SII-SWORD/CoKE huggingface dataset:
Inheritance of peroxisomes protein 1 (Inp1)
Type: Family

Inp1 is a peroxisomal membrane protein that binds Pex25p, Pex30p, and Vps1p, all of which are involved in controlling peroxisome division. The levels of Inp1p vary with the cell cycle, and Inp1 acts as a factor that retains peroxisomes in cells and controls peroxisome division . Inp1p promotes the retention of peroxisomes in mother cells and buds of budding yeast by attaching peroxisomes to as-yet-unidentified cortical structures .
UvrB, YAD/RRR-motif-containing domain (UvrB_YAD/RRR_dom)
Type: Domain

This entry represents a domain found towards the C terminus of the ultraviolet resistance protein B (UvrB). UvrB conveys mutational resistance against UV light to various different species . This domain is approximately 40 amino acids in length and contains two conserved sequence motifs: YAD and RRR.
Helix-turn-helix, conjugative transposon-like (HTH_dom_conjug_TS-like)
Type: Domain

This domain appears to be a helix-turn-helix domain, suggesting a transcriptional regulatory protein. Some proteins with this domain are annotated as conjugative transposon proteins.
Transcription factor IIIC, 90kDa subunit, N-terminal (TFIIIC_delta_N)
Type: Domain

This entry represents a domain found towards the N terminus of the 90kDa subunit of transcription factor IIIC (also known as subunit 9 in yeast ). The whole subunit is involved in RNA polymerase III-mediated transcription. It is possible that this N-terminal domain interacts with TFIIIC subunit 8 .
Vacuolar protein sorting protein 11, C-terminal (VPS11_C)
Type: Domain

This entry represents the C-terminal domain of vps11 and its orthologues in Saccharomyces cerevisiae known as E3 ubiquitin-protein ligase PEP5. It also represents RING finger protein PFE0100w found in Plasmodium falciparum, a malaria-causing parasite.

Vacuolar protein sorting protein 11 (vps11) aggregates with other Vps proteins to form the homotypic fusion and protein sorting complex (HOPS), which promotes the fusion of late endosomes and autophagosomes with lysosomes . Pep5 (also known as Vps11) was initially isolated as a protease deficient mutant and shown to be involved in protein trafficking and vacuole biogenesis pathways .
Transcription factor IIIC, putative zinc-finger (TFIIIC_Znf)
Type: Domain

This zinc-finger domain is at the very C terminus of a number of different TFIIIC subunit proteins. This domain might be involved in protein-DNA and/or protein-protein interactions .
TOBE-like domain (TOBE-like)
Type: Domain

The TOBE (transport-associated OB) domain always occurs as a dimer and it is found in ABC transporters immediately after the ATPase domain. This entry represents a TOBE-like domain, found in the C terminus of ATPase subunit CysA. CysA is part of the CysATWP ABC transporter complex, involved in sulphate/thiosulphate import .
Zinc finger, RING-H2-type (Znf_RING_H2)
Type: Domain

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This domain constitutes a conserved region found in proteins that participate in diverse functions relevant to chromosome metabolism and cell cycle control .The domain contains 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding.
Pre-mRNA-splicing factor 38, C-terminal (PRP38_C)
Type: Domain

This entry represents a hydrophilic domain found mainly at the C terminus of plant and animal pre-mRNA-splicing factor 38 proteins. The function of the domain is not known.
Meiosis regulator and mRNA stability factor 1 (Marf1)
Type: Family

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

Toxins A (TcdA) and B (TcdB) of Clostridium difficile belong to the family of clostridial glucosylating toxins. These toxins glucosylate small GTPases of Rho and Ras families, inhibiting the signalling and regulatory functions of these switch proteins. After receptor-binding, the toxins are endocytosed to reach acidic endosomal compartments from where the toxins are translocated into the cytosol .

