SII-SWORD/CoKE huggingface dataset:
Hepatitis C virus, Core protein, C-terminal (HCV_Core_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 .

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 .

This entry represents domain II and domain III (ER anchor sequence) of the core protein p23.
Hepatitis C virus, Core protein, N-terminal (HCV_core_N)
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 .

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 .

This entry covers domain I of the core protein.
Mg2+ transporter protein, CorA-like/Zinc transport protein ZntB (MgTranspt_CorA/ZnTranspt_ZntB)
Type: Family

This entry includes prokaryotic magnesium transport protein CorA and its related protein, zinc transport protein ZntB . This entry also includes eukaryotic magnesium transporters, such as mitochondrial inner membrane magnesium transporter Mrs2 and magnesium transporter Alr1 and Alr2. These proteins are characterised by the conserved GMN motif at the end of the first of two conserved transmembrane (TM) domains near the C terminus .

Thermotoga maritima CorA (TmCorA) has been reported to be an efflux system. It only has 2 TM domains,TM1 and TM2 . The loop connecting TM1 and TM2 contains the conserved CorA signature motifs YGMNF and MPEL. With its N- and C-terminal ends face the cytosol and its similarity to the class II CorA (a CorA group lacking the MPEL motif and may transport divalent cations out of the cell), TmCorA is predicted to be primarily involved in ion efflux . It forms a pentameric membrane protein channel featuring a possible ion discriminating aspartate ring at the cytoplasmic entrance of the pore and two distinct cytoplasmic metal binding sites per monomer, which could have regulatory roles .
Cation efflux protein (Cation_efflux)
Type: Family

Members of this family are integral membrane proteins, that are found to increase tolerance to divalent metal ions such as cadmium, zinc, and cobalt. These proteins are considered to be efflux pumps that remove these ions from cells , however others are implicated in ion uptake . The family has six predicted transmembrane domains. Members of the family are variable in length because of variably sized inserts, often containing low-complexity sequence.
Transposase IS110-like, N-terminal (Transp_IS110-like_N)
Type: Domain

Transposase proteins are necessary for efficient DNA transposition. This entry represents the N-terminal region of the pilin gene inverting protein (PIVML) and members of the IS111A/IS1328/IS1533 family of transposases .
Picornavirus 2B protein (Pico_P2B)
Type: Domain

Poliovirus infection leads to drastic alterations in membrane permeability late during infection. Proteins 2B and 2BC enhance membrane permeability .
Multi antimicrobial extrusion protein (MATE_fam)
Type: Family

In general, proteins from the MATE family are involved in exporting metabolites across the cell membrane and are often responsible for multidrug resistance (MDR) . These proteins mediate resistance to a wide range of cationic dyes, fluroquinolones, aminoglycosides and other structurally diverse antibodies and drugs. MATE proteins are found in bacteria, archaea and eukaryotes. These proteins are predicted to have 12 α-helical transmembrane regions, some of the animal proteins may have an additional C-terminal helix .
Zein seed storage protein (Zein)
Type: Family

Alpha-prolamins are the major seed storage proteins of species of the grass tribe Andropogonea. They are unusually rich in glutamine, proline, alanine, and leucine residues and their sequences show a series of tandem repeats presumed to be the result of multiple intragenic duplication . In Zea mays (Maize), the 22kDa and 19kDa zeins are encoded by a large multigene family and are the major seed storage proteins accounting for 70% of the total zein fraction. Structurally the 22kDa and 19kDa zeins are composed of nine adjacent, topologically antiparallel helices clustered within a distorted cylinder. The 22kDa alpha-zeins are encoded by 23 genes ; twenty-two of the members are found in a roughly tandem array forming a dense gene cluster. The expressed genes in the cluster are interspersed with nonexpressed genes. Interestingly, some of the expressed genes differ in their transcriptional regulation. Gene amplification appears to be in blocks of genes explaining the rapid and compact expansion of the cluster during the evolution of maize.
Hepatitis C virus, Non-structural protein E2/NS1 (HCV_NS1)
Type: Domain

The hypervariable region of the E2/NS1 region of Hepatitis C virus varies greatly between viral isolates. E2 is thought to encode a structurally unconstrained envelope protein .
Hantavirus glycoprotein Gc, N-terminal domain (Hanta_Gc_N)
Type: Domain

