SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF6326 (DUF6326)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria and archaea.
Protein of unknown function DUF6327 (DUF6327)
Type: Family

This family of proteins is functionally uncharacterised and found in bacteria. Proteins in this family have two conserved sequence motifs: KKY and YQK.
Protein of unknown function DUF6328 (DUF6328)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000219) is described by MIBiG as an example of the following biosynthetic classes, polyketide and saccharide, in particular the elloramycin biosynthetic gene cluster from Streptomyces olivaceus . This family appears to be predominantly found in Actinobacteria.
Domain of unknown function DUF6329 (DUF6329)
Type: Domain

This domain is predominantly found in uncharacterised bacterial proteins and its function is unknown. This domain is approximately 60 amino acids in length and it contains three conserved residues, a cysteine, a leucine and a tryptophan.
Protein of unknown function DUF6330 (DUF6330)
Type: Family

This family of bacterial proteins is functionally uncharacterised. Proteins in this family are approximately 70 amino acids in length.
Protein of unknown function DUF6331 (DUF6331)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001060) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the dynemicin A biosynthetic gene cluster from Micromonospora chersina .
Protein of unknown function DUF6332 (DUF6332)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001598) is described by MIBiG as an example of the following biosynthetic classes, NRP (non-ribosomal peptide) and polyketide, in particular the foxicins A-D biosynthetic gene cluster from Streptomyces diastatochromogenes . This family appears to be predominantly found in Actinobacteria.
Protein of unknown function DUF6334 (DUF6334)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001543) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the chejuenolide A biosynthetic gene cluster from Hahella chejuensis .
Protein of unknown function DUF6335 (DUF6335)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001615) is described by MIBiG as an example of the following biosynthetic class, NRP (non-ribosomal peptide), in particular hexose-palythine-serine biosynthetic gene cluster from Heteroscytonema crispum UCFS10 .
Protein of unknown function DUF6336 (DUF6336)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001593) is described by MIBiG as an example of the following biosynthetic class, NRP (non-ribosomal peptide), in particular the ficellomycin biosynthetic gene cluster from Streptomyces ficellus .
Protein of unknown function DUF6415 (DUF6415)
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 following biosynthetic class, saccharide, in particular the kanamycin biosynthetic gene cluster from Streptomyces kanamyceticus . This family appears to be predominantly found in Actinobacteria.
Protein of unknown function DUF6416 (DUF6416)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001300) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the anthracimycin biosynthetic gene cluster from Streptomyces sp. CNH365 .
Protein of unknown function DUF6417 (DUF6417)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000087) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the lasalocid biosynthetic gene cluster from Streptomyces lasaliensis . This family appears to be predominantly found in Actinobacteria.
Domain of unknown function DUF6418 (DUF6418)
Type: Domain

This entry represents a domain found in a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001589) is described by MIBiG as an example of the following biosynthetic class, saccharide, in particular the exopolysaccharides biosynthetic gene cluster from Burkholderia cenocepacia J2315 . This domain appears to be predominantly found in Proteobacteria proteins.
Protein of unknown function DUF6419 (DUF6419)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000299) is described by MIBiG as an example of the following biosynthetic class, NRP (non-ribosomal peptide), in particular the alterochromide A biosynthetic gene cluster from Pseudoalteromonas piscicida JCM 20779 .
Protein of unknown function DUF6420 (DUF6420)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000700) is described by MIBiG as an example of the following biosynthetic class, saccharide, in particular the istamycin biosynthetic gene cluster from Streptomyces tenjimariensis .
Protein of unknown function DUF6421 (DUF6421)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000877) is described by MIBiG as an example of the following biosynthetic class, other (unspecified), in particular the polyoxin A biosynthetic gene cluster from Streptomyces cacaoi subsp. asoensis . This family appears to be predominantly found in Actinobacteria.
Protein of unknown function DUF6422 (DUF6422)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001916) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the lavendiol biosynthetic gene cluster from Streptomyces lavendulae .
Protein of unknown function DUF6423 (DUF6423)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001503) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the amycolamycin A biosynthetic gene cluster from Amycolatopsis sp. .
Protein of unknown function DUF6424 (DUF6424)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000379) is described by MIBiG as an example of the following biosynthetic class, NRP (non-ribosomal peptide), in particular the glycinocin A biosynthetic gene cluster from streptomyces viridochromogenes .
Protein of unknown function DUF6425 (DUF6425)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001281) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the ustilagic acid biosynthetic gene cluster from Ustilago maydis 521 . This family appears to be predominantly found in fungi.
Protein of unknown function DUF6426 (DUF6426)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0001396) is described by MIBiG as an example of the following biosynthetic class, polyketide, in particular the aldgamycin J biosynthetic gene cluster from Streptomyces sp. A1(2016) .
Protein of unknown function DUF6454 (DUF6454)
Type: Family

