SII-SWORD/CoKE huggingface dataset:
Zinc finger, MIZ-type (Znf_MIZ)
Type: Domain

This entry represents MIZ-type zinc finger domains. Miz1 (Msx-interacting-zinc finger) is a zinc finger-containing protein with homology to the yeast protein, Nfi-1. Miz1 is a sequence specific DNA binding protein that can function as a positive-acting transcription factor. Miz1 binds to the homeobox protein Msx2, enhancing the specific DNA-binding ability of Msx2 . Other proteins containing this domain include the human pias family (protein inhibitor of activated STAT protein).

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.
GRAM domain (GRAM)
Type: Domain

The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. It is normally about 70 amino acids in length. It is thought to be an intracellular protein-binding or lipid-binding signalling domain, which has an important function in membrane-associated processes. The structure of the GRAM domain is similar to that found in PH domains . Mutations in the GRAM domain of myotubularins cause a muscle disease, which suggests that the domain is essential for the full function of the enzyme . Myotubularin-related proteins are a large subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids .
Extradiol ring-cleavage dioxygenase, class III enzyme, subunit B (Xdiol_dOase_suB)
Type: Domain

Dioxygenases catalyse the incorporation of both atoms of molecular oxygen into substrates using a variety of reaction mechanisms. Cleavage of aromatic rings is one of the most important functions of dioxygenases, which play key roles in the degradation of aromatic compounds. The substrates of ring-cleavage dioxygenases can be classified into two groups according to the mode of scission of the aromatic ring. Intradiol enzymes (

) use a non-haem Fe(III) to cleave the aromatic ring between two hydroxyl groups (ortho-cleavage), whereas extradiol enzymes use a non-haem Fe(II) to cleave the aromatic ring between a hydroxylated carbon and an adjacent non-hydroxylated carbon (meta-cleavage) . These two subfamilies differ in sequence, structural fold, iron ligands, and the orientation of second sphere active site amino acid residues. Extradiol dioxygenases are usually homo-multimeric, bind one atom of ferrous ion per subunit and have a subunit size of about 33kDa. Extradiol dioxygenases can be divided into three classes. Class I and II enzymes (

) show sequence similarity, with the two-domain class II enzymes having evolved from a class I enzyme through gene duplication. Class III enzymes are different in sequence and structure, but they do share several common active-site characteristics with the class II enzymes, in particular the coordination sphere and the disposition of the putative catalytic base are very similar.

Class III enzymes usually have two subunits, designated A and B. Enzymes that belong to the extradiol class III family include Protocatechuate 4,5-dioxygenase (4,5-PCD; LigAB) (

) ; and 2'-aminobiphenyl-2,3-diol 1,2-dioxygenase (CarBaBb) .

The crystal structure of dioxygenase LigAB revealed that the molecule is an alpha2beta2 tetramer. The active site contains a non-heme iron coordinated by His12, His61, Glu242, and a water molecule located in a deep cleft of the beta subunit, which is covered by the alpha subunit .

This entry represents the structural domain of subunit B.
Pyruvate formate lyase domain (PFL_dom)
Type: Domain

Pyruvate formate lyase (PFL) catalyses the non-oxidative conversion of pyruvate and CoA to formate and acetyl-CoA. Several other enzymes have been identified in the pyruvate formate lyase family: ketoacid formate lyase, glycerol dehydratase (GD), benzyl succinate synthetase and p-hydroxyphenylacetate decarboxylase .

The PFL domain has a unique α/β barrel arrangement, with five 'up' strands and three 'down' strands; the up and down strands are linked by a
unique β-finger that carries a key thiyl radical .
Glycoside hydrolase, family 13, N-terminal Ig-like domain (Glyco_hydro_13_lg-like_dom)
Type: Domain

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

E or "early" set domains are associated with the catalytic domain of the cyclomaltodextrinase (CDase) and pullulan-degrading enzymes at the N-terminal end. The N-terminal domain of the CDase and pullulan-degrading enzymes may be related to the immunoglobulin and/or fibronectin type III superfamilies. This domain may be involved in homodimeric/tetrameric/dodecameric interactions. Enzymes containing this domain belong to family 13 (

