SII-SWORD/CoKE huggingface dataset:
FADD, vertebrates (FADD_vert)
Type: Family

This entry includes FAS-associated death domain (FADD) proteins from vertebrates.

This entry includes the Fas-associated death domain (FADD) protein. This protein is an apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors . The resulting aggregate, called the death-inducing signalling complex (DISC), performs caspase-8 proteolytic activation . Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis .
Hepatocyte nuclear factor 4, ligand-binding domain (HNF4_LBD)
Type: Domain

This entry represents the LBD domain, which is also responsible for recruiting co-activator proteins .

HNF4 is a member of the nuclear receptor superfamily and plays a key role in establishing and maintenance of hepatocyte differentiation in the liver. It is a transcriptional regulator that controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes . Additionally, it plays an essential role in circadian rhythm maintenance and period regulation in the liver and colon cells . It is also expressed in gut, kidney, and pancreatic beta cells. HNF4 was originally classified as an orphan receptor, but later it is found that HNF4 binds with very high affinity to a variety of fatty acids. However, unlike other nuclear receptors, the ligands do not act as a molecular switch for HNF4. They seem to constantly bind to the receptor, which is constitutively active as a transcription activator. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, HNF4 has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD) .
Hepatocyte nuclear factor 4-like, DNA-binding domain (HNF4-like_DBD)
Type: Domain

This entry represents the DNA-binding domain of HNF4 and its homologues. More than 280 nuclear receptors are found in C. elegans, most of which are originated from an explosive burst of duplications of HNF4 .

HNF4 is a member of the nuclear receptor superfamily and plays a key role in establishing and maintenance of hepatocyte differentiation in the liver. It is a transcriptional regulator that controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes . Additionally, it plays an essential role in circadian rhythm maintenance and period regulation in the liver and colon cells . It is also expressed in gut, kidney, and pancreatic beta cells. HNF4 was originally classified as an orphan receptor, but later it is found that HNF4 binds with very high affinity to a variety of fatty acids. However, unlike other nuclear receptors, the ligands do not act as a molecular switch for HNF4. They seem to constantly bind to the receptor, which is constitutively active as a transcription activator. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, HNF4 has a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD) .
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7)
Type: Family

This entry represents the mitogen-activated protein kinase kinase kinase 7 (MAP3K7, also known as TAK-1), which is a component of a protein kinase signal transduction cascade, acting as a mediator of TGF-beta signal transduction. MAP3K7 stimulates NF-kappa-B (NFKB) activation and the p38 MAPK pathway through the phosphorylation and activation of several MAP kinase kinases . MAP3K7 binds both upstream activators and downstream substrates in multi-molecular complexes.
Bifunctional aspartokinase/homoserine dehydrogenase (AK-HD)
Type: Family

This entry represents the bifunctional enzyme aspartokinase/homoserine dehydrogenase (AK-HSDH) mainly found in bacteria, which catalyses the first and third steps of the aspartate pathway. Homoserine dehydrogenase (

) catalyses the conversion of L-homoserine to L-aspartate-4-semialdehyde using NAD(P), while aspartate kinase (

) catalyses the phosphorylation of L-aspartate to 4-phospho-L-aspartate. There are two genes encoding different isoforms of this bifunctional enzymes; one isoform is threonine-sensitive, while the other is methionine-sensitive .

Bifunctional enzymes that catalyse consecutive reactions offer the advantages of efficient channelling and protection of potentially reactive intermediates. AK-HSDH is unusual in its ability to catalyse two non-consecutive reactions. The enzyme that catalyses the intermediary step, aspartate semialdehyde dehydrogenase, is thought to provide a bridge to channel the intermediates between the non-consecutive reactions of AK-HSDH .

Bacteria, plants and fungi metabolise aspartic acid to produce four amino acids -lysine, threonine, methionine and isoleucine -in a series of reactions known as the aspartate pathway. Additionally, several important metabolic intermediates are produced by these reactions, such as diaminopimelic acid, an essential component of bacterial cell wall biosynthesis, and dipicolinic acid, which is involved in sporulation in Gram-positive bacteria. Members of the animal kingdom do not posses this pathway and must therefore acquire these essential amino acids through their diet. Research into improving the metabolic flux through this pathway has the potential to increase the yield of the essential amino acids in important crops, thus improving their nutritional value. Additionally, since the enzymes are not present in animals, inhibitors of them are promising targets for the development of novel antibiotics and herbicides. For more information see .
Transcriptional repressor RstR (RstR)
Type: Family

This entry represents the cryptic phage CTXphi transcriptional repressor RstR (

) and related proteins. RstR function as a transcriptional repressor of the integrated CTXPhi phage gene rstA2 .

