SII-SWORD/CoKE huggingface dataset:
Chorion protein (Chorion)
Type: Family

This family consists of the chorion superfamily proteins classes A, B, CA, CB and high-cysteine HCB from silk, gypsy and polyphemus moths. The chorion proteins make up the moths egg shell - a complex extracellular structure .
Protein from unkown function DUF29 (DUF29)
Type: Family

This family consists of various bacterial hypothetical proteins, none of which are functionally described. The family has several highly conserved sequence motifs, including YD/ExD, DxxNVxEEIE, and CPY/F/W, as well as conserved tryptophans.
RdgB/HAM1 (RdgB/HAM1)
Type: Family

This family contains a group of purine NTP pyrophosphatases, including dITP/XTP pyrophosphatase RdgB from E.coli and inosine triphosphate pyrophosphatase (ITPA, also known as HAM1) from Saccharomyces cerevisiae (Baker's yeast) (

), as well as archaeal and Caenorhabditis elegans homologues. S. cerevisiae HAM1 was originally identified as a gene that protects against the mutagenic effects of the base analogue 6-N-hydroxylaminopurine (HAP) which can be a natural product of monooxygenase activity on adenine . Subsequent studies demonstrated that HAM1 detoxifies abnormal pyrimidine as well as purine nucleotides . RdgB appears to act by intercepting non-canonical deoxyribonucleotide triphosphates from replication precursor pools .

Similarly, a Ham1-related protein from Methanococcus jannaschii is a novel NTPase that has been shown to hydrolyze nonstandard nucleotides such as XTP to XMP and ITP to IMP, but not the standard nucleotides, in the presence of Mg or Mn ions. The enzyme exists as a homodimer .

This entry also includes Dihydroneopterin triphosphate diphosphatase which is involved in the biosynthesis of tetrahydrofolate and catalyses the hydrolysis of dihydroneopterin triphosphate to dihydroneopterin monophosphate and pyrophosphate .
Quinolinate phosphoribosyl transferase, C-terminal (Quinolinate_PRibosylTrfase_C)
Type: Domain

Quinolinate phosphoribosyl transferase (QPRTase) or nicotinate-nucleotide pyrophosphorylase

is involved in the
de novo
synthesis of NAD in both prokaryotes and eukaryotes. It catalyses the reaction of quinolinic acid with 5-phosphoribosyl-1-pyrophosphate (PRPP) in the presence of Mg
2+
to give rise to nicotinic acid mononucleotide (NaMN), pyrophosphate and carbon dioxide . Unlike

, this domain also includes the molybdenum transport system protein ModD.
Urease accessory protein UreF (UreF)
Type: Family

This family consists of the urease accessory protein, UreF. The urease enzyme (urea amidohydrolase) hydrolyses urea into ammonia and carbamic acid . UreF is proposed to modulate the activation process of urease by eliminating the binding of nickel irons to noncarbamylated protein .

This entry also includes the URE6 from Cryptococcus neoformans which is a fungal homologue of UreF and pays a role in host brain invasion causing meningoencephalitis .
Arylesterase (Arylesterase)
Type: Family

The serum paraoxonases/arylesterases are enzymes that catalyse the hydrolysis of the toxic metabolites of a variety of organophosphorus insecticides. The enzymes hydrolyse a broad spectrum of organophosphate substrates, including paraoxon and a number of aromatic carboxylic acid esters (e.g., phenyl acetate), and hence confer resistance to organophosphate toxicity .

Mammals have 3 distinct paraoxonase types, termed PON1-3 . In mice and humans, the PON genes are found on the same chromosome in close proximity. PON activity has been found in variety of tissues, with highest levels in liver and serum -the source of serum PON is thought to be the liver. Unlike mammals, fish and avian species lack paraoxonase activity.

