SII-SWORD/CoKE huggingface dataset:
Calponin repeat (Calponin_repeat)
Type: Repeat

Calponin is a thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin, troponin C and tropomyosin. The interaction of calponin with actin inhibits the actomyosin MgATPase activity. Calponin is a basic protein of approximately 34 Kd. Multiple isoforms are found in smooth muscles. Calponin contains three repeats of a well conserved 26 amino acid domain. Such a domain is also found in vertebrate smooth muscle protein (SM22 or transgelin), and a number of other proteins whose physiological role is not yet established, including Drosophila synchronous flight muscle protein SM20, Caenorhabditis elegans unc-87 protein , rat neuronal protein NP25 , and an Onchocerca volvulus antigen .
Histone H2B (Histone_H2B)
Type: Family

Histone H2B is one of the five histones, along with H1/H5, H2A, H3 and H4. Two copies of each of the H2A, H2B, H3, and H4 histones ensemble to form the core of the nucleosome . The nucleosome forms octameric structure that wraps DNA in a left-handed manner. Histones can undergo several different types of post-translational modifications that affect transcription, DNA repair, DNA replication and chromosomal stability.
Formate-tetrahydrofolate ligase, FTHFS (Formate_THF_ligase)
Type: Family

Formate--tetrahydrofolate ligase (

) (formyltetrahydrofolate synthetase) (FTHFS) is one of the enzymes participating in the transfer of one-carbon units, an essential element of various biosynthetic pathways. FTHFS catalyzes the ATP-dependent activation of formate ion via its addition to the N10 position of tetrahydrofolate. FTHFS is a highly expressed key enzyme in both the Wood-Ljungdahl pathway of autotrophic CO
2
fixation (acetogenesis) and the glycine synthase/reductase pathways of purinolysis. The key physiological role of this enzyme in acetogens is to catalyze the formylation of tetrahydrofolate, an initial step in the reduction of carbon dioxide and other one-carbon precursors to acetate. In purinolytic organisms, the enzymatic reaction is reversed, liberating formate from 10-formyltetrahydrofolate with concurrent production of ATP . In many of these processes the transfers of one-carbon units are mediated by the coenzyme tetrahydrofolate (THF). In eukaryotes the FTHFS activity is expressed by a multifunctional enzyme, C-1-tetrahydrofolate synthase (C1-THF synthase), which also catalyses the dehydrogenase and cyclohydrolase activities. Two forms of C1-THF synthases are known , one is located in the mitochondrial matrix, while the second one is cytoplasmic. In both forms the FTHFS domain consists of about 600 amino acid residues and is located in the C-terminal section of C1-THF synthase. In prokaryotes FTHFS activity is expressed by a monofunctional homotetrameric enzyme of about 560 amino acid residues .

The crystal structure of N(10)-formyltetrahydrofolate synthetase from Moorella thermoacetica shows that the subunit is composed of three domains organised around three mixed β-sheets. There are two cavities between adjacent domains. One of them was identified as the nucleotide binding site by homology modelling. The large domain contains a seven-stranded β-sheet surrounded by helices on both sides. The second domain contains a five-stranded β-sheet with two α-helices packed on one side while the other two are a wall of the active site cavity. The third domain contains a four-stranded β-sheet forming a half-barrel. The concave side is covered by two helices while the convex side is another wall of the large cavity. Arg 97 is likely involved in formyl phosphate binding. The tetrameric molecule is relatively flat with the shape of the letter X, and the active sites are located at the end of the subunits far from the subunit interface .
Histidine phosphatase superfamily, clade-2 (His_Pase_clade-2)
Type: Family

This entry represents the clade 2 of histidine phosphatase superfamily.

Included in this group are:

Escherichia coli pH 2.5 acid phosphatase (gene appA).

E. coli glucose-1-phosphatase (

) (gene agp).

Yeast constitutive and repressible acid phosphatases (genes PHO3 and PHO5).

Schizosaccharomyces pombe acid phosphatase (gene pho1).

Aspergillus awamori phytases A and B (

) (gene phyA and phyB).

Mammalian lysosomal and prostatic acid phosphatase.

Several Caenorhabditis elegans hypothetical proteins.

The histidine phosphatase superfamily is so named because catalysis centres on a conserved His residue that is transiently phosphorylated during the catalytic cycle. Other conserved residues contribute to a 'phosphate pocket' and interact with the phospho group of substrate before, during and after its transfer to the His residue. Structure and sequence analyses show that different families contribute different additional residues to the 'phosphate pocket' and, more surprisingly, differ in the position, in sequence and in three dimensions, of a catalytically essential acidic residue. The superfamily may be divided into two main branches. The relationship between the two branches is not evident by (PSI-)BLAST but is clear from more sensitive sequence searches and structural comparisons .

