (UNK).

Unkempt is an evolutionary conserved RNA-binding protein that regulates translation of its target genes and is required for the establishment of the early bipolar neuronal morphology . It carries six CCCH zinc fingers (Znfs) forming two compact clusters, Znf1-3 and Znf4-6, that recognize distinct trinucleotide RNA substrates. These clusters, recognize an unexpectedly short stretch of RNA sequence-only three consecutive ribonucleotides-with a varying degree of specificity. Znf1-3 binds to the UUA motif of RNA substrates .
RNA-dependent RNA polymerase 6-like, second domain (RDR6-like_2nd)
Type: Domain

This entry represents the second domain of RNA-dependent RNA polymerase 6 (RDR6) from Arabidopsis and related plant sequences. This domain has similarity to PH domains and it is predicted to adopt similar β-barrel structure.

RDR6 is involved in post-transcriptional gene silencing (PTGS) and natural virus resistance. It possesses ssRNA and ssDNA-dependent polymerase activity. RDR6 is required for the production of trans-acting siRNA and other siRNA .
RNA-dependent RNA polymerase 6-like, RNA-binding domain (RDR6-like_RBD)
Type: Domain

This entry represents the RNA-binding domain (RBD) found at the N-terminal of RNA-dependent RNA polymerase 6 (RPR6) from Arabidopsis and related sequences from plants.

RDR6 is involved in post-transcriptional gene silencing (PTGS) and natural virus resistance. It possesses ssRNA and ssDNA-dependent polymerase activity. RDR6 is required for the production of trans-acting siRNA and other siRNA .
RNF34/RFFL, SAP domain (RNF34_RFFL_SAP)
Type: Domain

This entry represents the SAP domains found in RNF34, RFFL and similar animal proteins.

RNF34 and RFFL are of E3 ubiquitin-protein ligases that play a crucial role in various biological processes by mediating the ubiquitin-mediated proteasomal degradation of target proteins. They are involved in the regulation of apoptosis by ubiquitinating and promoting the degradation of caspases CASP8 and CASP10 . They also participate in the regulation of the tumour necrosis factor-mediated signalling pathway, mainly through the 'Lys-48'-linked polyubiquitination and degradation of RIPK1. Additionally, they have a role in the negative regulation of p53/TP53, either directly through ubiquitination or indirectly via the degradation of SFN . RNF34 is implicated in metabolic regulation by targeting PPARGC1A for degradation , influencing brown fat cell metabolism, and is thought to be involved in innate immunity by the ubiquitination of NOD1 . Additionally, RFFL is thought to be involved in endocytic recycling.
Rrp5, OB-fold domain (OB_Rrp5)
Type: Domain

This domain is found in the rRNA biogenesis protein Rrp5 from Arabidopsis thaliana and related plant proteins. This domain has a detectable similarity to OB fold domains, in particular to OB domain of 30S ribosomal protein S1 and it is predicted to adopt similar structure.

Rrp5 is involved in the biogenesis of rRNA. It is required for formation of both 18S and 5.8S rRNA in budding yeasts . In humans, it is also known as NFBP, which is essential for the generation of 18S rRNA . In Arabidopsis, it is essential for normal development of female gametophytes .
Rrp5, OB-fold domain 4 (Rrp5_OB_4th)
Type: Domain

This domain is the 4th OB-fold domain found in the rRNA biogenesis protein Rrp5 from Arabidopsis thaliana and related proteins. It has a detectable similarity to OB fold domains, in particular to OB domain of 30S ribosomal protein S1 and it is predicted to adopt similar structure.

Rrp5 is involved in the biogenesis of rRNA. It is required for formation of both 18S and 5.8S rRNA in budding yeasts . In humans, it is also known as NFBP, which is essential for the generation of 18S rRNA . In Arabidopsis, it is essential for normal development of female gametophytes .
Rrp5, S1 domain (Rrp5_S1)
Type: Domain

This entry represents several divergent S1 domains found in Rrp5 proteins.

Rrp5 is involved in the biogenesis of rRNA. It is required for formation of both 18S and 5.8S rRNA in budding yeasts . In humans, it is also known as NFBP, which is essential for the generation of 18S rRNA . In Arabidopsis, it is essential for normal development of female gametophytes .
Rod, N-terminal (Rod_N)
Type: Domain

This entry represents the predicted β-propeller domain found at the N-terminal of Rod (

) from Drosophila and related sequences from arthropods. Rod, the orthologue of human KNTC1, is the major subunit of the Rod-Zw10-Zwilch (RZZ) complex. RZZ is an essential component of the outer kinetochore during mitosis and helps monitor and correct kinetochore-microtubule attachments during pro-metaphase, thus, regulating mitotic progression.
PDE8-like, REC N-terminal domain (PDE8-like_REC_N)
Type: Domain

This domain is found at the N-terminal of high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8 (PDE8), PDE8A, and PDE8B, which are mainly found in vertebrates. PDE8A hydrolyses the second messenger cAMP, a key regulator of many important physiological processes . This domain is predicted to adopt a Rossmann fold similar to CheY-type chemotaxis response regulators. This domain is also called REC domain .

The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They are divided into 11 families. They regulate the localisation, duration and amplitude of cyclic nucleotide signalling within subcellular domains. PDEs are therefore important for signal transduction.

PDE enzymes are often targets for pharmacological inhibition due to their unique tissue distribution, structural properties, and functional properties. Inhibitors include: Roflumilast for chronic obstructive pulmonary disease and asthma , Sildenafil for erectile dysfunction and Cilostazol for peripheral arterial occlusive disease , amongst others.

Retinal 3',5'-cGMP phosphodiesterase is located in photoreceptor outer segments: it is light activated, playing a pivotal role in signal transduction . In rod cells, PDE is oligomeric, comprising an alpha-, a beta-and 2 gamma-subunits, while in cones, PDE is a homodimer of alpha chains, which are associated with several smaller subunits. Both rod and cone PDEs catalyse the hydrolysis of cAMP or cGMP to the corresponding nucleoside 5' monophosphates, both enzymes also binding cGMP with high affinity. The cGMP-binding sites are located in the N-terminal half of the protein sequence, while the catalytic core resides in the C-terminal portion.
PDIA6-like, C-terminal thioredoxin-like domain (Thioredox_PDIA6_C)
Type: Domain

This entry represents the C-terminal thioredoxin domain found in human Protein disulfide-isomerase A6 (PDIA6) and similar eukaryotic proteins such as PDI 2-2 and 2-3 in arabidopsis and PDI 2-3 in rice.

Protein disulfide-isomerase (PDI) is an enzyme primarily located in the endoplasmic reticulum of eukaryotes and the periplasm of bacteria. It catalyses the formation, isomerisation, and reduction or oxidation of disulfide bonds between cysteine residues within proteins as they fold. PDI plays a crucial role in protein folding by allowing proteins to quickly find the correct arrangement of disulfide bonds in their fully folded state. Additionally, PDI functions as a chaperone, assisting in the folding of misfolded proteins and their subsequent degradation. In the immune system, PDI is involved in loading antigenic peptides into MHC class I molecules and plays a role in the assembly of the MHC I complex with high-affinity antigens. PDI also participates in redox signalling in some organisms, such as chloroplasts of unicellular algae .
PelB, C-terminal domain (B-barrel_PelB_C)
Type: Domain

This transmembrane β-barrel domain is found at the C-terminal end of PelB from Pseudomonas aeruginosa and similar proteins from proteobacteria. PelB plays a key role in biofilm formation in this organism .