SII-SWORD/CoKE huggingface dataset:
Exportin-T, C-terminal domain (Exportin-T_C)
Type: Domain

This entry represents the C-terminal domain of Exportin-T, involved in RanGTP interaction. It consists of TPRs.

Exportin-T (Xpot) mediates the nuclear export of aminoacylated tRNAs . Its budding yeast homologue, known as Los1, is involved in nuclear export of pre-tRNA and in re-export of mature tRNAs . It binds to RanGTP and mature tRNAs cooperatively to form a nuclear export complex .
MoxR-vWA-beta-propeller ternary system domain bpX6 (bpX6)
Type: Domain

This domain is known as bpX6 and it is mainly found in proteobacteria.

This entry represents an uncharacterised domain found in the MoxR-vWA-β-propeller ternary system, a class of NTP-dependent biological conflict systems .
MoxR-vWA-beta-propeller ternary system domain bpX5 (bpX5)
Type: Domain

This domain is known as bpX5, mainly found in proteobacteria.

This entry represents an uncharacterised domain found in the MoxR-vWA-β-propeller ternary system, a class of NTP-dependent biological conflict systems .
MoxR-vWA-beta-propeller ternary system domain bpX4 (bpX4)
Type: Domain

This domain is known as bpX4, predominantly found in bacteroidetes.

This entry represents an uncharacterised domain found in the MoxR-vWA-β-propeller ternary system, a class of NTP-dependent biological conflict systems .
Acylamino-acid-releasing enzyme, N-terminal domain (AARE_N)
Type: Domain

This entry represents the N-terminal domain from the Acylamino-acid-releasing enzyme (AARE) (

) from eukaryotes.

This protein catalyses the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminal . In Arabidopsis, AARE plays a homeostatic role in sustaining the cytoplasmic antioxidative system and may contribute to the elimination of the oxidized proteins in the cytoplasm . This domain does not represent the catalytic domain which is found at the C-terminal of these proteins .
MoxR-vWA-beta-propeller ternary system domain bpX3 (bpX3)
Type: Domain

This domain is known as bpX3. Most members of this entry belong to the phylum Bacteroidetes.

This entry represents an uncharacterised domain found in the MoxR-vWA-β-propeller ternary system, a class of NTP-dependent biological conflict systems .
MoxR-vWA-beta-propeller ternary system domain bpX2 (bpX2)
Type: Domain

This domain is known as bpX2. Most members of this entry belong to the phylum Bacteroidetes.

This entry represents an uncharacterised domain found in the MoxR-vWA-β-propeller ternary system, a class of NTP-dependent biological conflict systems .
MoxR-vWA-beta-propeller ternary system domain bpX1 (bpX1)
Type: Domain

This domain is known as bpX1. Most members of this entry belong to the phylum Bacteroidetes.

This entry represents an uncharacterised domain found in the MoxR-vWA-β-propeller ternary system, a class of NTP-dependent biological conflict systems .
MoxR-vWA-beta-propeller ternary system domain bpX0 (bpX0)
Type: Domain

This domain is known as bpX0. Most members of this entry belong to the phylum Bacteroidetes.

This entry represents an uncharacterised domain found in the MoxR-vWA-β-propeller ternary system, a class of NTP-dependent biological conflict systems .
vWA-MoxR associated protein middle region 0 (VMAP-M0)
Type: Domain

This domain is known as VMAP-M0. Most members of this entry belong to the class Actinomycetia.

This domain represents a highly variable central region of the vWA-MoxR associated protein (VMAP) of the classical ternary system (vWA-MoxR-VMAP) in NTP-dependent conflict systems. Using sequence similarity-based clustering it has been possible to identify 29 distinct versions named VMAP-M0-28, that may be involved in sensing of invasive entities . It is predicted to adopt an all-α-helical secondary structure.
Domain of unknown function DUF6351 (DUF6351)
Type: Domain

This domain, found in bacteria, is functionally uncharacterised. The N-terminal domain of the o-phthalyl amidase from Xanthobacter agilis is a member of this entry.
Activity-regulated cytoskeleton-associated protein, N-terminal domain (Arc_N)
Type: Domain

This entry represents the N-terminal matrix-like (MA) domain of the Activity-Regulated Cytoskeleton-Associated protein (Arc). This domain might be involved in stabilising the relative domain orientations of the capside-like domain (CA) upon capsid assembly . Arc is a regulator of synaptic scaling and dendrite remodelling .
Protein of unknown function DUF6317 (DUF6317)
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 following biosynthetic classes, NRP (non-ribosomal peptide) and polyketide, in particular the phthoxazolin biosynthetic gene cluster from Streptomyces avermitilis .
Ribbon-helix-helix protein, RHH domain (RHH_9)
Type: Domain

