SII-SWORD/CoKE huggingface dataset:
Small ribosomal subunit protein eS6, conserved site (Ribosomal_eS6_CS)
Type: Conserved_site

A number of eukaryotic and archaeal ribosomal proteins have been grouped on the basis of sequence similarities. Small ribosomal subunit protein eS6, previously known as Ribosomal protein S6 is the major substrate of protein kinases in eukaryotic ribosomes and may play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA.

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 .
Small ribosomal subunit protein eS8, conserved site (Ribosomal_eS8_CS)
Type: Conserved_site

This entry represents the small ribosomal subunit protein eS8 from archaea and eukaryotes , which consists of a number of proteins with either about 220 amino acids (in eukaryotes) or about 125 amino acids (in archaea).

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 .
Methionyl-tRNA synthetase, N-terminal heteromerisation domain (Met-tRNA-synth_N)
Type: Domain

This entry represents the N-terminal domain of methionyl-tRNA synthetase (MetRS). This N-terminal appended domain mediates non-catalytic complex formation through its interaction with a domain in the tRNA aminoacylation cofactor Arc1p. The interacting domains of MetRS, GluRS (glutamyl-tRNA synthetase) and Arc1p form a ternary complex resembling a classical GST homo-dimer . Domain-swapping between symmetrically related MetRS-N and Arc1p-N domains generates a 2:2 tetramer held together by van der Waals forces. This domain is necessary for formation of the aminoacyl-tRNA synthetase complex necessary for tRNA nuclear export and shuttling as part of the translational apparatus.
Hap4 transcription factor, heteromerisation domain (Hap4_TF_heteromerisation)
Type: Domain

This entry represents an essential domain of the transcription activator Hap4 that allows it to associate with Hap2, Hap3 and Hap5 to form the Hap complex . In Saccharomyces cerevisiae (Baker's yeast), the haem-activated protein complex Hap2/3/4/5 plays a major role in the transcription of genes involved in respiration .
F420-dehydrogenase, subunit FpoO (F420H2-DH_FpoO)
Type: Family

This entry represents the FpoO subunit of membrane-bound multi-subunit F420H2 dehydrogenase, which oxidises the reduced coenzyme F420H2 to coenzyme F420 and feeds the electrons via an FeS cluster into an energy-conserving electron transport chain . This enzyme plays a role in the methanogenic pathway in methanogenic archaea. Reduced coenzyme F420H2 is the major cytoplasmic electron carrier of methanogens and a reversible hydride donor, much like NADH .

F420H2 + COB-S-S-CoM = F420 + CoM-SH + CoB-SH

Where CoB-S-S-CoM (the heterosulphide of 2-mercaptoethanesulphonate and 7-mercaptoheptanoylthreonine phosphate) is the terminal electron acceptor of the methanogenic pathway, and is reduced with the concomitant generation of a transmembrane proton potential and ATP synthesis.
MULE transposase domain (MULE_transposase_dom)
Type: Domain

This entry represents a domain found in Mutator-like elements (MULE)-encoded tranposases, some of which also contain a zinc-finger motif . This domain is also found in a transposase for the insertion sequence element IS256 in transposon Tn4001 .
MULE transposase, N-terminal all-beta domain (MULE_transposase_N)
Type: Domain

This entry represents a domain with an all-β structure that is found in Mutator-like elements (MULE)-encoded tranposases, some of which also contain a zinc-finger motif . This domain is found associated with the WRKY domain .
5 transmembrane protein, Schizosaccharomyces pombe (5TM-prot_SCHPO)
Type: Family

This entry represents a group of proteins containing five transmembrane regions. These proteins are found exclusively in Schizosaccharomyces pombe (Fission yeast).
43kDa postsynaptic, conserved site (Postsynaptic_CS)
Type: Conserved_site

