SII-SWORD/CoKE huggingface dataset:
Glycine transporter (Gly_transporter)
Type: Domain

This domain contains three transmembrane helices. Proteins containing this domain are important for glycine utilisation, being identified as glycine transporters. Some proteins containing this domain are also important for alanine utilisation. In these proteins this domain is found in pairs . An archaeal protein which contains this domain is a TRIC-type potassium channel .
Transport-associated OB, type 1 (Transp-assoc_OB_typ1)
Type: Domain

The TOBE domain (Transport-associated OB) always occurs as a dimer as the C-terminal strand of each domain is supplied by the partner. It is probably involved in the recognition of small ligands such as molybdenum (

,

) and sulphate (

), and is found in ABC transporters immediately after the ATPase domain.
Nitrite/Sulfite reductase ferredoxin-like domain (NiRdtase/SiRdtase_haem-b_fer)
Type: Domain

Sulphite reductases (SiRs) and related nitrite reductases (NiRs) catalyse the six-electron reduction reactions of sulphite to sulphide, and nitrite to ammonia, respectively. The Escherichia coli SiR enzyme is a complex composed of two proteins, a flavoprotein alpha-component (SiR-FP) and a hemoprotein beta-component (SiR-HP), and has an α(8)β(4) quaternary structure . SiR-FP contains both FAD and FMN, while SiR-HP contains a Fe(4)S(4) cluster coupled to a sirohaem through a cysteine bridge. Electrons are transferred from NADPH to FAD, and on to FMN in SiR-FP, from which they are transferred to the metal centre of SiR-HP, where they reduce the siroheme-bound sulphite.

SiR-HP has a two-fold symmetry, which generates a distinctive three-domain α/β fold that controls assembly and reactivity . This entry describes the ferrodoxin-like (α/β sandwich) domain. Two copies of this domain are found in Nitrite and Sulfite reductases and form a single structural domain.
Transcription-repair-coupling factor, C-terminal domain (TRCF_C)
Type: Domain

The transcription-repair coupling factor (TRCF, product of the mfd gene) couples transcription and DNA repair in bacteria. TRCF removes transcription elongation complexes stalled at DNA lesions and recruits the nucleotide excision repair (NER) machinery to the site. This protein, comprised of eight domains, including region of structurally similar to UvrB, shows to distinct activities: the relief of transcription-dependent inhibition of nucleotide excision repair (NER) by recognition and ATP-dependent removal of a stalled RNAP covering the damaged DNA; and the stimulation of DNA repair by recruitment of the Uvr(A)BC endonuclease. The C-terminal region of TRCF have been shown to be necessary for RNAP displacement .
LysR, substrate-binding (LysR_subst-bd)
Type: Domain

The LysR-type transcriptional regulator (LTTR) domain is a key component of one of the largest families of prokaryotic transcriptional regulators . Its structure, similar to periplasmic binding proteins, consists of an N-terminal DNA-binding domain (DBD) with a helix-turn-helix motif and a C-terminal effector-binding domain (EBD) connected by a long helix represented by this entry . LTTRs typically form homotetramers and function as dual-function repressor-activators, often negatively regulating their own expression [

. They bind to specific DNA sequences called LTTR boxes, and their binding can cause DNA bending . The EBD can interact with a diverse array of small-molecule ligands (effectors), including :

Amino acids

Sugar phosphates

Carboxylic acids

Reactive oxygen species (e.g., H2O2, HOCl)

Metabolites (e.g., homocysteine, citrate)

Signaling molecules (e.g., c-di-GMP, ppGpp)

The LysR-type transcriptional regulators (LTTRs) form one of the largest and most diverse families of bacterial regulators. These proteins are widely distributed and contribute to various aspects of bacterial metabolism and physiology. LTTRs are typically homotetramers, with each subunit consisting of an N-terminal DNA-binding domain

and a C-terminal effector-binding domain connected by a long helix

LTTRs generally function as dual-function repressor-activators, often negatively regulating their own expression while activating other genes . They respond to cellular signals by binding small-molecule ligands (effectors), which induce conformational changes altering DNA interactions and contact with RNA polymerase .