Human and rabbit PONs appear to have two distinct Ca2+ binding sites, one required for stability and one required for catalytic activity. The Ca2+ dependency of PONs suggests a mechanism of hydrolysis where Ca2+ acts as the electrophillic catalyst, like that proposed for phospholipase A2. The paraoxonase enzymes, PON1 and PON3, are high density lipoprotein (HDL)-associated proteins capable of preventing oxidative modification of low density lipoproteins (LPL) . Although PON2 has oxidative properties, the enzyme does not associate with HDL.

Within a given species, PON1, PON2 and PON3 share ~60% amino acid sequence identity, whereas between mammalian species particular PONs (1,2 or 3) share 79-90% identity at the amino acid level. Human PON1 and PON3 share numerous conserved phosphorylation and N-glycosylation sites; however, it is not known whether the PON proteins are modified at these sites, or whether modification at these sites is required for activity in vivo .

This family consists of arylesterases (Also known as serum paraoxonase)

. These enzymes hydrolyse organophosphorus esters such as paraoxon and are found in the liver and blood. They confer resistance to organophosphate toxicity . Human arylesterase (PON1)

is associated with HDL and may protect against LDL oxidation .
Patatin-like phospholipase domain (PNPLA_dom)
Type: Domain

The patatin glycoprotein is a nonspecific lipid acyl hydrolase that is found in high concentrations in mature potato tubers. Patatin is reported to play a role in plant signaling, to cleave fatty acids from membrane lipids, and to act as defense against plant parasites. Proteins encoding a patatin-like
phospholipase (PNPLA) domain are ubiquitously distributed across all life forms, including eukaryotes and prokaryotes, and are observed to participate in a miscellany of biological roles, including sepsis induction, host colonization, triglyceride metabolism, and membrane trafficking. PNPLA domain containing proteins display lipase and transacylase properties and appear to have major roles in lipid and energy homeostasis .

The ~180-amino acid PNPLA domain harbors the evolutionarily conserved consensus serine lipase motif Gly-X-Ser-X-Gly. It displays an α/β class protein fold with approximately three layers, basically α/β/α in content, in which a central six-stranded β-sheet is sandwiched essentially between α-helices front and back. The central β-sheet contains five parallel strands and an antiparallel strand at the edge of the
sheet. The PNPLA domain has a Ser-Asp catalytic dyad. The catalytic Ser resides in a sharp nucleophile elbow turn loop which follows a β-strand
(β5) of the central β-sheet and precedes a helix (helix C) .
Lysophospholipase, catalytic domain (LysoPLipase_cat_dom)
Type: Domain

This family consists of lysophospholipase / phospholipase B

and cytosolic phospholipase A2 which also has a C2 domain

. Phospholipase B enzymes catalyse the release of fatty acids from lysophsopholipids and are capable
in vitro
of hydrolyzing all phospholipids extractable from yeast cells . Cytosolic phospholipase A2 associates with natural membranes in response to physiological increases in Ca
2+
and selectively hydrolyses arachidonyl phospholipids , the aligned region corresponds the carboxy-terminal Ca
2+
-independent catalytic domain of the protein as discussed in .
Polyomavirus agnoprotein (Polyoma_agno)
Type: Family

This family consists of the DNA-binding protein or agnoprotein from various polyomaviruses. This protein is highly basic and can bind single stranded and double stranded DNA . Mutations in the agnoprotein produce smaller viral plaques, hence its function is not essential for growth in tissue culture cells but something has slowed in the normal replication cycle . There is also evidence suggesting that the agnogene and agnoprotein act as regulators of structural protein synthesis .
Photosystem II PsbZ, reaction centre (PSII_PsbZ)
Type: Family

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This family represents PsbZ (Ycf9), which is a core low molecular weight transmembrane protein of photosystem II in thylakoid-containing chloroplasts of cyanobacteria and plants. It is thought to be located at the interface of PSII and LHCII (light-harvesting complex II) complexes, the latter containing the light-harvesting antenna. PsbZ appears to act as a structural factor, or linker, that stabilises the PSII-LHCII supercomplexes, which fail to form in PsbZ-deficient mutants. This may in part be due to the marked decrease in two LHCII antenna proteins, CP26 and CP29, found in PsbZ-deficient mutants, which result in structural changes, as well as functional modifications in PSII . PsbZ may also be involved in photo-protective processes under sub-optimal growth conditions.
STAS domain (STAS_dom)
Type: Domain

The STAS (Sulphate Transporter and AntiSigma factor antagonist) domain is found in the bacterial anti-sigma factor antagonists (ASA) and the C-terminal region of SLC26 (SulP) anion transporters.

