SII-SWORD/CoKE huggingface dataset:
Copper amine oxidase, catalytic domain (Cu_amine_oxidase_C)
Type: Domain

This entry represents the C-terminal catalytic domain of copper amine oxidases, and has a super-sandwich fold consisting of 18 β-strands in 2 sheets . A domain with a similar structural fold can be found as the third domain in lysyl oxidase PplO .

Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (

) and copper-containing (

). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor :

RCH
2
NH
2
+ H
2
O + O
2
= RCHO + NH
3
+ H
2
O
2

Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen . In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling .

The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a β sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other .
Influenza matrix M1, N-terminal subdomain 2 (Flu_matrix_M1_N_sub2)
Type: Homologous_superfamily

Matrix protein (M1) of Influenza virus is a bifunctional membrane/RNA-binding protein that mediates the encapsidation of RNA-nucleoprotein cores into the membrane envelope. It is therefore required that M1 binds both membrane and RNA simultaneously . M1 is comprised of two domains connected by a linker sequence. The N-terminal domain has a multi-helical structure that can be divided into two subdomains: subdomain 1 forms an up-down helical bundle and subdomain 2 forms an orthogonal bundle . The C-terminal domain also contains α-helical structure.

This entry represents the second subdomain of the N-terminal domain of M1.
Copper amine oxidase, N2-terminal (Cu_amine_oxidase_N2)
Type: Domain

This entry represents one (N2) of the two N-terminal domains (N2/N3) that share a similar structure.

Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (

) and copper-containing (

). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor :

RCH
2
NH
2
+ H
2
O + O
2
= RCHO + NH
3
+ H
2
O
2

Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen . In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling .

The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a β sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other .
Copper amine oxidase, N3-terminal (Cu_amine_oxidase_N3)
Type: Domain

Amine oxidases (AO) are enzymes that catalyse the oxidation of a wide range of biogenic amines including many neurotransmitters, histamine and xenobiotic amines. There are two classes of amine oxidases: flavin-containing (

) and copper-containing (

). Copper-containing AO act as a disulphide-linked homodimer. They catalyse the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone as cofactor :

RCH
2
NH
2
+ H
2
O + O
2
= RCHO + NH
3
+ H
2
O
2

Copper-containing amine oxidases are found in bacteria, fungi, plants and animals. In prokaryotes, the enzyme enables various amine substrates to be used as sources of carbon and nitrogen . In eukaryotes they have a broader range of functions, including cell differentiation and growth, wound healing, detoxification and cell signalling .

The copper amine oxidases occur as mushroom-shaped homodimers of 70-95kDa, each monomer containing a copper ion and a covalently bound redox cofactor, topaquinone (TPQ). TPQ is formed by post-translational modification of a conserved tyrosine residue. The copper ion is coordinated with three histidine residues and two water molecules in a distorted square pyramidal geometry, and has a dual function in catalysis and TPQ biogenesis. The catalytic domain is the largest of the 3-4 domains found in copper amine oxidases, and consists of a β sandwich of 18 strands in two sheets. The active site is buried and requires a conformational change to allow the substrate access. The two N-terminal domains share a common structural fold, its core consisting of a five-stranded antiparallel β-sheet twisted around an α-helix. The D1 domains from the two subunits comprise the stalk, of the mushroom-shaped dimer, and interact with each other but do not pack tightly against each other .

This entry represents one (N3) of the two N-terminal domains (N2/N3) that share a similar structure.
Cysteine-tRNA ligase (Cys-tRNA-ligase)
Type: Family

Cysteine-tRNA ligase (also known as Cysteinyl-tRNA synthetase) (

) is an alpha monomer and belongs to class Ia . It is highly specific despite not possessing the amino acid editing activity characteristic of many other tRNA ligases .

The aminoacyl-tRNA synthetases (also known as aminoacyl-tRNA ligases) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction . These proteins differ widely in size and oligomeric state, and have limited sequence homology . The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric . Class II aminoacyl-tRNA synthetases share an anti-parallel β-sheet fold flanked by α-helices , and are mostly dimeric or multimeric, containing at least three conserved regions . However, tRNA binding involves an α-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine, and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c .
Pyruvate kinase, insert domain superfamily (Pyrv_Knase_insert_dom_sf)
Type: Homologous_superfamily

Pyruvate kinase (

) (PK) catalyses the final step in glycolysis , the conversion of phosphoenolpyruvate to pyruvate with concomitant phosphorylation of ADP to ATP:

ADP + phosphoenolpyruvate = ATP + pyruvate

The enzyme, which is found in all living organisms, requires both magnesium and potassium ions for its activity. In vertebrates, there are four tissue-specific isozymes: L (liver), R (red cells), M1 (muscle, heart and brain), and M2 (early foetal tissue). In plants, PK exists as cytoplasmic and plastid isozymes, while most bacteria and lower eukaryotes have one form, except in certain bacteria, such as Escherichia coli, that have two isozymes. All isozymes appear to be tetramers of identical subunits of ~500 residues.

