SII-SWORD/CoKE huggingface dataset:
Pilin-like (Pilin-like)
Type: Homologous_superfamily

This superfamily includes Pilin and related proteins, such as general secretion pathway protein G (GSPG) and autotransporter adhesin YadA-like proteins.

Pilin is a component of type IV pilus (T4P), a polar flexible filament, which consists of a single polypeptide chain arranged in a helical configuration of five subunits per turn, which is involved cell adhesion, microcolony formation, twitching motility and transformation . Gram-negative bacteria produce pilin which is characterised by the presence of a very short leader peptide of 6 to 7 residues, followed by a methylated N-terminal phenylalanine residue and by a highly conserved sequence of about 24 hydrophobic residues, of the NMePhe type pilin .

GSPG shares several sequence similarities with bacterial fimbrial protein, or pilin, the major structural protein of pili . Pili are polar flexible filamentous adhesions ~2500 nm in length, and diameter ~5.4 nm. Fimbrial and GSPG proteins share the following characteristics: a methylated, hydrophobic N-terminal residue; a hydrophobic leader peptide of 5-10 residues, terminating with glycine; glutamate as the fifth residue of the mature sequence; and a highly hydrophobic N-terminal. This system is homologous to the type IV pilus biogenesis and includes different proteins, termed psudopilins, which are structurally homologous to the type IV pilins .

Autotransporter adhesin YadA-like proteins are part of a class of pathogenicity factors that act as cell surface adhesion molecules, in which N-terminal head and neck domains extend from the bacterial outer membrane .
Diadenylate cyclase CdaA, N-terminal domain (CdaA_N)
Type: Domain

This entry represents the N-terminal domain found in diadenylate cyclase CdaA. This domain shows three helical transmembrane regions .

Diadenylate cyclase catalyses the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP), a signaling compound secreted into the host's cytosol by bacterial pathogens, such as Listeria monocytogenes. This compound triggers the cytosolic surveillance pathway (CSP), a host pathway of innate immunity . Apart from a role in the establishment of bacterial infection, c-di-AMP seems to be involved in coordinating bacterial growth, cell wall stability, and responses to stress .

Most bacteria possess one diadenylate cyclase (DAC) enzyme (CdaA, also called YbbP and DacA), while Bacillus subtilis has two additional DACs (CdaS, also called YojJ and DacB) and DisA . This entry includes CdaA from B.subtilis, which produces the c-di-AMP required for cell wall homeostasis but harmful in excess .
Diadenylate cyclase DacZ, N-terminal domain (DacZ_N)
Type: Domain

This entry represents the N-terminal domain of DacZ-type diadenylate cyclase (DAC) from archaea, including DacZ form Haloferax volcanii . Sequences analysis and homology modeling of 3D structures revealed that this domain has a fold similar to the C-terminal α/β domain of pyruvate kinase.
Ribitol-5-phosphate transferase FKTN, N-terminal (FKTN_N)
Type: Domain

This is the N-terminal domain of Ribitol-5-phosphate transferase FKTN (also referred to fukutin) which contains the transmembrane domain required for its localisation to the Golgi and participates in the interaction with POMGnT1 (Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1) for normal POMGnT1 location and activity . FKTN is a ribitol-phosphate transferase that forms a complex with FKRP (fukutin-related protein, also a ribitol-phosphate transferase) and TMEM5 (a ribitol xylosyltransferase). Fukutin, FKRP, and TMEM5 maintain each of their enzyme activities in the complex and may contribute to specific biosynthesis of glycans required for dystroglycan function .
Calsyntenin, C-terminal (CLSTN_C)
Type: Domain

This entry represents the cytoplasmic C-terminal domain of calsyntenin (CLSTN) proteins 1, 2 and 3 (also known as alcadein-alpha, beta and gamma). These are postsynaptic Ca2-binding proteins, evolutionarily conserved type I membrane proteins. CLSTN (also known as Alc) forms a tripartite complex with APP (amyloid beta-protein precursor) and X11L (a neuron-specific adaptor protein) in brain; this complex stabilizes both APP and CLSTN proteins metabolically. Deficiencies in the X11L-mediated interaction between CLSTN and APP and/or CTFbeta enhances the production of amyloid beta-protein and have been linked to the development or progression of Alzheimer's disease . Moreover, CLSTN1 strongly associates with kinesin-1 light chains (KLC1) and acts as a cargo that regulates kinesin-1 function. It may affect the transport of APP-containing vesicles by kinesin-1 . This domain includes the WD motifs required for KLC1 interaction (although one WD motif is sufficient), and the NP motif .
Protein of unknown function DUF6464 (DUF6464)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria.
Protein of unknown function DUF6463 (DUF6463)
Type: Family

