SII-SWORD/CoKE huggingface dataset:
Rad18, zinc finger UBZ4-type (Rad18_UBZ4)
Type: Domain

The ubiquitin-binding zinc finger (UBZ) is a type of zinc-coordinating β-β-α fold domain found mainly in proteins involved in DNA repair and transcriptional regulation. UBZ domains coordinate a zinc ion with cysteine or histidine residues; depending on their amino acid sequence, UBZ domains are classified into several families . Type 1 UBZs are CCHH-type zinc fingers found in tandem UBZ domains of TAX1-binding protein 1 (TAX1BP1) , type 2 UBZs are CCHC-type zinc fingers found in FAAP20 which is a subunit of the Fanconi anemia (FA) core complex , type 3 UBZs are CCHH-type zinc fingers found only in the Y-family translesion polymerase eta , and type 4 UBZs are CCHC-type zinc fingers found in Y-family translesion polymerase kappa, Werner helicase-interacting protein 1 (WRNIP1), and Rad18 .

This entry represents type 4 UBZ found in RAD18. The domain is a potential zinc finger for nucleic acid binding and a putative nucleotide binding sequence . Human RAD18 accumulates very rapidly and remains for a long period of time at sites of different types of DNA damage, and is required of DNA. RAD18 appears to respond to DNA damage in two distinct ways: replication-dependent and replication-independent. The RAD18-type zinc finger located in the middle of RAD18 is responsible for the replication-independent accumulation of RAD18 following DNA damage, while a second zinc finger, SAP-type, is responsible for replication-dependent accumulation .
Zasp-like motif (Zasp-like_motif)
Type: Domain

The Zasp-like motif is a short (26 amino acid) motif that is frequently found in association with
PDZ domains in a number of cytoskeletal and muscle proteins, such as Zasp .
Dystroglycan-type cadherin-like (Cadg)
Type: Domain

In animals, cadherin domain-containing proteins are adhesion molecules that modulate a wide variety of processes including cell polarization and migration but they have also been identified in yeast and magnetotactic bacteria. Crystal structures have revealed that multiple cadherin domains form Ca
2+
-dependent rod-like structures with a conserved Ca
2+
-binding pocket at the domain-domain interface .
NusG-like, N-terminal (NGN-like_dom)
Type: Domain

This is the N-terminal domain of transcription termination/antitermination protein NusG, which is involved in transcription elongation, termination and antitermination. It also occurs at the N-terminal of transcription antitermination protein RfaH and in the transcription elongation factor Spt5 .
Adenosine/AMP deaminase active site (A/AMP_deam_AS)
Type: Active_site

Adenosine deaminase (

) catalyzes the hydrolytic deamination of adenosine into inosine and AMP deaminase (

) catalyzes the hydrolytic deamination of AMP into IMP. It has been shown that these two enzymes share three regions of sequence similarities; these regions are centred on residues which are proposed to play an important role in the catalytic mechanism of these two enzymes. This entry presents one of these regions, it contains two conserved aspartic acid residues that are potential active site residues.
Kelch repeat type 1 (Kelch_1)
Type: Repeat

This entry represents a type of kelch sequence motif that comprises one β-sheet blade.

Kelch is a 50-residue motif, named after the Drosophila mutant in which it was first identified . This sequence motif represents one β-sheet blade, and several of these repeats can associate to form a β-propeller. For instance, the motif appears 6 times in Drosophila egg-chamber regulatory protein (also known as ring canal kelch protein), creating a 6-bladed β-propeller. The motif is also found in mouse protein MIPP and in a number of poxviruses. In addition, kelch repeats have been recognised in alpha-and beta-scruin , and in galactose oxidase from the fungus Dactylium dendroides . The structure of galactose oxidase reveals that the repeated sequence corresponds to a 4-stranded antiparallel β-sheet motif that forms the repeat unit in a super-barrel structural fold .

The known functions of kelch-containing proteins are diverse: scruin is an actin cross-linking protein; galactose oxidase catalyses the oxidation of the hydroxyl group at the C6 position in D-galactose; and kelch may have a cytoskeletal function, as it is localised to the actin-rich ring canals that connect the 15 nurse cells to the developing oocyte in Drosophila . Nevertheless, based on the location of the kelch pattern in the catalytic unit in galactose oxidase, functionally important residues have been predicted in glyoxal oxidase .
Tryptophan synthase, beta chain, conserved site (Trp_synth_b_CS)
Type: Conserved_site

Tryptophan synthase catalyses the last step in the biosynthesis of tryptophan :

L-serine + 1-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + glyceraldehyde 3-phosphate + H
2
O

It has two functional domains, each found in bacteria and plants on a separate subunit: alpha chain (

) is for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate and beta chain is for the synthesis of tryptophan from indole and serine. In fungi the two domains are fused together on a single multifunctional protein .

