SII-SWORD/CoKE huggingface dataset:
Anaphase-promoting complex subunit 1, middle domain (Apc1_MidN)
Type: Domain

Apc1 is the largest of the subunits of the anaphase-promoting complex or cyclosome. The anaphase-promoting complex is a multiprotein subunit E3 ubiquitin ligase complex that controls segregation of chromosomes and exit from mitosis in eukaryotes. Apc1 consists of a N-terminal WD40 β-propeller domain, followed by the middle domain (Mid-N), a PC domain and the C-terminal domain (MidC). This entry represents the middle domain of Apc1, MidN (also referred to as the first helical domain), that coalesced with the C-terminal domain to form Apc1Mid that connects Apc1WD40 with Apc1PC . Apc1Mid consists of an α-solenoid capped by a β-sandwich .
Transmembrane protein 127, transmembrane region (TMEM127_TM)
Type: Domain

Transmembrane protein 127 (TMEM127) modulates mTOR function in the endolysosome. Its interaction with early endosomal GTPase Rab5 to inhibit mTOR signalling seems to be related with its tumour-suppressing properties . This entry represents the transmembrane region of this protein and similar animal sequences.
Putative plant transposon protein domain (Transposase_32_dom)
Type: Domain

This entry represents a domain found in likely transposon related proteins from plants. This entry appears related to ORF1 from the ATHILA group of Arabidopsis thaliana retrotransposons

.
PD-(D/E)XK nuclease-like (PDDEXK_12)
Type: Domain

This entry contains uncharacterised fungal proteins. Structure prediction suggests it is likely to be an endonuclease enzyme related to the PD-(D/E)XK nuclease superfamily.
Tet-like 2OG-Fe(II) oxygenase (2OG-FeII_Oxy_6)
Type: Domain

This entry represents an uncharacterised family of fungal proteins. The AlphaFold prediction for an example protein shows that it is most closely related to Tet-like dioxygenases. This strongly suggests that this family of proteins are DNA modification enzymes.
ROXA-like, winged helix (ROXA-like_wH)
Type: Domain

This entry represents the C-terminal winged helix domain of ribosomal oxygenases, including ROXA from Escherichia coli, which is reminiscent of WH-domains involved in protein-protein and protein-nucleic acid interactions. However, this domain has an overall negative charge suggesting they do not directly bind nucleic acids .
Plexin, cytoplasmic RhoGTPase-binding domain (Plexin_RBD)
Type: Domain

This entry represents the RhoGTPase-binding domain found in the cytoplasmic domain of plexins [

,

]. Plexins are receptors for semaphorins, and plexin signalling is important in pathfinding and patterning of both neurons and developing blood vessels . The cytoplasmic region, which has been called a SEX domain , and is involved in downstream signalling pathways, by interaction with proteins such as Rac1, RhoD, Rnd1 and other plexins .
Glucose-6-phosphate dehydrogenase assembly protein OpcA, N-terminal domain (OpcA_G6PD_N)
Type: Domain

OpcA protein may play a role in the functional assembly of glucose-6-phosphate dehydrogenase . The opcA gene is found immediately downstream of zwf, the glucose-6-phosphate dehydrogenase (G6PDH) gene, in a number of species, including Mycobacterium tuberculosis, Streptomyces coelicolor, Nostoc punctiforme (strain ATCC 29133/PCC 73102), and Synechococcus sp. (strain PCC 7942). In the latter, disruption of opcA was shown to block assembly of G6PDH into active oligomeric forms.

This entry represents the N-terminal Rossmann-like domain.
Glucose-6-phosphate dehydrogenase assembly protein OpcA, C-terminal domain (OpcA_G6PD_C)
Type: Domain

This entry represents the C-terminal domain in OpcA and related proteins.

