SII-SWORD/CoKE huggingface dataset:
Glycosyl transferase 1, domain A (Glyco_trans_A_1)
Type: Domain

This entry represents a domain found predominantly at the N terminus of various prokaryotic alpha-glucosyltransferases. According to whether the domain exists as a whole molecule or as a half molecule determines the number of sugar residues that the molecule transfers. Two-domain proteins are processive in that they transfer more than one sugar residue, processively; single domain proteins transfer just one sugar moiety .
Domain of unknown function DUF1977, DnaJ-like (DUF1977_DnaJ-like)
Type: Domain

This C-terminal domain is functionally uncharacterised and predominantly found in Dnaj-like proteins.
Domain of unknown function DUF1978, IncA (DUF1978_IncA)
Type: Domain

This domain is found in various hypothetical proteins produced by the bacterium Chlamydia pneumoniae. Their exact function has not, as yet, been identified. This entry includes the IncA proteins
Transposase, MuDR, N-terminal (Transposase_MuDR_N)
Type: Domain

This N-terminal domain is functionally uncharacterised and found in various Oryza sativa (Rice) mutator-like transposases.
Protein of unknown function DUF1980 (DUF1980)
Type: Family

Members of this occur in gene pairs with members of

. The N-terminal region contains several predicted transmembrane helix regions while the few invariant residues (G, CxxD, and W) occur in the C-terminal region .
Mon2/Sec7/BIG1-like, HDS (Mon2/Sec7/BIG1-like_HDS)
Type: Domain

This entry represents a HDS (homology downstream of Sec7) domain found towards the C-terminal of guanine nucleotide exchange factors involved Golgi transport, such as budding yeast protein Sec7, protein Mon2 and BIG1-like proteins . Sec7 is involved in the secretory pathway as a protein binding scaffold for the COPII-COPI protein switch for maturation of the VTC intermediate compartments for Golgi compartment biogenesis . Sec7 has four conserved HDS1-4 domains which act to integrate the signals from several small GTPases, including Arf1 itself, to switch Sec7 from a strongly autoinhibited to a strongly auto activated form .
Sorting nexin/Vps5-like, C-terminal (Vps5_C)
Type: Domain

Vps5 is a sorting nexin that functions in membrane trafficking. This is the C-terminal dimerisation domain .
NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial-like (NDUFS1-like_C)
Type: Domain

This entry represents a domain found at the C-terminal end of various NADH dehydrogenases from bacteria and eukaryotes, including NADH-quinone oxidoreductase subunit G from Rickettsia typhi (NuoG) and NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial from humans (NDUFS1, also known as Complex I-75kD, CI-75kD).

NuoG shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain.

NDUFS1 is a core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyses electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor . This protein is associated with mitochondrial disorders leading to a group of highly heterogeneous conditions ranging from lethal neonatal disease to adult-onset neurodegenerative disorders .
Tip attachment protein J, central straight fiber domain (GpJ_CSF)
Type: Domain

This entry represents the central straight fiber (CSF) domain of Tip attachment protein J from Escherichia phage lambda (GpJ) and similar bacterial and viral proteins. This longitudinally oriented domain, folds into a mixed β-sheet prism and undergoes a range of structural rearrangements . It is often found in association with

.
This domain is also found at the C-terminal end of the putative tail tip fiber protein from Escherichia phage Phieco32 .

The Tip attachment protein J (GpJ) from Escherichia phage lambda is a crucial tail fibre protein responsible for recognising and binding the host cell's LamB receptor, thereby initiating infection. Structurally, GpJ forms the central tail fibre at the phage tip and undergoes conformational changes upon receptor engagement, which are essential for triggering DNA injection into the host . It interacts with other tail proteins during assembly, serving as a scaffold for tail tube formation and coordinating with the tape measure protein to regulate genome delivery . Mutations in GpJ can alter host specificity and affect phage stability, while its exposed position makes it a target for neutralising antibodies .
Phytochelatin synthase, C-terminal (Phytochelatin_synthase_C)
Type: Domain

This entry represents the C-terminal region of plant phytochelatin synthases (also known as glutathione gamma-glutamylcysteinyltransferase;

), which is involved in the synthesis of phytochelatins (PC) and homophytochelatins (hPC), the heavy-metal-binding peptides of plants. This enzyme is required for detoxification of heavy metals such as cadmium and arsenate. The N-terminal region of phytochelatin synthase contains the active site, as well as four highly conserved cysteine residues that appear to play an important role in heavy-metal-induced phytochelatin catalysis. The C-terminal region is rich in cysteines, and may act as a metal sensor, whereby the Cys residues bind cadmium ions to bring them into closer proximity and transferring them to the activation site in the N-terminal catalytic domain . The C-terminal region displays homology to the functional domains of metallothionein and metallochaperone.
Zinc finger, Mcm10/DnaG-type (Znf_Mcm10/DnaG)
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 zinc finger domain is found in Mcm10 proteins and DnaG-type primases .
D-lactate dehydrogenase, membrane binding, C-terminal (Lactate_DH_C)
Type: Domain

