SII-SWORD/CoKE huggingface dataset:
Nitrate/bicarbonate ABC transporter substrate-binding domain (NrtA/CpmA_ABC-bd_dom)
Type: Domain

This entry includes a domain found in nitrate (Nrt) and bicarbonate (Cmp) receptors. This domain is found in eubacterial periplasmic-binding proteins that serve as initial receptors in the ABC transport of bicarbonate, nitrate, taurine, or a wide range of aliphatic sulfonates . After binding its ligand with high affinity, it interacts with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energised by ATP hydrolysis. These binding proteins belong to the PBP2 superfamily of periplasmic-binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap .

In cyanobacteria, nitrate transport takes place through NRT system, a multicomponent ABC transporter. NRT consists of 4 proteins: a periplasmic substrate-binding protein (NrtA) involved in the specific and high affinity binding of nitrate and nitrite. NrtB is a hydrophobic protein with structural similarities to integral membrane subunits of ABC transporters . It is thought to form a pore across the membrane to allow the translocation of nitrate and nitrite. Finally, NrtC and NrtD are proposed to form a heterodimer associated to the inner side of the cytoplasmic membrane, and to be responsible of energising the transport system via ATP hydrolysis. In NrtC the binding site for ATP in found at the N-terminal .

The cmpA, cmpB, cmpC, and cmpD genes are strongly similar to the genes encoding the nitrate/nitrite transporter, nrtA, nrtB, nrtC, and nrtD, respectively. NrtB and CmpB are hydrophobic proteins with structural similarities to the integral membrane components of ABC transporters. CmpC and CmpD are ATP-binding cassette proteins strongly similar to NrtC and NrtD, respectively. CmpA is a cytoplasmic membrane protein, which is 46.5% identical to NrtA that functions as the membrane-anchored substrate (nitrate and nitrite)-binding protein . The similarity of CmpA to NrtA and its involvement in HCO(3)(-) uptake suggest that CmpA is the substrate-binding protein of the HCO(3)(-) transporter .
Persulfide dioxygenase-like, MBL-fold metallo-hydrolase domain (POD-like_MBL-fold)
Type: Domain

Persulfide dioxygenase (PDO, also known as sulfur dioxygenase, SDO,

) is a non-heme iron-dependent oxygenase that catalyses the oxidation of glutathione persulfide (GSSH) to glutathione (GSH) and persulfite and play important and varied roles in all kingdoms, including sulfide detoxification . These enzymes belong to the metallo-beta-lactamase (MBL) superfamily as they consist of the same structural fold of two β-sheets surrounded by α-helices, which supports the metal-binding feature. The PDOs share high sequence and structural similarity with glyoxalases II (classical di-zinc MBL hydrolase), specially at the metal-binding centre. PDOs have a Fe2 binding site and a secondary coordination sphere-based hydrogen bond network that is absent in glyoxalases II, in which the corresponding residues are involved in coordinating a second metal ion. This suggests that PDOs may evolve from a hydrolytic enzyme with two coordinated ions . Based on sequence analysis, three subclasses of PDO were described: ETHE1, which is present in animals, plants, and bacteria (in the latter they are also called type 1 PDOs), persulfide dioxygenase A (PDOA, or type 2 PDOs), also known as sulfur dioxygenase A (SdoA), which is common in Proteobacteria, and Blh, which is an acronym for beta-lactamase-like hydrolase . In humans, mutations in PDO ETHE1 cause a rare autosomal recessive metabolic disorder called ethylmalonic encephalopathy . In Arabidopsis thaliana, ETHE1 is essential for embryo and endosperm development .

This entry represents the MBL-fold metallo-hydrolase domain.
Sarcoplasmic/endoplasmic reticulum calcium ATPase regulator DWORF (DWORF)
Type: Family

DWarf Open Reading Frame (DWORF) is a small protein that plays a key role in heart muscle contraction. DWORF, Sarcolipin (SLN), and myoregulin (MRLN) are transmembrane regulators of the sarcoplasmic reticulum calcium transporting ATPase (SERCA). DWORF enhances SERCA activity by displacing phospholamban (PLN), a potent SERCA inhibitor. This makes DWORF an attractive candidate for a heart failure therapeutic . DWORF is also present in slow-twitch skeletal muscle fibres .
Chaperone protein SicP (SicP)
Type: Family

