SII-SWORD/CoKE huggingface dataset:
Potassium voltage-gated channel subfamily A member 7, BTB/POZ domain (KCNA7_BTB_POZ)
Type: Domain

This entry represents the BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in Potassium voltage-gated channel subfamily A member 7 (KCNA7) and similar sequences from vertebrates.

KCNA7, also called voltage-gated potassium channel subunit Kv1.7, mediates transmembrane potassium transport in excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a tetrameric potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. KCNA7 plays an important role in the repolarization of cell membranes.

Voltage-gated potassium (Kv) channels are composed of alpha subunits, which form the actual conductance pore, and cytoplasmic beta subunits, which are auxiliary proteins that associate with alpha subunits to modulate the activity of the Kv channel. KCNA7 is an alpha subunit that forms functional homo- or hetero-tetrameric channels (with other Kv1/KCNA alpha subunits) through its BTB/POZ domain, also known as tetramerization (T1) domain, which is a versatile protein-protein interaction motif .
Phosphoprotein, C-terminal domain, vesiculovirus (P-protein-C_vesiculovirus)
Type: Domain

This entry represents the C-terminal domain of the P protein (phosphoprotein) of plant viruses belonging to the Rhabdoviridae family such as Vesicular stomatitis Indiana virus (VSV). The family Rhabdoviridae belongs to the order Mononegavirales, which are nonsegmented negative-stranded RNA viruses (NNVs). The genomes of NNVs are encapsidated by their nucleocapsid (N) proteins to form N-RNA complexes which serves as a template for transaction and replication .

The C-terminal of P protein binds the nucleocapsid . The P protein is an essential component of the RNA polymerase transcription and replication complex; it plays multiple roles in transcription and translation, which include acting as a chaperone of nascent nucleoprotein (N), and as a cofactor of the viral polymerase (L) where P forms a two-subunit polymerase with a large catalytic subunit (L) and stabilizes the polymerase on its template of N-RNA .
Guanine-specific ADP-ribosyl transferase-like (ScARP-like)
Type: Family

This entry represents guanine-specific ADP-ribosyl transferase from Streptomyces coelicolor (ScARP) and similar sequences mainly found in Streptomyces. ScARP ADP-ribosylates the N2 amino group of guanosine, deoxyguanosine, GMP, dGMP, cGMP, GDP, GTP and dGTP; oligo-guanosine, oligo-deoxyguanosine and tRNA are ADP-ribosylated less efficiently, while dsDNA is a very poor substrate .
E3 ubiquitin-protein ligase TRIM65, PRY/SPRY domain (TRIM65_SPRY_PRY)
Type: Domain

This entry represent the C-terminal domain of TRIM65, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain. The SPRY/PRY combination is a possible component of immune defence .

E3 ubiquitin-protein ligase TRIM65 plays a role in several processes including innate immunity, autophagy or inflammation . It negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs . This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy .

TRIM65 promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5 which leads to innate signalling cascade upon enteroviral infection . It also plays a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation . In addition, negatively regulates inflammasome activation by promoting 'Lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages . TRIM65 selectively recognises MDA5 filaments that occur on dsRNAs. MDA5 is a RIG-I-like receptor (RLR) that performs antiviral functions distinct from RIG-I by detecting different groups of viral RNAs .
ATP-dependent fumaroyl-DAP ligase (DdaG_Ligase)
Type: Family

This entry represents the ATP-dependent fumaroyl-DAP ligase DdaG (also known as Fumarate--(S)-2,3-diaminopropanoate ligase

) that is involved in dapdiamide antibiotics biosynthesis. DdaG ligates fumarate and DAP to form N-fumaroyl-DAP in an ATP-dependent manner. It also forms N-succinoyl-DAP from succinate and DAP .
Semaphorin 5C, Sema domain (Sema5C_Sema)
Type: Domain

In Drosophila, Sema5C was identified as an early development gene, which is expressed in stage 2 embryos with a striped pattern emerging at later stages. Sema5c may play a role in odour-guided behaviour and in tumourigenesis . Sema5C belongs to class 5 semaphorin family of proteins, which are transmembrane glycoproteins characterised by unique thrombospondin specific repeats in the extracellular region of the protein.

