SII-SWORD/CoKE huggingface dataset:
Auxin response factor (ARF_plant)
Type: Family

The plant hormone auxin (indole-3-acetic acid) can regulate the gene expression of several families, including Aux/IAA, GH3 and SAUR families. Two related families of proteins, Aux/IAA proteins (

) and the auxin response factors (ARF), are key regulators of auxin-modulated gene expression . There are multiple ARF proteins, some of which activate, while others repress transcription. ARF proteins bind to auxin-responsive cis-acting promoter elements (AuxREs) using an N-terminal DNA-binding domain. It is thought that Aux/IAA proteins activate transcription by modifying ARF activity through the C-terminal protein-protein interaction domains found in both Aux/IAA and ARF proteins.
TOM1-like protein, plant (TOL_plant)
Type: Family

This entry includes TOM1-like protein 1-9 (TOL1-9) from Arabidopsis . In general, they contain the VHS and GAT domains that bind to phospholipids and ubiquitin . They may be part of the ESCRT (Endosomal Sorting Complex Required for Transport) complex contributing to the sorting of ubiquinated proteins to the MVB (multivesicular body) formation machinery. In plants they play a role in the control of plant morphogenesis . This entry also includes TOM1 from Dictyostelium discoideum .
B3 domain-containing protein REM16-like (REM16-like)
Type: Family

This entry represents a group of plant B3 domain-containing proteins, including REM16, At3g19184, At5g58280 and At5g42700 from Arabidopsis. They are part of the REM (Reproductive Meristem) gene family that may play a role during early stages of flower development .
Probable metalloprotease EGY1-like (EGY1-like)
Type: Family

This entry includes proteins from bacteria, archaea and plants. Some proteins in this entry belong to peptidase family M50, hence they have been predicted to be metalloendopeptidases. This entry includes the chloroplastic protein EGY1/2/3 from Arabidopsis. EGY1 is an ATP-independent metalloprotease required for development of both thylakoid grana and a well organized lamellae system in chloroplast .
Protein NDR1-like (NDR1-like)
Type: Family

This entry represents a group of plant NDR1-like proteins. In Arabidopsis, NDR1 is involved in disease resistance . It interacts with RIN4 and mediates the differential activation of multiple disease resistance pathways in Arabidopsis .
Nucleoporin Nup188 (Nup188)
Type: Family

Nup188 is one of the many peptides that make up the nucleoporin complex (NPC), and is found across eukaryotes . The Nup188 subcomplex (Nic96p-Nup188p-Nup192p-Pom152p) is one of at least six that make up the NPC, and as such is symmetrically localised on both faces of the NPC at the nuclear end, being integrally bound to the C terminus of Pom34p .
Transcription factor LUX/BOA-like (LUX/BOA-like)
Type: Family

This entry represents a group of plant Myb domain proteins, including LUX, BOA and MYBC1 from Arabidopsis. LUX and BOA are transcription factors and critical components of the regulatory circuit of the circadian clock . LUX also binds to ELF3 and associates with ELF4 in a diurnal complex which is required for the expression of the growth-promoting transcription factors PIF4 and PIF5 and subsequent hypocotyl growth in the early evening . MYBC1 has been shown to negatively regulate freezing tolerance in Arabidopsis .
RNA demethylase ALKBH9B/ALKBH10B-like (ALKBH9B/ALKBH10B-like)
Type: Family

This entry represents a group of plant dioxygenases, including ALKBH9B and ALKBH10B from Arabidopsis. ALKBH9B and ALKBH10B demethylate RNA by oxidative demethylation: specifically demethylates N6-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes . ALKBH10B-mediated mRNA m6A demethylation stabilizes the mRNA of the key flowering time regulators FT, SPL3 and SPL9, which are involved in the control of floral transition .
Trans-isoprenyl diphosphate synthases, bacterial-type (Trans_IPPS_bact-type)
Type: Family

Trans-Isoprenyl Diphosphate Synthases (Trans_IPPS) catalyze a head-to-head (HH) (1'-1) condensation reaction . This entry includes squalene and phytoene synthases which catalyze the 1'-1 condensation of two 15-carbon (farnesyl) and 20-carbon (geranylgeranyl) isoprenyl diphosphates, respectively . The catalytic site consists of a large central cavity formed by mostly antiparallel α helices with two aspartate-rich regions (DXXXD) located on opposite walls . These residues mediate binding of prenyl phosphates . A two-step reaction has been proposed for squalene synthase (farnesyl-diphosphate farnesyltransferase) in which, two molecules of FPP react to form a stable cyclopropylcarbinyl diphosphate intermediate, and then the intermediate undergoes heterolysis, isomerization, and reduction with NADPH to form squalene, a precursor of cholesterol. The carotenoid biosynthesis enzyme, phytoene synthase (CrtB), catalyses the condensation reaction of two molecules of geranylgeranyl diphosphate to produce phytoene, a precursor of beta-carotene . These enzymes produce the triterpene and tetraterpene precursors for many diverse sterol and carotenoid end products and are widely distributed among eukaryota, bacteria, and archaea .