The activity of bacterial sigma transcription factors is controlled by a regulatory cascade involving an antisigma-factor, the antisigma-factor antagonist (ASA) and a phosphatase. The antisigma-factor binds to sigma and holds it in an inactive complex. The ASA can also interact with the anti-sigma-factor, allowing the release of the active sigma factor. As the antisigma-factor is a protein kinase, it can phosphorylate the antisigma antagonist on a conserved serine residue of the STAS domain. This phosphorylation inactivates the ASA that can be reactivated through dephosphorylation by a phosphatase . The STAS domain of the ASA SpoIIAA binds GTP and ATP and possesses a weak NTPase activity. Strong sequence conservation suggests that the STAS domain could possess general NTP-binding activity, and it has been proposed that the NTPs are likely to elicit specific conformational changes in the STAS domain through binding and/or hydrolysis . Resolution of the solution structure of the ASA SpoIIAA from Bacillus subtilis has shown that the STAS domain consists of a four-stranded β-sheet and four α-helices. The STAS domain forms a characteristic α-helical handle-like structure .

The STAS domain of E. coli YchM protein, a SLC26 (SulP) family member, has been shown to interact with acyl carrier protein (ACP), which is an activated thiol ester carrier of acyl intermediates during fatty acid biosynthesis (FAB) and other acylation reactions .

Malfunctions in members of the SLC26A family of anion transporters are involved in three human diseases: diastrophic dysplasia/achondrogenesis type 1B (DTDST), Pendred's syndrome (PDS) and congenital chloride diarrhea (CLD). These proteins contain 12 transmembrane helices followed by a cytoplasmic STAS domain at the C terminus. The importance of the STAS domain in these transporters is illustrated by the fact that a number of mutations in PDS and DTDST map to it .
Poly A polymerase, head domain (PolA_pol_head_dom)
Type: Domain

This group includes nucleic acid independent RNA polymerases, such as polynucleotide adenylyltransferase (

), which adds the poly (A) tail to mRNA. This group also includes the tRNA nucleotidyltransferase that adds the CCA to the 3' of the tRNA (

).

CCA-adding enzymes add the sequence [cytidine(C)-cytidine-adenosine (A)]., one nucleotide at a time, onto the 3' end of tRNA, in a template-independent reaction . This Class II group is comprised mainly of eubacterial and eukaryotic enzymes and includes Bacillus stearothermophilus CCAase , Escherichia coli poly(A) polymerase I , human mitochondrial CCAase , and Saccharomyces cerevisiae CCAase (CCA1) . CCA-adding enzymes have a single catalytic pocket, which recognizes both ATP and CTP substrates . This family belongs to the Pol beta-like NT superfamily .

In the Pol beta-like NT superfamily , the majority of enzymes have two carboxylates, Dx[D/E], together with a third more distal carboxylate, which coordinate two divalent metal cations involved in a two-metal ion mechanism of nucleotide addition. These carboxylate residues are fairly well conserved in this family.
Adenylate dimethylallyltransferase (Tzs)
Type: Family

Adenylate dimethylallyltransferase transfers dimethylallyl groups to AMP as part of the biosynthesis of cytokinin phytohormones .
tRNA (guanine-N1-)-methyltransferase TrmD (tRNA_m1G_MeTrfase_TrmD)
Type: Family

In transfer RNA many different modified nucleosides are found, especially in the anticodon region. tRNA (guanine (N1))-methyltransferase TrmD

is one of several nucleases operating together with the tRNA-modifying enzymes before the formation of the mature tRNA. It catalyses the reaction:

