SII-SWORD/CoKE huggingface dataset:
Aquaporin 3 (Aquaporin_3)
Type: Family

Aquaporins are water channels, present in both higher and lower organisms, that belong to the major intrinsic protein family. Most aquaporins are highly selective for water, though some also facilitate the movement of small uncharged molecules such as glycerol . In higher eukaryotes these proteins play diverse roles in the maintenance of water homeostasis, indicating that membrane water permeability can be regulated independently of solute permeability. In microorganisms however, many of which do not contain aquaporins, they do not appear to play such a broad role. Instead, they assist specific microbial lifestyles within the environment, e.g. they confer protection against freeze-thaw stress and may help maintain water permeability at low temperatures . The regulation of aquaporins is complex, including transcriptional, post-translational, protein-trafficking and channel-gating mechanisms that are frequently distinct for each family member.

Structural studies show that aquaporins are present in the membrane as tetramers, though each monomer contains its own channel . The monomer has an overall "hourglass" structure made up of three structural elements: an external vestibule, an internal vestibule, and an extended pore which connects the two vestibules. Substrate selectivity is conferred by two mechanisms. Firstly, the diameter of the pore physically limits the size of molecules that can pass through the channel. Secondly, specific amino acids within the molecule regulate the preference for hydrophobic or hydrophilic substrates.

Aquaporins are classified into two subgroups: the aquaporins (also known as orthodox aquaporins), which transport only water, and the aquaglyceroporins, which transport glycerol, urea, and other small solutes in addition to water .

Aquaporin-3 (AQP3) forms a water-specific channel that renders the kidney medullary collecting duct highly permeability to water. It may function as a water and urea exit mechanism in antidiuresis in collecting duct cells, and is also slightly permeable to urea and glycerol. It may also play an important role in gastrointestinal tract water transport and in glycerol metabolism. It is widely expressed in epithelial cells of kidney (collecting ducts ) and airways, in keratinocytes, immature dendritic cells and erythrocytes. Expression studies have shown that cells transfected with AQP3 cDNA react strongly with anti-GIL antibodies . These studies hence report the first cases of human AQP3 deficiency and offer the molecular basis of a new blood group system, GIL, believed to be encoded by AQP3 .
Aquaporin 5 (Aquaporin_5)
Type: Family

Aquaporins are water channels, present in both higher and lower organisms, that belong to the major intrinsic protein family. Most aquaporins are highly selective for water, though some also facilitate the movement of small uncharged molecules such as glycerol . In higher eukaryotes these proteins play diverse roles in the maintenance of water homeostasis, indicating that membrane water permeability can be regulated independently of solute permeability. In microorganisms however, many of which do not contain aquaporins, they do not appear to play such a broad role. Instead, they assist specific microbial lifestyles within the environment, e.g. they confer protection against freeze-thaw stress and may help maintain water permeability at low temperatures . The regulation of aquaporins is complex, including transcriptional, post-translational, protein-trafficking and channel-gating mechanisms that are frequently distinct for each family member.

Structural studies show that aquaporins are present in the membrane as tetramers, though each monomer contains its own channel . The monomer has an overall "hourglass" structure made up of three structural elements: an external vestibule, an internal vestibule, and an extended pore which connects the two vestibules. Substrate selectivity is conferred by two mechanisms. Firstly, the diameter of the pore physically limits the size of molecules that can pass through the channel. Secondly, specific amino acids within the molecule regulate the preference for hydrophobic or hydrophilic substrates.

Aquaporins are classified into two subgroups: the aquaporins (also known as orthodox aquaporins), which transport only water, and the aquaglyceroporins, which transport glycerol, urea, and other small solutes in addition to water .

