SII-SWORD/CoKE huggingface dataset:
UPF0047 protein YjbQ-like (UPF0047_YjbQ-like)
Type: Family

This family contains small uncharacterised proteins of 14 to 16kDa mainly from bacteria although the signatures also occur in a hypothetical protein from archaea and eukaryotes. Members of this protein family, designated YjbQ in E. coli, have been studied extensively by crystallography. Members from several different species have been shown to have sufficient thiamine phosphate synthase activity ([ec:2.5.1.3)) to complement thiE mutants. However, it is presumed that this is a secondary activity, and the primary function of the YjbQ family enzyme remains unknown .
DNA/RNA non-specific endonuclease/pyrophosphatase/phosphodiesterase domain (Endo_G_ENPP1-like_dom)
Type: Domain

This entry represents a domain found in a group of DNA/RNA non-specific endonucleases (

) and nucleotide pyrophosphatase/phosphodiesterases from eukaryotes and bacteria, including human Endonuclease G, mitochondrial and Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 .

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 also includes Salivary proteins Tsal1 and Tsal2A, both high affinity nucleic acid binding proteins with residual nuclease activity and with a preference for dsDNA in a broad pH range.
Pleckstrin homology domain, spectrin-type (PH_dom-spectrin-type)
Type: Domain

Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane; it associates with band 4.1 and actin to form the cytoskeletal super-structure. The native spectrin molecule is a tetramer comprising two anti-parallel heterodimers joined head to head, such that the C terminus of the alpha-subunit and the N terminus of the beta-subunit are included within the same molecule.

Spectrin is similar to alpha-actinin and dystrophin, and contains a pleckstrin homology (PH) domain. The exact function of the PH domain is unknown, but evidence suggests that it contains an electrostatically-polarised pocket that facilitates binding of a ligand (e.g., a peptide). The PH domain contains a number of hydrophobic residues that form a hydrophobic core responsible for protein stability. The spectrin PH domain , which has the familiar 7-stranded anti-parallel up and down β-barrel capped by a C-terminal amphiphilic α helical cap , contains insertions that confer 2 additional turns of α-helix in the loop between strands 3 and 4. The C-terminal helix is packed into a gorge between strands 1 and 2, and lies parallel to strand 7 .
ARID DNA-binding domain (ARID_dom)
Type: Domain

The AT-rich interaction domain (ARID) is an ~100-amino acid DNA-binding module found in a large number of eukaryotic transcription factors that regulate cell proliferation, differentiation, and development . The ARID domain appears as a single-copy motif and can be found in association with other domains, such as JmjC, JmjN, Tudor and PHD-type zinc finger .

The basic structure of the ARID domain appears to be a series of six α-helices separated by β-strands, loops, or turns, but the structured region may extend to an additional helix at either or both ends of the basic six. Based on primary sequence homology, they can be partitioned into three structural classes:

Minimal ARID proteins that consist of a core domain formed by six α-helices;

ARID proteins that supplement the core domain with an N-terminal α-helix;

Extended-ARID proteins, which contain the core domain and additional α-helices at their N-and C-termini.

Minimal ARIDs are distributed in all eukaryotes, while extended ARIDs are restricted to metazoans. The ARID domain binds DNA as a monomer, recognising the duplex through insertion of a loop and an α-helix into the major groove and by extensive non-specific anchoring contacts to the adjacent sugar-phosphate backbone .

Some proteins known to contain an ARID domain are listed below:

Eukaryotic transcription factors of the jumonji family.

Mammalian Bright, a B-cell-specific trans-activator of IgH transcription.

Mammalian PLU-1, a protein that is upregulated in breast cancer cells.

Mammalian RBP1 and RBP2, retinoblastoma-binding factors.

Mammalian Mrf-1 and Mrf-2, transcriptional modulators of the cytomegalovirus major intermediate-early promoter.

Drosophila melanogaster dead ringer protein, a transcriptional regulatory protein required for early embryonic development.

Yeast SWI1 protein, from the SWI/SNF complex involved in chromatin remodelling and broad aspects of transcription regulation.

Drosophila melanogaster Osa. It is structurally related to SWI1 and associates with the brahma complex, which is the Drosophila equivalent of the SWI/SNF complex.
Zinc finger, UBP-type (Znf_UBP)
Type: Domain

This entry represents UBP-type zinc finger domains, which display some similarity with the Zn-binding domain of the insulinase family. The UBP-type zinc finger domain is found only in a small subfamily of ubiquitin C-terminal hydrolases (deubiquitinases or UBP) , All members of this subfamily are isopeptidase-T, which are known to cleave isopeptide bonds between ubiquitin moieties.