The beta chain of the enzyme, represented here, requires pyridoxal-phosphate as a cofactor. The pyridoxal-phosphate group is attached to a lysine residue. The region around this lysine residue also contains two histidine residues which are part of the pyridoxal-phosphate binding site.
Tryptophan synthase, beta chain (Trp_synth_beta)
Type: Family

Tryptophan synthase catalyses the last step in the biosynthesis of tryptophan :

L-serine + 1-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + glyceraldehyde 3-phosphate + H
2
O

It has two functional domains, each found in bacteria and plants on a separate subunit: alpha chain (

) is for the aldol cleavage of indoleglycerol phosphate to indole and glyceraldehyde 3-phosphate and beta chain is for the synthesis of tryptophan from indole and serine. In fungi the two domains are fused together on a single multifunctional protein .

The beta chain of the enzyme, represented here, requires pyridoxal-phosphate as a cofactor. The pyridoxal-phosphate group is attached to a lysine residue. The region around this lysine residue also contains two histidine residues which are part of the pyridoxal-phosphate binding site.
Molybdopterin oxidoreductase, prokaryotic, conserved site (Mopterin_OxRdtase_prok_CS)
Type: Conserved_site

A number of different prokaryotic oxidoreductases that require and bind a molybdopterin cofactor have been shown to share a number of regions of sequence similarity. These enzymes are:

Escherichia coli respiratory nitrate reductase (EC 1.7.99.4). This enzyme complex allows the bacteria to use nitrate as an electron acceptor during anaerobic growth. The enzyme is composed of three different chains: alpha, beta and gamma. The alpha chain (gene narG) is the molybdopterin-binding subunit. Escherichia coli encodes for a second, closely related, nitrate reductase complex which also contains a molybdopterin-binding alpha chain (gene narZ).

Escherichia coli anaerobic dimethyl sulfoxide reductase (DMSO reductase). DMSO reductase is the terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds. DMSO reductase is composed of three chains: A, B and C. The A chain (gene dmsA) binds molybdopterin.

Escherichia coli biotin sulfoxide reductases (genes bisC and bisZ). This enzyme reduces a spontaneous oxidation product of biotin, BDS, back to biotin. It may serve as a scavenger, allowing the cell to use biotin sulfoxide as a biotin source.

Methanobacterium formicicum formate dehydrogenase (EC 1.2.1.2). The alpha chain (gene fdhA) of this dimeric enzyme binds a molybdopterin cofactor.

Escherichia coli formate dehydrogenases -H (gene fdhF), -N (gene fdnG) and -O (gene fdoG). These enzymes are responsible for the oxidation of formate to carbon dioxide. In addition to molybdopterin, the alpha (catalytic) subunit also contains an active site, selenocysteine.

Wolinella succinogenes polysulfide reductase chain. This enzyme is a component of the phosphorylative electron transport system with polysulfide as the terminal acceptor. It is composed of three chains: A, B and C. The A chain (gene psrA) binds molybdopterin.

Salmonella typhimurium thiosulfate reductase (gene phsA). - Escherichia coli trimethylamine-N-oxide reductase (EC 1.6.6.9) (gene torA) .

Nitrate reductase (EC 1.7.99.4) from Klebsiella pneumoniae (gene nasA), Alcaligenes eutrophus, Escherichia coli, Rhodobacter sphaeroides, Thiosphaera pantotropha (gene napA), and Synechococcus PCC 7942 (gene narB).

These proteins range from 715 amino acids (fdhF) to 1246 amino acids (narZ) in size.

This entry represents a conserved region located in these enzymes.
Molybdopterin oxidoreductase (Mopterin_OxRdtase)
Type: Domain

This domain is found in a number of molybdopterin-containing oxidoreductases, tungsten formylmethanofuran dehydrogenase subunit d (FwdD), and molybdenum formylmethanofuran dehydrogenase subunit (FmdD); where a single domain constitutes almost the entire subunit. This domain is also found in periplasmic nitrate reductases, trimethylamine-N-oxide reductases, dimethyl sulfoxide reductase DmsA among other dehydrogenases/reductases. The formylmethanofuran dehydrogenase catalyses the first step in methane formation from CO2 in methanogenic archaea and has a molybdopterin dinucleotide cofactor .
Molybdopterin dinucleotide-binding domain (MoPterin_dinucl-bd_dom)
Type: Domain

