SII-SWORD/CoKE huggingface dataset:
3-ketodihydrosphingosine reductase KDSR-like (KDSR-like)
Type: Family

This entry represents a group of 3-ketodihydrosphingosine reductases, including KDSR from animals and Tsc10 from yeasts and plants. They catalyse the reduction of 3-ketodihydrosphingosine (KDS) to dihydrosphingosine (DHS) and are required for sphingolipid biosynthesis .

Proteins in this entry show strong conservation of the active site tetrad and glycine rich NAD-binding motif of the classical SDRs. SDRs are a functionally diverse family of oxidoreductases that have a single domain with a structurally conserved Rossmann fold (α/β folding pattern with a central β-sheet), an NAD(P)(H)-binding region, and a structurally diverse C-terminal region. Classical SDRs are typically about 250 residues long, while extended SDRs are approximately 350 residues. Sequence identity between different SDR enzymes are typically in the 15-30% range, but the enzymes share the Rossmann fold NAD-binding motif and characteristic NAD-binding and catalytic sequence patterns. These enzymes catalyse a wide range of activities including the metabolism of steroids, cofactors, carbohydrates, lipids, aromatic compounds, and amino acids, and act in redox sensing .

Classical SDRs have an TGXXX[AG]XG cofactor binding motif and a YXXXK active site motif, with the Tyr residue of the active site motif serving as a critical catalytic residue (Tyr-151, human 15-hydroxyprostaglandin dehydrogenase (15-PGDH) numbering). In addition to the Tyr and Lys, there is often an upstream Ser (Ser-138, 15-PGDH numbering) and/or an Asn (Asn-107, 15-PGDH numbering) contributing to the active site; while substrate binding is in the C-terminal region, which determines specificity. The standard reaction mechanism is a 4-pro-S hydride transfer and proton relay involving the conserved Tyr and Lys, a water molecule stabilized by Asn, and nicotinamide. Extended SDRs have additional elements in the C-terminal region, and typically have a TGXXGXXG cofactor binding motif. Complex (multidomain) SDRs such as ketoreductase domains of fatty acid synthase have a GGXGXXG NAD(P)-binding motif and an altered active site motif (YXXXN). Fungal type ketoacyl reductases have a TGXXXGX(1-2)G NAD(P)-binding motif. Some atypical SDRs have lost catalytic activity and/or have an unusual NAD(P)-binding motif and missing or unusual active site residues. Reactions catalyzed within the SDR family include isomerization, decarboxylation, epimerization, C=N bond reduction, dehydratase activity, dehalogenation, Enoyl-CoA reduction, and carbonyl-alcohol oxidoreduction .
Acyl-[acyl-carrier-protein] hydrolase FATA/B (FATA/B)
Type: Family

This family represents acyl-acyl carrier protein (ACP) thioesterases ([ec:3.1.2.-]), enzymes from bacteria and plants that control the termination of fatty acid synthesis by hydrolyzing the acyl-ACP complexes and determines the fatty acid profiles produced by an organism . These enzymes are classified as FatA and FatB. FatA thioesterases (or oleoyl-thioesterases) are highly conserved between different plant species and have high specificity for oleoyl-ACP . Unlike FatA, FatB thioesterases are much more variable and preferentially hydrolyse acyl-ACPs with saturated fatty acyl chains; they can be classified in subfamilies depending on their substrate of preference .
Alternative NADH dehydrogenase (NDH-2)
Type: Family

This entry represents a group of alternative NADH:quinone oxidoreductases (also known as NDH-2) that deliver electrons to the respiratory chain by oxidation of NADH and reduction of quinones but does not pump protons . NDH-2 have particular relevance in yeasts like Saccharomyces cerevisiae and in several prokaryotes, whose respiratory chains are devoid of complex I, in which NDH-2 keep the balance and are the main entry point of electrons into the respiratory chains . Structures of NDH-2 from the yeast Saccharomyces cerevisiae, also called Ndi1 (

and

), and those from bacteria, Caldalkalibacillus thermarum (

) and Staphylococcus aureus (

), have been determined . Interestingly, since NDH-2s are present only in bacteria and certain plant, fungal and protozoan mitochondria, but not in mammals, they have been used as a drug target for Mycoplasma tuberculosis, Plasmodium falciparum and Toxoplasma gondii .
TPP-binding domain containing protein HACL1-like (HACL1-like)
Type: Family

