SII-SWORD/CoKE huggingface dataset:
PML, C-terminal domain (PML_C)
Type: Domain

This domain is found at the C-terminal in human and mice Protein PML and its orthologues in animals.

TRIM19, also known as PML, acts in association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, such as tumour suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defence mechanisms. It acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. PML exhibits antiviral activity as it stimulates the SUMOylation of a viral protein, which is supposed to serve as a cellular mechanism to compromise specific functions of the viral effector IE1p72 .
POGZ/Z280C-D-like, double Zinc finger (Znf_POGZ/Z280C-D-like)
Type: Domain

This zinc finger domain is found in several zinc-finger proteins such as Zinc finger protein 280C and 280D as well as protein Pogo transposable element with ZNF domain (POGZ) find in eukaryotes. This domain contains two consecutive zinc fingers that are predicted to adopt structures similar to the classical C2H2 zinc fingers.

280C and 280D are probably involved in transcriptional regulation. POGZ plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. It is an essential protein that links HP1alpha dissociation with Aurora B kinase activation during mitosis . POGZ also promotes the repair of DNA double-strand breaks through the homologous recombination pathway .
Poor homologous synapsis 1, PH domain (PH_PHS1)
Type: Domain

This entry represents a pleckstrin homology (PH) domain found in Poor Homologous Synapsis from Arabidopsis thaliana (PHS1) and similar plant proteins.

PHS1 is required for accurate chromosome segregation in meiosis and for pairing to occur between homologous chromosomes. It acts in early recombination steps and ensures pairing fidelity and proper repair of meiotic DNA double-strand-breaks .
POT1A/B-like, OB fold domain (POT1A/B-like_OB)
Type: Domain

This domain is found towards the C-terminal end of Protection of telomeres protein 1a/b from Arabidopsis thaliana (POT1A) an similar proteins mainly found in plants. This domain is predicted to adopt an OB fold.

POT1A is a component of the telomerase ribonucleoprotein complex that is essential for the positive regulation of telomere length . POT1B negatively regulates telomerase activity and participates in chromosome end protection .
Ketohexokinase, prokaryotic (Khk_prokaryotic)
Type: Family

This prokaryotic protein family includes Ketohexokinase from Haloferax volcanii, which catalyses the ATP-dependent phosphorylation of the ketose sugar fructose to fructose-1-phosphate .
Probable histone-arginine methyltransferase CARM1-like, N-terminal PH domain (CARM1-like_PH)
Type: Domain

This entry represents the N-terminal PH domain found in Probable histone-arginine methyltransferase CARM1 from Oryza sativa, Arabidopsis thaliana and similar plant proteins. The domain is found N-terminal to the methyltransferase catalytic domain

and the PRMT C-terminal domain

. These enzymes are involved in histone arginine methylation, an important epigenetic modification.
PUB 12/19-like, N-terminal domain (PUB12-19-like_N)
Type: Domain

This domain is found at the N-terminal end of U-box domain-containing protein 12-19 from Arabidopsis thaliana (PUB12-19) and similar plant E3 ubiquitin ligases. This domain is usually found associated with

and

and is predicted to show an all-α configuration.

The U-box domain-containing proteins function as E3 ubiquitin ligases. These proteins play a crucial role in the ubiquitination process, which is essential for protein degradation, signal transduction, and various cellular processes. The U-box domain is a type of E3 ligase that facilitates the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to specific substrate proteins, marking them for degradation by the proteasome. This activity is vital for maintaining protein homeostasis and regulating numerous cellular pathways .
Telomere ends associated, alpha-helical domain (Tea_helical)
Type: Domain

This entry represents a small domain that is present four times in Protein telomere ends associated (Tea) from Drosophila and related fly sequences. This domain may adopt an α-helical fold.

Tea protects telomeres from fusion and it likely functions as a component of the MTV complex along with moi and ver. The complex binds single-stranded DNA in a sequence-independent manner and can protect it from DNA degradation .
Telomere repeat-binding protein 1-6-like, ubiquitin-like domain (TPR1-6-like_ubiquitin)
Type: Domain

This domain is found in Telomere repeat-binding protein 1-6 from Arabidopsis thaliana (TPR1-6) and similar plant proteins. This domain is predicted to adopt a ubiquitin-like fold.

