SII-SWORD/CoKE huggingface dataset:
Flagellin, H7-serospecific domain (FliC_H7)
Type: Domain

This domain is typically between 125 and 147 amino acids in length, and is found in some flagellins . There are two completely conserved G residues that may be functionally important.
tRNA nucleotidyltransferase/poly(A) polymerase, RNA and SrmB- binding domain (PolyA_RNA-bd)
Type: Domain

This region encompasses much of the RNA and SrmB binding motifs on polymerase A .
Helicase XPB/Ssl2, N-terminal domain (XPB/Ssl2_N)
Type: Domain

This domain is found in the N-terminal region of XPB/Ssl2. XPB/Ssl2 is a component of RNA polymerase transcription factor TFIIH holoenzyme required for DNA unwinding during transcription initiation . It plays a dual role in transcription and DNA repair .
LPS-assembly lipoprotein LptM, conserved region (LptM_cons)
Type: Conserved_site

This entry includes LPS-assembly lipoprotein LptM, a component of the lipopolysaccharide (LPS) transport (Lpt) pathway that promotes efficient assembly of the outer membrane LPS translocon (LptDE) by the BAM complex . It binds to LptD translocon subunit and facilitates oxidative maturation of LptD by stabilising a conformation of the LPS translocon in which LptD can efficiently acquire native disulfide bonds, thereby activating the LPS translocon . This entry represents the short conserved core of this protein.
Sensor histidine kinase NatK-like, C-terminal domain (NatK-like_C)
Type: Domain

This domain is found C-terminal in sensor histidine kinases related to NatK. NatK is part of the two-component regulatory system NatK-NatR that regulates expression of the natAB operon encoding an ABC transporter for sodium ion extrusion .
Rho GTPase-activating protein, FF domain (RhoGAP-FF1)
Type: Domain

This entry represents the FF domain of the Rho GTPase activating proteins (GAPs). These are the key proteins that make the switch between the active guanosine-triphosphate-bound form of Rho guanosine triphosphatases (GTPases) and the inactive guanosine-diphosphate-bound form. Rho guanosine triphosphatases (GTPases) are a family of proteins with key roles in the regulation of actin cytoskeleton dynamics.

The RhoGAP-FF1 domain have been implicated in binding to the transcription factor TFII-I; and phosphorylation of Tyr308 within the first FF domain inhibits this interaction. The RhoGAP-FF1 domain constitutes the first solved structure of an FF domain that lacks the first of the two highly conserved Phe residues, but the substitution of Phe by Tyr does not affect the domain fold .
DsrE2-like family (DsrE2-like)
Type: Family

DsrE2 is found in sulphur-oxidising bacteria and is linked to complexes involved in sulphur oxidation (Dsr). DsrE2 is involved in cytoplasmic sulphur trafficking during dissimilatory sulphur oxidation, probably transferring sulphur from persulfide intermediates to dissimilatory sulfite reductase . This family also includes uncharacterised YrkE proteins.
Glycerol-1-phosphate dehydrogenase (G1PDH)
Type: Family

This entry includes glycerol-1-phosphate dehydrogenases (G1PDH) from archaea and bacteria. G1PDH catalyses the NAD(P)H-dependent reduction of dihydroxyacetonephosphate (DHAP or glycerone phosphate) to glycerol 1-phosphate (G1P) .
VWA-Hint protein, Vwaint domain (Vwaint_dom)
Type: Domain

VWA-Hint proteins carry this conserved domain of around 300 residues, named the Vwaint domain. Generally, this domain lies between the N-terminal VWA domain and the more C-terminal 'Vint'-type Hint domain. The exact function of this domain is not known .
Rab3-GAP regulatory subunit, N-terminal (RAB3GAP_N)
Type: Domain

This family includes the N terminus of the Rab3 GTPase-activating protein (GAP) non-catalytic subunit.