This family of proteins is functionally uncharacterised. It can be found in bacteria and some fungal species.
Protein of unknown function DUF6465 (DUF6465)
Type: Family

This family of proteins is functionally uncharacterised, predominantly found in bacteria. Proteins in this family have a highly charged N terminus.
Protein of unknown function DUF6466 (DUF6466)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is mainly found in Bacteria. Proteins in this family are approximately 190 amino acids in length. They contain the conserved motifs QQQQ, SxxLT and KPW. Members in this family are probably cell surface proteins, some of them are likely elastin binding proteins.
Protein of unknown function DUF5344 (DUF5344)
Type: Family

This is a bacterial family of unknown function which includes YxiC and YwqI proteins from Bacillus subtilis. Family members are predicted to belong to Type VII secretion (T7S) system. There is a conserved YxxxD/E sequence. It is a general secretion signal that is present in all known mycobacterial T7S substrates or substrate complexes .
Domain of unknown function DUF4922 (DUF4922)
Type: Domain

This domain is found in uncharacterised proteins of around 310 residues in length and is mainly found in various Bacteroides species. Several members are annotated as putative glycosyltransferases, but the specific function of this domain is still unknown.
DUF4931, N-terminal domain (DUF4931)
Type: Domain

This entry represents the N-terminal domain found in a group of uncharacterised proteins mainly found in various bacillus species. Some members of this entry are annotated as Galactose-1-phosphate uridylyltransferases, but the specific function of this family is unknown.
Homeobox protein Hox-A1/B1/D1 (HXA1/B1/D1)
Type: Family

This entry represents a group of homeobox proteins, including HOX-A1/B1/D1 (HXA1/B1/D1) and related proteins from animals. The homeobox domain is a DNA binding domain.

Human HOX genes are critical for development of the central nervous system . They have been also implicated in vascular development and angiogenesis, particularly with regulation of genes involved in cell-cell or cell-extracellular matrix (ECM) interactions . HXA1 has been linked to the Bosley-Salih-Alorainy syndrome (BSAS) or the Athabascan brainstem dysgenesis syndrome (ABDS) . HXB1 is a transcription factor that play important roles in early vertebrate development and its expression is associated with tumours . HOXD1 plays a significant role in endothelial cell functions by regulating the expression of ITGB1 .

Homeobox protein rough from Drosophila melanogaster is a member of this group of proteins. It is required to establish the unique cell identity of photoreceptors R2 and R5 and consequently for ommatidial assembly in the developing eye imaginal disk in the organism .
ETS family (ETS_fam)
Type: Family

This entry represents ETS family of transcription factors, including ETS translocation variant 1-5 (ETV1-5) and related proteins from animals. Most members of this protein family contain an ETS (erythroblast transformation specific) domain and belong to the winged helix DNA-binding domain superfamily.

ETV1-5 are overexpressed in multiple cancers . ETV1 is critical for fast conduction physiology in the heart . ETV3 is a transcriptional repressor that contribute to growth arrest during terminal macrophage differentiation by repressing target genes involved in Ras-dependent proliferation . ETV4 is a transcriptional activator that may play a role in keratinocyte differentiation .
Solute carrier organic anion transporter family member 4A1-like (SO4A1-like)
Type: Family

This entry represents SO4A1 (solute carrier organic anion transporter family member 4A1) and related proteins from chordates. Members of this protein family contain a Kazal domain and belongs to the Major facilitator superfamily.