This family includes type III secretion system (T3SS) chaperone proteins similar to Salmonella enterica SicP. In S. enterica, many of its serovars being serious human pathogens, the T3SS allows injection of the effector SptP, a virulence protein that is involved in bacterial invasion into a host cell. Chaperone SicP forms a complex with SptP at an early stage of the effector protein secretion process in order to avoid premature degradation; also, the complex is dissociated at a late stage to secrete only SptP with the help of the ATPase InvC which is part of the related T3SS injectisome .
Protein BREVIS RADIX-like (BRX-like)
Type: Family

This entry include Protein BREVIS RADIX (BRX) and related proteins such as BRXL1-4 from plants. BRX has been identified through a natural loss-of-function allele in the Arabidopsis accession Umkirch-1 (Uk-1), and results in reduced root meristem size, reduced mature cell size, and thus reduced root growth . BRX has been shown to regulate the growth rate in both the root and shoot. It mediates cross-talk between the auxin and brassinosteroid pathways .

Despite the protein sequence similarity between Arabidopsis BRXL proteins, analysis of brx brx-like multiple mutants indicates that functional redundancy of BRXLs is limited .
FCS-Like Zinc finger 1/2/3 (FLZ1/2/3)
Type: Family

This entry represents a group of plant FCS-Like Zinc finger-containing proteins, including FLZ1-3 from Arabidopsis. They are DUF581 proteins that may act as an adapter to facilitate the interaction of SnRK1 complex with effector proteins, conferring tissue- and stimulus-type specific differences in the SnRK1 regulation pathway .
TPR repeat-containing thioredoxin TTL1-4 (TTL1-4)
Type: Family

This entry represents a group of tetratricopeptide thioredoxin-like proteins (TTLs), including TTL1-4 from Arabidopsis. They are characterised by the presence of six tetratricopeptide repeats in conserved positions and a C-terminal region known as the thioredoxin-like domain with homology to thioredoxins. TTL2 is specific to pollen grains, while TTL1/3/4 display ubiquitous expression in normal growing conditions but differential expression patterns in response to osmotic and NaCl stresses. TTL1, TTL3, and TTL4 have partially overlapping yet specific functions in abiotic stress tolerance while TTL2 is involved in male gametophytic transmission .
Peroxisomal targeting signal 2 receptor (PEX7)
Type: Family

Peroxisomal proteins catalyse metabolic reactions. The import of proteins from the cytosol into the peroxisomes matrix depends on more than a dozen peroxin (PEX) proteins, among which PEX5 and PEX7 serve as receptors that shuttle proteins bearing one of two peroxisome-targeting signals (PTSs) into the organelle. PEX5 is the PTS1 receptor, while PEX7 is the PTS2 receptor. In plants, PEX7 depends on PEX5 binding to deliver PTS2 cargo into the peroxisome, and PEX7 also facilitates PEX5 accumulation and import of PTS1 cargo into peroxisomes .

This entry represents PEX7 from animals, fungi and plants. In plants it plays important roles in embryonic development, seedling establishment, and vegetative growth . Budding yeast PEX7 homologue, Pas7, is necessary for import of thiolase (a PTS2-containing protein) . In humans PEX7 has been linked to several diseases, such as Rhizomelic chondrodysplasia punctata 1 (RCDP1) and Peroxisome biogenesis disorder 9B (PBD9B) .
Putative zinc metalloprotease Rip2-like (Rip2-like)
Type: Family

This family represents a group of uncharacterised homologues of Site-2 protease (S2P), zinc metalloproteases from the MEROPS family M50, which cleave transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms. Members of the S2P/M50 family of RIP proteases transfer information across membranes through its proteolytic activity, connecting gene expression with physiologic stresses occurring in another cellular compartment . In eukaryotic cells they regulate different processes including sterol and lipid metabolism and endoplasmic reticulum stress responses. In prokaryotes they regulate sporulation, cell division, stress response, and cell differentiation. This group includes S2P/M50s homologues with a minimal core protein and no PDZ domains , including the putative zinc metalloprotease Rip2 from Mycobacterium tuberculosis.
Vacuolar protein sorting-associated protein Vta1-like (Vta1-like)
Type: Family

This entry represents yeast Vta1 and its homologues from animals and plants. Vta1 interacts with the AAA ATPase Vps4 and is required for multivesicular body (MVB) sorting . This entry also includes LIP5 from Arabidopsis. LIP5 is a positive regulator of the Suppressor of K(+) Transport Growth Defect1 (SKD1) AAA ATPase in MVB biogenesis. It is also a target of pathogen-responsive mitogen-activated protein kinases (MPKs) and plays a critical role in plant basal resistance . Mammalian Vta1 homologue functions in MVB sorting and is required for HIV release .
Pachytene checkpoint protein 2-like (Pch2-like)
Type: Family

This entry represents a group of AAA ATPases, including Pch2 from eukaryotes. It is required for the meiotic checkpoint that prevents chromosome segregation when recombination and chromosome synapsis are defective . In humans it is linked to Mosaic variegated aneuploidy syndrome 3 (MVA3) .