This entry represents the polyprotein region which forms the N-terminal region of Gc glycoprotein. It has been shown that the N-terminal region of glycoprotein Gc has the conserved CNP motif, suggested to be an integrin-binding motif . Gc protein has a typical class II fusion protein fold consisting of a central β-sandwich domain (termed domain I) made of eight β-strands arranged in two antiparallel β-sheets, domain II which has an elongated shape with two subdomains (a central, opened β-barrel proximal to domain I and a distal β-sandwich 'tip'), and domain III, which has an Ig-like fold . This entry represents the N-terminal region of Gc containing the central and dimerisation domains (which includes domain I and II).

The medium (M) genome segment of Hantaviruses (family Bunyaviridae) encodes the two virion glycoproteins , Gn and Gc (also known as G1 and G2, respectively) as a polyprotein precursor . Gn and Gc forms homotetramers at the surface of the virion, which attach the virion to host cell receptors including integrin beta3/ITGB3 and induce internalization, predominantly through clathrin-dependent endocytosis .
Alphavirus E3 spike glycoprotein (Alpha_E3_glycop)
Type: Domain

Alphaviruses are enveloped RNA viruses that use arthropods such as mosquitoes for transmission to their vertebrate hosts, and include Semliki Forest and Sindbis viruses . Alphaviruses consist of three structural proteins: the core nucleocapsid protein C, and the envelope proteins P62 and E1 (

) that associate as a heterodimer. The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through membrane fusion. The proteolytic maturation of P62 into E2 (

) and E3 causes a change in the viral surface. Together the E1, E2, and sometimes E3 glycoprotein "spikes" form an E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike . Upon exposure of the virus to the acidity of the endosome, E1 dissociates from E2 to form an E1 homotrimer, which is necessary for the fusion step to drive the cellular and viral membranes together . This entry represents the alphaviral E3 glycoprotein. Most alphaviruses lose the peripheral protein E3, but in Semliki viruses it remains associated with the viral surface.
Hantavirus glycoprotein Gn, head (Hanta_Gn-H)
Type: Domain

This entry represents the Gn glycoprotein in which, the N-terminal two-thirds has been denoted as 'head' (Gn-H) interacts with Gc ectodomain. Release of Gn-H at acid pH induces a further conformational change of the Gc domain II tip which exposes non-polar side chains for insertion into the endosomal membrane . The C-terminal region of the Gn ectodomain is denoted as Gn base (Gn-B), which contributes the most to the intra-spike tetrameric contacts.

The medium (M) genome segment of Hantaviruses (family Bunyaviridae) encodes the two virion glycoproteins , Gn and Gc (also known as G1 and G2, respectively) as a polyprotein precursor . Gn and Gc forms homotetramers at the surface of the virion, which attach the virion to host cell receptors including integrin beta3/ITGB3 and induce internalization, predominantly through clathrin-dependent endocytosis .
Flavivirus polyprotein propeptide (Flavi_propep)
Type: Domain

The Flaviviruses are small enveloped animal viruses containing a single positive strand genomic RNA . The genome encodes one large ORF, a polyprotein which undergos proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. This entry consists of a propeptide region of approximately 90 amino acids in length .
Bromovirus movement protein (Bromo_MP)
Type: Family

Members of this family are found in the bromoviridae, assembling into long tubular structures at the surface of the infected protoplast. These proteins aid the infection of the virus .
MaoC-like dehydratase domain (MaoC-like_dom)
Type: Domain

The maoC gene is part of an operon with maoA which is involved in the synthesis of monoamine oxidase . The MaoC protein shares similarity with a region found in a wide variety of enzymes, such as peroxisomal hydratase-dehydrogenase-epimerase and fatty acid synthase beta subunit. A deletion mutant of the C-terminal 271 amino acids in peroxisomal hydratase-dehydrogenase-epimerase (

), corresponding to the MaoC domain, abolished its 2-enoyl-CoA hydratase activity, suggesting that this region may be a hydratase enzyme . Several bacterial proteins that are composed solely of this domain have (R)-specific enoyl-CoA hydratase activity .
Peptidase S30, polyprotein P1, potyvirus (Pept_S30_P1_potyvir)
Type: Domain

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

The potyviridae are a family of positive strand RNA viruses, members of which include Zucchini yellow mosaic virus, and Turnip mosaic virus (strain Japanese) which cause considerable losses of crops worldwide.

