SII-SWORD/CoKE huggingface dataset:
Hepatitus C virus, Non-structural 5a protein, C-terminal (HCV_NS5a_C)
Type: Domain

Although Hepatitis A virus, Hepatitis B virus, and Hepatitis C virus have similar names, because they all cause liver inflammation, these are distinctly different viruses both genetically and clinically. The Hepatitis C virus (HCV) is a small (50-80 nm in diameter), enveloped, single-stranded, positive sense RNA virus. It is member of the family Flaviviridae. There are seven genotypes and a number of subtypes with diverse geographic distributions. The genome of HCV consists of a single open reading frame. At the 5' and 3' ends of the RNA are the UTR regions that are not translated into proteins but are important to translation and replication of the viral RNA. The 5' UTR has a ribosome binding site (IRES - Internal ribosome entry site) that starts the translation of unique polyprotein that is later cut by cellular and viral proteases into 10 active structural and non-structural smaller proteins .

This entry represents the C-terminal region of the Hepatitus C virus, NS5a protein. The molecular function of the non-structural 5a protein is uncertain. The NS5a protein is phosphorylated when expressed in mammalian cells. It is thought to interact with the dsRNA dependent (interferon inducible) kinase PKR .
Tegument protein UL11, Herpesvirus (Tegument_UL11_Herpesvir)
Type: Family

The UL11 gene product (also known as cytoplasmic envelopment protein 3) of herpes simplex virus is a membrane-associated tegument protein that is incorporated into the HSV virion and functions in viral envelopment . UL11 is acylated, which is crucial for lipid raft association .
Protein of unknown function DUF3871 (DUF3871)
Type: Family

This entry represents proteins of unknown function found primarily in Bacteroides species. The B. thetaiotaomicron gene appears to be upregulated in the presence of host or other bacterial species compared to growth in pure culture .
Hepatitis A virus, protein VP1-2A (Hepatitis_A_VP1-2A)
Type: Family

This is a family of the viral protein found in hepatitis A viruses. HAV is unique among picornaviruses in targeting the liver .
Conjugative transposon protein TraQ, bacteroidetes (TraQ_bacteroidetes)
Type: Family

This entry represents the conjugative transposon protein TraQ from Bacteroides thetaiotaomicron and similar sequences from Bacteroides species. TraQ shares structural similarity to other proteins involved in pili production for bacterial cell attachment . The gene coding for this protein, located in a conjugate transposon, appears to be upregulated in the presence of host or other bacterial species compared to growth in pure culture .
Protein of unknown function DUF3873 (DUF3873)
Type: Family

This entry represents a family of uncharacterised proteins found primarily in Bacteroides species. The Bacteroides thetaiotaomicron gene appears to be upregulated in the presence of host or other bacterial species compared to growth in pure culture .
Argonaut, glycine-rich domain (Argonaut_Gly-rich)
Type: Domain

This domain is found in the N terminus of some argonaut proteins. Argonaut (AGO) proteins are involved in RNA-mediated post-transcriptional gene silencing .
Non-structural protein NSP3, N-terminal, betacoronavirus (NSP3_N_bCoV)
Type: Domain

The multi-domain non-structural protein NSP3 is the largest protein encoded by the coronavirus (CoV) genome, with an average molecular mass of about 200 kD. While some of the domains differ between CoV genera, eight domains of NSP3 exist in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (also called "hypervariable region"), a macrodomain (also named "X domain"), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2pro), the NSP3 ectodomain (3Ecto, also called "zinc-finger domain"), as well as the domains Y1 and CoV-Y of unknown functions. There are also two transmembrane regions, TM1 and TM2, which exist in all CoVs .