This entry includes squalene and phytoene synthases found in bacteria, archaea, fungi, plant chloroplasts and insects.
Trans-isoprenyl diphosphate synthases, eukaryotic-type (Trans_IPPS_euk-type)
Type: Family

This entry includes squalene and phytoene synthases found in bacteria, archaea, fungi, plants and vertebrates.

Trans-Isoprenyl Diphosphate Synthases (Trans_IPPS) catalyze a head-to-head (HH) (1'-1) condensation reaction . This entry includes squalene and phytoene synthases which catalyze the 1'-1 condensation of two 15-carbon (farnesyl) and 20-carbon (geranylgeranyl) isoprenyl diphosphates, respectively . The catalytic site consists of a large central cavity formed by mostly antiparallel α helices with two aspartate-rich regions (DXXXD) located on opposite walls . These residues mediate binding of prenyl phosphates . A two-step reaction has been proposed for squalene synthase (farnesyl-diphosphate farnesyltransferase) in which, two molecules of FPP react to form a stable cyclopropylcarbinyl diphosphate intermediate, and then the intermediate undergoes heterolysis, isomerization, and reduction with NADPH to form squalene, a precursor of cholesterol. The carotenoid biosynthesis enzyme, phytoene synthase (CrtB), catalyses the condensation reaction of two molecules of geranylgeranyl diphosphate to produce phytoene, a precursor of beta-carotene . These enzymes produce the triterpene and tetraterpene precursors for many diverse sterol and carotenoid end products and are widely distributed among eukaryota, bacteria, and archaea .
Glycosyltransferase HPAT/SRGT1-like (HPAT/SRGT1-like)
Type: Family

This entry represents a group of plant glycosyltransferases, including HPAT1-3 and SERGT1 from Arabidopsis. HPAT1 is a hydroxyproline O-arabinosyltransferase involved in the O-arabinosylation of several proteins including extensins and small signaling peptides . It catalyses the transfer of the initial L-arabinose to the hydroxyl group of Hyp residues . SERGT1, also known as AtSGT1, is a peptidyl serine O-alpha-galactosyltransferase .

Proteins in this entry also include PLENTY from Lotus japonicus and RDN1/2 (ROOT DETERMINED NODULATION1/2) from Medicago truncatula .
Glycoside hydrolase family 10 (GH10)
Type: Family

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.

Glycoside hydrolase family 10

comprises enzymes with a number of known activities; xylanase (

); endo-1,3-beta-xylanase (

); cellobiohydrolase (

). These enzymes were formerly known as cellulase family F.

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

), cellobiohydrolases (

) (exoglucanases), or xylanases (

) . Fungi and bacteria produces a spectrum of cellulolytic enzymes (cellulases) and xylanases which, on the basis of sequence similarities, can be classified into families. One of these families is known as the cellulase family F or as the glycosyl hydrolases family 10 .
Transcription repressor KANADI (KAN_fam)
Type: Family

This entry represents KANADI (Kan), a family of plant transcription factors. In Arabidopsis, there are four Kan members, KAN1-4, which are expressed in the phloem. KAN1 may control cambium activity through acting on auxin transport by inhibiting PIN gene expression . KAN1 has also been shown to repress the transcription of AS2 (ASYMMETRIC LEAVES2) in abaxial cells and regulate adaxial-abaxial polarity . It also plays a role in lateral root formation and development . This entry also includes RL9 (also known as SHALLOT-LIKE1, SLL1) from Oryza sativa subsp. japonica. RL9 controls rice leaf rolling by regulating leaf abaxial cell development .
Ion channel CASTOR/POLLUX/SYM8-like (CASTOR/POLLUX/SYM8-like)
Type: Family

This entry includes proteins that belong to the CASTOR/POLLUX/SYM8 family of ion channels, which are found in plants . They have been implicated in modulating the nuclear membrane envelope potential . It has been shown that Os-CASTOR and Os-POLLUX are indispensable for mycorrhizal symbiosis in rice . This entry also includes uncharacterised bacterial proteins.
Cysteine-rich and transmembrane domain-containing protein WIH1-like (WIH1-like)
Type: Family

