SII-SWORD/CoKE huggingface dataset:
Oligodendrocyte transcription factor 1, basic helix-loop-helix domain (Olig1_bHLH)
Type: Domain

Oligodendrocyte transcription factor 1 (Olig1) is a basic-helix-loop-helix (bHLH) transcription factor that promotes oligodendrocyte progenitor cell commitment, differentiation, and subsequent myelination primarily in brain, but not spinal cord . Olig1 shares structure and protein sequence similarity with Olig2, however, they have non-overlapping developmental functions in patterning, neuron subtype specification and the formation of oligodendrocytes .

This entry represents the bHLH (basic Helix-Loop-Helix) domain of Olig1, which is approximately 60 amino acids long and consists of a DNA-binding basic region followed by two α-helices separated by a variable loop region (HLH). The HLH domain promotes dimerisation, allowing the formation of homo- or heterodimeric complexes between different family members. Many bHLH proteins have been shown to act as transcriptional regulators .
Oligodendrocyte transcription factor 2, basic helix-loop-helix domain (Olig2_bHLH)
Type: Domain

Oligodendrocyte transcription factor 2 (Olig2) is a basic-helix-loop-helix (bHLH) transcription factor that is involved in motoneuron and oligodendrocyte development . Olig2 overexpression has been shown to enhance OPC (oligodendrocyte precursor cell) differentiation, maturation, and migration as well as remyelination following chemical demyelination. Therefore, OLIG2 overexpression in oligodendrocyte progenitor cells has been suggested to be a possible therapeutic mechanism for enhancing myelin repair . Olig2 shares structure and protein sequence similarity with Olig1, however, they have non-overlapping developmental functions in patterning, neuron subtype specification and the formation of oligodendrocytes .

This entry represents the bHLH (basic Helix-Loop-Helix) domain of Olig2, which is approximately 60 amino acids long and consists of a DNA-binding basic region followed by two α-helices separated by a variable loop region (HLH). The HLH domain promotes dimerisation, allowing the formation of homo- or heterodimeric complexes between different family members. Many bHLH proteins have been shown to act as transcriptional regulators .
Oligodendrocyte transcription factor 3, basic helix-loop-helix domain (Olig3_bHLH)
Type: Domain

Oligodendrocyte transcription factor 3 (Olig3) is a basic-helix-loop-helix (bHLH) transcription factor that coordinatess the specification of dorsal neurons in the spinal cord . It marks the dorsal neuroepithelium of the hindbrain and is essential for the development of brainstem nuclei .

This entry represents the bHLH (basic Helix-Loop-Helix) domain of Olig3, which is approximately 60 amino acids long and consists of a DNA-binding basic region followed by two α-helices separated by a variable loop region (HLH). The HLH domain promotes dimerisation, allowing the formation of homo- or heterodimeric complexes between different family members. Many bHLH proteins have been shown to act as transcriptional regulators .
Transcription factor ATOH8, basic helix-loop-helix domain (ATOH8_bHLH)
Type: Domain

Transcription factor ATOH8 , previously known as Protein atonal homologue 8 (ATOH8, also known as Math6), is a basic helix loop helix (bHLH) transcription factor that has been implicated in development of various tissues, such as pancreas, retina and skeletal muscle, during early development . Interestingly, hepatic ATOH8 mRNA levels were up-regulated in mice chronically fed a high iron diet and down-regulated in those fed an iron-deficient diet . ATOH8 has also been found to regulate iron hormone hepcidin (HAMP) transcription and cellular pSMAD1,5,8 levels . ATOH8 can also serve as a marker in human muscle fibre regeneration .

This entry represents the bHLH (basic Helix-Loop-Helix) domain of ATOH8, which is approximately 60 amino acids long and consists of a DNA-binding basic region followed by two α-helices separated by a variable loop region (HLH). The HLH domain promotes dimerisation, allowing the formation of homo- or heterodimeric complexes between different family members. Many bHLH proteins have been shown to act as transcriptional regulators .
Transcription factor ATOH1, basic helix-loop-helix domain (ATOH1_bHLH)
Type: Domain

Transcription factor ATOH1, previously known as Protein atonal homologue 1 (ATOH1/Math1), is a basic helix-loop-helix (bHLH) transcription factor that is essential for the differentiation of hair cells (HCs), mechanotransducers that convert sound into auditory signals in the mammalian organ of Corti (OC) . It also controls cerebellar granule cells - the most abundant neurons in the mammalian brain - differentiation . ATOH1 has been found to affect the differentiation of cancer cells .

