SII-SWORD/CoKE huggingface dataset:
CO/COL/TOC1, conserved site (CCT_CS)
Type: Conserved_site

The short CCT (CO, COL, TOC1) motif is found in a number of plant proteins, including Constans (CO), Constans-like (COL) and TOC1. The CCT motif is about 45 amino acids long and contains a putative nuclear localisation signal within the second half of the CCT motif . The CCT motif is found in the Arabidopsis circadian rhythm protein TOC1, an autoregulatory response regulator homologue the controls the photoperiodic flowering through its clock function .
SFR1/Mei5 family (SFR1/Mei5)
Type: Family

This entry includes Mei5 from budding yeasts and SFR1 from animals and fission yeasts. Although the fission yeast Swi5-Sfr1 complex is critical for homologous recombination repair, the budding yeast counterpart Sae3-Mei5 complex is meiosis-specific, interacts with Dmc1, and promotes assembly of Dmc1 on meiotic chromosomes .

SFR is a component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination .
Dual oxidase maturation factor (Dual_oxidase_maturation_fac)
Type: Family

DuoxA (Dual oxidase maturation factor) is the essential protein necessary for the final release of DUOX2 (an NADPH:O2 oxidoreductase flavoprotein) from the endoplasmic reticulum. Dual oxidases (DUOX1 and DUOX2) constitute the catalytic core of the hydrogen peroxide generator, which generates H2O2 at the apical membrane of thyroid follicular cells, essential for iodination of thyroglobulin by thyroid peroxidases. DuoxA carries five membrane-integral regions including a reverse signal-anchor with external N terminus (type III) and two N-glycosylation sites . It is conserved from nematodes to humans.
Periplasmic metal-binding protein Tp34-type (Metal-bd_Tp34-typ)
Type: Family

This is a family of metal-binding periplasmic proteins. Tp34 has been classified together with other proteins in a group of uncharacterised proteins probably involved in high affinity Fe2+ transport. However, the structural and functional aspects of this group of proteins remain undetermined. Tp34 may bind zinc and the iron-sequestering lactoferrin and may have a role in metal ion homeostasis .
Large ribosomal subunit protein mL64 (Ribosomal_mL64)
Type: Family

This entry represents the large ribosomal subunit protein mL64, also known as Growth arrest and DNA damage-inducible proteins-interacting protein 1. Members of this family of proteins act as negative regulators of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. Inhibitory effects are additive with GADD45 proteins but occur also in the absence of GADD45 proteins. Furthermore, they act as a repressor of the orphan nuclear receptor NR4A1 by inhibiting AB domain-mediated transcriptional activity . They may be involved in the hormone-mediated regulation of NR4A1 transcriptional activity.
Hermes trasposase, DNA-binding domain (Hermes_transposase_DNA-db)
Type: Domain

This domain confers specific DNA-binding on Hermes transposase .
Uncharacterised protein family YqaI (Uncharacterised_Yqai)
Type: Family

The hypothetical protein YqaI is expressed in bacteria, particularly Bacillus subtilis. It forms a homo-dimer, with each monomer containing an α helix and four β strands.
Luciferase, helical bundle domain (Luciferase_hlx-bundle_domain)
Type: Domain

This domain is found associated with the the catalytic domain of dinoflagellate luciferase. Luciferase is involved in catalysing the light emitting reaction in bioluminescence. This domain has a three helix bundle structure that holds four important histidines that are thought to play a role in the pH regulation of the enzyme .
Glycerophosphoryl diester phosphodiesterase, membrane domain (GlyceroP-diester-Pdiesterase_M)
Type: Domain

Members of this family comprise the membrane domain of the prokaryotic enzyme glycerophosphoryl diester phosphodiesterase .
Bicaudal-D protein (BICD)
Type: Family

Bicaudal-D (BicD) is a family of motor adaptor proteins consist of three coiled-coiled domains. BicD plays an essential for the correct localization of maternal mRNAs in Drosophila's oocyte and functions as a regulator of the Golgi to ER retrograde transport in mammalian cells . BicD was suggested to be a linker bridging cargo and dynein and have roles in the regulation of cargo motility . It also functions as a novel regulator of neurotrophin (NT) signaling .
Sporulation transcription regulator WhiA, N-terminal domain (Sporu_reg_WhiA_N_dom)
Type: Domain

This entry represents the N-terminal domain of sporulation transcription factor WhiA . This domain is related to the LAGLIDADG homing endonuclease domain, while the C-terminal domain of WhiA is predicted to be a DNA binding helix-turn-helix domain .
Monopolin complex subunit Lrs4/Mde4 (Lrs4/Mde4)
Type: Family