This family of integral membrane proteins is functionally uncharacterised. This family of proteins is found in bacteria.
Protein of unknown function DUF6462 (DUF6462)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria, mainly in Firmicutes. Proteins in this family are typically between 62 and 78 amino acids in length. Some of the members are probably transcriptional regulators. This family has overlaps with families in clan CL0123, which suggests that they share the helix-turn-helix motif.
Protein of unknown function DUF6461 (DUF6461)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria.
Atg11, middle domain (Atg11_middle)
Type: Domain

This domain represents a region comprised between residues 522 and 583 from fission yeast protein Atg11 (also known as Taz1-interacting factor 1). This domain is necessary and sufficient for Atg11 autophagy function and for supporting Atg1 kinase activity as it harbours an Atg1-binding domain at the N terminus and a homodimerization domain at the C terminus. The N-terminal part of this domain contains the conserved aromatic residues Phe and Tyr necessary for the direct and specific interaction with the tMIT domain of Atg1. This interaction is required for the autophagy function of Atg11. The C-terminal part of this domain, residues 546-583, is predicted to adopt a coiled-coil conformation which mediates Atg11 homodimerization . Proteins containing this domain seem to be restricted to Schizosaccharomyces.
Domain of unknown function DUF6460 (DUF6460)
Type: Domain

This domain of unknown function is found at the C-terminal of uncharacterised proteins, found in Alphaproteobacteria. There is a conserved motif GAxI/VVxP. Some members of this entry are likely integrases.
Protein of unknown function DUF6459 (DUF6459)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria.
Domain of unknown function DUF6458 (DUF6458)
Type: Domain

This domain is primarily found in proteins from Actinobacteria.
Domain of unknown function DUF6457 (DUF6457)
Type: Domain

This presumed domain is functionally uncharacterised. This domain can sometimes be found C-terminal to an MobA-like guanyltransferase domain.
Domain of unknown function DUF6456 (DUF6456)
Type: Domain

This presumed domain can be found in proteins from bacteria.
RelA/SpoT, AH and RIS domains (RelA/SpoT_AH_RIS)
Type: Domain

This entry represents the α helical (AH) and Ribosome-InterSubunit (RIS) domains found in RelA/SpoT proteins, adjacent to the ACT domain . AH interacts with A/R tRNA and connects the RIS domain with the TGS domain. RIS domain is part of the binding interface between the C-terminal region and the ribosome, bridging the large and the small ribosomal subunits. RIS contains a four-stranded β-sheet and a short α-helix.

RelA/SpoT-homologue proteins (RHS) mediate the stringent response in bacteria which enables its metabolic adaptation under stress conditions. These enzymes synthesize the second messenger (p)ppGpp, a small molecule also known as 'alarmone', which is a regulatory metabolite of the stringent response, characterised by growth arrest and the modulation of gene expression in response to various nutritional stresses . Including in this group of proteins are RelA and SpoT, whose functions differ somewhat. RelA (

) produces pppGpp (or ppGpp) from ATP and GTP (or GDP), while SpoT (

) is a bifunctional enzyme that degrades ppGpp, but can also act as a ppGpp synthetase. In many species, a single homologue to SpoT and RelA , Rsh, appears responsible for both ppGpp synthesis and ppGpp degradation . ppGpp together with c-di-GMP play an important role to control biofilm formation in response to translational stress .

These enzymes consist of a N-terminal domain which harbor (p)ppGpp hydrolase and synthetase activity and a stress-perceiving and regulatory C-terminal domain, which comprising four sub-domains: the TGS (ThrRS, GTPase, and SpoT), AH (α-helical), RIS (ribosome inter-subunit), and ACT (aspartate kinase, chorismate mutase, TyrA) .
Domain of unknown function DUF6455 (DUF6455)
Type: Domain

This domain, found in proteins from Proteobacteria, is functionally uncharacterised. This presumed domain contains a conserved histidine and four conserved cysteines suggestive of zinc binding.
MARF1, first and second LOTUS domain (MARF1_LOTUS)
Type: Domain

This entry represents the first and second LOTUS domains of MARF1. This domain provides RNA-binding properties to this protein, acting as an adapter to recruit targets for the effector domain NYN at the N-terminal (RNase activity) .