) of the glycosyl hydrolases. Members of this subgroup include CDase, maltogenic amylase, and neopullulanase, all of which are capable of hydrolyzing all or two of the following three types of substrates: cyclomaltodextrins (CDs), pullulan, and starch. These enzymes hydrolyze CDs and starch to maltose and pullulan to panose by cleavage of alpha-1,4 glycosidic bonds whereas alpha-amylases essentially lack activity on CDs and pullulan. They also catalyze transglycosylation of oligosaccharides to the C3-, C4- or C6-hydroxyl groups of various acceptor sugar molecules .
Epstein Barr virus nuclear antigen-1, DNA-binding (EBNA1_DNA-bd)
Type: Domain

The Epstein-Barr virus (strain GD1) nuclear antigen 1 (EBNA1) binds to and activates DNA replication from the latent origin of replication. The crystal structure of the DNA-binding and dimerization domains were solved , and it was found that EBNA1 appears to bind DNA via two independent regions, the core and the flanking DNA-binding domains. This DNA-binding domain has a ferredoxin-like fold.
Phenylalanine-tRNA ligase, class II, N-terminal (Phe-tRNA_ligase_II_N)
Type: Domain

Phenylalanine-tRNA ligase (also known as phenylalanyl-tRNA synthetase) from Thermus thermophilus has an α2/β2 type quaternary structure and is one of the most complicated members of the ligase family. Identification of phenylalanine-tRNA ligase a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other ligases . This is the N-terminal domain of phenylalanine-tRNA ligase.

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 .
Bacteriophage Mu, transposase (Phage_Mu_transposase)
Type: Domain

This transposase is essential for integration, replication-transposition and excision of Bacteriophage Mu DNA. Transposition requires transposase and a transposition enhancer, and the DNA can be transposed into multiple sites in bacterial genomes.

The crystal structure of the core domain of Mu transposase, MuA, has been determined. The first of two subdomains contains the active site and, despite very limited sequence homology, exhibits a striking similarity to the core domain of Human immunodeficiency virus 1 integrase. The enzymatic activity of MuA is known to be activated by formation of a DNA-bound tetramer of the protein .
DNA polymerase processivity factor (DNA_pol_proc_fac)
Type: Domain

The DNA polymerase processivity factor is a replisome sliding clamp subunit, which is responsible for tethering the catalytic subunit of DNA polymerase to the DNA during high speed replication. The crystal structure of the Bacteriophage RB69 sliding clamp has been solved. It has shown that the peptide binds to the sliding clamp at the same position as that of a replication inhibitor peptide bound to PCNA. This suggests that the replication inhibitor protein p21CIP1 competes with eukaryotic polymerases for the same binding pocket on the clamp .
Integrase, Tn916-type, N-terminal DNA binding (Integrase_Tn916-type_DNA-bd_N)
Type: Domain

The integrase family of site-specific recombinases catalyze a diverse array of DNA rearrangements in archaebacteria, eubacteria and yeast. The structure of the
DNA binding domain of the the conjugative transposon Tn916 integrase protein was determined using NMR spectroscopy. The N-terminal domain was found to be structurally similar to the double stranded RNA binding domain (dsRBD). Experimental evidence suggests that the integrase protein interacts with DNA using residues located on the face of its three stranded β-sheet .
Cytochrome b-c1 complex subunit Rieske, transmembrane domain (Rieske_TM)
Type: Domain

The ubiquinol cytochrome c reductase (cytochrome bc1) complex is a respiratory chain that generates an electrochemical potential coupled to ATP synthesis. The bc1 complex contains 11 subunits, 3 respiratory subunits (cytochrome B, cytochrome C1, Rieske protein), 2 core proteins and 6 low-molecular weight proteins . Each subunit of the cytochrome bc1 complex provides a single helix to make up the transmembrane region of the complex.

