SII-SWORD/CoKE huggingface dataset:
Small ribosomal subunit protein eS4, central region (Ribosomal_eS4_central_region)
Type: Domain

A number of eukaryotic and archaeal ribosomal proteins can be grouped on the basis of sequence similarities. One of them consists of the small ribosomal subunit protein eS4 from archaea and eukaryotes. Small ribosomal subunit protein eS4A from yeast is also known as S7/YS6; archaeal members are also known as S4e; and mammalian and plant cytoplasmic proteins were previously known as S4 . Two highly similar isoforms of mammalian S4 exist, one coded by a gene on chromosome Y, and the other on chromosome X. These proteins have 233 to 264 amino acids.

This entry represents the central region of these 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 .
mRNA capping enzyme, C-terminal (mRNA_cap_enzyme_C)
Type: Domain

This domain is found at the C terminus of the mRNA capping enzyme. The mRNA capping enzyme in yeasts is composed of two separate chains: alpha a mRNA guanyltransferase and beta an RNA 5'-triphosphate. X-ray crystallography reveals a large conformational change during guanyl transfer by mRNA capping enzymes . Binding of the enzyme to nucleotides is specific to the GMP moiety of GTP. The viral mRNA capping enzyme is a monomer that transfers a GMP cap onto the end of mRNA that terminates with a 5'-diphosphate tail.
POU domain (POU)
Type: Domain

POU proteins are eukaryotic transcription factors containing a bipartite DNA binding domain referred to as the POU domain. The acronym POU (pronounced 'pow') is derived from the names of three mammalian transcription factors, the pituitary-specific Pit-1, the octamer-binding proteins Oct-1 and Oct-2, and the neural Unc-86 from Caenorhabditis elegans. POU domain genes have been described in organisms as divergent as C. elegans, Drosophila, Xenopus, zebrafish and human but have not been yet identified in plants and fungi. The various members of the POU family have a wide variety of functions, all of which are related to the development of an organism .
Methylthiotransferase, N-terminal (Methylthiotransferase_N)
Type: Domain

The methylthiotransferase (MTTase) or miaB-like family is named after the (dimethylallyl)adenosine tRNA MTTase miaB protein, which catalyses a C-H to C-S bond conversion in the methylthiolation of tRNA. A related bacterial enzyme rimO performs a similar methylthiolation, but on a protein substrate. RimO acts on the ribosomal protein uS12 and forms a separate MTTase subfamily. The miaB-subfamily includes mammalian CDK5 regulatory subunit-associated proteins and similar proteins in other eukaryotes. Two other subfamilies, yqeV and CDKAL1, are named after a Bacillus subtilis and a human protein, respectively. While yqeV-like proteins are found in bacteria, CDKAL1 subfamily members occur in eukaryotes and in archaebacteria. The likely MTTases from these 4 subfamilies contain an N-terminal MTTase domain, a central radical generating fold and a C-terminal TRAM domain (see

). The core forms a radical SAM fold (or AdoMet radical), containing a cysteine motif CxxxCxxC that binds a [4Fe-4S] cluster . A reducing equivalent from the [4Fe-4S]+ cluster is used to cleave S-adenosylmethionine (SAM) to generate methionine and a 5'-deoxyadenosyl radical. The latter is thought to produce a reactive substrate radical that is amenable to sulphur insertion . The N-terminal MTTase domain contains 3 cysteines that bind a second [4Fe-4S] cluster, in addition to the radical-generating [4Fe-4S] cluster, which could be involved in the thiolation reaction. The C-terminal TRAM domain is not shared with other radical SAM proteins outside the MTTase family. The TRAM domain can bind to RNA substrate and seems to be important for substrate recognition. The tertiary structure of the central radical SAM fold has six β/α motifs resembling a three-quarter TIM barrel core (see

) . The N-terminal MTTase domain might form an additional [β/α]2 TIM barrel unit .
DNA helicase, Holliday junction RuvA type, domain I, bacterial (DNA_helicase_Holl-junc_RuvA_I)
Type: Domain

In prokaryotes, RuvA, RuvB, and RuvC process the universal DNA intermediate of homologous recombination, termed Holliday junction. The tetrameric DNA helicase RuvA specifically binds to the Holliday junction and facilitates the isomerization of the junction from the stacked folded configuration to the square-planar structure . In the RuvA tetramer, each subunit consists of three domains, I, II and III, where I and II form the major core that is responsible for Holliday junction binding and base pair rearrangements of Holliday junction executed at the crossover point, whereas domain III regulates branch migration through direct contact with RuvB.