This domain is found in various molybdopterin-containing oxidoreductases, such as Molybdenum-containing formylmethanofuran dehydrogenase 1 subunit C (FmdC). The formylmethanofuran dehydrogenase catalyses the first step in methane formation from CO2 in methanogenic archaea and has a molybdopterin dinucleotide cofactor . This domain corresponds to the C-terminal domain IV in dimethyl sulfoxide (DMSO) reductase which interacts with the 2-amino pyrimidone ring of both molybdopterin guanine dinucleotide molecules .
Molybdopterin guanine dinucleotide-containing S/N-oxide reductase (BisC)
Type: Family

This enzyme family shares sequence similarity and a requirement for a molydenum cofactor as the only prosthetic group. The form of the cofactor is a single molybdenum atom coordinated by two molybdopterin guanine dinucleotide molecules. Members of the family include biotin sulphoxide reductase, dimethylsulphoxide reductase, and trimethylamine-N-oxide reductase, although a single member may show all those activities and related activities; it may not be possible to resolve the primary function for members of this family by sequence comparison alone. A number of similar molybdoproteins in which the N-terminal region contains a CXXXC motif and may bind an iron-sulphur cluster are excluded from this set, including formate dehydrogenases and nitrate reductases. Also excluded is the A chain of a heteromeric, anaerobic DMSO reductase, which also contains the CXXXC motif .
Arsenate reductase (Arsenate_reductase)
Type: Family

This entry describes a distinct clade, including ArsC itself, of the broader family of ArsC and related proteins. This clade is almost completely restricted to the proteobacteria. An anion-translocating ATPase has been identified as the product of the arsenical resistance operon of resistance plasmid R773 . When expressed in Escherichia coli this ATP-driven oxyanion pump catalyses extrusion of the oxyanions arsenite, antimonite and arsenate. The pump is composed of two polypeptides, the products of the arsA and arsB genes. The pump alone produces resistance to arsenite and antimonite. This protein, ArsC, catalyzes the reduction of arsenate to arsenite, and thus extends resistance to include arsenate. ArsC contains a single catalytic cysteine, within a thioredoxin fold, that forms a covalent thiolate-As(V) intermediate, which is reduced by GRX through a mixed GSH-arsenate intermediate . This family of predominantly bacterial enzymes is unrelated to two other families of arsenate reductases which show similarity to low-molecular-weight acid phosphatases and phosphotyrosyl phosphatases .
Arsenate reductase-like (Arsenate_reductase-like)
Type: Family

Several bacterial taxon have a chromosomal resistance system, encoded by the ars operon, for the detoxification of arsenate, arsenite, and antimonite . This system transports arsenite and antimonite out of the cell. The pump is composed of two polypeptides, the products of the arsA and arsB genes. This two-subunit enzyme produces resistance to arsenite and antimonite. Arsenate, however, must first be reduced to arsenite before it is extruded. A third gene, arsC, expands the substrate specificity to allow for arsenate pumping and resistance. ArsC is an approximately 150-residue arsenate reductase that uses reduced glutathione (GSH) to convert arsenate to arsenite with a redox active cysteine residue in the active site. ArsC forms an active quaternary complex with GSH, arsenate, and glutaredoxin 1 (Grx1). The three ligands must be present simultaneously for reduction to occur .

The arsC family also comprises the Spx proteins which are GRAM-positive bacterial transcription factors that regulate the transcription of multiple genes in response to disulphide stress .

The arsC protein structure has been solved . It belongs to the thioredoxin superfamily fold which is defined by a β-sheet core surrounded by α-helices. The active cysteine residue of ArsC is located in the loop between the first β-strand and the first helix, which is also conserved in the Spx protein and its homologues.
Outer membrane protein, bacterial (OMP_bac)
Type: Domain

Most of the bacterial outer membrane proteins in this group are porin-like integral membrane proteins (such as ompA) , but some are small lipid-anchored proteins (such as pal) . They are present in the outer membrane of many Gram-negative organisms . The C-terminal half of these proteins and is well conserved. The N-terminal half is variable although some of the proteins in this group have the OmpA-like transmembrane domain

at the N terminus.
OmpA-like domain (OmpA-like)
Type: Domain

This entry represents a domain with a β/α/β/α-β(2) structure found in the C-terminal region of many Gram-negative bacterial outer membrane proteins , such as porin-like integral membrane proteins (such as ompA) , small lipid-anchored proteins (such as pal) , and MotB proton channels . The N-terminal half is variable although some of the proteins in this group have the OmpA-like transmembrane domain

at the N terminus. OmpA from Escherichia coli is required for pathogenesis, and can interact with host receptor molecules . MotB (and MotA) serves two functions in E. coli, the MotA(4)-MotB(2) complex attaches to the cell wall via MotB to form the stator of the flagellar motor, and the MotA-MotB complex couples the flow of ions across the cell membrane to movement of the rotor .