This entry also includes a group of uncharacterised AAA domain-containing proteins from bacteria, including Cap6 (also known as TRIP13) from Pseudomonas aeruginosa. Cap6 is a homologue of Pch2. It is part of the CBASS (cyclic oligonucleotide-based antiphage signaling system) and functions as an AAA+ ATPase that prevents the CdnD:Cap7:Cap8 complex from synthesizing 2',3',3'-cyclic AMP-AMP-AMP (cAAA), which is a second messenger . Cap6 binds and disassembles the active CD-NTase:HORMA complex, and hence functions as a negative regulator of CBASS .
FAF1, UBA-like domain (FAF1_UBA)
Type: Domain

FAS-associated factor 1 (FAF1) is a multidomain protein involved in various biological processes, including regulation of apoptosis and NFkappaB activity, and ubiquitination and proteasomal degradation . It has been linked to cancer, asbestos-induced mesotheliomas, and Parkinson's disease . FAF1 contains multiple ubiquitin-related domains, including ubiquitin-associated (UBA), ubiquitin-like 1 and 2 (UBL1, UBL2), and ubiquitin regulatory X (UBX) domains. FAF1 interacts with polyubiquitinated proteins via its N-terminal UBA domain and with valosin containing protein (VCP) via its C-terminal UBX domain .

This entry represents the UBA-like domain found in FAF1.
N-alpha-acetyltransferase 30-like (NAA30-like)
Type: Family

Protein N(alpha)-terminal acetylation is one of the most common protein modifications in eukaryotic cells. This entry includes N-alpha-acetyltransferase 30 (NAA30), also known as Mak3, and related proteins. In budding yeast it's the catalytic subunit of the NatC Nalpha-terminal acetyltransferase . Human NatC (hNatC) complex also contains the catalytic subunit hMak3 and the auxiliary subunits hMak10 and hMak31 . However, Arabidopsis AtMAK3 function does not require NatC complex formation as in yeast .
Uncharacterized cysteine-rich protein YhjQ-like (YHJQ-like)
Type: Family

This family represents functionally uncharacterised proteins found in bacteria, including YhjQ from Bacillus subtilis. They form a 4-helical bundle with a bromodomain-like topology and contain highly conserved cysteines in a repeated pattern, whose side chains appear buried.
Uncharacterized protein AF_0060, NTP Pyrophosphohydrolase MazG-like domain (AF0060_NTP-PPase_MazG-like)
Type: Domain

This domain is found in an uncharacterised protein from Archaeoglobus fulgidus (AF_0060) and its homologues from bacteria. The biological function of this protein remains unclear, however, AF_0060 shows high sequence similarity to the dimeric 2-deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTP pyrophosphatase or dUTPase) and NTP-PPase MazG proteins. Members in this entry consist of a single MazG-like domain that contains a well conserved divalent ion-binding motif EXX[E/D] .
Transcription factor IBH1-like, bHLH domain (bHLH_AtIBH1-like)
Type: Domain

This entry represents the bHLH domain found in a group of transcription factors from plants, including IBH1 (ILI1-BINDING BHLH 1), IBHL1 and related proteins such as UPBEAT1, PAR1 and PAR2 from Arabidopsis. IBH1 (also known as AtbHLH158) and IBHL1 are atypical and probable non DNA-binding bHLH transcription factors that act as transcriptional repressors that negatively regulate cell and organ elongation in response to gibberellin (GA) and brassinosteroid (BR) signaling . IBH1 forms heterodimer with BHLH49, thus inhibiting DNA binding of BHLH49. Another atypical transcription factors included in this entry are PAR1 (also termed AtbHLH165) and PAR2 (also termed AtbHLH166) that act as negative regulators of a variety of shade avoidance syndrome (SAS) responses . UPBEAT1 (also known as AtbHLH151 or EN 146), modulates the balance between cellular proliferation and differentiation in root growth .
Lipid III flippase WzxE (WzxE)
Type: Family