This entry represents the bHLH (basic Helix-Loop-Helix) domain of ATOH1, which is approximately 60 amino acids long and consists of a DNA-binding basic region followed by two α-helices separated by a variable loop region (HLH). The HLH domain promotes dimerisation, allowing the formation of homo- or heterodimeric complexes between different family members. Many bHLH proteins have been shown to act as transcriptional regulators .
Transcription factor ATOH7, basic helix-loop-helix (ATOH7_bHLH)
Type: Domain

The bHLH (basic Helix-Loop-Helix) proteins contain the bHLH domain that is approximately 60 amino acids long and consists of a DNA-binding basic region followed by two α-helices separated by a variable loop region (HLH). The HLH domain promotes dimerisation, allowing the formation of homo- or heterodimeric complexes between different family members. Many bHLH proteins have been shown to act as transcriptional regulators .

Transcription factor ATOH7 (previously known as Protein atonal homologue 7, Atoh7, and Math5) is a basic helix-loop-helix transcription factor that is involved in early stages of retinal neurogenesis . It is specifically expressed in the embryonic neural retina and is required for the genesis of retinal ganglion cells (RGCs) and optic nerves .

This entry represents the bHLH domain of ATOH7 and similar proteins from chordates.
TmcA/NAT10/Kre33 (TmcA/NAT10/Kre33)
Type: Family

This entry includes bacterial tRNA(Met) cytidine acetyltransferase TmcA and eukaryotic N-acetyltransferase 10 (NAT10). They consist of an RNA helicase domain and a GCN5-related N-acetyltransferase (GNAT) domain.

The bacterial tRNA(Met) cytidine acetyltransferase (TmcA) catalyses the formation of N(4)-acetylcytidine (ac4C) at the wobble position of tRNA(Met), by using acetyl-CoA as an acetyl donor and either ATP or GTP . This modification is thought to ensure precise recognition of the AUG codon by strengthening C-G base-pair interaction and also prevent misrecognition of the near cognate AUA codon . RNA cytidine acetyltransferas (NAT10) are RNA cytosine acetyltransferases with specificity toward both 18S rRNA and tRNAs and contain additional putative nuclear and nucleolar localisation signals (NLS and NoLS respectively) .
DNA photolyase class 2, conserved site (DNA_photolyase_2_CS)
Type: Conserved_site

The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals . On the basis of the primary structure, the cryptochrome/DNA photolyase family can be grouped into two classes . The first class contains cryptochromes and DNA photolyases from eubacteria, archaea, fungi, animals and plants. The second class contains DNA photolyases from prokaryotes, plants and animals.

This entry represents a number of conserved sequence regions found in the C-terminal region of the class 2 DNA photolyases.
LRR-containing bacterial E3 ligase, N-terminal (LRR_E3_ligase_N)
Type: Domain

This domain is found in the N terminus of a group of bacterium-specific E3 enzymes that function as type three secretion system (T3SS) effectors in Salmonella, Shigella, and other Gram-negative bacteria. It is approximately 50 amino acids in length. There are two completely conserved residues (Y and W) that may be functionally important. Proteins containing this domain include SspH1 from Salmonella typhimurium and IpaH9.8 from Shigella flexneri . The structure of the Shigella IpaH and Salmonella SspH1 has been solved .
Leucine-rich repeat domain superfamily (LRR_dom_sf)
Type: Homologous_superfamily

This superfamily represents a leucine-rich repeat (LRR), right-handed β-α superhelix domain, such as that found in bacterial invasion protein internalin or in the L domain from members of the epidermal growth-factor receptor (EGFR) family .

