SII-SWORD/CoKE huggingface dataset:
Mediator complex, subunit Med7 superfmaily (Mediatior_Med7_sf)
Type: Homologous_superfamily

This superfamily consists of several eukaryotic proteins, which are homologues of the yeast MED7 protein. Activation of gene transcription in metazoans is a multistep process that is triggered by factors that recognise transcriptional enhancer sites in DNA. These factors work with co-activators such as MED7 to direct transcriptional initiation by the RNA polymerase II apparatus .

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11.
TccP2/EspF(U)-like superfamily (TccP2/EspF(U)-like_sf)
Type: Homologous_superfamily

This superfamily includes EspF(U) and related proteins.

Enteropathogenic Escherichia coli O127:H6 attaches to the intestinal mucosa through actin pedestals that are created after it has injected the Type III secretion protein EspF (E. coli secreted protein F-like protein from prophage U) into the cells. EspF recruits the actin machinery by activating the WASP (Wiscott-Aldrich syndrome protein) family of actin nucleating factors . Subsequent cell-death (apoptosis) is caused by EspF being targeted to the mitochondria as a consequence of its mitochondrial targeting sequence. Import into mitochondria leads to a loss of membrane potential, leakage of cytochrome c and activation of the apoptotic caspase cascade. Mutation of leucine to glutamic at position 16 of EspF (L16E) resulted in the failure of EspF import into mitochondria; mitochondrial membrane potential was not affected and cell death abolished. This suggests that the targeting of EspF to mitochondria is essential for bacterial pathogenesis and apoptosis .
TMEM14 superfamily (TMEM14_sf)
Type: Homologous_superfamily

This entry includes a group of transmembrane proteins, including protein FATTY ACID EXPORT 1 (FAX1) from Arabidopsis and TMEM14 from animals. FAX1 mediates the export of free fatty acid from the plastids and is required for biogenesis of the outer pollen cell wall, in particular for the assembly of exine and pollen coat and for the release of ketone wax components . The Zebrafish TMEM14 is required for normal heme biosynthesis . The structure of human TMEM14 showed a three helical bundle .
Histone chaperone Rtt106, N-terminal domain superfamily (Rtt106_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal domain of Rtt106 from Saccharomyces cerevisiae. Rtt106 is a histone chaperone that contributes to the deposition of newly synthesized acetylated Histone 3 Lysine 56 (H3K56ac) carrying H3-H4 complex on replicating DNA. The N-terminal domain of Rtt106 homodimerizes and interacts with H3-H4 independently of acetylation .
Ribosomal protein L3, domain 3, archaeal-type superfamily (Ribosomal_L3_dom_3_arc_sf)
Type: Homologous_superfamily

This entry represents a domain found in L3 proteins from archaea and eukaryotes.

Ribosomal protein L3 (also known as uL3) is one of the proteins from the large ribosomal subunit. In Escherichia coli, L3 is known to bind to the 23S rRNA and may participate in the formation of the peptidyltransferase centre of the ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities includes bacterial, red algal, cyanelle, mammalian, yeast and Arabidopsis thaliana L3 proteins; archaeal Haloarcula marismortui HmaL3 (HL1), and yeast mitochondrial YmL9 .
RNA polymerase Rpb1, clamp domain superfamily (RNA_pol_Rpb1_clamp_domain)
Type: Homologous_superfamily

RNA polymerases catalyse the DNA-dependent polymerisation of RNA. Prokaryotes contain a single RNA polymerase compared to three in eukaryotes (not including mitochondrial and chloroplast polymerases). This clamp domain is a mobile domain involved in positioning the DNA, maintenance of the transcription bubble and positioning of the nascent RNA strand .
TubC, N-terminal docking domain superfamily (TubC_N_sf)
Type: Homologous_superfamily

This is the N-terminal docking domain (also termed the amino acid adenylation domain) found in TubC proteins from the tubulysin polyketide synthase and nonribosomal polypeptide synthetase (PKS-NRPS) system, which binds to C-terminal docking domain of TubB . This domain can also be found at the N terminus of bacitracin synthase 2 (BacB) from Bacillus licheniformis and Pyochelin synthetase PchF from Pseudomonas aeruginosa.
Kinetochore null protein 2, Myb-like DNA-binding domain superfamily (Knl-2_Myb-like_DNA-bd_sf)
Type: Homologous_superfamily

This superfamily represents the Myb-like DNA-binding domain of Knl2 (kinetochore null protein 2) from C. elegans, a Myb DNA-binding domain-containing protein required for CENP-A loading and kinetochore assembly . It has an all-helical structure.
Hepatitis C virus core protein, chain A superfamily (HCV_core_chain_A)
Type: Homologous_superfamily

This superfamily represents the N-terminal chain A region of the Hepatitis C virus core protein.