This entry represents a group of TPP-binding domain containing proteins, including oxalyl-CoA decarboxylase from E. coli, IorA from Thermococcus kodakarensis and HACL1 from animals. In general, they are thiamine pyrophosphate-dependent enzymes that catalyse the carbon-carbon bond cleavage . In humans, HACL1 is a peroxisomal 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the fatty acid alpha-oxidation in a thiamine pyrophosphate (TPP)-dependent manner . It is also involved in the degradation of 3-methyl-branched fatty acids like phytanic acid and the shortening of 2-hydroxy long-chain fatty acids .
L10-interacting MYB domain-containing protein (LIMYB)
Type: Family

L10-interacting MYB domain-containing protein (LIMYB) is a transcriptional repressor that associates with ribosomal protein promoters . It interacts with NIK1, a leucine-rich repeat receptor-like kinase (LRR-RLK), the virulence target of the begomovirus nuclear shuttle protein, leading to global translation suppression as an antiviral immunity strategy in plants .
Homer family (Homer)
Type: Family

Homer (also known as Vesl) family members, including Homer1/2/3, are synaptic scaffolding proteins that regulate localisation of group 1 metabotropic glutamate receptors (mGluRs), which are known to play major roles in neural signal transduction. Homer family members contain the EVH1 domain at the N terminus for receptor binding, two leucine zipper motifs at the C terminus for clustering, and a linking region whose function is unclear. Besides binding to mGluR, Homer family members also recognise the PPXXF motif found in other binding partners . Homer2 and Homer3, but not Homer1, have been shown to bind to nuclear factor of activated T cells (NFAT) and serve as negative regulators of NFAT-dependent signaling in T cells .
LysM and putative peptidoglycan-binding domain-containing protein 1-4 (LYSM1-4)
Type: Family

This entry represents a group of LysM and putative peptidoglycan-binding domain-containing proteins, including LYSMD1-4 from humans. The lysin motif (LysM) of LysMDs is likely related to a previously described peptidoglycan-binding LysM found in bacteria. LysMD3 is a type II membrane protein .
Dihydropteroate synthase-like (DHP_synth-like)
Type: Family

Dihydropteroate synthase (

) (DHPS), a functional homodimer, catalyses the condensation of 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate to para-aminobenzoic acid to form 7,8-dihydropteroate. This is the second step in the three-step pathway leading from 6-hydroxymethyl-7,8-dihydropterin to 7,8-dihydrofolate. DHPS is the target of sulfonamides, which are substrate analogues that compete with para-aminobenzoic acid. Bacterial DHPS (gene sul or folP) is a protein of about 275 to 315 amino acid residues that is either chromosomally encoded or found on various antibiotic resistance plasmids. In the lower eukaryote Pneumocystis carinii, DHPS is the C-terminal domain of a multifunctional folate synthesis enzyme (gene fas) . Prokaryotes (and some lower eukaryotes) must synthesize folate de novo, while higher eukaryotes are able to utilize dietary folate and therefore lack DHPS.

This entry also includes the uncharacterised protein MJ0107 from Methanocaldococcus jannaschii (

), which does not possess DHPS activity.
Pectin lyase family (PEL)
Type: Family

Pectate lyase

is an enzyme involved in the maceration and soft rotting of plant tissue. Pectate lyase is responsible for the eliminative cleavage of pectate, yielding oligosaccharides with 4-deoxy-alpha-D-mann-4-enuronosyl groups at their non-reducing ends. The protein is maximally expressed late in pollen development. It has been suggested that the pollen expression of pectate lyase genes might relate to a requirement for pectin degradation during pollen tube growth .

The structure and the folding kinetics of one member of this family, pectate lyase C (pelC)1 from Erwinia chrysanthemi has been investigated in some detail . PelC contains a parallel β-helix folding motif. The majority of the regular secondary structure is composed of parallel β-sheets (about 30%). The individual strands of the sheets are connected by unordered loops of varying length. The backbone is then formed by a large helix composed of β-sheets. There are two disulphide bonds in pelC and 12 proline residues. One of these prolines, Pro220, is involved in a cis peptide bond. he folding mechanism of pelC involves two slow phases that have been attributed to proline isomerization.
Protein PIN-LIKES 1/3/4/5/7 (PILS1/3/4/5/7)
Type: Family