This entry represents domain I of RuvA, which has an OB-fold structure. This domain forms the RuvA tetramer contacts .
Transcription factor Otx, C-terminal (Otx_TF_C)
Type: Domain

Otx proteins constitute a class of vertebrate homeodomain-containing transcription factors that have been shown to be essential for anterior head formation, including brain morphogenesis. They are orthologous to the product of the Drosophila head gap gene, orthodenticle (Otd), and appear to play similar roles in both, since the developmental abnormalities caused by disruption of these transcription factors in one, can be recovered by substitution of the factor(s) from the other. Such studies have provided strong evidence that there exists a conserved genetic programme for insect and mammalian brain development, which presumably arose in a more primitive common ancestor .

Two vertebrate orthodenticle-related transcription factors have been indentified, Otx1 and Otx2, which have sizes of 355 and 289 residues respectively. They contain a bicoid-like homeodomain, which features a conserved lysine residue at position 9 of the DNA recognition helix, which is thought to confer high-affinity binding to TAATCC/T elements on DNA . Otd-like transcription factors have also been found in zebrafish and certain lamprey species.
Translation elongation factor P/YeiP, conserved site (Transl_elong_P/YeiP_CS)
Type: Conserved_site

Elongation factor P (EF-P) is a prokaryotic protein translation factor required for efficient peptide bond synthesis on 70S ribosomes from fMet-tRNAfMet . Probably functions indirectly by altering the affinity of the ribosome for aminoacyl-tRNA, thus increasing their reactivity as acceptors for peptidyl transferase.

This entry represents a conserved sequence region found near the C terminus.
Galactitol permease IIC component (EIIC-GAT)
Type: Family

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS), a major carbohydrate active-transport system, catalyses the phosphorylation of incoming sugar substrates concomitant with their translocation across the cell membrane.

This family represents the IIC component of the PTS galactitol-specific family. Gat family PTS systems typically have 3 components: IIA, IIB and IIC .
Transcription factor AP-2, C-terminal (TF_AP2_C)
Type: Domain

Activator protein-2 (AP-2) transcription factors constitute a family of closely related and evolutionarily conserved proteins that bind to the DNA
consensus sequence 5'-GCCNNNGGC-3' and stimulate target gene transcription . Five different isoforms of AP-2 have been identified in mammals, termed AP-2 alpha, beta, gamma, delta and epsilon. Each family member shares a common structure, possessing a proline/glutamine-rich domain in the N-terminal region, which is responsible for transcriptional activation , and a helix-span-helix domain in the C-terminal region, which mediates dimerisation and site-specific DNA binding .

The AP-2 family have been shown to be critical regulators of gene expression during embryogenesis. They regulate the development of facial prominence and limb buds, and are essential for cranial closure and development of the lens ; they have also been implicated in tumorigenesis. AP-2 protein expression levels have been found to affect cell transformation, tumour growth and metastasis, and may predict survival in some types of cancer . Mutations in human AP-2 have been linked with bronchio-occular-facial syndrome and Char Syndrome, congenital birth defects characterised by craniofacial deformities and patent ductus arteriosus, respectively .

This entry represents the C-terminal region of these proteins, including the helix-span-helix domain.
Cdc37, N-terminal domain (Cdc37_N_dom)
Type: Domain

Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases. This entry corresponds to the N-terminal kinase binding domain of these proteins . It is found N-terminal to a Hsp90 chaperone (heat shock protein 90) binding domain (

). Expression of a construct consisting of only the N-terminal domain of Saccharomyces pombe Cdc37 has been shown to result in cellular viability. This indicates that interactions with the cochaperone Hsp90 may not be essential for Cdc37 function .
Peptidase M4 domain (Peptidase_M4_domain)
Type: Domain

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This group of metallopeptidases that belong to the MEROPS peptidase family M4 (thermolysin family, clan MA(E)). The protein fold of the peptidase domain of thermolysin (MEROPS identifier M04.001), is the type example for members of the clan MA. The thermolysin family is composed only of secreted eubacterial endopeptidases. The zinc-binding residues of thermolysin are H-142, H-146 and E-166, with E-143 acting as the catalytic residue. Thermolysin also contains four calcium-binding sites, which contribute to its unusual thermostability. The family also includes enzymes from a number of pathogens, including Legionella and Listeria, and the protein pseudolysin (MEROPS identifier M04.005), all with a substrate specificity for an aromatic residue in the P1' position. Three-dimensional structure analysis has shown that the enzymes undergo a hinge-bend motion during catalysis. Pseudolysin has a broader specificity, acting on large molecules such as elastin and collagen, possibly due to its wider active site cleft .