The HCV core protein is located at the N terminus of the polyprotein and is followed by the signal sequence located between the core protein and the E1 envelope glycoprotein. This signal sequence targets the nascent HCV polyprotein to the endoplasmic reticulum (ER), allowing the translocation of E1 to the ER lumen. Cleavage by a signal peptidase in the ER lumen releases the N-terminal end of E1, leaving the 191-amino acids (aa) core protein anchored by its C-terminal signal peptide . This 191aa polypeptide, also known as p23, is the immature form of the core protein; p23 is further processed by an intramembrane protease, the signal peptide peptidase (SPP), that removes the ER anchor , releasing p21, the N-terminal 179aa mature form of the core protein . Core protein (p21) is responsible for packaging viral RNA to form a viral nucleocapsid, and it also promotes virion budding .
Inositol polyphosphate 1-phosphatase, domain 1 (INPP1_dom_1)
Type: Homologous_superfamily

This superfamily represents a domain found in inositol polyphosphate 1-phosphatase INPP1 from animals. INPP1 is involved in the inositol phosphate second messenger signalling pathway. It has a core of 155 residues, which includes residues essential for metal binding and catalysis. An interesting property of the enzymes of this superfamily is their sensitivity to Li+. The targets and mechanism of action of Li+ are unknown, but overactive inositol phosphate signalling may account for symptoms of manic depression .
Cyclin-dependent kinase inhibitor domain superfamily (CDI_dom_sf)
Type: Homologous_superfamily

Cell cycle progression is negatively controlled by cyclin-dependent kinases inhibitors (CDIs). CDIs are involved in cell cycle arrest at the G1 phase. This superfamily represents a domain found in CDIs .
Secreted effector protein SptP, N-terminal domain superfamily (SptP_N_sf)
Type: Homologous_superfamily

This superfamily represents a domain found in the Salmonella effector protein SptP, which interacts with SicP chaperone dimers mainly through four regions of its chaperone-binding domain. The structure of the SptP-SicP complex contains four molecules of SicP, aligned in a linear fashion and arranged in two sets of tightly bound homodimers that bind two SptP molecules. The SicP homodimers do not interact with each other, but are held together by a molecular interface formed between two SptP molecules. Each SptP molecule is wrapped around by three SicP chaperones (two chaperones from one homodimer and a third one from the opposite homodimer pair) .
Photosystem II CP43 reaction centre protein superfamily (PSII_PsbC_sf)
Type: Homologous_superfamily

PSII is a multisubunit protein-pigment complex containing polypeptides both intrinsic and extrinsic to the photosynthetic membrane . Within the core of the complex, the chlorophyll and β-carotene pigments are mainly bound to the antenna proteins CP43 (PsbC) and CP47 (PsbB), which pass the excitation energy on to the reaction centre proteins D1 (Qb, PsbA) and D2 (Qa, PsbD) that bind all the redox-active cofactors involved in the energy conversion process. The PSII oxygen-evolving complex (OEC) oxidises water to provide protons for use by PSI, and consists of OEE1 (PsbO), OEE2 (PsbP) and OEE3 (PsbQ). The remaining subunits in PSII are of low molecular weight (less than 10kDa), and are involved in PSII assembly, stabilisation, dimerisation, and photo-protection .

