SII-SWORD/CoKE huggingface dataset:
Polyketide synthase-like, phosphopantetheine-binding domain (PKS_PP-bd)
Type: Domain

This entry represents the phosphopantetheine-binding domain from polyketide synthases and related synthase proteins. Polyketide synthases are large multidomain proteins involved in the synthesis of secondary metabolites .

Phosphopantetheine (or pantetheine 4' phosphate) is the prosthetic group of acyl carrier proteins (ACP) in some multienzyme complexes where it serves as a 'swinging arm' for the attachment of activated fatty acid and amino-acid groups .

The amino-terminal region of the ACP proteins is well defined and consists of four α helices arranged in a right-handed bundle held together by interhelical hydrophobic interactions. The Asp-Ser-Leu (DSL) motif is conserved in all of the ACP sequences, and the 4'-PP prosthetic group is covalently linked via a phosphodiester bond to the serine residue. The DSL sequence is present at the amino terminus of helix II, a domain of the protein referred to as the recognition helix and which is responsible for the interaction of ACPs with the enzymes of type II fatty acid synthesis .
Polyketide/metazoan fatty acid synthase-like, dehydratase domain (PKS_DH)
Type: Domain

This entry represents the dehydratase domain (DH) found in polyketide synthases, fatty acid synthase and some nodulation proteins.

The fundamental polymers of biology proteins, DNA, and RNA are products of repetitive condensation of simple amino acid or nucleotide building blocks and are comparatively easy to assemble. However, other biomolecules require additional reactions beyond condensation of building blocks. Examples are the fatty acids and the polyketide and nonribosomal peptide secondary metabolites. These molecules are produced by complex enzyme assembly lines that include multiple catalytic domains.

Modular polyketide synthases (PKSs) systems are thought to share a common ancestor with metazoan fatty acid synthases (mFAS). Both have multifunctional polypeptide chains with catalytic domains for elongation and modification of intermediate products, which are covalently attached to an acyl carrier protein (ACP) domain via a thioester linkage. In the mFAS and modular PKS pathways, intermediate compounds are extended by the action of two elongation domains: the acyltransferase (AT) and ketosynthase (KS). The beta-keto product of the elongation reactions may be altered by the sequential actions of ketoreductase (KR), dehydratase (DH), and enoylreductase (ER) modifying domains, which form a hydroxyl group, double bond and single bond, respectively. Although fatty acids are synthesized in an iterative fashion, with the intermediate chain extended and modified within the same polypeptide, modular PKS systems operate in an assembly-line fashion, in which intermediates are passed to successive modules in a megacomplex.

Dehydratase domains catalyse formation of an α,β-double bond in the nascent polyketide intermediate. The mFAS and PKS dehydratase domains are evident products of gene duplication and fusion, and share a common ancestor with the bacterial FAS DH enzymes (FabA and FabZ) . The product template (PT) domains are PKS/mFAS DH domains that act as an aldol cyclase to control theregiospecific aldol cyclisation of the extremely reactive poly-beta-ketone intermediate assembled by an iterative type I polyketide synthases (PKSs) .

The PKS/mFAS DH domain comprises two repeats of the hotdog fold. The ~125-residue N-terminal hotdog is slightly shorter than the ~140-residue C-terminal hotdog. The double-hotdog fold forms a continuous antiparallel β sheet in which the β strands curve around the "hotdog" helices (alphaHD1 from the N-terminal and alphaHD2 from the C-terminal hotdog folds). The double-hotdog core is topped by a cap motif comprising a 3(10)
helix, a four-stranded β sheet, and a single α-helix, and additionally, a short C-terminal 3(10) helix can be considered part of the cap. The DH
active site is a His-Asp "catalytic dyad" with the histidine from the N-terminal hotdog and the aspartate from the C-terminal hotdog .
Bacterial microcompartments protein, conserved site (Bact_microcomp_CS)
Type: Conserved_site

Bacterial microcompartments (BMCs) are large proteinaceous structures comprised of a roughly icosahedral shell and a series of encapsulated enzymes. The shells of BMCs are made primarily of a family of proteins whose structural core is the BMC domain, and variations upon this core provide functional diversity. This domain is found in a variety of polyhedral organelle shell proteins (CcmK), including CsoS1A, CsoS1B and CsoS1C of Thiobacillus neapolitanus (Halothiobacillus neapolitanus) and their orthologues from other bacteria .