This entry represents the pore forming domain of TcdA and TcdB. It is also found in other toxins.
TcdA/TcdB toxin, catalytic glycosyltransferase domain (TcdA/TcdB_cat)
Type: Domain

Toxins A (TcdA) and B (TcdB) of Clostridium difficile belong to the family of clostridial glucosylating toxins. These toxins glucosylate small GTPases of Rho and Ras families, inhibiting the signalling and regulatory functions of these switch proteins. After receptor-binding, the toxins are endocytosed to reach acidic endosomal compartments from where the toxins are translocated into the cytosol .

This entry represents the N-terminal glucosyltransferase domain from TcdA and TcdB. It is also found in other toxins. The GTD of TcdB has been shown to glycosylate the host's RhoA protein .
SUZ domain (SUZ)
Type: Domain

The SUZ domain is a conserved RNA-binding domain found in eukaryotes and enriched in positively charged amino acids. It was first characterised in the Caenorhabditis elegans protein SZY-20 where it has been shown to bind RNA and allow their localization to the centrosome .
TcdA/TcdB toxin, N-terminal helical domain (TcdA/TcdB_N)
Type: Domain

Toxins A (TcdA) and B (TcdB) of Clostridium difficile belong to the family of clostridial glucosylating toxins. These toxins glucosylate small GTPases of Rho and Ras families, inhibiting the signalling and regulatory functions of these switch proteins. After receptor-binding, the toxins are endocytosed to reach acidic endosomal compartments from where the toxins are translocated into the cytosol .

This entry represents a short helical bundle domain found associated with the catalytic domain of TcdA and TcdB . It is also found in some other toxins. The function of this domain is unknown, but it may be involved in substrate recognition.
Pleckstrin homology domain, Mcp5-type (PH_dom-Mcp5-type)
Type: Domain

This pleckstrin homology domain is found in eukaryotic proteins, including Mcp5, a fungal protein that anchors dynein at the cell cortex during the horsetail phase (prophase I) of meiosis. During prophase I of fission yeast all the telomeres become bundled at the spindle pole body and subsequently the nucleus undergoes a dynamic oscillation, resulting in elongated nuclear morphology known as "horsetail" nucleus. The pleckstrin homology domain is necessary for the cortical localisation of the Mcp5 protein during meiosis .
DinB-like domain (DinB-like)
Type: Domain

DinB from Bacillus subtilis and related Gram-positive bacteria is a DNA-damage-induced gene and the corresponding protein contains a four helix bundle. This fold is shared by diverse proteins .

This entry represents a DinB-like structural domain found in uncharacterised proteins and putative metal-dependent hydrolases.
Putative cellulase (Put_cellulase)
Type: Family

This entry represents a family of putative cellulase enzymes. The structure is a TIM-barrel.
2OGFeDO JBP1/TET, oxygenase domain (2OGFeDO_JBP1/TET_oxygenase_dom)
Type: Domain

This entry represents the catalytic domain from nucleic-acid modifying members of the 2-oxoglutarate (2OG)-Fe(II)-dependent dioxygenase (2OGFeDO) superfamily . These proteins catalyse nucleic acid modifications, such as thymidine hydroxylation during base J synthesis in kinetoplastids , and the conversion of 5 methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (hmC) , or further oxidation to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) . Metazoan TET proteins contain a cysteine-rich region inserted into the core of the DSBH fold. Vertebrate TET proteins are oncogenes that are mutated in various myeloid cancers . Fungal and algal versions of this family are linked to a predicted transposase and show lineage-specific expansions .
Merozoite surface protein, C-terminal (MSP_C)
Type: Domain

Merozoite surface protein 7 (MSP7) is a protein of the malaria parasite that has been found to be associated with processed fragments from the MSP1 protein in a complex involved in red blood cell invasion .