The smaller clade-2 is composed mainly of acid phosphatases and phytases. Acid phosphatases are a heterogeneous group of proteins that hydrolyse phosphate esters, optimally at low pH. The catalytic functions of these proteins include phytase, glucose-1-phosphatase and multiple inositol polyphosphate phosphatase. Fungal phytases are histidine acid phosphatases that catalyse the hydrolysis of phytate (myo-inositol hexakisphosphate) to myo-inositol and inorganic phosphate .
Fibronectin type II domain (FN_type2_dom)
Type: Domain

Fibronectin is a multi-domain glycoprotein, found in a soluble form in plasma, and in an insoluble form in loose connective tissue and basement membranes, that binds cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in a number of important functions e.g., wound healing; cell adhesion; blood coagulation; cell differentiation and migration; maintenance of the cellular cytoskeleton; and tumour metastasis .

The major part of the sequence of fibronectin consists of the repetition of three types of domains, which are called type I, II, and III (also called FN1, FN2 and FN3 respectively). In fibronectin the type II domain is duplicated. Type II domain is approximately forty residues long, contains four conserved cysteines involved in disulphide bonds and is part of the collagen-binding region of fibronectin. Type II domains have also been found in a range of proteins including blood coagulation factor XII; bovine seminal plasma proteins PDC-109 (BSP-A1/A2) and BSP-A3 ; cation-independent mannose-6-phosphate receptor ; mannose receptor of macrophages ; 180 Kd secretory phospholipase A2 receptor . DEC-205 receptor ; 72 Kd and 92 Kd type IV collagenase (

) ; and hepatocyte growth factor activator .
Flagellar assembly protein FliH (Flag_FliH)
Type: Family

Many flagellar proteins are exported by a flagellum-specific export pathway. Attempts have been made to characterise the apparatus responsible for this process, by designing assays to screen for mutants with export defects. Experiments involving filament removal from temperature-sensitive flagellar mutants of Salmonella typhimurium have shown that, while most mutants were able to regrow filaments, flhA, fliH, fliI and fliN mutants showed no or greatly reduced regrowth. This suggests that the corresponding gene products are involved in the process of flagellum-specific export . The sequence of fliH has been deduced and shown to encode a protein of molecular mass of 25,782 Da.
DNA topoisomerase, type IIA, subunit B (Topo_IIA_B)
Type: Family

Type IIA topoisomerases together manage chromosome integrity and topology in cells. Topoisomerase II (called gyrase in bacteria) primarily introduces negative supercoils into DNA. In bacteria, topoisomerase II consists of two polypeptide subunits, gyrA and gyrB, which form a heterotetramer: (BA)2. In most eukaryotes, topoisomerase II consists of a single polypeptide, where the N- and C-terminal regions correspond to gyrB and gyrA, respectively; this topoisomerase II forms a homodimer that is equivalent to the bacterial heterotetramer. There are four functional domains in topoisomerase II: domain 1 (N-terminal of gyrB) is an ATPase, domain 2 (C-terminal of gyrB) is responsible for subunit interactions (differs between eukaryotic and bacterial enzymes), domain 3 (N-terminal of gyrA) is responsible for the breaking-rejoining function through its capacity to form protein-DNA bridges, and domain 4 (C-terminal of gyrA) is able to non-specifically bind DNA .

Topoisomerase IV primarily decatenates DNA and relaxes positive supercoils, which is important in bacteria, where the circular chromosome becomes catenated, or linked, during replication . Topoisomerase IV consists of two polypeptide subunits, parE and parC, where parC is homologous to gyrA and parE is homologous to gyrB.

This entry represents subunit B found in topoisomerase II (gyrB) and topoisomerase IV (parE), primarily of bacterial origin, and which functions in ATP hydrolysis and subunit interaction. It does not include the topoisomerase II enzymes composed of a single polypeptide, as are found in most eukaryotes.

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks . These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis . DNA topoisomerases are divided into two classes: type I enzymes (

; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (

; topoisomerases II, IV and VI) break double-strand DNA .

Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils .
Lipocalin/cytosolic fatty-acid binding domain (Lipocln_cytosolic_FA-bd_dom)
Type: Domain

This entry represents the lipocalin/cytosolic fatty-acid binding domain of a group of proteins that belong to the calycin superfamily.

Proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids share limited regions of sequence homology and a common tertiary structure architecture . This is an eight stranded antiparallel β-barrel with a repeated + 1 topology enclosing a internal ligand binding site . The name 'lipocalin' has been proposed for this protein family, but cytosolic fatty-acid binding proteins are also included. The sequences of most members of the family, the core or kernal lipocalins, are characterised by three short conserved stretches of residues, while others, the outlier lipocalin group, share only one or two of these . Proteins known to belong to this family include alpha-1-microglobulin (protein HC); alpha-1-acid glycoprotein (orosomucoid) ; aphrodisin; apolipoprotein D; beta-lactoglobulin; complement component C8 gamma chain ; crustacyanin ; epididymal-retinoic acid binding protein (E-RABP) ; insectacyanin; odorant-binding protein (OBP); human pregnancy-associated endometrial alpha-2 globulin; probasin (PB), a rat prostatic protein; prostaglandin D synthase (

) ; purpurin; Von Ebner's gland protein (VEGP) ; and lizard epididymal secretory protein IV (LESP IV) .
ATP synthase, F0 complex, subunit A (ATP_synth_F0_asu)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.

This entry represents subunit A (or subunit 6) found in the F0 complex of F-ATPases. This subunit is a key component of the proton channel, and may play a direct role in the translocation of protons across the membrane. Catalysis in the F1 complex depends upon the rotation of the central stalk and F0 c-ring, which in turn is driven by the flux of protons through the membrane via the interface between the F0 c-ring and subunit A. The peripheral stalk links subunit A to the external surface of the F1 domain, and is thought to act as a stator to counter the tendency of subunit A and the F1 α(3)β(3) catalytic portion to rotate with the central rotary element
.
HECT domain (HECT_dom)
Type: Domain

The HECT (Homologous to the E6-AP Carboxyl Terminus) domain is an around 350 amino acids motif that has been identified in proteins that all belong to a particular E3 ubiquitin-protein ligase family . HECT domain containing proteins accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then transfer it to lysine side chains of target proteins, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains. The site of ubiquitin thioester formation is a conserved cysteine residue located in the last 32-36 aa of the HECT domain . The amino-terminal part of the HECT domain has been involved in E2 binding . Once linked to ubiquitin, the target proteins are degraded in the 26 S proteasome.
Zinc finger, CCCH-type (Znf_CCCH)
Type: Domain

This entry represents C-x8-C-x5-C-x3-H (CCCH) type Zinc finger (Znf) domains.

Proteins containing CCCH Znf domains include Znf proteins from eukaryotes involved in cell cycle or growth phase-related regulation, e.g. human TIS11B (butyrate response factor 1, also known as mRNA decay activator protein ZFP36L1), a probable regulatory protein involved in regulating the response to growth factors, and the mouse TTP growth factor-inducible nuclear protein, which has the same function. The mouse TTP protein is induced by growth factors. Another protein containing this domain is the human splicing factor U2AF 35kDa subunit, which plays a critical role in both constitutive and enhancer-dependent splicing by mediating essential protein-protein interactions and protein-RNA interactions required for 3' splice site selection. It has been shown that different CCCH-type Znf proteins interact with the 3'-untranslated region of various mRNA . This type of Znf is very often present in two copies.

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.
Oxidoreductase, molybdopterin-binding domain (OxRdtase_Mopterin-bd_dom)
Type: Domain

A number of different eukaryotic oxidoreductases that require and bind a molybdopterin cofactor have been shown to share a few regions of sequence similarity. These enzymes include xanthine dehydrogenase (

), aldehyde oxidase (

), nitrate reductase (

), and sulphite oxidase (

). The multidomain redox enzyme NAD(P)H:nitrate reductase (NR) catalyses the reduction of nitrate to nitrite in a single polypeptide electron transport chain with electron flow from NAD(P)H-FAD-cytochrome b5-molybdopterin-NO(3). Three forms of NR are known, an NADH-specific enzyme found in higher plants and algae (

); an NAD(P)H-bispecific enzyme found in higher plants, algae and fungi (

); and an NADPH-specific enzyme found only in fungi (

) . The mitochondrial enzyme sulphite oxidase (sulphite:ferricytochrome c oxidoreductase;

) catalyses oxidation of sulphite to sulphate, using cytochrome c as the physiological electron acceptor. Sulphite oxidase consists of two structure/function domains, an N-terminal haem domain, similar to cytochrome b5; and a C-terminal molybdopterin domain .
Aconitase A/isopropylmalate dehydratase small subunit, swivel domain (AconitaseA/IPMdHydase_ssu_swvl)
Type: Domain

This entry represents the 'swivel' domain found at the C-terminal of eukaryotic mAcn, cAcn/IPR1 and IRP2, and bacterial AcnA. This domain has a three layer β/β/α structure, and in cytosolic Acn is known to rotate between the cAcn and IRP1 forms of the enzyme. This domain is also found in the small subunit of isopropylmalate dehydratase (LeuD).