PK helps control the rate of glycolysis, along with phosphofructokinase (

) and hexokinase (

). PK possesses allosteric sites for numerous effectors, yet the isozymes respond differently, in keeping with their different tissue distributions . The activity of L-type (liver) PK is increased by fructose-1,6-bisphosphate (F1,6BP) and lowered by ATP and alanine (gluconeogenic precursor), therefore when glucose levels are high, glycolysis is promoted, and when levels are low, gluconeogenesis is promoted. L-type PK is also hormonally regulated, being activated by insulin and inhibited by glucagon, which covalently modifies the PK enzyme. M1-type (muscle, brain) PK is inhibited by ATP, but F1,6BP and alanine have no effect, which correlates with the function of muscle and brain, as opposed to the liver.

The structure of several pyruvate kinases from various organisms have been determined . The protein comprises three-four domains: a small N-terminal helical domain (absent in bacterial PK), a β/α-barrel domain, a β-barrel domain (inserted within the β/α-barrel domain), and a 3-layer α/β/α sandwich domain.

This superfamily represents the β-barrel domain (note: it does not include the β/α-barrel it is inserted into).
Histidine-tRNA ligase (His-tRNA-ligase)
Type: Family

Histidine-tRNA ligase (also known as histidyl-tRNA synthetase) (

) is an alpha2 dimer that belongs to class IIa. Every completed genome includes a histidine-tRNA ligase. Apparent second copies from Bacillus subtilis, Synechocystis sp. (strain PCC 6803), and Aquifex aeolicus are slightly shorter, more closely related to each other than to other hisS proteins, and not demonstrated to act as histidine-tRNA ligases (see

). The regulatory protein kinase GCN2 of Saccharomyces cerevisiae (YDR283c), and related proteins from other species designated eIF-2 alpha kinase, have a domain closely related to histidine-tRNA ligase that may serve to detect and respond to uncharged tRNA(his), an indicator of amino acid starvation, but these regulatory proteins are not orthologous.
Photosynthetic reaction centre, H subunit, N-terminal (Photo_RC_H_N)
Type: Domain

This entry represents the N-terminal domain of the photosynthetic reaction centre H subunit, which includes the transmembrane domain and part of the cytoplasmic domain .

The photosynthetic apparatus in non-oxygenic bacteria consists of light-harvesting (LH) protein-pigment complexes LH1 and LH2, which use carotenoid and bacteriochlorophyll as primary donors . LH1 acts as the energy collection hub, temporarily storing it before its transfer to the photosynthetic reaction centre (RC) . Electrons are transferred from the primary donor via an intermediate acceptor (bacteriopheophytin) to the primary acceptor (quinine Qa), and finally to the secondary acceptor (quinone Qb), resulting in the formation of ubiquinol QbH2. RC uses the excitation energy to shuffle electrons across the membrane, transferring them via ubiquinol to the cytochrome bc1 complex in order to establish a proton gradient across the membrane, which is used by ATP synthetase to form ATP .

The core complex is anchored in the cell membrane, consisting of one unit of RC surrounded by LH1; in some species there may be additional subunits . RC consists of three subunits: L (light), M (medium), and H (heavy). Subunits L and M provide the scaffolding for the chromophore, while subunit H contains a cytoplasmic domain . In Rhodopseudomonas viridis, there is also a non-membranous tetrahaem cytochrome (4Hcyt) subunit on the periplasmic surface.
Methyl-coenzyme M reductase, alpha subunit, N-terminal subdomain 1 (Me_CoM_Rdtase_asu_N_sub1)
Type: Homologous_superfamily

Methyl-coenzyme M reductase (MCR) catalyses the reduction of methyl-coenzyme M (CH3-SCoM) and coenzyme B (HS-CoB) to methane and the corresponding heterosulphide CoM-S-S-CoB (

), the final step in methane biosynthesis. This reaction proceeds under anaerobic conditions by methanogenic Archaea , and requires a nickel-porphinoid prosthetic group, coenzyme F430, which is in the EPR-detectable Ni(I) oxidation state in the active enzyme. Studies on a catalytically inactive enzyme aerobically co-crystallized with coenzyme M displayed a fully occupied coenzyme M-binding site with no alternate conformations. The binding of coenzyme M appears to induce specific conformational changes that suggests a molecular mechanism by which the enzyme ensures that methyl-coenzyme M enters the substrate channel prior to coenzyme B, as required by the active-site geometry .