This entry represents a C-terminal domain found in MSP7 and other Plasmodium merozoite surface proteins.
Transducer of regulated CREB activity, N-terminal (TORC_N)
Type: Domain

This entry represents the N-terminal domain of TORC proteins. TORC (transducer of regulated CREB activity) is a protein family of coactivators that enhances the activity of CRE-dependent transcription via a phosphorylation-independent interaction with the bZIP DNA binding/dimerisation domain of CREB (cAMP Response Element-Binding) . The proteins display a highly conserved predicted N-terminal coiled-coil domain and an invariant sequence matching a protein kinase A (PKA) phosphorylation consensus sequence (RKXS) . The coiled-coil structure interacts with the bZIP domain of CREB . This interaction may occur via ionic bonds because it is disrupted under high-salt conditions . In addition to CREB-binding, the N-terminal domain plays a role in the tetramer formation of TORCs , but the physiological function of the multimeric complex has not been clarified yet.
Transducer of regulated CREB activity, middle domain (TORC_M)
Type: Domain

This domain represents the region between the N and C terminus of TORC proteins. TORC (transducer of regulated CREB activity) is a protein family of coactivators that enhances the activity of CRE-dependent transcription via a phosphorylation-independent interaction with the bZIP DNA binding/dimerisation domain of CREB (cAMP Response Element-Binding) . Although the C- and N- terminal domains of the TORC proteins have been well characterised , no functional role has yet been assigned to the central region.
Transducer of regulated CREB activity, C-terminal (TORC_C)
Type: Domain

This entry represents the C-terminal domain of TORC proteins. TORC (transducer of regulated CREB activity) is a protein family of coactivators that enhances the activity of CRE-dependent transcription via a phosphorylation-independent interaction with the bZIP DNA binding/dimerisation domain of CREB (cAMP Response Element-Binding) . The C-terminal domain is negatively charged, resembling transcription activation domains, and experimental studies indicate that it may play a role in activation of transcription .
CREB-regulated transcription coactivator (TORC)
Type: Family

CREB-regulated transcription coactivator (also known as TORC, transducer of regulated CREB activity) enhances the activity of CRE-dependent transcription via a phosphorylation-independent interaction with the bZIP (basic region/leucine zipper) DNA binding/dimerisation domain of CREB (cAMP Response Element-Binding . The TORC family includes TORC1, TORC2 and TORC3; all three activate CREB-dependent transcription but are differentially expressed and regulated by upstream signals such as AMP-activated protein kinase and LKB1 .
EcsC protein (EcsC)
Type: Family

Proteins in this family are related to EcsC from Bacillus subtilis. This protein is found in an operon with EcsA and EcsB which are components of an ABC transport system . The function of this protein is unknown.
Malectin-like domain (Malectin-like_Carb-bd_dom)
Type: Domain

Malectin is a membrane-anchored protein of the endoplasmic reticulum that recognises and binds Glc2-N-glycan . The domain is found on a number of plant receptor kinases and is distantly related to malectin domains.
Anaphase-promoting complex subunit 4 (APC4)
Type: Family

The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome .

This family represents the anaphase-promoting complex subunit 4 (APC4). This entry also includes APC4 homologue, EMB-30, from Caenorhabditis elegans .
Anaphase-promoting complex subunit 4, long domain (APC4_long_dom)
Type: Domain

Apc4 is one of the larger of the subunits of the anaphase-promoting complex (APC) 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 . Results in Caenorhabditis elegans show that the primary essential role of the spindle assembly checkpoint is not in the chromosome segregation process itself but rather in delaying anaphase onset until all chromosomes are properly attached to the spindle. The APC is likely to be required for all metaphase-to-anaphase transitions in a multicellular organism .

This entry represents the long domain downstream of the WD40 repeat/s that are present on the Apc4 subunits.
Cytochrome c oxidase subunit III (Cyt_c/ubiquinol_Oxase_su3)
Type: Family

Cytochrome c oxidase (

) is the terminal enzyme of the respiratory chain of mitochondria and many aerobic bacteria. It catalyses the transfer of electrons from reduced cytochrome c to molecular oxygen:

4 cytochrome c
+2
+ 4 H
+
+ O
2
--> 4 cytochrome c
+3
+ 2 H
2
O

This reaction is coupled to the pumping of four additional protons across the mitochondrial or bacterial membrane .