This entry represents lipid III flippase WzxE. WzxE is involved in the Enterobacterial common antigen (ECA) biosynthesis, which is part of bacterial outer membrane biogenesis. ECA is a specific surface antigen (polysaccharide) shared by all members of the Enterobacteriaceae and is restricted to this family . WzxE mediates the transbilayer movement of Und-PP-GlcNAc-ManNAcA-Fuc4NAc (lipid III) from the inner to the outer leaflet of the cytoplasmic membrane during the assembly of ECA . It is required for the assembly of the phosphoglyceride-linked form of ECA (ECA(PG)) and the water-soluble cyclic form of ECA (ECA(CYC)) .
GDSL esterase/lipase GLIP1-5/GLL25 (GLIP1-5/GLL25)
Type: Family

GDSL-type esterases/lipases are hydrolytic enzymes with multifunctional properties, such as broad substrate specificity, regiospecificity, and stereoselectivity . They have been identified in microbes and many plants. They have diverse physical functions such as affecting the germination rate and early growth of seedlings subjected to high concentrations of glucose, or being involved in biotic stress responses .

This entry represents a group of plant GDSL esterases/lipases, including GLIP1-5 and GLL25 from Arabidopsis. GDSL LIPASE-LIKE 1 (GLIP1) modulates systemic immunity through the regulation of ethylene signaling components . GLIP1 and GLIP3 have been shown to contribute to the plant resistance to Botrytis cinerea . GLIP2 is involved in the resistance to Erwinia carotovora via the negative regulation of auxin signaling . GLL25 (also known as GOLD36 or MVP1), have lost the conserved active site 'GDSL' motif and have no lipase activity. GLL25 is Involved in organisation of the endomembrane system and is required for endoplasmic reticulum morphology and organelle distribution .
ANCHR, B-box-type 1 zinc finger domain (Bbox1_ANCHR)
Type: Domain

Abscission/NoCut checkpoint regulator (ANCHR), also known as MLL partner containing FYVE domain or zinc finger FYVE domain-containing protein 19, is a key regulator of the abscission step in cytokinesis as it is part of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage. ANCHR acts in an Aurora-B-dependent manner and associates with VPS4 at the midbody ring .

This entry represents the B-box motif found in ANCHR, it shows high sequence similarity with B-Box-type 1 (Bbox1) zinc finger found in tripartite motif-containing proteins (TRIMs). Bbox1 zinc finger is characterised by a C6H2 zinc-binding consensus motif.
Anaphase-promoting complex subunit 2 (ANAPC2)
Type: Family

This entry represents APC subunit 2 (ANAPC2), which is a distant member of the cullin protein family that functions as a scaffold in SCF assembly .

ANAPC2 is part of the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle .

The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome .
Protein WUSCHEL-like (WUSCHEL-like)
Type: Family

This entry includes WUSCHEL and homeodomain WUSCHEL-RELATED (WOX) proteins from plants. Proteins in this entry have been classified as a WOX clade that contains the WUS, WOX1, WOX2, WOX3, WOX5, WOX6 and WOX7. WUSCHEL is a transcription factor that plays a central role during early embryogenesis, oogenesis and flowering . WOXs are transcription factors that regulate meristem development in embryos, as well as vegetative and reproductive organs .
Endonuclease II-like, GIY-YIG domain (EndoII-like_GIY-YIG)
Type: Domain

This is the GIY-YIG domain present in Bacteriophage T4 endonuclease II (EndoII) and related proteins. EndoII is encoded by gene denA and catalyses the initial step in degradation of host DNA, which allows scavenging of host-derived nucleotides for phage DNA synthesis. It binds to two DNA substrates as an X-shaped tetrameric structure composed as a dimer of dimers . Divalent metal-ion cofactors are required for their catalytic events, but not for the substrates binding .
WUSCHEL-related homeobox 8/9-like (WOX8/9-like)
Type: Family

This entry includes WUSCHEL-related homeobox 8/9 (WOX8/9) from Arabidopsis . They are homeodomain transcription factors that required for embryo development . Cytokinin signaling has been shown to be involved in activation of WOX9 expression in meristematic tissues, which is essential for maintaining the meristematic fate . WOX8 promotes cotyledon boundary formation .
WUSCHEL-related homeobox 11-like (WOX11-like)
Type: Family

This entry includes WUSCHEL-related homeobox 11 (WOX11) from Arabidopsis. Together with WOX12 it is involved in de novo root organogenesis .
WUSCHEL-related homeobox 13-like (WOX13-like)
Type: Family