AtTRP1 binds specifically to the plant telomeric double-stranded DNA sequences 5'-GGTTTAG-3' . It interacts with the ethylene receptor ERS1 and modulates development in Arabidopsis . AtTRP4, also known as AtTBP1 (AT5G13820), is required for telomere length homeostasis and its Myb-extension domain stabilises plant telomeric DNA binding .
Temptin, Cys/Cys disulfide domain (S-S_Temptin)
Type: Domain

This domain is found in Temptin and similar proteins in eukaryotes and bacteria. This domain contains two highly conserved cysteines that are predicted to form a disulphide bond. It is also enriched with conserved acidic residues.

Temptin is a component of the complex of water-borne protein pheromones that stimulates attraction and mating behaviour. It modulates pheromone signalling by direct binding to attractin .
Teneurin 1-4-like, FN-plug domain (FN-plug_TEN1-4)
Type: Domain

This entry represents the FN-plug domain found near the central region of Teneurins 1 to 4. This domain forms numerous hydrogen-bonding and hydrophobic interactions with the YD-shell interior .

Teneurins are a family of phylogenetically conserved transmembrane glycoproteins expressed during pattern formation and morphogenesis . Originally discovered as ten-m and ten-a in Drosophila melanogaster, the teneurin family is conserved from Caenorhabditis elegans (ten-1) to vertebrates, in which four paralogs exist (teneurin-1 to -4 or odz-1 to -4). Their distinct domain architecture is highly conserved between invertebrate and vertebrate teneurins, particularly in the extracellular part. The intracellular domains of Ten-a, Ten-m/Odz and C. elegans Ten-1 are significantly different, both in size and structure, from the comparable domains of vertebrate teneurins, but the extracellular domains of all of these proteins are remarkably similar.

The large C-terminal extracellular domain consists of eight EGF-like repeats (see

), a region of conserved cysteines and unique YD-repeats. The N-terminal intracellular domain of vertebrate teneurins contains two EF-hand-like calcium-binding motifs and two polyproline regions involved in protein-protein interactions, followed by a single-span transmembrane domain. The intracellular domain is linked to the cytoskeleton through its interaction with the adaptor protein CAP/ponsin and can be cleaved near (or possibly in) the transmembrane domain and transported to the nucleus , giving teneurins the potential to act as transcription factors

,

]. There is considerable divergence between intracellular domains of invertebrate and vertebrate teneurins as well as between different invertebrate proteins .

Teneurin proteins are involved in the development and function of the nervous system . They are ancient cell-cell adhesion receptors that play a vital role in establishing precise connectivity within the nervous system, including the formation of topographic projections, dendrite morphogenesis, and axon targeting . These proteins mediate both homophilic and heterophilic cell-cell adhesion, which is essential for synapse assembly and the formation of neural circuits. They also act as ligands for specific receptors, contributing to axon guidance and intracellular signal transduction. Additionally, certain members are implicated in gene transcription regulation, cytoskeleton reorganisation, and neuroplasticity. Teneurins may also contribute to the differentiation of specific cell types, and play roles in stress response and neuroprotection. Their functions are fundamental to neural development and the establishment of proper nervous system connectivity .
Teneurin-1-4-like, galactose-binding domain-like (Teneurin1-4_GBD)
Type: Domain

This galactose-binding domain (GBD) is found in Teneurin-1-4 from Mus musculus (Ten1-4) and its orthologues in animal proteins such as Teneurin a and m in Drosophila melanogaster.

Teneurins are a family of phylogenetically conserved transmembrane glycoproteins expressed during pattern formation and morphogenesis . Originally discovered as ten-m and ten-a in Drosophila melanogaster, the teneurin family is conserved from Caenorhabditis elegans (ten-1) to vertebrates, in which four paralogs exist (teneurin-1 to -4 or odz-1 to -4). Their distinct domain architecture is highly conserved between invertebrate and vertebrate teneurins, particularly in the extracellular part. The intracellular domains of Ten-a, Ten-m/Odz and C. elegans Ten-1 are significantly different, both in size and structure, from the comparable domains of vertebrate teneurins, but the extracellular domains of all of these proteins are remarkably similar.