MCR is a hexamer composed of 2 alpha, 2 beta, and 2 gamma subunits with two identical nickel porphinoid active sites, which form two long active site channels with F430 embedded at the bottom .

This entry represents a subdomain of the N-terminal region of the alpha subunit. The N-terminal domain has a ferredoxin-like α/β-sandwich fold with a duplicated β-α-β topology. This subdomain has a complex α/β topology.
Integrin beta subunit (Integrin_bsu)
Type: Family

This entry represents the family of integrin beta subunit proteins and integrin beta-like proteins. It also includes integrin beta-pat-3 (pat-3) from Caenorhabditis elegans. Integrin alpha ina-1/beta pat-3 are receptors for laminin. Pat-3 is required for muscle development and maintenance and plays a role in axon regeneration after injury .

Integrin beta subunits consist of an extracellular domain with a head region, a stalk/leg section, a transmembrane domain, and a cytoplasmic tail. The head region contains a β-I-like domain inserted into a hybrid domain, connected to a plexin-semaphorin-integrin (PSI) [

]. C-terminal to the PSI domain is an A-domain, which has been predicted to adopt a Rossmann fold similar to that of the alpha subunit, but with additional loops between the second and third β strands. This domain is referred to as VWA [

]. Many VWA domains bind metal ions via a noncontiguous sequence motif called metal ion-dependent adhesion site (MIDAS) . This is followed by a β-subunit stalk/leg section that contains four cysteine-rich integrin epidermal growth factor-like (I-EGF) modules [

], [

],

]. Finally, this is followed by the β-ankle TM domain [

] and a cytoplasmic tail [

] .

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways . An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits . There are at least 18 types of alpha and 8 types of beta subunits recognised in humans . Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule . Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.
Pyruvate/Phosphoenolpyruvate kinase-like domain superfamily (Pyrv/PenolPyrv_kinase-like_dom)
Type: Homologous_superfamily

Pyruvate kinase controls the exit from the glysolysis pathway, catalysing the transfer of phosphate from phosphooenolpyruvate (PEP) to ADP. Mammalian pyruvate kinase is a homotetramer, where each polypeptide subunit consists of four domains: N-terminal, A domain, B domain and C-terminal. Activation of the enzyme is believed to occur via the clamping down of the B domain onto the A domain to dehydrate the active site cleft. The N- and C-terminal domains are situated at inter-subunit contact sites, and could be involved in assembly and communication within the complex. The N-terminal domain has a TIM β/α-barrel structure. Homologous TIM-barrel domains are found in the following proteins:

N-terminal of pyruvate kinase (

), which is interrupted by an all-beta domain .

C-terminal of pyruvate phosphate dikinase (

), which has a similar mode of substrate binding to pyruvate kinase .

Phosphoenolpyruvate carboxylase (

); this domain has additional helices .

Phosphenolpyruvate mutase(

)/Isocitrate lyase (

), where it forms a swapped dimer .

HpcH/HpaI aldolases, such as the beta subunit of citrate lyase, where it forms a swapped dimer, and contains a pyruvate kinase-type metal binding site .

Ketopantoate hydroxymethyltransferase PanB (

), where a C-terminal helix exchange is observed in some enzymes .
Phosphogluconate dehydrogenase, NAD-binding, putative, C-terminal (Pgluconate_DH_NAD-bd_C)
Type: Domain

This domain has been found in a number of eukaryotic and prokaryotic proteins, some of which are predicted to be 6-phosphogluconate dehydrogenase, NAD-binding proteins.
3-hydroxyisobutyrate dehydrogenase-related (HIBADH-related)
Type: Family

This entry contains related reductases/dehydrogenases:

3-hydroxyisobutyrate dehydrogenase (HIBADH) (

) catalyzes the NAD-dependent, reversible oxidation of 3-hydroxbutyrate to methylmalonate . In eukaryotes, it is a homodimeric mitochondrial protein involved in valine catabolism. In Pseudomonas aeruginosa (gene mmsB), it is involved in the distal valine metabolic pathway.