This entry represents the Ribbon-helix-helix (RHH) domain found in bacterial proteins, mainly from proteobacteria.
4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase-like, C-terminal (LigC_C)
Type: Domain

This entry represents the C-terminal domain found in a group of bacterial oxidoreductases, such as 4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase (LigC) from Sphingobium sp., involved in the degradation of protocatechuate (PCA) via the PCA 4,5-cleavage pathway . Proteins containing this domain belong to the Gfo/Idh/MocA protein family, whose members catalyse various different chemical reactions such as oxidation and reduction of carbohydrates, oxidation of trans-dihydrodiols, reduction of biliverdin, and hydrolysation of glycosidic bonds, using NAD(P) as a hydride donor or acceptor. This is likely to be an α/β-domain involved in substrate binding and oligomerisation .
Neuromedin-U receptor 2, C-terminal domain (NMU-R2_C)
Type: Domain

This entry represents the C-terminal domain of the Neuromedin-U receptor 2 (NMU-R2). These proteins are G-protein-coupled receptors (GPCR) for the neuromedin-U and neuromedin-S neuropeptides expressed in specific regions of the brain . It contains two potential casein kinase II phosphorylation sites at threonines residues and one protein kinase C phosphorylation site at a serine residue, which are important to regulate the receptor functionality . Its physiological roles are related to modulation of sensory function, neuroendocrine control, food intake as well as with circadian rhythm. However, peripheral expression of this receptor has been determined and includes kidney (medulla), lung and trachea . The use of selective agonists for this molecule are being studied as treatment for disorders such as obesity .
ATP-dependent DNA helicase RecG, domain 3, C-terminal (RecG_dom3_C)
Type: Domain

This domain is found at the C-terminal of Domain 3 of the ATP-dependent DNA helicase RecG and also includes the around 50 residues that extend from Domain 3 end that cross back to Domain 1 forming a hook that wraps around the extended α-helix. This interaction provides a link between Domain 1 and 3 and it is likely that these residues are involved in conformational changes associated with domain movements arising from ATP binding and hydrolysis .

The ATP-dependent DNA helicase RecG

plays a critical role in recombination and DNA repair. It helps to process Holliday junction intermediates to mature products by catalysing branch migration. This entry includes RecG from bacteria the homologue from Arabidopsis, which has a critical role in recombination and DNA repair. RecG has DNA unwinding activity characteristic of a DNA helicase with 3' to 5' polarity. RecG unwind branched duplex DNA (Y-DNA) and has a role in constitutive stable DNA replication (CsdR) and R-loop formation . It is genetically synergistic to RadA and RuvABC . RecG comprises three structural domains, the largest N-terminal Domain 1 which interacts with DNA junctions, and Domains 2 and 3 at the C-terminal which contain the characteristic motifs that identify RecG as an SF2 helicase .
ZSWIM1/3, C-terminal domain (ZSWIM1/3_C)
Type: Domain

This entry represents a domain of unknown function found at the C-terminal of Zinc finger SWIM domain-containing proteins 1/3 (ZSWIM1/3) from vertebrates. The function of these proteins is currently unknown. ZSWIM1 may play a role in the development or function of T helper cells .
Protein of unknown function DUF5910 (DUF5910)
Type: Family

This entry corresponds to a group of uncharacterised proteins of unknown function found in fungi. A protein precursor of a peptide from the edible fungi Cordyceps militaris is a member of this group, which induces apoptosis in mammalian cell lines in vitro .
Phage capsid protein (Phage_capsid_2)
Type: Family

This entry represents a family of phage capsid protein. This family of proteins is found in bacteria and phage. Proteins in this family are approximately 280 amino acids in length.
Putative endonuclease SegE-like, GIY-YIG domain (SegE-like_GIY-YIG)
Type: Domain

This is a GIY-YIG domain mainly found in phages proteins, related to the putative endonuclease segE from Bacteriophage T4. This domain is also found in some uncharacterised bacterial sequences. Proteins containing this domain are approximately 145-300 amino acids in length.

Nucleases of the GIY-YIG family are involved in many cellular processes, including DNA repair and recombination, transfer of mobile genetic elements, and restriction of incoming foreign DNA. The GIY-YIG superfamily groups together nucleases characterised by the presence of a domain of typically ~100 amino acids, with two short motifs "GIY" and "YIG" in the N-terminal part, followed by an Arg residue in the centre and a Glu residue in the C-terminal part .