This entry represents a C-terminal region from various plant potyvirus P1 proteins (found at the N terminus of the polyprotein). The C terminus of P1 is a serine peptidase belonging to MEROPS peptidase family S30 (clan PA(S)). It is the protease responsible for autocatalytic cleavage between P1 and the helper component protease, which is a cysteine peptidase belonging to MEROPS peptidase family C6

. The P1 protein may be involved in virus-host interactions , and evasion of immune responses .
Cytochrome c assembly protein (Cyt_c_assembly)
Type: Domain

This domain is found in various proteins involved in cytochrome c assembly from mitochondria, chloroplast and bacteria; including among others CycK from Rhizobium leguminosarum , CcmC and CcmF from Escherichia coli , CcsA from Chlamydomonas , and orf240 from Triticum aestivum (wheat) mitochondria .

CcmC interacts directly with heme, and it is the only protein of the ccm operon that is strictly required for heme transfer . CcmF contains a b-type heme and is thought to be a cytochrome c synthetase . CcsA is required during biogenesis of c-type cytochromes at the step of heme attachment . R. leguminosarum CycK and wheat orf240 also contain a putative heme-binding motif .
T20D4.11-like domain (T20D4.11-like_dom)
Type: Domain

This domain is found in a group of uncharacterised proteins from nematodes, including

(T20D4.11) and Excretory canal abnormal exc-13 from Caenorhabditis elegans. Members of this group have been reported to be negative regulators of growth and development in response to some stress and environmental conditions that are probably involved in growth inhibition under mitochondrial stress conditions . The domain is roughly 130 amino acids long and contains 12 conserved cysteines, which suggests that it is an extracellular domain and that these cysteines form six intra-domain disulphide bridges. Structural prediction shows an all-α configuration. This domain was formerly known as DUF19.
FtsK domain (FtsK_dom)
Type: Domain

The FtsK domain is a hydrophilic domain of about 200 residues, which is found in:

Bacterial cell division protein ftsK (known as sporulation protein SpoIIIE in Bacillus subtilis).

A set of conjugative plasmid- and conjugative transposon-encoded proteins, generally called Tra proteins. These proteins come from an extremly wide range of species, including Gram-positive and Gram-negative bacilli and cocci, Streptomyces species, Agrobacterium spp., and archaebacteria. In cases in which a function is known, the protein is required for intercellular DNA transfer.

The FtsK domain contains a highly conserved putative ATP-binding P-loop motif and is assumed to be cytoplasmic. It can be found in one to three copies and is thought to be involved in DNA translocation by coupling ATP hydrolysis to movement relative to the long axis of DNA .
CheW-like domain (CheW-lke_dom)
Type: Domain

The CheW-like domain is an around 150-residue domain that is found in proteins involved in the two-component signaling systems regulating bacterial chemotaxis. Two components systems are composed of a receptor kinase, which monitors the environmental conditions and its substrate, the response regulator, which acts as a binary switch depending on the phosphorylation state. In Escherichia coli, the signal transduction pathway for chemotaxis consists of specialised membrane receptors, termed chemotaxis transducers; a CheA-CheY two-component system, which transmits the signal from transducers to flagellar motors; and a docking protein, CheW, which couples the CheA histidine kinase to transducers. Whereas CheW is only made of a CheW-like domain, CheA additionally contains an HPt domain and an histidine kinase domain. The CheW-like domain has been shown to mediate the interaction between CheA and the adaptor protein CheW. Some bacteria contain another bifunctional protein, CheV, consisting of an N- terminal CheW-like domain and a C-terminal response regulatory domain. Although its precise function in chemotaxis is unknown, CheV probably acts in adaptation to attractants .