The proteins in the RstR family contain a Cro/C1-type helix-turn-helix domain

.
CBU_0585/lpg0581-like (CBU_0585/lpg0581-like)
Type: Family

The founding members of this family are Cbu_0585 from Coxiella burnetii (

) and lpg0581 from Legionella pneumophila (

). They were described as potential type IV secretion system (T4SS) virulence effectors because of their homology to each other but absence from a number of related bacteria that lack T4SS . However, this statement hasn't yet been confirmed.
Thivi_2564 membrane protein (THIVI_2564-like)
Type: Family

This entry represents Thivi_2564 from Thiocystis violascens DSM 198 (

) and related bacterial proteins. A related ORF located between lpg1798 and lpg1799 can be found in Legionella pneumophila. Members of this family are, in average, about 60 amino acids long and are highly hydrophobic.
Bifunctional endo-1,4-beta-xylanase/feruloyl esterase (Xylase_Ferestase)
Type: Family

This entry represents the bifunctional endo-1,4-beta-xylanase/feruloyl esterase from Prevotella ruminicola (

) and related bacterial proteins exclusively from Bacteroidales. This enzyme is involved in degradation of plant cell wall polysaccharides. It has endo-xylanase activity towards substrates such as oat spelt xylan (OSX), acetylated xylo-oligosaccharides and acetylated xylan, producing primarily xylobiose. It also has feruloyl esterase activity, releasing ferulic acid from methylferulate, and from the more natural substrates such as wheat bran and corn fibre .
Beta-lactamase L2 (Beta-lactam_L2)
Type: Family

This entry represents a group of proteins from Stenotrophomonas species, including Beta-lactamase L2 from Stenotrophomonas maltophilia (

), a class A, functional class 2e beta-lactamase whose induction depends on the AmpR regulator .
Gas vesicle protein GvpU-like (GvpU-like)
Type: Family

This entry represents a group of gas vesicle proteins mainly found in proteobacteria and firmicutes, including Gas vesicle protein GvpU from Bacillus megaterium (

). Gas vesicles are permeable to ambient gases by diffusion and provide buoyancy, enabling cells to move upwards in liquid to access oxygen and/or light .
Geranyl diphosphate 2-C-methyltransferase (GPPMT_Stmyces)
Type: Family

This entry represents the geranyl diphosphate 2-C-methyltransferase and related proteins mainly found in Actinomycetes. This enzyme catalyses the SAM-dependent methylation of geranyl diphosphate to yield (E)-2-methylgeranyl diphosphate . This enzymatic reaction is important step in the biosynthesis of 2-methylisonorneol (2-MIB), which is responsible for taste and odour problems in drinking water. Geranyl diphosphate 2-C-methyltransferase adopts typical methyltransferase fold that assembles into an unique homohexamer (

,

) .
Gas vesicle protein GvpT/GvpP-like (GvpT/GvpP-like)
Type: Family

This entry represents a group of gas vesicle proteins from firmicutes, including Gas vesicle protein GvpT/GvpP from Bacillus megaterium. Gas vesicles are permeable to ambient gases by diffusion and provide buoyancy, enabling cells to move upwards in liquid to access oxygen and/or light .
Gas vesicle protein GvpQ-like (GvpQ-like)
Type: Family

This entry represents a group of gas vesicle proteins from firmicutes, including Gas vesicle protein GvpQ from Bacillus megaterium [

]. Gas vesicles are permeable to ambient gases by diffusion and provide buoyancy, enabling cells to move upwards in liquid to access oxygen and/or light .
Aldehyde oxidoreductase molybdenum-binding subunit PaoC-like (PaoC-like)
Type: Family

This entry represents a group of proteins mainly from proteobacteria, including Aldehyde oxidoreductase molybdenum-binding subunit PaoC from Escherichia coli (PaoC,

), which oxidises aldehydes to the corresponding carboxylic acids with a preference for aromatic aldehydes. PaoC might play a role in the detoxification of aldehydes to avoid cell damage . It forms part
of the periplasmic aldehyde oxidoreductase PaoABC. The enzyme is known formally as carboxylate reductase (

) . The E.coli PaoABC complex structure was determined (

) in which PaoC was found to contain the Moco active site. Apparently, this is the only known example of an E. coli Moco enzyme where cytosine is found in the dinucleotide form of the cofactor .
Lipoprotein DVU_2496-like, C-terminal domain (DVU2496-like_C)
Type: Domain

