SII-SWORD/CoKE huggingface dataset:
D-lactate dehydrogenase, cap domain, subdomain 1 (D-lactate_DH_C-sub1)
Type: Homologous_superfamily

The D-lactate dehydrogenase (d-LDH) structure is composed of three discontinuous domains: the FAD-binding domain (residues 1-268 and 520-571), the cap domain (residues 269-310, 388-425, and 450-519), and the membrane-binding domain (residues 311-387 and 426-449, of which residues 329-376 are in the disordered region) [[cite10944213]].

The cap domain of certain FAD-linked oxidases consist of two structural subdomains: subdomain 1 is a 2-layer a/b or 3-layer a/b/a sandwich, and subdomain 2 is either an orthogonal α-bundle or a second 2-layer a/b sandwich. This entry represents the first (N-terminal) subdomain with a 2-layer α/β sandwich fold. This subdomain is found in D-lactate dehydrogenases (

,

-cytochrome), a peripheral membrane respiratory enzyme involved in electron transfer for the energization of active transport of a variety of sugars and amino acids in bacteria . It is also found in certain cholesterol oxidases (

), monomeric flavoenzymes that catalyses the oxidation and isomerisation of cholesterol to cholest-4-en-3-one .
D-lactate dehydrogenase, cap domain, subdomain 2 (D-lactate_DH_C-sub2)
Type: Homologous_superfamily

The D-lactate dehydrogenase (d-LDH) structure is composed of three discontinuous domains: the FAD-binding domain (residues 1-268 and 520-571), the cap domain (residues 269-310, 388-425, and 450-519), and the membrane-binding domain (residues 311-387 and 426-449, of which residues 329-376 are in the disordered region) [[cite10944213]].

The cap domain of certain FAD-linked oxidases consist of two structural subdomains: subdomain 1 is a 2-layer a/b or 3-layer a/b/a sandwich, and subdomain 2 is either an orthogonal α-bundle or a second 2-layer a/b sandwich. This entry represents the second (C-terminal) subdomain with a 2-layer α/β sandwich fold. This subdomain is found in D-lactate dehydrogenases (

,

-cytochrome), a peripheral membrane respiratory enzyme involved in electron transfer for the energization of active transport of a variety of sugars and amino acids in bacteria .
Di-haem cytochrome, transmembrane (Di-haem_cyt_TM)
Type: Homologous_superfamily

This entry represents a haem-binding domain with a 4-helical bundle structure that is found in transmembrane di-haem cytochromes. The domain contains four transmembrane helices in an up-and-down bundle, and binds two haem groups in between the helices; three of the four haem-binding residues is conserved between family members. Proteins containing this domain include:

N-terminal domain of mitochondrial cytochrome b subunit, in which the domain contains an extra transmembrane linker helix that is absent in plant and cyanobacteria subunits .

Cytochrome b6 subunit of the cytochrome b6f complex, which provides the electronic connection between the photosystems I and II reaction centres of oxygenic photosynthesis, and generates a transmembrane electrochemical proton gradient for adenosine triphosphate synthesis .

Cytochrome gamma subunit of formate dehydrogenase-N (Fdn-N), which acts as a major component of Escherichia coli nitrate respiration .

Please note, this entry also identifies a number of proteins that are cleaved into two chains - a truncated non-functional cytochrome oxidase 1 and an intron-encoded endonuclease.
Cobalamin (vitamin B12)-dependent enzyme, catalytic (Cbl-dep_enz_cat)
Type: Homologous_superfamily

This superfamily represents a structural domain with a TIM β/α barrel fold found in cobalamin (vitamin B12)-dependent enzymes, including:

N-terminal coenzyme A-binding domain of both the alpha and beta subunits of methylmalonyl-CoA mutase (

) (only the alpha subunit is active) .

The large subunit of glutamate mutase (

) .

The alpha subunit of diol dehydratase (

) .

The large subunit of glycerol dehydratase (

) .

The alpha subunit of D-lysine 5,6-aminomutase (

) .
DNA-binding domain superfamily (DNA-bd_dom_sf)
Type: Homologous_superfamily

This superfamily represents a DNA-binding domain with a 2-layer β(3)-α fold that is found in several DNA-binding proteins, including:

DNA-binding domain of tn916 integrase .