This entry represents a group of cysteine-rich and transmembrane domain-containing proteins, including WIH1 (also known as CYSTEINE-RICH TRANSMEMBRANE MODULE 13), At3g57160 and CYSTEINE-RICH TRANSMEMBRANE MODULE (CYSTM) 1, 3-6 and 8 from Arabidopsis. WIH1 is required for the promotion of megasporogenesis, or promotion of germ cell formation from somatic precursor cells. It functions in a genetic pathway downstream of SPL/NZZ and WUS and together with TORNADO2 (TRN2) in promoting megasporogenesis . WIH1 is also involved in resistance to abiotic stress . CYSTMs, are ubiquitous non-secreted cysteine-rich proteins, which play an important role in resistance to abiotic stress . CYSTM3 negatively regulates salt stress responses and Na+ homeostasis .
Wax synthase (Wax_synthase)
Type: Family

This entry includes a group of membrane bound O-acyltransferases, including long-chain-alcohol O-fatty-acyltransferase (wax synthases) from plants and fungi and acyl-CoA sterol acyl transferase 1 from Arabidopsis . This entry also includes the fungal Acetyltransferase FUP5 that catalyses the final step of the pathway by adding an acetyl group at the C-24 position of terpestacin to yield fusaproliferin .
WW domain-binding protein 2-like (WBP2-like)
Type: Family

This entry represents WBP2 and related proteins from animals, fungi and plants.

WBP2 encodes the WW domain-binding protein 2 that acts as a transcriptional coactivator for the estrogen and progesterone receptors . WBP2 binds to the target gene promoter and is required for the binding of the phosphorylated form of RNA polymerase II to the same promoter. Furthermore, it is also essential for histone acetylation at the same target region .

WWP2 N-terminal-like (WBP2NL), also known as post-acrosomal sheath WW domain-binding protein (PAWP), is a testis-specific protein localized in the post-acrosomal sheath of spermatozoa . The WBP2NL protein enters the oocyte during fertilization, and induces meiotic resumption and oocyte activation events . It may be associated with cellular proliferation and tumourigenic processes .
IrrE, HTH domain (G3DSA:1.10.10.1030)
Type: Homologous_superfamily

This superfamily represents the HTH (helix-turn-helix) central domain from the metalloprotease IrrE, a central regulator of DNA damage repair in Deinococcaceae . It is folded in a three-helix bundle, with the second and third helices forming the HTH motif. The IrrE HTH domain shows a high level of structural similarity to HTH domains of the Lrp/AsnC transcriptional regulatory family, although it is not located as expected at either C- or N-terminal of the protein. Its central location was suggested to endow it with some specific properties .

The domain is also found at the C-terminal of the catalytic domain of the protein ImmA (MEROPS identifier M78.001), a metallopeptidase containing an HEXXH zinc-binding motif.
Signal transduction protein PmrD (PmrD_dom)
Type: Domain

PmrA/PmrB and PhoP/PhoQ are a pair of two-component systems (TCSs) that allow the Gram-negative bacteria to survive the cationic antimicrobial peptide polymyxin B. The two TCSs are linked by the polymyxin resistance protein, PmrD . This entry represents a domain found in PmrD. This domain can also be found in anti-adapter protein IraM, a protein which inhibits rpoS proteolysis by regulating rssB activity, thereby increasing the stability of the sigma stress factor rpoS during magnesium starvation .

The Salmonella PmrA/PmrB two-component system is required for resistance to the cationic peptide antibiotic olymyxin B, resistance to Fe(3+)-mediated killing, growth in soil, virulence in mice, and infection of chicken macrophages. PmrA-activated genes encode periplasmic and integral membrane proteins as well as cytoplasmic products mediating the modification of the lipopolysaccharide, suggesting a role for the PmrA/PmrB system in remodeling of the Gram-negative envelope .

The PmrA/PmrB two-component system of Salmonella enterica is activated by Fe(3+), which is sensed by the PmrB protein, and by low Mg(2+), which is sensed by the PhoQ protein. The low Mg(2+) activation requires pmrD, a PhoPPhoQ-activated gene that activates the response regulator PmrA at a posttranscriptional level. However, under conditions that activate the PmrA protein independently of pmrD, such as exposure to Fe3, lower levels of pmrD transcription occur. It has been demonstrated that PmrA binds to the pmrD promoter, suppressing transcription. Negative regulation of the PhoP/PhoQ-activated pmrD gene by the PmrA/ PmrB system closes a regulatory circuit designed to maintain proper cellular levels of activated PmrA protein, and constitutes a singular example of a multicomponent feedback loop .
CoA-transferase family III domain 3 superfamily (CoA-Trfase_III_dom3_sf)
Type: Homologous_superfamily

This superfamily represents the small domain (domain 3) of family III CoA-transferases .