This entry corresponds to the N-terminal domain of NSP3 found in betacoronavirus. This includes the NSP3a domain which has the ubiquitin-like 1 (UB1) and glutamic acid-rich acidic (AC) hypervariable domains . NSP3a interacts with numerous other proteins involved in replication and transcription and may serve as a scaffolding protein for these processes. The N-terminal NSP3a domain interacts with N protein to co-localise genomic RNA with the nascent replicase-transcriptase complex at the earliest stages of infection, essential for the virus . The C-terminal Glu-rich subdomain is best described as a flexible tail attached to the globular UB1 subdomain .
Peroxisome assembly protein 22 (Peroxin-22)
Type: Family

Peroxin-22 is an integral peroxisomal membrane protein. The N terminus of peroxin-22 is located in the matrix, while the C terminus is located in the cytosol. Peroxin-22 interacts with the ubiquitin-conjugating enzyme Pex4p, anchoring it at the peroxisomal membrane . This association is required for ubiquitination of peroxisomal import receptor Pex5p mediated by Pex4p .
Cytoplasmic envelopment protein 3, herpesvirus (Herpesvirus_CEP3)
Type: Family

This entry contains viral proteins that are involved in virion envelopment and egress. It includes Epstein-Barr virus (EBV) BBLF1 protein (also known as cytoplasmic envelopment protein 3 and Herpesvirus UL11 homologue), which is present in the tegument layer of EBV and is involved in virion maturation. BBLF1 also participates in viral entry at the fusion step probably by regulating the core fusion machinery. BBLF1 has been shown to localize to the trans-Golgi network along with gp350/220, a site where final envelopment of EBV particles takes place. BBLF1 shares 13 to 15% amino acid sequence identity with the herpes simplex virus 1 UL11 and cytomegalovirus UL99 tegument proteins, and like these it is a myristoylated and palmitoylated protein .
Bacteroidetes-Associated Carbohydrate-binding Often N-terminal (BACON)
Type: Domain

The BACON (Bacteroidetes-Associated Carbohydrate-binding Often N-terminal) domain is an all-β domain found in diverse architectures, principally in combination with carbohydrate-active enzymes and proteases. These architectures suggest a carbohydrate-binding function, which is also supported by the nature of BACON's few conserved amino-acids. The phyletic distribution of BACON and other data tentatively suggest that it may frequently function to bind mucin . Further work with the characterised structure of a member of glycoside hydrolase family 5 enzyme,

, has found no evidence for carbohydrate-binding for this domain .
Protein of unknown function DUF2685 (DUF2685)
Type: Family

This is a family of uncharacterised bacteriophage proteins. Their function in unknown.
Protein of unknown function DUF3853 (DUF3853)
Type: Family

This entry represents a family of uncharacterised proteins that were found by clustering human gut metagenomic sequences .
Baseplate hub assembly protein, bacteriophage T4-like (Baseplate_phage_T4-like)
Type: Family

Proteins in this family are found in T4-like viruses. They have a single completely conserved residue S that may be functionally important. The family includes the two base plate proteins from bacteriophage T4: Gp51 and Gp26, encoded by late genes .

Gp26 is a structural component of central hub of the baseplate. It associates with Gp25 (tail lysozyme) in the assembly process. Gp51 is essential for the formation of the central hub of the phage baseplate, playing a catalytic role for the central hub formation. It is also a structural component of the hub .
Protein of unknown function DUF3839 (DUF3839)
Type: Family

This is a family of uncharacterised proteins that are found in Trichomonas.
Alpha-ketoglutarate-dependent dioxygenase FTO, C-terminal (FTO_C)
Type: Domain

Alpha-ketoglutarate-dependent dioxygenase FTO, also known as Fat mass and obesity-associated protein, is a nucleus protein which belongs to the FTO family. This enzyme is a dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation . FTO activity is highest towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. FTO has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine ,

]. FTO has no activity towards 1-methylguanine. It has no detectable activity towards double-stranded DNA. FTO requires molecular oxygen, alpha-ketoglutarate and iron. FTO contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. It contributes to the regulation of body size and body fat accumulation as well .