The large C-terminal extracellular domain consists of eight EGF-like repeats (see

), a region of conserved cysteines and unique YD-repeats. The N-terminal intracellular domain of vertebrate teneurins contains two EF-hand-like calcium-binding motifs and two polyproline regions involved in protein-protein interactions, followed by a single-span transmembrane domain. The intracellular domain is linked to the cytoskeleton through its interaction with the adaptor protein CAP/ponsin and can be cleaved near (or possibly in) the transmembrane domain and transported to the nucleus , giving teneurins the potential to act as transcription factors

,

]. There is considerable divergence between intracellular domains of invertebrate and vertebrate teneurins as well as between different invertebrate proteins .

Teneurin proteins are involved in the development and function of the nervous system . They are ancient cell-cell adhesion receptors that play a vital role in establishing precise connectivity within the nervous system, including the formation of topographic projections, dendrite morphogenesis, and axon targeting . These proteins mediate both homophilic and heterophilic cell-cell adhesion, which is essential for synapse assembly and the formation of neural circuits. They also act as ligands for specific receptors, contributing to axon guidance and intracellular signal transduction. Additionally, certain members are implicated in gene transcription regulation, cytoskeleton reorganisation, and neuroplasticity. Teneurins may also contribute to the differentiation of specific cell types, and play roles in stress response and neuroprotection. Their functions are fundamental to neural development and the establishment of proper nervous system connectivity .
Terminase small subunit, actinomycetes phage-type (Terminase_6)
Type: Domain

The small subunit of terminase, a DNA packaging enzyme of bacteriophages, plays a role in binding and cutting the phage DNA during packaging into the capsid. This entry represents diverse small subunits from a wide range of actinobacteriophages and some Bacillota phages. The domain is often found at the N-terminal of proteins, followed by a disordered or low-complexity region at the C-terminal. In some larger proteins, additional C-terminal domains may also be present.
Tubulin polyglutamylase complex subunit 1-like, C-terminal (TPGS1_C)
Type: Domain

This is the C-terminal domain of human TPGS1 and similar animal proteins. This domain is predicted to adopt a mainly α-helical configuration.

Tubulin polyglutamylase complex subunit 1-like TPGS1 (also known as PGs1) is part of the tubulin polyglutamylase complex, which plays a role in post-translational addition of glutamate residues to C-terminal tubulin tails . It is required for sperm axoneme assembly and normal animal behaviour .
Tumor necrosis factor receptor superfamily member 11B, Death domain (Death_TNF11B)
Type: Domain

This entry represents the Death domains found in two tandem copies at the C-terminal of human Tumor Necrosis Factor Receptor Superfamily Member 11B (TNF11B, also known as osteoprotegerin, OPG) and similar proteins from vertebrates. Death domains typically form an antiparallel α-helical bundle with 6-7 helices arranged in a conserved topology . In TNFRSF11B, these domains mediate homodimerisation, which is essential for ligand binding and inhibition of osteoclastogenesis. .

The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins. Family members are defined based on similarity in their extracellular domain -a region that contains many cysteine residues arranged in a specific repetitive pattern . The cysteines allow formation of an extended rod-like structure, responsible for ligand binding .

Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences . Activation of TNFRs can therefore induce a range of disparate effects, including cell proliferation, differentiation, survival, or apoptotic cell death, depending upon the receptor involved .

TNFRs are widely distributed and play important roles in many crucial biological processes, such as lymphoid and neuronal development, innate and adaptive immunity, and maintenance of cellular homeostasis . Drugs that manipulate their signalling have potential roles in the prevention and treatment of many diseases, such as viral infections, coronary heart disease, transplant rejection, and immune disease .

TNF receptors 11A and 11B mediate the effects of receptor activator for NF-kappa-B ligand (RANKL), an essential osteoclast regulatory factor. The receptors have opposing effects -activation of TNF receptor 11A by RANKL promotes osteoclast differentiation , while TNF receptor 11B acts as a soluble decoy receptor for the ligand, thus inhibiting differentiation .