The GIY-YIG domain forms a compact structural domain, which serves as a scaffold for the coordination of a divalent metal ion required for catalysis of the phosphodiester bond cleavage. The GIY-YIG domain has an α/β-sandwich architecture with a central three-stranded antiparallel β-sheet flanked by three-helices. The three-stranded antiparallel β-sheet contains the GIY-YIG sequence elements. The most conserved and putative catalytic residues are located on a shallow, concave surface and include a metal coordination site .

The GIY-YIG domain has been implicated in a variety of cellular processes involving DNA cleavage, from self-propagation with or without introns, to restriction of foreign DNA, to DNA repair and maintenance of genome stability .

Some proteins known to contain a GIY-YIG domain include:

Eukaryotic Slx-1 proteins, involved in the maintenance of the rDNA copy number. They have a C-terminal RING finger Zn-binding domain.

Mammalian ankyrin repeat and LEM domain- containing protein 1 (ANKLE1).

Bacterial and archaeal UvrC subunits of (A)BC excinucleases, which remove damaged nucleotides by incising the damaged strand on both sides of the lesion.

Phage T4 endonucleases SegA to E, probably involved in the movement of the endonuclease-encoding DNA.

Phage T4 intron-associated endonuclease 1 (I-TevI), specific to the thymidylate synthase (td) gene splice junction and involved in intron homing.
CofH/MqnC-like, C-terminal domain (CofH/MnqC-like_C)
Type: Domain

This entry represents the C-terminal domain found in members of the CofH family (CofH/H1/H2 and FbiC) and MqnC/E enzymes. These are Radical SAM enzymes found in bacteria and archaea.
Metalloprotease TldD/E, C-terminal domain (Metalloprtase-TldD/E_C)
Type: Domain

This entry represents the C-terminal domain of of PmbA/TldE and TldD. This domain is also found at the C-terminal of uncharacterised proteins from archaea.

This entry includes a group of metalloproteases, such as TldD and TldE (also known as PmbA) from E. coli, which interact to form a heterodimeric metalloprotease. TldD and TldE were originally related to the biosynthesis of microcin B17 (MccB17), a peptide antibiotic produced by Escherichia coli strains carrying the pMccB17 plasmid that targets the DNA gyrase from sensitive bacteria. Later, they are shown to be metalloproteases involved in CcdA/CcdA41 degradation .
Metalloprotease TldD/E, central domain (Metalloprtase-TldD/E_cen_dom)
Type: Domain

This entry represents the central domain of TldD and TldE. This domain is also found in the central region of uncharacterised proteins from archaea.

This entry includes a group of metalloproteases, such as TldD and TldE (also known as PmbA) from E. coli, which interact to form a heterodimeric metalloprotease. TldD and TldE were originally related to the biosynthesis of microcin B17 (MccB17), a peptide antibiotic produced by Escherichia coli strains carrying the pMccB17 plasmid that targets the DNA gyrase from sensitive bacteria. Later, they are shown to be metalloproteases involved in CcdA/CcdA41 degradation .
Repeat of unknown function DUF5907 (DUF5907)
Type: Repeat

This entry represents protein repeats whose length varies between 50 and 80 residues. It is found in a variety of virus and bacteria. It may be distantly related to minor tail protein found in phages.
Type III restriction enzyme, C-terminal endonuclease domain (RE_endonuc_C)
Type: Domain

This entry represents the C-terminal endonuclease domain found in a variety of class III restriction endonuclease proteins including Type III restriction-modification system EcoPI/EcoP15I Res subunit from E. coli and Type III restriction-modification enzyme BceSI Res subunit from Bacillus cereus .
Alpha-(1,6)-fucosyltransferase, N- and catalytic domain (Fut8_N_cat)
Type: Domain

This domain includes the N-terminal coil-coiled domain and the catalytic domain of alpha-(1,6)-fucosyltransferase Fut8. The catalytic domain comprises two structures, an open sheet α/β structure, which contains five helices and three β-strands at the N-terminal, and a Rossmann fold that contains five helices and five β-strands at the C-terminal. The latter is conserved among the alpha1,2-, alpha1,6-, and protein O-fucosyltransferases and is similar to GT-B group glycosyltransferases .