Cytochrome c oxidase is an oligomeric enzymatic complex that is located in the mitochondrial inner membrane of eukaryotes and in the plasma membrane of aerobic prokaryotes. The core structure of prokaryotic and eukaryotic cytochrome c oxidase contains three common subunits, I, II and III. In prokaryotes, subunits I and III can be fused and a fourth subunit is sometimes found, whereas in eukaryotes there are a variable number of additional small polypeptidic subunits . The functional role of subunit III is not yet understood.

As the bacterial respiratory systems are branched, they have a number of distinct terminal oxidases, rather than the single cytochrome c oxidase present in the eukaryotic mitochondrial systems. Even though the cytochrome o complex oxidises quinol (ubiquinol) and does not catalyse the oxidation of reduced cytochrome c, they belong to the same haem-copper oxidase superfamily as cytochrome c oxidases. Members of this family share sequence similarities in all three core subunits: subunit I is the most conserved subunit, whereas subunit II is the least conserved .
Rho GDP-dissociation inhibitor domain superfamily (RhoGDI_dom_sf)
Type: Homologous_superfamily

The GDP dissociation inhibitor for rho proteins, rho GDI, regulates GDP/GTP exchange by inhibiting the dissociation of GDP from them. The protein contains 204 amino acids, with a calculated Mr value of 23,421. Hydropathy analysis shows it to be largely hydrophilic, with a single hydrophobic region. The protein plays an important role in the activation of the superoxide (O2-)-generating NADPH oxidase of phagocytes. This process requires the interaction of membrane-associated cytochrome b559 with 3 cytosolic components: p47-phox, p67-phox and a heterodimer of the small G-protein p21rac1 and rho GDI . The association of p21rac and GDI inhibits dissociation of GDP from p21rac, thereby maintaining it in an inactive form. The proteins are attached via a lipid tail on p21rac that binds to the hydrophobic region of GDI . Dissociation of these proteins might be mediated by the release of lipids (e.g., arachidonate and phosphatidate) from membranes through the action of phospholipases . The lipids may then compete with the lipid tail on p21rac for the hydrophobic pocket on GDI.

Two homologues of rho GDP-dissociation inhibitors have been identified in Dicytostelium: GDI1 and GDI2. They are cytosolic proteins. GDI1 has been found to play a central role in cytokinesis through the regulation of Rho family GTPases Rac1s and/or RacE .

Rho GDI in yeast has been shown to have similar properties as mammalian rho GDI .

The rhoGDI structural domain contains both a structured, immunoglobulin-like fold, and a highly flexible N terminus of 50-60 residues . The N-terminal region becomes ordered upon complex formation and contributes more than 60% to the interface area .
Thrombin inhibitor hirudin (Hirudin)
Type: Homologous_superfamily

Hirudin (MEROPS identifier I14.001) is a potent thrombin inhibitor secreted by the salivary glands of the Hirudinaria manillensis (buffalo leech) and Hirudo medicinalis (medicinal leech) . It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen. The structure of hirudin has been solved by NMR , and the structure of a recombinant hirudin-thrombin complex has been determined by X-ray crystallography to 2.3A . Hirudin consists of an N-terminal globular domain and an extended C-terminal domain. Residues 1-3 form a parallel β-strand with residues 214-217 of thrombin, the nitrogen atom of residue 1 making a hydrogen bond with the Ser195 O gamma atom of the catalytic site. The C-terminal domain makes numerous electrostatic interactions with an anion-binding exosite of thrombin, while the last five residues are in a helical loop that forms many hydrophobic contacts .
Large ribosomal subunit protein eL15 core domain superfamily (Rbsml_eL15_core_dom_sf)
Type: Homologous_superfamily

A number of eukaryotic and archaebacterial ribosomal proteins can be grouped on the basis of sequence similarities . One of these families consists of:

Mammalian eL15.

Insect eL15.

Plant eL15y/z.

Yeast eL15A/B.

Archaebacterial eL15.

