SII-SWORD/CoKE huggingface dataset:
Protein SUPPRESSOR OF GENE SILENCING 3 (SGS3)
Type: Family

This entry represents a group of plant proteins, including Protein SUPPRESSOR OF GENE SILENCING 3 (SGS3) from Arabidopsis. Post-transcriptional gene silencing (PTGS) in plants requires at least two proteins-SGS3 and MET1 (a DNA-methyltransferase) . SGS3 is required for juvenile development and the production of trans-acting siRNAs . SGS3 is also involved in a mechanism for plant resistance to viruses .
ZNF598/HEL2 (ZNF598/HEL2)
Type: Family

This entry includes E3 ubiquitin-protein ligase ZNF598 and yeast E3 ubiquitin-protein ligase HEL2.

ZNF598 plays a key role in the ribosome quality control (RQC), a pathway that takes place when the ribosome has stalled during translation, leading to degradation of nascent peptide chains. ZNF598 is activated when ribosomes are stalled following translation of prematurely polyadenylated mRNAs . Independently of its role in RQC, this protein may also act as a negative regulator of interferon-stimulated gene expression . ZNF598 is associates with eukaryotic initiation factor 4E (eIF4E) homologous protein from mammalian (m4EHP) through binding to Grb10-interacting GYF protein 2 (GIGYF2). The m4EHP-GIGYF2 complex functions as a translational repressor and is essential for normal embryonic development of mammalian .

HEL2 in addition to its role in the ribosome quality control, also acts as an activator of the No-Go decay (NGD) pathway by mediating polyubiquitination of monoubiquitinated RPS3/uS3 and RPS7/es7. RPS3/uS3 and RPS7/es7 are first monoubiquitinated by MAG2 and MOT2/NOT4, respectively, and HEL2 mediates formation of 'Lys-63'-linked polyubiquitin chains on monoubiquitin, leading to activation of the NGD pathway in a CUE2-mediated endonucleolytic cleavage . Hel2 is involved ubiquitination and degradation of excess histones .
RING-H2 finger protein ATL67-70 (ATL67-70)
Type: Family

This entry represents a group of plant RING zinc-finger domain proteins, including ATL67/ATL68/ATL69/ATL70 from Arabidopsis. They belong to the ATL family of ubiquitin ligases . Arabidopsis ATL consists of 91 members that contain the RING-H2 variation and a hydrophobic domain located at the N-terminal end .
Arabinosyltransferase RRA1/2/3 (RRA1/2/3)
Type: Family

This entry represents a group of plant arabinosyltransferases, including RRA1/2/3 from Arabidopsis. They have been implicated in extensin (a plant cell wall component) glycosylation . The arabinosylation of extensin is important for root hair cell development .
Zinc finger protein GIS/GIS2/ZFP8 (GIS/GIS2/ZFP8)
Type: Family

This entry represents a group of C2H2 transcription factors, including GIS, ZFP8 and GIS2 from Arabidopsis. They play partially redundant and essential roles in inflorescence trichome initiation and in its regulation by GA and cytokinins .
Regulatory protein NPR (NPR)
Type: Family

This entry represents a group of plant regulatory proteins, including NPR1-4 from Arabidopsis. NPR1 is a central regulator of salicylic-acid (SA)-mediated defense signaling in Arabidopsis. It contains a BTB/POZ domain at the N-terminal and an ankyrin-repeat domain in the central region. It binds to TGA1, a member of the TGA family of transcription factors that activate SA-responsive elements in the promoters of PR (PATHOGENESIS-RELATED) genes. It also has cytosolic function in cross-communication between SA- and JA-dependent defense signaling pathways . NPR1 is functionally conserved in diverse plant species, including rice (Oryza sativa L.) . NPR3 and NPR4 have also been shown to be required for basal defense against pathogens .
Transcription factor PRE (PRE)
Type: Family