Alpha-(1,6)-fucosyltransferase Fut8 catalyses the alpha1,6-linkage of a fucose residue from a donor substrate to N-linked oligosaccharides on glycoproteins in a process called core fucosylation, which is crucial for growth factor receptor-mediated biological functions. Fut8-deficient mice show severe growth retardation, early death, and a pulmonary emphysema-like phenotype . Fut8 is also implicated to play roles in ageing and cancer metastasis . It contains an N-terminal coiled-coil domain, a catalytic domain, and a C-terminal SH3 domain. The SH3 domain of Fut8 is located in the lumen and its role in glycosyl transfer is unclear .
Astrotactin-1/2, Fn3 domain (ASTN1_2_Fn3)
Type: Domain

This domain localises to the middle of the C-terminal region of ASTN1 and 2, which comprises a fibronectin type III (Fn3) domain . This domain is located between the MACPF and annexin-like domains. The structure of Fn3 from ASTN2 revealed an unexpected feature which has two additional β-strands folded across the core. The junction between EGF-4 and Fn3 domains in ASTN2 (but not in ASTN1) is thought to be an inositol triphosphate binding site .

Astrotactin-1 and 2 (ASTN1/2) are integral membrane perforin-like, vertebrate-specific proteins that play critical roles in neurodevelopment . They consist of an N-terminal cytosolic domain suspended between two transmembrane α-helices with a large C-terminal domain, extracellular for ASTN1 and endosome luminal for ASTN2. ASTN1 acts as a neuronal receptor for granule neuron migration along astroglial fibres . ASTN2 forms a complex with ASTN1, which regulates the surface expression of ASTN1. It mediates ASTN1 recycling by promoting its internalisation and transport during endocytosis . ASTN2 is also involved in the planar cell polarity pathway in hair cells .
Astrotactin-1/2, N-terminal (ASTN_1_2_N)
Type: Domain

This entry represents the N-terminal domain of ASTN1/2. This domain includes the transmembrane and cytosolic regions .

Astrotactin-1 and 2 (ASTN1/2) are integral membrane perforin-like, vertebrate-specific proteins that play critical roles in neurodevelopment . They consist of an N-terminal cytosolic domain suspended between two transmembrane α-helices with a large C-terminal domain, extracellular for ASTN1 and endosome luminal for ASTN2. ASTN1 acts as a neuronal receptor for granule neuron migration along astroglial fibres . ASTN2 forms a complex with ASTN1, which regulates the surface expression of ASTN1. It mediates ASTN1 recycling by promoting its internalisation and transport during endocytosis . ASTN2 is also involved in the planar cell polarity pathway in hair cells .
DNA-directed RNA polymerase III subunit RPC5, C-terminal (RPC5_C)
Type: Domain

This entry represents the C-terminal domain of DNA-directed RNA polymerase III subunit RPC5 from metazoans.

DNA-dependent RNA polymerase catalyses the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. RNA polymerase III (Pol III) is a complex consisting of 17 subunits, which synthesizes small RNAs, such as 5S rRNA and tRNAs. Pol III is essential for efficient transcription from both the type 2 VAI and type 3 U6 RNA polymerase III promoters and plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses, being involved in innate immune response, as it induces type I interferon and NF-Kappa-B through the RIG-I pathway . DNA-directed RNA polymerase III subunit RPC5 is a specific peripheric component of RNA polymerase III complex. This subunit forms a subcomplex with RPC4 which is close to the active centre allowing the formation of the open promoter complex and facilitates termination and reinitiation. RPC5 mutations are associated with impaired type I INF and increased susceptibility to viral infections .
Sentrin-specific protease 3/5, conserved domain (SENP3_5_cons_dom)
Type: Domain

Sentrin/SUMO-specific proteases (SENPs) reversibly regulate the covalent modification of proteins by SUMO. SENP3 and 5 share considerable sequence homology and exhibit similar substrate specificity, as they are active against SUMO-2 and SUMO-3 but less so for SUMO-1. They are more closely related than to SENP1/2. This entry covers the N-terminal region of SENP3/5 containing a conserved domain directly preceding the catalytic domain. This domain is responsible for the subcellular localisation . SENP3/5 co-localise in the nucleolus and their depletion causes defects in ribosome biogenesis .
Ubiquitin carboxyl-terminal hydrolase 47, C-terminal (USP47_C)
Type: Domain

This entry represents the C-terminal domain of ubiquitin carboxyl-terminal hydrolase 47 (USP47), a ubiquitin-specific protease that de-ubiquitinates monoubiquitinated DNA polymerase beta (Polbeta), and therefore plays a role in DNA base excision repair (BER) . USP47 also regulates cell growth and genome integrity. In general, the C-terminal domain of Ubiquitin Specific Proteases (USPs) mediates protein-protein interactions .
Acylglycerol kinase, C-terminal (AGK_C)
Type: Domain

