SII-SWORD/CoKE huggingface dataset:
I/LWEQ domain superfamily (I/LWEQ_dom_sf)
Type: Homologous_superfamily

The I/LWEQ domain is a ~250-residue actin-binding module that is found in the C termini of functionally diverse proteins from yeast to mammals. The I/LWEQ domain contains four conserved blocks and has been named after the conserved initial residues of blocks 1-4. The I/LWEQ domain is generally found near the C terminus and in association with other domains, such as FERM or ENTH. The I/LWEQ domain has been shown to bind to F-actin and to bundle actin filaments .

The I/LWEQ domain contains a proteolysis resistant-core that has an all-α-helical structure composed of five long down-up-down-up-down antiparallelhelices connected by short loops and one short connecting α helix arranged in a progressive topology. The proteolysis-resistant core is
followed by a C-terminal latch region that adopts an α-helical conformation. The latch region can mediate oligomerization of I/LWEQ domains,
possibly as dimers, and this seems to enhance the F-actin-binding ability of the proteolysis-resistant core .

It's worth noting that the I/LWEQ domain has also been called the talin-HIP1/R/Slap2p actin- tethering C-terminal homology (THATCH) domain (HIP1/R/Slap2p denotes similarity of Slap2p to HIP1 and HIP1R) .
PAS domain superfamily (PAS-like_dom_sf)
Type: Homologous_superfamily

PAS domains are involved in many signalling proteins where they are used as a signal sensor domain . PAS domains appear in archaea, bacteria and eukaryotes. Several PAS-domain proteins are known to detect their signal by way of an associated cofactor. Heme,
flavin, and a 4-hydroxycinnamyl chromophore are used in different proteins. The PAS domain was named after three proteins that it occurs in:

Per- period circadian protein

Arnt- Ah receptor nuclear translocator protein

Sim- single-minded protein.

PAS domains are often associated with PAC domains

. It appears that these domains are directly linked, and that together they form the conserved 3D PAS fold. The division between the PAS and PAC domains is caused by major differences in sequences in the region connecting these two motifs . In human PAS kinase, this region has been shown to be very flexible, and adopts different conformations depending on the bound ligand . Probably the most surprising identification of a PAS domain was that in EAG-like K

-channels .
Phosphofructokinase superfamily (PKF_sf)
Type: Homologous_superfamily

The enzyme-catalysed transfer of a phosphoryl group from ATP is an important reaction in a wide variety of biological processes . One enzyme that utilises this reaction is phosphofructokinase (PFK), which catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, a key regulatory step in the glycolytic pathway . PFK exists as a homotetramer in bacteria and mammals (where each monomer possesses 2 similar domains), and as an octomer in yeast (where there are 4 alpha- (PFK1) and 4 beta-chains (PFK2), the latter, like the mammalian monomers, possessing 2 similar domains ). PFK is ~300 amino acids in length, and structural studies of the bacterial enzyme have shown it comprises two similar (α/β) lobes: one involved in ATP binding and the other housing both the substrate-binding site and the allosteric site (a regulatory binding site distinct from the active site, but that affects enzyme activity). The identical tetramer subunits adopt 2 different conformations: in a 'closed' state, the bound magnesium ion bridges the phosphoryl groups of the enzyme products (ADP and fructose-1,6-bisphosphate); and in an 'open' state, the magnesium ion binds only the ADP , as the 2 products are now further apart. These conformations are thought to be successive stages of a reaction pathway that requires subunit closure to bring the 2 molecules sufficiently close to react .

Deficiency in PFK leads to glycogenosis type VII (Tarui's disease), an autosomal recessive disorder characterised by severe nausea, vomiting, muscle cramps and myoglobinuria in response to bursts of intense or vigorous exercise . Sufferers are usually able to lead a reasonably ordinary life by learning to adjust activity levels .
SWAP/Surp superfamily (SWAP/Surp_sf)
Type: Homologous_superfamily

SWAP is derived from the Suppressor-of-White-APricot splicing regulator from Drosophila melanogaster. The domain is found in regulators responsible for pervasive, nonsex-specific alternative pre-mRNA splicing characteristics and has been found in splicing regulatory proteins . These ancient, conserved SWAP proteins share a colinearly arrayed series of novel sequence motifs .
ATP synthase, F1 complex, gamma subunit superfamily (ATP_synth_F1_ATPase_gsu)
Type: Homologous_superfamily

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.