This entry represents a domain found in peptidase M4 family members.
NADH:ubiquinone oxidoreductase intermediate-associated protein 30 (NADH-UbQ_OxRdtase-assoc_prot30)
Type: Domain

Mitochondrial complex I intermediate-associated protein 30 (CIA30) is present in human and mouse, and also in Schizosaccharomyces pombe (Fission yeast) which does not contain the NADH dehydrogenase component of complex I, or many of the other essential subunits. This means it is not directly involved in oxidative phosphorylation . In Drosophila it has been shown to be a chaperone required for assembly complex I .
Peptidase M10 serralysin, C-terminal (Peptidase_M10B_C)
Type: Domain

Serralysins are peptidases related to mammalian matrix metallopeptidases (MMPs). The peptidase unit is found at the N-terminal, while this domain at the C-terminal forms a corkscrew and is thought to be important for secretion of the protein through the bacterial cell wall. This domain contains the hemolysin-type calcium-binding repeat.
SWI/SNF and RSC complexes subunit Ssr4, N-terminal (Ssr4_N)
Type: Domain

This is the N-terminal domain of the SWI/SNF and RSC complexes subunit Ssr4 from S. pombe, a member of the chromatin structure remodeling complex (RSC) and the SWI/SNF complex . RSC is involved in transcription regulation and nucleosome positioning which controls, particularly, membrane and organelle development genes. The ATP-dependent chromatin remodelling complex SWI/SNF is required for the positive and negative regulation of gene expression of a large number of genes through the regulation of nucleosome remodelling .

The structure of this domain revealed that it has a novel fold comprising an antiparallel β-sheet of seven strands with α-helices on one side and random coil on the other . It contains the highly conserved motif WxxxxxPxxGxxxxxxxxxxxxxxxDG.
Nitrogen regulatory protein areA, GATA-like domain (AreA_GATA)
Type: Domain

This entry represents fungal proteins containing GATA domains, including nitrogen regulatory protein areA, a transcription activator that binds the consensus DNA element 5'-CGATAG-3' and mediates nitrogen metabolite repression . The entry also contains

that is thought to be a negative regulator of RAS-cAMP pathway in S. cerevisiae and the S. pombe member is a GAF1 transcription factor

.
TMEM115/Pdh1/Rbl19 (TMEM115/Pdh1/Rbl19)
Type: Family

This entry represents a group of eukaryotic transmembrane proteins, including TMEM115 from animals, Pdh1 from fission yeasts and Rbl19 from Arabisopsis. Human TMEM115 is an integral membrane protein of the Golgi complex involved in retrograde transport . Budding yeast TMEM115 homologue, YOL107W, has been shown to localise COP II vesicles .
Inositolphosphorylceramide synthase subunit Kei1 (Kei1)
Type: Family

Kei1 is a subunit of Saccharomyces cerevisiae inositol phosphorylceramide (IPC) synthase . It is localised to the Golgi and is cleaved by the late Golgi processing endopeptidase Kex2 . Kei1 is essential for both the activity and the Golgi localization of IPC synthase .
Vacuolar import/degradation Vid27, C-terminal (VID27_C)
Type: Domain

Vid27 is a cytoplasmic protein of unknown function, possibly regulates import of fructose-1,6-bisphosphatase into Vacuolar Import and Degradation (Vid) vesicles and is not essential for proteasome-dependent degradation of fructose-1,6-bisphosphatase (FBPase) .

This entry represents the C-terminal region of Vid27, which is predicted to contain a WD40 repeat domain .
Protein FAM32A (FAM32A)
Type: Family

FAM32A, also known as OTAG12, has been linked to ovarian tumour in humans and mice .
Sphingolipid delta4-desaturase, N-terminal (Sphingolipid_d4-desaturase_N)
Type: Domain

This small domain appears to be specific to sphingolipid delta 4-desaturase. Sphingolipids are important membrane signalling molecules involved in many different cellular functions in eukaryotes. Sphingolipid delta 4-desaturase catalyses the formation of (E)-sphing-4-enine . Some proteins with this domain have bifunctional delta 4-desaturase/C-4-hydroxylase activity. Delta 4-desaturated sphingolipids may play a role in early signalling required for entry into meiotic and spermatid differentiation pathways during Drosophila spermatogenesis .
Telomere repeat-binding factor, dimerisation domain (Telomere_rpt-bd_fac_dimer_dom)
Type: Domain