Some of the proteins containing an UBP zinc finger include:

Human ubiquitin carboxyl-terminal hydrolase 13 (UBPD), Homo sapiens

Ubiquitin carboxyl-terminal hydrolase 5, Homo sapiens

Ubiquitin carboxyl-terminal hydrolase, Social amoeba

Ubiquitin carboxyl-terminal hydrolase 8, Saccharomyces cerevisiae

Ubiquitin carboxyl-terminal hydrolase 14, Saccharomyces cerevisiae

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

Alanine racemase plays a role in providing the D-alanine required for cell wall biosynthesis by isomerising L-alanine to D-alanine.

The molecular structure of alanine racemase from Bacillus stearothermophilus was determined by X-ray crystallography to a resolution of 1.9 A . The alanine racemase monomer is composed of two domains, an eight-stranded α/β barrel at the N terminus, and a C-terminal domain essentially composed of β-strands. The pyridoxal 5'-phosphate (PLP) cofactor lies in and above the mouth of the α/β barrel and is covalently linked via an aldimine linkage to a lysine residue, which is at the C terminus of the first β-strand of the α/β barrel.

This N-terminal domain is also found in the PROSC (proline synthetase co-transcribed bacterial homologue) family of proteins, which are not known to have alanine racemase activity.
Myosin head, motor domain-like (Myosin_head_motor_dom-like)
Type: Domain

Muscle contraction is caused by sliding between the thick and thin filaments of the myofibril. Myosin is a major component of thick filaments and exists as a hexamer of 2 heavy chains , 2 alkali light chains, and 2 regulatory light chains. The heavy chain can be subdivided into the N-terminal globular head and the C-terminal coiled-coil rod-like tail, although some forms have a globular region in their C-terminal. There are many cell-specific isoforms of myosin heavy chains, coded for by a multi-gene family . Myosin interacts with actin to convert chemical energy, in the form of ATP, to mechanical energy . The 3-D structure of the head portion of myosin has been determined and a model for actin-myosin complex has been constructed .

The globular head is well conserved, some highly-conserved regions possibly relating to functional and structural domains . The rod-like tail starts with an invariant proline residue, and contains many repeats of a 28 residue region, interrupted at 4 regularly-spaced points known as skip residues. Although the sequence of the tail is not well conserved, the chemical character is, hydrophobic, charged and skip residues occuring in a highly ordered and repeated fashion .

This domain is also found in chitinases present in filamentous fungi, enzymes that play a critical role in promoting the synthesis of chitin at the hyphal tip, thus influencing fungal growth and the architecture of fungal infection structures .
PAC motif (PAC)
Type: Repeat

PAC motifs occur C-terminal to a subset of all known PAS motifs (see

). It is proposed to contribute to the PAS domain fold .
Leucine-rich repeat (Leu-rich_rpt)
Type: Repeat

Leucine-rich repeats (LRR) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape . LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions .Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response .

Sequence analyses of LRR proteins suggested the existence of several different subfamilies of LRRs. The significance of this classification is that repeats from different subfamilies never occur simultaneously and have most probably evolved independently. It is, however, now clear that all major classes of LRR have curved horseshoe structures with a parallel β sheet on the concave side and mostly helical elements on the convex side. At least six families of LRR proteins, characterised by different lengths and consensus sequences of the repeats, have been identified. Eleven-residue segments of the LRRs (LxxLxLxxN/CxL), corresponding to the β-strand and adjacent loop regions, are conserved in LRR proteins, whereas the remaining parts of the repeats (herein termed variable) may be very different. Despite the differences, each of the variable parts contains two half-turns at both ends and a "linear" segment (as the chain follows a linear path overall), usually formed by a helix, in the middle. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins.
3D structure of some LRR proteins-ligand complexes show that the concave surface of LRR domain is ideal for interaction with α-helix, thus supporting earlier conclusions that the elongated and curved LRR structure provides an outstanding framework for achieving diverse protein-protein interactions . Molecular modeling suggests that the conserved pattern LxxLxL, which is shorter than the previously proposed LxxLxLxxN/CxL is sufficient to impart the characteristic horseshoe curvature to proteins with 20-to 30-residue repeats .
Caveolin (Caveolin)
Type: Family

Caveolae are 50-100 nm invaginations located at the plasma membrane of many cell types and are known to transport molecules across endothelial cells . Caveolae require the caveolin protein for formation. Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signalling molecules. Mammals have three caveolin proteins:caveolin-1 (Cav-1, or VIP21), caveolin-2 and caveolin-3 (or M-caveolin). Various classes of signalling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain' .