Monopolin is a protein complex, originally identified in Saccharomyces cerevisiae (Baker's yeast), that is required for the segregation of homologous centromeres to opposite poles of a dividing cell during meiosis I . The orthologous complex in Schizosaccharomyces pombe (Fission yeast) is not required for meiosis I chromosome segregation, but is proposed to play a similar physiological role in clamping microtubule binding sites . In S. cerevisiae this subunit is called Lrs4, and in S. pombe it is known as Mde4 .
Phospho-N-acetylmuramoyl-pentapeptide transferase, conserved site (PNAcMuramoyl-5peptid_Trfase_CS)
Type: Conserved_site

Phospho-N-acetylmuramoyl-pentapeptide-transferase (

) (MraY) is a bacterial enzyme responsible for the formation of the first lipid intermediate of the cell wall peptidoglycan synthesis . It catalyses the formation of undecaprenyl-pyrophosphoryl-N-acetylmuramoyl-pentapeptide from UDP-MurNAc-pentapeptide and undecaprenyl-phosphate.

This entry represents two conserved sites found in these proteins. The first site is located at the end of the first cytoplasmic loop and the beginning of the second transmembrane domain. The second site is located in the third cytoplasmic loop.
Zinc finger C4H2 domain-containing protein (Znf-C4H2)
Type: Family

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents a family of proteins which appears to have a highly conserved zinc finger domain at the C-terminal end, described as -C-X2-CH-X3-H-X5-C-X2-C-. The structure is predicted to contain a coiled coil. Members of this family are annotated as being tumour-associated antigen HCA127 in humans, but this could not be confirmed.
Carbohydrate kinase, FGGY, conserved site (Carb_kinase_FGGY_CS)
Type: Conserved_site

FGGY carbohydrate kinases carry out ATP-dependent phosphorylation on one out of at least nine distinct sugar substrates . These enzymes include L-ribulokinase (

) (gene araB); Erythriol kinase (

) (gene eryA); L-fucolokinase (

) (gene fucK); gluconokinase (

) (gene gntK); glycerol kinase (

) (gene glpK); xylulokinase (

) (gene xylB); L-xylulose kinase (

) (gene lyxK), D-ribulokinase (

) (gene rbtK); and rhamnulokinase (

) (gene rhaB). This family also contains a divergent subfamily functioning in quorum sensing, which phosphorylates AI-2, a bacterial signaling molecule derived from 4,5-dihydroxy-2,3-pentanedione (DPD) .

This entry represents conserved regions found in the central and C-terminal regions of these enzymes.
Carbohydrate kinase FGGY, N-terminal (FGGY_N)
Type: Domain

This entry represents the N-terminal domain of these proteins. It adopts a ribonuclease H-like fold and is structurally related to the C-terminal domain .

FGGY carbohydrate kinases carry out ATP-dependent phosphorylation on one out of at least nine distinct sugar substrates . These enzymes include L-ribulokinase (

) (gene araB); Erythriol kinase (

) (gene eryA); L-fucolokinase (

) (gene fucK); gluconokinase (

) (gene gntK); glycerol kinase (

) (gene glpK); xylulokinase (

) (gene xylB); L-xylulose kinase (

) (gene lyxK), D-ribulokinase (

) (gene rbtK); and rhamnulokinase (

) (gene rhaB). This family also contains a divergent subfamily functioning in quorum sensing, which phosphorylates AI-2, a bacterial signaling molecule derived from 4,5-dihydroxy-2,3-pentanedione (DPD) .

All described members of this enzyme family are composed of two homologous actin-like ATPase domains. A catalytic cleft is formed by the interface between these two domains, where the sugar substrate and ATP co-substrate bind.
Carbohydrate kinase FGGY, C-terminal (FGGY_C)
Type: Domain

This entry represents the C-terminal domain of these proteins. It adopts a ribonuclease H-like fold and is structurally related to the N-terminal domain .

FGGY carbohydrate kinases carry out ATP-dependent phosphorylation on one out of at least nine distinct sugar substrates . These enzymes include L-ribulokinase (

) (gene araB); Erythriol kinase (

) (gene eryA); L-fucolokinase (

) (gene fucK); gluconokinase (

) (gene gntK); glycerol kinase (

) (gene glpK); xylulokinase (

) (gene xylB); L-xylulose kinase (

) (gene lyxK), D-ribulokinase (

) (gene rbtK); and rhamnulokinase (

) (gene rhaB). This family also contains a divergent subfamily functioning in quorum sensing, which phosphorylates AI-2, a bacterial signaling molecule derived from 4,5-dihydroxy-2,3-pentanedione (DPD) .