This superfamily represents a domain found in the intrinsic antenna protein CP43 (PsbC), which is one of two such proteins found in the reaction centre of PSII, both of which can bind to chlorophyll 'a' and β-carotene, passing the excitation energy on to the reaction centre . It has a mainly α-helical structure.
Malto-oligosyltrehalose trehalohydrolase, E-set domain superfamily (Trehalose_TreZ_E-set_sf)
Type: Homologous_superfamily

This superfamily represents the E-set ("early" set) domain of the trehalose biosynthetic enzyme malto-oligosyltrehalose trehalohydrolase, formally known as 4-alpha-D-{(1->4)-alpha-D-glucano}trehalose trehalohydrolase (

), which adopts an immunoglobulin-like fold. It is the TreZ protein of the TreYZ pathway for trehalose biosynthesis, and alternative to the OtsAB system.
Dinoflagellate luciferase repeat (Dino_Luciferase_rpt_sf)
Type: Homologous_superfamily

This entry represents the repeats found in dinoflagellate luciferases.

Luciferase is involved in catalysing the light emitting reaction in bioluminescence, and luciferin binding protein (LBP) is known to bind to luciferin (the substrate for luciferase) to stop it reacting with the enzyme and therefore switching off the bioluminescence function. The expression of these two proteins is controlled by a circadian clock at the translational level, with synthesis and degradation occurring on a daily basis .
Luciferase, helical bundle domain superfamily (Luciferase_hlx-bundle_dom_sf)
Type: Homologous_superfamily

This domain superfamily is found associated with the catalytic domain of dinoflagellate luciferase. Luciferase is involved in catalysing the light emitting reaction in bioluminescence. This domain has a three helix bundle structure that holds four important histidines that are thought to play a role in the pH regulation of the enzyme .
3,4-dihydroxyphenylacetate 2,3-dioxygenase, C-terminal domain superfamily (HPCD_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal mobile fragment found in 3,4-dihydroxyphenylacetate 2,3-dioxygenase . This domain is C-terminal to the C-terminal barrel domain.

HPCD catalyses the second step in the degradation of 4-hydroxyphenylacetate to succinate and pyruvate. The aromatic ring of 4-hydroxyphenylacetate is opened by this dioxygenase to yield the 3,4-diol product, 2-hydroxy-5-carboxymethylmuconate semialdehyde. HPCD is a homotetramer and each monomer contains two structurally homologous barrel-shaped domains at the N- and C- terminus. The active-site metal is located in the C-terminal barrel and plays an essential role in the catalytic mechanism. Most extradiol dioxygenases contain Fe(II) in their active site, but HPCD can be activated by either Mn(II) or Fe(II). These enzymes belong to the type I class II family of extradiol dioxygenases. The class III 3,4-dihydroxyphenylacetate 2,3-dioxygenases belong to a different superfamily .
Resuscitation-promoting factor Rpf1, C-terminal superfamily (Rpf1_C_sf)
Type: Homologous_superfamily

This entry represents the C-terminal domain of Resuscitation-promoting factor Rpf1 from Corynebacterium glutamicum, a factor that stimulates resuscitation or dormant cells . The function of this domain is not known.
Nitrate reductase, alpha subunit, N-terminal domain superfamily (Nitr_red_alph_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal tail of the respiratory nitrate reductase alpha chain. The nitrate reductase complex is a dimer of heterotrimers each consisting of an alpha, beta and gamma chain. The N-terminal tail of the alpha chain interacts with the beta chain and contributes to the stability of the heterotrimer .
Photosystem I reaction centre subunit N superfamily (PSAN_sf)
Type: Homologous_superfamily

Photosystem I reaction centre subunit N (PSAN, also known as PSI-N) may function in mediating the binding of the antenna complexes to the PSI reaction centre and core antenna . PSI-N subunit does not bind pigments .
Nitrosopumilus output domain 5-like superfamily (NitrOD5-like_sf)
Type: Homologous_superfamily

NitrOD5 (Nitrosopumilus output domain 5) is found in thaumarchaea, either in stand-alone form or in combination with the signal transduction response regulator, receiver domain (

) .
TM_1086 superfamily (TM_1086_sf)
Type: Homologous_superfamily

This domain superfamily can be found at the N terminus of TM_1086 (

) and related proteins.
TM_1086, SG structure domain (TM_1086_SG_dom)
Type: Homologous_superfamily

This domain superfamily can be found in TM_1086 and related proteins. This domain consists of 3-layer sandwich.
V-type ATP synthase C/D subunit, domain 3 superfamily (V-type_ATPase_csu/dsu_dom_3)
Type: Homologous_superfamily

This superfamily represents the third domain of V-type ATPase which is made up of helices from the N-terminal and C-terminal domains arranged in two central and four peripheral helices. These subunits are divided into three similar domains, each of which has essentially the same topology .