Some autotrophic and non-autotrophic organisms form polyhedral organelles, carboxysomes/enterosomes . The best studied is the carboxysome of Halothiobacillus neapolitanus, which is composed of at least 9 proteins: six shell proteins, CsoS1A, CsoS1B, CsoS1C, Cso2A, Cso2B and CsoS3 (carbonic anhydrase) , one protein of unknown function and the large and small subunits of RuBisCo (CbbL and Cbbs). Carboxysomes appear to be approximately 120 nm in diameter, most often observed as regular hexagons, with a solid interior bounded by a unilamellar protein shell. The interior is filled with type I RuBisCo, which is composed of 8 large subunits and 8 small subunits; it accounts for 60% of the carboxysomal protein, which amounts to approximately 300 molecules of enzyme per carboxysome. Carboxysomes are required for autotrophic growth at low CO
2
concentrations and are thought to function as part of a CO
2
-concentrating mechanism .

Polyhedral organelles, enterosomes, from non-autotrophic organisms are involved in coenzyme B
12
-dependent 1,2-propanediol utilisation (e.g., in Salmonella enterica ) and ethanolamine utilisation (e.g., in Salmonella typhimurium ). Genes needed for enterosome formation are located in the 1,2-propanediol utilisation
pdu
or ethanolamine utilisation
eut
operons, respectively. Although enterosomes of non-autotrophic organisms are apparently related to carboxysomes structurally, a functional relationship is uncertain. A role in CO
2
concentration, similar to that of the carboxysome, is unlikely since there is no known association between CO
2
and coenzyme B12-dependent 1,2-propanediol or ethanolamine utilisation . It seems probable that enterosomes help protect the cells from reactive aldehyde species in the degradation pathways of 1,2-propanediol and ethanolamine .

The BMC domain fold consists of three α-helices (designated A, B, and C) and four β-strands (

). Some instances of the BMC shell protein reveal a circular permutation in which a highly similar tertiary structure is built from secondary structure elements occurring in a different order. The secondary structure elements contributed by the C-terminal region of the typical BMC fold are instead contributed by the N-terminal region of the BMC circularly permuted domain (

) .

This entry represents a conserved region found at the N-terminal of the Bacterial microcompartment (BMC) domain from BMC proteins.
Enolase, conserved site (Enolase_CS)
Type: Conserved_site

This entry represents a conserved region located in the C-terminal third of the sequence.

Enolase (2-phospho-D-glycerate hydrolase) is an essential glycolytic enzyme that catalyses the interconversion of 2-phosphoglycerate and phosphoenolpyruvate . In vertebrates, there are 3 different, tissue-specific isoenzymes, designated alpha, beta and gamma. Alpha is present in most tissues, beta is localised in muscle tissue, and gamma is found only in nervous tissue. The functional enzyme exists as a dimer of any 2 isoforms. In immature organs and in adult liver, it is usually an alpha homodimer, in adult skeletal muscle, a beta homodimer, and in adult neurons, a gamma homodimer. In developing muscle, it is usually an alpha/beta heterodimer, and in the developing nervous system, an alpha/gamma heterodimer . The tissue specific forms display minor kinetic differences. Tau-crystallin, one of the major lens proteins in some fish, reptiles and birds, has been shown to be evolutionary related to enolase.

Neuron-specific enolase is released in a variety of neurological diseases, such as multiple sclerosis and after seizures or acute stroke. Several tumour cells have also been found positive for neuron-specific enolase. Beta-enolase deficiency is associated with glycogenosis type XIII defect.
Enolase, C-terminal TIM barrel domain (Enolase_C)
Type: Domain

Enolase (2-phospho-D-glycerate hydrolase) is an essential, homodimeric enzyme that catalyses the reversible dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate as part of the glycolytic and gluconeogenesis pathways . The reaction is facilitated by the presence of metal ions . In vertebrates, there are 3 different, tissue-specific isoenzymes, designated alpha, beta and gamma. Alpha is present in most tissues, beta is localised in muscle tissue, and gamma is found only in nervous tissue. The functional enzyme exists as a dimer of any 2 isoforms. In immature organs and in adult liver, it is usually an alpha homodimer, in adult skeletal muscle, a beta homodimer, and in adult neurons, a gamma homodimer. In developing muscle, it is usually an alpha/beta heterodimer, and in the developing nervous system, an alpha/gamma heterodimer . The tissue specific forms display minor kinetic differences. Tau-crystallin, one of the major lens proteins in some fish, reptiles and birds, has been shown to be evolutionary related to enolase.