This entry represents the paclobutrazol-resistant (PRE) family of helix-loop-helix (HLH) factors, including PRE1-6 from Arabidopsis and Increased Leaf Inclination (ILI) family of atypical bHLH transcription factors in rice. The members of this family ILI1/2/3/4/5/6/7 lack the basic region for DNA binding and have been implicated in brassinosteroids signalling . They are involved in development in Arabidopsis and rice . They lack the basic domain required for DNA binding but dimerises with DNA binding bHLH factors to inhibit their DNA binding. Moreover, they also antagonize their interacting HLH or bHLH proteins .
Lipase-like (Lipase-like)
Type: Family

This entry represents a group of lipases, including Lipid droplet phospholipase 1 (Lpl1) and Rog1 from budding yeasts. This entry also includes some putative lipases, such as YDL109C/YDR444W from budding yeasts, C4A8.10 from fission yeasts and FAM135A/B from animals.
Transcription factor BIM1/2/3 (BIM1/2/3)
Type: Family

This entry represents a group of plant transcription factors, including BIM1-3. BIM1 interacts with BES1 and binds to E box (CANNTG) sequences present in many BR (brassinosteroid)-induced promoters .
Heavy metal-associated isoprenylated plant protein 46 (HIPP46)
Type: Family

This entry represents a group of plant putative heavy metal binding proteins, including HIPP46. They contain an apparent HMA-like domain but similarly to

lacks the core conserved Cys-X-X-Cys motif .
Protein CELLULOSE SYNTHASE INTERACTIVE 1/2/3 (CSI1/2/3)
Type: Family

This entry represents a group of plant cellulose synthase interacting proteins, including CSI1/2/3 from Arabidopsis. They are non-cellulose synthase (CESA) proteins associated with cellulose synthase complexes and are required for cellulose biosynthesis . CSI1 is also a microtubule-associated protein that bridges CESA complexes and cortical microtubules . CSI3 has been shown to regulate plant cellulose biosynthesis and plant anisotropic cell growth that modulates the velocity of cellulose synthase complexes in both a microtubule-dependent and microtubule-independent manner .
Adenine/Thymine-DNA glycosylase (MIG/MutY)
Type: Family

This family includes DNA glycosylases involved in DNA damage repair, including Adenine-DNA glycosylase MutY and its homologues (MutYH) and Thymine-DNA glycosylase MIG. MutY plays an important role in the prevention of DNA mutations resulting from the presence of the oxidatively damaged lesion 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-OxoG). 8-OxoG can mispair with 2'-deoxycytidine 5'-triphosphate or with 2'-deoxyadenosine triphosphate during DNA replication, forming C*8-oxoG and A*8-oxoG mispairs. If unrepaired, the A=8-oxoG mispairs can result in deleterious C:G to A:T transversions. MutY, with its DNA glycosylase activity, excises adenine paired with guanine or 8-oxoG . Mutations in this enzyme cause MUTYH-associated polyposis (MAP) which results in the accumulation of G:T mismatched DNA caused by oxidative damage . MIG excises thymine from T/G mismatches and it also has a weak DNA glycosylase activity on uracil paired with various bases .
Zinc finger protein GIS3/ZFP5/ZFP6 (GIS3/ZFP5/ZFP6)
Type: Family

This entry represents a group of plant putative transcription factors, including GIS3/ZFP5/ZFP6 from Arabidopsis. GIS3/ZFP5/ZFP6 have been shown to regulates trichome initiation . ZFP5 also regulates root hair initiation and morphogenesis , while ZFP6 also acts as negative regulator of abscisic acid (ABA) signaling during germination and early seedling development .
Protein SENSITIVE TO PROTON RHIZOTOXICITY 1/2 (STOP1/2)
Type: Family