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

The V-ATPases (or V1V0-ATPase) and A-ATPases (or A1A0-ATPase) are each composed of two linked complexes: the V1 or A1 complex contains the catalytic core that hydrolyses/synthesizes ATP, and the V0 or A0 complex that forms the membrane-spanning pore. The V-ATPase folding, localisation, and stability is made possible through the formation of a luminal glycan coat by the glycolipids and the glycosylated V0 subunits . The V- and A-ATPases both contain rotary motors, one that drives proton translocation across the membrane and one that drives ATP synthesis/hydrolysis . The V- and A-ATPases more closely resemble one another in subunit structure than they do the F-ATPases, although the function of A-ATPases is closer to that of F-ATPases.
Epidermal growth factor receptor, juxtamembrane domain (Egfr_JX_dom)
Type: Homologous_superfamily

Receptor tyrosine kinases (RTKs) are transmembrane receptors that have intrinsic, cytoplasmic tyrosine kinase activity. Juxtamembrane regions in RTKs have been shown to play important regulatory functions. Their kinase activity is generally autoinhibited by its JX domain in the absence of ligand-stimulated tyrosine phosphorylation, due to the inhibitory Tyr phosphorylation sites found in the JX domain . This superfamily represents the JX domain of the EGF receptor .
P-type trefoil domain superfamily (P_trefoil_dom_sf)
Type: Homologous_superfamily

A cysteine-rich domain of approximately forty five amino-acid residues has been found in some extracellular eukaryotic proteins . It is known as either the 'P', 'trefoil' or 'TFF' domain, and contains six cysteines linked by three disulphide bonds with connectivity 1-5, 2-4, 3-6. This leads to a characteristic three leafed structure ('trefoil'). The P-type domain is clearly composed of three looplike regions. The central core of the domain consists of a short two-stranded antiparallel β-sheet, which is capped by an irregular loop and forms a central hairpin (loop 3). The β-sheet is preceded by a short α-helix, with majority of the remainder of the domain contained in two loops, which lie on either side of the central hairpin.

This domain has been found in a variety of extracellular eukaryotic proteins , including:

Protein pS2 (TFF1), a protein secreted by the stomach mucosa

Spasmolytic polypeptide (SP) (TFF2), a protein of about 115 residues that inhibits gastrointestinal motility and gastric acid secretion

Intestinal trefoil factor (ITF) (TFF3)

Xenopus laevis stomach proteins xP1 and xP4

Xenopus integumentary mucins A.1 (FIM-A.1 or preprospasmolysin) and C.1 (FIM-C.1), proteins which may be involved in defence against microbial infections by protecting the epithelia from the external environment

Xenopus skin protein xp2 (or APEG)

Zona pellucida sperm-binding protein B (ZP-B)

Intestinal sucrase-isomaltase (

/

), a vertebrate membrane bound, multifunctional enzyme complex which hydrolyses sucrose, maltose and isomaltose

Lysosomal alpha-glucosidase (

)
Endosialidase, C-terminal domain superfamily (Endosialidase_C_dom_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of endosialidase, which is approximately 160 amino acids in length. There are two conserved sequence motifs: VSR and YGA. The endosialidase protein forms homotrimeric molecules and this domain complexes into a tail-spike stalk. The stalk region folds in a triple β-helix that is interrupted by a small triple β-prism domain. The tail-spike is a multifunctional protein device used by the phage to fulfil the following functions: (i) to adsorb to the bacterial polySia capsule (ii) to de-polymerise the capsule to gain access to the outer bacterial membrane, and finally (iii) to mediate tight adhesion to the membrane, a prerequisite for the initiation of the infection cycle .
Short tail fibre protein, C-terminal superfamily (Short_tail_fibre_C_sf)
Type: Homologous_superfamily

This superfamily represents the C-terminal domain of the bacteriophage T4 short tail fibre.