Members of this entry are predominantly found in prokaryotic D-lactate dehydrogenase, forming the cap-membrane-binding domain, which consists of a large seven-stranded antiparallel β-sheet flanked on both sides by α-helices. They allow for membrane association .
Domain of unknown function DUF1985 (DUF1985)
Type: Domain

This domain is functionally uncharacterised; it is predominantly found in proteins from Magnoliopsida (flowering plants).
Replication factor Mcm10, C-terminal (Rep_factor_Mcm10_C)
Type: Domain

This entry represents a domain found in the C-terminal region of the Mcm10 protein, which is a eukaryotic DNA replication factor that regulates the stability and chromatin association of DNA polymerase alpha .
Methionyl/Leucyl tRNA synthetase (Methionyl/Leucyl_tRNA_Synth)
Type: Domain

This entry represents the methionyl and leucyl tRNA synthetases, which are class I aminoacyl-tRNA synthetases.

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 .
Transmembrane protein TMEM64 (TMEM64)
Type: Family

This entry contains a group of transmemberane proteins, including TMEM64. The yeast member of this family, Tvp38 (

), localises with the t-SNARE Tlg2 .
Spastin/Vps4, C-terminal (Spast_Vps4_C)
Type: Domain

This domain is found at the C-terminal of a group of eukaryotic and archaeal proteins that belong to the AAA ATPase family, including human Spastin and Vacuolar protein sorting-associated protein 4 (Vps4) from Saccharomyces cerevisiae . It forms an α-helix structure and is required for oligomerisation .
Zinc finger, H2C2-type, histone UAS binding (Znf_H2C2_histone_UAS-bd)
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 an H2C2-type zinc finger that binds to histone upstream activating sequence (UAS) elements found in histone gene promoters .
Glycine/sarcosine/betaine reductase complex, protein B, subunit alpha/ beta (Gly_reductase_pB_sua/b)
Type: Family

This is a family of glycine reductase, sarcosine reductase and betaine reductases. These enzymes catalyse the following reactions:

sarcosine reductase: Acetyl phosphate + methylamine + thioredoxin disulphide = N-methylglycine + phosphate + thioredoxin.

glycine reductase: Acetyl phosphate + NH3 + thioredoxin disulphide = glycine + phosphate + thioredoxin.

betaine reductase: Acetyl phosphate + trimethylamine + thioredoxin disulphide = N,N,N-trimethylglycine + phosphate + thioredoxin.
Chromatin modification-related protein Eaf6 (Eaf6)
Type: Family

Eaf6 is a component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of selected genes principally by acetylation of nucleosomal histone H4 and H2A. The NuA4 histone acetyltransferase complex is conserved from yeast to humans . Budding yeast Eaf6 is also a component of the NuA3 histone acetyltransferase complex that acetylates Lys-14 of histone H3 , while human Eaf6 is a component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity .
CTAG/Pcc1 family (CTAG/Pcc1)
Type: Family

This entry represents the CTAG/Pcc1 family. Its members include yeast EKC/KEOPS complex subunit Pcc1, mammalian EKC/KEOPS complex subunit Lage3 and human cancer/testis antigen (CTAG) 1/2.

In Saccharomyces cerevisiae, Pcc1 is a component of the EKC/KEOPS protein complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t6A37) in tRNAs that read codons beginning with adenine .

Similar to its S. cerevisiae homologue, human LAGE3 is part of the EKC complex that is essential for a universal tRNA modification. The human EKC complex interacts with tumour antigen PRAME (preferentially expressed antigen in melanoma), and hence involved in oncogenesis .
Peptidase S1A, nudel (Peptidase_S1A_nudel)
Type: Domain

This domain is found in serine endopeptidases belonging to MEROPS peptidase family S1A (clan PA). It is found in unusual mosaic proteins, which are encoded by the Drosophila nudel gene (see

). Nudel is involved in defining embryonic dorsoventral polarity. Three proteases; ndl, gd and snk process easter to create active easter. Active easter defines cell identities along the dorsal-ventral continuum by activating the spz ligand for the Tl receptor in the ventral region of the embryo. Nudel, pipe and windbeutel together trigger the protease cascade within the extraembryonic perivitelline compartment which induces dorsoventral polarity of the Drosophila embryo .