Semaphorins are regulatory molecules involved in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer . The Sema domain, represented in this entry, is located at the N-terminal and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor -recognition and -binding module.
MlrA-like, HTH domain (MlrA-like_HTH)
Type: Domain

This entry represents the N-terminal HTH domain of MlrA. Many MlrA-like proteins in this group appear to lack the long dimerisation helix seen in the N-terminal domains of typical MerR-like proteins .

The HTH transcription regulator MlrA (merR-like regulator A), also known as YehV, has been shown to control cell-cell aggregation by co-regulating the expression of curli and extracellular matrix production in Escherichia coli and Salmonella typhimurium . Its close homologue, CarA from Myxococcus xanthus (not included in this entry), is involved in activation of the carotenoid biosynthesis genes by light . MlrA is part of a signalling cascade that regulates curli biosynthesis. The cascade is composed of two c-di-GMP control modules, in which c-di-GMP controlled by the DgcE/PdeH pair (module I) regulates the activity of the DgcM/PdeR pair (module II), which in turn regulates activity of the transcription factor MlrA .

These proteins belong to the MerR superfamily of transcription regulators that promote expression of several stress regulon genes by reconfiguring the spacer between the -35 and -10 promoter elements. Their conserved N-terminal domains contain HTH motifs that mediate DNA binding, while the dissimilar C-terminal domains bind specific coactivator molecules.
Rv2640c-like (Rv2640c-like)
Type: Family

This entry represents a group of ArsR-related transcriptional regulators from actinomycetes, including Rv2640c from Mycobacterium tuberculosis (

) and Rv2642 (

), encoded nearby. Members of this family have two invariant CC motifs, one at (or a single amino acid away from) the C terminus .
RNA polymerase recycling motor HelD-like, actinomycetes (HelD-like_actinomycetes)
Type: Family

This entry represents a group of proteins from actinomycetes, including

from Mycolicibacterium smegmatis (MSMEG_2174) , an homologue of HelD (

,

), an helicase-like motor protein that play a role in transcription, removing and recycling stalled transcription complexes that could interfere with normal transcription or with DNA replication .
RNA polymerase recycling motor HelD-like, bacillota (HelD_bacillota)
Type: Family

This entry represents the RNA polymerase recycling motor proteins HelD from Bacillus subtilis and similar sequences from bacillota. HelD is ATP-dependent motor proteins distantly related to helicases that play a role in transcription, removing and recycling stalled transcription complexes that could interfere with normal transcription or with DNA replication .
Beta-galactosidase GalB-like (GalB-like)
Type: Family

This entry represents Beta-galactosidase GalB (also known as Gal02II) from Xanthomonas campestris (

) and similar bacterial sequences. GalB belongs to the glycosyl hydrolase (GH) family 2 enzyme .
Beta-galactosidase GalA-like (GalA-like)
Type: Family

This entry represents Beta-galactosidase GalA (also known as Gal02I) from Xanthomonas campestris (

) and similar bacterial sequences. GalA belongs to the glycosyl hydrolase (GH) family 2 enzyme .
Cell-division control histidine kinase PdhS (PdhS_histid_kinase)
Type: Family

This entry includes the histidine kinase PdhS found in Brucella species. PdhS is a cytoplasmic histidine kinase essential for cell viability. It localises at the old pole of dividing cells and controls cell division and maturation, probably through control of DivK phosphorylation status and cellular distribution, which in turn regulates CtrA, a transcriptional regulator of the minB operon. The asymmetrical localisation of this protein is probably required for cells to enter a new division cycle .
Tetraspanin-6/7, EC2 domain (TSN6/7_LEL)
Type: Domain

Tetraspanins are transmembrane proteins with 4 transmembrane segments. Both the N- and C-terminal ends lie on the intracellular side of the membrane. Tetraspanins are involved in diverse processes and their various functions may relate to their ability to act as molecular facilitators. Tetraspanins associate laterally with one another and cluster dynamically with numerous partner domains in membrane microdomains, forming a network of multimolecular complexes, the 'tetraspanin web' .