This entry represents the transmembrane domain of the iron-sulfur subunit Rieske.
Glycoside hydrolase, family 13, N-terminal (Glyco_hydro_13_N)
Type: Domain

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Enzymes containing this domain belong to family 13 (

) of the glycosyl hydrolases. This domain is found in a range of enzymes that act on branched substrates ie. isoamylase, pullulanase and branching enzyme. Isoamylase hydrolyses 1,6-alpha-D-glucosidic branch linkages in glycogen, amylopectin and dextrin; 1,4-alpha-glucan branching enzyme functions in the formation of 1,6-glucosidic linkages of glycogen; and pullulanase is a starch-debranching enzyme.
Head decoration protein D (Head_decoration_D)
Type: Family

Bacteriophage lambda head decoration protein D stabilises the head shell after the rearrangement of GP7 subunits of the head shell lattice that accompanies expansion of the head. There are approximately 420 copies of protein D per mature phage.
Scaffold protein D (Scaffold_D)
Type: Family

The assembly of a macromolecular structure proceeds via a specific pathway of ordered events and occurs by changing of protein conformations as they join the assembly. The assembly process is aided by scaffolding proteins, which act as chaperones. In bacteriophages, scaffolding proteins B and D are responsible for procapsid formation. Copies of protein D (240) form the external scaffold, while 60 copies of protein B form the internal scaffold .
Cellulase, Ig-like domain (Cellulase_Ig-like)
Type: Domain

Cellulases (Endoglucanases)

catalyse the endohydrolysis of 1,4-beta-D-glucosidic linkages in cellulose.
This is the N-terminal ig-like domain of cellulase, enzymes containing this domain belong to family 9 of the glycoside hydrolases (

).
Zinc finger, C5HC2-type (Znf_C5HC2)
Type: Domain

This entry represents a predicted zinc finger with eight potential zinc ligand binding residues. This domain is found in proteins enconded by the Jumonji gene , and may have a DNA binding function. The mouse jumonji

protein is required for neural tube formation, and is essential for normal heart development. It also plays a role in the down-regulation of cell proliferation signalling.

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.
Beta galactosidase small chain/ domain 5 (B-gal_small/dom_5)
Type: Domain

This domain comprises the small chain of dimeric beta-galactosidases

. This domain is also found in single chain beta-galactosidase, which is comprised of five domains, where it represents domain 5. It contains an N-terminal loop that swings towards the active site upon the deep binding of a ligand to produce a closed conformation .
CDC48, domain 2 (Cdc48_dom2)
Type: Domain

The CDC48 N-terminal domain is a protein domain found in AAA ATPases including cell division protein 48 (CDC48), VCP-like ATPase (VAT) and N-ethylmaleimide sensitive fusion protein. It is a substrate recognition domain which binds polypeptides, prevents protein aggregation, and catalyses refolding of permissive substrates. It is composed of two equally sized subdomains. The amino-terminal subdomain forms a double-psi β-barrel whose pseudo-twofold symmetry is mirrored by an internal sequence repeat of 42 residues. The carboxy-terminal subdomain forms a novel six-stranded β-clamp fold . Together these subdomains form a kidney-shaped structure.

This entry represents the carboxy-terminal subdomain.
Cytochrome c oxidase subunit VIIc (COX7C/Cox8)
Type: Family

Cytochrome c oxidase (

) is an oligomeric enzymatic complex which is a component of the respiratory chain complex and is involved in the transfer of electrons from cytochrome c to oxygen . In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane.
Cytochrome c oxidase subunit IV family (Cyt_c_oxidase_su4_fam)
Type: Family

Cytochrome c oxidase (CcO) (

), the terminal oxidase in the respiratory chains of eukaryotes and most bacteria, is a multi-chain transmembrane protein located in the inner membrane of mitochondria and the cell membrane of prokaryotes. It catalyses the reduction of O2 and simultaneously pumps protons across the membrane. The number of subunits varies from three to five in bacteria and up to 13 in mammalian mitochondria. Subunits I, II, and III of mammalian CcO are encoded within the mitochondrial genome and the remaining 10 subunits are encoded within the nuclear genome. Found only in eukaryotes, subunit IV is the largest of the nuclear-encoded subunits. It binds ATP at the matrix side, leading to an allosteric inhibition of enzyme activity at high intramitochondrial ATP/ADP ratios. In mammals, subunit IV has a lung-specific isoform and a ubiquitously expressed isoform .

This family is composed of cytochrome c oxidase subunit 4 , and subunits 5A and 5B . Proteins in this entry also include the yeast COX IV subunit, Mtc3 (maintenance of telomere cappining 3) protein .
Cytochrome c oxidase subunit 7e/7s (Cox7e/7s)
Type: Family

Cytochrome c oxidase (CcO;

), a 13 subunit complex, is the terminal oxidase in the mitochondrial electron transport chain. Cytochrome c oxidase is the component of the respiratory chain that catalyses the reduction of oxygen to water .