SO4A1 (also known as OATP4A1) is ubiquitously expressed and mediates the sodium ion-independent transport of the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and other organic anions such as estrone sulfate and taurocholate. It is the most abundantly expressed transporter in colorectal cancer (CRC) and its role in the transport of estrone sulfate, which is used in hormone replacement therapy (HRT), affects the outcome of the treatment .
DEAD box protein 17, ATP-binding domain (DDX17_ATP-bd-dom)
Type: Domain

This entry represents the ATP-binding domain of DEAD box protein 17 (DDX17, also known as p72) found in chordates. This protein is a member of the DEAD-box helicase family, a diverse family of proteins involved in ATP-dependent RNA unwinding, needed in a variety of cellular processes including splicing, ribosome biogenesis and RNA degradation .

DDX17 has a wide variety of functions including regulating the alternative splicing of exons exhibiting specific features such as the inclusion of AC-rich alternative exons in CD44 transcripts, playing a role in innate immunity, and promoting mRNA degradation mediated by the antiviral zinc-finger protein ZC3HAV1 in an ATPase-dependent manner .
GPALPP motifs-containing protein 1-like (GPAM1-like)
Type: Family

This entry represents GPALPP motifs-containing protein 1 from humans (GPAM1) and similar proteins found in eukaryotes. The function of GPAM1 is not clear. It has been shown to be overexpressed in follicular lymphoma (FL), a frequent type of Mature B-cell non-Hodgkin lymphoma .
Small ubiquitin-related modifier 1, Ubl domain (SUMO1_Ubl)
Type: Domain

This entry represents the ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier 1 (SUMO1) and similar proteins from animals. SUMO1 is a binding partner of the RAD51/52 nucleoprotein filament proteins, which mediate DNA strand exchange . Its conjugation to cellular proteins has been implicated in multiple important cellular processes, such as nuclear transport, cell cycle control, oncogenesis, inflammation, and the response to virus infection .
Homeobox protein Hox-A10/abdominal-B-like (HXA10/ABDB-like)
Type: Family

This entry represents a group of homeobox proteins from animals, including Hox-A/B10 from Danio rerio, Hox-A/C/D10 from humans and Homeobox protein abdominal-B from Drosophila melanogaster. The homeobox domain binds DNA through a helix-turn-helix (HTH) structure. Some proteins in this family are known to function as sequence-specific transcription factors .
Transcriptional regulator LacI/GalR-like, sensor domain (LacI/GalR-like_sensor)
Type: Domain

This domain is found in a variety of transcriptional regulatory proteins from the LacI/GalR family, including HTH-type transcriptional regulators GalR, CytR, LacR and the transcriptional repressor PurR . It is related to bacterial periplasmic binding proteins, although this domain is unlikely to be found in the periplasm. This domain acts as the sensor domain which binds ligands that the DNA-binding domain responds to. This domain recognises sugars, sugar phosphates, sugar acids and purines .

The LacI/GalR family, which includes the LacL superfamily, represents one of the largest and most diverse groups of bacterial transcriptional regulators. These proteins play crucial roles in regulating various aspects of bacterial metabolism, particularly carbohydrate utilisation . Characterised by a conserved N-terminal helix-turn-helix (HTH) DNA-binding motif

and a C-terminal regulatory domain that binds effector molecules

, members of this family can function as both repressors and activators, though most act as repressors . They typically respond to specific effector molecules, often sugars or metabolites, which modulate their DNA-binding affinity and consequently their regulatory activity. This allows bacteria to fine-tune gene expression in response to environmental conditions and available carbon sources . Some well-characterised members of this family include:

LacI (lactose operon repressor) in Escherichia coli

GalR (galactose operon repressor) in Escherichia coli

PurR (purine biosynthesis repressor) in various bacteria

CcpA (catabolite control protein A) in Gram-positive bacteria

FruR (fructose repressor) in Enterobacteriaceae
Lon protease, N-terminal domain superfamily (Lon_prtase_N_sf)
Type: Homologous_superfamily

This entry represents the N-terminal substrate-binding domain of the Lon protease. This ATP-dependent enzyme, a serine peptidase belonging to the MEROPS peptidase family S16, is conserved in archaeal, bacterial and eukaryotic organisms and catalyses rapid turnover of short-lived regulatory proteins and many damaged or denatured proteins. In eukaryotes, the majority of the proteins are located in the mitochondrial matrix . In yeast, Pim1, is located in the mitochondrial matrix and required for mitochondrial function. It is constitutively expressed but is increased after thermal stress, suggesting that Pim1 may play a role in the heat shock response .

The structure of this domain has been determined and it represents a general protein and polypeptide interaction domain .
GAIN domain superfamily (GAIN_dom_sf)
Type: Homologous_superfamily

This superfamily represents the GAIN domain which contains the GPS motif (

). The GAIN domain is conserved in all cell-adhesion GPCRs and all PKD1-related proteins and is the functional unit for autoproteolysis. The ancient
GPS motif exists in primitive ancestor organisms and it needs to be within the context of the GAIN domain to mediate autoproteolysis .

The structure of the GAIN domain from aGPCR latrophilin 1 revealed that it contains an N-terminal subdomain A composed of six-α-helices, and a C-terminal subdomain B that consists of a twisted β-sandwich of 13 β-strands and 2 small α-helices, of which the last 5 β-strands constitute the GPS motif .
SET domain superfamily (SET_dom_sf)
Type: Homologous_superfamily

The SET domain is a 130 to 140 amino acid, evolutionary well conserved sequence motif that was initially characterised in the Drosophila proteins Su(var)3-9, Enhancer-of-zeste and Trithorax . In eukaryotic organisms, it appears in proteins with an important role in regulating chromatin-mediated gene transcriptional activation and silencing. In viruses,bacteria and archaea, its function is not clear yet .

This superfamily includes eukaryotic proteins with histone methyltransferase activity, which requires the combination of the SET domain with the adjacent cysteine-rich regions, one located N-terminally (pre-SET) and the other posterior to the SET domain (post-SET). Post- and pre- SET regions seem then to play a crucial role when it comes to substrate recognition and enzymatic activity . Other SET domain-containing proteins function as transcription factors (such as PR domain zinc finger protein 1 from humans ).

The structure of the SET domain and the two adjacent regions pre-SET and post-SET have been solved . The SET domain structure is all-β, but consists only in sets of few short strands composing no more than a couple of small sheets. Consequently the SET structure is mostly defined by turns and loops. An unusual feature is that the SET core is made up of two discontinuous segments of the primary sequence forming an approximate L-shape . Two of the most conserved motifs in the SET domain are constituted by a stretch at the C-terminal containing a strictly conserved tyrosine residue and a preceding loop inside which the C-terminal segment passes forming a knot-like structure, but not quite a true knot. These two regions have been proven to be essential for SAM binding and catalysis, particularly the invariant tyrosine where in all likelihood catalysis takes place .
CBS domain superfamily (CBS_dom_sf)
Type: Homologous_superfamily

CBS domains are evolutionarily conserved structural domains found in a variety of non functionally-related proteins from all kingdoms of life. These domains pair together to form a intramolecular dimeric structure (CBS pair), termed Bateman domain . CBS domains have been shown to bind mainly ligands with an adenosyl group such as AMP, ATP and S-AdoMet, but may also bind metal ions, or nucleic acids . Hence, they play an essential role in the regulation of the activities of numerous proteins, and mutations in them are associated with several hereditary diseases . CBS domains are found attached to a wide range of other protein domains suggesting that CBS domains may play a regulatory role making proteins sensitive to adenosyl-carrying ligands. The region containing the CBS domains in cystathionine-beta synthase is involved in regulation by S-AdoMet . CBS domain pairs from AMPK bind AMP or ATP . The CBS domains from IMPDH, which bind ATP, have shown to have a role in the regulation of adenylate nucleotide synthesis .
TAF6, C-terminal HEAT repeat domain superfamily (TAF6_C_sf)
Type: Homologous_superfamily