OpcA protein may play a role in the functional assembly of glucose-6-phosphate dehydrogenase . The opcA gene is found immediately downstream of zwf, the glucose-6-phosphate dehydrogenase (G6PDH) gene, in a number of species, including Mycobacterium tuberculosis, Streptomyces coelicolor, Nostoc punctiforme (strain ATCC 29133/PCC 73102), and Synechococcus sp. (strain PCC 7942). In the latter, disruption of opcA was shown to block assembly of G6PDH into active oligomeric forms.
DNA-dependent protein kinase catalytic subunit, CC1/2 (DNAPKcs_CC1-2)
Type: Domain

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. It folds into three well-defined large structural units, consisting of a N-terminal region, 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 CCs form a curved elliptical ring that serves as a scaffold to maintain the integrity of the whole complex. This entry represents CC1 and CC2, which contain the Highly conserved region I (HCR-I) .
DNA-PKcs, N-terminal (DNA-PKcs_N)
Type: Domain

This entry represents the N-terminal domain of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which is arranged in four supersecondary α-helical structures, N1 to N4, that resemble HEAT repeats. Therefore, this domain is also known as N-HEAT. This domain likely mediates DNA binding and, together with the Circular Cradle (CC), forms a ring through which Ku70/80 may present DNA for repair. DNA-PKcs is involved in DNA nonhomologous end joining (NHEJ), required for double-strand break (DSB) repair . It is recruited by Ku70/80 heterodimer to DNA ends.
Tra1, HEAT repeat ring region (Tra1_ring)
Type: Repeat

This entry represents part of the Tra1 protein composed of α-solenoid repeats that form a ring region .

This entry includes transcription-associated protein 1 (Tra1) from yeast and TRRAP from mammals. Budding yeast Tra1 is a subunit of SAGA and NuA4 histone acetyltransferase complexes . Human TRRAP is an adapter protein found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT) .

This entry also includes Tra2 which is a component of the NuA4 histone H4/H2A acetyltransferase involved in transcription and DNA repair .
MrpA C-terminal/MbhE (MrpA_C/MbhE)
Type: Domain

Hydrogen gas-evolving membrane-bound hydrogenase (MBH) is a respiratory complex homologous to the quinone-reducing Complex I which share a common ancestor, the Mrp antiporter . Like Complex I, MBH has peripheral and membrane arms. MBH is made of 14 subunits (MbhA-N). MbhJ, K, L, N and M form the Membrane-anchored hydrogenase module. MbhJ, K, L, N are predicted to be exposed to the cytoplasm and form the peripheral arm. The remaining 10 subunits are predicted to be integral membrane proteins forming the membrane arm, made of 44 transmembrane helices (TMH) . MbhA, B, C and F form the Sodium translocation module. MbhD, E, G and H form the Proton translocation module. MbhI is the linker between the hydrogenase module and the proton-translocating membrane module. It anchors the discontinuous TMH7 of MbhH via its middle lateral helix and the C-terminal of TMH2, found in MbhE. MbhD and MbhE together are equivalent to Nqo10 of Complex I and the C-terminal of MrpA . MbhE has two transmembrane helices: TMH1 and TMH2.
Tra1, HEAT repeat central region (Tra1_central)
Type: Repeat

This entry represents part of the Tra1 protein composed of α-solenoid repeats that forms the central region . This is named as central due to its position relative to the ring region.

This entry includes transcription-associated protein 1 (Tra1) from yeast and TRRAP from mammals. Budding yeast Tra1 is a subunit of SAGA and NuA4 histone acetyltransferase complexes . Human TRRAP is an adapter protein found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT) .