This entry represents a domain found C-terminal in DVU_2496 from Desulfovibrio vulgaris (

) and related bacterial proteins. In contrast to the N-terminal region, this domain is more conserved. The N-terminal region frequently contains a lipoprotein lipid attachment site .
ADP-ribosylarginine hydrolase Tri1-like (Tri1-like)
Type: Family

This entry represents a group of proteins from gammaproteobacteria, including ADP-ribosylarginine hydrolase Tri1 from Pseudomonas putida, an immunity component of an interbacterial competition system (also called effector-immunity systems). Expression of Tri1 in E.coli neutralises the toxic effects of non-cognate S.proteamaculans effector protein Tre1 (Tre1-Sp) . The structure of this complex revealed two distinct immunity mechanisms which concomitantly utilise active site occlusion to inactivate cognate effector proteins and a promiscuous ADP-ribosylhydrolase (ARH) activity to reverse ART-catalyzed modifications

.
HTH-type transcriptional activator RamA-like (HTH-type_RamA-like)
Type: Family

This entry represents a group of proteins from actinomycetes, including HTH-type transcriptional activator RamA from Corynebacterium glutamicum (

), a master regulator of acetate metabolism. RamA positively controls the expression of acnA, aceA, aceB, ack, pta and ramB genes in the presence of acetate and a positive regulator of rpf2 gene expression during growth on glucose as the sole carbon source .
Electron transfer flavoprotein PplA-like (PplA-like)
Type: Family

This entry represents PplA and related proteins found mainly in Firmicutes. PplA was initially found in the extracellular electron transfer (EET) locus of Listeria monocytogenes and it is a cell surface flavoprotein with covalently attached FMN. Within the eight-gene cluster responsible for EET, the fmnB gene which encodes an ApbE-like protein is responsible for the flavinylation of PplA at two sites
Anti-phage protein ZorB, Zorya type II system (ZorB-like_t2)
Type: Family

This family includes anti-phage ZorB-like proteins found mainly in Enterobacterales species. ZorB is a component of the antiviral defense Zorya type II system, composed of ZorA, ZorB, and ZorE. The expression of Zorya type II system in E.coli (strain MG1655) confers resistance to phages SECphi7 and T7 .

These proteins contain a OmpA-like domain (

).
Fe(3+) dicitrate transport protein FecA-like (FecA-like)
Type: Family

This entry represents a group of proteins from gammaproteobacteria, including Fe(3+) dicitrate transport protein FecA from Escherichia coli (

), the outer membrane receptor protein in the Fe3 dicitrate transport system . FecA consists of three distinct domains: the barrel (

), plug (

), and NH2-terminal extension (

). Ferric citrate binding triggers a conformational change of the extracellular loops that close the external pocket of FecA .
Transcriptional regulator ClgR-like (ClgR-like)
Type: Family

This entry represents a group of proteins from actinomycetes, including Transcriptional regulator ClgR from Mycolicibacterium smegmatis (

), a key stress-response regulator that plays an important role in multiple regulatory networks in response to different stress conditions. ClgR probably controls the response to vancomycin treatment . This protein adopts an α-helical globular structure containing HTH motif

.
MXAN_6627.5-like (MXAN_6627.5-like)
Type: Family

This protein family represents MXAN_6627.5 and similar sequences from Myxococcales. MXAN_6627.5 is a MYXO-CTERM protein, depending on myxosortase and type II secretion for expression presumably on the cell surface. This protein is encoded between loci MXAN_6627 and MXAN_6628, but missed in previous annotation of that genome. The central region of the protein has four invariant Cys residues.
Anthranilate 1,2-dioxygenase system ferredoxin--NaD(+) reductase component (AndAa)
Type: Family

This entry represents a group of proteins from betaproteobacteria, including Anthranilate 1,2-dioxygenase system ferredoxin--NAD(+) reductase component from Burkholderia cepacia (AndAa,

), part of the multicomponent anthranilate dioxygenase, that converts anthranilate to catechol. It probably transfers electrons from ferredoxin (AndAb) to NADH .
Anti-phage protein ZorB, Zorya type I system (ZorB-like_t1)
Type: Family

This family includes anti-phage ZorB-like proteins found mainly in gammaproteobacteria. ZorB is a component of the antiviral defense Zorya type I system, composed of ZorA, ZorB, ZorC, and ZorD. The expression of Zorya type I system in E.coli (strain MG1655) confers resistance to phages SECphi7, lambda, and T7 .