Other Gram-negative outer membrane proteins with this domain:

Outer membrane protein P5 from Haemophilus influenzae.

Outer membrane protein P.III/class IV from Neisseria.

Outer membrane porin F (gene oprF) from Pseudomonas.

Protein TpN50 from Treponema pallidum .

Peptidoglycan-associated lipoprotein (gene pal) from Escherichia coli, Haemophilus influenzae, Legionella pneumophila and Pseudomonas putida.

Outer membrane lipoprotein P6 from Haemophilus influenzae.

Escherichia coli hypothetical lipoprotein yiaD.

Vibrio parahaemolyticus sodium-type flagellar protein motY .

The OmpA-like domain is thought to be responsible for non-covalent interactions with peptidoglycan .
SLC41A/MgtE, integral membrane domain (SLC41_membr_dom)
Type: Domain

This entry represents the integral membrane region of SLC41 transporter proteins. SLC41 family of divalent cation transporters includes SLC41A1/2/3 from eukaryotes and MgtE from prokaryotes . MgtE is the prokaryote homologue of SLC41A1 magnesium transporter which adopts a homodimeric architecture with five transmembrane domains in the C terminus and cytosolic N terminus domains . Bacterial family members have one copy of this region while archaeal and eukaryotic sequences have two.
Magnesium transporter, MgtE intracellular domain (Mg_transptr_MgtE_intracell_dom)
Type: Domain

This domain is found at the N terminus of eubacterial magnesium transporters of the MgtE family

. This domain is an intracellular domain that has an α-helical structure. The crystal structure of the MgtE transporter shows two of 5 magnesium ions are in the interface between the N domain and the CBS domains. In the absence of magnesium there is a large shift between the N and CBS domains.
Magnesium transporter MgtE (MgtE_transporter)
Type: Family

This entry represents the MgtE family of magnesium transporters. MgtE is a highly Mg2+-selective channel gated by Mg2+ . It is an SLC41A1 orthologue found in prokaryotes, which consists of a homodimer architecture with five transmembrane domains in the C terminus and cytosolic N terminus domains. Structural and functional analyses showed MgtE conserved acidic side-chains play a key role as part of its selectivity filter. Proteins in this family contains two highly conserved aspartates that may be involved in cation binding .
Cyclin, N-terminal (Cyclin_N)
Type: Domain

Cyclins contain two domains of similar all-α fold, of which this entry is associated with the N-terminal domain.

Cyclins are eukaryotic proteins that play an active role in controlling nuclear cell division cycles , and regulate cyclin dependent kinases (CDKs). Cyclins, together with the p34 (cdc2) or cdk2 kinases, form the Maturation Promoting Factor (MPF). There are two main groups of cyclins, G1/S cyclins, which are essential for the control of the cell cycle at the G1/S (start) transition, and G2/M cyclins, which are essential for the control of the cell cycle at the G2/M (mitosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed as cells exit from mitosis (at the end of the M-phase). In most species, there are multiple forms of G1 and G2 cyclins. For example, in vertebrates, there are two G2 cyclins, A and B, and at least three G1 cyclins, C, D, and E.

Cyclin homologues have been found in various viruses, including Saimiriine herpesvirus 2 (Herpesvirus saimiri) and Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus). These viral homologues differ from their cellular counterparts in that the viral proteins have gained new functions and eliminated others to harness the cell and benefit the virus .
Mnh complex subunit C1 (Mnh_C1_su)
Type: Family

This entry represents subunit C of the Mnh complex, which is a cation antiporter, involved in K(+) and Na(+) excretion. It shares significant protein sequence similarity with various chains of the NADH-ubiquinone/plastoquinone (complex I) .
HD domain (HD_domain)
Type: Domain

The HD domain is found in a superfamily of enzymes with a predicted or known phosphohydrolase activity . These enzymes appear to be involved in the nucleic acid metabolism, signal transduction and possibly other functions in bacteria, archaea and eukaryotes.
The fact that all the highly conserved residues in the HD superfamily are histidines or aspartates suggests that coordination of divalent cations is essential for the activity of these proteins .
HDIG domain (HDIG_dom)
Type: Domain