S-adenosyl-L-methionine + guanine37 in tRNA ->S-adenosyl-L-homocysteine + tRNA containing N1-methylguanine

It methylates guanosine(G) to N1-methylguanine (1-methylguanosine (m1G)) at position 37 of tRNAs that read CUN (leucine), CCN(proline), and CGG (arginine) codons. The presence of m1G improves the cellular growth rate and the polypeptide steptime and also prevents the tRNA from shifting the reading frame .
Sulphate adenylyltransferase (Sulphate_adenylyltransferase)
Type: Family

Sulphate adenylyltransferase or ATP-sulfurylase (

) forms adenosine 5'-phosphosulphate (APS) from ATP and free sulphate, the first step in the formation of the activated sulphate donor 3'-phosphoadenylylsulphate (PAPS) . In some cases, it is found in a bifunctional protein in which the other domain, adenosyl phosphosulphate (APS) kinase, catalyses the second and final step, the phosphorylation of APS to PAPS . The combined ATP sulfurylase/APS kinase may be called PAPS synthase. In some organisms it is used to generate APS from sulfate and ATP, while in others it proceeds in the opposite direction to generate ATP from APS and pyrophosphate. ATP sulfurylase can be a monomer, a homodimer, or a homo-oligomer, depending on the organism. It belongs to a large superfamily of nucleotidyltransferases that includes pantothenate synthetase (PanC), phosphopantetheine adenylyltransferase (PPAT), the amino-acyl tRNA synthetases, and the dissimilatory sulphate adenylyltransferase (sat) of the sulphate reducer Archaeoglobus fulgidus. The enzymes of this family are structurally similar and share a dinucleotide-binding domain. .
Importin-alpha, importin-beta-binding domain (Importin-a_IBB)
Type: Domain

This entry represents the N-terminal IBB domain of importin-alpha that contains the auto-regulatory region.

The exchange of macromolecules between the nucleus and cytoplasm takes place through nuclear pore complexes within the nuclear membrane. Active transport of large molecules through these pore complexes require carrier proteins, called karyopherins (importins and exportins), which shuttle between the two compartments.

Members of the importin-alpha (karyopherin-alpha) family can form heterodimers with importin-beta. As part of a heterodimer, importin-beta mediates interactions with the pore complex, while importin-alpha acts as an adaptor protein to bind the nuclear localisation signal (NLS) on the cargo through the classical NLS import of proteins. Proteins can contain one (monopartite) or two (bipartite) NLS motifs. Importin-alpha contains several armadillo (ARM) repeats, which produce a curving structure with two NLS-binding sites, a major one close to the N terminus and a minor one close to the C terminus.

Ran GTPase helps to control the unidirectional transfer of cargo. The cytoplasm contains primarily RanGDP and the nucleus RanGTP through the actions of RanGAP and RanGEF, respectively. In the nucleus, RanGTP binds to importin-beta within the importin/cargo complex, causing a conformational change in importin-beta that releases it from importin-alpha-bound cargo. The N-terminal importin-beta-binding (IBB) domain of importin-alpha contains an auto-regulatory region that mimics the NLS motif . The release of importin-beta frees the auto-regulatory region on importin-alpha to loop back and bind to the major NLS-binding site, causing the cargo to be released .
Zinc finger, A20-type (Znf_A20)
Type: Domain

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.

This entry represents the zinc finger domain found in A20. A20 is an inhibitor of cell death that inhibits NF-kappaB activation via the tumour necrosis factor receptor associated factor pathway . The zinc finger domains appear to mediate self-association in A20. These fingers also mediate IL-1-induced NF-kappa B activation.
Glycosyl transferase, family 25 (Glyco_trans_25)
Type: Family

The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases. These enzymes catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. A classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugar and sugar phosphates ([ec:2.4.1.-]) and related proteins into distinct sequence based families has been described . This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. The same three-dimensional fold is expected to occur within each of the families. Because 3-D structures are better conserved than sequences, several of the families defined on the basis of sequence similarities may have similar 3-D structures and therefore form 'clans'.