N-terminal DNA-binding domain of lambda integrase .

GCC-box DNA-binding domains of certain transcription factors .

Methyl-CpG DNA-binding domain found in Methyl-CpG-binding protein 2 (MECP2) and methylation-dependent transcriptional repressor MBD1/PCM1 .
Insulin-like (Insulin-like)
Type: Domain

This entry represents a disulphide-rich α-helical domain found in insulin , as well as in related proteins, such as insulin-like growth factor , relaxin and bombyxin .

Insulin is found in many animals, and is involved in the regulation of normal glucose homeostasis. It also has other specific physiological effects, such as increasing the permeability of cells to monosaccharides, amino acids and fatty acids, and accelerating glycolysis and glycogen synthesis in the liver . Insulin exerts its effects by interaction with a cell-surface receptor, which may also result in the promotion of cell growth .

The insulin/IGF/relaxin superfamily is an ancient family of functionally diverse proteins . The 3D structures of a number of family members have been determined . The fold comprises two polypeptide chains (A and B) linked by two disulphide bonds: all share a conserved arrangement of four cysteines in their A chain, the first of which is linked by a disulfide bond to the third, while the second and fourth are linked by interchain disulfide bonds to cysteines in the B chain.

This family includes:

Insulin and insulin-like proteins

Relaxin and prorelaxin

Insect prothoracicotropic hormone (bombyxin)

Insulin-like growth factors (IGF1 and IGF2)

Mammalian Leydig cell-specific insulin-like peptide (gene INSL3)

Invertebrates insulin-related peptides (IRPs)
Acyl-CoA N-acyltransferase (Acyl_CoA_acyltransferase)
Type: Homologous_superfamily

This entry represents a structural domain found in several acyl-CoA acyltransferase enzymes. This domain has a 3-layer α/β/α structure that contains mixed β-sheets, and can be found in the following proteins:

N-acetyl transferase (NAT) family members, including aminoglycoside N-acetyltransferases , the histone acetyltransferase domain of P300/CBP associating factor PCAF , the catalytic domain of GCN5 histone acetyltransferase , and diamine acetyltransferase 1 .

Autoinducer synthetases, such as protein LasI and acyl-homoserinelactone synthase EsaI .

Leucyl/phenylalanyl-tRNA-protein transferase (LFTR), a close relative of the non-ribosomal peptidyltransferases; there is a deletion of the N-terminal half of the N-terminal NAT-like domain after the domain duplication/swapping events .

Ornithine decarboxylase antizyme, which may have evolved a different function for this domain, although the putative active site maps to the same location in the common fold.

Arginine N-succinyltransferase, alpha chain, AstA, which contains an extra C-terminal domain that is similar to the double-psi β-barrel fold domain (missing one strand and untangled ψ-loops).

Several proteins carry a duplication of this domain, which consists of two NAT-like domains swapped with the C-terminal strands, including:

N-myristoyl transferase (NMT) .

FemXAB non ribosomal peptidyl transferases, including methicillin-resistance protein FemA (transfer glycyl residue from tRNA-Gly) and peptidyl transferase FemX .

Hypothetical protein cg14615-pa from Drosophila melanogaster (Fruit fly).
Copper amine oxidase, N-terminal (Cu_amine_oxidase_N-reg)
Type: Homologous_superfamily

This entry represents the N-terminal region of copper amine oxidases, and has a core structure consisting of α-β(4), where the helix packs against the coiled antiparallel β-sheet . A domain with a similar structural fold can be found as the first and second domains 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 .
Leukocidin/Hemolysin toxin (Leukocidin/Hemolysin_toxin)
Type: Domain

This entry represents a structural domain consisting of a β-sandwich fold with an immunoglobulin-like Greek-key topology, and a β-ribbon arm that forms an oligomeric transmembrane barrel. Haemolysins attack blood cell membranes and cause cell rupture by forming water-filled homoheptameric transmembrane pores. Leukocidin consists of two polypeptides, F and S, and form pores in polymorphonuclear leukocytes .
Capsid/spike protein, ssDNA virus (Capsid/spike_ssDNA_virus)
Type: Homologous_superfamily