FTO contains two well-defined domains: an N- (residues 32-326) and a C- (residues 327-498) terminal domain. The N-terminal domain of this protein is a DNA demethylase . This entry represents the C-terminal domain (CTD). This domain is α-helical with α7, α8 and α10 forming a three-helix bundle. One end of the helix bundle interacts with the N-terminal domain of FTO, and it has been suggested that the CTD plays a role in stabilising the NTD's conformation since the NTD only exhibits enzymatic activity when co-expressed with the CTD .
Alpha-ketoglutarate-dependent dioxygenase FTO, catalytic domain (FTO_cat_dom)
Type: Domain

Alpha-ketoglutarate-dependent dioxygenase FTO, also known as Fat mass and obesity-associated protein, is a nucleus protein which belongs to the FTO family. This enzyme is a dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation . FTO activity is highest towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. FTO has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine ,

]. FTO has no activity towards 1-methylguanine. It has no detectable activity towards double-stranded DNA. FTO requires molecular oxygen, alpha-ketoglutarate and iron. FTO contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. It contributes to the regulation of body size and body fat accumulation as well .

This domain is the catalytic AlkB-like domain from the FTO protein . This domain catalyses a demethylase activity with a preference for 3-methylthymidine.
Extender of the chronological lifespan protein Ecl1/2/3 (Ecl1/2/3)
Type: Family

This family is involved in the chronological life-span (CLS) of yeast. Over-expression leads to an extended viability of wild-type strains, indicating a role in regulation . There are four cysteine residues conserved in the N-terminal region involved in zinc binding and have been shown to be essential for protein functions. Ecl family proteins are essential for sexual development caused by zinc depletion in S. pombe. They are also important for cellular response to zinc limitation .

Ecl family genes are involved in not only CLS extension but also cellular responses, such as stress tolerance, autophagy, cell cycle arrest, and sexual differentiation, under conditions of starvation of various nutrients, including metals . Ecl family proteins from fission yeast were reported as novel factors that suppressed the target of rapamycin (TOR) complex 1 (TORC1), an evolutionarily conserved nutrient-sensing kinase . Ecl1 physically interacts with TORC1 subunit RAPTOR (Mip1), suggesting that TORC1 suppression by Ecl1 occurs through this physical interaction .
PBP domain (PBP_domain)
Type: Domain

This entry represents members of the periplasmic binding domain superfamily . It is often associated with a helix-turn-helix domain.
Acetyl-coenzyme A transporter 1-like (AcetylCoA_trans_1-like)
Type: Family

Acetyl-coenzyme A transporter 1 (also known as acatn) is a multipass transmembrane protein that appears to promote 9-O-acetylation in gangliosides .
Proteasome component Ecm29, N-terminal (Ecm29_N)
Type: Domain

Ecm29 is an adapter/scaffolding protein that tethers the proteasome core particle to the regulatory particle, stabilising the interaction between these two components . This entry represents a HEAT-repeats containing domain found at the N-terminal of ECM29. The N-terminal half of the protein binds the endocytic components Vps11, Rab11-FIP4, and rabaptin .

The proteasome (or macropain) (

) is a multicatalytic proteinase complex in eukaryotes and archaea, and in some bacteria, that is involved in an ATP/ubiquitin-dependent non-lysosomal proteolytic pathway. In eukaryotes the 20S proteasome is composed of 28 distinct subunits which form a highly ordered ring-shaped structure (20S ring) of about 700kDa. Proteasome subunits can be classified on the basis of sequence similarities into two groups, alpha (A) and beta (B). The proteasome consists of four stacked rings composed of α/β/β/α subunits. There are seven different alpha subunits and seven different beta subunits . Three of the seven beta subunits are peptidases, each with a different specificity. Subunit beta1c (MEROPS identifier T01.010) has a preference for cleaving glutaminyl bonds ("peptidyl-glutamyl-like" or "caspase-like"), subunit beta2c (MEROPS identifier T01.011) has a preference for cleaving arginyl and lysyl bonds ("trypsin-like"), and subunit beta5c (MEROPS identifier T01.012) cleaves after hydrophobic amino acids ("chymotrypsin-like") . The proteasome subunits are related to N-terminal nucleophile hydrolases, and the catalytic subunits have an N-terminal threonine nucleophile.
Bacteriophage T4, IpI (Phage_T4_IpI)
Type: Family