The 43kDa postsynaptic protein is a peripheral membrane protein thought to be involved in the anchoring or stabilisation of the nicotinic acetylcholine receptor at synaptic sites . It may link the receptor to the postsynaptic cytoskeleton through direct association with actin or spectrin. The 43kDa protein is highly conserved across species. Two highly conserved regions, one encompassing the N terminus and the other near the C terminus, may be important for interaction of the protein with other components of the postsynaptic membrane. This entry represents the N-terminal sequence of the mature protein (after removal of the initiator methionine); the resulting N-terminal glycine is thought to be myristoylated.
4-diphosphocytidyl-2C-methyl-D-erythritol synthase, conserved site (ISPD_synthase_CS)
Type: Conserved_site

4-diphosphocytidyl-2C-methyl-D-erythritol synthase, a bacterial ispD protein, catalyzes the third step of the deoxyxylulose-5-phosphate pathway (DXP) of isoprenoid biosynthesis; the formation of 4-diphosphocytidyl-2C-methyl-D-erythritol from CTP and 2C-methyl-D-erythritol 4-phosphate . The isoprenoid pathway is a well known target for anti-infective drug development .

This entry represents a pattern that identifies IspD. The pattern is centred on a central conserved region that contains a conserved Asp and Arg residues.
FLAP/GST2/LTC4S, conserved site (FLAP/GST2/LTC4S_CS)
Type: Conserved_site

These are proteins of 150 to 160 residues that contain three transmembrane segments. As a signature for these proteins a conserved region between the first and second transmembrane domains has been used.
Acid phosphatase, class A, bacterial, conserved site (Acid_Pase_classA_bac_CS)
Type: Conserved_site

Class A bacterial acid phosphatases (

) are a group of related proteins that catalyse the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate . This reaction is non-specific and occurs in the periplasm. The enzyme is found as a homotetramer in Morganella morganii (Proteus morganii) and possibly as a homodimer in Salmonella typhimurium, where it is regulated by a 2-component regulatory system formed by the products of the phoP and phoQ genes .
Adenylyl cyclase class-4/guanylyl cyclase, conserved site (A/G_cyclase_CS)
Type: Conserved_site

Guanylate cyclases (

) catalyze the formation of cyclic GMP (cGMP) from GTP. cGMP acts as an intracellular messenger, activating cGMP-dependent kinases and regulating CGMP-sensitive ion channels. The role of cGMP as a second messenger in vascular smooth muscle relaxation and retinal photo-transduction is well established. Guanylate cyclase is found both in the soluble and particular fraction of eukaryotic cells. The soluble and plasma membrane-bound forms differ in structure, regulation and other properties.

Most currently known plasma membrane-bound forms are receptors for small polypeptides. The topology of such proteins is the following: they have a N-terminal extracellular domain which acts as the ligand binding region, then a transmembrane domain, followed by a large cytoplasmic C-terminal region that can be subdivided into two domains: a protein kinase-like domain that appears important for proper signalling and a cyclase catalytic domain. This topology is schematically represented below.

+-----------------------xxxxx----------------------+------------+
| Ligand-binding XXXXX Protein Kinase like | Cyclase |
+-----------------------xxxxx----------------------+------------+
Extracellular Transmembrane Cytoplasmic

The known guanylate cyclase receptors are:

The sea-urchins receptors for speract and resact, which are small peptides that stimulate sperm motility and metabolism.

The receptors for natriuretic peptides (ANF). Two forms of ANF receptors with guanylate cyclase activity are currently known: GC-A (or ANP-A) which seems specific to atrial natriuretic peptide (ANP), and GC-B (or ANP-B) which seems to be stimulated more effectively by brain natriuretic peptide (BNP) than by ANP.

The receptor for Escherichia coli heat-stable enterotoxin (GC-C). The endogenous ligand for this intestinal receptor seems to be a small peptide called guanylin.