Meiosis regulator and mRNA stability factor 1 (also known as meiosis arrest female protein 1, MARF1, or Limkain-b1) was first identified as a novel peroxisomal autoantigen that co-localizes with a subset of cytoplasmic microbodies marked by ABCD3 . Later, it was found that it is an essential regulator of oogenesis required for female meiotic progression and retrotransposon surveillance, therefore, involved in the maintenance of genomic integrity. It acts as a RNAse that efficiently cleaves ssRNAs and down-regulates RNA transcripts, either at transcriptional or post-transcriptional level . It may function both as an adaptor to recruit specific RNA targets and an effector to catalyse the specific cleavages of target RNAs. MARF1 consists of three major domains, the N-terminal NYN domain, two RNA recognition motifs (RRMs) and a C-terminal repeat of LOTUS (also known as OST-HTH) domains.
QcrA subunit, N-terminal (QcrA_N)
Type: Domain

This entry represents the N-terminal region of the bacterial QcrA subunit (also known as Cytochrome bc1 complex Rieske iron-sulfur subunit) which is part of respiratory complex III . This entry includes anchoring transmembrane helical regions.
Protein of unknown function DUF6453 (DUF6453)
Type: Family

This family of uncharacterised proteins can be found in phages. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches. There are several conserved motifs: FxxI, GxxxxP and FSxxxxP, and also 7 additional conserved Glycine residues.
3-ketosteroid-9-alpha-monooxygenase, oxygenase component-like, C-terminal domain (KshA-like_C)
Type: Domain

This entry represents the C-terminal catalytic domain of the 3-ketosteroid-9-alpha-monooxygenase (KshA) from bacteria. KshA is the oxygenase component of the 3-ketosteroid 9-alpha-hydroxylase (KshAB), a two-component Rieske oxygenase involved in the degradation of cholesterol . This domain shares the TBP-like fold found in other Rieske oxygenases . It also appears in Cholesterol 7-desaturase nvd/daf-36, which is involved in cholesterol metabolism in organisms like Xenopus laevis and Drosophila melanogaster .
ATXR3, C-terminal (ATXR3_C)
Type: Domain

This domain includes the POST_SET domain located at the C-terminal of SDG2, although there is no significant sequence homology with other Arabidopsis SDGs outside of the SET domain .

Histone-lysine N-methyltransferase (ATXR3), also known as SET DOMAIN GROUP 2 (SDG2), is involved in the trimethylation of lysine 4 on histone H3 (H3K4me3), a critical post-translational modification that regulates chromatin structure and gene expression. It is essential for both sporophyte and gametophyte development , . Acting as a diurnal 'writer', it counteracts the nocturnal demethylase activity of JMJ14, thus orchestrating the circadian rhythm of histone modifications like H3K4me3 and modulating the rhythmic expression of target genes that follow a diurnal cycle. This process relies on the circadian clock oscillators CCA1 and LHY to maintain the proper timing of these modifications .
Protein of unknown function DUF6452 (DUF6452)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in Bacteroidetes. This proteins contain the conserved motifs PL and SxxCG.
Trypsin-co-occurring domain 2 (Trypco2)
Type: Domain

Trypsin-like peptidase effector in the classical NTP-dependent ternary system (vWA-MoxR-VMAP) frequently co-occurs with one of two proteins (Trypco1 or Trypco2) which are mostly mutually exclusively . This entry also includes a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000949) is described by MIBiG as an example of the following biosynthetic class, NRP (non-ribosomal peptide). It includes a member from the A-500359 A biosynthetic gene cluster from Streptomyces griseus and appears to be predominantly found in bacteria .
Domain of unknown function DUF6451 (DUF6451)
Type: Domain

This presumed domain is functionally uncharacterised. Proteins containing this domain are found in eukaryotes, predominantly in Platyhelminthes. It contains the conserved sequences QLxNIWNSK and KxRIFN. Some proteins containing this domain also contain a reverse transcriptase domain.
Domain of unknown function DUF6450 (DUF6450)
Type: Domain