Telomeres function to shield chromosome ends from degradation and end-to-end fusions, as well as preventing the activation of DNA damage checkpoints. Telomeric repeat binding factor (TRF) proteins TRF1 and TRF2 are major components of vertebrate telomeres required for regulation of telomere stability. TRF1 and TRF2 bind to telomeric DNA as homodimers. Dimerisation involves the TRF homology (TRFH) subdomain contained within the dimerisation domain. The TRFH subdomain is important not only for dimerisation, but for DNA binding, telomere localisation, and interactions with other telomeric proteins. The dimerisation domains of TRF1 and TRF2 show the same multi-helical structure, arranged in a solenoid conformation similar to TPR repeats, which can be divided into an α-α superhelix and a long α hairpin .

The two related human TRF proteins hTRF1 and hTRF2 form homodimers and bind directly to telomeric TTAGGG repeats via the myb DNA binding domain

at the carboxy terminus . TRF1 is implicated in telomere length regulation and TRF2 in telomere protection . Other telomere complex associated proteins are recruited through their interaction with either TRF1 or TRF2. The fission yeast protein Taz1p (telomere-associated in Schizosaccharomyces pombe (Fission yeast) has similarity to both hTRF1 and hTRF2 and may perform the dual functions of TRF1 and TRF2 at fission yeast telomeres .

This entry represents the dimerisation domain.
Tethering factor for nuclear proteasome Cut8/Sts1 (Cut8/Sts1_fam)
Type: Family

This entry includes fission yeast Cut8 protein and its homologue, Sts1.
Protein of unknown function DUF1757 (DUF1757)
Type: Family

This entry shows proteins that are about 150 amino acids in length and have no known function.
Large ribosomal subunit protein mL54 (Ribosomal_mL54)
Type: Family

This entry represents the large ribosomal subunit protein mL54 from eukaryotes , previously known as MRPL37 in yeast and MRPL54 in human .

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 .
Cysteine-rich secretory protein (Cysteine_rich_secretory)
Type: Domain

This entry is found on Crisp proteins which contain

and has been termed the Crisp domain. It is found in the mammalian reproductive tract and the venom of reptiles, and has been shown to regulate ryanodine receptor Ca2+ signalling . It contains 10 conserved cysteines which are all involved in disulphide bonds and is structurally related to the ion channel inhibitor toxins BgK and ShK .
p53, transactivation domain (p53_transactivation_domain)
Type: Domain

The binding of the p53 transactivation domain by regulatory proteins regulates p53 transcription activation. This entry is comprised of a single amphipathic α helix and contains a highly conserved motif .

The p53 tumour suppressor is a protein found in increased amounts in a wide variety of transformed cells. It is also detectable in many proliferating non-transformed cells, but it is undetectable or present at low levels in resting cells. It is frequently mutated or inactivated in many types of cancer. p53 seems to act as a tumour suppressor in some, but probably not all, tumour types. p53 has been implicated in cell cycle regulation, particularly in the monitoring of genomic DNA integrity prior to replication; for this reason it has been dubbed 'guardian of the genome'. p53 can be divided into different functional domains: an N-terminal transactivation domain (

), a proline-rich domain, a DNA-binding domain (

) which contains a conserved site (

), a tetramerisation domain (

) and a C-terminal regulatory region.
Cdc37, C-terminal (Cdc37_C)
Type: Domain

Cdc37 is a protein required for the activity of numerous eukaryotic protein kinases. This entry corresponds to the C-terminal domain whose function is unclear. It is found C-terminal to the Hsp90 chaperone (heat shock protein 90) binding domain (

) and the N-terminal kinase binding domain of Cdc37 (

) .
Cdc37, Hsp90 binding (Cdc37_Hsp90-bd)
Type: Domain

Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases. This entry corresponds to the Hsp90 chaperone (heat shock protein 90) binding domain of Cdc37 . It is found between the N-terminal Cdc37 domain (

), which is predominantly involved in kinase binding, and the C-terminal domain of Cdc37 (

) whose function is unclear.
Mitochondrial import protein Pam17 (Pam17)
Type: Family

The presequence translocase-associated motor (PAM) drives the completion of preprotein translocation into the mitochondrial matrix. The Pam17 subunit is required for formation of a stable complex between cochaperones Pam16 and Pam18 and promotes the association of Pam16-Pam18 with the presequence translocase . Mitochondria lacking Pam17 are selectively impaired in the import of matrix proteins .