This entry also includes Tra2 which is a component of the NuA4 histone H4/H2A acetyltransferase involved in transcription and DNA repair .
Double strand break localizing Dbl7 (Dbl7)
Type: Family

This family represents the Schizosaccharomyces specific protein double strand break localizing Dbl7 . Dbls localize to DNA double-strand breaks (DSBs) and are involved in DSB repair .
Lipoprotein YfjS/YafY domain (YfjS_YafY_dom)
Type: Domain

This domain is found in the E. coli YfjS and YafY lipoproteins and similar sequences from Gammaproteobacteria.
Ezrin/radixin/moesin, alpha-helical domain (ERM_helical)
Type: Domain

The ERM family consists of three closely-related proteins, ezrin, radixin and moesin . Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin-binding protein . ERM proteins crosslink actin filaments with plasma membranes. They co-localise with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains . A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein) . ERM molecules contain 3 domains, an N-terminal globular domain, an extended α-helical domain and a charged C-terminal domain (

) . Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. This entry represents the α-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, that regulate the activity of these proteins .
RNA-directed RNA polymerase, thumb subdomain, flavivirus (Flavi_NS5_thumb)
Type: Domain

Flaviviruses produce a large polyprotein from the ssRNA genome, encoding structural proteins required for virus assembly and non-structural (NS1-5) proteins involved in replication of the viral genome . This polyprotein is cleaved by viral and cellular proteases to produce mature viral proteins. NS5 is the largest mature viral protein and contains a N-terminal methyltransferase (MTase) domain separated by a short linker from the C-terminal RNA-directed RNA polymerase domain (RdRp) that adopts a characteristic right-handed fingers-palm-thumb fold and possesses a number of short regions and motifs homologous to other RdRps . This entry represents the thumb domain of NS5 RdRp. NS5 binds to a the stem loop A (SLA) at the 5' extremity of Flavivirus genome and regulates translation of the viral genome .
RNA-directed RNA polymerase, palm domain superfamily, Birnavirus (Birnavirus_RdRp_palm_sf)
Type: Homologous_superfamily

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This superfamily represents the "palm" domain of RdRp from Birnavirus. These proteins lack the highly conserved Gly-Asp-Asp (GDD) sequence, a component of the proposed catalytic site of this enzyme family that exists in the conserved motif VI of the palm domain of other RNA-directed RNA polymerases . The catalytic motifs are arranged in a permuted order, thus, adopting a unique active site topology . This domain adopts and α/β structure.
RNA-directed RNA polymerase, thumb domain superfamily, Birnavirus (Birnavirus_RdRp_thumb_sf)
Type: Homologous_superfamily

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This entry represents the thumb domain of RdRp from Birnavirus, which contain the conserved RdRp motifs that reside in the catalytic "palm" domain (

) of all classes of polymerases but in a characteristic permuted order, thus, it adopts a unique active site topology . Additionally, the birnavirus RdRps lack the highly conserved Gly-Asp-Asp (GDD) sequence, a component of the proposed catalytic site of this enzyme family that exists in the conserved motif VI of the palm domain of other RdRps . This domain adopts an α-helical bundle arrangement.
RNA-directed RNA polymerase, C-terminal domain superfamily, Avibirnavirus (Avibirnavurs_RdRp_C_sf)
Type: Homologous_superfamily

RNA-directed RNA polymerase (RdRp) (

) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage . It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear.
The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product .

This entry represents the C-terminal domain of RdRp from avibirnaviruses, which lack the highly conserved Gly-Asp-Asp (GDD) sequence, a component of the proposed catalytic site of this enzyme family that exists in the conserved motif VI of the palm domain (

) of other RdRps . These enzymes have the five essential RNA polymerase motifs in a permuted order of C-A-B-D-E to form a conserved catalytic active site . This domain is mostly α-helical and runs across the canyon in the front of the palm, wrapping around the fingers subdomain , which may function to prevent back-primed RNA synthesis during protein priming. This domain adopts an α-helical orthogonal bundle structure.
P2X purinoreceptor 7, intracellular domain (P2RX7_C)
Type: Domain

P2X purinoceptors are cell membrane ion channels, gated by adenosine 5'-triphosphate (ATP) and other nucleotides; they have been found to be widely expressed on mammalian cells, and, by means of their functional properties, can be differentiated into three sub-groups. The first group is almost equally well activated by ATP and its analogue alpha,betamethylene-ATP, whereas, the second group is not activated by the latter compound. A third type of receptor (also called P2Z) is distinguished by the fact that repeated or prolonged agonist application leads to the opening of much larger pores, allowing large molecules to traverse the cell membrane. This increased permeability rapidly leads to cell death, and lysis.

