SII-SWORD/CoKE huggingface dataset:
OTU domain-containing protein 6A/6B, ovarian tumor domain (OTU_OTUD6)
Type: Domain

This entry represents the OTU (ovarian tumor) domain of human OTU domain-containing proteins 6A (OTUD6A, also called DUBA-2) and 6B (OTUD6B, also called DUBA-5) and similar animal sequences. These proteins are deubiquitinating enzymes/ubiquitinyl hydrolases (

). OTUD6A hydrolyses 'Lys-27'-, 'Lys-29'-, and 'Lys-33'-linked polyubiquitin chains, and may also be able to hydrolyse 'Lys-11'-linked ubiquitin chains. It deubiquitylates and stabilises dynamin-related protein 1 (Drp1), a cytosolic protein responsible for mitochondrial fission and is essential in the initiation and development of several human diseases including cancer, thereby facilitating tumourigenesis. OTUD6B may play a role in the ubiquitin-dependent regulation of protein synthesis downstream of mTORC1, and may modify the ubiquitination of the protein synthesis initiation complex to repress translation . Biallelic variants in OTUD6B cause an intellectual disability syndrome that is associated with seizures and dysmorphic features . This group of proteins belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as a catalytic triad.
AF10-like, coiled-coil domain (AF10-like_CC)
Type: Domain

This entry represents the coiled-coil domain from AF10 and its homologues.

This entry includes AF10 (ALL1-Fused gene from chromosome 10 protein) from mammals and its homologue from C. elegans, zinc finger protein zfp-1. AF10 is one of mixed-lineage leukemia 1 (MLL1)-fusion partners that function in acute myeloid leukemia (ALL) and plays a key role in the survival of uncommitted hematopoietic cells. Aberration of the mixed-lineage leukemia (MLL) gene is implicated in acute leukemia; chromosomal translocations of MLL1 generate oncogenic chimeric proteins, containing the non-catalytic N-terminal portion of MLL1 fused with many partners such as AF10. The MLL-AF10 fusion oncoprotein recruits DOT1L (disruptor of telomeric-silencing 1-like) to the homeobox A . The aberrant recruitment of DOT1L, a histone methyltransferase that methylates H3 lysine residues (H3K79), by MLL fusions and the resulting H3K79 methylation are thought to affect gene expression by altering chromatin accessibility . AF10 and DOT1L interact through their coiled coil domains . AF-10 also functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-10 contains an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger .

C.elegans zpf-1 recruits the histone methyltransferase dot-1.1 to chromatin to methylate 'Lys-79' of histone H3 and activate transcription of target genes . It also recognizes and binds histone H3 methylated at 'Lys-4' (H3K4me) at the promoters of target genes . In response to stress, binds to the pdk-1 promoter to negatively regulate pdk-1 expression, which negatively modulates daf-16/FOXO-mediated gene expression . It plays a role in Insulin/IGF-1-like signalling (IIS)- and diet restriction-mediated lifespan extension by controlling daf-16/FOXO and pha-4/FOXA recruitment to target promoters .
Hormogonium polysaccharide biosynthesis protein HpsA-like (EPS_HpsA-like)
Type: Family

This entry represents hormogonium polysaccharide biosynthesis protein HpsA from Nostoc punctiforme and related proteins found in filamentous cyanobacteria. HpsA gene is a member of a gene cluster involved in hormogonium polysaccharide (HPS) production. Deletion of HpsA completely abolish motility and polysaccharide secretion in N. punctiforme .
AF-10, extended PHD finger (AF10_ePHD)
Type: Domain

This entry represents the ePHD domain of AF10.

This entry includes AF10 (ALL1-Fused gene from chromosome 10 protein), one of mixed-lineage leukemia 1 (MLL1)-fusion partners that function in acute myeloid leukemia (ALL) and plays a key role in the survival of uncommitted hematopoietic cells. Aberration of the mixed-lineage leukemia (MLL) gene is implicated in acute leukemia; chromosomal translocations of MLL1 generate oncogenic chimeric proteins, containing the non-catalytic N-terminal portion of MLL1 fused with many partners such as AF10. The MLL-AF10 fusion oncoprotein recruits DOT1L (disruptor of telomeric-silencing 1-like) to the homeobox A . The aberrant recruitment of DOT1L, a histone methyltransferase that methylates H3 lysine residues (H3K79), by MLL fusions and the resulting H3K79 methylation are thought to affect gene expression by altering chromatin accessibility . AF10 and DOT1L interact through their coiled-coil domains .

AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-10 contains an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger .
Membrane protein YoeI-like (YoeI-like)
Type: Family

This entry represents the YoeI protein (

) from E.coli and related proteins found mainly in Enterobacteria. YoeI is a hydrophobic protein of only 20 amino acids and it is known to be expressed in E. coli in high levels especially in exponential phase . Changes in the YoeI expression levels were observed in response to stress or different growth conditions .
SCO2524-like (SCO2524-like)
Type: Family

This entry represents the uncharacterised protein SCO2522 of Streptomyces coelicolor (

) and related proteins from Actinomycetes. This family of proteins is part of a conserved gene neighborhood encoding proteins SCO2521-SCO2524.
Heterocyst differentiation protein HetZ-like (HetZ-like)
Type: Family

This entry represents HetZ, a heterocyst differentiation protein from Anabaena sp., and related proteins found mainly in cyanobacteria . HetZ is among the most important factors involved in heterocyst differentiation . HetZ functions in the patterning stage of differentiation. Deletion of hetZ fails to express the developmental genes hetR, patS, hetP and hetZ correctly and fails to produce heterocysts .
Kinesin-like protein KIF1A, forkhead associated domain (FHA_KIF1A)
Type: Domain

This entry represents the forkhead associated (FHA) domain found in human Kinesin-like protein KIF1A and similar proteins from vertebrates. This domain is a small phosphopeptide recognition module, but this group may lack the conserved residues that are required for binding phosphothreonine

KIF1A, also called axonal transporter of synaptic vesicles (ATSV), microtubule-based motor KIF1A, Unc-104- and KIF1A-related protein, or Unc-104, is an axonal transporter of synaptic vesicles, which is mutated in hereditary sensory and autonomic neuropathy type 2. It is also required for neuronal dense core vesicle (DCV) transport to dendritic spines and axons. The calcium-dependent interaction with CALM1 increases vesicle motility, and the interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites .
Kinesin-like protein KIF1A/B, pleckstrin homology domain (PH_KIFIA_KIFIB)
Type: Domain

This entry represents the pleckstrin homology (PH) domain located at the C-terminal end of human Kinesin-like protein KIF1A and KIF1B and similar proteins from animals, including the KIF1A homologue Kinesin-like protein unc-104 from Drosophila melanogaster . KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). Members of this group have an N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain.

PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. The specificity of this domain is usually determined by loop regions or insertions at the N terminus of the domain, which are not conserved across all PH domains .
AF-10/AF-17, PHD finger (AF10/AF17_PHD)
Type: Domain

This entry represents the PHD finger from AF10, its homologues and AF17.

This entry includes AF10 (ALL1-Fused gene from chromosome 10 protein) from mammals, its homologue from C. elegans, zinc finger protein ZPF-1 and AF-17 (also termed ALL1-fused gene from chromosome 17 protein).

AF-10/AF-17 have been identified in hematological malignancies as translocation partners of the mixed-lineage leukemia gene (MLL) which functions in acute myeloid leukemia (ALL); chromosomal translocations of MLL1 generate oncogenic chimeric proteins, containing the non-catalytic N-terminal portion of MLL1 fused with many partners. AF-10 plays a key role in the survival of uncommitted hematopoietic cells. The MLL-AF10 fusion oncoprotein recruits DOT1L (disruptor of telomeric-silencing 1-like) to the homeobox A . The aberrant recruitment of DOT1L, a histone methyltransferase that methylates H3 lysine residues (H3K79), by MLL fusions and the resulting H3K79 methylation are thought to affect gene expression by altering chromatin accessibility . AF10 and DOT1L interact through their coiled coil domains . AF-10 also functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-17 is a putative transcription factor that may play a role in multiple signalling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signalling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure . These proteins contain an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger .

C.elegans ZPF-1 recruits the histone methyltransferase dot-1.1 to chromatin to methylate 'Lys-79' of histone H3 and activate transcription of target genes . It also recognises and binds histone H3 methylated at 'Lys-4' (H3K4me) at the promoters of target genes . In response to stress, binds to the pdk-1 promoter to negatively regulate pdk-1 expression, which negatively modulates daf-16/FOXO-mediated gene expression . It plays a role in Insulin/IGF-1-like signalling (IIS)- and diet restriction-mediated lifespan extension by controlling daf-16/FOXO and pha-4/FOXA recruitment to target promoters .
Pilus assembly protein FilE-like (FilE-like)
Type: Family

This entry represents the FilE protein. FilE is found almost exclusively in Acinetobacter, and is assigned as a putative pilus system protein from local genomic contexts that include several additional putative pilus system proteins. Some members of this protein family contain proline-rich repeat regions.
ABC transporter permease TupB-like (ABC_perm_TupB-like)
Type: Family

Proteins of this family are permease subunits of ABC transporter complexes. Included in this family is the protein TupB (

), which is involved in tungstate transport .
Multiple sugar-binding periplasmic receptor ChvE-like (ChvE-like)
Type: Family

This entry represents the Multiple sugar-binding periplasmic receptor ChvE and related bacterial proteins. ChvE belongs to a family of pentose/hexose sugar-binding proteins of the type 1 periplasmic binding protein (PBP1) superfamily, which consists of two α/β globular domains (known as Venus flytrap-like domains) . In XylS (D-xylose-binding periplasmic protein), member of this family, these Venus flytrap-like domains undergo a transition from an open to a closed conformational state upon ligand binding . These domains are homologous to the ligand-binding domains of eukaryotic receptors such as glutamate receptor (GluR) and DNA-binding transcriptional repressors such as LacI and GalR .
GT-D fold-like domain, firmicutes (GT-D-like_firm)
Type: Domain

This entry describes a domain related to the GT-D fold glycotransferase domain (

). These protein domains share a common sequence motif R[VIL]GDGE, significant structural similarity based on the predicted AF2 model, but only about 16 percent sequence identity. This domain is found standalone and in combination with other domains in a number of proteins mainly from Firmicutes.
RNA-binding protein rnc1, third type I K homology RNA-binding domain (Rnc1_KH-I_3)
Type: Domain

This entry represents the third type I K homology (KH) RNA-binding domain found in Schizosaccharomyces pombe RNA-binding protein rnc1 (

) and similar fungal proteins. Rnc1, also called RNA-binding protein that suppresses calcineurin deletion 1, is an RNA-binding protein that acts as an important regulator of the posttranscriptional expression of the MAPK phosphatase Pmp1 in fission yeast. It binds and stabilises pmp1 mRNA and hence acts as a negative regulator of pmk1 signalling. Overexpression of Rnc1 suppresses the Cl(-) sensitivity of calcineurin deletion. The nuclear export of Rnc1 requires mRNA-binding ability and the mRNA export factor Rae1. Rnc1 contains three K-homology (KH) RNA-binding domains .
Ras-association domain-containing protein 6, C-terminal SARAH domain (SARAH_RASSF6)
Type: Domain

This entry represents the C-terminal SARAH (Salvador-RassF-Hippo) domain found in human Ras-association domain-containing protein 6 (RASSF6) and similar sequences from vertebrates. RASSF6 is one of six related proteins, the classical RASSF proteins (RASSF1-6), that contain a conserved RalGDS/AF6 Ras association (RA) domain located towards the C terminus. It acts as a tumour suppressor protein involved in the induction of apoptosis, through both caspase-dependent and caspase-independent pathways. RASSF6 may function as a Ras effector protein. It is ubiquitinated and degraded by interacting with MDM2 to stabilise p53, and it regulates apoptosis and the cell cycle. RASSF6 is expressed as four transcripts via alternative splicing. All transcript variants of RASSF6 contain the RA (

) and SARAH domains. SARAH domains mediate protein-protein interactions crucial in the pathways that induce cell cycle arrest and apoptosis .
Nucleotide 5'-monophosphate nucleosidase PpnN (PpnN)
Type: Family