This entry represents a group of plant zinc finger proteins, including STOP1/STOP2 from Arabidopsis and their homologues, Os01g0871200/STAR3 from rice. They are putative transcription factors that regulate gene expression associated with multiple stress tolerances in plant roots . STOP1 (sensitive to proton rhizotoxicity 1) regulates transcription of multiple genes critical for tolerance to aluminum (Al) and low pH in Arabidopsis . STOP2 is a physiologically minor isoform of STOP1, but it can activate expression of some genes regulated by STOP1 . In rice, ART1 regulates multiple genes implicated in aluminum tolerance .
Pathogenesis-related protein-4 (PR4)
Type: Family

The pathogenesis-related protein-4 (PR-4) family is a group of proteins containing a BARWIN-like domain. This entry includes BARWIN from barley, PR4A/B from wheat, and AtHEL from Arabidopsis. In barley BARWIN is induced by wounding or pathogens . Homologues of the BARWIN protein are also involved in the plant response to fungal infection and mechanical wounding . Even though PR-4 proteins have been classified as chitinases, however, several BARWIN homologues have been shown to possess ribonuclease activity . Antifungal DNase activity has also been observed, together with RNase activity, for the Theobroma cacao TcPR-4b protein .
Costars family (Costars)
Type: Family

Costars significantly resembles the C-terminal region of the striated muscle activator of Rho signaling (STARS), a mammalian protein that regulates the serum response factor transcriptional activity through actin binding and Rho GTPase activation. Costars is involved in modulating actin dynamics and cell motility in Dictyostelium. Costars has been shown to directly bind to F-actin in vitro, however, it does not associate tightly with either G- or F-actin within the cellular context .
Zinc finger protein ZAT1/4/9 (ZAT1/4/9)
Type: Family

This entry represents a group of plant zinc finger proteins, including ZAT1/4/9 from Arabidopsis. They may regulate the maturation of the outermost cells of the root cap in Arabidopsis . Overexpression of ZAT1 has been shown to induce the ectopic expression of PUTATIVE ASPARTIC PROTEASE3 involved in the programmed cell death. ZAT1 possesses two conserved EAR motifs, the second EAR motif is essential for the growth inhibition by ZAT1 .
Iron-sulfur protein NUBPL-like (NUBPL-like)
Type: Family

This family represents a group of proteins that bind and transfer iron-sulfur (Fe-S) clusters to target proteins and are required for Fe-S cluster assembly. They belong to the conserved family of P-loop ATPases. Iron-sulfur protein NUBPL, an IND1 homologue, is required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) . Also included in this family is Fe-S cluster assembly factor HCF101 from Arabidopsis, which specifically assembles 4Fe-4S clusters and transfers them to the chloroplast PSI and ferredoxin-thioredoxin (FTR) complexes . Iron-sulfur cluster carrier proteins APBC from Bacteria and Archaea are also included in this family .
Non-structural protein 5, deltacoronavirus (NSP5_Mpro_deltaCoV)
Type: Domain

Proteins containing this domain include the coronavirus (CoV) non-structural protein 5 (NSP5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in deltacoronaviruses .

CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/NSP5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/NSP5 consist of three domains with the first two containing anti-parallel β barrels and the third consisting of an arrangement of α-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/NSP5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs .
Non-structural protein 5, gammacoronavirus (NSP5_Mpro_GammaCoV)
Type: Domain

Proteins containing this domain include coronavirus (CoV) non-structural protein 5 (NSP5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), from gammacoronaviruses .

CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/NSP5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/NSP5 consist of three domains with the first two containing anti-parallel β barrels and the third consisting of an arrangement of α-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/NSP5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs .
Non-structural protein 5, alphacoronavirus (NSP5_Mpro_alphaCoV)
Type: Domain

Proteins containing this domain include (CoV) non-structural protein 5 (NSP5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in alphacoronaviruses .

CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/NSP5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/NSP5 consist of three domains with the first two containing anti-parallel β barrels and the third consisting of an arrangement of α-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/NSP5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs .
mRNA-capping enzyme P5, phytoreovirus (P5_Phytoreov)
Type: Family

This entry represents the putative mRNA-capping enzyme P5 of Phytoreovirus, like rice dwarf virus. It is a nucleoside-2'-O-methyltransferase (2'OMTase) involved in the mRNA capping .
Accessory protein N2-like (N2-like_embe-CoV)
Type: Domain

This entry includes protein I (also known as accessory protein N2) from bovine enteritic coronavirus-F15 strain (BECV-F15) and related Embecoviruses (A lineage) including murine hepatitis virus . The gene encoding protein I is included in the N gene as an alternative ORF . Protein I appears to have no homologous proteins in Sarbecovirus lineage B, which includes Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and SARS-CoV-2 (2019 novel coronavirus, 2019-nCoV). BECV-F15 protein I is not essential for viral replication. It is related to the ORF8b accessory protein of Middle East respiratory syndrome-related coronavirus (MERS-CoV) and other related merbecoviruses (C lineage); the gene encoding ORF8b is an internal ORF that is overlapped by the N (nucleocapsid) protein gene (ORF8a) .
MERS-CoV ORF8b protein-like (merbe_CoV_ORF8b-like)
Type: Family

This entry includes the ORF8b accessory protein from Middle East respiratory syndrome-related coronavirus (MERS-CoV) and related merbecoviruses (C lineage). The gene encoding ORF8b is an internal ORF that is overlapped by the N (nucleocapsid) protein gene (ORF8a) . ORF8b appear to have no homologous proteins in Sarbecovirus (lineage B), which includes Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and SARS-CoV-2 (2019 novel coronavirus, 2019-nCoV). MERS-CoV ORF8b is not essential for viral replication. It is related to protein I (also known as accessory protein N2) of bovine enteritic coronavirus-F15 strain (BECV-F15) and other related Embecoviruses; the gene encoding protein I is included in the N gene as an alternative ORF .
Nonstructural protein 14, alphacoronavirus (NSP14_alphaCoV)
Type: Domain

This entry includes non-structural protein 14 (Nsp14) from alphacoronavirus.

Nonstructural protein 14 (NSP14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain . ExoN is important for proofreading and therefore, the prevention of lethal mutations . The association of NSP14 with NSP10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The NSP10/NSP14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. NSP14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or NSP14 has been found to interfere with protein translation of cellular mRNAs . NSP14 inhibits host translation, an activity that is enhanced when NSP14 forms the complex with NSP10. This abolishes the type I interferon (IFN-I)-dependent induction of interferon-stimulated genes (ISGs), and therefore, is one of the SARS-CoV-2 mechanisms to impair host innate immune responses .
NSP11, NendoU domain, arterivirus (NSP11_NendoU_Av)
Type: Domain

Nidovirus endoribonucleases (NendoUs) are uridylate-specific endoribonucleases, which release a cleavage product containing a 2',3'-cyclic phosphate at the 3' terminal end. They are conserved among this order and a genetic marker of nidoviruses . A feature of these viruses' evolutionary relationship is the organisation and processing of the genome, which is translated in two large precursor polyproteins (pp1a and pp1ab) from the replicase gene, that are proteolytically processed by virus proteases into 13 to 16 nonstructural proteins (NSPs) .

Proteins containing the NendoU domain include NSP15 from coronaviruses and NSP11 from arteriviruses, both of which participate in the viral replication process and in the evasion of the host immune system. Although they are similar and conserved, they only share 27% identical residues and show structural differences . NSP11 has an N-terminal domain and a C-terminal NendoU catalytic domain. NSP11 functions as a dimer and Mg2 is dispensable for its activity. In Porcine reproductive and respiratory syndrome virus (PRRSV), NSP11 induces STAT2 degradation to inhibit interferon signaling. Mutagenesis studies revealed that the amino acid residue K59 located at the N-terminal domain of NSP11 is indispensable for inducing STAT2 reduction . This domain is not conserved in those nidovirus branches that replicate in invertebrate hosts (Mesoniviridae, Roniviridae), suggesting specific roles in vertebrate hosts.