TNF receptor 11B (also known as osteoprotegerin (OPG)) is a secreted protein that contains two death domains within its C-terminal region. Mutations in the TNF receptor 11B gene are associated with the autosomal recessive osteopathy juvenile Paget disease . The receptor may also be involved in vascular calcification, and high expression levels in serum are a risk factor for the progression of atherosclerosis and the onset of cardiovascular disease .
ZNF598/HEL2, PAH domain (PAH_ZNF598/HEL2)
Type: Domain

This PAH domain is found in the human E3 ubiquitin-protein ligase ZNF598, yeast E3 ubiquitin-protein ligase HEL2 and related eukaryotic proteins.

ZNF598 plays a key role in the ribosome quality control (RQC), a pathway that takes place when the ribosome has stalled during translation, leading to degradation of nascent peptide chains. ZNF598 is activated when ribosomes are stalled following translation of prematurely polyadenylated mRNAs . Independently of its role in RQC, this protein may also act as a negative regulator of interferon-stimulated gene expression . ZNF598 is associates with eukaryotic initiation factor 4E (eIF4E) homologous protein from mammalian (m4EHP) through binding to Grb10-interacting GYF protein 2 (GIGYF2). The m4EHP-GIGYF2 complex functions as a translational repressor and is essential for normal embryonic development of mammalian .

HEL2 in addition to its role in the ribosome quality control, also acts as an activator of the No-Go decay (NGD) pathway by mediating polyubiquitination of monoubiquitinated RPS3/uS3 and RPS7/es7. RPS3/uS3 and RPS7/es7 are first monoubiquitinated by MAG2 and MOT2/NOT4, respectively, and HEL2 mediates formation of 'Lys-63'-linked polyubiquitin chains on monoubiquitin, leading to activation of the NGD pathway in a CUE2-mediated endonucleolytic cleavage . Hel2 is involved ubiquitination and degradation of excess histones .
Tsg, N-terminal (Tsg_N)
Type: Domain

This entry represents the N-terminal helical domain of Tsg. This domain forms a compact bundle of three α-helices stabilised by 7 disulphide bonds. This unique fold lacks homology to other known protein structures. This domain occupies the BMP type 1 receptor binding site on BMPs .

Twisted gastrulation (Tsg) was identified in Drosophila melanogaster as being required to specify the dorsal-most structures in the embryo, for example, the amnioserosa. Biochemical experiments have revealed three key properties of Tsg:

It can synergistically inhibit Dpp/BMP action in both D. melanogaster and vertebrates by forming a tripartite complex between itself, SOG/chordin and a BMP ligand;

Tsg seems to enhance the Tld/BMP-1-mediated cleavage rate of SOG/chordin and may change the preference of site utilisation;

Tsg can promote the dissociation of chordin cysteine-rich-containing fragments from the ligand to inhibit BMP signalling .
Zona pellucida sperm-binding protein 2, third Ig-like domain (Ig_ZP2_3rd)
Type: Domain

This entry represents the third Ig-like domain at the N-terminal in Zona pellucida sperm-binding protein 2 (ZP2) from mouse and similar proteins from vertebrates .

ZP2 is a component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding and induction of the acrosome reaction and prevents post-fertilisation polyspermy .
Zona pellucida sperm-binding protein 2, first Ig-like domain (Ig_ZP2_1st)
Type: Domain

This entry represents the first Ig-like domain at the N-terminal in Zona pellucida sperm-binding protein 2 (ZP2) from mouse and similar proteins from vertebrates .

ZP2 is a component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding and induction of the acrosome reaction and prevents post-fertilisation polyspermy .
Zona pellucida sperm-binding protein 2, second Ig-like domain (Ig_ZP2_2nd)
Type: Domain

This entry represents the second Ig-like domain at the N-terminal in Zona pellucida sperm-binding protein 2 (ZP2) from mouse and similar proteins from vertebrates .

ZP2 is a component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding and induction of the acrosome reaction and prevents post-fertilisation polyspermy .
TXNDC16, N-terminal (TXNDC16_N)
Type: Domain

This entry represents the N-terminal domain of TXNDC16. This domain adopts a thioredoxin-like fold.