This entry includes proteins PIN-LIKES 1/3/4/5/7 from Arabidopsis. They regulate intracellular auxin accumulation at the endoplasmic reticulum and thus auxin availability for nuclear auxin signalling .
O-acyltransferase WSD1-like (O-acyltransferase_WSD1-like)
Type: Family

This entry represents O-acyltransferases mainly from plants and bacteria, including WSD1 from Arabidopsis thaliana, a bifunctional wax ester synthase/diacylglycerol acyltransferase, which is involved in cuticular wax biosynthesis and is required to reduce leaf water loss, especially during drought . This family also includes tgs1-4 from Mycobacterium tuberculosis, which function as triacylglycerol synthases with very weak or no wax synthase activity .
Metal-nicotianamine transporter YSL-like (YSL-like)
Type: Family

This family represents a group of oligopeptide transporters, including YSL1-18 from plants and related proteins from fungi, bacteria and archaea. YSL1-18 may be involved in the lateral transport of nicotianamine-chelated metals in the vasculature . They are members of the OPT superfamily of small oligopeptides transporters.
Spartin-like (Spartin-like)
Type: Family

This entry includes senescence/dehydration-associated proteins from plants and Spartin from animals. This group of proteins share the C-terminal AAA ATPase domain .

Besides its C-terminal AAA ATPase domain, Spartin contains an N-terminal MIT (contained within microtubule-interacting and transport molecules) domain and a -P-P-x-Y- motif. Spastin monomers assemble into hexameric, ring-shaped ATPases that sever microtubules along their lengths
. In flies, Spartin has been shown to regulates both synaptic development and neuronal survival by controlling microtubule stability via the BMP-dFMRP-Futsch pathway . In humans, Spartin (also known as SPG20) has been linked to Troyer syndrome, characterised by spastic dysarthria, cognitive impairment, short stature, and distal muscle wasting in addition to lower extremity spastic weakness . SPG20 has been shown to be recruited to the midbody and participates in cytokinesis .

In plants, this group of proteins have been linked to senescence and dehydration . Different from their animal homologues, they don't have the MIT domain. In Hemerocallis, petals have a genetically based program that leads to senescence and cell death approximately 24 hours after the, flower opens, and it is believed that senescence proteins produced around that time have a role in this program .
Protein AIG2-like (AIG2-like)
Type: Family

Gamma-glutamyl cyclotransferases (GGCTs) are ubiquitous enzymes found in bacteria, plants, and metazoans. This family includes AIG2 proteins from Arabidopsis, which exhibit RPS2- and avrRpt2-dependent induction early after infection with Pseudomonas syringae pv maculicola strain ES4326 carrying avrRpt2 . Its structure consists of a five-stranded β-barrel surrounded by two α-helices and a small β-sheet. A long flexible α-helix protrudes from the structure at the C-terminal end. Conserved residues in a hydrophilic cavity, which are able to bind small ligands, may act as an active site in AIG2-like proteins .
Acetyltransferase NSI-like (NSI-like)
Type: Family

This entry represents acetyltransferases found in pro- and eukaryotes.

This entry includes a group of plant acetyltransferases, including NSI from Arabidopsis (also known as GCN5-related N-acetyltransferase 2), SNAT1/2 from rice and Histone acetyltransferase TAP1/2 from Glycine max (Soybean). NSI is a vascular-expressed acetyltransferase that interacts with NSP, which is a nuclear shuttle protein . It has dual specificity triggering both N-alpha-acetylation (NTA), with a preference for alanine, serine, threonine, methionine and to a lower extent valine as substrates (can also use glycine and leucine), and epsilon-lysine acetylation (KA) of several plastid proteins . NSI is also involved in melatonin biosynthesis by catalysing the formation of N-acetylserotonin (NAS) from serotonin and of melatonin (N-acetyl-5-methoxytryptamine) from 5-methoxytryptamine (5-MT) . It has been shown to regulate the nuclear export of the viral genome and potentially other non transcriptional nuclear events in plant cells . SNAT1 catalyses the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin . TAP1 acts as a susceptibility factor that is hijacked by Avh52 in order to promote acetylation of histones H2A and H3 during early infection by Phytophthora sojae .