This entry represents a coat protein found in ssDNA viruses, such as the capsid protein F and the spike protein G in Microviridae , the Parvovirus capsid protein , the Dependovirus capsid protein and the Densovirus capsid protein . These proteins share a β-sandwich structure consisting of 8 β-strands in two sheets with a jelly-roll fold, although some members can have an additional 1-2 strands; characteristic interaction between the domains of this fold allows the formation of five-fold and pseudo six-fold assemblies.
Pre-ATP-grasp domain superfamily (PreATP-grasp_dom_sf)
Type: Homologous_superfamily

The pre-ATP-grasp domain is a structural component found in many ATP-grasp enzymes. It is an N-terminal domain that precedes the core ATP-grasp fold in these proteins . While not directly involved in ATP binding, the pre-ATP-grasp domain likely plays a role in substrate recognition and binding, contributing to the overall catalytic function of the enzymes.

The ATP-grasp fold is one of several distinct ATP-binding folds, and is found in enzymes that catalyse the formation of amide bonds, catalysing the ATP-dependent ligation of a carboxylate-containing molecule to an amino or thiol group-containing molecule . This fold is found in many different enzyme families, including various peptide synthetases, biotin carboxylase, synapsin, succinyl-CoA synthetase, pyruvate phosphate dikinase, and glutathione synthetase, glutathionylspermidine synthase, amongst others . These enzymes contribute predominantly to macromolecular synthesis, using ATP-hydrolysis to activate their substrates.
C-type lectin-like/link domain superfamily (C-type_lectin-like/link_sf)
Type: Homologous_superfamily

Lectins occur in plants, animals, bacteria and viruses. Initially described for their carbohydrate-binding activity , they are now recognised as a more diverse group of proteins, some of which are involved in protein-protein, protein-lipid or protein-nucleic acid interactions . There are at least twelve structural families of lectins, of which C-type (Ca+-dependent) lectins is one. C-type lectins can be further divided into seven subgroups based on additional non-lectin domains and gene structure: (I) hyalectans, (II) asialoglycoprotein receptors, (III) collectins, (IV) selectins, (V) NK group transmembrane receptors, (VI) macrophage mannose receptors, and (VII) simple (single domain) lectins .

The term 'C-type lectin domain' was introduced to distinguish a carbohydrate-recognition domain (CRD) which is present in all Ca2+-dependent lectins, but not in other types of animal lectins. However, there are proteins with modules similar in overall structure to CRDs that serve functions other than sugar binding. Therefore, a more general term C-type lectin-like domain was introduced to refer to such domains, although both terms are sometimes used interchangeably .

This superfamily represents a structural domain found in C-type lectins, as well as in other proteins, including:

The C-terminal domain of invasin and intimin .

Link domain, which includes the Link module of tumor necrosis factor-inducible gene 6 protein (TSG-6) (a hyaladherin with important roles in inflammation and ovulation) and the hyaluronan binding domain of CD44 (which contains extra N-terminal β-strand and C-terminal β-hairpin) . The Link domain may have emerged as a result of a deletion of the long loop region from an ancestral canonical C-type lectin domain .

Endostatin and the endostatin domain of collagen alpha 1 (XV) , these domains being decorated with many insertions in the common fold.
C-type lectin fold (CTDL_fold)
Type: Homologous_superfamily

Lectins occur in plants, animals, bacteria and viruses. Initially described for their carbohydrate-binding activity , they are now recognised as a more diverse group of proteins, some of which are involved in protein-protein, protein-lipid or protein-nucleic acid interactions . There are at least twelve structural families of lectins, of which C-type (Ca+-dependent) lectins is one. C-type lectins can be further divided into seven subgroups based on additional non-lectin domains and gene structure: (I) hyalectans, (II) asialoglycoprotein receptors, (III) collectins, (IV) selectins, (V) NK group transmembrane receptors, (VI) macrophage mannose receptors, and (VII) simple (single domain) lectins .

This entry represents a structural domain found in C-type lectins, as well as in other proteins, including:

The N-terminal domain of aerolysin and the N-terminal domain of the S2/S3 subunit of pertussis toxin .

The C-terminal domain of invasin and intimin .

Link domain, which includes the Link module of TSG-6 (a hyaladherin with important roles in inflammation and ovulation) and the hyaluronan binding domain of CD44 (which contains extra N-terminal β-strand and C-terminal β-hairpin) .