This entry contains the subunits 7e and 7s of cytochrome c oxidase (also known as Cytochrome c oxidase polypeptide VIIe and VIIs), which are found only in eukaryotes. Their specific function remains unclear.
Cytochrome b-c1 complex subunit 8 (Cyt_bc1_su8)
Type: Family

The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multi-enzyme complex , which recognises a mitochondrial targeting presequence. The bc1 complex contains 11 subunits: 3 respiratory subunits (cytochrome b, cytochrome c1 and Rieske protein), 2 core proteins and 6 low molecular weight proteins. This family represents the 9.5kDa subunit of the complex, known as subunit 8 or protein QP-C . This subunit together with cytochrome B binds to ubiquinone.
mRNA triphosphatase Cet1-like (mRNA_triPase_Cet1)
Type: Domain

The mRNA capping enzyme in yeast is composed of two subunits, alpha and beta. The alpha subunit has guanylyltransferase activity, whilst the beta subunit is an RNA 5'-triphosphatase (RTPase) . This entry represents a domain found in the mRNA capping enzyme beta subunit Cet1. RTPase catalyzes the first step in the mRNA cap formation process, the removal of the gamma-phosphate of triphosphate terminated pre-mRNA. This activity is metal-dependent. The 5'-end of the resulting mRNA diphosphate is subsequently capped with GMP by RNA guanylytransferase, and then further modified by one or more methyltransferases. The mRNA cap-forming activity is an essential step in mRNA processing. The RTPases are not conserved among eukarya and this subgroup includes fungal and protozoal RTPases. The RTPase domain of the mimivirus RTPase-GTase fusion mRNA capping enzyme also belongs to this subgroup. The domain is related to the CYTH domain. Cet1 has a novel active site fold whereby an eight-strand β-barrel forms a topologically closed tunnel known as the "triphosphate tunnel" . Enzymes with similar structures are able to bind triphosphorylated substrates and requiring divalent metal ions as activators. They were thus called triphosphate tunnel metalloenzymes (TTMs) .

Cetl paralogue, Ctl1 (capping enzyme RNAtriphosphatase-like 1), is a RNA 5'-triphosphatase probably involved in an RNA processing event other than mRNA capping .
Ferredoxin thioredoxin reductase, alpha chain (Fd_thioredoxin_Rdtase_alpha)
Type: Domain

Ferredoxin thioredoxin reductase is a [4FE-4S] protein which plays an important role in the ferredoxin/thioredoxin regulatory chain. It converts an electron signal (photoreduced ferredoxin) to a thiol signal (reduced thioredoxin), regulating enzymes by reduction of specific disulphide groups. It catalyses the light-dependent activation of several photosynthesis enzymes. Ferredoxin thioredoxin reductase is a heterodimer of subunit a and subunit b. Subunit a is the variable subunit, and b is the catalytic chain .
Influenza non-structural protein (NS1) (NS1)
Type: Family

A specific region of the Influenza B virus NS1 protein, which includes part of its effector domain, blocks the covalent linkage of mouse ISG15 to its target proteins both
in vitro
and in infected cells. Of the several hundred proteins induced by interferon (IFN) alpha/beta, the ubiquitin-like ISG15 protein is one of the most predominant. Influenza A virus employs a different strategy: its NS1 protein does not bind the ISG15 protein, but little or no ISG15 protein is produced during infection .
Ferredoxin thioredoxin reductase catalytic beta subunit (FTR_bsu)
Type: Family

Ferredoxin thioredoxin reductase is a [4FE-4S] protein present in organisms performing oxygenic photosynthesis, and plays an important role in the ferredoxin/thioredoxin regulatory chain. It converts an electron signal (photoreduced ferredoxin) to a thiol signal (reduced thioredoxin), regulating enzymes by reduction of specific disulphide groups. It catalyses the light-dependent activation of several photosynthetis enzymes. Ferredoxin thioredoxin reductase is a heterodimer of subunit alpha and subunit beta. Subunit alpha is the variable subunit, and beta is the catalytic chain .

The structure of the beta subunit has been determined and found to fold around the FeS cluster .