Some well-studied members of the LysR family include :

AmpR: regulator of β-lactamase expression

CatM and CatR: involved in aromatic compound degradation

CysB: regulator of cysteine biosynthesis

MetR: methionine biosynthesis regulator

NhaR: sodium/proton antiporter regulator
UPF3 domain (UPF3_dom)
Type: Domain

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism by which eukaryotic cells detect and degrade transcripts containing premature termination codons. Three 'up-frameshift' proteins, UPF1, UPF2 and UPF3, are essential for this process in organisms ranging from yeast, human to plants . Exon junction complexes (EJCs) are deposited ~24 nucleotides upstream of exon-exon junctions after splicing. Translation causes displacement of the EJCs, however, premature translation termination upstream of one or more EJCs triggers the recruitment of UPF1, UPF2 and UPF3 and activates the NMD pathway .

This entry contains UPF3. The crystal structure of the complex between human UPF2 and UPF3b, which are, respectively, a MIF4G (middle portion of eIF4G) domain and an RNP domain (ribonucleoprotein-type RNA-binding domain) has been determined to 1.95A. The protein-protein interface is mediated by highly conserved charged residues in UPF2 and UPF3b and involves the β-sheet surface of the UPF3b ribonucleoprotein (RNP) domain, which is generally used by these domains to bind nucleic acids. In UPF3b the RNP domain does not bind RNA, whereas the UPF2 construct and the complex do. It is clear that some RNP domains have evolved for specific protein-protein interactions rather than as nucleic acid binding modules .
Ferrodoxin-fold anticodon-binding domain (Fdx_antiC-bd)
Type: Domain

Aminoacyl-tRNA synthetases (aaRSs) play a crucial role in the translation of the genetic code by means of covalent attachment of amino acids to their cognate tRNAs. Phenylalanine-tRNA synthetase (PheRS, also known as Phenylalanine-tRNA ligase) is known to be among the most complex enzymes of the aaRS family. Bacterial and mitochondrial PheRSs share a ferredoxin-fold anticodon binding (FDX-ACB) domain, which represents a canonical double split α+β motif having no insertions. The FDX-ACB domain displays a typical RNA recognition fold (RRM) (see

) formed by the four-stranded antiparallel β sheet, with two helices packed against it .
Uracil-DNA glycosylase-like (Uracil-DNA_glycosylase-like)
Type: Domain

This entry represents various uracil-DNA glycosylases and related DNA glycosylases (

), such as uracil-DNA glycosylase , thermophilic uracil-DNA glycosylase , G:T/U mismatch-specific DNA glycosylase (Mug) , and single-strand selective monofunctional uracil-DNA glycosylase (SMUG1) . These proteins have a 3-layer α/β/α structure.

Uracil-DNA glycosylases are DNA repair enzymes that excise uracil residues from DNA by cleaving the N-glycosylic bond, initiating the base excision repair pathway. Uracil in DNA can arise either through the deamination of cytosine to form mutagenic U:G mispairs, or through the incorporation of dUMP by DNA polymerase to form U:A pairs . These aberrant uracil residues are genotoxic . The sequence of uracil-DNA glycosylase is extremely well conserved in bacteria and eukaryotes as well as in herpes viruses. More distantly related uracil-DNA glycosylases are also found in poxviruses .
Oxoglutarate/iron-dependent dioxygenase domain (Oxoglu/Fe-dep_dioxygenase_dom)
Type: Domain

Enzymes with the Fe(2+) and 2-oxoglutarate (2OG)-dependent dioxygenase domain typically catalyse the oxidation of an organic substrate using a dioxygen molecule, mostly by using ferrous iron as the active site cofactor and 2OG as a co-substrate which is decarboxylated to succinate and CO2 . Iron 2OG dioxygenase domain proteins are widespread among eukaryotes and bacteria. In metazoans, prolyl hydroxylases containing the domain act as oxygen sensors and catalyse the hydroxylation of conserved prolyl residues in hypoxia-inducible transcription factor (HIF) alpha . In plants, Fe(II) 2OG dioxygenase domain enzymes catalyse the formation of plant hormones, such as ethylene, gibberellins, anthocyanidins and pigments such as flavones. In bacteria and fungi Fe(II) 2OG dioxygenase domain enzymes participate in the biosynthesis of antibiotics such as penicillin and cephalosporin. The eukaryotic and bacterial protein AlkB that also shows this structural domain is involved in DNA-repair .

