SII-SWORD/CoKE huggingface dataset:
Penicillin binding protein transglycosylase domain (PBP_transglycosylase)
Type: Homologous_superfamily

Penicillin-binding proteins, such as Escherichia coli PBP1b, are bifunctional transglycosylases that consist of a transmembrane helix, a transglycosylase domain and a transpeptidase domain . The transglycosylase domain catalyses the polymerisation of murein glycan chains . This domain is also found on its own in monofunctional peptidoglycan transglycosylases .
Aromatic amino acid hydroxylase superfamily (ArAA_hydroxylase_sf)
Type: Homologous_superfamily

Phenylalanine, tyrosine and tryptophan hydroxylases constitute a superfamily 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 superfamily 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.
Parvovirus coat protein VP1/VP2 (VP1/VP2)
Type: Homologous_superfamily

Parvoviruses are some of the smallest viruses containing linear, non-segmented single-stranded DNA genomes, with an average genome size of 5000 nucleotides. Parvoviruses have been described that infect a wide range of invertebrates and vertebrates and are well known for causing enteric disease in mammals. Genomes contain two large ORFs: NS1 and VP1; other ORFs are found in some sub-types and different gene products can arise from splice variants and the use of different start codons .

The Parvovirus coat protein VP1 together with VP2 forms a capsomer. Both of these proteins are formed from the same transcript using alternative translation start codons. As a result, VP1 and VP2 differ only in the N terminus region. VP2 is involved in packaging the viral DNA . The mature viron contains three capsid proteins VP1, VP2, and VP3 and a noncapsid protein NS1. VP3 may arise from a third start codon with a favorable translation initiation context which is present at position 3067 in the ChPV genome and which has been described in the goose and Muscovy duck parvoviruses .

Parvovirus coat proteins have a β-barrel fold .
Transcription elongation factor GreA/GreB, C-terminal domain superfamily (GreA/GreB_C_sf)
Type: Homologous_superfamily

Bacterial proteins GreA and GreB are necessary for efficient RNA polymerase transcription elongation past template-encoded arresting sites. Arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked DNA/RNA/ polymerase ternary complexes. Cleavage of the nascent transcript by cleavage factors, such as GreA or GreB, allows the resumption of elongation from the new 3' terminus . Escherichia coli GreA and GreB are sequence homologues and have homologues in every known bacterial genome . GreA induces cleavage two or three nucleotides behind the terminus and can only prevent the formation of arrested complexes while greB releases longer sequences up to eighteen nucleotides in length and can rescue preexisting arrested complexes. These functional differences correlate with a distinctive structural feature, the distribution of positively charged residues on one face of the N-terminal coiled coil. Remarkably, despite close functional similarity, the prokaryotic Gre factors have no sequence or structural similarity with eukaryotic TFIIS.

GreA and GreB are made up of two domains, each comprising about half of the protein. The C-terminal domain consists primarily of an α helix cradled by a five-strand β-sheet .
Collagen IV, non-collagenous domain superfamily (Collagen_IV_NC_sf)
Type: Homologous_superfamily

Collagens are major components of the extracellular matrices of all metazoan life and play crucial roles in developmental processes and tissue homeostasis. Collagens are composed of three polypeptide chains (alpha chains) that fold together to form the characteristic triple helical collagenous domain. Some types of triple helical protomers contain genetically identical alpha chains forming homotrimers, whereas others contain two or three different alpha chains forming heterotrimers. The sequences required to form a collagenous domain are Gly-X-Y repeats in which the X and Y positions are frequently proline and hydroxyproline. Glycine is required every third residue as it is the only amino acid small enough to pack into the central core of the triple helix. The triple helix-forming parts are surrounded by non-collagenous (NC) domains of variable sequence, size, and shape. Even if the triple helical parts represent the most striking feature of collagens, tissue specificity as well as defined binding of non-collagens seem to be encoded in the NC domains. The terminal NC domains are excised, modified, or incorporated directly into the final suprastructure, depending on protomer type and function .

Type IV collagen is one of the major constituents of basement membranes, a specialised form of extracellular matrix underlying epithelia that compartmentalises tissues and provides molecular signals for influencing cell behaviour. Each type IV chain contains a long triple-helical collagenous domain flanked by a short 7S domain of 25 residues and a globular non-collagenous NC1 domain of ~230 residues at the N and C terminus, respectively. In protomer assembly, the NC1 domains (monomers) of three chains interact, forming an NC1 trimer, to select and register chains for triple helix formation. In network assembly, the NC1 trimers of two protomers interact, forming a NC1 hexamer structure, to select and connect protomers .