This presumed domain is functionally uncharacterised. Proteins containing this domain can be found in phages. It contains the conserved sequences WSxxxLTxY and DPTFIASVFTG.
Domain of unknown function DUF6449 (DUF6449)
Type: Domain

This presumed domain functionally uncharacterised is found in ABC transporter permeases. Proteins containing this domain can be found in bacteria.
Domain of unknown function DUF5914 (DUF5914)
Type: Domain

This entry represents a presumed domain found to the C-terminal of the Rieske [2Fe-2S] iron-sulphur domain, predominantly found in bacterial proteins. The Rieske domain-containing protein CrtV from Streptomyces griseus (strain NBRC 13350) [

] contain this domain and is predicted to be a methylesterase .
Protein of unknown function DUF6448 (DUF6448)
Type: Family

This family of proteins is functionally uncharacterised and can be found in bacteria and archaea.
Protein of unknown function DUF6136 (DUF6136)
Type: Family

This entry represents a presumed member of a biosynthetic gene cluster (BGC). This BGC (BGC0000299) is described by MIBiG as an example of the NRP (non-ribosomal peptide) biosynthetic class. It includes a member from the alterochromide A biosynthetic gene cluster from Pseudoalteromonas piscicida JCM 20779 and appears to be predominantly found in gammaproteobacteria .
Protein of unknown function DUF6447 (DUF6447)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria.
Protein of unknown function DUF6446 (DUF6446)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is predominantly found in Rhodobacterales. There are some conserved motifs: IDA/S, SSPxRxRACF and DG.
Protein of unknown function DUF6445 (DUF6445)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria.
Domain of unknown function DUF6444 (DUF6444)
Type: Domain

This entry represents a domain that is sometimes found at the N-terminal of the insertion element IS66 transposase. It can also be found as part of a shorter protein.
Domain of unknown function DUF6443 (DUF6443)
Type: Domain

This presumed domain is functionally uncharacterised. This domain is predominantly found in Bacteroidetes, and is about 100 amino acids in length. This domain contains a highly conserved YDxxGR motif which suggests that it is related to the RHS repeats, that appear to be involved in ligand binding. RHS repeats share structural similarity with the eukaryotic tyrosine-aspartate (YD) repeat .
Protein of unknown function DUF6442 (DUF6442)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria.
ABC transporter type 1, GsiC-like, N-terminal domain (BPD_transp_1_N)
Type: Domain

This entry represents the N-terminal transmembrane domain found in a group of ABC transporters type 1, members of the Binding-protein-dependent transport system from bacteria, including Glutathione transport system permease protein (GsiC) from Escherichia coli K12 , the Dipeptide transport system permease protein (DppB) from Lactococcus lactis strain MG1363 , responsible for the translocation of the substrate across the membrane.
Protein of unknown function DUF6441 (DUF6441)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria.
LigXa-like, C-terminal domain (LigXa_C)
Type: Domain

This entry represents the C-terminal domain of a Rieske domain-containing oxygenase enzyme. This entry includes the 5,5'-dehydrodivanillate O-demethylase oxygenase subunit from Sphingobium [

], part of a three-component monooxygenase involved in the catabolism of 5,5'-dehydrodivanillate (DDVA), an intermediate in the biodegradation of lignin .
Protein of unknown function DUF6427 (DUF6427)
Type: Family

This entry represents a set of uncharacterised bacterial proteins that are likely integral membrane proteins.
D-3-phosphoglycerate dehydrogenase, ASB domain (PGDH_ASB_dom)
Type: Domain

This entry represents the allosteric substrate binding domain (also known as intervening domain) of type 1 D-3-phosphoglycerate dehydrogenases, located between the substrate-binding and regulatory domains. It serves as an anion-binding site and may function as an allosteric site for the control of enzyme activity .