This domain is found in a few known nucleotidyltransferases and in a large number of uncharacterised proteins. It contains four widely separated His residues, the second of which is part of an invariant dipeptide His-Asp in a region matched approximately by the motif HDIG. It appears to be related to the HD domain.
tRNA-splicing endonuclease (tRNA_splic)
Type: Family

tRNA-splicing endonucleases (

) catalyse the endonucleolytic cleavage of pre tRNA at the 5' and 3' splice sites to release the intron and produces two half tRNA molecules bearing 5' hydroxyl and 2', 3'-cyclic phosphate termini . The genes encoding these proteins are homologous in eukaryotes and archea. The eukaryotic tRNA-splicing endonucleases are heterotetrameric while the archaeal endonucleases can be split into homodimeric and homotetrameric subgroups.
tRNA intron endonuclease, catalytic domain-like (tRNA_intron_Endonuc_cat-like)
Type: Domain

This entry represents a three-layer α/β/α domain found as the catalytic domain at the C-terminal in homotetrameric tRNA-intron endonucleases , and as domains 2 and 4 (C-terminal) in the homodimeric enzymes . tRNA-intron endonucleases (

) remove tRNA introns by cleaving pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-hydroxyl termini . These enzymes recognise a pseudosymmetric substrate in which two bulged loops of three bases are separated by a stem of four bp . Although homotetrameric enzymes contain four active sites, only two participate in the cleavage, and should therefore, be considered as a dimer of dimers.
tRNA intron endonuclease, N-terminal (tRNA_intron_Endonuc_N)
Type: Domain

This entry represents a 2-layer α/β domain found at the N terminus of the homotetrameric tRNA-intron endonucleases , and as domains 1 (N-terminal) and 3 in the homodimeric enzymes . tRNA-intron endonucleases (

) remove tRNA introns by cleaving pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-hydroxyl termini . These enzymes recognise a pseudosymmetric substrate in which 2 bulged loops of 3 bases are separated by a stem of 4 bp . Although homotetrameric enzymes contain four active sites, only two participate in the cleavage, and should therefore, be considered as a dimer of dimers.
Adenine deaminase (Adenine_deam)
Type: Family

Adenine deaminase (

) hydrolyses adenine to form hypoxanthine and ammonia. The enzyme is part of a large metal dependent hydrolase superfamily . The adenine deaminase reaction is important for adenine utilization as a purine and also as a nitrogen source . It plays an important role in the purine salvage pathway and in nitrogen catabolism.
Amidohydrolase-related (Amidohydro-rel)
Type: Domain

Proteins containing this domain are enzymes from a large metal-dependent hydrolase superfamily

. The family includes adenine deaminase (

) that hydrolyses adenine to form hypoxanthine and ammonia. This reaction is important for adenine utilisation as a purine and also as a nitrogen source . The entry also includes dihydroorotase and N-acetylglucosamine-6-phosphate deacetylases (

). The domain is also found in the urease alpha subunit, where it is the catalytic domain .
Conserved hypothetical protein CHP00267 (CHP00267)
Type: Family

This family of uncharacterised proteins shows a low level of similarity (possibly meaningful) to the predicted membrane protein YLR220W, which is involved in calcium homeostatis. It shows no similarity to any other characterised protein.
This family is represented in three of the first four completed archaeal genomes, with two members in Archaeoglobus fulgidus.
Thioesterase domain (Thioestr_dom)
Type: Domain

A wide variety of enzymes contain this domain, principally thioesterases. Proteins containing this domain include 4HBT (4-hydroxybenzoyl-CoA thioesterase) (

) which catalyses the final step in the biosynthesis of 4-hydroxybenzoate from 4-chlorobenzoate in the soil dwelling microbe Pseudomonas CBS-3 . It also includes various cytosolic long-chain acyl-CoA thioester hydrolases. Long-chain acyl-CoA hydrolases hydrolyse palmitoyl-CoA to CoA and palmitate, they also catalyse the hydrolysis of other long chain fatty acyl-CoA thioesters .
Acyl-CoA thioester hydrolase YbgC/YbaW family (YbgC/YbaW)
Type: Family

This entry describes a subset of related acyl-CoA thioesterases that include several partially characterised proteins. YbgC is an acyl-CoA thioesterase associated with the Tol-Pal system and appears to be involved in phospholipid metabolism . Long-chain acyl-CoA thioesterase FadM (YbaW) is part of the FadM regulon and has a preference for 3,5-tetradecadienoyl-CoA .