SII-SWORD/CoKE huggingface dataset:
Photosynthetic reaction centre, cytochrome c subunit (Photosyn_RC_cyt_c-su)
Type: Family

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

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

In the purple bacterium Rhodocyclus gelatinosus (Rhodopseudomonas gelatinosa), a high potential Fe-S protein (HiPIP) acts as an electron donor to reaction centre-bound cyt bc1 under anaerobic conditions in the light, while cyt c acts as a soluble electron carrier under aerobic conditions in the dark in order to re-reduce the oxidized electron donor .
Polysaccharide lyase family 8, central domain (Lyase_8_central_dom)
Type: Domain

Proteins containing this central domain consist of a group of secreted bacterial lyase enzymes capable of acting on a variety of substrates. One such enzyme is hyaluronate lyase, a Streptococcal surface enzyme that degrades hyaluronan and chondroitin, thereby helping to spread the bacteria throughout host tissues . Hyaluronate lyase (

) is a four-domain enzyme containing an N-terminal carbohydrate-binding domain, a spacer domain, a catalytic domain, and a C-terminal domain that modulates access to the catalytic cleft of the enzyme. The central domain has a β-sandwich topology, with 18 strands in two sheets. Other bacterial enzymes that display this structure include the central domain of chondroitin AC lyase (

) , the central domain of xanthan lyase (

) , and the third domain of chondroitin ABC lyase (

) . This entry represents these domains of hyaluronate lyase, chondroitin AC lyase, xanthan lyase and chondroitin ABC lyase. This domain if almost always associated with the polysaccharide lyase family 8 C-terminal domain (

).
Transcription initiation factor TAFII31 (TFIID-31)
Type: Family

Human transcription initiation factor TFIID is composed of the TATA-binding polypeptide (TBP) and at least 13 TBP-associated factors (TAFs) that collectively or individually are involved in activator-dependent transcription . This entry represents the N terminus of the 31kDa subunit (42kDa in Drosophila) of transcription initiation factor IID (TAFII31), also known as transcription initiation factor TFIID subunit 9 (TAF9). It has been shown that TAF9 interacts directly with different transcription factors such as p53, herpes simplex virus activator vp16 and the basal transcription factor TFIIB. Binding to p53 is an essential requirement for p53 mediated transcription activation.

TAF9 is a component other TBP-free TAF complexes containing the GCN5-type histone acetyltransferase. Several TAFs interact via histone-fold (HFD) motifs; HFD is the interaction motif involved in heterodimerization of the core histones and their assembly into nucleosome octamers. The minimal HFD contains three α-helices linked by two loops and is found in core histones, TAFS and many other transcription factors. TFIID has a histone octamer-like substructure. TFIID has a histone octamer-like substructure. TAF9 is a shared subunit of both, histone acetyltransferase complex (SAGA) and TFIID complexes. TAF9 domain interacts with TAF6 to form a novel histone-like heterodimer that is structurally related to the histone H3 and H4 oligomer .
Transcription regulator HTH, APSES-type DNA-binding domain (Tscrpt_reg_HTH_APSES-type)
Type: Domain

The APSES (ASM-1, Phd1, StuA, EFG1, and Sok2) domain is a ~110-residue sequence-specific DNA-binding domain found in a family of fungal transcription factors and other DNA-binding proteins. The APSES domain is found associated with ankyrin repeats (see

,

) and a heterodimerization domain .

The APSES domain consists of a six-stranded β-sheet segment folded against two pairs of α-helices in the topology of the winged helix-turn-helix (HTH) family of proteins . The αA/αB helical pair corresponds to the HTH motif . Some proteins known to contain an APSES domain are listed below:

Saccharomyces cerevisiae (Baker's yeast) Mlu-1 box binding protein (MBP1,

); Mlu-1 and Swi6 together make up the transcription factor complex MBF (Mlu-1-binding factor), which binds to the Mlu1 cell-cycle box (MCB) elements found in the promoters of many DNA synthesis genes .