Aquaporin-5 takes part in saliva production , the release of tears in the lacrimal glands, and water homeostasis in the lungs. It is water specific and is expressed mainly in the lung epithelium. Aquaporin-5 is therefore connected with certain lung pathologies following lung trauma, and some pathological conditions leading to dysfunction in the salivary and lacrimal glands .
Aquaporin 8 (Aquaporin_8)
Type: Family

Aquaporins are water channels, present in both higher and lower organisms, that belong to the major intrinsic protein family. Most aquaporins are highly selective for water, though some also facilitate the movement of small uncharged molecules such as glycerol . In higher eukaryotes these proteins play diverse roles in the maintenance of water homeostasis, indicating that membrane water permeability can be regulated independently of solute permeability. In microorganisms however, many of which do not contain aquaporins, they do not appear to play such a broad role. Instead, they assist specific microbial lifestyles within the environment, e.g. they confer protection against freeze-thaw stress and may help maintain water permeability at low temperatures . The regulation of aquaporins is complex, including transcriptional, post-translational, protein-trafficking and channel-gating mechanisms that are frequently distinct for each family member.

Structural studies show that aquaporins are present in the membrane as tetramers, though each monomer contains its own channel . The monomer has an overall "hourglass" structure made up of three structural elements: an external vestibule, an internal vestibule, and an extended pore which connects the two vestibules. Substrate selectivity is conferred by two mechanisms. Firstly, the diameter of the pore physically limits the size of molecules that can pass through the channel. Secondly, specific amino acids within the molecule regulate the preference for hydrophobic or hydrophilic substrates.

Aquaporins are classified into two subgroups: the aquaporins (also known as orthodox aquaporins), which transport only water, and the aquaglyceroporins, which transport glycerol, urea, and other small solutes in addition to water .

Aquaporin-8 forms a mercury-sensitive water-specific channel . It may have an important role in spermatogenesis, in fertilisation, and in the secretion of pancreatic juice and saliva . It is also found in the liver, in bile canalicular membranes, where it takes part in bile formation .
Ethylene insensitive 3-like protein, DNA-binding domain superfamily (Ethylene_insens-like_DNA-bd)
Type: Homologous_superfamily

Ethylene-insensitive3 (EIN3) and EIN3-like (EIL) proteins are essential transcription factors in the ethylene signaling of higher plants. The EIN3/EIL proteins bind to the promoter regions of the downstream genes and regulate their expression. This superfamily represents the DNA-binding domain of EIN3 family proteins, which consist of 5 α-helices which come together to form a globular domain .
Hydroxymethylglutaryl-CoA reductase, N-terminal (HMG_CoA_Rdtase_N)
Type: Homologous_superfamily

There are two distinct classes of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase enzymes: class I consists of eukaryotic and most archaeal enzymes (

), while class II consists of prokaryotic enzymes (

) .

Class I HMG-CoA reductases catalyse the NADP-dependent synthesis of mevalonate from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). In vertebrates, membrane-bound HMG-CoA reductase is the rate-limiting enzyme in the biosynthesis of cholesterol and other isoprenoids. In plants, mevalonate is the precursor of all isoprenoid compounds . The reduction of HMG-CoA to mevalonate is regulated by feedback inhibition by sterols and non-sterol metabolites derived from mevalonate, including cholesterol. In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids . Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal), a large L-domain, and a small S-domain (inserted within the L-domain). The L-domain binds the substrate, while the S-domain binds NADP.

Class II HMG-CoA reductases catalyse the reverse reaction of class I enzymes, namely the NAD-dependent synthesis of HMG-CoA from mevalonate and CoA . Some bacteria, such as Pseudomonas mevalonii, can use mevalonate as the sole carbon source. Class II enzymes lack a membrane domain. Their catalytic region is structurally related to that of class I enzymes, but it consists of only two domains: a large L-domain and a small S-domain (inserted within the L-domain). As with class I enzymes, the L-domain binds substrate, but the S-domain binds NAD (instead of NADP in class I).