Retinal guanylate cyclase (retGC) which probably plays a specific functional role in the rods and/or cones of photoreceptors. It is not known if this protein acts as receptor, but its structure is similar to that of the other plasma membrane-bound GCs.

The soluble forms of guanylate cyclase are cytoplasmic heterodimers. The two subunits, alpha and beta are proteins of from 70 to 82 Kd which are highly related. Two forms of beta subunits are currently known: beta-1 which seems to be expressed in lung and brain, and beta-2 which is more abundant in kidney and liver.
Alkaline phosphatase, active site (Alkaline_phosphatase_AS)
Type: Active_site

Alkaline phosphatase ([ec:EC 3.1.3.1]) (ALP) is a zinc and magnesium-containing metalloenzyme which hydrolyzes phosphate esters, optimally at high pH. It is found in nearly all living organisms, with the exception of some plants. In Escherichia coli, ALP is found in the periplasmic space. In yeast, it is found in lysosome-like vacuoles and in mammals, it is a glycoprotein attached to the membrane by a GPI-anchor.

In mammals, four different isozymes are currently known . Three of them are tissue-specific: the placental, placental-like (germ cell) and intestinal isozymes. The fourth form is tissue non-specific and was previously known as the liver/bone/kidney isozyme.

Streptomyces species involved in the synthesis of streptomycin (SM), an antibiotic, express a phosphatase (

) (gene strK) which is highly related to ALP. It specifically cleaves both streptomycin-6-phosphate and, more slowly, streptomycin-3"-phosphate .
Aminotransferase, class IV, conserved site (Aminotrans_IV_CS)
Type: Conserved_site

Aminotransferases share certain mechanistic features with other pyridoxal-phosphate dependent enzymes, such as the covalent binding of the pyridoxal-phosphate group to a lysine residue. On the basis of sequence similarity, these various enzymes can be grouped into subfamilies.

One of these, called class-IV, currently consists of proteins of about 270 to 415 amino-acid residues that share a few regions of sequence similarity. Surprisingly, the best conserved region does not include the lysine residue to which the pyridoxal-phosphate group is known to be attached, in ilvE, but is located some 40 residues at the C terminus side of the pyridoxal-phosphate-lysine. The D-amino acid transferases (D-AAT), which are among the members of this entry, are required by bacteria to catalyse the synthesis of D-glutamic acid and D-alanine, which are essential constituents of bacterial cell wall and are the building block for other D-amino acids. Despite the difference in the structure of the substrates, D-AATs and L-ATTs have strong similarity .
Aromatic amino acid hydroxylase, iron/copper binding site (ArAA_hydroxylase_Fe/CU_BS)
Type: Binding_site

Phenylalanine, tyrosine and tryptophan hydroxylases constitute a family of tetrahydrobiopterin-dependent aromatic amino acid hydroxylases, all of which are rate-limiting catalysts for important metabolic pathways . The proteins are structurally and functionally related, each containing iron, and catalysing ring hydroxylation of aromatic amino acids, using tetra-hydrobiopterin (BH4) as a substrate. All are regulated by phosphorylation at serines in their N-termini. It has been suggested that the proteins each contain a conserved C-terminal catalytic (C) domain and an unrelated N-terminal regulatory (R) domain. It is possible that the R domains arose from genes that were recruited from different sources to combine with the common gene for the catalytic core. Thus, by combining with the same C domain, the proteins acquired the unique regulatory properties of the separate R domains.

A variety of enzymes belong to this family that includes, phenylalanine-4-hydroxylase from Chromobacterium violaceum where it is copper-dependent; it is iron-dependent in Pseudomonas aeruginosa, phenylalanine-4-hydroxylase catalyzes the conversion of phenylalanine to tyrosine. In humans, deficiencies are the cause of phenylketonuria, the most common inborn error of amino acid metabolism , tryptophan 5-hydroxylase catalyzes the rate-limiting step in serotonin biosynthesis: the conversion of tryptophan to 3-hydroxy-anthranilate and tyrosine 3-hydroxylase catalyzes the rate limiting step in catecholamine biosynthesis: the conversion of tyrosine to 3,4-dihydroxy-L-phenylalanine.