TXNDC genes are members of the thioredoxin superfamily and were shown to play a role in redox homeostasis, protein folding, electron transfer, and also acting as cellular adapters. However, the function of TXDNC16 is still not clear. They have been identified as a meningioma-associated antigen .
WalK sensor protein kinase, Chache domain (Cache_WalK)
Type: Domain

This entry represents the Cache domain found in the sensor protein kinase WalK (or YycG) from bacteria, mainly from firmicutes. This domain is extracellular and is involved in WalK dimerisation necessary for protein function .

The WalK protein, alongside its response regulator WalR, is a member of the two-component regulatory system WalK/WalR, involved in the regulation of the ftsAZ operon, the yocH, ykvT, cwlO, lytE, ydjM, yjeA, yoeB genes and the tagAB and tagDEF operons. It is essential for cell wall metabolism, virulence regulation, and biofilm production, among many other cellular processes .
W02B3.4-like, N-terminal domain (W02B3_4_N)
Type: Domain

This domain is found at the N-terminal end of the uncharacterised protein W02B3.4 from Caenorhabditis elegans and similar animal proteins. This domain is predicted to adopt an α-β fold.
TXNDC16, second thioredoxin-like domain (TXNDC16_2nd)
Type: Domain

This entry represents the second thioredoxin-like domain of TXNDC16. The function of this domain is unknown. It contains an α+β three layer fold.

TXNDC genes are members of the thioredoxin superfamily and were shown to play a role in redox homeostasis, protein folding, electron transfer, and also acting as cellular adapters. However, the function of TXDNC16 is still not clear. They have been identified as a meningioma-associated antigen .
WD repeat-containing protein 75, second beta-propeller (Beta-prop_WDR75_2nd)
Type: Domain

This entry represents the second β-propeller found in WD repeat-containing protein 75 (WDR75) from animals. The function of this domain is unknown. This domain is also found in U3 small nucleolar RNA-associated protein 13 and 17 (UTP13 and UTP17), which are WDR75 orthologs from yeast.

WDR75 is an essential factor in the early stages of ribosome assembly. It is a component of the small subunit (SSU) processome, which is the first precursor of the eukaryotic small ribosomal subunit . WDR75 has a crucial positive role in ribosome biogenesis and its malfunction activates p53, leading to cellular senescence . WDR75 is required for pre-rRNA transcription, supporting the maintenance of physiological levels of RPA194, a key subunit of RNA polymerase I. Its depletion leads to reduced rRNA synthesis and destabilization of RPA194, but not RPA135, another RNA Pol I component
TXNDC16, third thioredoxin-like domain (TXNDC16_3rd)
Type: Domain

This entry represents the third thioredoxin-like domain of TXNDC16. The function of this domain is unknown. It contains a α+β three layer fold. This domain is found next to the thioredoxin domain

.

TXNDC genes are members of the thioredoxin superfamily and were shown to play a role in redox homeostasis, protein folding, electron transfer, and also acting as cellular adapters. However, the function of TXDNC16 is still not clear. They have been identified as a meningioma-associated antigen .
WDHD1, first WD40 domain (WD40_WDHD1_1st)
Type: Domain

This entry represents the WD40 domain found at the N-terminal of WDHD1 (also known as AND-1), Protein ENHANCER OF LHP1 1 and Minichromosome loss protein 1.

WDHD1 is an adaptor molecule crucial for DNA replication . It is a core replisome component that acts as a replication initiation factor. It binds directly to the CMG complex and functions as a hub to recruit additional proteins to the replication fork .
U exon-like (U_exon-like)
Type: Family

This protein family includes U exon protein from Fowl aviadenovirus 4 and similar viral short sequences .
PUB 62/63, C-terminal (PUB62-63_C)
Type: Domain

This is a domain found at the C-terminal of Plant U-Box 62/63 (PUB62/63) from Arabidopsis thaliana and similar proteins from plants. According to structure predictions, this domain may adopt an SH3-like barrel fold.

The U-box domain-containing proteins function as E3 ubiquitin ligases. These proteins play a crucial role in the ubiquitination process, which is essential for protein degradation, signal transduction, and various cellular processes. The U-box domain is a type of E3 ligase that facilitates the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to specific substrate proteins, marking them for degradation by the proteasome. This activity is vital for maintaining protein homeostasis and regulating numerous cellular pathways .