Leucine-rich repeats (LRR) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape . LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions .Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response .
Putative L,D-transpeptidase tautomerase (YkuD_2)
Type: Family

This entry represents a group of putative L,D-transpeptidase found in bacteria. It is related to

.
GTP cyclohydrolase II (GTP_cyclohydro_II)
Type: Domain

This domain is found in members of the GTP cyclohydrolase II RibA-like superfamily. Members in this family includes GTP cyclohydrolase II, riboflavin biosynthesis protein RibBA and 3,4-dihydroxy-2-butanone 4-phosphate synthase.
tRNA synthetases class I, catalytic domain (tRNA-synt_1_cat_dom)
Type: Domain

This entry represents the catalytic (Rossmann-fold) domain found in cysteinyl tRNA synthetases which is responsible for the ATP-dependent formation of the enzyme bound aminoacyl-adenylate. It contains the characteristic class I HIGH and KMSKS motifs, which are involved in ATP binding.

Cysteine-tRNA ligase (also known as cysteinyl-tRNA synthetase) (

) is an alpha monomer and belongs to class Ia . It aminoacylates the 2'-OH of the nucleotide at the 3' of the appropriate tRNA. It is highly specific despite not possessing the amino acid editing activity characteristic of many other tRNA ligases .
Sin1, N-terminal (Sin1_N)
Type: Domain

This entry represents the N-terminal domain of Sin1 (stress-activated map kinase interacting 1). Sin1 homologue from mammals, MAPKAP1, is part of the Target Of Rapamycin Complex 2 (TORC2) complex that plays an essential role in signal transduction .
SUN domain-containing protein 1, N-terminal (SUN1_N)
Type: Domain

This entry represents the N-terminal domain of animal Sun1 proteins. Sun1 is a nuclear envelope (NE) protein that interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton .
HlyD family secretion protein (HlyD_2)
Type: Family

This family is related to Haemolysin secretion protein D (HlyD) from E. coli (

), and consists of uncharacterised bacterial proteins of the Clostridia class.
Condensin complex subunit 1, C-terminal (Cnd1_C)
Type: Domain

This entry represents the conserved C-terminal domain of Cnd1. It is also found in non-SMC subunit D3 of condensin II, a second condensin complex present in vertebrates .

Condensin subunit 1 (known as Cnd1 in Schizosaccharomyces pombe (Fission yeast), and XCAP-D2 in Xenopus laevis laevis) represents one of the non-SMC subunits in the complex. This subunit is phosphorylated at several sites by Cdc2. This phosphorylation process increases the supercoiling activity of condensin .

Condensin is a multi-subunit protein complex that acts as an essential regulator of chromosome condensation . It contains both SMC (structural maintenance of chromosomes) and non-SMC subunits. Condensin plays an important role during mitosis in the compaction and resolution of chromosomes to remove and prevent catenations that would otherwise inhibit segregation. This is thought to be achieved by the introduction of positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. During interphase condensin promotes clustering of dispersed loci into subnuclear domains and inhibits associations between homologues. In meiosis, condensin has been shown to influence the number of crossover events by regulating programmed double-strand breaks. Roles in gene regulation and lymphocyte development have also been defined.
Malate dehydrogenase enzyme, N-terminal (Malate_DH)
Type: Domain

This domain is found in bacteria, and is approximately 30 amino acids in length. The domain is found in association with

,

,

. There is a conserved AAL sequence motif. There is a single completely conserved residue R that may be functionally important. Malate dehydrogenase is one of the enzymes involved in the citric acid cycle in mitochondria. It converts malate to oxaloacetate using NAD as a cofactor.
Pyruvate ferredoxin oxidoreductase beta subunit, C-terminal (PFO_beta_C)
Type: Domain

This domain is found in bacteria and archaea, and is approximately 70 amino acids in length. The domain is found in association with

. There are two completely conserved residues (A and G) that may be functionally important. Pyruvate ferredoxin oxidoreductase (PFO) is involved in carbon dioxide fixation via a reductive TCA cycle. It forms a heterodimer (alpha/beta). The beta subunit has binding motifs for Fe-S clusters and thiamine pyrophosphate.
HTH-type transcriptional regulator AraC-type, N-terminal (AraC-type_N)
Type: Domain

This domain is found in AraC-type transcriptional regulators, such as VqsM or VirS . These proteins also have a HTH-type DNA-binding domain at the C terminus (

).
ABC-2 type transporter permease protein NosY/YtrC-like (ABC2_NosY/YtrC-like)
Type: Family

This family is related to the ABC-2 membrane transporter family . Proteins in this entry include NosY from Pseudomonas whoch is required for the assembly of the copper chromophores of nitrous oxide reductase and YtrC from Bacillus subtilis, which is part of the ABC transporter complex YtrBCDEF that plays a role in acetoin utilization during stationary phase and sporulation .
TraD/TraG, TraM recognition site (TraG-D_C)
Type: Domain