This is the C-terminal domain of the TAF6 subunit of the general transcription factor TFIID. The crystal structure reveals the presence of five conserved HEAT repeats. This region is necessary for the complexing together of the subunits TAF5, TAF6 and TAF9 .
TraB/PryY-like (TraB_PrgY-like)
Type: Family

This entry includes TraB/PrgY proteins which have been identified in gut bacterium Enterococcus faecalis, and are induced by pheromones. This induction rends the host bacterium insensitive to self-induction by its own pheromones, and prevents the transfer of the pheromone-inducible conjugative plasmids to bacteria that already contain it . TraB proteins belong to the Tiki-like superfamily, and based on its homology to Tiki, it has been proposed that TraB acts as a protease in the inactivation of mating pheromone, cleaving at the amino-terminus .

This family includes TraB domain-containing proteins from mammals, whose function is not clear, and TraB-like proteins from bacteria.
Aminoacid dehydrogenase-like, N-terminal domain superfamily (Aminoacid_DH-like_N_sf)
Type: Homologous_superfamily

This superfamily represents a domain found at the N-terminal of a wide range of dehydrogenases from bacteria, eukaryotes and archaea, including tetrahydrofolate dehydrogenase/cyclohydrolase , methylene-tetrahydromethanopterin dehydrogenase , shikimate dehydrogenase , amino acid dehydrogenases (Glutamate/phenylalanine/leucine/valine dehydrogenases) and malic enzymes . It has a core fold of three layers in an α/β/α configuration. Its central parallel β-sheet of four strands has the order 2134. In amino acid dehydrogenases, this domain participates in dimerisation .
Basic-leucine zipper domain superfamily (bZIP_sf)
Type: Homologous_superfamily

The basic-leucine zipper (bZIP) domain transcription factors of eukaryotic are proteins that contain a basic region mediating sequence-specific DNA-binding followed by a leucine zipper region required for dimerisation.

Several structure of bZIP have been solved. The basic region and the leucine zipper form a contiguous α-helix where the four hydrophobic residues of the leucine zipper are oriented on one side. This conformation allows dimerisation in parallel and it bends the helices so that the newly functional dimer forms a flexible fork where the basic domains, at the N-terminal open end, can then interact with DNA. The two leucine zipper are therefore oriented perpendicular to the DNA .
SIS domain superfamily (SIS_dom_sf)
Type: Homologous_superfamily

The sugar isomerase (SIS) domain is a phosphosugar-binding module that is found in a variety of eubacterial, archaebacterial and eukaryotic proteins
that have a role in phosphosugar isomerization or regulation . In enzymes, the SIS domain can have a catalytic function as an isomerase and bind to phosphorylated sugars. In bacterial transcriptional regulators of the rpiR family, the domain seems to bind substrates implicated in the genes for sugar metabolism that are controlled by the regulator. The SIS domain is found in one or two copies and can be linked to additional domains, such as helix-turn-helix (HTH), CBS, glutamine amidotransferases type 2, or phosphopantetheine-attachment .

The SIS domain has an α-β structure and is dominated by a five-stranded parallel β-sheet flanked on either side by α-helices forming a three-layer α-β-α sandwich . The fold shows similarities to that of glucose-6-phosphate isomerase.
C1-like domain superfamily (C1-like_sf)
Type: Homologous_superfamily

This superfamily includes variations of the protein kinase C1 domain that is characterised by a rich cysteine and histidine content. The C1 domain is the N-terminal region of conservation found in protein kinase C domains. This domain is involved in binding many ligands, which include diacylglycerol, phorbol esters and zinc . This superfamily also includes the C-terminal domain of General transcription factor IIH subunit 2 whose structure revealed homology with the regulatory domain of protein kinase C .