This superfamily represents the N-terminal structural domain of HMGR.
ABATE domain superfamily (ABATE_dom_sf)
Type: Homologous_superfamily

This superfamily represents the ABATE domain found in DUF1470 .
Pa2218-like domain superfamily (Pa2218-like_dom_sf)
Type: Homologous_superfamily

This domain superfamily is found in putative formylmethanofuran dehydrogenases.
Af2093, N-terminal (Af2093-N)
Type: Homologous_superfamily

This superfamily represents a domain found at the N-terminal of the uncharacterised protein AF2093

, which has no known function.
NTP pyrophosphohydrolase-like domain superfamily (NTP_PyroPHydrolase-like_dom_sf)
Type: Homologous_superfamily

This superfamily represents a putative pyrophosphohydrolase-like domain. It is a variant of the all-α-helical NTP pyrophosphatase fold family and contains an unusual intertwined swapping of helical segments, resulting in an obligatory dimer that cannot dissociate without unfolding of the monomers. This novel "linked dimer" defines a new subfamily of the α-helical NTP pyrophosphatase fold and is distinct from other previously observed domain-swapped dimers .
Deoxyguanosinetriphosphate triphosphohydrolase, central domain superfamily (dGTP_triP_hydro_central_sf)
Type: Homologous_superfamily

This domain superfamily is found in the central region of prokaryotic deoxyguanosinetriphosphate triphosphohydrolase proteins.
Tachylectin 2 (Tachylectin2)
Type: Domain

This entry represents a five-bladed β propeller domain from Tachylectin 2. It consists of five four-stranded antiparallel β-sheets are arranged around a water channel. Tachylectin 2 binds specifically to N-acetylglucosamine and N-acetylgalactosamine and is part of the organism's immunity host defense systems . Tachylectin 2 has five binding sites (one on each β-sheet)for substrate carbohydrate recognition; by combining specificity for N-acetylcarbohydrates with a high density of ligand binding sites, tachylectin 2 is able to recognise foreign sugars.
Hyaluronate lyase, beta-sheet domain superfamily (Hyaluronate_lyase_beta_dom_sf)
Type: Homologous_superfamily

This entry represents the N-terminal β-sheet domain which adopts a Ig-like fold and may serve as a connection of the α-domain with another structural domain .

Hyaluronate lyase degrades hyaluronan and certain chondroitin sulfates at beta-1,4 glycosidic linkages and constitutes a virulence factor of Streptococcus agalactiae . It consists of three structural domains, an N-terminal β-sheet domain (also referred as to beta1), a middle catalytic α-helical domain (

) and a C-terminal β-sheet domain (beta2,

) .
Glycosyl hydrolase, five-bladed beta-propeller domain superfamily (Glyco_hydro_beta-prop_sf)
Type: Homologous_superfamily

This is a five-bladed β-propeller fold catalytic domain where each blade has four twisted antiparallel β-strands radially orientated around a pseudo-5-fold axis . It can be found in the glycosyl hydrolase family 43 (GH43) members, including beta-xylosidases, alpha-L-arabinanases and bifunctional beta-xylosidases/alpha-L-arabinofuranosidases . This domain can also be found in other GH families, such as GH32, GH62 and GH68 .
P-type ATPase, transmembrane domain superfamily (ATPase_P-typ_TM_dom_sf)
Type: Homologous_superfamily

This superfamily represents the ten transmembrane helices domain found in P-type ATPases .

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.

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.
P-type ATPase, cytoplasmic domain N (ATPase_P-typ_cyto_dom_N)
Type: Homologous_superfamily

This superfamily represents the cytoplasmic domain N found in P-type ATPases. The cytoplasmic loops of the P-type ATPases form three separate modules, commonly named the A, P and N-domains . The N-domain comprises the nucleotide binding site . This domain forms a seven-stranded antiparallel β-sheet with two additional β-strands forming a hairpin and five α-helices .

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.
Ammonia/methane monooxygenase, subunitB, N-terminal (NH3_CH4_mOase_suB_N)
Type: Homologous_superfamily

Ammonia monooxygenase and the particulate methane monooxygenase are both integral membrane proteins, occurring in ammonia oxidisers and methanotrophs respectively, which are thought to be evolutionarily related . These enzymes have a relatively wide substrate specificity and can catalyse the oxidation of a range of substrates including ammonia, methane, halogenated hydrocarbons and aromatic molecules . These enzymes are composed of 3 subunits - A (

), B (

,

) and C (

) - and contain various metal centres, including copper. Particulate methane monooxygenase from Methylococcus capsulatus str. Bath is an ABC homotrimer, which contains mononuclear and dinuclear copper metal centres, and a third metal centre containing a metal ion whose identity in vivo is not certain.