Endostatin and the endostatin domain of collagen alpha 1 (XV) , these domains being decorated with many insertions in the common fold.

The noncollagenous (NC1) domain of collagen IV, which consists of a duplication of the C-type lectin domain, with segment swapping within and between individual domains .

Sulphatase-modifying factors (C-alpha-formyglycine-generating enzyme), where the fold is decorated with many additional structures .

The C-terminal domain of the major tropism determinant (Mtd), where the fold is decorated with many additional structures, and has an overall similarity to the sulphatase modifying factor family but lacking the characteristic disulphide .
PurM-like, N-terminal domain (PurM-like_N)
Type: Domain

This entry represents a structural domain with a core structure consisting of β-α-β-α-β(2), which is found in two enzymes of the purine biosynthetic pathway: at the N-terminal of aminoimidazole ribonucleotide (AIR) synthetase (PurM) , as well as the N1 and N2 domains of formylglycinamide ribonucleotide (FGAR) amidotransferase (PurL) (PurM-like module) . PurM and PurL utilise ATP to activate the oxygen of an amide within their substrate toward nucleophilic attack by a nitrogen. PurM uses the product of PurL, formylglycinamidine ribonucleotide (FGAM) and ATP to make AIR, ADP and P(i). It is also found as domains 1 and 3 in phosphoribosylformylglycinamidine synthase II (smPurL) (

) (carries a duplication: tandem repeats of two PurM-like units arranged like the PurM subunits in the dimer) .

This domain is also found at the N-terminal of thiamine monophosphate kinase (

) (ThiL) . ThiL phosphorylates thiamine monophosphate to form thiamine pyrophosphate, an essential cofactor that is synthesized de novo by Salmonella typhimurium.
Translation initiation factor IF2/IF5, N-terminal (Transl_init_fac_IF2/IF5_N)
Type: Homologous_superfamily

The beta subunit of archaeal and eukaryotic translation initiation factor 2 (IF2beta) and the N-terminal domain of translation initiation factor 5 (IF5) show significant sequence homology . Archaeal IF2beta contains two independent structural domains: an N-terminal mixed α/β core domain (topological similarity to the common core of ribosomal proteins L23 and L15e), and a C-terminal domain consisting of a zinc-binding C4 finger . Archaeal IF2beta is a ribosome-dependent GTPase that stimulates the binding of initiator Met-tRNA(i)(Met) to the ribosomes, even in the absence of other factors . The C-terminal domain of eukaryotic IF5 is involved in the formation of the multi-factor complex (MFC), an important intermediate for the 43S pre-initiation complex assembly . IF5 interacts directly with IF1, IF2beta and IF3c, which together with IF2-bound Met-tRNA(i)(Met) form the MFC.

This superfamily represents the N-terminal α/β domain found in IF2beta and IF5.
Translation initiation factor IF2/IF5, zinc-binding (Transl_init_fac_IF2/IF5_Zn-bd)
Type: Homologous_superfamily

The beta subunit of archaeal and eukaryotic translation initiation factor 2 (IF2beta) and the N-terminal domain of translation initiation factor 5 (IF5) show significant sequence homology . Archaeal IF2beta contains two independent structural domains: an N-terminal mixed α/β core domain (topological similarity to the common core of ribosomal proteins L23 and L15e), and a C-terminal domain consisting of a zinc-binding C4 finger . Archaeal IF2beta is a ribosome-dependent GTPase that stimulates the binding of initiator Met-tRNA(i)(Met) to the ribosomes, even in the absence of other factors . The C-terminal domain of eukaryotic IF5 is involved in the formation of the multi-factor complex (MFC), an important intermediate for the 43S pre-initiation complex assembly . IF5 interacts directly with IF1, IF2beta and IF3c, which together with IF2-bound Met-tRNA(i)(Met) form the MFC.