This superfamily covers the entire collagen IV NC1 domain.
AP2/ERF domain superfamily (AP2/ERF_dom_sf)
Type: Homologous_superfamily

Ethylene is an endogenous plant hormone that influences many aspects of plant growth and development. Some defense related genes that are induced by ethylene contain a cis-regulatory element known as the Ethylene-Responsive Element (ERE) . Sequence analysis on various ERE regions has identified a short motif rich in G/C nucleotides, the GCC-box, essential for the response to ethylene. This short motif is recognised by a family of transcrition factors, the ERE binding factors (ERF) .

ERF proteins contain a domain of around 60 amino acids which is also found in the APETALA2 (AP2) protein . This AP2/ERF domain has been shown in various proteins to be necessary and sufficient to bind the GCC-box .

The structure of the AP2/ERF domain in complex with the target DNA has been solved . The structure resembles that of bacteriophage integrases and the methyl-CpG-binding domain (MBD): a three-stranded β-sheet and an α helix almost parallel to the β-sheet. It contacts DNA via Arg and Trp residues located in the β-sheet.

Some proteins known to contain an AP2/ERF domain include:

Arabidopsis thaliana ERF1 to 6.

Tobacco ethylene-responsive element-binding proteins (EREBPs), homologues of ERF proteins.

Arabidopsis thaliana AP2 protein. It regulates meristeme identity, floral organ specification and seed coat development.

Arabidopsis thaliana C-repeat/dehydration-responsive element (DRE) binding factor 1 (CBF1 or DREB1) and DREB2. They bind a GCC-box-like element found in dehydratation responsive element. Binding to this element mediates cold-inducible transcription.

Arabidopsis thaliana and maize abscisic acid (ABA)-insensitive 4 (ABI4) proteins. They bind to a GCC-box-like element found in ABA-responsive genes.

Octadecanoid-derivative responsive catharenthus AP2-domain (ORCA2) protein. It binds a GCC-box-like element in the jasmonate responsive element of Str promoter.

Tomato Pto-interacting proteins 4 to 6 (Pti4 to Pti6). Pti5 and 6 bind a GCC-box-like element in regulatory regions of various pathogenesis-related (PR) genes.

Trichodesmium erythraeum, Tetrahymena thermophila, Enterobacteria phage RB49 and bacteriophage Felix 01 HNH endonucleases. HNH endonucleases are homing endonucleases that move extensively via lateral gene transfer .

This entry represents the AP2/ERF domain superfamily.
Impact, N-terminal domain superfamily (Impact_N_sf)
Type: Homologous_superfamily

The Impact protein is a translational regulator that ensures constant high levels of translation under amino acid starvation. It acts by interacting with Gcn1/Gcn1L1, thereby preventing activation of Gcn2 protein kinases (EIF2AK1 to 4) and subsequent down-regulation of protein synthesis. It is evolutionary conserved from eukaryotes to archaea .

This entry represents the N-terminal domain superfamily of the Impact proteins.
Zinc finger, PARP-type superfamily (Znf_PARP_sf)
Type: Homologous_superfamily

This entry represents the PARP (poly ADP-ribose polymerase) type zinc finger domain superfamily.

PARP, also known as NAD(+) ADP-ribosyltransferase (

), is a eukaryotic enzyme that catalyses the covalent attachment of ADP-ribose units from NAD(+) to various nuclear acceptor proteins . This post-translational modification of nuclear proteins is dependent on DNA. It appears to be involved in the regulation of various important cellular processes such as differentiation, proliferation and tumour transformation as well as in the regulation of the molecular events involved in the recovery of the cell from DNA damage. Structurally, NAD(+) ADP-ribosyltransferase consists of three distinct domains: an N-terminal zinc-dependent DNA-binding domain, a central automodification domain and a C-terminal NAD-binding domain. The DNA-binding region contains a pair of PARP-type zinc finger domains which have been shown to bind DNA in a zinc-dependent manner. The PARP-type zinc finger domains seem to bind specifically to single-stranded DNA and to act as a DNA nick sensor. DNA ligase III contains, in its N-terminal section, a single copy of a zinc finger highly similar to those of PARP.
Peptidase C12, ubiquitin carboxyl-terminal hydrolase superfamily (Peptidase_C12_UCH_sf)
Type: Homologous_superfamily

This group of cysteine peptidases belong to the MEROPS peptidase family C12 (ubiquitin C-terminal hydrolase family, clan CA). Families within the CA clan are loosely termed papain-like as protein fold of the peptidase unit resembles that of papain, the type example for clan CA. The type example is the human ubiquitin C-terminal hydrolase UCH-L1.