This family of proteins represents IPI from bacteriophage T4. This protein is a nuclease inhibitor which is injected by T4 to protect its DNA from gmrS/gmrD CT of pathogenic Escherichia coli into the infected host . The structure of this protein consists of two small β-sheets flanked by N and C termini by α-helices. The protein has a gmrS/gmrD hydrophobic binding site .
Bacteriophage phi-29 scaffolding protein Gp7 (Phage_phi-29_Gp7)
Type: Family

This protein is also referred to as Gp7. The protein contains a DNA-binding function and may have a role in mediating the structural transition from prohead to mature virus and also scaffold release .Gp7 is arranged within the capsid as a series of concentric shells .
Non-structural protein NSP3, SUD-M domain, betacoronavirus (NSP3_bCoV)
Type: Domain

This entry represents the macrodomain referred to as SUD-M (middle SUD subdomain) of the SARS-unique domain (SUD) which binds G-quadruplexes (unusual nucleic-acid structures formed by consecutive guanosine nucleotides) . It can be found in non-structural protein 3 (NSP3) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and related coronaviruses . NSP3 binds to viral RNA, nucleocapsid protein, as well as other viral proteins, and participates in polyprotein processing. It is a multifunctional protein comprising up to 16 different domains and regions . In SARS-CoV the SUD-M (527-651) domain has been shown to bind single-stranded poly(A). It has been shown through the contact area with this RNA on the protein surface, and the electrophoretic mobility shift assays, that SUD-M has higher affinity for purine bases than for pyrimidine bases .

SUD consists of three globular domains separated by short linker peptide segments: SUD-N, SUD-M, and SUD-C . Among these, SUD-N and SUD-M are macrodomains. The SUD-N domain is a related macrodomain which also binds G-quadruplexes . While SUD-N is specific to the NSP3 of SARS and betacoronaviruses of the sarbecovirus subgenera (B lineage), SUD-M is present in most NSP3 proteins except the NSP3 from betacoronaviruses of the embecovirus subgenera (A lineage). SUD-M, despite its name, is not specific to SARS. SUD-C adopts a frataxin-like fold, has structural similarity to DNA-binding domains of DNA-modifying enzymes, binds single-stranded RNA, and regulates the RNA binding behavior of the SUD-M macrodomain. SARS-CoV Nsp3 contains a third macrodomain (the X-domain). The X-domain may function as a module binding poly(ADP-ribose); however, SUD-N and SUD-M do not bind ADP-ribose, as the triple glycine sequence involved in its binding is not conserved in these .

Nsp3c-N and Nsp3c-M each display a typical α/β/α Macro domain fold, in spite of the complete absence of sequence similarities. The central β-sheet with six β-strands in the order β1-β6-β5-β2-β4-β3 is flanked by two (or three) helices on either side. Only the last strand, β3, is antiparallel to the other strands. Currently, most known functions of Nsp3c-N/M are connected with RNA binding. All the residues important for binding ADP-ribose and for de-MARylation/de-PARylation activity are not conserved in Nsp3c-N/M; therefore Nsp3c-N/M cannot bind ADP-ribose. Both Nsp3c-N and Nsp3c-M domains bind unusual nucleic acid structures formed by consecutives guanosine nucleotides, where four strands of nucleic acid are forming a superhelix (so-called G-quadruplexes) .
Phlebovirus, non structural protein (RVFV_non-structural)
Type: Family

This family contains several Phlebovirus non structural proteins which act as a major determinant of virulence by antagonising interferon beta gene expression or by downregulating the host basal transcription factor TFIIH subunit p62 .
RNA-binding protein, B2 (RNA-bd_B2)
Type: Family

Protein B2 binds double-strand RNA (dsRNA) with high affinity and suppresses the host RNA silencing-based antiviral response. B2 is expressed by the insect Flock House virus (FHV) as a counter-defense mechanism against antiviral RNA silencing during infection. In vitro, B2 binds to dsRNA as a dimer and inhibits the cleavage of it by Dicer. B2 blocks cleavage of the FHV genome by Dicer and also the incorporation of FHV small interfering RNAs into the RNA-induced silencing complex .
RNA-directed RNA polymerase, hantavirus, N-terminal (RNA-dir_pol_N_hantavirus)
Type: Domain