Schizosaccharomyces pombe (Fission yeast) cell division cycle-related proteins res1/sct1 (

) and res2/pct1 (

), which are homologous to MBP1.

S. pombe start control protein cdc10 (

).

Emericella nidulans (Aspergillus nidulans) cell pattern formation-associated protein stuA (

). It regulates the transformation of undifferentiated hyphal elements into a complex multicellular structure.

S. cerevisiae transcription factor PHD1 (

).

S. cerevisiae protein SOK2 (

). It represses the transition from unicellular growth to pseudohyphae.

Candida albicans (Yeast) enhanced filamentous growth protein (EFG1,

)).

Neurospora crassa ascospore maturation 1 protein (Asm-1,

). It has a role in spore maturation.

S. pombe bouquet formation protein 4 (

), which is a nuclear membrane protein that connects telomeres to the nuclear envelop (NE) during both vegetative growth and meiosis. Bqt4 does not seem to bind DNA, but acts as an adaptor between Bqt3 and Rap1 .
Clathrin adaptor, alpha-adaptin, appendage, C-terminal subdomain (Clathrin_a-adaptin_app_sub_C)
Type: Domain

Proteins synthesized on the ribosome and processed in the endoplasmic reticulum are transported from the Golgi apparatus to the trans-Golgi network (TGN), and from there via small carrier vesicles to their final destination compartment. These vesicles have specific coat proteins (such as clathrin or coatomer) that are important for cargo selection and direction of transport . Clathrin coats contain both clathrin (acts as a scaffold) and adaptor complexes that link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. The two major types of clathrin adaptor complexes are the heterotetrameric adaptor protein (AP) complexes, and the monomeric GGA (Golgi-localising, Gamma-adaptin ear domain homology, ARF-binding proteins) adaptors .

AP (adaptor protein) complexes are found in coated vesicles and clathrin-coated pits. AP complexes connect cargo proteins and lipids to clathrin at vesicle budding sites, as well as binding accessory proteins that regulate coat assembly and disassembly (such as AP180, epsins and auxilin). There are different AP complexes in mammals. AP1 is responsible for the transport of lysosomal hydrolases between the TGN and endosomes . AP2 associates with the plasma membrane and is responsible for endocytosis . AP3 is responsible for protein trafficking to lysosomes and other related organelles . AP4 is less well characterised. AP complexes are heterotetramers composed of two large subunits (adaptins), a medium subunit (mu) and a small subunit (sigma). For example, in AP1 these subunits are gamma-1-adaptin, beta-1-adaptin, mu-1 and sigma-1, while in AP2 they are alpha-adaptin, beta-2-adaptin, mu-2 and sigma-2. Each subunit has a specific function. Adaptins recognise and bind to clathrin through their hinge region (clathrin box), and recruit accessory proteins that modulate AP function through their C-terminal ear (appendage) domains. Mu recognises tyrosine-based sorting signals within the cytoplasmic domains of transmembrane cargo proteins . One function of clathrin and AP2 complex-mediated endocytosis is to regulate the number of GABA(A) receptors available at the cell surface .

AP adaptor alpha-adaptin can be divided into a trunk domain and the C-terminal appendage domain (or ear domain), separated by a linker region. The C-terminal appendage domain regulates translocation of endocytic accessory proteins to the bud site .

This entry represents a subdomain of the appendage (ear) domain of alpha-adaptin from AP clathrin adaptor complexes. This domain has a three-layer arrangement, α-β-α, with a bifurcated antiparallel β-sheet .
Piwi domain (Piwi)
Type: Domain

The piwi domain is a protein domain found in piwi proteins and a large number of related nucleic acid-binding proteins, especially those that bind and cleave RNA. The function of the domain is double stranded-RNA-guided hydrolysis of single stranded-RNA, as has been determined in the argonaute family of related proteins .
Transcription factor TFIIE beta subunit, DNA-binding domain (TFIIE_bsu_DNA-bd)
Type: Domain

This entry represents the central core DNA-binding domain of the TFIIE beta subunit.