Glycosyltransferase family 25 (

) comprises enzymes with only one known activity: as a lipopolysaccharide biosynthesis protein. These enzymes catalyse the transfer of various sugars onto the growing lipopolysaccharide chain during its biosynthesis .
Acyl-CoA oxidase, C-terminal (Acyl-CoA_oxidase_C)
Type: Domain

Acyl-CoA oxidase (ACO) acts on CoA derivatives of fatty acids with chain lengths from 8 to 18. It catalyses the first and rate-determining step of the peroxisomal beta-oxidation of fatty acids .

Acyl-CoA oxidase is a homodimer and the polypeptide chain of the subunit is folded into the N-terminal alpha-domain, beta-domain, and C-terminal alpha-domain . Functional differences between the peroxisomal acyl-CoA oxidases and the mitochondrial acyl-CoA dehydrogenases are attributed to structural differences in the FAD environments .
Acyltransferase 3 domain (Acyl_transf_3_dom)
Type: Domain

This entry represents the acyltransferase domain present in a wide range of acyltransferase enzymes, including, mainly, bacterial proteins which catalyse the transfer of acyl groups, other than amino-acyl, from one compound to another, such as Glucans biosynthesis protein C (OPGC) or protein OatA from Listeria monocytogenes serovar 1/2a and Staphylococcus aureus, an integral membrane protein which is responsible for O-acetylation at the C6-hydroxyl group of N-acetylmuramyl residues, forming the corresponding N,6-O-diacetylmuramic acid of the peptidoglycan, a modification that determines lysozyme resistance . The pathogenic bacteria, Staphylococcus aureus, is able to cause persistent infections due to its ability to resist the immune defence system. Lysozyme, a cell wall-lytic enzyme, is one of the first defence compounds induced in serum and tissues after the onset of infection . This entry also includes NolL proteins. NolL-dependent acetylation is specific for the fucosyl penta-N-acetylglucosamine species. In addition, the NolL protein caused elevated production of lipo-chitin oligosaccharides (LCOs). The NolL protein obtained from Rhizobium loti (Mesorhizobium loti) functions as an acetyl transferase .

This domain is also present in eukaryotic proteins, namely O-acyltransferase like protein (OACYL) from mouse and RHY1 (Regulator of hypoxia-inducible factor 1) and NRF6 (Nose resistant to fluoxetine protein 6) from Caenorhabditis elegans.
Bile acid:sodium symporter/arsenical resistance protein Acr3 (BilAc:Na_symport/Acr3)
Type: Family

This family of proteins are found both in prokaryotes and eukaryotes. They are related to the human bile acid:sodium symporters (TC 2.A.28), which are transmembrane proteins functioning in the liver in the uptake of bile acids from portal blood plasma, a process mediated by the co-transport of Na
+
.

This entry also includes members of the ACR3 family of arsenite (As(III)) permeases, which confer resistance to arsenic by extrusion from cells . They exist in prokaryotes and eukaryotes (lower plants and fungi) . The ACR3 permeases have ten-transmembrane span topology . Corynebacterium glutamicum has three Acr3 proteins, CgAcr3-1, CgAcr3-2, and CgAcr3-3. CgAcr3-1 is thought to be an antiporter that catalyses arsenite-proton exchange .

The Shewanella oneidensis Acr3 is not able to transport As(III) and confers resistance only to arsenate (As(V)) , whereas the Acr3 orthologue from Synechocystis mediates tolerance to As(III), As(V) and antimonite (Sb(III)) .

In budding yeast, overexpression of the Acr3 gene confers an arsenite- but not an arsenate-resistance phenotype . Saccharomyces cerevisiae Acr3 is a plasma membrane metalloid/H+ antiporter that transports arsenite and antimonite .