Small G proteins of the Rab family are regulators of intracellular vesicle traffic. Their rate of GTP hydrolysis is enhanced by specific GTPase-activating proteins (GAPs) that switch G proteins to their inactive form . Rab3GAP1 (catalytic subunit) has been shown to form a heterodimeric complex with Rab3GAP2 (the regulatory subunit), and this complex acts as a guanosine nucleotide exchange factor for Rab3 subfamily (RAB3A, RAB3B, RAB3C and RAB3D). Rab3GAP complex may participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters . It also activates Rab18 and promotes autolysosome maturation through the Vps34 Complex I .

Mutations in the Rab3GAP1/2 gene cause Warburg micro syndrome (WMS), a hereditary autosomal neuromuscular disorder .
CFAP91 domain (CFAP91_dom)
Type: Domain

This entry represents a domain found in the CFAP91 protein.

CFAP91 (also known as AMY-1-associating protein expressed in testis 1 or AAT-1) is a component of a spoke-associated complex, regulates flagellar dynein activity by mediating regulatory signals between the radial spokes and dynein arms . It binds to AMY1 and may play a role in spermatogenesis .
Arterivirus polyprotein, nsp2, non-essential region (NSP2_assoc)
Type: Domain

This non-essential region of the nsp2 subunit of the polyprotein of arterivirus, such as porcine arterivirus PRRSV and equine arterivirus EAV, may offer immunogenic surfaces to B-cells.
Cleavage inducing molecular chaperone, Jiv (Jiv)
Type: Domain

This entry represents Jiv (J-domain protein interacting with viral protein), a domain found in the DnaJ protein from eukaryotes . It can also be found in the N-terminal region of the pestivirus viral polypeptide. The viral protein interacts stably with non structural (NS) protein NS2, causing a conformational change in NS2-NS3 and stimulates NS2-NS3 cleavage in trans. Cleavage of NS2-NS3 increases cytopathogenicity and consequently aids viral replication. Jiv therefore acts as a regulating cofactor for NS2 auto-protease. The efficient release of NS3 from the viral polypeptide by Jiv is considered crucial to the pestivirus cytopathogenicity . In eukaryotes, it usually lies 40 residues downstream of DnaJ domain (

). However, the function of this domain in eukaryotes is still unknown.
Pre-mRNA-processing factor 17 (PRPF17)
Type: Family

Pre-mRNA splicing takes place by two consecutive trans-esterification reactions. In the first step, the border between the 5' exon and the intron is cleaved, whereas in the second step the 3' splice site is cleaved and the two exons are joined, creating a mature RNA. Pre-mRNA-processing factor 17 (Prp17) functions in the second step of pre-mRNA splicing . Prp17 may be part of the core NTC (NineTeen Complex), a spliceosomal subcomplex essential for spliceosome activation .

Saccharomyces cerevisiae Prp17 is also known as cell division cycle CDC40, as it was first identified through a mutation that affects the mitotic and meiotic cell cycles . The Caenorhabditis elegans orthologue functions in meiotic entry and sex determination, indicating a role for pre-mRNA splicing in the regulation of these aspects .
Sex-determining transformer protein 2 (Ce-Tra-2)
Type: Family

Sex-determining transformer protein 2 (Tra-2) plays a major role in controlling sexual cell fates in Caenorhabditis . Tra-2 functions to promote female development . It interacts with and suppresses the male-promoting activity of an intracellular protein complex containing FEM-1, FEM-2, and FEM-3 . Tra-2 is a transmembrane receptor inactivated by Her-1, a protein required for male development .
DNA oxidative demethylase ALKBH2 (ALKBH2)
Type: Family

AlkB is a dioxygenase that repairs alkylation damage to DNA and RNA . AlkB homologues (ABHs) are found in all multicellular organisms, as well as in many bacteria and fungi, and some viruses . Nine mammalian AlkB homologues exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes .

This entry represents AlkB homologue 2 (ALKBH2, ABH2), which has a strong preference for double-stranded DNA . Together with alkyl-N-adenine-DNA glycosylase, comprises the cellular defence against 1,N(6)-ethenoadenine lesions . ABH2 also has an important role in maintaining ribosomal DNA gene integrity and transcription . This entry also includes uncharacterised bacterial homologues.
Alkylated DNA repair protein alkB homologue 3 (ALKBH3)
Type: Family

AlkB proteins are dioxygenases that repair alkylation damage to DNA and RNA . Nine mammalian AlkB homologues exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes .

This entry represents AlkB homologue 3 (ALKBH3, ABH3), which has a strong preference for single-stranded DNA also demethylates 1-methyladenine (1meA) and 3-methylcytosine (3meC) in RNA . ALKBH3 is overexpressed in various cancers and contributes to cancer cell survival .
Arterivirus polyprotein, nsp2, immunogenic region (NSP2-B_epitope)
Type: Domain

This domain is in a non-essential part of the nsp2 (non-structural protein) subunit section of the arterivirus polyprotein. This domain carries seven small sequence-regions that are predicted to be potential B-cell epitopes .
Putative glycogen debranching enzyme, N-terminal (GDE_N_bis)
Type: Domain

This domain is found at the N terminus of some putative glycogen debranching enzymes and is usually followed by GDE_C (

). In this sense it is analogous (but probably not homologous) to the GDE_N (

). Its exact function is unknown.
Alpha-ketoglutarate-dependent dioxygenase alkB homologue 4 (ALKBH4)
Type: Family

Based on homology with E. coli AlkB, nine mammalian AlkB homologues have been identified. Like E. coli AlkB, ALKBH2 and ALKBH3 have been shown to possess DNA repair activity. However, findings suggest a wide functional diversity for other mammalian AlkB proteins, with substrates ranging from DNA and RNA to protein .

ALKBH4 has been demonstrated to be an active Fe(II)/2OG-dependent decarboxylase
in vitro
. ALKBH4 mediates demethylation of actin and thereby regulates the actin-myosin II interaction. Depletion of ALKBH4 leads to defects in cytokinesis and cell motility .

This entry also includes Nmad-1, one of the five members of the ALKB family found in C. elegans, which is a 6mA DNA demethylase and may be involved in epigenetic inheritance .
Cbb3-type cytochrome c oxidase subunit CcoP, N-terminal (CcoP_N)
Type: Domain

This is the N-terminal domain of Cbb3-type cytochrome c oxidase subunit CcoP . The exact function is this domain not known.
GTPase Der, C-terminal KH-domain-like (KH_dom-like)
Type: Domain

This domain can be found in the C terminus of the bacterial GTPases Der. The two adjacent GTPase domains (GD1 and GD2) pack at either side of the C-terminal domain. This C-terminal domain resembles a KH domain but is missing the distinctive RNA recognition elements .
RNA demethylase ALKBH5 (ALKBH5)
Type: Family

Based on homology with E. coli AlkB, nine mammalian AlkB homologues have been identified. Like E. coli AlkB, ALKBH2 and ALKBH3 have been shown to possess DNA repair activity. However, findings suggest a wide functional diversity for other mammalian AlkB proteins, with substrates ranging from DNA and RNA to protein .

ALKBH5 is an dioxygenase that has been shown to specifically demethylate m(6)A in single-stranded RNA . Reversible m(6)A modification is one of the most abundant RNA modifications, and is probably involved in broad and fundamental functions in mammalian cells . ALKBH5 may have a role in the regulation of cellular responses to hypoxia .
Xylanase inhibitor, N-terminal (TAXi_N)
Type: Domain

This entry represents a domain found N-terminal in some aspartic proteinases and in xylanase inhibitors. The activity of these proteins is vital for plant-survival as xylanase produced by phytopathogens destroys
plant cells .
Alpha-ketoglutarate-dependent dioxygenase alkB homologue 6 (ALKBH6)
Type: Family

This entry represents a family of AlkB homologs. Based on similarity with E. coli AlkB, nine mammalian AlkB homologues have been identified. Like E. coli AlkB, ALKBH2 and ALKBH3 have been shown to possess DNA repair activity. However, findings suggest a wide functional diversity for other mammalian AlkB proteins, with substrates ranging from DNA and RNA to protein .