Caveolins are proteins of about 20 Kd, they form high molecular mass homo-oligomers. Structurally they seem to have N-terminal and C-terminal hydrophilic segments and a long central transmembrane domain that probably forms a hairpin in the membrane. Both extremities are known to face the cytoplasm. Caveolae are enriched with cholesterol and Cav-1 is one of the few proteins that binds cholesterol tightly and specifically.
Flavin amine oxidase (Flavin_amine_oxidase)
Type: Family

Monoamine oxidases (MAO) A and B are encoded by two genes derived from a common ancestral gene . The enzymes catalyse the oxidative deamination of biogenic and xenobiotic amines and have important roles in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues . MAO-A preferentially oxidises biogenic amines such as 5-hydroxytryptamine, norepinephrine and epinephrine. MAO-A deficiency has been linked to Brunner's syndrome, a form of X-linked nondysmorphic mild mental retardation .

The protein contains two similarly-sized subunits, one of which contains covalently-bound flavin adenine dinucleotide (FAD). The FAD binding site lies near the C terminus; at the N terminus are features characteristic of the ADP-binding fold, suggesting that this region is also involved in FAD binding . The A and B forms of the enzyme share 70% sequence identity; both contain the pentapeptide Ser-Gly-Gly-Cys-Tyr, the cysteine of which binds FAD .
Myelin proteolipid protein PLP (Myelin_PLP)
Type: Family

The myelin sheath is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction . Myelin proteolipid protein (PLP or lipophilin) is the major myelin protein from the central nervous system (CNS). It probably plays an important role in the formation or maintenance of the multilamellar structure of myelin. In man point mutations in PLP are the cause of Pelizaeus-Merzbacher disease (PMD), a neurologic disorder of myelin metabolism. In animals dismyelinating diseases such as mouse 'jimpy' (jp), rat md, or dog 'shaking pup' are also caused by mutations in PLP.

PLP is a highly conserved hydrophobic protein of 276 to 280 amino acids which seems to contain four transmembrane segments, two disulphide bonds and which covalently binds lipids (at least six palmitate groups in mammals) .

PLP is highly related to M6, a neuronal membran glycoprotein .
Delta-endotoxin CytB (Endotoxin_CytB)
Type: Family

Bacillus thuringiensis produces the delta-endotoxin CytB, a membrane pore-forming protein, which is active against insects . The toxin kills the larvae of dipteran insects by making pores in the epithelial cell membrane of the insect midgut. The crystal protein is produced during sporulation and is accumulated both as an inclusion and as part of the spore coat.
Alphaherpesvirus alkaline exonuclease (Herpes_alk_exo)
Type: Family

This entry includes an alkaline nuclease (product of the UL98 gene) from herpesviruses. The nuclease acts as both an endo-and an exonuclease, and accepts both single-and double-stranded DNA as substrates. DNA is digested in the 5'->3' direction to produce 5'-monophosphate nucleosides. The nuclease activity results in the production of mature packaged unit-length linear progeny viral DNA molecules by processing non linear or branched viral DNA intermediates .
Sec1-like protein (Sec1-like)
Type: Family

Sec1-like molecules have been implicated in a variety of eukaryotic vesicle transport processes including neurotransmitter release by exocytosis . They regulate vesicle transport by binding to a t-SNARE from the syntaxin family. This process is thought to prevent SNARE complex formation, a protein complex required for membrane fusion. Whereas Sec1 molecules are essential for neurotransmitter release and other secretory events, their interaction with syntaxin molecules seems to represent a negative regulatory step in secretion .
Dopamine D3 receptor (Dopamine_D3_rcpt)
Type: Family

Dopamine receptors are members of the rhodopsin-like G-protein coupled receptor family and are prominent in the vertebrate central nervous system (CNS). Dysfunction of dopaminergic neurotransmission in the CNS has been implicated in a variety of neuropsychiatric disorders , including social phobia , Tourette's syndrome , Parkinson's disease , schizophrenia , neuroleptic malignant syndrome , attention-deficit hyperactivity disorder (ADHD) and drug and alcohol dependence . As a result, dopamine receptors are common drug targets; antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors .

There are at least five different known subtypes of dopamine receptors designated D1, D2, D3, D4 and D5 . They are distinguished by their G-protein coupling, ligand specificity, anatomical distribution and physiological effects. Dopamine receptors are divided into two further subfamilies. The D1-like family consists of D1 and D5 receptors, which couple to Gs and mediate excitatory neurotransmission. The D2-like family, meanwhile, consists of D2, D3 and D4 receptors, which couple to Gi/Go and mediate inhibitory neurotransmission. Although dopamine receptors are widely distributed in the brain, they are found in different locations that have different receptor type densities, presumably reflecting different functional roles . D1 and D2 receptor subtypes are found at 10-100 times the levels of the D3, D4, D5 subtypes .

This entry represents the dopamine D3 receptors, which have a similar pharmacological profile to D2 receptors. They are expressed predominantly in the limbic area (including the olfactory tubercle, nucleus accumbens, islands of Calleja and hypothalamus), and they are present in lower levels in the caudate-putamen and cerebral cortex. The receptors are also found in dopamine cell bodies in the substantia nigra. The distribution of dopamine D3 receptors is consistent with a role in cognition and emotional functions and they may be a target of antipsychotic therapy involving dopamine antagonists . The receptors have been implicated in modulation of cocaine self-administration .
Fungal ligninase (Ligninase)
Type: Family

Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions. Peroxidases are found in bacteria, fungi, plants and animals. Fungal ligninases are extracellular haem enzymes involved in the degradation of lignin. They include lignin peroxidases (LiPs), manganese-dependent peroxidases (MnPs) and versatile peroxidases, which combine the substrate-specificity characteristics of the other two . In MnP, Mn
2+
serves as the reducing substrate .

It is commonly thought that the plant polymer lignin is the second most abundant organic compound on Earth, exceeded only by cellulose. Higher plants synthesise vast quantities of insoluble macromolecules, including lignins. Lignin is an amorphous three-dimensional aromatic biopolymer composed of oxyphenylpropane units. Biodegradation of lignins is slow - it is probable that their decomposition is the rate-limiting step in the biospheric carbon-oxygen cycle, which is mediated almost entirely by the catabolic activities of microorganisms. The white-rot fungi are able extensively to decompose all the important structural components of wood, including both cellulose and lignin. Under the proper environmental conditions, white-rot fungi completely degrade all structural components of lignin, with ultimate formation of CO
2
and H
2
O. The first step in lignin degradation is depolymerisation, catalysed by the LiPs (ligninases). LiPs are secreted, along with hydrogen peroxide (H
2
O
2
), by white-rot fungi under conditions of nutrient limitation. The enzymes are not only important in lignin biodegradation, but are also potentially valuable in chemical waste disposal because of their ability to degrade environmental pollutants .

To date, 3D structures have been determined for LiP and MnP from Phanerochaete chrysosporium (White-rot fungus), and for the fungal peroxidase from Arthromyces ramosus . All these proteins share the same architecture and consist of 2 all-alpha domains, between which is embedded the haem group. The helical topography of LiPs is nearly identical to that of yeast cytochrome c peroxidase (CCP) , despite the former having four disulphide bonds, which are absent in CCP (MnP has an additional disulphide bond at the C terminus).
Flagellar hook-basal body complex protein FliE (FliE)
Type: Family

Four genes from the major Bacillus subtilis chemotaxis locus have been shown to encode proteins that are similar to the Salmonella typhimurium FlgB, FlgC, FlgG and FliF proteins; a further gene product is similar to the Escherichia coli FliE protein . All of these proteins are thought to form part of the hook-basal body complex of the bacterial flagella . The FlgB, FlgC and FlgG proteins are components of the proximal and distal rods; FliF forms the M-ring that anchors the rod assembly to the membrane; but the role of FliE has not yet been determined . The similarity between the proteins in these two organisms suggests that the structures of the M-ring and the rod may be similar . Nevertheless, some differences in size and amino acid composition between some of the homologues suggest the basal body proteins may be organised slightly differently within B. subtilis .

From gel electrophoresis and autoradiography of 35S-labelled S. typhimurium hook-basal body complexes and the deduced number of sulphur-containing residues in FliE, the stoichiometry of the protein in the hook-basal body complex has been estimated to be about nine subunits . FliE does not undergo cleavage of a signal peptide, nor does it show any similarity to the axial components like the rod or hook proteins, which are thought to be exported by the flagellum-specific export pathway . On this evidence, it has been suggested that FliE may be in the vicinity of the MS ring, perhaps acting as an adaptor protein between ring and rod substructures .