This domain can be found in both TraG and TraD as well as VirD4 proteins. TraG is essential for DNA transfer in bacterial conjugation. These proteins are thought to mediate interactions between the DNA-processing (Dtr) and the mating pair formation (Mpf) systems . This domain interacts with the relaxosome component TraM via the latter's tetramerisation domain. TraD is a hexameric ring ATPase that forms the cytoplasmic face of the conjugative pore .
CDP-archaeol synthase (CarS)
Type: Family

This entry includes the CDP-archaeol synthase from archaea and a group of putative integral membrane proteins from bacteria. CDP-archaeol synthase functions in the archaeal lipid biosynthetic pathway. It catalyses the transfer of the nucleotide to its specific archaeal lipid substrate, leading to the formation of a CDP-activated precursor (CDP-archaeol) to which polar head groups are attached .
Mon2/Sec7/BIG1-like, HUS domain (Mon2/Sec7/BIG1-like_HUS)
Type: Domain

This entry represent the HUS regulatory domain found towards the N terminus in guanine nucleotide exchange factors involved Golgi transport, such as budding yeast protein Sec7, protein Mon2 and BIG1-like proteins .

Sec7 and its homologues are guanine nucleotide exchange factors (GEFs) involved in the secretory pathway . The full-length Sec7 functions proximally in the secretory pathway as a protein binding scaffold for the coat protein complexes COPII-COPI . The COPII-COPI-protein switch is necessary for maturation of the vesicular-tubular cluster, VTC, intermediate compartments for Golgi compartment biogenesis. This N-terminal domain however does not appear to be binding either of the COP or the ARF .

Mon2 is distantly related to the Arf1 guanine nucleotide exchange factors (GEFs), such as Sec7. However, it lacks the Sec7 domain that catalyses nucleotide exchange on Arf1. Instead, Mon2 acts as a scaffold to recruit the Golgi-localised pool of Dop1 .
Integral membrane protein YccS, N-terminal (YccS_N)
Type: Domain

This entry represents the N-terminal domain of uncharacterised proteins, such as YccS, with similarities to the fusaric acid resistance protein. These proteins are lodged in the inner membrane .
YtkA-like domain (YtkA-like_dom)
Type: Domain

This entry represents a domain found in protein YtkA from Bacillus subtilis. This domain can also be found in the C-terminal of the copper transport protein YcnJ. YcnJ is involved in uptake of extracellular oxidized copper under copper-limiting conditions .
Copper transport protein C/D (CopC/D)
Type: Family

This entry represents copper transport protein C and D. Copper resistance protein C (CopC) is a bacterial blue copper protein that binds 1 atom of copper per protein molecule. Along with CopA, CopC mediates copper resistance by sequestration of copper in the periplasm . CopD, together with CopC, perform copper uptake into the cytoplasm .
Integrin domain superfamily (Integrin_dom_sf)
Type: Homologous_superfamily

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton, and activate many intracellular signalling pathways . An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a VWA domain inserted within the integrin domain at the N-terminal.

Most integrins recognise relatively short peptide motifs and, in general, require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits . There are at least 18 types of alpha and 8 types of beta subunits recognised in humans . Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule . Each association of alpha and beta subunits has its binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activates or inhibits another.

This superfamily represent the C-terminal domain of integrin alpha (which can be further subdivided in the thight, calf-1 and calf-2 domains) and the central region of integrin beta known as the hybrid domain .
Squalene cyclase, C-terminal (SQ_cyclase_C)
Type: Domain

This entry represents the C-terminal domain of squalene cyclases .