All described members of this enzyme family are composed of two homologous actin-like ATPase domains. A catalytic cleft is formed by the interface between these two domains, where the sugar substrate and ATP co-substrate bind.
Hemopexin, conserved site (Hemopexin_CS)
Type: Conserved_site

Hemopexin (

) is a serum glycoprotein that binds haem and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation . Hemopexin prevents haem-mediated oxidative stress. Structurally hemopexin consists of two similar halves of approximately two hundred amino acid residues connected by a histidine-rich hinge region. Each half is itself formed by the repetition of a basic unit of some 35 to 45 residues. Hemopexin-like domains have been found in two other types of proteins, vitronectin , a cell adhesion and spreading factor found in plasma and tissues, and matrixins MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-11, MMP-12, MMP-14, MMP-15 and MMP-16, members of the matrix metalloproteinase family that cleave extracellular matrix constituents . These zinc endopeptidases, which belong to MEROPS peptidase subfamily M10A, have a single hemopexin-like domain in their C-terminal section. It is suggested that the hemopexin domain facilitates binding to a variety of molecules and proteins, for example the HX repeats of some matrixins bind tissue inhibitor of metallopeptidases (TIMPs).

This entry represents a conserved sequence region located at the beginning of the second repeat in the hemopexin domain.
Hemopexin-like repeats (Hemopexin-like_repeat)
Type: Repeat

Hemopexin (

) is a serum glycoprotein that binds haem and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation . Hemopexin prevents haem-mediated oxidative stress. Structurally hemopexin consists of two similar halves of approximately two hundred amino acid residues connected by a histidine-rich hinge region. Each half is itself formed by the repetition of a basic unit of some 35 to 45 residues. Hemopexin-like domains have been found in two other types of proteins, vitronectin , a cell adhesion and spreading factor found in plasma and tissues, and matrixins MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, MMP-11, MMP-12, MMP-14, MMP-15 and MMP-16, members of the matrix metalloproteinase family that cleave extracellular matrix constituents . These zinc endopeptidases, which belong to MEROPS peptidase subfamily M10A, have a single hemopexin-like domain in their C-terminal section. It is suggested that the hemopexin domain facilitates binding to a variety of molecules and proteins, for example the HX repeats of some matrixins bind tissue inhibitor of metallopeptidases (TIMPs).

The hemopexin domain exhibits the shape of an oblate ellipsoidal disk. The polypeptide chain is organised in four β-sheet (blades) I to IV, which are almost symmetrically arranged around a central axis in consecutive order, giving rise to the formation of a four-bladed propeller. Each propeller blade or repeat is made up of four antiparallel β-strands connected in a W-like strand topology, and is strongly twisted .

This entry represents the repeats found in hemopexin and related domains.
Cyclic nucleotide-binding, conserved site (cNMP-bd_CS)
Type: Conserved_site

Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues . The best studied of these proteins is the prokaryotic catabolite gene activator (also
known as the cAMP receptor protein) (gene crp) where such a domain is known to be composed of three α-helices and a distinctive eight-stranded, antiparallel β-barrel structure. There are six invariant amino acids in this domain, three of which are glycine residues that are thought to be essential for maintenance of the structural integrity of the β-barrel. cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain. The cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain. The cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section. Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. Two such cations channels have been fully characterised, one is found in rod cells where it plays a role in visual signal transduction.
Cyclic nucleotide-binding domain superfamily (cNMP-bd_dom_sf)
Type: Homologous_superfamily

Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues . The best studied of these proteins is the prokaryotic catabolite gene activator (also
known as the cAMP receptor protein) (gene crp) where such a domain is known to be composed of three α-helices and a distinctive eight-stranded, antiparallel β-barrel structure. There are six invariant amino acids in this domain, three of which are glycine residues that are thought to be essential for maintenance of the structural integrity of the β-barrel. cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain. The cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain. The cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section. Vertebrate cyclic nucleotide-gated ion-channels also contain this domain. Two such cations channels have been fully characterised, one is found in rod cells where it plays a role in visual signal transduction.
SLC12A transporter, C-terminal (SLC12_C)
Type: Domain

This entry represents a domain found in the C-terminal of the solute carrier family 12 (SLC12) members, which are K-Cl cotransporters. The SLC12 family members are predicted to have 12 transmembrane (TM) regions in a central hydrophobic domain, together with hydrophilic N- and C-termini that are likely cytoplasmic. Comparison of their sequences with those of other ion-tranporting membrane proteins reveals that they are part of a new superfamily of cation-chloride co-transporters, which includes the Na-Cl and Na-K-2Cl co-transporters .
Ribosomal protein eL8/Nhp2 family (Ribosomal_eL8/Nhp2)
Type: Family

This entry includes large ribosomal subunit protein eL8 (in human is also known as L7a and in yeast is also known as L4) and several other ribosomal proteins that have been found to share sequence similarity with eL8/L7a, including Saccharomyces cerevisiae NHP2 .