These ribosomal proteins have a structure corresponding to a 3-layer (α-β-α) sandwich.
T4 endonuclease V (T4_endonuc_V)
Type: Homologous_superfamily

Pyrimidine dimer DNA glycosylases are enzymes responsible for initiating the base excision repair pathway, excising pyrimidine dimers by hydrolysis of the glycosylic bond of the 5' pyrimidine, followed by the intra-pyrimidine phosphodiester bond . One such enzyme is T4 endonuclease V, an enzyme responsible for the first step of a pyrimidine-dimer-specific excision-repair pathway . Bacteriophage T4 that are deficient in these enzymes are extremely sensitive to UV.

The crystal structure of bacteriophage T4 endonuclease V reveals an enzyme composed of a single compact domain classified as an all-alpha structure .
MAB21L/Cyclic GMP-AMP synthase-like receptor (MAB21L/cGLR)
Type: Family

This protein family includes Mab-21 and Mab-21-like (MAB21L) proteins, and the homologues cyclic GMP-AMP synthase-like receptors (cGLRs). MAB21L are putative nucleotidyltransferases required for several aspects of embryonic development including normal development of the eye . cGLRs are nucleotidyltransferases that catalyse the formation of cyclic GMP-AMP (3',2'-cGAMP) from ATP and GTP and play a key role in antiviral innate immunity . This entry also includes inositol 1,4,5-triphosphate receptor-interacting proteins, which are predicted to contain a partial Mab-21 domain .
Polycomb protein ASX/ASX-like (ASX/ASX-like)
Type: Family

Polycomb group proteins are transcriptional repressors that control processes ranging from the maintenance of cell fate decisions and stem cell pluripotency in animals to the control of flowering time in plants. Additional sex combs (Asx) is a member of the polycomb group which is required for maintenance of stable repression of homeotic genes during Drosophila development .
Tetratricopeptide repeat protein 24 (TPR_24)
Type: Family

This entry represents a family of tetratricopeptide repeat-containing proteins whose function is not currently known.
Coilin (Coilin)
Type: Family

Coilin is a nuclear phosphoprotein that serves as an assembly centre in Cajal bodies (CBs) and has a role in small nuclear ribonucleoprotein (snRNP) biogenesis, involved in the modification and assembly of nucleoplasmic snRNPs . Coilin also acts to repress polymerase I activity in response to cisplatin-induced DNA damage, which could indicate a link between the DNA damage response and the inhibition of rRNA synthesis .
Growth arrest and DNA damage-inducible protein GADD45 (GADD45)
Type: Family

The growth arrest and DNA damage GADD45 proteins, which include GADD45A, GADD45B , and GADD45G, are implicated as stress sensors that modulate the response of mammalian cells to genotoxic/physiological stress, and modulate tumor formation . GADD45 proteins interact with a number of other proteins implicated in stress responses, including PCNA, p21, Cdc2/CyclinB1, MEKK4, and p38 kinase. GADD45 stimulates DNA excision repair in vitro and inhibits the entry of cells into S phase during the cell cycle.
Uroplakin-3a (Uroplakin-3a)
Type: Family

This entry represents uroplakin-3a. Defects in uroplakin-3a are a cause of renal adysplasia, a condition in which one or both kidneys are absent at birth .

Uroplakins (UPs) are a family of proteins that associate with each other to form plaques on the apical surface of the urothelium, the pseudo-stratified epithelium lining the urinary tract from renal pelvis to the bladder outlet . UPs are classified into 3 types: UPIa and UPIb, UPII, and UPIIIa and IIIb. UPIs are tetraspanins that have four transmembrane domains separating one large and one small extracellular domain while UPII and UPIIIs are single-pass transmembrane proteins. UPIa and UPIb form specific heterodimers with UPII and UPIII, respectively, which allows them to exit the endoplasmatic rediculum. UPII/UPIa and UPIIIs/UPIb form heterotetramers and six of these tetramers form the 16nm particle, seen in the hexagonal array of the asymmetric unit membrane, which is believed to form a urinary tract barrier . Uroplakins are also believed to play a role during urinary tract morphogenesis .
DNA polymerase delta/II small subunit family (DNA_pol_delta/II_ssu)
Type: Family

This entry represents the homologous small subunits from eukaryotic DNA polymerase delta and archaeal DNA polymerase II. The function of the small subunit is not known for either enzyme.