F-ATPases (also known as ATP synthases, F1F0-ATPase, or H(+)-transporting two-sector ATPase) (

) are composed of two linked complexes: the F1 ATPase complex is the catalytic core and is composed of 5 subunits (alpha, beta, gamma, delta, epsilon), while the F0 ATPase complex is the membrane-embedded proton channel that is composed of at least 3 subunits (A-C), with additional subunits in mitochondria. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back. In the F1 complex, the central gamma subunit forms the rotor inside the cylinder made of the α(3)β(3) subunits, while in the F0 complex, the ring-shaped C subunits forms the rotor. The two rotors rotate in opposite directions, but the F0 rotor is usually stronger, using the force from the proton gradient to push the F1 rotor in reverse in order to drive ATP synthesis . These ATPases can also work in reverse in bacteria, hydrolysing ATP to create a proton gradient.

The ATPase F1 complex gamma subunit forms the central shaft that connects the F0 rotary motor to the F1 catalytic core. The gamma subunit functions as a rotary motor inside the cylinder formed by the α(3)β(3) subunits in the F1 complex . The most conserved region of the gamma subunit is its C terminus, which seems to be essential for assembly and catalysis.
Rab-GAP-TBC domain superfamily (Rab-GAP_TBC_sf)
Type: Homologous_superfamily

The ~200 amino acid TBC/rab GTPase-activating protein (GAP) domain is well conserved across species and has been found in a wide range of different proteins from plant adhesion molecules to mammalian oncogenes. The name TBC derives from the name of the murine protein Tbc1 in which this domain was first identified based on its similarity to sequences in the tre-2 oncogene, and the yeast regulators of mitosis, BUB2 and cdc16 . The connection of this domain with rab GTPase activation stems from subsequent in-depth sequence analyses and alignments and recent work demonstrating that it appears to contain the catalytic activities of the yeast rab GAPs, GYP1, and GYP7 .

The TBC/rab GAP domain has also been named PTM after three proteins known to contain it: the Drosophila pollux, the human oncoprotein TRE17 (oncoTRE17), and a myeloid cell line-expressed protein . The TBC/rab GAP domain contains six conserved motifs named A to F . A conserved arginine residue in the sequence motif B has been shown to be critical for the full GAP activity . Resolution of the 3D structure of the TBC/rab GAP domain of GYP1 has shown that it is a fully α-helical V-shaped molecule. The conserved arginine residue is positioned at the side of the narrow cleft on the concave site of the V-shaped molecule. It has been proposed that this cleft is the binding site for the GTPase. The conserved arginine residue probably functions as a catalytic arginine finger analogous to that seen in ras and Rho-GAPs. The two key features of the arginine finger activation mechanism appear to be (i) the positioning of the catalytically essential GTPase glutamine side chain via a hydrogen bonding interaction between the glutamine carbamoyl-NH2 group and the main chain carbonyl group of the GAP arginine, and (ii) the polarization of the gamma-phosphate group or the stabilization of charge on it via the interaction of the positively charged side chain guanidinoyl group of the GAP arginine .
Large ribosomal subunit protein eL19 superfamily (60S_ribosomal_eL19_sf)
Type: Homologous_superfamily

This entry represents the large ribosomal subunit protein eL19, found in archaea and eukaryotes .
Cellulose-binding domain superfamily (CBD_sf)
Type: Homologous_superfamily

The microbial degradation of cellulose and xylans requires several types of enzymes, such as endoglucanases (

), cellobiohydrolases (

) (exoglucanases), or xylanases (

) . Structurally, cellulases and xylanases generally consist of a catalytic domain joined to a CBD by a short linker sequence rich in proline and/or hydroxy-amino acids. The CBD of several fungal cellulases has been shown to consist of 36 amino acid residues, and it is found either at the N-terminal or at the C-terminal extremity of the enzymes. As it is shown in the following schematic representation, there are four conserved cysteines in this type of CBD domain, all involved in disulphide bonds.