Neuron-specific enolase is released in a variety of neurological diseases, such as multiple sclerosis and after seizures or acute stroke. Several tumour cells have also been found positive for neuron-specific enolase. Beta-enolase deficiency is associated with glycogenosis type XIII defect.
Enolase, N-terminal (Enolase_N)
Type: Domain

Enolase (2-phospho-D-glycerate hydrolase) is an essential, homodimeric enzyme that catalyses the reversible dehydration of 2-phospho-D-glycerate to phosphoenolpyruvate as part of the glycolytic and gluconeogenesis pathways . The reaction is facilitated by the presence of metal ions . In vertebrates, there are 3 different, tissue-specific isoenzymes, designated alpha, beta and gamma. Alpha is present in most tissues, beta is localised in muscle tissue, and gamma is found only in nervous tissue. The functional enzyme exists as a dimer of any 2 isoforms. In immature organs and in adult liver, it is usually an alpha homodimer, in adult skeletal muscle, a beta homodimer, and in adult neurons, a gamma homodimer. In developing muscle, it is usually an alpha/beta heterodimer, and in the developing nervous system, an alpha/gamma heterodimer . The tissue specific forms display minor kinetic differences. Tau-crystallin, one of the major lens proteins in some fish, reptiles and birds, has been shown to be evolutionary related to enolase.

Neuron-specific enolase is released in a variety of neurological diseases, such as multiple sclerosis and after seizures or acute stroke. Several tumour cells have also been found positive for neuron-specific enolase. Beta-enolase deficiency is associated with glycogenosis type XIII defect.
Fibrillarin, conserved site (Fibrillarin_CS)
Type: Conserved_site

Fibrillarin is a component of a nucleolar small nuclear ribonucleoprotein (SnRNP), functioning
in vivo
in ribosomal RNA processing . It is associated with U3, U8 and U13 small nuclear RNAs in mammals and is similar to the yeast NOP1 protein . Fibrillarin has a well conserved sequence of around 320 amino acids, and contains 3 domains, an N-terminal Gly/Arg-rich region; a central domain resembling other RNA-binding proteins and containing an RNP-2-like consensus sequence; and a C-terminal α-helical domain. An evolutionarily related pre-rRNA processing protein, which lacks the Gly/Arg-rich domain, has been found in various archaebacteria.

The signature pattern for this entry encompasses the RNP-2 like octapeptide sequence.
Small ribosomal subunit protein bS6, plastid/chloroplast (Ribosomal_S6_plastid/chlpt)
Type: Family

This entry represents the small ribosomal subunit protein bS6 family.

The small subunits of bacterial and eukaryotic ribosomes have the same overall shapes (with structural elements described as head, body, platform, beak and shoulder). Ribosomal protein bS6 is one of the proteins from the small ribosomal subunit. . In Escherichia coli, bS6 is known to bind together with bS18 to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacterial, red algal chloroplast and cyanelle bS6 ribosomal proteins.

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 bS6, conserved site (Ribosomal_bS6_CS)
Type: Conserved_site

This entry represents a conserved region located in the N-terminal section of the small ribosomal subunit protein bS6 family.

The small subunits of bacterial and eukaryotic ribosomes have the same overall shapes (with structural elements described as head, body, platform, beak and shoulder). Ribosomal protein bS6 is one of the proteins from the small ribosomal subunit. . In Escherichia coli, bS6 is known to bind together with bS18 to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacterial, red algal chloroplast and cyanelle bS6 ribosomal proteins.

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 .
Histone-like DNA-binding protein, conserved site (Histone-like_DNA-bd_CS)
Type: Conserved_site

This entry represents a twenty residue sequence which includes three perfectly conserved positions. According to the tertiary structure of one of these proteins , this pattern spans exactly the first half of the flexible DNA-binding arm.

Bacteria synthesise a set of small, usually basic proteins of about 90 residues that bind DNA and are known as histone-like proteins . Examples include the HU protein in Escherichia coli which is a dimer of closely related alpha and beta chains and in other bacteria can be a dimer of identical chains. HU-type proteins have been found in a variety of eubacteria, cyanobacteria and archaebacteria, and are also encoded in the chloroplast genome of some algae . The integration host factor (IHF), a dimer of closely related chains which seem to function in genetic recombination as well as in translational and transcriptional control is found in enterobacteria and viral proteins include the African Swine fever virus protein Pret-047 (also known as A104R or LMW5-AR) .