Enzymes that belong to this family are functionally as well as structurally related . Their size ranges from 260 residues for bacterial PAH, to about 500 residues for eukaryotic PAH, TYH and TRH. The signature pattern used in this entry is to a conserved region in the central part of these enzymes, which contains two conserved histidines that are involved in the binding to iron or copper .
Kinetochore protein Cenp-F/LEK1, Rb protein-binding domain (CenpF/LEK1_Rb-prot-bd)
Type: Domain

This entry represents the Rb protein-binding domain from the centromere protein Cenp-F. Cenp-F is a centromeric kinetochore, microtubule-binding protein consisting of two 1,600-amino acid-long coils, that is involved in chromosome segregation during mitosis and is essential for the full functioning of the mitotic checkpoint pathway . Cenp-F interacts with retinoblastoma protein (RB), CENP-E and BUBR1. This domain is at the very C terminus of the C-terminal coiled-coil region, and binds to the Rb family of tumour suppressors .
P-type ATPase, phosphorylation site (ATPase_P-typ_P_site)
Type: PTM

This entry represents the several classes of P-type ATPases, including those that transport K
+
(

), Mg
2+
(

), Cd
2+
(

), Cu
2+
(

), Zn
2+
(

), Na
+
(

), Ca
2+
(

), Na
+
/K
+
(

), and H
+
/K
+
(

). These P-ATPases are found in both prokaryotes and eukaryotes . They are cation transport ATPases which form an aspartyl phosphate intermediate in the course of ATP hydrolysis. The region around the phosphorylated aspartate residue is perfectly conserved in all these ATPases and it is represented by this entry.
Transcription regulator protein Rtt102 (Rtt102)
Type: Family

Rtt102 (Regulator of Ty1 Transposition Protein 102) is a component of both the SWI/SNF and the RSC chromatin remodelling complexes .
Large ribosomal subunit protein mL50 (Ribosomal_m50)
Type: Family

This entry represents the large ribosomal subunit protein mL50 from animals and fungi, previously known as L50 in humans and L13 in yeast .
Bacteriophage T5, Orf172 DNA-binding (Phage_T5_Orf172_DNA-bd)
Type: Domain

This entry represents a DNA-binding domain found in bacteriophage T5, ORF172 . The domain is related to the Bro-N and KilA-N domains that are widespread in large-DNA viruses infecting bacteria and eukaryotes .
AVL9/DENND6 domain (ABL9/DENND6_dom)
Type: Domain

This domain is found in late secretory protein Avl9, which is required for the generation of secretory vesicles as well as for actin polarization and polarized growth. It is also found in DENND6 proteins, which act as guanine nucleotide exchange factors (GEF) for RAB14 .
Transcription regulator PadR, C-terminal (Tscrpt_reg_PadR_C)
Type: Domain

Phenolic acids, also called substituted hydroxycinnamic acids, are abundant in the plant kingdom because they are involved in the structure of plant cell walls and are present in some vacuoles. In plant-soil ecosystems they are released as free acids by hemicellulases produced by several fungi and bacteria. Of these weak acids, the most abundant are p-coumaric, ferulic, and caffeic acids, considered to be natural toxins that inhibit the growth of microorganisms, especially at low pHs. In spite of this chemical stress, some bacteria can use phenolic acids as a sole source of carbon. For other microorganisms, these compounds induce a specific response by which the organism adapts to its environment. The ubiquitous lactic acid bacterium Lactobacillus plantarum exhibits an inducible phenolic acid decarboxylase (PAD) activity which converts these substrates into less-toxic vinyl phenol derivatives. PadR acts as a repressor of padA gene expression in the phenolic acid stress response . This entry represents the C-terminal domain.
Putative endonuclease, Z1 domain (Put_endonuclease_Z1-dom)
Type: Domain