The NendoU domain packs into two β-sheets which constitute the catalytic-site cleft located at one side of the domain. A group of small α-helices packed at the other side of the domain face the concave surface of the β-sheets. The active site, located in the shallow groove between the two β-sheets, carries the catalytic triad made of two histidines and a lysine .

This entry represents the C-terminal NendoU catalytic domain of NSP11 from arteriviruses.
Nonstructural protein 14, betacoronavirus (NSP14_betaCoV)
Type: Domain

This entry includes non-structural protein 14 (NSP14) from betacoronavirus. There are not yet publicly available structures of SARS-CoV-2 NSP14, but computed homology model based on the structure of SARS-CoV-1 NSP14 (

), revealed that they share ~95% sequence identity. Superposition of the methyltransferase catalytic centers of SARS-CoV-1 and SARS-CoV-2 NSP14 showed 100% conservation of active site residues, including both the cap binding residues and the S-adenosylmethionine (SAM) binding residues. The active site of the exoribonuclease proofreading domain of NSP14 contains a DEDDH motif, which is identical to the corresponding motif found in SARS-CoV-1 NSP14 .

Nonstructural protein 14 (NSP14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain . ExoN is important for proofreading and therefore, the prevention of lethal mutations . The association of NSP14 with NSP10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The NSP10/NSP14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. NSP14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or NSP14 has been found to interfere with protein translation of cellular mRNAs . NSP14 inhibits host translation, an activity that is enhanced when NSP14 forms the complex with NSP10. This abolishes the type I interferon (IFN-I)-dependent induction of interferon-stimulated genes (ISGs), and therefore, is one of the SARS-CoV-2 mechanisms to impair host innate immune responses .
Nonstructural protein 14, gammacoronavirus (NSP14_gammaCoV)
Type: Domain

This entry includes non-structural protein 14 (NSP14) from gammacoronavirus.

Nonstructural protein 14 (NSP14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain . ExoN is important for proofreading and therefore, the prevention of lethal mutations . The association of NSP14 with NSP10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The NSP10/NSP14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. NSP14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or NSP14 has been found to interfere with protein translation of cellular mRNAs . NSP14 inhibits host translation, an activity that is enhanced when NSP14 forms the complex with NSP10. This abolishes the type I interferon (IFN-I)-dependent induction of interferon-stimulated genes (ISGs), and therefore, is one of the SARS-CoV-2 mechanisms to impair host innate immune responses .
Nonstructural protein 14, deltacoronavirus (NSP14_deltaCoV)
Type: Domain

This entry includes non-structural protein 14 (NSP14) from deltacoronavirus.

Nonstructural protein 14 (NSP14) of coronavirus (CoV) plays an important role in viral replication and transcription. It consists of 2 domains with different enzymatic activities: an N-terminal exoribonuclease (ExoN) domain and a C-terminal cap (guanine-N7) methyltransferase (N7-MTase) domain . ExoN is important for proofreading and therefore, the prevention of lethal mutations . The association of NSP14 with NSP10 stimulates its ExoN activity; the complex hydrolyzes double-stranded RNA in a 3' to 5' direction as well as a single mismatched nucleotide at the 3'-end mimicking an erroneous replication product. The NSP10/NSP14 complex may function in a replicative mismatch repair mechanism. N7-MTase functions in mRNA capping. NSP14 can methylate GTP, dGTP as well as cap analogs GpppG, GpppA and m7GpppG. The accumulation of m7GTP or NSP14 has been found to interfere with protein translation of cellular mRNAs . NSP14 inhibits host translation, an activity that is enhanced when NSP14 forms the complex with NSP10. This abolishes the type I interferon (IFN-I)-dependent induction of interferon-stimulated genes (ISGs), and therefore, is one of the SARS-CoV-2 mechanisms to impair host innate immune responses .