This entry also includes ArgA amino-acid acetyltransferase from Mycobacterium tuberculosis that catalyses the conversion of L-glutamate to alpha-N-acetyl-L-glutamate .
PORR family (PORR_fam)
Type: Family

This entry represents the PORR (plant organelle RNA recognition domain, previously DUF860) family of proteins which localise to either mitochondria or chloroplasts, and it seems likely that most PORR proteins function in organellar RNA metabolism. Including in this family are Protein root primordium defective 1-like (RPD1) and Protein WHAT'S THIS FACTOR1 . RPD1 is involved in pre-arranging the maintenance of the active cell proliferation during root primordium development . WTF1 is a RNA-binding protein involved in the chloroplastic group II intron splicing .
Mechanosensitive ion channel protein YnaI-like (YnaI-like)
Type: Family

This entry represents a group of mechanosensitive channel proteins from bacteria and plants, including YnaI from E. coli and MSL2/3 from Arabidopsis. YnaI has been shown to protect cells against hypoosmotic stress when highly overexpressed . MSL2/3 are chloroplastic proteins that regulate chloroplast size and FtsZ ring formation .
Late embryogenesis abundant protein Lea14-like (Lea14-like)
Type: Family

This family includes Lea14-like proteins which contain a Water Stress and Hypersensitive response (WHy) domain, a region of unknown function found in several plant proteins involved in either the response to water stress or the response to bacterial infection . This entry also includes WHy domain-containing proteins from bacteria. Their function is not clear.

LEA (late embryogenesis abundant) proteins were first identified in land plants. Plant LEA proteins have been found to accumulate to high levels during the last stage of seed formation (when a natural desiccation of the seed tissues takes place) and during periods of water deficit in vegetative organs. Later, LEA homologues have also been found in various species . They have been classified into several subgroups in Pfam and according to Bray and Dure .
Vacuolar protein sorting-associated protein 9-like (Vps9-like)
Type: Family

Proteins in this entry contain the VPS9 domain that can act as guanine nucleotide exchange factors (GEFs) against small G proteins of the Rab5 family. In budding yeasts, Vps9 is involved in vesicle-mediated vacuolar transport .
N-acetyltransferase Ard1-like (Ard1-like)
Type: Family

Ard1 and Nat1 form a stable N-terminal acetyltransferase complex and are conserved from yeast to human . This entry represents Ard1, which is the catalytic subunit. The ARD1-NAT1 complex mediates N-terminal acetylation of nascent polypeptides that emerge from ribosomes after translation .
F-box only protein 31/39 (FBXO31/39)
Type: Family

This entry represents a group of F-box only proteins, including FBXO31/39 from humans and HAWAIIAN SKIRT (At3g61590) from Arabidopsis.

HAWAIIAN SKIRT (HWS; At3G61590) is a F-box dependent factor involved in miRNA function . Loss of function of HWS exhibits pleiotropic phenotypes including sepal fusion .

F-box only protein 31 is a component of the SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. It specifically recognises phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest .
Choline-phosphate cytidylyltransferase Pcy1-like (Pcy1-like)
Type: Family

This entry represents a group of choline-phosphate cytidylyltransferases (CCTs), including PCYT1A/B (CCT-alpha/beta) from humans and Pcy1 from budding yeasts. CCT catalyses the key rate-limiting step in CDP-choline pathway for phosphatidylcholine biosynthesis .
Synaptotagmin, plant (Synaptotagmin_plant)
Type: Family

This entry represents a group of plant synaptotagmins and related proteins. In Arabodopsis, there are five members, SYT1-5. Structurally, they have a short uncleaved N-terminal signal peptide that overlaps a transmembrane (TM) domain, followed by a cytosolic variable region and two C-terminal C2 domains, C2A and C2B. Whereas C2A and C2B each bind phospholipids in a Ca2+-dependent manner, fold independently and act synergistically, C2B is essential for activity . Arabidopsis SYT1, also known as SYTA, plays an important role in maintaining plasma membrane integrity during freezing and osmotic stresses . It also serves as a virus movement protein that transports its cargos to plasmodesmata for cell-to-cell spread via an endocytic recycling pathway .
Subtilisin-like protease (SBT)
Type: Family

This entry represents a group of subtilisin-like proteases mostly from plants and bacteria. Proteins in this entry include melon cucumisin, Arabidopsis thaliana Ara12, a nodule specific serine protease from Alnus glutinosa ag12, members of the tomato P69 family, and tomato LeSBT2. These proteins belong to the peptidase S8 family.