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .
Pyridoxal phosphate-dependent transferase, major domain (PyrdxlP-dep_Trfase_major)
Type: Homologous_superfamily

The monomer of PLP-dependent transferases consists of two domains, a large domain and a small domain. This entry represents the large domain, which has a 3-layer α/β/α sandwich topology . This domain can be found in the following PLP-dependent transferase families:

Aspartate aminotransferase (AAT)-like enzymes, such as aromatic aminoacid aminotransferase AroAT, glutamine aminotransferase and kynureninase .

Beta-eliminating lyases, such as tyrosine phenol lyase and tryptophanase .

Pyridoxal-dependent decarboxylases, such as DOPA decarboxylase and glutamate decarboxylase beta (GadB) .

Cystathionine synthase-like enzymes, such as cystalysin, methionine gamma-lyase (MGL), and cysteine desulphurase (IscS) .

GABA-aminotransferase-like enzymes, such as ornithine aminotransferase and serine hydroxymethyltransferase .

Ornithine decarboxylase major domain .

CMP-5'-(3-aminopropyl)phosphonate synthase .

Canavanine gamma-lyase .

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination . PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy .

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic .
Pyridoxal phosphate-dependent transferase, small domain (PyrdxlP-dep_Trfase_small)
Type: Homologous_superfamily

The monomer of PLP-dependent transferases consists of two domains, a large domain and a small domain. This entry represents small domain, which has a complex α/β structure . It can be found in the following PLP-dependent transferase families:

Aspartate aminotransferase (AAT)-like enzymes, such as aromatic aminoacid aminotransferase AroAT, glutamine aminotransferase and kynureninase .

Beta-eliminating lyases, such as tyrosine phenol lyase and tryptophanase .

Pyridoxal-dependent decarboxylases, such as DOPA decarboxylase and glutamate decarboxylase beta (GadB) .

Cystathionine synthase-like enzymes, such as cystalysin, methionine gamma-lyase (MGL), and cysteine desulphurase (IscS) .

GABA-aminotransferase-like enzymes, such as ornithine aminotransferase and serine hydroxymethyltransferase .

Ornithine decarboxylase .

CMP-5'-(3-aminopropyl)phosphonate synthase .

Canavanine gamma-lyase .

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination . PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy .

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic .
Influenza matrix M1, N-terminal subdomain 1 (Flu_matrix_M1_N_sub1)
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 first subdomain of the N-terminal domain of M1.
Pyridoxal phosphate-dependent transferase (PyrdxlP-dep_Trfase)
Type: Homologous_superfamily

This entry represents the major region of PLP-dependent transferases. This domain has a three layer α/β/α sandwich topology, with mixed β-sheets of 7 strands. The major region can be found in the following PLP-dependent transferase families:

Aspartate aminotransferase (AAT)-like enzymes, such as aromatic aminoacid aminotransferase AroAT, glutamine aminotransferase and kynureninase .

Beta-eliminating lyases, such as tyrosine phenol lyase and tryptophanase .

Pyridoxal-dependent decarboxylases, such as DOPA decarboxylase and glutamate decarboxylase beta (GadB) .

Cystathionine synthase-like enzymes, such as cystalysin, methionine gamma-lyase (MGL), and cysteine desulphurase (IscS) .

GABA-aminotransferase-like enzymes, such as ornithine aminotransferase and serine hydroxymethyltransferase .

Ornithine decarboxylase major domain .

CMP-5'-(3-aminopropyl)phosphonate synthase .

Canavanine gamma-lyase .

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). Pyridoxal 5'-phosphate (PLP) is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination . PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors . Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy .

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the ε-amino group of an active site lysine residue on the enzyme. The α-amino group of the substrate displaces the lysine ε-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic .
Formin, FH2 domain (FH2_Formin)
Type: Domain

Formin homology (FH) proteins play a crucial role in the reorganisation of the actin cytoskeleton, which mediates various functions of the cell cortex including motility, adhesion, and cytokinesis . Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins, although some formins have been assigned functions within the nucleus. Formins are characterised by the presence of three FH domains (FH1, FH2 and FH3), although members of the formin family do not necessarily contain all three domains . The proline-rich FH1 domain mediates interactions with a variety of proteins, including the actin-binding protein profilin, SH3 (Src homology 3) domain proteins, and WW domain proteins. The FH2 domain is required for the self-association of formin proteins through the ability of FH2 domains to directly bind each other , and may also act to inhibit actin polymerisation . The FH3 domain (

) is less well conserved and may be important for determining intracellular localisation of formin family proteins. In addition, some formins can contain a GTPase-binding domain (GBD) (

) required for binding to Rho small GTPases, and a C-terminal conserved Dia-autoregulatory domain (DAD).

This entry represents the FH2 domain, which was shown by X-ray crystallography to have an elongated, crescent shape containing three helical subdomains .