The soluble regions of these enzymes derive primarily from the B subunit. This subunit forms two antiparallel β-barrel-like structures and contains the mono- and di- nuclear copper metal centres .

This entry represents the N-terminal β-barrel-like domain of subunit B.
Peptidase S9A, N-terminal domain (Pept_S9A_N)
Type: Domain

This entry represents the β-propeller domain found at the N-terminal of prolyl oligopeptidase from the MEROPS peptidase family S9A. The prolyl oligopeptidase family consist of a number of evolutionary related peptidases whose catalytic activity seems to be provided by a charge relay system similar to that of the trypsin family of serine proteases, but which evolved by independent convergent evolution. The N-terminal domain of prolyl oligopeptidases form an unusual 7-bladed β-propeller consisting of seven 4-stranded β-sheet motifs.

Prolyl oligopeptidase is a large cytosolic enzyme involved in the maturation and degradation of peptide hormones and neuropeptides, which relate to the induction of amnesia. The enzyme contains a peptidase domain, where its catalytic triad (Ser554, His680, Asp641) is covered by the central tunnel of the N-terminal β-propeller domain. In this way, large structured peptides are excluded from the active site, thereby protecting larger peptides and proteins from proteolysis in the cytosol .
Ammonia/methane monooxygenase, subunit B, C-terminal (NH3_CH4_mOase_suB_C)
Type: Homologous_superfamily

Ammonia monooxygenase and the particulate methane monooxygenase are both integral membrane proteins, occurring in ammonia oxidisers and methanotrophs respectively, which are thought to be evolutionarily related . These enzymes have a relatively wide substrate specificity and can catalyse the oxidation of a range of substrates including ammonia, methane, halogenated hydrocarbons and aromatic molecules . These enzymes are composed of 3 subunits - A (

), B (

,

) and C (

) - and contain various metal centres, including copper. Particulate methane monooxygenase from Methylococcus capsulatus str. Bath is an ABC homotrimer, which contains mononuclear and dinuclear copper metal centres, and a third metal centre containing a metal ion whose identity in vivo is not certain.

The soluble regions of these enzymes derive primarily from the B subunit. This subunit forms two antiparallel β-barrel-like structures and contains the mono- and di- nuclear copper metal centres .

This entry represents the C-terminal β-barrel-like domain of subunit B.
Endoglucanase F, domain 2 (Endo-1-4-beta-glucanase_dom2)
Type: Homologous_superfamily

This structural domain is found in endoglucanase F. Proteins containing this domain include endoglucanases and exoglucanases. They are involved in the cellulose catabolic process.
Methuselah ectodomain, domain 2 (Methusela_ecto_dom_2)
Type: Homologous_superfamily

Drosophila Methuselah (Mth) mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage. The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family. Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site .

This entry represents a structural subdomain found at the C-termimus of the Methusela ectodomain.
Putative nitroreductase, C-terminal, bacterial (Put_nitroreductase_C_bac)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain found in proteins putatively annotated as bacterial nitroreductases.
Ubiquitin-conjugating enzyme, active site (UBQ-conjugating_AS)
Type: Active_site

Ubiquitin-conjugating enzymes (

, UBC or E2 enzymes) catalyse the covalent attachment of ubiquitin to target proteins. Ubiquitin is conjugated to the target protein through the coordinated action of three enzyme activities designated E1, E2, and E3. The E1 or ubiquitin-activating enzyme forms, in an ATP-dependent manner, a thioester linkage between its active site cysteine and the carboxy terminus of ubiquitin. The activated ubiquitin moiety is then transferred from E1 to the active site cysteine in E2 through a trans-thiol esterification reaction. The UBC enzyme later ligates ubiquitin directly to substrate proteins with or without the assistance of 'N-end' recognizing proteins (E3) . In most species there are many forms of UBC (at least 9 in yeast) which are implicated in diverse cellular functions.
5-Dehydro-2-deoxygluconokinase-like superfamily (Myo_inos_IolC-like_sf)
Type: Homologous_superfamily