This domain corresponds to the C-terminal of mitochondrial acylglycerol kinase (AGK, also known as MuLK) . AGK is a metazoan-specific protein integrated into the mitochondrial inner membrane through a short N-terminal transmembrane domain. This large C-terminal domain is adjacent the kinase domain and it is oriented to the intermembrane space. AGK is a subunit of the human TIM22 complex which stabilises the complex and regulates the import and assembly of mitochondrial carrier proteins, a function independent of its kinase activity . Disturbances in both functions of AGK (phospholipid metabolism and mitochondrial protein biogenesis) contribute to the pathogenesis of Sengers syndrome, which is characterised by cataracts, hypertrophic cardiomyopathy, and skeletal myopathy .
PIK3 catalytic subunit gamma, adaptor-binding domain (PIK3CG_ABD)
Type: Domain

This entry represents the N-terminal domain of PI3-kinase catalytic subunit gamma (PIK3CG, also known as p110 catalytic subunit gamma). This domain contains the adaptor-binding domain (ABD). PIK3CG interacts with the regulatory subunit of the p101 type .

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that phosphorylate 4,5-bisphonate (PI(4,5) P2 or PIP2) at the 3-position of the inositol ring, and thus generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), which, in turns, initiates a vast array of signaling events. PI3Ks can be grouped into three classes based on their domain organisation. Class I PI3Ks are heterodimers consisting of a p110 catalytic subunit and a regulatory subunit of either the p85 type (associated with the class IA p110 isoforms p110alpha, p110beta or p110delta) or the p101 type (associated with the class IB p110
isoform p110gamma). Common to all catalytic subunits are an N-terminal adaptor-binding domain (ABD) that binds to p85/p101, a Ras-binding domain (RBD), a putative membrane-binding domain (C2), a helical domain of unknown function, and a kinase catalytic domain .

PI3K_ABD is a small globular domain of about 100 residues in length with an α/β-sandwich topology .
DNA-dependent protein kinase catalytic subunit, CC5 (DNAPKcs_CC5)
Type: Domain

This entry represents the C-terminal region of the Circular Cradle segment (CC) of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), containing most of the supersecondary structure CC4 and the complete CC5. Structural studies revealed that this domain contains the Ku-binding site B and one of the caspase-3 cleavage sites .

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is involved in DNA nonhomologous end joining (NHEJ), which is recruited by Ku70/80 heterodimer to DNA ends and required for double-strand break (DSB) repair. DNA-PKcs phosphorylates a number of protein substrates, including the heat shock protein 90 (HSP90), the transcription factors p53, specificity protein 1 (Sp1) and MYC23, and a majority of NHEJ factors. It folds into three well-defined large structural units, consisting of a N-terminal region (arranged in four supersecondary α-helical structures, N1 to N4), the Circular Cradle (consisting of five supersecondary α-helical structures CC1 to CC5), and the C-terminal Head (comprising FAT, FRB, kinase, and FATC). The N-terminal and CCs regions resemble HEAT repeats, and thus, they are also referred to as N-HEAT and M-HEAT ('middle'), respectively. The N-terminal region likely mediates DNA binding and, together with the CCs, forms a ring through which Ku70/80 may present DNA for repair. The CCs form a curved elliptical ring that serves as a scaffold to maintain the integrity of the whole complex. It has been suggested that the binding of Ku or DNA activates the allosteric mechanism required for communication between the N terminus and the CC with the kinase in the Head .
Trehalase-like, N-terminal domain (Trehalase-like_N)
Type: Domain

This presumed domain is found at the N-terminal region of bacterial and archaeal trehalases which catalyse the hydrolysis of alpha,alpha-trehalose into two molecules of D-glucose, followed by the glycoside hydrolase domain. This domain is also found in the uncharacterised protein C4H3.03c from S. pombe. Members of this entry belong to the glycosyl hydrolase 15 family

. The function of this domain is not clear.
Phosphorylase b kinase regulatory subunit alpha/beta, C-terminal domain (KPBA/B_C)
Type: Domain

This entry represents the C-terminal domain of KPBA/B, that has been proposed as the second calcineurin B-like (CBL-2) containing a gamma subunit-binding site .

Phosphorylase kinase (PHK) is a hexadecameric enzyme complex consisting of four copies each of four different subunits: alpha, beta, delta and gamma that plays a role in glycogen metabolism. During activation of glycogenolysis, this protein complex phosphorylates and activates glycogen phosphorylase (GP). The gamma subunit is the catalytic protein kinase, while alpha, beta and delta subunits control its activity. This entry represents several phosphorylase kinase regulatory alpha and beta subunits (KPBA/B), which interact directly with GP .

Mutations in the gene encoding the alpha subunit of PHK (PHKA2) have been shown to be responsible for X-linked liver glycogenosis (XLG). XLG, a frequent type of glycogen storage disease, is characterised by hepatomegaly and growth retardation .