This entry represents the extracellular domain (EC2) between the 3rd and 4th transmembrane segment, also referred to as the large extracellular loop (LEL) from tetraspanin-6 (TSN-6, also known as transmembrane 4 superfamily 6) and tetraspanin-7 (TSN-7, also known as transmembrane 4 superfamily 2). TNS-7 has been identified to be involved in some forms of X-linked mental impairments .
Monocarboxylate transporter 13 (MFS_MCT_13)
Type: Family

Monocarboxylate transporter 13 (MCT13), also called Solute carrier family 16 member 13 (SLC16A13), is an orphan transporter whose substrates are yet to be determined. MCT13 is expressed in breast and bone marrow stem cells. MCT13 belongs to the Monocarboxylate transporter (MCT) family of the Major Facilitator Superfamily (MFS) of membrane transport proteins . MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement .
DNA distortion polypeptide 1-like (DDP1-like)
Type: Family

This entry represents a group of proteins from enterobacterales, including DDP1 (also known as TaxA), which putatively binds DNA and regulates R6K-like plasmids transfer . DDP1 is structurally related to relaxosome TraY family

.
Ceruloplasmin-like, fifth cupredoxin domain (Ceruloplasmin-like_CuRO_5)
Type: Domain

Ceruloplasmin is a serum multicopper oxidase essential for normal iron homeostasis and copper transport in blood but it is also membrane-bound via a glycosylphosphatidylinositol (GPI)-anchor in astrocytes and kidney . It also functions in amine oxidation and as an antioxidant preventing free radicals in serum. The protein has 6 cupredoxin domains with six copper centres; three mononuclear sites in domain 2, 4 and 6 and three in the form of trinuclear clusters at the interface of domains 1 and 6. Ceruloplasmin exhibits internal sequence homology that appears to have evolved from the triplication of a sequence unit composed of two tandem cupredoxin domains. This entry represents the fifth cupredoxin domain of ceruloplasmin .

This entry also includes the ceruloplasmin homologue hephaestin , which is involved in the metabolism and homeostasis of iron. It is a transmembrane copper-dependent ferroxidase responsible for transporting dietary iron from intestinal enterocytes into the circulatory system. The highest expression of hephaestin is found in small intestine.
DNA distortion polypeptide 3-like (DDP3-like)
Type: Family

This entry represents a group of proteins from enterobacterales, including DDP3 (also known as TaxD), which putatively binds DNA and regulates R6K-like plasmids transfer . Some members of the this family contain the domain of unknown function DUF2726
(

).
Kappa-carrageenase (K-carrageenase)
Type: Family

This entry represents the Kappa-carrageenase (

) from the marine bacterium Rhodopirellula sallentina and similar bacterial sequences. Members of this family belong to the glycosyl hydrolases family 16 (GH16) family and contain the domain

.
Probable hydrolase YcaC (YcaC)
Type: Family

This entry represents Probable hydrolase YcaC from Escherichia coli and similar proteins from bacteria and some fungal species. YcaC is an homooctameric isochorismatase-like protein with unknown specificity. Despite its weak sequence similarity, it is structurally related to other amidohydrolases and shares conserved active site residues with them . Members of this familly contain the domain

. Multimerisation interface seems not to be conserved in all proteins .
Polarized growth protein Scy (Scy)
Type: Family

This entry represents the Polarized growth protein Scy and similar sequences from Streptomyces species. Scy (for Streptomyces cytoskeletal element) is a coiled-coil protein that coordinates polarised growth and chromosome segregation .
Replication initiator protein, streptomyces (RepSA_streptomyces)
Type: Family

This entry represents the Replication initiator protein from Streptomyces ambofaciens (RepSA) and similar proteins from Streptomyces species.

RepSA is an essential part of actinomycete integrative and conjugative elements (AICEs) replication .