Cucumisin from the juice of melon fruits is a thermostable serine peptidase, with a broad substrate specificity for oligopeptides and proteins. A. thaliana Ara12 is a thermostable, extracellular serine protease, found chiefly in silique tissue and stem tissue. Ara12 is stimulated by Ca2+ ions. A. glutinosa ag12 is expressed at high levels in the nodules, and at low levels in the shoot tips; it is implicated in both symbiotic and non-symbiotic processes in plant development. The tomato P69 protease family is comprised of various protein isoforms of approximately 69kDa. These isoforms accumulate extracellularly. Some of the P69 genes are tightly regulated in a tissue specific fashion, and by environmental and developmental signals. For example: infection with avirulent bacteria activates transcription of the genes for the P69 B and C isoforms, the P69 E transcript was detected only in roots, and the P69F transcript only in hydathodes. The Tomato LeSBT2 subtilase transcript was not detected in flowers and roots, but was present in cotyledons and leaves. The significance of the PA domain to these proteins has not been ascertained. It may be a protein-protein interaction domain. At peptidase active sites, the PA domain may participate in substrate binding and/or promoting conformational changes, which influence the stability and accessibility of the site to substrate.
Copine (Copine)
Type: Family

Copines are a widely distributed class of Ca2+-dependent lipid-binding proteins. Most have a characteristic domain structure: two C2 domains in the N-terminal region and a von Willebrand A (VWA) domain in the C-terminal region. They are potentially involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth . In plants, they are known as BONZAI proteins . The copine family in plants may have effects in promoting growth and development in addition to repressing cell death . Caenorhabditis elegans copine, also known as Nra1, is Involved in nicotinic acetylcholine receptor (nAChR)-mediated sensitivity to nicotine and levamisole .
Mannan endo-1,4-beta-mannosidase-like (MAN-like)
Type: Family

This family includes mannan endo-1,4-beta-mannosidases from plants and fungi (

). They catalyse the random hydrolysis of (1->4)-beta-D-mannosidic linkages in mannans, galactomannans and glucomannans and are crucial for depolymerization of seed galactomannans and wood galactoglucomannans . The deconstruction of the plant cell wall has had increasing importance as a key biological process in the development of a sustainable biofuel industry . In plants, they are related to the process of weakening the tissues surrounding the embryo during seed germination .

This entry also includes cellulase domain-containing proteins from bacteria.
Prolyl 4-hydroxylase (P4HA-like)
Type: Family

This entry includes prolyl 4-hydroxylases from eukaryotes and related proteins from prokaryotes.

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 .
DNA2/NAM7-like helicase (DNA2/NAM7-like)
Type: Family

This entry represents a group of helicases, including DNA2 and Nam7. Proteins in this family contain a conserved domain with is a P-loop motif that is characteristic of the AAA superfamily. They are DEAD-like helicases belonging to superfamily (SF)1, a diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. Similar to SF2 helicases, SF1 helicases do not form toroidal structures like SF3-6 helicases. Their helicase core consists of two similar protein domains that resemble the fold of the recombination protein RecA .

DNA2 is a DNA replication factor with single-stranded DNA-dependent ATPase, ATP-dependent nuclease, (5'-flap endonuclease) and helicase activities . Nam7 (also known as Upf1) is an ATP-dependent RNA helicase involved in the nonsense-mediated mRNA decay (NMD) pathway .
Nucleolar protein Nop56/Nop58 (Nop56/Nop58)
Type: Family

This entry includes a group of pre-RNA processing ribonucleoproteins (RNPs), including Nop56/Nop58 from animals and their homologue, Nop5, from archaea. Proteins in this family contains the Nop domain, which is a RNP binding module, exhibiting RNA and protein binding surfaces. It is oval-shaped and exclusively α-helical .

Nucleolar protein 56 and 58 (NOP56/58) are required for 60S ribosomal subunit synthesis . They are core components of box C/D small nucleolar ribonucleoprotein (snoRNP) particles . In humans, NOP56 is associated with a type of slowly progressive neurodegenerative disorder characterised by late-onset ataxia followed by variable involvement of the motor neuron system .
Gcn5-related N-acetyltransferase (Gcn5-rel_NAT)
Type: Family

This family represents Gcn5-related N-acetyltransferases (GNAT) ([ec:2.3.1.-]), which catalyse the transfer of the acetyl from the CoA donor to a primary amine of the acceptor and share a domain composed of four conserved sequence motifs A-D . It includes Protein NATD1 from animals, Acetyltransferase At1g77540 from Arabidopsis and the uncharacterised protein YjdJ from E.coli. At1g77540 is a H3/H4 histone acetyltransferase .