Phosphoglycerate dehydrogenases (PGDH) have at least two different structural domains: the nucleotide binding and the substrate binding. There are three types of PGDH: type 3 enzymes are composed only of these two domains, type2 enzymes contain an extra C-terminal regulatory domain (ACT domain), type 1 enzymes contain both the regulatory domain and an extra allosteric domain . This entry represents the type 1 enzyme. Interestingly, this type of PGDH is found in bacteria such as Mycobacterium, Bacillus subtilis, Corynebacterium, plants such as Arabidopsis, and higher order eukaryotes, including mammals. The PGDHs from E. coli and some lower eukaryotes, such as yeast and Neurospora, belong to the type2 PGDH and are not included in this entry .
F-box/LRR-repeat protein 18, LRR domain (FBXL18_LRR)
Type: Domain

In general, F-box proteins share a F-box motif and also have either WD40 repeat domains, LRR domains or various other domains. F-box proteins recruit specific substrates for ubiquitination via different protein-protein interaction domains, such as WD40 repeats and leucine rich repeats (LRRs) .

This entry represents the leucine-rich repeats (LRR) domain of F-box/LRR repeat protein 18 (FBXL18). This protein is a component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The SCF-Fbxl18 complex has been shown to ubiquitinate Fbxl7 and LRRK2 and promote their degradation through the proteasome pathway .
Helicase Lhr-like, winged helix domain (Lhr_WH_dom)
Type: Domain

This entry represents the third domain of ATP-dependent helicases such as the DNA damage-inducible superfamily 2 helicase Lhr from Mycobacteria, an enzyme that uses adenosine triphosphate (ATP) hydrolysis to drive unidirectional 3' to 5' translocation along single-stranded DNA (ssDNA). This domain with a winged helix (WH) domain fold appears C-terminal to two Rec-A-like modules and is involved in the binding of the 3' end of the ssDNA .
Protein of unknown function DUF6232 (DUF6232)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000223) is described by MIBiG as an example of the polyketide biosynthetic class. It includes a member from the rabelomycin biosynthetic gene cluster from uncultured bacterium BAC AB649/1850 . This family is found in bacteria.
Domain of unknown function DUF6316 (DUF6316)
Type: Domain

This domain is found in bacterial proteins, which are functionally uncharacterised. It is approximately 60 amino acids in length and it has the conserved sequence TRExxxxGPF/Y.
Protein of unknown function DUF6315 (DUF6315)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000081) is described by MIBiG as an example of the polyketide biosynthetic class, in particular the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 .
Domain of unknown function DUF6314 (DUF6314)
Type: Domain

This domain, found in bacteria and eukaryotes, is functionally uncharacterised.
Protein of unknown function DUF6414 (DUF6414)
Type: Family

This entry represents a family of uncharacterised proteins found in bacteria. These proteins share a conserved β-barrel domain with extensive variable insertions. The N and C terminus of these proteins are the most conserved regions and interact with each other.
Protein of unknown function DUF6413 (DUF6413)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001749) is described by MIBiG as an example of the polyketide biosynthetic class, in particular the epipyriculol biosynthetic gene cluster from Pyricularia oryzae 70-15 . This family appears to be predominantly found in fungi.
Protein of unknown function DUF6412 (DUF6412)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001514) is described by MIBiG as an example of the other (unspecified) biosynthetic class, in particular the aristeromycin biosynthetic gene cluster from Streptomyces citricolor . This family appears to be predominantly found in Actinobacteria.
Protein of unknown function DUF6411 (DUF6411)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001740) is described by MIBiG as an example of the NRP (non-ribosomal peptide) and polyketide biosynthetic classes, in particular the phthoxazolin biosynthetic gene cluster from Streptomyces avermitilis .
Protein of unknown function DUF6410 (DUF6410)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001062) is described by MIBiG as an example of the polyketide biosynthetic class, in particular the TLN-05220 biosynthetic gene cluster from Micromonospora echinospora subsp. challisensis .
Protein of unknown function DUF6409 (DUF6409)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000703) is described by MIBiG as an example of the saccharide biosynthetic class, in particular the kanamycin biosynthetic gene cluster from Streptomyces kanamyceticus .
Protein of unknown function DUF6408 (DUF6408)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000106) is described by MIBiG as an example of the polyketide biosynthetic class, in particular the naphthomycin A biosynthetic gene cluster from Streptomyces sp. CS .
Protein of unknown function DUF6407 (DUF6407)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000926) is described by MIBiG as an example of the other (unspecified) biosynthetic class, in particular the rhizocticin A biosynthetic gene cluster from Bacillus subtilis subsp. spizizenii ATCC 6633 .