The iron 2OG dioxygenase domain has a conserved β-barrel structure , which forms a double-stranded β-helix core fold that forms the predominant class of the cupin superfamily ('cupa' means a small barrel in Latin) . Two histidines and an aspartate residue catalytically bind a metal ion, in general iron but in some cases another metal, directly involved in catalysis. A conserved arginine or lysine residue further near the C-terminal part acts as the basic residue that interacts with the acidic substrate.
Vacuolar (H+)-ATPase G subunit (V-ATPase_G)
Type: Family

This family represents the eukaryotic vacuolar (H+)-ATPase (V-ATPase) G subunit. V-ATPases generate an acidic environment in several intracellular compartments. Correspondingly, they are found as membrane-attached proteins in several organelles. They are also found in the plasma membranes of some specialised cells. V-ATPases consist of peripheral (V1) and membrane integral (V0) heteromultimeric complexes. The G subunit is part of the V1 subunit, but is also thought to be strongly attached to the V0 complex. It may be involved in the coupling of ATP degradation to H+ translocation.
NapC/NirT cytochrome c, N-terminal (NapC/NirT_cyt_c_N)
Type: Domain

Within the NapC/NirT family of cytochrome c proteins, some members, such as NapC

and NirT

, bind four haem groups, while others, such as TorC

, bind five haems. This family aligns the common N-terminal region that contains four haem-binding C-X(2)-CH motifs.
Giardia variant-specific surface protein (Giardia_VSP)
Type: Family

During infection, the intestinal protozoan parasite Giardia lamblia virus undergoes continuous antigenic variation which is determined by diversification of the parasite's major surface antigen, named VSP (variant surface protein).
Alpha-acetolactate decarboxylase (Acetolactate_a_deCO2ase)
Type: Family

Alpha-acetolactate decarboxylase converts acetolactate into acetoin. In Streptococcus thermophilus, it regulates leucine and valine biosynthesis by diverting the flux of alpha-acetolactate towards acetoin when the branched-chain amino acids are present in high concentration .
SIMIBI class G3E GTPase, ArgK/MeaB (GTPase_ArgK)
Type: Family

This family includes ArgK (also known as YgfD) from E. coli, Methylmalonic aciduria type A protein (MMA) from human and similar proteins , which belong to the G3E family of P-loop GTPases, a family defined by the glutamate residue in the Walker B motif and an intact NKxD, members of which include: UreG, HypB, CobW, and MeaB . These may function as G-protein chaperones that assist AdoCbl cofactor delivery to the methylmalonyl-CoA mutase and reactivation of the enzyme during catalysis

ArgK is involved in the transport of positively charged amino acids (lysine, arginine, and ornithine) and has arginine kinase activity. It is found in a small, but phylogenetically diverse array of bacteria and archaea, and in Caenorhabditis and Leishmania among the eukaryotes . Although ArgK was characterised as an ATPase originally , it has been shown to bind and cleave GTP. Therefore, its actual substrate in vivo is GTP rather than ATP .

MMA is involved in intracellular vitamin B12 metabolism where it mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis .
Serine dehydratase-like, alpha subunit (Ser_deHydtase-like_asu)
Type: Domain

L-serine dehydratase is found as a heterodimer of alpha and beta chain or as a fusion of the two chains in a single protein. This enzyme catalyses the deamination of serine to form pyruvate. This enzyme is part of the gluconeogenesis pathway. This entry also describes a number of proteins with no known function. Members included in this entry adopt an all-helical structure .
Serine dehydratase beta chain (Ser_deHydtase_bsu)
Type: Domain