Initiation of eukaryotic mRNA transcription requires melting of promoter DNA with the help of the general transcription factors TFIIE and TFIIH. In higher eukaryotes, the general transcription factor TFIIE consists of two subunits: the large alpha subunit (

) and the small beta (

). TFIIE beta has been found to bind to the region where the promoter starts to open to be single-stranded upon transcription initiation by RNA polymerase II. The approximately 120-residue central core domain of TFIIE beta plays a role in double-stranded DNA binding of TFIIE .

The TFIIE β-central core DNA-binding domain consists of three helices with a β-hairpin at the C terminus, resembling the winged helix proteins. It shows a novel double-stranded DNA-binding activity where the DNA-binding surface locates on the opposite side to the previously reported winged helix motif by forming a positively charged furrow .

Transcription Factor IIE (TFIIE) β winged-helix (or forkhead) domain is located at the central core region of TFIIE beta. The winged-helix is a form of helix-turn-helix (HTH) domain which typically binds DNA with the 3rd helix. The winged-helix domain is distinguished by the presence of a C-terminal β-strand hairpin unit (the wing) that packs against the cleft of the tri-helical core. Although most winged-helix domains are multi-member families, TFIIE β-winged-helix domain is typically found as a single orthologous group .
Nitrile hydratase, beta subunit (Nitrile_hydratase_bsu)
Type: Family

This entry represents the beta subunit.

Nitrile hydratases (

) are bacterial enzymes that catalyse the hydration of nitrile compounds to the corresponding amides. They are used as biocatalysts in acrylamide production, one of the few commercial scale bioprocesses, as well as in environmental remediation for the removal of nitriles from waste streams. Nitrile hydratases are composed of two subunits, alpha and beta, and are normally active as a tetramer, α(2)β(2). Nitrile hydratases contain either a non-haem iron or a non-corrinoid cobalt centre, both types sharing a highly conserved peptide sequence in the alpha subunit (CXLCSC) that provides all the residues involved in coordinating the metal ion. Each type of nitrile hydratase specifically incorporated its metal with the help of activator proteins encoded by flanking regions of the nitrile hydratase genes that are necessary for metal insertion. The Fe-containing enzyme is photo-regulated: in the dark the enzyme is inactivated due to the association of nitric oxide (NO) to the iron, while in the light the enzyme is active by photo-dissociation of NO. The NO is held in place by a claw setting formed through specific oxygen atoms in two modified cysteines and a serine residue in the active site . The cobalt-containing enzyme is unaffected by NO, but was shown to undergo a similar effect with carbon monoxide . Fe-and cobalt-containing enzymes also display different inhibition patterns with nitrophenols.

Thiocyanate hydrolase (SCNase) is a cobalt-containing metalloenzyme with a cysteine-sulphinic acid ligand that hydrolyses thiocyanate to carbonyl sulphide and ammonia .

The two enzymes, nitrile hydratase and SCNase, are homologous over regions corresponding to almost the entire coding regions of the genes: the beta and alpha subunits of thiocyanate hydrolase were homologous to the amino-and carboxyl-terminal halves of the beta subunit of nitrile hydratase, and the gamma subunit of thiocyanate hydrolase was homologous to the alpha subunit of nitrile hydratase .
GYF domain (GYF)
Type: Domain

The glycine-tyrosine-phenylalanine (GYF) domain is an around 60-amino acid domain which contains a conserved GP[YF]xxxx[MV]xxWxxx[GN]YF motif. It was identified in the human intracellular protein termed CD2 binding protein 2 (CD2BP2), which binds to a site containing two tandem PPPGHR segments within the cytoplasmic region of CD2. Binding experiments and mutational analyses have demonstrated the critical importance of the GYF tripeptide in ligand binding. A GYF domain is also found in several other eukaryotic proteins of unknown function . It has been proposed that the GYF domain found in these proteins could also be involved in proline-rich sequence recognition .