Ubiquitin is highly conserved, commonly found conjugated to proteins in eukaryotic cells, where it may act as a marker for rapid degradation, or it may have a chaperone function in protein assembly . The ubiquitin is released by cleavage from the bound protein by a protease . A number of deubiquitinising proteases are known: all are activated by thiol compounds , and inhibited by thiol-blocking agents and ubiquitin aldehyde , and as such have the properties of cysteine proteases .

The deubiquitinsing proteases can be split into 2 size ranges: 20-30kDa (this entry) and 100-200kDa (

) . The 20-30kDa group includes the yeast yuh1, which is known to be active only against small ubiquitin conjugates, being inactive against conjugated beta-galactosidase . A mammalian homologue, UCH (ubiquitin conjugate hydrolase), is one of the most abundant proteins in the brain . Only one conserved cysteine can be identified, along with two conserved histidines. The spacing between the cysteine and the second histidine is thought to be more representative of the cysteine/histidine spacing of a cysteine protease catalytic dyad .
T-box superfamily (T-box_sf)
Type: Homologous_superfamily

Transcription factors of the T-box family are required both for early cell-fate decisions, such as those necessary for formation of the basic vertebrate body plan, and for differentiation and organogenesis . The T-box is defined as the minimal region within the T-box protein that is both necessary and sufficient for sequence-specific DNA binding, all members of the family so far examined bind to the DNA consensus sequence TCACACCT. The T-box is a relatively large DNA-binding domain, generally comprising about a third of the entire protein (17-26kDa) .

These genes were uncovered on the basis of similarity to the DNA binding domain of Mus musculus (Mouse) Brachyury (T) gene product, which similarity is the defining feature of the family. The Brachyury gene is named for its phenotype, which was identified 70 years ago as a mutant mouse strain with a short blunted tail. The gene, and its paralogues, have become a well-studied model for the family, and hence much of what is known about the T-box family is derived from the murine Brachyury gene.

Consistent with its nuclear location, Brachyury protein has a sequence-specific DNA-binding activity and can act as a transcriptional regulator . Homozygous mutants for the gene undergo extensive developmental anomalies, thus rendering the mutation lethal . The postulated role of Brachyury is as a transcription factor, regulating the specification and differentiation of posterior mesoderm during gastrulation in a dose-dependent manner .

T-box proteins tend to be expressed in specific organs or cell types, especially during development, and they are generally required for the development of those tissues, for example, Brachyury is expressed in posterior mesoderm and in the developing notochord, and it is required for the formation of these cells in mice .
Glycoside hydrolase, family 3, N-terminal domain superfamily (Glyco_hydro_3_N_sf)
Type: Homologous_superfamily

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 3

comprises enzymes with a number of known activities; beta-glucosidase (

); beta-xylosidase (

); N-acetyl beta-glucosaminidase (

); glucan beta-1,3-glucosidase (

); cellodextrinase (

); exo-1,3-1,4-glucanase (

).
These enzymes are two-domain globular proteins that are N-glycosylated at three sites . This domain is often N-terminal to the glycoside hydrolase family 3, C-terminal domain

.
Tat domain superfamily (Tat_dom_sf)
Type: Homologous_superfamily

Like other lentiviruses, Human immunodeficiency virus 1 (HIV-1) encodes a trans-activating regulatory protein (Tat), which is essential for efficient transcription of the viral genome . Tat acts by binding to an RNA stem-loop structure, the trans-activating response element (TAR), found at the 5' ends of nascent HIV-1 transcripts. In binding to TAR, Tat alters the properties of the transcription complex, recruits a positive transcription elongation complex (P-TEFb) and hence increases the production of full-length viral RNA . Tat protein also associates with RNA polymerase II complexes during early transcription elongation after the promoter clearance and before the synthesis of full-length TAR RNA transcript. This interaction of Tat with RNA polymerase II elongation complexes is P-TEFb-independent. There are two Tat binding sites on each transcription elongation complex; one is located on TAR RNA and the other one on RNA polymerase II near the exit site for nascent mRNA transcripts which suggests that two Tat molecules are involved in performing various functions during a single round of HIV-1 mRNA synthesis .

The minimum Tat sequence that can mediate specific TAR binding
in vitro
has been mapped to a basic domain of 10 amino acids, comprising mostly Arg and Lys residues. Regulatory activity, however, also requires the 47 N-terminal residues, which interact with components of the transcription complex and function as a transcriptional activation domain .
Ras guanine-nucleotide exchange factor, catalytic domain superfamily (RASGEF_cat_dom_sf)
Type: Homologous_superfamily

Ras proteins are membrane-associated molecular switches that bind GTP and GDP and slowly hydrolyze GTP to GDP in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. The balance between the GTP bound (active) and GDP bound (inactive) states is regulated by the opposite action of proteins activating the GTPase activity and that of proteins which promote the loss of bound GDP and the uptake of fresh GTP . The latter proteins are known as guanine-nucleotide exchange (or releasing) factors (GEFs or GRFs) (or also as guanine-nucleotide dissociation stimulators (GDSs)). GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors .

The crystal structure of the GEF region of human Sos1 complexes with Ras has been solved . The structure consists of two distinct α helical structural domains: the N-terminal domain which seems to have a purely structural role and the C-terminal domain which is sufficient for catalytic activity and contains all residues that interact with Ras. A main feature of the catalytic domain is the protrusion of a helical hairpin important for the nucleotide-exchange mechanism. The N-terminal domain is likely to be important for the stability and correct placement of the hairpin structure.

Some proteins known to contain a Ras-GEF domain are listed below:

Cdc25 from yeast.

Scd25 from yeast.

Ste6 from fission yeast.

Son of sevenless (gene sos) from Drosophila and mammals.

p140-RAS GRF (cdc25Mm) from mammals. This protein possesses both a domain belonging to the CDC25 family and one belonging to the CDC24 family.

Bud5 from yeast, that may interact with the ras-like protein RSR1/BUD1.

Lte1 from yeast, whose target protein is not yet known.

ralGDS from mammals, which interacts with the ras-like proteins ralA and ralB .

This entry represents the C-terminal catalytic domain of the Ras guanine-nucleotide exchange factors.
Terpene synthase, N-terminal domain superfamily (Terpene_synth_N_sf)
Type: Homologous_superfamily

Sequences containing this domain belong to the terpene synthase family . It has been suggested that this gene family be designated tps (for terpene synthase). Sequence comparisons reveal similarities between the monoterpene (C
10
) synthases, sesquiterpene (C
15
) synthases and the diterpene (C
20
) synthases. It has been split into six subgroups on the basis of phylogeny, called Tpsa-Tpsf .

Tpsa includes vetispiridiene synthase

, 5-epi- aristolochene synthase,

and (+)-delta-cadinene synthase

.

Tpsb includes (-)-limonene synthase,

.

Tpsc includes copalyl diphosphate synthase (kaurene synthase A),

.

Tpsd includes taxadiene synthase,

, pinene synthase,

and myrcene synthase,

.

Tpse includes ent-kaurene synthase B

.

Tpsf includes linalool synthase

.

In the fungus Phaeosphaeria sp. (strain L487) the synthesis of ent-kaurene from geranylgeranyl diphosphate is promoted by a single bifunctional protein .
Carbohydrate-binding module 3 superfamily (CBM3_sf)
Type: Homologous_superfamily

Carbohydrate-binding modules (CBM) have been classified into more than 40 families according to sequence homology. Several cellulolytic enzymes share a conserved region of about 150 amino acid residues, the CBM3 domain . It has been classified in three different subtypes, termed family IIIa, IIIb and IIIc. The family IIIa (scaffoldin) and IIIb (mainly free enzymes) are closely similar in their primary structures and both types bind strongly to crystalline cellulose . Members of the family IIIc, fail to bind crystalline cellulose, but serve in a 'helper' capacity by feeding a single incoming cellulose chain into the active site of the neighbouring catalytic module pending hydrolysis .

The CBM3 domain is mainly found C-terminal to the catalytic domain, which correspond to a wide range of bacterial glycosyl hydrolases like family 9, family 5 and family 10.

The crystal structure of CBM3 has been solved . It consists of nine β-strands which form a compact domain that has an overall prismatic shape. It is arranged in two antiparallel β-sheets that stack face-to-face to form a β sandwich with jelly roll topology. Two defined surfaces, located on opposite sides of the molecule, contain conserved polar and aromatic residues which are probably involved in the binding of the CBM to cellulose . The first one forms a planar strip whereas the second one forms a shallow groove.

Some proteins known to contain a CBM3 domain are listed below:

Clostridial cellulosomal scaffolding proteins cipA, cipC and cbpA. They promote the binding of cellulose to the catalytic domains of the cellulolytic enzymes.

Bacterial cellulases A, B, F, G, I, N, Y, Z (Endo-1,4-beta-glucanase,

).

This entry represents the CBM3 domain, which is also known as cellulose-binding domain family III (CBD III).
Small ribosomal subunit protein uS11 superfamily (Ribosomal_uS11_sf)
Type: Homologous_superfamily

Small ribosomal subunit protein uS11, previously known as Ribosomal protein S11 , plays an essential role in selecting the correct tRNA in protein biosynthesis. It is located on the large lobe of the small ribosomal subunit.

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 .