During virus attachment, Bacteriophage T4 binds Escherichia coli with its long tail fibres and then binds irreversibly to the lipopolysaccharides component on the cell surface using its short tail fibres . The short tail fibres are composed of a single protein, gp12. The C-terminal domain of gp12 is a receptor-binding domain consisting of three extensively intertwined monomers .
DNA-directed primase/polymerase protein (PRIMPOL)
Type: Family

PRIMPOL has both DNA polymerase and DNA/RNA primase activities. It is involved in downstream repriming of stalled forks during both nuclear and mitochondrial DNA replication. It pays an important part in DNA damage tolerance . It is predicted to possess an archaeo-eukaryotic primase and a UL52-like zinc finger domain . The primase activity of PRIMPOL is essential for many functions in the nucleus. However, the role of PRIMPOL polymerase activity is still unclear, as PRIMPOL synthesizes DNA with limited processivity, rarely incorporating more than four nucleotides on an undamaged template .
DUF3349, helical bundle (DUF3349_helical)
Type: Homologous_superfamily

This superfamily contains mainly functionally uncharacterised proteins found in bacteria, typically between 99 to 124 amino acids in length. The most representative domain was characterised in Rv0543c - a monomeric bundle of five α-helices rigidly held together by a largely conserved group of hydrophobic amino acid side chains. The fold observed for Rv0543c may be unique for Rv0543c and the other members of the DUF3349 superfamily. According to literature, the DUF3349 proteins are predicted to be good drug targets because they are predominantly in the Mycobacterium and Rhodococcus bacterial species .
HP0184-like superfamily (HP0184-like_sf)
Type: Homologous_superfamily

This superfamily includes HP0184 and related proteins. Their function is not clear.
tRNA uridine 5-carboxymethylaminomethyl modification enzyme, C-terminal subdomain superfamily (MnmG_C_subdom_sf)
Type: Homologous_superfamily

This entry represents the C-terminal subdomain of MnmG (also known as GidA). It consists of the last highly conserved 3 helices of the C-terminal domain, which are rather short and form a small bundle . MnmG is a tRNA modification enzyme found in bacteria and mitochondria that forms a complex with MnmE which is involved in the formation of methyluridine derivatives at the wobble uridine base in some tRNAs . Based on mutational analysis the C-terminal domain has been suggested to be implicated in binding of the D-stem of tRNA and to be responsible for the interaction with protein MnmE .
DUF2063, N-terminal superfamily (DUF2063_N_sf)
Type: Homologous_superfamily

This superfamily represents the N-terminal part of uncharacterised proteins, including a Neisseria protein (

,

) which comprises an α-helical bundle with 4 main helices. From genomic context and the fold of the C-terminal part, it is suggested that this protein is involved in transcriptional regulation .
PolC, middle finger subdomain superfamily (PolC_middle_finger_sf)
Type: Homologous_superfamily

The structure of DNA polymerases adopts a shape resembling a right hand with thumb (guides the nascent DNA duplex as it leaves the active site), finger (binds the incoming nucleotide), and palm (active site) domains. This superfamily represents the middle finger subdomain of DNA polymerase III PolC-type .
HAD-superfamily hydrolase, subfamily IA, REG-2-like, capping domain superfamily (HAD-SF_hydro_IA_REG-2-like_cap)
Type: Homologous_superfamily

This family of proteins includes uncharacterised sequences from eukaryotes, cyanobacteria and Leptospira as well as the DREG-2 protein from Drosophila melanogaster (Fruit fly) which has been identified as a rhythmically (diurnally) regulated gene . This family is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs . The subfamilies are defined based on the location and the observed or predicted fold of a so-called, capping domain, , or the absence of such a domain. This family is a member of subfamily 1A in which the cap domain consists of a predicted α helical bundle found in between the first and second catalytic motifs. A distinctive feature of this family is a conserved tandem pair of tryptophan residues in the cap domain. The most divergent sequences included within the scope of this entry are from plants and have "FW" at this position instead. Most likely, these sequences, like the vast majority of HAD sequences, represent phosphatase enzymes.

This superfamily represents the inserted capping domain between the first and second catalytic domains.