+----------------+
| +-----|---------+
| | | |
xxxxxxxCxxxxxxxxxxCxxxxxCxxxxxxxxxCx
Gamma-carboxyglutamic acid-rich (GLA) domain superfamily (GLA-like_dom_SF)
Type: Homologous_superfamily

The GLA (gamma-carboxyglutamic acid-rich) domain contains glutamate residues that have been post-translationally modified by vitamin K-dependent carboxylation to form gamma-carboxyglutamate (Gla) . All glutamic acid (Glu) residues present in the GLA domain are potential carboxylation sites; in coagulation proteins, all Gu residues are modified to Gla, while in osteocalcin and matrix Gla proteins only some Glu residues are modified to Gla.
Cytochrome c oxidase subunit III-like superfamily (Cyt_c_oxidase_su3-like_sf)
Type: Homologous_superfamily

Cytochrome c oxidase (

) is the terminal enzyme of the respiratory chain of mitochondria and many aerobic bacteria. It catalyses the transfer of electrons from reduced cytochrome c to molecular oxygen:

4 cytochrome c
+2
+ 4 H
+
+ O
2
--> 4 cytochrome c
+3
+ 2 H
2
O

This reaction is coupled to the pumping of four additional protons across the mitochondrial or bacterial membrane .

Cytochrome c oxidase is an oligomeric enzymatic complex that is located in the mitochondrial inner membrane of eukaryotes and in the plasma membrane of aerobic prokaryotes. The core structure of prokaryotic and eukaryotic cytochrome c oxidase contains three common subunits, I, II and III. In prokaryotes, subunits I and III can be fused and a fourth subunit is sometimes found, whereas in eukaryotes there are a variable number of additional small polypeptidic subunits . The functional role of subunit III is not yet understood.

As the bacterial respiratory systems are branched, they have a number of distinct terminal oxidases, rather than the single cytochrome c oxidase present in the eukaryotic mitochondrial systems. Even though the cytochrome o complex oxidises quinol (ubiquinol) and does not catalyse the oxidation of reduced cytochrome c, they belong to the same haem-copper oxidase superfamily as cytochrome c oxidases. Members of this family share sequence similarities in all three core subunits: subunit I is the most conserved subunit, whereas subunit II is the least conserved .

This entry represents a structural domain found in cytochrome c and ubiquinol oxidase subunit III. The overall structure of these enzymes is similar .
Rap/Ran-GAP superfamily (Rap/Ran-GAP_sf)
Type: Homologous_superfamily

Structural domains comprising this superfamily share the structure of two shown to be homologous GTPase activating proteins for Rap and Ran. Both are Ras-like guanine-nucleotide-binding proteins (GNBPs) involved in a variety of signal-transduction processes and their activity is regulated by GEFs and GAPs.

Rap small G proteins have been implicated in various cellular processes such as exocytosis, cAMP signalling, cell adhesion and cell proliferation. Rap proteins acts as molecular switches, with an active GTP-bound form and an inactive GDP-bound form . The inactive GDP bound form is promoted by GTPase-activating proteins (GAPs). GAP proteins specific for Rap contain a conserved region of around 200 amino-acid residues, the RapGAP domain. This domain can accelerate the GTP hydrolysis activity of Rap by five orders of magnitude .

Ran, also known as GTP-binding nuclear protein, is on the other hand essential for the translocation of RNA and proteins through the nuclear pore complex and has been implicated in the control of DNA synthesis and cell cycle progression.
E2/EBNA1, C-terminal (E2/EBNA1_C_sf)
Type: Homologous_superfamily

This superfamily represents a ferredoxin-like fold found in the C terminus of the Papillomavirus E2 protein and the the Epstein-Barr virus (strain GD1) nuclear antigen 1 (EBNA1). This region is the DNA-binding and dimerisation domain found in EBNA1 .

E2 is an early regulatory protein found in the dsDNA papillomaviruses. The viral genome is a 7.9-kb circular DNA that codes for at least eight early and two late (capsid) proteins. The products of the early genes E6 and E7 are oncoproteins that destabilise the cellular tumour suppressors p53 and pRB. The product of the E1 gene is a helicase necessary for viral DNA replication. The products of the E2 gene play key roles in the regulation of viral gene transcription and DNA replication. During early stages of viral infection, the E2 protein represses the transcription of the oncogenes E6 and E7, reintroduction of E2 into cervical cancer cell-lines leads to repression of E6/E7 transcription, stabilisation of the tumour suppressor p53, and cell-cycle arrest at the G1 phase of the cell cycle. E2 can also induce apoptosis by a p53-independent mechanism.
Sushi/SCR/CCP superfamily (Sushi/SCR/CCP_sf)
Type: Homologous_superfamily