This entry represents the zinc-binding C4 domain with a zinc-bound β-ribbon motif, which is found in IF2beta and IF5 .
Ribonuclease/ribotoxin (Ribonuclease/ribotoxin)
Type: Homologous_superfamily

This entry represents a structural domain consisting of a single helix packed against anti-parallel β-sheet, which is found in both bacterial and fungal ribonucleases, as well as in ribotoxins such as restrictocin and alpha-sarcin.
APOBEC/CMP deaminase, zinc-binding (APOBEC/CMP_deaminase_Zn-bd)
Type: Binding_site

Cytidine deaminase (

) (cytidine aminohydrolase) catalyzes the hydrolysis of cytidine into uridine and ammonia while deoxycytidylate deaminase (

) (dCMP deaminase) hydrolyzes dCMP into dUMP. Both enzymes are known to bind zinc and to require it for their catalytic activity . These two enzymes do not share any sequence similarity with the exception of a region that contains three conserved histidine and cysteine residues which are thought to be involved in the binding of the catalytic zinc ion.

Such a region is also found in other proteins :

Yeast cytosine deaminase (

) (gene FCY1) which transforms cytosine into uracil.

Mammalian apolipoprotein B mRNA editing protein, responsible for the postranscriptional editing of a CAA codon into a UAA (stop) codon in the APOB mRNA.

Riboflavin biosynthesis protein ribG, which converts 2,5-diamino-6-(ribosylamino)-4(3H)-pyrimidinone 5'-phosphate into 5-amino-6-(ribosylamino)-2,4(1H,3H)-pyrimidinedione 5'-phosphate.

Bacillus cereus blasticidin-S deaminase (

), which catalyzes the deamination of the cytosine moiety of the antibiotics blasticidin S, cytomycin and acetylblasticidin S.

Bacillus subtilis protein comEB. This protein is required for the binding and uptake of transforming DNA.

B. subtilis hypothetical protein yaaJ.

Escherichia coli hypothetical protein yfhC.

Yeast hypothetical protein YJL035c.
Cytidine deaminase-like (Cytidine_deaminase-like)
Type: Homologous_superfamily

This superfamily represents a structural domain with a core fold consisting of α-β(2)-(α-β)2 that folds into three layers (α/β/α); some members may contain an extra C-terminal strand. This domain is found in several types of proteins, including:

Cytidine deaminase (

), including both mono-domain enzymes and two-domain enzymes that arose through a duplication and which contain extra helices in the N-terminal domain .

Deoxycytidylate (dCMP) deaminase (

) .

Guranine deaminase GuaD (

) .

Cytosine deaminase (

) .

AICAR transformylase domain (

) of the bifunctional purine biosynthesis enzyme ATIC; this protein consists of two domains of this fold with extra secondary structures within and in between the two core motifs .

Hypothetical protein TM1506 from Thermotoga maritima also contains a domain of this structure.
SPOC-like, C-terminal domain superfamily (SPOC-like_C_dom_sf)
Type: Homologous_superfamily

This superfamily represents the Spen Paralogue and Orthologue C-terminal (SPOC) domain and its structural homologues. This domain has a closed β-barrel fold of complex topology. Proteins that carry a SPOC-like domain include:

Spen proteins, such as SHARP (SMRT/HDAC1-associated repressor protein), which carry a SPOC domain at the C-terminal and an RNA-binding motif in the N-terminal; Spen proteins regulate the expression of key transcriptional effectors in diverse signalling pathways, the SHARP protein being a component of transcriptional repression complexes in both nuclear receptor and Notch/RBP-Jkappa signalling pathways .

The middle domains of Ku70 and Ku80 (which includes the C-terminal α-helical arm and the DNA encircling insertion); the Ku heterodimer, which is composed of Ku70 and Ku80 subunits, contributes to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the non-homologous end-joining pathway .
Polymerase/histidinol phosphatase-like (Pol/histidinol_Pase-like)
Type: Homologous_superfamily

This entry represents a PHP-like (Polymerase and Histidinol Phosphatase) domain, the catalytic site of which has four motifs with conserved histidine residues. This domain has a 7-stranded β/α barrel fold; this structure shows some similarity to the TIM-barrel fold metallohydrolases. PHP-like domains are found in alpha-subunit of bacterial DNA polymerase III (

) and family X DNA polymerases in addition to histidinol phosphatase (

) . Proteins carrying a distorted (α/β)7 barrel PHP-like fold include the hypothetical protein YcdX from Escherichia coli (which contains a trinuclear metal-binding site on the C-terminal side of the barrel) , as well as ribonuclease P protein component 3 (Rnp3) (

) from Pyrococcus horikoshii (no metal site on the C-terminal side of the barrel) .