This entry includes WUSCHEL-related homeobox (WOX8/10/13/14) from Arabidopsis. The expression of AtWOX14 isrestricted to the early stages of lateral root formation and specific to developing anthers, while AtWOX13 is expressed during primary and lateral root initiation and development, in gynoecium and during embryo development .
Monooxygenase-like (MOase)
Type: Family

This entry includes monooxygenase (MO) 1, 2 and 3 from plants. MO1 shares homology with monooxygenases that degrade salicylic acid. It is up-regulated in the compatible interaction of Alternaria brassicicola with Arabidopsis thaliana ecotype DiG . This entry also includes pqsH 2-heptyl-3,4-dihydroxyquinoline synthase involved in the terminal step of the biosynthesis of quinolone .
L-threonine ammonia-lyase, ACT domain (ACT_ThrD-II-like)
Type: Domain

This entry represents the ACT domain found in L-threonine ammonia-lyase from Geobacter sulfurreducens which catalyses the conversion of threonine to 2-oxobutanoate and ammonia. It acts in the threonine-dependent pathway of isoleucine biosynthesis, which is the minor pathway for isoleucine biosynthesis in G.sulfurreducens .

This entry also includes the uncharacterized protein MJ1601 from Methanocaldococcus jannaschii.
Protein C2-DOMAIN ABA-RELATED (CAR1-11)
Type: Family

This entry includes C2-domain abscisic acid-related protein CAR1-11 from Arabidopsis and GTPase activating protein 1 (OsGAP1) from rice. CARs interact with the PYR/PYL ABA receptors and recruit them to membranes in a Ca2+-dependent manner . OsGAP1 is a soluble protein that can loosely associate with plasma membrane. It can also interact with an unconventional G-protein, OsYchF1, and stimulate its NTPase activities .
Protein Sgt1-like (Sgt1-like)
Type: Family

This entry includes protein Sgt1 (Suppressor of G2 allele of SKP1) and its homologues. In budding yeasts, Sgt1 is required for both SCF (Skp1p/Cdc53p-Cullin-F-box)-mediated ubiquitination, cyclic AMP pathway activity and kinetochore function . Its Schizosaccharomyces pombe homologue, Git7, is required for glucose and cyclic AMP signaling, cell wall integrity, and septation . Its two homologues in Arabidopsis, SGT1a and SGT1b, can complement two yeast temperature-sensitive sgt1 mutant alleles, suggesting that fundamental cellular function(s) of yeast SGT1in SCF-mediated protein ubiquitylation. Moreover, SGT1a and SGT1b can act as cochaperones with HSP90 and HSC70 and function in regulating multiple resistance (R) genes and environmental responses .
Voltage-gated sodium channel alpha subunit, inactivation gate (Na_chnl_inactivation_gate)
Type: Domain

Voltage-dependent sodium channels are transmembrane (TM) proteins responsible for the depolarising phase of the action potential in most
electrically excitable cells . They may exist in 3 states : the resting state, where the channel is closed; the activated state, where the channel is open; and the inactivated state, where the channel is closed and refractory to opening. Several different structurally and functionally distinct isoforms are found in mammals, coded for by a multigene family, these being responsible for the different types of sodium ion currents found in excitable tissues.

There are nine pore-forming alpha subunit of voltage-gated sodium channels consisting of four membrane-embedded homologous domains (I-IV), each consisting of six α-helical segments (S1-S6), three cytoplasmic loops connecting the domains, and a cytoplasmic C-terminal tail. The S6 segments of the four domains form the inner surface of the pore, while the S4 segments bear clusters of basic residues that constitute the channel's voltage sensors .

This domain represents the cytoplasmic loop connecting domains III and IV of the alpha subunits of voltage-gated sodium channels. It forms the channel inactivation gate, acting through a hinged lid mechanism, which is responsible for fast inactivation of the channel and it is essential for proper physiological function . This domain contains the highly conserved hydrophobic isoleucine-phenylalanine-methionine (IFM) triad, essential for the fast inactivation mechanism. In particular the phenylalanine residue is suggested to bind to an inactivation gate receptor that causes the loop to occlude the channel pore during the inactivation process. Mutation of this residue causes a severe impairment of the inactivation process, while full mutation of the triad abolishes completely inactivation .
Vesicle-trafficking protein Sec22 (Sec22)
Type: Family

Sec22 is an nonessential SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER .
Polyamine transporter RMV1-like (RMV1-like)
Type: Family

This entry represents a group of amino acid and polyamine transporters from bacteria and plants, including RMV1 from Arabidopsis and PUT1 from rice. RMV1 and PUT1 are polyamine transporters involved in the polyamine uptake in cells .