CoA-transferases are found in organisms from all kingdoms of life. They catalyse reversible transfer reactions of coenzyme A groups from CoA-thioesters to free acids. There are at least three families of CoA-transferases, which differ in sequence and reaction mechanism:

Family I consists of CoA-transferases for 3-oxoacids (

,

), short-chain fatty acids (

,

) and glutaconate (

). Most use succinyl-CoA or acetyl-CoA as CoA donors.

Family II consists of the homodimeric alpha-subunits of citrate lyase and citramalate lyase (

,

). These enzymes catalyse the transfer of acyl carrier protein (ACP) with a covalently bound CoA derivative, but can accept free CoA thioesters as well.

Family III consists of formyl-CoA:oxalate CoA-transferase , succinyl-CoA:(R)-benzylsuccinate CoA-transferase , (E)-cinnamoyl-CoA:(R)-phenyllactate CoA-transferase , succinyl-CoA:mesaconate CoA-transferase and butyrobetainyl-CoA:(R)-carnitine CoA-transferase . These CoA-transferases occur in prokaryotes and eukaryotes, and catalyse CoA-transfer reactions in a highly substrate-and stereo-specific manner .
Malate synthase, C-terminal superfamily (Malate_synth_C_sf)
Type: Homologous_superfamily

Malate synthase (MS) (

) catalyses the aldol condensation of glyoxylate with acetyl-CoA to form malate as part of the second step of the glyoxylate bypass and an alternative to the tricarboxylic acid cycle in bacteria, fungi and plants. There have been identified two isoforms, A and G (MSA and MSG, respectively) that differ in size and is attributed to an inserted α/β domain in MSG that may have regulatory function . MSA and MSG consist of an N-terminal α-helical clasp domain, a central TIM-barrel domain and a C-terminal helical plug domain. In malate synthases, the TIM β/α-barrel fold and the C-terminal helical domain are well conserved and the cleft between them forms the active site .

This superfamily represents the α-helical C-terminal domain of malate synthases that caps the active site .
Type VII secretion system EccB, repeat 1 domain (T7SS_EccB_R1)
Type: Homologous_superfamily

The ESX-1 type VII (T7SS) secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. The protein EccB1, a core component of the T7SS, is an ATPase required for the secretion of virulence factors by the ESX-1 system. The periplasmic domain of EccB1 is composed of five domains, 4 repeat domains and a central domain. The repeat domains of EccB1 are structurally similar to a known peptidoglycan binding protein which suggest their role in anchoring the ESX-1 system within the periplasmic space .

This superfamily represents the repeat 1 (R1) domain of EccB1.
Stomagen, C-terminal domain (Stomagen_C)
Type: Domain

This entry represents the C-terminal domain of Stomagen.

Stomagen (epidermal patterning factor-like protein 9) is a defensin-like secretory epidermal patterning factor (EPF) peptide hormones which acts as a positive regulator of stomatal development .

The structure of stomagen is composed of a loop and a scaffold containing three disulphide bonds .
Allene oxide cyclase/Dirigent protein (Allene_oxi_cyc_Dirigent)
Type: Homologous_superfamily

This superfamily consists of several plant specific allene oxide cyclase proteins (

). The allene oxide cyclase (AOC)-catalysed step in jasmonate (JA) biosynthesis is important in the wound response of tomato .

The superfamily also contains Dirigent proteins. Dirigent proteins impart stereoselectivity on the phenoxy radical-coupling reaction, yielding optically active lignans from two molecules of coniferyl alcohol in the biosynthesis of lignans, flavonolignans, and alkaloids and thus plays a central role in plant secondary metabolism .

Dirigent proteins and allene oxide cyclases exert stereochemical control on a cyclization reaction. Both share common structural features .
Methuselah ectodomain, domain 1 (Methusela_ecto_dom_1)
Type: Homologous_superfamily

Drosophila Methuselah (Mth) mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage. The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family. Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site .