This entry represents the PpnN protein from Escherichia coli (

) (also known as YgdH) and related proteins found mainly in gammaproteobacteria. PpnN (pyrimidine/purine nucleotide 5'-monophosphate nucleosidase) catalyzes the hydrolysis of the N-glycosidic bond of diverse pyrimidine and purine nucleotide 5'-monophosphates, to form ribose 5-phosphate and the corresponding free base, and plays an essential role in purine homeostasis . It can bind the the stringent response alarmones ppGpp and pppGpp and then, because of allosteric changes, have a much higher rate of cleavage of preferred substrate GMP .
ArsI/CadI-like (ArsI/CadI-like)
Type: Family

This entry includes Trivalent organoarsenical cleaving enzyme from Thermomonospora curvata (ArsI), Cadmium-induced protein CadI from Mycobacterium tuberculosis, and related bacterial proteins. ArsI is a nonhaeme iron-dependent dioxygenase that can break carbon-arsenic bonds, playing a role in the detoxification of environmental organoarsenical compounds. It catalyses the oxygen-dependent demethylation of highly toxic methylarsonous acid (MAs(III)) to arsenite, which can then be exported out of the cell . Proteins in this entry contain a VOC (Vicinal Oxygen Chelate) domain (

). Members of this family have an invariant CC sequence motif at about position 95, and have poorly conserved C-terminal regions that frequently contain at least one addition CC motif .
Rv3655c/TadE (Rv3655c/TadE)
Type: Family

This entry represents the Rv3655c family as it is found in Mycobacterium tuberculosis (

) and related species mainly from actinomycetes. Rv3655c belongs to an operon that produces a bacterial type IV pilus (Tad genes). Rv3655c is an effector protein involved in inhibiting macrophage apoptosis through the blockage of the extrinsic pathway. It hinders caspase-8 activation and associates with the host E3 ubiquitin-protein ligase RNF213, which, when fused with other proteins, exerts anti-apoptotic effects .
STM0539-like (STM0539-like)
Type: Family

This entry represents the STM0539 protein (

), from Salmonella enterica strain LT2, and related proteins found in Enterobacteria. The members of family have about 145 amino acids in length. Their function is unknown.
PA1414-like (PA1414-like)
Type: Family

This entry represents the PA1414 protein from Pseudomonas aeruginosa, and its homologues from Pseudomonadaceae species. The function of this small protein is unknown.
Mobilization protein MbpA-like (MbpA-like)
Type: Family

This entry represents the mobilization protein MbpA (

) from Bacteroides fragilis and related bacterial proteins. MbpA was identified as a member of a gene cluster, the products of which have roles in the mobilization process. MbpA was found to function in trans and to be required for mobilization .
DISARM protein DrmE (DrmE)
Type: Family

This entry represents DISARM protein DrmE (

) from Bacillus paralicheniformis, and related bacterial proteins.

DrmE is a component of antiviral defense system DISARM (defense island system associated with restriction-modification), composed of DrmE, DrmA, DrmB, DrmC and DrmMII. DISARM is probably a multi-gene restriction module, but DrmE has an unknown function. Expression of DISARM in B.subtilis (strain BEST7003) confers resistance to phages Nf, phi29, phi105, phi3T, SPO1, SPR and SPP1. DISARM does not interfere with phage adsorption, but instead interferes with (phi3T) DNA replication early in its cycle, preventing replication, circularization and lysogeny and probably causes phage DNA degradation .
LpxT activity modulator PmrR (PmrR)
Type: Family

This entry represents the PrmR protein (

), from E.coli and related proteins from Enterobacteria. PrmR is an extremely small hydrophobic protein of 29 amino acids in length that controls the modification of the lipid A indirectly. It localises to the inner membrane and interacts with LpxT hindering LpxT-mediated modification of lipid A .
CdiI immunity protein-like (CdiI_Ct-like)
Type: Family

CDI toxins are expressed by gram-negative bacteria as part of a mechanism to inhibit the growth of neighboring cells. This entry represents the inhibitor (CdiI, also called CdiI immunity protein) of the CdiA effector protein from Cupriavidus taiwanensis, and similar proteins. CdiA secretion is dependent on the outer membrane protein CdiB. Upon binding to a receptor on the surface of target bacteria, the CDI toxin is delivered via its C-terminal domain (CdiA-CT). The CdiI immunity proteins are intracellular proteins that inactivate the toxin/effector protein to prevent auto-inhibition. They are specific for their cognate CdiA-CT and do not protect cells from the toxins of other CDI bacteria. Thus, CDI systems encode a complex network of toxin-immunity protein pairs that are deployed for intercellular competition. This CdiI is α-helical and binds its cognate toxin CdiA-CT domain with high affinity .
HYExAFE motif-containing protein (HYExAFE)
Type: Family