AlkB homologue 6 (ALKBH6) is a probable dioxygenase that requires molecular oxygen, alpha-ketoglutarate and iron. Its function is not known.
Prokaryotic E2 family C (Prok-E2_C)
Type: Family

This entry represents a divergent member of the E2/UBC superfamily of proteins found in bacteria. Members of the family contain a conserved cysteine in place of the histidine of the classical E2/UBC proteins . Members of this family are usually fused to an E1 domain at their C terminus. The protein is usually in the gene neighbourhood of a gene encoding a JAB peptidase and another encoding a predicted metal binding domain .
Prokaryotic E2 family A (Prok-E2_A)
Type: Family

This entry represents the member A of the E2/UBC superfamily of proteins found in several bacteria. The active site residues are very similar to the eukaryotic E2 proteins . Members of this family are usually fused to E1 and JAB domains C-terminal to the E2 domain. The protein is usually in the gene neighbourhood of a gene encoding a distinct metallobetalactamase family protein .
Prokaryotic Ubiquitin (Prok_Ub)
Type: Family

This entry represents a Ubiquitin-superfamily protein that is present across several bacterial lineages, and found in gene neighbourhoods with components of the ubiquitin modification system such as the E1, E2 and JAB proteins, and a novel α-helical protein, which is predicted to be enzymatic .
DYW domain (DYW_dom)
Type: Domain

This entry represents a highly conserved C-terminal DYW domain found in some plant pentatricopeptide repeat (PPR) proteins . This domain contains a characteristic zinc binding motif (CXXC, HXE), which has been shown to bind zinc ions. The glutamate residue of the HXE motif is catalytically required in the reaction catalysed by cytidine deaminase . This domain is required for RNA editing, a process that deaminates specific cytidines (C) to uridines (U) .
Alpha-ketoglutarate-dependent dioxygenase FTO (FTO)
Type: Family

Nine mammalian AlkB homologues exist, ALKBH1-8 and FTO . FTO, also known as Fat mass and obesity-associated protein, is an alpha-ketoglutarate-dependent dioxygenase involved in alkylated DNA and RNA repair . FTO activity is highest towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine . It has no detectable activity towards double-stranded DNA. FTO requires molecular oxygen, alpha-ketoglutarate and iron. FTO contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis, as well as the regulation of body size and body fat accumulation .
WHH domain-containing protein (WHH_dom_containing)
Type: Family

WHH domain containing protein is a predicted nuclease of the HNH/ENDO VII superfamily. The name is derived from the conserved motif WHH. It is found in bacterial polymorphic toxin systems and functions as a toxin module. It is the shortest version of HNH nuclease families. Like AHH and LHH, the WHH nuclease contains 4 conserved histidines of which the first one is predicted to bind a metal-ion and other three ones are involved in activation of water molecule for hydrolysis .
Alpha-ketoglutarate-dependent dioxygenase alkB homologue 7-like (ALKBH7-like)
Type: Family

This entry represents a family of eukaryotic proteins that includes ALKBH7 from mammals and the related protein 2OG and iron (Fe(II)) dependent dioxygenase Ofd2 from Schizosaccharomyces pombe.

Nine mammalian AlkB homologues exist, ALKBH1-8 and FTO . Differently to other AlkB homologues, AlkB homologue 7 (ALKBH7) does not exhibit any demethylase activity in DNA or RNA and its substrate is still unknown . ALKBH7 is located in the mitochondrial matrix. It is a key protein for programmed necrosis and fat metabolism . After agent-induced DNA-damage, it triggers the collapse of mitochondrial membrane potential and large-scale loss of mitochondrial function that lead to energy depletion and cellular demise .
AHH domain-containing protein (AHH_dom_containing)
Type: Family