2-hydroxy-3-oxopropionate reductase (

) catalyses the NAP(P)H dependent reduction of 2-hydroxy-3-oxopropionate (tartronate semialdehyde) to D-glycerate.

2-(hydroxymethyl)glutarate dehydrogenase (

) catalyses the conversion of 2-formylglutarate to (S)-2-hydroxymethylglutarate .

L-threonate dehydrogenase catalyses oxidation of L-threonate to 2-oxo-tetronate .

Putative oxidoreductase GLYR1, also known as 3-hydroxyisobutyrate dehydrogenase-like protein or nuclear protein NP60, which regulates p38 MAP kinase activity .
Vitellinogen, beta-sheet N-terminal (Vitellinogen_b-sht_N)
Type: Homologous_superfamily

Vitellinogen precursors provide the major egg yolk proteins that are a source of nutrients during early development of oviparous vertebrates and invertebrates. Vitellinogen precursors are multi-domain apolipoproteins that are cleaved into distinct yolk proteins. Different vitellinogen precursors exist, which are composed of variable combinations of yolk protein components; however, the cleavage sites are conserved .

In vertebrates, a complete vitellinogen is composed of an N-terminal signal peptide for export, followed by four regions that can be cleaved into yolk proteins: lipovitellin-1, phosvitin, lipovitellin-2, and a von Willebrand factor type D domain (YGP40). Vitellinogens are post-translationally glycosylated and phosphorylated in the endoplasmic reticulum and Golgi complex of hepatocytes, before being secreted into the circulatory system to be taken up by oocytes. In the ovary, vitellinogens bind to specific Vtgr receptors on oocyte membranes to become internalised by endocytosis, where they are cleaved into yolk proteins by cathepsin D. YGP40 is released into the yolk plasma before or during compartmentation of lipovitellin-phosvitin complex into the yolk granule.

The different yolk proteins have distinct roles. Phosvitins are important in sequestering calcium, iron and other cations for the developing embryo. Phosvitins are one of the most phosphorylated (10%) proteins in nature, the high concentration of phosphate groups providing efficient metal-binding sites in clusters . Lipovitellins are involved in lipid and metal storage, and contain a heterogeneous mixture of about 16% (w/w) noncovalently bound lipid, most being phospholipid. Lipovitellin-1 contains two chains, LV1N and LV1C .

This entry represents a β-sheet shell region found at the N terminus of vitellinogen proteins, which generally corresponds to the N-terminal of the lipovitellin-1 peptide product.
Vitellinogen, open beta-sheet, subdomain 1 (Vitellinogen_open_b-sht_sub1)
Type: Homologous_superfamily

Vitellinogen precursors provide the major egg yolk proteins that are a source of nutrients during early development of oviparous vertebrates and invertebrates. Vitellinogen precursors are multi-domain apolipoproteins that are cleaved into distinct yolk proteins. Different vitellinogen precursors exist, which are composed of variable combinations of yolk protein components; however, the cleavage sites are conserved .

In vertebrates, a complete vitellinogen is composed of an N-terminal signal peptide for export, followed by four regions that can be cleaved into yolk proteins: lipovitellin-1, phosvitin, lipovitellin-2, and a von Willebrand factor type D domain (YGP40). Vitellinogens are post-translationally glycosylated and phosphorylated in the endoplasmic reticulum and Golgi complex of hepatocytes, before being secreted into the circulatory system to be taken up by oocytes. In the ovary, vitellinogens bind to specific Vtgr receptors on oocyte membranes to become internalised by endocytosis, where they are cleaved into yolk proteins by cathepsin D. YGP40 is released into the yolk plasma before or during compartmentation of lipovitellin-phosvitin complex into the yolk granule.

The different yolk proteins have distinct roles. Phosvitins are important in sequestering calcium, iron and other cations for the developing embryo. Phosvitins are one of the most phosphorylated (10%) proteins in nature, the high concentration of phosphate groups providing efficient metal-binding sites in clusters . Lipovitellins are involved in lipid and metal storage, and contain a heterogeneous mixture of about 16% (w/w) noncovalently bound lipid, most being phospholipid. Lipovitellin-1 contains two chains, LV1N and LV1C .

This entry represents an open β-sheet subdomain found in vitellinogen, which generally corresponds to a domain within the lipovitellin-1 peptide product. This domain adopts a structure consisting of one of several large open β-sheets. This subdomain is also found in apolipophorins, the major component of lipophorin, which mediates transport for various types of lipids in hemolymph.