The exact function of these proteins is not yet clear but they are capable of wrapping DNA and stabilising it from denaturation under extreme environmental conditions. The structure is known for one of these proteins . The protein exists as a dimer and two "β-arms" function as the non-specific binding site for bacterial DNA.
GroES chaperonin family (Chaperonin_GroES)
Type: Family

The chaperonins are 'helper' molecules required for correct folding and subsequent assembly of some proteins . These are required for normal cell growth , and are stress-induced, acting to stabilise or protect disassembled polypeptides under heat-shock conditions. Type I chaperonins present in eubacteria, mitochondria and chloroplasts require the concerted action of 2 proteins, chaperonin 60 (cpn60) and chaperonin 10 (cpn10) .
ENPP1-3/EXOG-like, endonuclease/phosphodiesterase domain (ENPP1-3/EXOG-like_nuc-like)
Type: Domain

A family of bacterial and eukaryotic endonucleases

share the following characteristics: they act on both DNA and RNA, cleave double-stranded and single-stranded nucleic acids and require a divalent ion such as magnesium for their activity. A histidine has been shown to be essential for the activity of the Serratia marcescens nuclease. This residue is located in a conserved region which also contains an aspartic acid residue that could be implicated in the binding of the divalent ion.

This entry represents the nuclease/phosphodiesterase domain found in proteins from bacteria and eukaryotes, including ENPP1-3, mitochondrial Endonuclease G and Nuclease EXOG from animals, venom phosphodiesterases and related proteins.

ENPP1 is a nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels . It preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3',5'-cAMP to AMP . ENPP2, also known as autotaxin, is a secreted lysophospholipase D that hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids . ENPP3 metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP .

Endonuclease G and EXOG act on DNA, preferentially double-stranded 5-hydroxymethylcytosine (5hmC)-modified DNA and supercoiled DNA, a preference for single-stranded DNA and 5'-3' exonuclease activity , respectively.
Cell division protein FtsA (Cell_div_FtsA)
Type: Family

FtsA is essential for bacterial cell division, and co-localizes to the septal ring with FtsZ. It has been suggested that the interaction of FtsA-FtsZ has arisen through coevolution in different bacterial strains .
Phenylalanyl-tRNA synthetase-like, B3/B4 (Phe-tRNA_synthase-like_B3/B4)
Type: Homologous_superfamily

This entry represents the B3/B4 domain found in tRNA synthetase beta subunits as well as in some non-tRNA synthetase proteins. This domain has a 3-layer structure, and contains a β-sandwich fold of unusual topology, and contains a putative tRNA-binding structural motif . In Thermus thermophilus, both the catalytic alpha- and the non-catalytic beta-subunits comprise the characteristic fold of the class II active-site domains. The presence of an RNA-binding domain, similar to that of the U1A spliceosomal protein, in the beta-subunit of tRNA synthetase indicates structural relationships among different families of RNA-binding proteins.
Transketolase binding site (Transketolase_BS)
Type: Binding_site

This entry represents a short region of conserved acidic residues that are located in the central section of a group of transketolase proteins widespread among all cellular organisms. This region may participate in substrate-binding .

Transketolase

(TK) catalyses the reversible transfer of a two-carbon ketol unit from xylulose 5-phosphate to an aldose receptor, such as ribose 5-phosphate, to form sedoheptulose 7-phosphate and glyceraldehyde 3- phosphate. This enzyme, together with transaldolase, provides a link between the glycolytic and pentose-phosphate pathways. TK requires thiamine pyrophosphate as a cofactor. In most sources where TK has been purified, it is a homodimer of approximately 70 Kd subunits. TK sequences from a variety of eukaryotic and prokaryotic sources show that the enzyme has been evolutionarily conserved. In the peroxisomes of methylotrophic yeast Pichia angusta (Yeast) (Hansenula polymorpha), there is a highly related enzyme, dihydroxy-acetone synthase (DHAS)

(also known as formaldehyde transketolase), which exhibits a very unusual specificity by including formaldehyde amongst its substrates.

1-deoxyxylulose-5-phosphate synthase (DXP synthase) is an enzyme so far found in bacteria (gene dxs) and plants (gene CLA1) which catalyses the thiamine pyrophosphoate-dependent acyloin condensation reaction between carbon atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (dxp), a precursor in the biosynthetic pathway to isoprenoids, thiamine (vitamin B1), and pyridoxol (vitamin B6). DXP synthase is evolutionary related to TK. The N-terminal section, contains a histidine residue which appears to function in proton transfer during catalysis . This entry represents the central section there are conserved acidic residues that are part of the active cleft and may participate in substrate-binding . This group of proteins includes transketolase enzymes

and 2-oxoisovalerate dehydrogenase beta subunit

. Both these enzymes utilise thiamine pyrophosphate as a cofactor, suggesting there may be common aspects in their mechanism of catalysis.