AHH containing protein is a predicted nuclease of the HNH/ENDO VII superfamily of the treble clef fold. The name is derived from the conserved motif, AHH. It is found in bacterial polymorphic toxin systems and functions as a toxin module. Like WHH and LHH, the AHH nuclease contains 4 conserved histidines of which, the first one is predicted to bind a metal-ion and the other three ones are involved in activation of a water molecule for hydrolysis.
Wall-associated receptor kinase, C-terminal (WAK_assoc_C)
Type: Domain

This domain is cysteine-rich and frequently lies C-terminal to the galacturonan-binding domain (

).
DDE domain (DDE_dom)
Type: Domain

This putative DDE endonuclease domain is found in a wide variety of transposases including those found in IS240, IS26, IS6100 and IS26.
Succinyl-CoA synthetase-like, flavodoxin domain (Succ_CoA_lig_flav_dom)
Type: Domain

This domain contains the catalytic domain from Succinyl-CoA ligase alpha subunit and other related enzymes. A conserved histidine is involved in phosphoryl transfer .
Tip attachment protein J (J_dom)
Type: Domain

This domain can be found in the tip attachment protein J from Enterobacteria phage lambda. J is a tail fibre protein that attaches the virion to the host receptor LamB, inducing viral DNA ejection .
Transposase IS204/IS1001/IS1096/IS1165, helix-turn-helix domain (Transposase_HTH)
Type: Domain

This entry represents the HTH (helix-turn-helix) domain found in the IS204 , IS1001 , IS1096 and IS1165 transposases.
FixG, C-terminal immunoglobulin-like domain (FixG_C)
Type: Domain

This domain is part of a transmembrane protein, FixG, itself part of the FixGHIS operon closely associated with the FixNOPQ operon that is the symbiotically essential cbb3-type haem-copper oxidase complex. FixG expression is induced by oxygen-deprivation. This C-terminal domain adopts an E-set Ig-like fold .
CSC1/OSCA1-like, N-terminal transmembrane domain (CSC1/OSCA1-like_N)
Type: Domain

This entry represents the first three transmembrane regions of calcium permeable stress-gated cation channel 1 (Csc1). Csc1 is a cation channel that is permeable to calcium and gated by physical signals such as hyperosmotic stress .
Oberon-like, PHD finger domain (Oberon-like_PHD)
Type: Domain

This entry represents a plant homeodomain (PHD) finger domain of Oberon proteins from plants. Oberon is necessary for maintenance and/or establishment of both the shoot and root apical meristems in Arabidopsis. Oberon proteins are made up of a PHD finger domain and a coiled-coil domain. The PHD-finger domain is found in a wide variety of proteins involved in the regulation of chromatin structure . Oberon proteins mediate the TMO7 (the direct target of MP) expression through modification of, or binding to, chromatin at the TMO7 locus. TMO7 stands for the target of Monopteros 7 (MP) (or Auxin response factor 7) .

This domain can also be found in protein VERNALIZATION INSENSITIVE 3 (VIN3) and related proteins. VIN3 is involved in both the vernalization and photoperiod pathways in Arabidopsis . VIN3-like protein 1 (also known as VRN5) functions in the epigenetic silencing of Arabidopsis FLOWERING LOCUS C .
SrkA/RdoA protein kinase (SrkA/RdoA)
Type: Family

Srk protein kinase, also known as rdoA or yihE, is a Ser/Thr protein kinase that regulates programmed cell death in bacteria .
6-phosphogluconate dehydrogenase, archaea (6PGDH_archaea)
Type: Family

This entry represents 6-phosphogluconate dehydrogenase (6PGDH) from archaea. Proteins in this entry share protein sequence similarity with B. subtilis YqeC, which is a truncated 6PGD that possesses a NAD+-dependent activity .
NAD-dependent glucose-6-phosphate dehydrogenase, archaea (Glc6PDH_archaea)
Type: Family

This entry represents NAD-dependent glucose-6-phosphate dehydrogenase (Glc6PDH, encoded by zwf for zwischenferment) from archaea.