This entry represents a structural subdomain found at the N-termimus of the Methusela ectodomain.
Isopenicillin N synthase-like, Fe(2+) 2OG dioxygenase domain (IPNS-like_FE2OG_OXY)
Type: Domain

This entry represents the Fe(2) 2-oxoglutarate dioxygenase domain found in isopenicillin N synthase PcbC from fungi and related proteins such as procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) from humans and 1-aminocyclopropane-1-carboxylate oxidase 1 from plants.

The iron 2OG dioxygenase domain has a conserved β-barrel structure , which forms a double-stranded β-helix core fold that forms the predominant class of the cupin superfamily ('cupa' means a small barrel in Latin) . Two histidines and an aspartate residue catalytically bind a metal ion, in general iron but in some cases another metal, directly involved in catalysis. A conserved arginine or lysine residue further near the C-terminal part acts as the basic residue that interacts with the acidic substrate.

Isopenicillin N synthase (IPNS) catalyses conversion of the linear tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N (IPN), the central step in biosynthesis of the beta-lactam antibiotics . IPNS is a nonhaem-Fe2+-dependent enzyme. It belongs to a class of nonhaem Fe2+-containing enzymes which includes 2-oxoglutarate-dependent dioxygenases, 2-oxoglutarate-dependent hydroxy- lases, and enzymes involved in ethylene formation and anthocyaninidin biosynthesis.

The IPNS structure shows that the active site is buried within the hydrophobic pocket of an eight-stranded jelly roll barrel .
Prolyl 4-hydroxylase alpha subunit, Fe(2+) 2OG dioxygenase domain (Pro_4_hyd_alph_FE2OG_OXY)
Type: Domain

This entry represents the Fe(2) 2-oxoglutarate dioxygenase domain found in prolyl 4-hydroxylase alpha subunit 1/2/3 from animals and related proteins such as PKHD-type hydroxylase YbiX from bacteria.

The iron 2OG dioxygenase domain has a conserved β-barrel structure , which forms a double-stranded β-helix core fold that forms the predominant class of the cupin superfamily ('cupa' means a small barrel in Latin) . Two histidines and an aspartate residue catalytically bind a metal ion, in general iron but in some cases another metal, directly involved in catalysis. A conserved arginine or lysine residue further near the C-terminal part acts as the basic residue that interacts with the acidic substrate.

Mammalian prolyl 4-hydroxylase alpha catalyses the posttranslational formation of 4-hydroxyproline in -xaa-pro-gly-sequences in collagens and other proteins. Prokaryotic enzymes might catalyse hydroxylation of antibiotic peptides. These are 2-oxoglutarate-dependent dioxygenases, requiring 2-oxoglutarate and dioxygen as cosubstrates and ferrous iron as a cofactor .
Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain (NIRAN)
Type: Domain

Positive-stranded RNA (+RNA) viruses that belong to the order Nidovirales infect a wide range of vertebrates (families Arteriviridae and Coronaviridae) or invertebrates (Mesoniviridae and Roniviridae). Examples of nidoviruses with high economic and societal impact are the arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) and the zoonotic coronaviruses (CoVs) causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Covid-19 (SARS-CoV-2) in humans. In all nidoviruses, at least two-thirds of the capacity of the polycistronic genome is occupied by the two large open reading frames (ORFs; 1a and 1b) that together constitute the replicase gene. The two polyproteins produced, pp1a (ORF1a-encoded) and pp1ab (ORF1a/ORF1b-encoded), are processed to a dozen or more proteins by the virus main protease (3CLpro, encoded in ORF1a) with possible involvement of other protease(s). These and other proteins form a membrane-bound replication-transcription complex (RTC) that invariably includes two key ORF1b-encoded subunits: the RNA-dependent RNA polymerase (RdRp) and a superfamily 1 helicase domain (HEL1), which is fused with a multinuclear Zn-binding domain (ZBD). The RNA-dependent RNA polymerase (RdRp) domain of nidoviruses resides in a cleavage product of the replicase polyprotein named non- structural protein (nsp) 12 in coronaviruses and nsp9 in arteriviruses. In all nidoviruses, the C-terminal RdRp domain is linked to a conserved N-terminal domain, which has been coined NiRAN (nidovirus RdRp-associated nucleotidyl transferase). The NiRAN domain has an essential nucleotidylation activity and its potential functions in nidovirus replication may include RNA ligation, protein-primed RNA synthesis, and the guanylyl-transferase function that is necessary for mRNA capping .

The NiRAN domain is characterised by an α+β fold composed of eight α-helices and a five stranded β-sheet. In addition, an N-terminal β-hairpin interacts with the palm subdomain of the RdRp domain .