This domain is found in the RNA-directed RNA polymerase. It is located towards the N terminus and is approximately 40 amino acids in length. There is a conserved MFNLKF sequence motif. There are two completely conserved residues (E and P) that may be functionally important.
Waikavirus, capsid protein 1 (Waikavirus_capsid-1)
Type: Family

This entry represents capsid protein 1 of Rice tungro spherical virus .
Domain of unknown function DUF3848 (DUF3848)
Type: Domain

This domain is found in a family of uncharacterised proteins found by clustering human gut metagenomic sequences.
Protein of unknown function DUF2561 (DUF2561)
Type: Family

This family of proteins with unknown function appears to be found predominantly in Mycobacterium spp.
Vacuolar sorting protein Vps3844, C-terminal domain (Vps3844_C)
Type: Domain

This entry represents the C-terminal domain (previously known as DUF3844) of the uncharacterised endoplasmic reticulum membrane protein C1709.03 from S. pombe, which was renamed to vacuolar sorting protein Vps3844 . This domain contains 8 largely conserved cysteine residues and the region comprising amino acids 354 to 380 is important for protein trafficking to the vacuole. This protein is conserved in fungi, particularly S. pombe, but lacks representation in S. cerevisiae .
Domain of unknown function DUF3849 (DUF3849)
Type: Domain

This domain is found in a family of uncharacterised proteins found by clustering human gut metagenomic sequences .
Protein of unknown function DUF2742 (DUF2742)
Type: Family

Members of this family of actinobacterial proteins are described as putative PhiRv1/PhiRv2 prophage proteins, however their function is unknown. This two prophages have been detected in the genome sequence of Mycobacterium tuberculosis .
Domain of unknown function DUF3854 (DUF3854)
Type: Domain

This domain of unknown function was found by clustering human gut metagenomic sequences . It may be related to the Toprim domain.
Protein of unknown function DUF2532 (DUF2532)
Type: Family

This bacterial family of proteins has no known function.
Peptidase C3G, Picornavirus (Pept_C3G_Picornavir)
Type: Domain

Viruses in the order Picornavirales infect different vertebrate, invertebrate, and plant hosts and are responsible for a variety of human, animal, and plant diseases. These viruses have a single-stranded, positive sense RNA genome that generally translates a large precursor polyprotein which is proteolytically cleaved after translation to generate mature functional viral proteins. This process is usually mediated by (more than one) proteases, and a 3C (for the family Picornaviridae) or 3C-like (3CL) protease (for other families) plays a central role in the cleavage of the viral precursor polyprotein. In addition to this key role, 3C/3C-like protease is able to cleave a number of host proteins to remodel the cellular environment for virus reproduction . The Picornavirales 3C/3C-like protease domain forms the MEROPS peptidase family C3 (picornain family) of clan PA.

The 3C/3CL protease domain adopts a chymotrypsin-like fold with a cysteine nucleophile in place of a commonly found serine which suggests that the cysteine and serine perform an analogous catalytic function. The catalytic triad is made of a histidine, an aspartate/glutamate and the conserved cysteine in this sequential order. The 3C/3CL protease domain folds into two antiparallel β barrels that are linked by a loop with a short α-helix in its middle, and flanked by two other α-helices at the N- and C-terminal. The two barrels are topologically equivalent and are formed by six antiparallel β strands with the first four organised into a Greek key motif. The active-site residues are located in the cleft between the two barrels with the nucleophilic Cys from the C-terminal barrel and the general acid base His-Glu/Asp from the N-terminal barrel .

This entry represents a rice tungro spherical waikavirus-type peptidase that belongs to MEROPS peptidase family C3G. It is a picornain 3C-type protease, and is responsible for the self-cleavage of the positive single-stranded polyproteins of a number of plant viral genomes. The location of the protease activity of the polyprotein is at the C-terminal end, adjacent and N-terminal to the putative RNA polymerase .
Large ribosomal subunit protein mL58 (Ribosomal_mL58)
Type: Family

This entry represents the essential mitochondrial ribosomal mL58 (also known as 54S ribosomal L20) family from fungi .

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 .