Molecular cloning studies have identified seven P2X receptor subtypes, designated P2XR1-P2XR7, however, P2X1R, P2X2R, P2X3R, P2X4R, and P2X7R are functional . These receptors are proteins that share 35-48% amino acid identity, and possess two putative transmembrane (TM) domains, separated by a long (~270 residues) intervening sequence, which is thought to form an extracellular loop. Around 1/4 of the residues within the loop are invariant between the cloned subtypes, including 10 characteristic cysteines.

Studies of the functional properties of heterologously expressed P2X receptors, together with the examination of their distribution in native tissues, suggests they likely occur as both homo-and hetero multimers in vivo . Stimulation of these receptors induces changes in intracellular ion homeostasis leading to multiple key responses crucial for initiation, propagation, and resolution of inflammation . The P2X7 subtype has an important role in the activation of lymphocyte, granulocyte, macrophage and dendritic cell responses and, therefor, it may be a promising target for anti-inflammatory therapies.

This entry represents the intracellular domain found at the C-terminal domain of P2X7 (also known as P2Z receptor). P2X7 receptor has different functional properties from those of P2X1-P2X6. Key properties of the current produced are little rectification or desensitisation, and strong potentiation of responses when the concentration of extracellular Ca2 and/or Mg2 are reduced. It is also found to be relatively insensitive to ATP. In certain studies, prolonged activation of expressed P2X7 receptors causes cell permeabilization, and lysis. This domain is critical for the receptor to initiate apoptosis and not undergo desensitization. It shows a globular structure and is shaped like a wedge with three β-strands forming an antiparallel β-sheet followed by eight α-helices separated by loops that form a helical bundle .
MmeI-like, DNA-methyltransferase domain (MmeI_Mtase)
Type: Domain

Type IIL Restriction-Modification Enzyme MmeI is a large enzyme that integrates DNA recognition and methyltransferase and endonuclease activities within the same polypeptide . MmeI is composed of five domains. An N-terminal endonuclease domain (residues 1-155), connects to a DNA-methyltransferase domain (MTase, residues 301-320) via a multi-helical spacer (residues 156-300). These are followed by the target recognition domain (TRD, residues 621-825), and a final C-terminal helical bundle (residues 826-919) . The DNA is embedded between the TRD and the MTase domain. The TRD makes contacts to the DNA bases primarily in the major groove, while the MTase domain makes several contacts to the DNA in the minor groove . This entry includes DNA methyltransferase A, a MmeI homologue that lacks endonuclease activity .

This domain corresponds to the DNA-methyltransferase. Structurally, it consists of a twisted β-sheet flanked by α-helices on both sides.
MmeI-like, N-terminal domain (MmeI_N)
Type: Domain

Type IIL Restriction-Modification Enzyme MmeI is a large enzyme that integrates DNA recognition and methyltransferase and endonuclease activities within the same polypeptide . MmeI is composed of five domains. An N-terminal endonuclease domain (residues 1-155), connects to a DNA-methyltransferase domain (MTase, residues 301-320) via a multi-helical spacer (residues 156-300). These are followed by the target recognition domain (TRD, residues 621-825), and a final C-terminal helical bundle (residues 826-919) . This domain corresponds to the N-terminal endonuclease, it cuts the two DNA strands at one site simultaneously with enzyme bound at two sites interacting to accomplish the cleavage . This entry includes DNA methyltransferase A, a MmeI homologue that lacks endonuclease activity .
MmeI-like, C-terminal domain (MmeI_C)
Type: Domain