This entry represents the Z1 domain of unknown function that is found in a group of putative endonucleases. This domain is found associated with a helicase domain of superfamily type II .
Autoinducer synthesis, conserved site (Autoind_synth_CS)
Type: Conserved_site

Bacterial species have many methods of controlling gene expression and cell growth. Regulation of gene expression in response to changes in cell density is termed quorum sensing . Quorum-sensing bacteria produce, release and respond to hormone-like molecules (autoinducers) that accumulate in the external environment as the cell population grows. Once a threshold of these molecules is reached, a signal transduction cascade is triggered that ultimately leads to behavioural changes in the bacterium . Autoinducers are thus clearly important mediators of molecular communication.

Conjugal transfer of Agrobacterium octopine-type Ti plasmids is activated by octopine, a metabolite released from plant tumours . Octopine causes conjugal donors to secrete a pheromone, Agrobacterium autoinducer (AAI),and exogenous AAI further stimulates conjugation. The putative AAI synthase and an AAI-responsive transcriptional regulator have been found to be encoded by the Ti plasmid traI and traR genes, respectively. TraR and TraI are similar to the LuxR and LuxI regulatory proteins of Vibrio fischeri, and AAI is similar in structure to the diffusable V. fischeri autoinducer, the inducing ligand of LuxR. TraR activates target genes in the presence of AAI and also activates traR and traI themselves, creating two positive-feedback loops. TraR-AAI-mediated activation in wild-type Agrobacterium strains is enhanced by culturing on solid media, suggesting a possible role in cell density sensing .

Production of light by the marine bacterium V. fischeri and by recombinant hosts containing cloned lux genes is controlled by the density
of the culture . Density-dependent regulation of lux gene expression has been shown to require a locus consisting of the luxR and luxI genes.

In these and other Gram-negative bacteria, N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) acts as the autoinducer by binding to transcriptional regulatory proteins and activating them . OHHL and related molecules, such as N-butanoyl- (BHL), N-hexanoyl- (HHL) and N-oxododecanoyl- (PAI) homoserine lactones, are produced by a family of proteins that share a high level of sequence similarity.

Proteins which currently members of this family include:

luxI from V. fischeri.

ahyI and asaI from Aeromonas species, which synthesize BHL and whose targets are ahyR and asaR respectively.

carI from Erwinia carotovora. The target of OHHL is carR which activates genes involved in the biosynthesis of carbapenem antibiotics.

eagI from Enterobacter agglomerans. The target of OHHL is not yet known.

esaI from Erwinia stewartii.

expI from E. carotovora.

lasI from Pseudomonas aeruginosa, which synthesizes PAI and whose target is lasR which activates the transcription of the elastase gene.

rhlI (or vsmI) from P. aeruginosa, which synthesizes BHL and HHL and whose target is rhlR.

swrI from Serratia liquefaciens, which synthesizes BHL.

yenI from Yersinia enterocolitica.

This entry represents proteins sequences that match a pattern found in the best conserved region, which is located in the N terminus.
Chromosomal replication control, initiator DnaA, conserved site (Chromosome_initiator_DnaA_CS)
Type: Conserved_site

The bacterial dnaA protein plays an important role in initiating and regulating chromosomal replication. DnaA is an ATP- and DNA-binding protein. It binds specifically to 9 bp nucleotide repeats known as dnaA boxes which are found in the chromosome origin of replication (oriC).

DnaA is a protein of about 50kDa that contains two conserved regions: the first is located in the N-terminal half and corresponds to the ATP-binding domain, the second is located in the C-terminal half and could be involved in DNA-binding. The protein may also bind the RNA polymerase beta subunit, the dnaB and dnaZ proteins, and the groE gene products (chaperonins) .

The signature pattern in this entry is located in the most conserved part of the putative DNA-binding domain.