Several enzymes catalyse mechanistically related reactions which involve the highly complex cyclic rearrangement of squalene or its 2,3 oxide. Squalene cyclase (SQCY) and 2,3-oxidosqualene cyclase (OSQCY) are integral membrane proteins that catalyse a cationic cyclisation cascade converting linear triterpenes to fused ring compounds . Lanosterol synthase (

) (oxidosqualene-lanosterol cyclase) catalyses the cyclisation of (S)-2,3-epoxysqualene to lanosterol, the initial precursor of cholesterol, steroid hormones and vitamin D in vertebrates and of ergosterol in fungi (gene ERG7). Cycloartenol synthase (

) (2,3-epoxysqualene-cycloartenol cyclase), is a plant enzyme that catalyses the cyclization of (S)-2,3-epoxysqualene to cycloartenol , and hopene synthase (

) (squalene-hopene cyclase), is a bacterial enzyme that catalyses the cyclisation of squalene into hopene or diplopterol, a key step in hopanoid (triterpenoid) metabolism also found in Aspergillus fumigatus as part of the gene cluster that mediates the biosynthesis fumihopaside A . These enzymes are evolutionary related proteins of about 70 to 85kDa and have an alpha 6 - alpha 6 barrel fold. Deletion of a single glycine residue of Alicyclobacillus acidocaldarius SQCY alters its substrate specificity into that of eukaryotic OSQCY . Both enzymes have a second minor domain, which forms an α-α barrel that is inserted into the major domain.
Squalene cyclase, N-terminal (SQ_cyclase_N)
Type: Domain

This entry represents the N-terminal domain of squalene cyclases .

Several enzymes catalyse mechanistically related reactions which involve the highly complex cyclic rearrangement of squalene or its 2,3 oxide. Squalene cyclase (SQCY) and 2,3-oxidosqualene cyclase (OSQCY) are integral membrane proteins that catalyse a cationic cyclisation cascade converting linear triterpenes to fused ring compounds . Lanosterol synthase (

) (oxidosqualene-lanosterol cyclase) catalyses the cyclisation of (S)-2,3-epoxysqualene to lanosterol, the initial precursor of cholesterol, steroid hormones and vitamin D in vertebrates and of ergosterol in fungi (gene ERG7). Cycloartenol synthase (

) (2,3-epoxysqualene-cycloartenol cyclase), is a plant enzyme that catalyses the cyclization of (S)-2,3-epoxysqualene to cycloartenol , and hopene synthase (

) (squalene-hopene cyclase), is a bacterial enzyme that catalyses the cyclisation of squalene into hopene or diplopterol, a key step in hopanoid (triterpenoid) metabolism also found in Aspergillus fumigatus as part of the gene cluster that mediates the biosynthesis fumihopaside A . These enzymes are evolutionary related proteins of about 70 to 85kDa and have an alpha 6 - alpha 6 barrel fold. Deletion of a single glycine residue of Alicyclobacillus acidocaldarius SQCY alters its substrate specificity into that of eukaryotic OSQCY . Both enzymes have a second minor domain, which forms an α-α barrel that is inserted into the major domain.
Protein SirB1, N-terminal (SirB1_N)
Type: Domain

This domain can be found in the N terminus of the bacterial SirB1 protein. It can also be found in the mammalian F-box only protein 21 (FBXO21).
Izumo protein, immunoglobulin domain (Izumo-Ig)
Type: Domain

This is the immunoglobulin domain on Izumo proteins from higher eukaryotes. Izumo is a typical type I membrane glycoprotein with one immunoglobulin-like domain and a putative N-glycoside link motif - glycosylation site. The full-length human IZUMO1 protein is a molecule with a single immunoglobulin (Ig) domain. It is thought that Izumo proteins bind to putative Izumo receptors on the oocyte. Izumo is not detectable on the surface of fresh sperm but becomes exposed only after an exocytotic process, the acrosome reaction, has occurred. Studies have shown that knock-out mice (Izumo-/- males) were sterile despite normal mating behaviour and ejaculation, indicating the importance of the protein in fertilisation . There are cysteine residues thought to form a disulphide bridge. Izumo is a typical type I membrane glycoprotein with one immunoglobulin-like domain and a putative N-glycoside link motif (Asn 204) . There is a conserved GCL sequence motif. Izumo expression has been found to be testis-specific .
Izumo sperm-egg fusion protein 1 (IZUMO1)
Type: Family

Izumo sperm-egg fusion protein 1 (IZUMO1) is an essential sperm cell-surface protein required for fertilisation by acting as a ligand for IZUMO1R/JUNO receptor on eggs . It is a member of an immunoglobulin superfamily and possesses a well-conserved putative N-glycosylation site. However, glycosylation is not essential for the function of IZUMO, but has a role in protecting it from fragmentation in cauda epididymis .