Resolution of the structure of the CD2BP2 GYF domain by NMR spectroscopy revealed a compact domain with a β-β-α-β-β topology, where the single α-helix is tilted away from the twisted, anti-parallel β-sheet. The conserved residues of the GYF domain create a contiguous patch of predominantly hydrophobic nature which forms an integral part of the ligand-binding site . There is limited homology within the C-terminal 20-30 amino acids of various GYF domains, supporting the idea that this part of the domain is structurally but not functionally important .
UDP-N-acetylenolpyruvoylglucosamine reductase (MurB)
Type: Family

Members of this family are UDP-N-acetylenolpyruvoylglucosamine reductase enzymes, which are also called UDP-N-acetylmuramate dehydrogenases.

This enzyme is responsible for the synthesis of UDP-N-acetylmuramic acid in bacterial cell wall biosynthesis and consequently provides an attractive target for the design of antibacterial agents.
Methylenetetrahydrofolate reductase-like (Mehydrof_redctse-like)
Type: Family

This represents the catalytic domain of 5,10-methylenetetrahydrofolate reductase from prokaryotes and methylenetetrahydrofolate reductase (MTHFR) from eukaryotes (

). Both generate 5-methyltetrahydrofolate from 5,10-methylenetetrahydrofolate.

Mammalian and yeast MTHFRs are homodimers in which each subunit contains an N-terminal catalytic domain, and a C-terminal regulatory domain [(interpro:IPR053806]) to which the allosteric inhibitor adenosylmethionine binds . NADPH is the preferred reductant. In humans, there are several clinically significant mutations in MTHFR that result in hyperhomocysteinemia, which is a risk factor for the development of cardiovascular disease .

The bacterial enzyme is a homotetramer. MTHFRs of enteric bacteria comprise shorter chains around 300 residues in length. Their sequences can be aligned with the N-terminal catalytic domains of the eukaryotic MTHFRs . Escherichia coli MTHFR, along with plant MTHFRs, prefer NADHs as the source of reducing equivalents . The structure of E. coli MTHFR is known to be a TIM barrel .
MD-2-related lipid-recognition domain (ML_dom)
Type: Domain

The MD-2-related lipid-recognition (ML) domain is implicated in lipid recognition, particularly in the recognition of pathogen related products. It has an immunoglobulin-like β-sandwich fold similar to that of E-set Ig domains. This domain is present in proteins from plants, animals and fungi, including the following proteins:

Epididymal secretory protein E1 (also known as Niemann-Pick C2 protein -Npc2), which is known to bind cholesterol. Niemann-Pick disease type C2 is a fatal hereditary disease characterised by accumulation of low-density lipoprotein-derived cholesterol in lysosomes .

House-dust mite allergen proteins such as Der f 2 from Dermatophagoides farinae and Der p 2 from Dermatophagoides pteronyssinus .
Transcriptional coactivator p15 (PC4), C-terminal (PC4_C)
Type: Domain

This entry represents a ssDNA binding domain found at the C-terminal end of YdbC from Lactococcus lactis, Activated RNA polymerase II transcriptional coactivator p15 from humans and other PC4 family members.

YdbC, which adopts a dimeric fold, shows a concave four-stranded antiparallel sheet followed by a C-terminal helix in a similar configuration to PC4 .

p15 has a bipartite structure composed of an amino-terminal regulatory domain and a carboxy-terminal cryptic DNA-binding domain . The DNA-binding activity of the carboxy-terminal is disguised by the amino-terminal p15 domain. Activity is controlled by protein kinases that target the regulatory domain. Its interaction with the tumor suppressor protein p53 may play a role in certain neurodegenerative diseases .
Alpha trans-inducing protein (Alpha-TIF) (Alpha_TIF)
Type: Family