This superfamily represents a β-sheet structural domain found at the N terminus of 5-dehydro-2-deoxygluconokinases , which catalyse the fifth step in degradation from myo-inositol or closely related compounds.
SynGAP C2 domain, N-terminal (SynGAP_C2_N)
Type: Homologous_superfamily

This entry represents a small structural domain found at the extreme N terminus of the C2 domain of Ras GTPase-activating protein SynGAP .
Peptidase S1A, plasmin (Pept_S1A_plasmin)
Type: Family

Plasmin is a serine peptidase belonging to MEROPS peptidase family S1 (chymotrypsin family, clan PA(S)), subfamily S1A.

Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes, including embryonic development, tissue remodeling, tumor invasion, and inflammation ; in ovulation it weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. It cleaves fibrin, fibronectin, thrombospondin, laminin and von Willebrand factor. Its specificity is similar to trypsin but it is less efficient and, thus, cleaves only after certain Lys and Arg residues.

Following the signal sequence, plasmin contains one PAN (formerly apple) domain, five kringle domains, and a trypsin domain.
Ubiquitin activating enzyme, alpha domain superfamily (Ub_act_enz_dom_a_sf)
Type: Homologous_superfamily

Ubiquitin-activating enzyme (E1 enzyme) activates ubiquitin by first adenylating with ATP its C-terminal glycine residue and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding an ubiquitin-E1 thiolester and free AMP. Later the ubiquitin moiety is transferred to a cysteine residue on one of the many forms of ubiquitin-conjugating enzymes (E2) . This domain carries the last of five conserved cysteines that is part of the active site of the enzyme, responsible for ubiquitin thiolester complex formation, the active site being represented by the sequence motif PICTLKNFP . Not all proteins in this entry contain a functional active site.

This superfamily represents an α orthogonal bundle domain found in ubiquitin-activating enzyme and ubiquitin-like NEDD8-activating enzyme.
Tex-like protein, HTH domain superfamily (Tex-like_HTH_dom_sf)
Type: Homologous_superfamily

Tex (toxin expression) is a highly conserved bacterial protein involved in expression of critical toxin genes . The overall structure is notably flat and elongated. The most striking structural feature is a long, central helix comprising from amino acid residue 274 to 322. The rest of the protein wraps around the central helix at both the N-terminal and C-terminal ends. Although the Tex structure is fairly compact, it can be largely described as a series of distinct domains .

This superfamily represents an N-terminal domain with a helix-turn-helix structure.
PINIT domain (PINIT)
Type: Domain

This entry represents the PINIT domain found in the Siz/PIAS RING family of SUMO E3 ligases . These proteins present a tripartite architecture with an N-terminal PINIT domain, a central zinc-containing RING-like SP-RING domain, and a C-terminal domain desginated SP-CTD. Structural and biochemical studies have shown that both SP-RING and SP-CTD are required for activation of the E2-SUMO thioester while the PINIT domain is required for redirecting SUMO conjugation to the proliferating cell nuclear antigen (PCNA) at lysine 164, a non-consensus lysine residue that is not modified by the SUMO E2 in the absence of Siz1 .
Outer surface lipoprotein domain superfamily (OM_lipoprot_dom_sf)
Type: Homologous_superfamily

The ospA and ospB genes encode the major outer membrane proteins of the Lyme disease spirochaete Borrelia burgdorferi . The deduced gene products OspA and OspB, contain 273 and 296 residues respectively . The two Osp proteins show a high degree of sequence similarity, indicating a recent evolutionary event. Molecular analysis and sequence comparison of OspA and OspB with other proteins has revealed similarity to the signal peptides of prokaryotic lipoproteins .

This superfamily represents a structural domain, which consists of 21 stranded sheet partly folded upon itself at the ends, found in outer surface lipoproteins.