Horizontal Gene Transfer (HGT) is a powerful force generating genomic diversity in bacterial populations. HGT in Streptomyces is in large part driven by conjugation thanks to plasmids, Integrative and Conjugative elements (ICEs) and Actinomycete ICEs (AICEs) .
Antitoxin MazE (MazE)
Type: Family

This entry represents Antitoxin MazE from Staphylococcus aureus and similar proteins predominantly found in Staphylococcus species. MazE is the antitoxin component of a type II toxin-antitoxin (TA) system from Staphylococcus. MazE binds to cognate MazF toxin and counteracts its endoribonuclease activity .
Terminal beta-(1->2)-arabinofuranosyltransferase-like (AftB-like)
Type: Family

This entry represents Terminal beta-(1->2)-arabinofuranosyltransferase from Mycobacterium tuberculosis (AftB) and similar sequences specific to mycobacteriales. AftB is involved in the biosynthesis of the arabinogalactan (AG) region of the mycolylarabinogalactan-peptidoglycan (mAGP) complex, an essential component of the mycobacterial cell wall. It catalyses the transfer of arabinofuranosyl (Araf) residues from the sugar donor decaprenyl-phospho-arabinose (DPA) to the arabinan domain to form terminal beta-(1->2)-linked Araf residues, which marks the end point for AG arabinan biosynthesis before decoration with mycolic acids .
DinQ-like type I toxin DqlB (DqlB-like)
Type: Family

This entry represents a group of proteins from enterobacterales, including the DinQ-like toxin DqlB from Escherichia coli. DinQ-like proteins are transmembrane peptides. These proteins have characterised as membrane-depolarising type I toxins that provoke reactive oxygen species formation under oxidative stress and have a putative regulatory role in modulating membrane-dependent activities in bacteria .
Nuclear receptor subfamily 2 group C member 1/2-like, DNA-binding domain (NR2C1/2-like_DBD)
Type: Domain

This entry represents the DNA-binding domain (DBD) of human Nuclear receptor subfamily 2 group C members 1 and 2 (NR2C1/2, also known as TR2 and TR4 for testicular receptor 2 and 4) and similar animal sequences. NR2C1 and 2 interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. They are orphan nuclear receptors whose physiological ligand is as yet unidentified. NR2C1 is abundantly expressed in the androgen-sensitive prostate. NR2C2 transcripts are expressed in many tissues, including central nervous system, adrenal gland, spleen, thyroid gland, and prostate. It has been shown that human NR2C1 binds to a wide spectrum of natural hormone response elements (HREs) with distinct affinities suggesting that it may cross-talk with other gene expression regulation systems. The genes responding to these proteins include genes that are regulated by retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor .

NR2C1/2 binds to HREs as dimers. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TR2-like receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). This domain is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom .
Nuclear receptor subfamily 2 group C member 1/2-like, ligand binding domain (NR2C1/2-like_LBD)
Type: Domain

This entry represents the C-terminal ligand binding domain (LBD) of human Nuclear receptor subfamily 2 group C members 1 and 2 (NR2C1/2, also known as TR2 and TR4 for testicular receptor 2 and 4) and similar animal sequences. NR2C1 and 2 interact with specific DNA sites upstream of the target gene and modulate the rate of transcriptional initiation. They are orphan nuclear receptors whose physiological ligand is as yet unidentified. NR2C1 is abundantly expressed in the androgen-sensitive prostate. NR2C2 transcripts are expressed in many tissues, including central nervous system, adrenal gland, spleen, thyroid gland, and prostate. It has been shown that human NR2C1 binds to a wide spectrum of natural hormone response elements (HREs) with distinct affinities suggesting that it may cross-talk with other gene expression regulation systems. The genes responding to these proteins include genes that are regulated by retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor .

NR2C1/2 binds to HREs as dimers. Like other members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors, TR2-like receptors have a central well conserved DNA binding domain (DBD), a variable N-terminal domain, a flexible hinge and a C-terminal ligand binding domain (LBD). This domain is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom .
Eukaryotic translation initiation factor 2D, N-terminal domain (eIF2D_N)
Type: Domain

This entry represents the N-terminal domain of human Eukaryotic translation initiation factor 2D (eIF2D) and similar eukaryotic proteins.

eIF2D (also known as ligatin) is involved in the recruitment and delivery of aminoacyl-tRNAs to the P-site of the eukaryotic ribosome in a GTP-independent manner. This domain co-occurs with a PUA domain .
Eukaryotic translation initiation factor 2D-like, PUA RNA-binding domain (PUA_eIF2d-like)
Type: Domain

This entry represents the RNA-binding PUA (PseudoUridine synthase and Archaeosine transglycosylase) domain of human Eukaryotic translation initiation factor 2D (eIF2D) and similar eukaryotic proteins. eIF2D (also known as ligatin) is involved in the recruitment and delivery of aminoacyl-tRNAs to the P-site of the eukaryotic ribosome in a GTP-independent manner .

The yeast homologue Translation machinery-associated protein 64 (Tma64) from Saccharomyces cerevisiae, which is uncharacterised but also interacts with the 40S ribosomal subunit , is also included in this group of proteins.
Far upstream element-binding protein 1, first type I KH domain (KH-I_FUBP1_dom1)
Type: Domain

This entry represents first type I K homology (KH) RNA-binding domain found in human Far upstream element-binding protein 1 (FUBP1) (

) and similar proteins from vertebrates.

FUBP1, also called FBP, or FUSE-binding protein 1, or DNA helicase V, or DH V, binds RNA and single-stranded DNA (ssDNA) and may act both as activator and repressor of transcription. It regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. FUBP1 contains four K-homology (KH) RNA-binding domains .
Far upstream element-binding protein 1, second type I KH domain (KH-I_FUBP1_dom2)
Type: Domain

This entry represents second type I K homology (KH) RNA-binding domain found in human Far upstream element-binding protein 1 (FUBP1) (

) and similar proteins from vertebrates.

FUBP1, also called FBP, or FUSE-binding protein 1, or DNA helicase V, or DH V, binds RNA and single-stranded DNA (ssDNA) and may act both as activator and repressor of transcription. It regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. FUBP1 contains four K-homology (KH) RNA-binding domains .
Far upstream element-binding protein 1, third type I KH domain (KH-I_FUBP1_dom3)
Type: Domain

This entry represents third type I K homology (KH) RNA-binding domain found in human Far upstream element-binding protein 1 (FUBP1) (

) and similar proteins from vertebrates.

FUBP1, also called FBP, or FUSE-binding protein 1, or DNA helicase V, or DH V, binds RNA and single-stranded DNA (ssDNA) and may act both as activator and repressor of transcription. It regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. FUBP1 contains four K-homology (KH) RNA-binding domains .
Far upstream element-binding protein 1, fourth type I KH domain (KH-I_FUBP1_dom4)
Type: Domain

This entry represents fourth type I K homology (KH) RNA-binding domain found in human Far upstream element-binding protein 1 (FUBP1) (

) and similar proteins from vertebrates.

FUBP1, also called FBP, or FUSE-binding protein 1, or DNA helicase V, or DH V, binds RNA and single-stranded DNA (ssDNA) and may act both as activator and repressor of transcription. It regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. FUBP1 contains four K-homology (KH) RNA-binding domains .
Homocitrate synthase, catalytic TIM barrel domain, fungi/bacteria (DRE_TIM_HCS_fun_bact)
Type: Domain

This entry represents the catalytic TIM barrel domain of Homocitrate synthase from Saccharomyces cerevisiae and similar proteins from fungi and some bacterial species. This domain consists of a core (β/α)8 motif with the eight parallel β-strands forming an enclosed barrel surrounded by eight α-helices. The domain has a catalytic centre containing a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel. In addition, the catalytic site includes three invariant residues - an aspartate (D), an arginine (R), and a glutamate (E) - which is the basis for the domain name "DRE-TIM".

Homocitrate synthase (HCS) catalyses the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate, the first step in the lysine biosynthesis pathway. This family includes the Yarrowia lipolytica and Saccharomyces cerevisiae homologues. This family belongs to the DRE-TIM metallolyase superfamily .