These proteins contain a OmpA-like domain (

).
Anti-phage protein ZorC, Zorya type I system (ZorC-like_t1)
Type: Family

This family includes anti-phage ZorC-like proteins found mainly in gammaproteobacteria. ZorC is a component of the antiviral defense Zorya type I system, composed of ZorA, ZorB, ZorC, and ZorD. The expression of Zorya type I system in E.coli (strain MG1655) confers resistance to phages SECphi7, lambda, and T7 . These proteins contain the so-called EH signature domain (

).
Anti-phage protein ZorD, Zorya type I system (ZorD-like_t1)
Type: Family

This family includes anti-phage ZorD-like proteins found mainly in gammaproteobacteria. ZorD is a component of the antiviral defense Zorya type I system, composed of ZorA, ZorB, ZorC, and ZorD. The expression of Zorya type I system in E.coli (strain MG1655) confers resistance to phages SECphi7, lambda, and T7 .

These proteins contain a Helicase domain (

).
MZA anti-phage system associated ATPase MzaB (MzaB)
Type: Family

Proteins, members of this family are components of the MZA anti-phage system (MutL, Z1, and AIPR) . The function of these proteins in the MZA anti-phage system is not understood yet.
Anti-phage protein ZorE, Zorya type II system (ZorE-like_t2)
Type: Family

This family includes anti-phage ZorE-like proteins found mainly in Enterobacterales. ZorE is a component of the antiviral defense Zorya type II system, composed of ZorA, ZorB, and ZorE. The expression of Zorya type II system in E.coli (strain MG1655) confers resistance to phages SECphi7 and T7 .
MZA anti-phage system associated protein MzaC (MzaC)
Type: Family

This entry represents the homologues of MzaC, a component of the MZA anti-phage system (MutL, Z1, and AIPR) . MraC contains Z1 domain

. The function of this protein in the MZA anti-phage system is not understood yet.
MZA anti-phage system associated PD-(D/E)XK motif protein MzaD (MzaD)
Type: Family

This entry represents the homologues of MzaD, a component of the MZA anti-phage system (MutL, Z1, and AIPR) . The function of this protein in the MZA anti-phage system is not understood yet.
MZA anti-phage system associated protein MzaE (MzaE)
Type: Family

This entry represents the homologues of MzaE, a component of the MZA anti-phage system (MutL, Z1, and AIPR) . MzaE is related to AIPR family

. The function of this protein in the MZA anti-phage system is not understood yet.
Anthranilate 1,2-dioxygenase regulatory protein (AndR)
Type: Family

This entry represents a group of proteins from betaproteobacteria, including Anthranilate 1,2-dioxygenase regulatory protein from Burkholderia cepacia (AndR,

), which is involved in anthranilate degradation through activation of expression of the anthranilate 1,2-dioxygenase subunits .
Anti-phage protein ZorA, Zorya type II system (ZorA-like_t2)
Type: Family

This family includes anti-phage ZorA-like proteins found mainly in Enterobacterales species. ZorA is a component of the antiviral defense Zorya type II system, composed of ZorA, ZorB, and ZorE. The expression of Zorya type II system in E.coli (strain MG1655) confers resistance to phages SECphi7 and T7 .
Anti-phage protein ZorA, Zorya type I system (ZorA-like_t1)
Type: Family

This family includes anti-phage ZorA-like proteins in gammaproteobacteria. ZorA is a component of the antiviral defense Zorya type I system, composed of ZorA, ZorB, ZorC, and ZorD. The expression of Zorya type I system in E.coli (strain MG1655) confers resistance to phages SECphi7, lambda, and T7 .
Choice-of-anchor W domain (Choice_anch_W)
Type: Domain

This entry represents a domain found in a group of proteins, majority of which are PEP-CTERM proteins that are thought to be sorted to the cell surface in an exosortase-dependent process. Some members have a possible alternative anchoring sequence with a TWGxxK sequence motif near the C terminus. A few proteins, containing this domain, have additional domains and a C-terminal LPXTG (sortase-dependent) sorting signal, or other unusual C-terminal regions whose significance is not yet clear.
Exosortase-dependent surface protein XDP1 (Xrt_dep_XDP1)
Type: Family

This entry represents a family of proteins, here named XDP1 (exosortase-dependent surface protein 1), which have an N-terminal signal peptide and a C-terminal sorting signal for recognition and cleavage by exosortase family intramembrane endopeptidases. The sorting signal is typically VPEP-CTERM, but variant forms of the motif, such as VSEP or VPLPA, do occur in the family.
Qat anti-phage system ATPase QatA (QatA)
Type: Family