L-serine dehydratase is found as a heterodimer of alpha and beta chain or as a fusion of the two chains in a single protein. This enzyme catalyses the deamination of serine to form pyruvate and is part of the gluconeogenesis pathway. Members of this entry adopt an α/β fold .
Na+/H+ antiporter subunit G (PhaG_MnhG_YufB)
Type: Family

This is a family of small, transmembrane proteins believed to be components of Na+/H+ and K+/H+ antiporters. Members, including proteins designated MnhG from Staphylococcus aureus and PhaG from Rhizobium meliloti (Sinorhizobium meliloti), show some similarity to chain L of the NADH dehydrogenase I, which also translocates protons.
Uncharacterised protein family UPF0114 (UPF0114)
Type: Family

This conserved hypothetical protein family with four predicted transmembrane regions is found in
Escherichia coli, Haemophilus influenzae, and Helicobacter pylori 26695, among completed genomes.
Endonuclease/exonuclease/phosphatase (Endo/exonuclease/phosphatase)
Type: Domain

This domain is found in a large number of proteins including magnesium dependent endonucleases and phosphatases involved in intracellular signalling . Proteins this domain is found in include: AP endonuclease proteins (

), DNase I proteins (

), Synaptojanin an inositol-1,4,5-trisphosphate phosphatase (

) and Sphingomyelinase (

).
Membrane complex biogenesis protein, BtpA family (BtpA)
Type: Family

Members of this family are found in Caenorhabditis elegans, Synechocystis sp., E. coli, and several of the Archaea. Members in Cyanobacteria have been shown to play a role in protein complex biogenesis, and designated BtpA (biogenesis of thylakoid protein) . BtpA appears to act at the level of Photosystem I (PSI) stabilisation . Homologues in non-photosynthetic species, where thylakoid intracytoplasmic membranes are lacking, are likely to act elsewhere in membrane protein biogenesis.
Aerolysin/Pertussis toxin domain (APT_dom)
Type: Domain

This is the N-terminal domain of aerolysin and pertussis toxin which contains a type-C lectin like fold.

Aerolysin causes the pathogenicity of Aeromonas hydrophila, a bacterium associated with diarrhoeal diseases and deep wound infections. Like many other microbial toxins, the protein changes in a multistep process from a completely water-soluble form to produce a transmembrane channel that breaks the permeability barrier of cells .

Pertussis toxin is a major virulence factor of Bordetella pertussis, which causes whooping cough. The protein is a hexamer containing a catalytic subunit (S1) that is tightly associated with a pentameric cell-binding component (B-oligomer). ATP, detergents and phospholipids assist in activating the holotoxin by destabilising the interaction between S1 and the B-oligomer . Pertussis toxin is an exotoxin and is an essential component of acellular vaccines . The catalytic A-subunit (S1) shares structural homology with other ADP-ribosylating bacterial toxins, although differences in the carboxy-terminal portion explain its unique activation mechanism . The diverse biological activities of the toxin depend on its ability to recognise carbohydrate-containing receptors on a wide variety of eukaryotic cells.
Peptide chain release factor (PCRF)
Type: Domain

This domain is found in bacterial, mitochondrial and chloroplastic peptide chain release factors. In bacteria, termination of protein synthesis depends on the type I release factors, RF1 and RF2 . Both contain this domain.
eRF1 domain 1/Pelota-like (eRF1_1_Pelota)
Type: Domain

This domain is found in the release factor eRF1 which terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase centre. The crystal structure of human eRF1 is known . The overall shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl transferase centre. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site .

This domain is also found in other proteins for which the precise molecular function is unknown. Many of them are from Archaebacteria. These proteins may also be involved in translation termination but this awaits experimental verification.
eRF1 domain 2 (eRF1_2)
Type: Domain

This domain is found in the release factor eRF1 which terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase centre. The crystal structure of human eRF1 is known . The overall shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl transferase centre. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site .