The CheW-like domain is composed of two β-sheet subdomains, each of which forms a loose five-stranded β-barrel around an internal hydrophobic core. The interactions between the subdomains are contributed by a third hydrophobic core sandwiched between the two β-sheet subdomains. The CheW-like structure is stabilised by extensive hydrophobic interactions .
Myogenic muscle-specific protein, N-terminal (MyoD_N)
Type: Domain

Members of the bHLH family of transcription factors share homology within a basic domain and an adjacent helix-loop-helix motif. Myogenic factor MyoD belongs to the bHLH family .

This domain can be found at the N terminus of MyoD, which is muscle specific protein that control muscle development. This domain includes the predicted N-terminal transcription activation domain and part of the basic domain .
tRNA-binding domain (tRNA-bd_dom)
Type: Domain

This domain is found in prokaryotic methionyl-tRNA synthetases, prokaryotic phenylalanyl tRNA synthetases, the yeast GU4 nucleic-binding protein (G4p1 or p42, ARC1) , human tyrosyl-tRNA synthetase , endothelial-monocyte activating polypeptide II and export-related chaperon CsaA . G4p1 binds specifically to tRNA form a complex with methionyl-tRNA synthetases . In human tyrosyl-tRNA synthetase, this domain may direct tRNA to the active site of the enzyme . This domain may perform a common function in tRNA aminoacylation . In ARC1, this domain has been shown to have a catalytic activity .
Alphavirus E1 glycoprotein (Alpha_E1_glycop)
Type: Domain

Alphaviruses are enveloped RNA viruses that use arthropods such as mosquitoes for transmission to their vertebrate hosts, and include Semliki Forest and Sindbis viruses . Alphaviruses consist of three structural proteins: the core nucleocapsid protein C, and the envelope proteins P62 and E1 that associate as a heterodimer. The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through membrane fusion. The proteolytic maturation of P62 into E2 (

) and E3 (

) causes a change in the viral surface. Together the E1, E2, and sometimes E3, glycoprotein "spikes" form an E1/E2 dimer or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike . Upon exposure of the virus to the acidity of the endosome, E1 dissociates from E2 to form an E1 homotrimer, which is necessary for the fusion step to drive the cellular and viral membranes together. The alphaviral glycoprotein E1 is a class II viral fusion protein, which is structurally different from the class I fusion proteins found in influenza virus and HIV. The structure of the Semliki Forest virus revealed a structure that is similar to that of flaviviral glycoprotein E, with three structural domains in the same primary sequence arrangement . This entry represents all three domains of the alphaviral E1 glycoprotein.
Transmembrane protein TqsA-like (AI-2E-like)
Type: Family

This entry consists of proteins from eukaryotes and prokarytotes. It includes Escherichia coli autoinducer-2 (AI-2) transport protein TqsA (YdgG), which controls the transport of the quorum-sensing signal AI-2 either by enhancing its secretion or inhibiting its uptake and consequently represses biofilm formation and motility and affects the global gene expression in biofilms . TqsA exhibit a uniform topology with 8 putative transmembrane segments (TMSs), a structure shared by proteins in this family. The function of proteins in this family are mostly unknown, however, it has been suggested that they may transport a variety of compounds, possibly all related in structure . This entry also includes transport proteins such as sodium-lithium/proton antiporter from Halobacillus and sporulation protein YtvI from Bacillus subtilis, a putative permease .

This entry also includes uncharacterised transmembrane protein 245 (TMEM245) from eukaryotes.
CNNM, transmembrane domain (CNNM)
Type: Domain

Proteins containing the ancient conserved domain protein/cyclin M (CNNM) are integral membrane proteins that are conserved from bacteria to humans. CNNM family members influence metal ion homeostasis through mechanisms that may not involve direct membrane transport of the ions. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a transmembrane domain, a "Bateman module", which consists of two cystathionine-beta-synthase (CBS) domains, and a C-terminal cNMP (cyclic nucleotide monophosphate) binding domain .

The CNNM transmembrane domain contains four hydrophobic regions and forms a dimer through hydrophobic contacts between TM2 and TM3, in which each chain is composed of three transmembrane helices (TM1-3), a pair of short helices exposed on the intracellular side, and a juxtamembrane (JM) helix that forms a belt-like structure . The homodimer adopts an inward-facing conformation with a negatively charged cavity containing a conserved pi-helical turn in TM3 that coordinates a Mg2 ion .