Members of this family are the proteins containing a KAP NTPase domain (

) called QatA, which have been identified as components of the Qat (QueC-like associated with ATPase and TatD DNase) anti-phage system .
Ion-translocating oxidoreductase complex subunit RnfA, Methanosarcinaceae (Ion_transpt_RnfA_Methano)
Type: Family

This entry represents the Ion-translocating oxidoreductase complex subunit A (RnfA,

) from Methanosarcina acetivorans and related proteins found in Methanosarcinaceae species. RnfA is part of a membrane-bound complex that couples electron transfer with translocation of ions across the membrane. RnfA catalyses sodium transport, most probably coupled to electron transfer from reduced ferredoxin to methanophenazine and heterodisulfide reductase. It is involved in heterodisulfide reduction during methanogenesis from acetate .
Qat anti-phage system associated protein QatB (QatB)
Type: Family

This entry represents the QatB family of proteins. Members of this family are components of the Qat anti-phage system (QueC-like associated with ATPase and TatD DNase) .
Qat anti-phage system protein QatC (QatC)
Type: Family

Members of this family are the proteins containing a Rossmann-like domain (

) called QatC, which have been identified as components of the Qat (QueC-like associated with ATPase and TatD DNase) anti-phage system .
Qat anti-phage system nuclease QatD (QatD)
Type: Family

Members of this family are the proteins containing a hydrolase domain (

) called QatD, which have been identified as components of the Qat (QueC-like associated with ATPase and TatD DNase) anti-phage system .
GTPase virulence factor LeoA (LeoA-like)
Type: Family

This entry represents the GTPase virulence factor LeoA (

) and related bacterial proteins. LeoA is encoded within a pathogenicity island from enterotoxigenic Escherichia coli (ETEC) strain H10407 . The structure of LeoA reveals its relation to prokaryotic and eukaryotic dynamin-like proteins (

) . LeoA functions in concert with a second dynamin-like protein that is made up of LeoB and LeoC, encoded by two upstream genes. Disruption of the leoAB genes leads to a reduction in secretion of periplasmic Tat-GFP and outer membrane OmpA. LeoABC dynamin-like proteins are thought to play a role in potentiating virulence through membrane vesicle associated toxin secretion .
Ion-translocating oxidoreductase complex subunit RnfB, Methanosarcinaceae (Ion_transpt_RnfB_Methano)
Type: Family

This entry represents the Ion-translocating oxidoreductase complex subunit B (RnfB,

) from Methanosarcina acetivorans and related proteins found in Methanosarcinaceae species. RnfB is part of a membrane-bound complex that couples electron transfer with translocation of ions across the membrane. RnfB catalyses sodium transport, most probably coupled to electron transfer from reduced ferredoxin to methanophenazine and heterodisulfide reductase. It is involved in heterodisulfide reduction during methanogenesis from acetate .
Choline/ethanolamine transporter FLVCR1-2/SLC49-like (FLVCR1-2_SLC49-like)
Type: Family

This protein family includes human Solute carrier family 49 members A1 (SLC49A1 or FLVCR1), A2 (SLC49A2 or FLVCR2), A3 (SLC49A3 or MFSD7) and 4 (SLC49A4 or DIRC2) from mammals and similar sequences widespread among all cellular organisms.

FLVCR1/2 are uniporters that mediate the transport of extracellular choline and ethanolamine into cells, the precursors of phosphatidylcholine and phosphatidylethanolamine, respectively, the two most abundant phospholipids, thereby playing a key role in phospholipid biosynthesis . This transport is not coupled with proton transport and is exclusively driven by the choline (or ethanolamine) gradient across the plasma membrane . They are also haem b transporters that mediates haem efflux from the cytoplasm to the extracellular compartment. Haem export depends on the presence of HPX and is required to maintain intracellular free haem balance, protecting cells from haem toxicity . Mutations in the genes coding for these proteins are related with serious human disorders . DIRC2 mediates H -dependent pyridoxine transport . Members of this family belong to the Major Facilitator Superfamily (MFS) of transporters.
Zinc finger protein HVO_A0556-like (HVO_A0556-like)
Type: Family

This entry represents the HVO_A0556 zinc finger protein from Haloferax volcanii (

) and related proteins from Halobacteria. HVO_A0556 is predicted to have a single domain zinc finger with a rubredoxin-like fold. Deletion of HVO_A0556 gene was shown to have a pleiotropic phenotype under four different conditions .