This entry represents an uncharacterised family of proteins mainly found in Planctomycetes. The family is named after the most conserved region, the sequence motif HY[ED]xAFE, found near the N terminus of the family members. The function of these proteins is unknown.
LWR-salt (LWR_salt)
Type: Family

This entry represents a family of uncharacterised proteins found in Halobacteria. This family was named after a well-conserved sequence motif LWR (part of the longer motif WxFFRDxLWRG).
SitI3-like (SitI3-like)
Type: Family

This entry represents SitI3 from Myxococcus xanthus (

) and related bacterial proteins. SitI3 is an immunity protein encoded immediately downstream of a lipoprotein toxin, SitA3, that can move between cells by means of a transfer system for exchange of outer membrane lipoproteins involved in kin recognition . It is not clear what fraction of the members of this family are immunity proteins from other toxin/immunity-type conflict systems.
Chemotaxis regulatory protein ChePep (Chtaxis_ChePep)
Type: Family

This entry represents the chemotaxis regulatory protein ChePep (

) and related proteins from Helicobacter species. ChePep plays an essential role in chemotaxis. It regulates flagellar rotation through the formation of a complex with chemotaxis protein CheZ . It also plays a major role in the colonisation of the stomach and establishing of the bacterial colonies deep in the gastric glands .
Type VII secretion system-associated protein-like (T7SS_assoc-like)
Type: Family

Members of this family are found mainly in Streptomyces sp., and are associated with a type VII secretion system (T7SS). Their function is unknown.
RhsC-like, type sIX effector domain (RhsC-like_FIX)
Type: Domain

This entry represents the Found in type sIX effector (FIX) domain of RhsC (

) from Dickeya dadantii and similar sequences mainly found in proteobacteria. This domain is located N-terminal to known toxin domains and is genetically and functionally linked to type VI secretion system (T6SS), a widespread mechanism used by Gram-negative bacteria to antagonise neighbouring cells. In some members of this group, the FIX domain is found associated with C-terminal nuclease toxin PoNe (Polymorphic Nuclease effector), which is associated with several toxin delivery systems including type V, type VI, and type VII; in others with the C-terminal Ntox15 (Novel toxin 15,

), a predicted RNase toxin that possesses a conserved HxxD motif; and in others with extended RHS repeats (

) .
Thiocillin RiPP-like (RiPP_thiocil-like)
Type: Family

Members of this family are ribosomally synthesized and post-translationally modified peptide natural product (RiPP) precursors. Nearly all contain at least one Cys residues expected to be involved in thiazolyl peptide modifications, and are expected to behave at least in part as antibiotics . Some species, such as Bacillus atrophaeus, may contain multiple paralogues.
Choice-of-anchor L domain (Choice_anch_L)
Type: Domain

This entry represents the choice-of-anchor L domain primarily identified in Flavobacteriales. It spans about 220 amino acid residues and constitutes an extracellular domain frequently accompanied by a C-terminal T9SS type B sorting domain (

).
Lasso peptide Benenodin-like (Lasso_benenodin)
Type: Family

This family consists of both the leader (removed) and core (mature) portions of precursor peptides from the benenodin family of lasso peptides, found in proteobacteria. Lasso peptide benenodin-1 exhibits conformational switching between two distinct threaded conformers upon actuation by heat. This thermally induced conformational switching of benenodin-1 may be relevant to its biological function .

Lasso peptides are a class of ribosomally synthesised and post-translationally modified peptides (RiPPs) . Up to date, they have been only isolated from proteo- and actinobacterial sources. Typically, lasso peptide biosynthetic gene clusters encode enzymes for biosynthesis and export but not for tailoring. A wide range of interesting biological activities are known for these RiPPs, including antimicrobial, enzyme inhibitory, and receptor antagonistic activities. Generally, all known lasso peptides carry a Gly, Ala, Cys, or Ser residue at position 1 and a ring-forming Glu or Asp residue at positions 7-9. Their respective processing enzymes are highly specific for the nature and location of these residues .