Type IIL Restriction-Modification Enzyme MmeI is a large enzyme that integrates DNA recognition and methyltransferase and endonuclease activities within the same polypeptide . This entry includes DNA methyltransferase A, a MmeI homologue that lacks endonuclease activity . MmeI is composed of five domains. An N-terminal endonuclease domain (residues 1-155), connects to a DNA-methyltransferase domain (MTase, residues 301-320) via a multi-helical spacer (residues 156-300). These are followed by the target recognition domain (TRD, residues 621-825), and a final C-terminal helical bundle (residues 826-919) . The DNA is embedded between the TRD and the MTase domain. The TRD makes contacts to the DNA bases primarily in the major groove, while the MTase domain makes several contacts to the DNA in the minor groove . This domain corresponds to the C-terminal region.
MmeI-like, helicase spacer domain (MmeI_hel)
Type: Domain

Type IIL Restriction-Modification Enzyme MmeI is a large enzyme that integrates DNA recognition and methyltransferase and endonuclease activities within the same polypeptide . This entry also includes DNA methyltransferase A, a MmeI homologue that lacks endonuclease activity . MmeI is composed of five domains. An N-terminal endonuclease domain (residues 1-155), connects to a DNA-methyltransferase domain (MTase, residues 301-320) via a multi-helical spacer (residues 156-300). These are followed by the target recognition domain (TRD, residues 621-825), and a final C-terminal helical bundle (residues 826-919) . The endonuclease cuts the two DNA strands at one site simultaneously with enzyme bound at two sites interacting to accomplish the cleavage . This domain corresponds to the multi-helical spacer. It is thought to play a key role in positioning the endonuclease cleavage domain correctly.
MmeI-like, target recognition domain (MmeI_TRD)
Type: Domain

Type IIL Restriction-Modification Enzyme MmeI is a large enzyme that integrates DNA recognition and methyltransferase and endonuclease activities within the same polypeptide . This entry includes DNA methyltransferase A, a MmeI homologue that lacks endonuclease activity . MmeI is composed of five domains. An N-terminal endonuclease domain (residues 1-155), connects to a DNA-methyltransferase domain (MTase, residues 301-320) via a multi-helical spacer (residues 156-300). These are followed by the target recognition domain (TRD, residues 621-825), and a final C-terminal helical bundle (residues 826-919) . The DNA is embedded between the TRD and the MTase domain. The TRD makes contacts to the DNA bases primarily in the major groove, while the MTase domain makes several contacts to the DNA in the minor groove . This domain corresponds to the TRD. It consists of two α/β subdomains.
PD-(D/E)XK nuclease domain (PDDEXK_11)
Type: Domain

This domain is found in many hypothetical bacterial proteins. It has been identified as a member of the PD-(D/E)XK nuclease superfamily.
BLOC-2 complex member HPS6, C-terminal domain (HPS6_C)
Type: Domain

This entry represents the C-terminal α-solenoid domain of the HPS6 protein.

This entry includes BLOC-2 complex, Hps6 subunit, which may regulate the synthesis and function of lysosomes and of highly specialized organelles . It acts as cargo adapter for the dynein-dynactin motor complex to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Hsp6 facilitates retrograde lysosomal trafficking by linking the motor complex to lysosomes, and perinuclear positioning of lysosomes is crucial for the delivery of endocytic cargos to lysosomes, for lysosome maturation and function .
BLOC-2 complex member HPS6, N-terminal domain (HPS6_N)
Type: Domain

This entry represents the N-terminal β-propeller domain of the HPS6 protein.

This entry includes BLOC-2 complex, Hps6 subunit, which may regulate the synthesis and function of lysosomes and of highly specialized organelles . It acts as cargo adapter for the dynein-dynactin motor complex to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Hsp6 facilitates retrograde lysosomal trafficking by linking the motor complex to lysosomes, and perinuclear positioning of lysosomes is crucial for the delivery of endocytic cargos to lysosomes, for lysosome maturation and function .