Alpha-TIF (VP16) from Herpes Simplex virus is an essential tegument protein involved in the transcriptional activation of viral immediate early (IE) promoters (alpha genes) during the lytic phase of viral infection. VP16 associates with cellular transcription factors to enhance transcription rates, including the general transcription factor TFIIB and the transcriptional coactivator PC4. The N-terminal residues of VP16 confer specificity for the IE genes, while the C-terminal residues are responsible for transcriptional activation. Within the C-terminal region are two activation regions that can independently and cooperatively activate transcription . VP16 forms a transcriptional regulatory complex with two cellular proteins, the POU-domain transcription factor Oct-1 and the cell-proliferation factor HCF-1 . VP16 is an alpha/beta protein with an unusual fold. Other transcription factors may have a similar topology.
Cyclin-dependent kinase inhibitor domain (CDI_dom)
Type: Domain

Cell cycle progression is negatively controlled by cyclin-dependent kinases inhibitors (CDIs). CDIs are involved in cell cycle arrest at the G1 phase. This entry represents a domain found in CDIs .
Adenovirus DNA-binding, all-alpha domain (Adenovirus_DNA-bd_a)
Type: Domain

This entry represents a domain of the viral DNA-binding protein, a multi functional protein involved in DNA replication and transcription control .
Cytochrome c oxidase subunit VIIa, metazoa (Cytc_oxidase_su7a_met)
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.

In eukaryotes, in addition to the three large subunits, I, II and III, that form the catalytic centre of the enzyme complex, there are a variable number of small polypeptidic subunits. This family is composed of the heart and liver isoforms of cytochrome c oxidase subunit VIIa. Subunit VIIa has two tissue-specific isoforms that are expressed in a developmental manner. VIIa-H is expressed in heart and skeletal muscle but not smooth muscle. VIIa-L is expressed in liver and non-muscle tissues .
Methyl-coenzyme M reductase, gamma subunit (Me_CoM_Rdtase_gsu)
Type: Family

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

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

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

This entry represents the gamma subunit, which has a complex α-helical/β-sheet topology.
Methyl-coenzyme M reductase, beta subunit (Me_CoM_Rdtase_bsu)
Type: Family

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

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

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

This entry represents the beta subunit.
Methylpurine-DNA glycosylase (MPG)
Type: Family

Methylpurine-DNA glycosylase (MPG, or alkyladenine DNA glycosylase (AAG)) is a base excision-repair protein, catalyzing the first step in base excision repair by cleaving damaged DNA bases within double-stranded DNA to produce an abasic site. MPG bends DNA by intercalating between the base pairs, causing the damaged base to flip out of the double helix and into the enzyme active site for cleavage. It is responsible for the hydrolysis of the deoxyribose N-glycosidic bond, excising 3-methyladenine and 3-methylguanine from damaged DNA . Its action is induced by alkylating chemotherapeutics, as well as deaminated and lipid peroxidation-induced purine adducts . MPG without an N-terminal extension excises hypoxanthine with one-third of the efficiency of full-length MPG under similar conditions, suggesting that is function may largely be attributable to the N-terminal extension .

Although AAG represents one of six DNA glycosylase classes, it lacks the helix-hairpin-helix active site motif associated with other base excision repair glycosylases and is structurally distinct from them.
Large coat protein (Como_LCP)
Type: Family

The virus capsid is composed 60 icosahedral units, each of which is composed of one copy of each of the two coat proteins. This family contains the large coat protein (LCP) of the comoviridae viral family.
RNA2 polyprotein (RNA2_polyprotein)
Type: Family

RNA2 is a polyprotein movement protein: transports viral genome to neighbouring plant cells directly through plasmosdesmata, without any budding. The movement protein allows efficient cell to cell propagation, by bypassing the host cell wall barrier. It acts by forming a tubular structure at the host plasmodesmata, enlarging it enough to allow free passage of virion capsids .