This domain is also found in other proteins which may also be involved in translation terminatio
eRF1 domain 3 (eRF1_3)
Type: Domain

This domain is found in the release factor eRF1 which terminates protein biosynthesis by recognizing stop codons at the A site of the ribosome and stimulating peptidyl-tRNA bond hydrolysis at the peptidyl transferase centre. The crystal structure of human eRF1 is known . The overall shape and dimensions of eRF1 resemble a tRNA molecule with domains 1, 2, and 3 of eRF1 corresponding to the anticodon loop, aminoacyl acceptor stem, and T stem of a tRNA molecule, respectively. The position of the essential GGQ motif at an exposed tip of domain 2 suggests that the Gln residue coordinates a water molecule to mediate the hydrolytic activity at the peptidyl transferase centre. A conserved groove on domain 1, 80 A from the GGQ motif, is proposed to form the codon recognition site .

This domain is also found in other proteins which may also be involved in translation termination but this awaits experimental verification.
Transcription factor LuxR-like, autoinducer-binding domain (TF_LuxR_autoind-bd_dom)
Type: Domain

This domain binds N-acyl homoserine lactones (AHLs), which are also known as autoinducers. These are small, diffusible molecules used as communication signals in a large variety of proteobacteria. It is almost always found in association with the DNA-binding LuxR domain (

). The autoinducer binding domain forms the N-terminal region of the protein, while the DNA-binding domain forms the C-terminal region. In most cases, binding of AHL by this N-terminal domain leads to unmasking of the DNA-binding domain, allowing it to bind DNA and activate transcription . In rare cases, some LuxR proteins such as EsaR, act as repressors . In these proteins binding of AHL to this domain leads to inactivation of the protein as a transcriptional regulator. A large number of processes have been shown to be regulated by LuxR proteins, including bioluminescence, production of virulence factors in plant and animal pathogens, antibiotic production and plasmid transfer.

Structural studies of TraR from Agrobacterium tumefaciens show that the functional protein is a homodimer. Binding of the cognate AHL is required for protein folding, resistance to proteases and dimerisation. The autoinducer binding domain binds its cognate AHL in an α/β/α sandwich and provides an extensive dimerisation surface, though residues from the C-terminal region also make some contribution to dimerisation. The autoinducer binding domain is also required for interaction with RpoA, allowing transcription to occur .

There are some proteins which consist solely of the autoinducer binding domain. The function of these is not known, but TrlR from Agrobacterium has been shown to inhibit the activity of TraR by the formation of inactive heterodimers .
ATP-cone domain (ATP-cone_dom)
Type: Domain

The ATP-cone is an evolutionarily mobile, ATP-binding regulatory domain which is found in a variety of proteins including ribonucleotide reductases, phosphoglycerate kinases and transcriptional regulators .

In ribonucleotide reductase protein R1 (

) from Escherichia coli this domain is located at the N terminus, and is composed mostly of helices . It forms part of the allosteric effector region and contains the general allosteric activity site in a cleft located at the tip of the N-terminal region . This site binds either ATP (activating) or dATP (inhibitory), with the base bound in a hydrophobic pocket and the phosphates bound to basic residues. Substrate binding to this site is thought to affect enzyme activity by altering the relative positions of the two subunits of ribonucleotide reductase.
Threonylcarbamoyl-AMP synthase, C-terminal domain (Sua5_C)
Type: Domain

This domain can be found in the C terminus of threonylcarbamoyl-AMP synthases, including Sua5 from Saccharomyces cerevisiae and YwlC from Bacillus subtilis.
Threonylcarbamoyl-AMP synthase is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t6A37) in tRNAs that read codons beginning with adenine .

This domain adopts the Rossmann fold and may be involved in GTP and/or tRNA binding based on structural similarity with both GTP and tRNA binding proteins .
B3/B4 tRNA-binding domain (B3/B4_tRNA-bd)
Type: Domain

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.
tRNA synthetase, B5-domain (tRNA_synthase_B5-dom)
Type: Domain

Domain B5 is found in phenylalanine-tRNA synthetase beta subunits. This domain has been shown to bind DNA through a winged helix-turn-helix motif . Phenylalanine-tRNA synthetase may influence common cellular processes via DNA binding, in addition to its aminoacylation function.