Haloferax volcanii Glc6PDH is involved in the oxidative pentose phosphate pathway (OPPP). It catalyses the NAD-dependent oxidation of glucose 6-phosphate (Glc6P) to 6-phosphogluconolactone . It is a homodimeric enzyme of 32kDa subunits, catalysing the NAD+ specific oxidation of Glc6P. Interestingly, it is not related to the classical Glc6PDH of the OPPP in bacteria and eukarya .
DNA double-strand break repair protein Mre11, archaea-type (Mre11_archaea-type)
Type: Family

This entry includes DNA double-strand break repair protein Mre11 mainly from archaea. Similar to the eukaryotic Mre11-Rad50 complex, the archaeal Mre11-Rad50 complex is involved in the early steps of DNA double-strand break (DSB) repair. The Haloferax volcanii Mre11-Rad50 complex may restrain the repair of DSBs by HR (homologous recombination), allowing another pathway to act as the primary mode of repair .
tRNA-dihydrouridine(16) synthase (DusC)
Type: Family

Dihydrouridine (D) is a highly conserved modified base found in tRNAs from all domains of life. D is formed by reduction of the carbon-carbon double bond at positions 5 and 6 of the uridine base by dihydrouridine synthases (Dus), and is mostly found in the D-loop of tRNAs for which it is named .

This entry represents DusC, also known as tRNA-dihydrouridine(16) synthase, which is specific toward U16 of tRNA .
tRNA-dihydrouridine synthase B (DusB)
Type: Family

Dihydrouridine (D) is a highly conserved modified base found in tRNAs from all domains of life. D is formed by reduction of the carbon-carbon double bond at positions 5 and 6 of the uridine base by dihydrouridine synthases (Dus), and is mostly found in the D-loop of tRNAs for which it is named .

This entry represents DusB, also known as tRNA-dihydrouridine synthase B, which catalyses the synthesis of 5,6-dihydrouridine (D) via the reduction of the C5-C6 double bond in target uridines .
Histidine N-alpha-methyltransferase, Actinobacteria-type (EgtD_Actinobacteria)
Type: Family

This entry represents histidine N-alpha-methyltransferase EgtD mostly from Actinobacteria. EgtD catalyses the SAM-dependent triple methylation of the alpha-amino group of histidine to form hercynine, a step in the biosynthesis pathway of ergothioneine . Ergothioneine is a histidine-derived thiol that may protect against oxidative stress .
Gamma-glutamyl-hercynylcysteine sulfoxide hydrolase, Actinobacteria (EgtC_Actinobacteria)
Type: Family

This entry represents gamma-glutamyl-hercynylcysteine sulfoxide hydrolase EgtC from Actinobacteria. EgtC catalyses the hydrolysis of the gamma-glutamyl amide bond of hercynyl-gamma-L-glutamyl-L-cysteine sulfoxide to produce hercynylcysteine sulfoxide, a step in the biosynthesis pathway of ergothioneine . Ergothioneine is a histidine-derived thiol that may protect against oxidative stress .

The structure of EgtC has been revealed .
Hercynine oxygenase, Actinobacteria (EgtB_Actinobacteria)
Type: Family

This entry represents hercynine oxygenase EgtB from Actinobacteria. EgtB catalyses the oxidative sulfurization of hercynine (N-alpha,N-alpha,N-alpha-trimethyl-L-histidine) into hercynyl-gamma-L-glutamyl-L-cysteine sulfoxide, a step in the biosynthesis pathway of ergothioneine . Ergothioneine is a histidine-derived thiol that may protect against oxidative stress .
UDP-N-acetyl-D-mannosamine dehydrogenase WecC (WecC)
Type: Family

This entry represents UDP-N-acetyl-D-mannosamine dehydrogenase wecC (also known as RffD) from Enterobacteriaceae. WecC 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 . It catalyses the four-electron oxidation of UDP-N-acetyl-D-mannosamine (UDP-ManNAc), reducing NAD+ and releasing UDP-N-acetylmannosaminuronic acid .