The extracellular sushi domain is characterised by a consensus sequence spanning ~60 residues containing four invariant cysteine residues forming two disulfide-bridges (I-III and II-IV), a highly conserved tryptophan, and conserved glycine, proline, and hydrophobic residues . Sushi domains are known to be involved in many recognition processes, including the binding of several complement factors to fragments C3b and C4b . The sushi domain is also known as the complement control protein (CCP) module or the short consensus repeat (SCR).
Large ribosomal subunit protein bL36 superfamily (Ribosomal_bL36_sp)
Type: Homologous_superfamily

Ribosomal protein bL36 (also known as L36) is the smallest protein from the large subunit of the prokaryotic ribosome. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities can be grouped into: bacterial L36; algal and plant chloroplast L36; Cyanelle L36; fungal and animal L36. L36 is a small basic and cysteine-rich protein of around 40 amino-acid residues probably involved in late assembly of the 50S particle, in vitro translation and cell growth. This protein shows a zinc-binding CxxC motif. Its paralogue encoded by ykgO (as named in Escherichia coli), lacks the zinc-binding site and replaces RpmJ when zinc availability is low .

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
RNA-binding domain superfamily (RBD_domain_sf)
Type: Homologous_superfamily

Many eukaryotic proteins containing one or more copies of a putative RNA-binding domain of about 90 amino acids are known to bind single-stranded RNAs . The largest group of single strand RNA-binding proteins is the eukaryotic RNA recognition motif (RRM) family that contains an eight amino acid RNP-1 consensus sequence . RRM proteins have a variety of RNA binding preferences and functions, and include heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing (SR, U2AF, Sxl), protein components of small nuclear ribonucleoproteins (U1 and U2 snRNPs), and proteins that regulate RNA stability and translation (PABP, La, Hu) . The RRM in heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) appears to have two RRM-like domains with specialised features for protein recognition . The motif also appears in a few single stranded DNA binding proteins.

The typical RRM consists of four anti-parallel β-strands and two α-helices arranged in a β-α-β-β-α-β fold with side chains that stack with RNA bases. Specificity of RNA binding is determined by multiple contacts with surrounding amino acids. A third helix is present during RNA binding in some cases . The RRM is reviewed in a number of publications .

This entry also includes some bacterial putative RNA-binding proteins.
Small ribosomal subunit protein bS6 superfamily (Ribosomal_bS6_sf)
Type: Homologous_superfamily

The small subunits of bacterial and eukaryotic ribosomes have the same overall shapes (with structural elements described as head, body, platform, beak and shoulder). Ribosomal protein bS6 is one of the proteins from the small ribosomal subunit. . In Escherichia coli, bS6 is known to bind together with bS18 to 16S ribosomal RNA. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities, groups bacterial, red algal chloroplast and cyanelle bS6 ribosomal proteins.

Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites . About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits.

Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome .
Photosystem I reaction centre subunit PsaK superfamily (PSI_centre_PsaK_sf)
Type: Homologous_superfamily

Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product .

Photosystem I (PSI) is an integral membrane protein complex that uses light energy to mediate electron transfer from plastocyanin to ferredoxin. It is found in the chloroplasts of plants and cyanobacteria. PSI is composed of at least 14 different subunits, two of which are small hydrophobic proteins of about 7 to 9 Kd and evolutionary related, PsaG (also known as PSI-G) and PsaK (also known as PSI-K), both integral membrane proteins. Cyanobacteria contain only PsaK . While cyanobacterial PSI have phycobilisomes to harvest light, eukaryotic PSI have a membrane-imbedded peripheral antenna .
HECT, E3 ligase catalytic domain (Hect_E3_ubiquitin_ligase)
Type: Homologous_superfamily

The HECT (Homologous to the E6-AP Carboxyl Terminus) domain is an around 350 amino acids motif that has been identified in proteins that all belong to a particular E3 ubiquitin-protein ligase family . HECT domain containing proteins accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then transfer it to lysine side chains of target proteins, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains. The site of ubiquitin thioester formation is a conserved cysteine residue located in the last 32-36 aa of the HECT domain . The amino-terminal part of the HECT domain has been involved in E2 binding . Once linked to ubiquitin, the target proteins are degraded in the 26 S proteasome.