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 .
Gas vesicle protein A-like, conserved site (GvpA-like_CS)
Type: Conserved_site

This entry represents conserved sequence regions located in the N- and C-terminal domains of Gas vesicle protein A from Streptomyces sp. and similar prokaryotic sequences.

Gas vesicles (GVs) are small, hollow, gas filled protein structures found in several cyanobacterial and archaebacterial microorganisms . They allow the positioning of the bacteria at the favourable depth for growth. Gas vesicles are hollow cylindrical tubes, closed by a hollow, conical cap at each end. Both the conical end caps and central cylinder are made up of 4-5 nm wide ribs that run at right angles to the long axis of the structure. Gas vesicles seem to be constituted of two different protein components, GvpA and GvpC. GvpA, a small protein of about 70 amino acid residues, is the main constituent of gas vesicles and form the essential core of the structure, while GvpC binds the exterior of the GV and provides additional structural reinforcement . The sequence of GVPa is extremely well conserved. GvpJ and GvpM, two proteins encoded in the cluster of genes required for gas vesicle synthesis in the archaebacteria Halobacterium salinarum and Halobacterium mediterranei (Haloferax mediterranei), have been found to be evolutionary related to GVPa. The exact function of these two proteins is not known, although they could be important for determining the shape determination gas vesicles. The N-terminal domain of Aphanizomenon flos-aquae protein GvpA/J is also related to GvpA.
Oxysterol-binding protein, conserved site (Oxysterol-bd_CS)
Type: Conserved_site

A number of eukaryotic proteins that seem to be involved with sterol synthesis and/or its regulation have been found to be evolutionary related. These include mammalian oxysterol-binding protein (OSBP), a protein of about 800 amino-acid residues that binds a variety of oxysterols (oxygenated derivatives of cholesterol) ; yeast Osh1, a protein of 859 residues that also plays a role in ergosterol synthesis ; yeast proteins Hes1 and Kes1, highly related proteins of 434 residues that seem to play a role in ergosterol synthesis ; Probable transporter efuK from the fungi Hormonema carpetanum, which is involved in the biosynthesis of enfumafungin ; and OSBP-related proteins (ORP) from plants such as Arabidopsis thaliana .

This entry represents a sequence region in these proteins that contains a conserved pentapetide.
Succinate dehydrogenase, cytochrome b subunit, conserved site (Succ_DH_cyt_bsu_CS)
Type: Conserved_site

Succinate dehydrogenase (SDH) is a membrane-bound complex of two main components: a membrane-extrinsic component composed of an FAD-binding flavoprotein and an iron-sulphur protein, and a hydrophobic component composed of a cytochrome b and a membrane anchor protein. The cytochrome b component is a mono-haem transmembrane protein belonging to a family that includes:

Cytochrome b-556 from bacterial SDH (gene sdhC).

Cytochrome b560 from the mammalian mitochondrial SDH complex, which is encoded in the mitochondrial genome of some algae and in the plant Marchantia polymorpha.

Cytochrome b from yeast mitochondrial SDH complex (gene SDH3 or CYB3).

Protein cyt-1 from Caenorhabditis elegans.

These cytochromes are proteins of about 130 residues that comprise three transmembrane regions. There are two conserved histidines which may be involved in binding the haem group.
Pseudouridine synthase, RsuA/RluB/E/F, conserved site (PsdUridine_synth_RsuA/RluB_CS)
Type: Conserved_site

Pseudouridine synthases catalyse the isomerisation of uridine to pseudouridine (Psi) in a variety of RNA molecules, and may function as RNA chaperones. Pseudouridine is the most abundant modified nucleotide found in all cellular RNAs. There are four distinct families of pseudouridine synthases that share no global sequence similarity, but which do share the same fold of their catalytic domain(s) and uracil-binding site and are descended from a common molecular ancestor. The catalytic domain consists of two subdomains, each of which has an α+β structure that has some similarity to the ferredoxin-like fold (note: some pseudouridine synthases contain additional domains). The active site is the most conserved structural region of the superfamily and is located between the two homologous domains. These families are :

Pseudouridine synthase I, TruA.

Pseudouridine synthase II, TruB, which contains and additional C-terminal PUA domain.

Pseudouridine synthase RsuA. RluB, RluE and RluF are also part of this family.

Pseudouridine synthase RluA. TruC, RluC and RluD belong to this family.

Pseudouridine synthase TruD, which has a natural circular permutation in the catalytic domain, as well as an insertion of a family-specific α+β subdomain.

This entry represents several different pseudouridine synthases from family 3, including: RsuA (acts on small ribosomal subunit), RluB, RluE and RluF (act on large ribosomal subunit).