Aconitase (aconitate hydratase;

) is an iron-sulphur protein that contains a [4Fe-4S]-cluster and catalyses the interconversion of isocitrate and citrate via a cis-aconitate intermediate. Aconitase functions in both the TCA and glyoxylate cycles, however unlike the majority of iron-sulphur proteins that function as electron carriers, the [4Fe-4S]-cluster of aconitase reacts directly with an enzyme substrate. In eukaryotes there is a cytosolic form (cAcn) and a mitochondrial form (mAcn) of the enzyme. In bacteria there are also 2 forms, aconitase A (AcnA) and B (AcnB). Several aconitases are known to be multi-functional enzymes with a second non-catalytic, but essential function that arises when the cellular environment changes, such as when iron levels drop . Eukaryotic cAcn and mAcn, and bacterial AcnA have the same domain organisation, consisting of three N-terminal α/β/α domains, a linker region, followed by a C-terminal 'swivel' domain with a β/β/α structure (1-2-3-linker-4), although mAcn is small than cAcn. However, bacterial AcnB has a different organisation: it contains an N-terminal HEAT-like domain, followed by the 'swivel' domain, then the three α/β/α domains (HEAT-4-1-2-3) .

3-isopropylmalate dehydratase (or isopropylmalate isomerase; IPMI;

) catalyses the stereo-specific isomerisation of 2-isopropylmalate and 3-isopropylmalate, via the formation of 2-isopropylmaleate. This enzyme performs the second step in the biosynthesis of leucine, and is present in most prokaryotes and many fungal species. The prokaryotic enzyme is a heterodimer composed of a large (LeuC) and small (LeuD) subunit, while the fungal form is a monomeric enzyme. Both forms of isopropylmalate are related and are part of the larger aconitase family .
Tymovirus coat protein (Tymo_coat)
Type: Domain

This signature is found in coat proteins from the related tymoviruses. The coat protein is also known as the virion protein. The virus coat is composed of 180 copies of the coat protein arranged in an icosahedral shell.
LacY/RafB permease family (LacY/RafB_perm_fam)
Type: Family

In bacteria there are a number of families of transport proteins, including symporters and antiporters, that mediate the intake of a variety of sugars with the concomitant uptake of hydrogen ions (proton symporters) . The LacY family of Escherichia coli and Klebsiella pneumoniae are proton/beta-galactoside symporters, which, like most sugar transporters, are integral membrane proteins with 12 predicted transmembrane (TM) regions. Also similar to the LacY family are the rafinose (RafB) and sucrose (CscB) permeases from E. coli and melibiose permease (MelY) from Enterobacter cloacae .
Carbohydrate kinase, FGGY (Carb_kinase_FGGY)
Type: Family

This entry represents FGGY carbohydrate kinase family.

FGGY carbohydrate kinases carry out ATP-dependent phosphorylation on one out of at least nine distinct sugar substrates . These enzymes include L-ribulokinase (

) (gene araB); Erythriol kinase (

) (gene eryA); L-fucolokinase (

) (gene fucK); gluconokinase (

) (gene gntK); glycerol kinase (

) (gene glpK); xylulokinase (

) (gene xylB); L-xylulose kinase (

) (gene lyxK), D-ribulokinase (

) (gene rbtK); and rhamnulokinase (

) (gene rhaB). This family also contains a divergent subfamily functioning in quorum sensing, which phosphorylates AI-2, a bacterial signaling molecule derived from 4,5-dihydroxy-2,3-pentanedione (DPD) .
Cation-transporting P-type ATPase A/B (Cation-trans_P-type_ATPase_A/B)
Type: Family

P-ATPases (also known as E1-E2 ATPases) (

) are found in bacteria and in a number of eukaryotic plasma membranes and organelles . P-ATPases function to transport a variety of different compounds, including ions and phospholipids, across a membrane using ATP hydrolysis for energy. There are many different classes of P-ATPases, which transport specific types of ion: H
+
, Na
+
, K
+
, Mg
2+
, Ca
2+
, Ag
+
and Ag
2+
, Zn
2+
, Co
2+
, Pb
2+
, Ni
2+
, Cd
2+
, Cu
+
and Cu
2+
. P-ATPases can be composed of one or two polypeptides, and can usually assume two main conformations called E1 and E2.

This entry represents cation-transporting P-type ATPase A (CtpA) and B (CtpB), which are bacterial proteins that belong to the IB subfamily of P-type ATPases . CtpA has been identified as a copper-exporting P-type ATPase .