SII-SWORD/CoKE huggingface dataset:
IML1, N-terminal double psi beta-barrel domain (IML1_double_psi_beta_barrel)
Type: Domain

This entry represents the N-terminal double psi β-barrel domain found in IML1 proteins predominantly from animals.

The IML1 protein family is involved in the regulation of the mTORC1 signaling pathway, particularly in response to amino acid availability. Members of this family are components of the GATOR1 complex, which acts as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway . When amino acids are scarce, GATOR1 increases GTP hydrolysis by Rag GTPases, converting them to their inactive GDP-bound state, thus detaching mTORC1 from the lysosomal surface and inhibiting its signaling. This action is crucial for cellular adaptation to nutrient deprivation, promoting catabolic metabolism and autophagy. Conversely, in the presence of abundant amino acids, GATOR1 is negatively regulated by GATOR2, allowing mTORC1 signaling to proceed. The IML1 family proteins interact with the nucleotide-binding pocket of Rag GTPases, coordinating their nucleotide loading states, but do not possess GAP activity themselves.
DSP-PTPase phosphatase fused to NAD+ Kinase (PTP-NADK)
Type: Domain

This domain is found in NAD kinase 2 from Arabidopsis thaliana, related sequences from plants and uncharacterised sequences from bacteria. While the land plant version of this DSP-PTPase domain is likely inactive as the catalytic cysteine is replaced by serine or threonine, the rest are predicted to be active. Keeping with the proposed sugar phosphatase activity in related members, these domains could potentially function as phosphatases converting NADP+ to NAD+ .
Sperm-associated microtubule inner protein 5 domain (SPMIP5_dom)
Type: Domain

This entry represents a domain found in Sperm-associated microtubule inner protein 5 (SPMIP5 also known as C10orf82) and its homologues. SPMIP5 is a mammalian sperm-specific microtubule inner protein that probably plays a role in the stabilisation of the axonemal microtubules . This domain binds to tubulin.
Ant venom allergen Sol i 2/4 (Sol_i_2/4)
Type: Domain

Sol i 2, one of four known potent allergens from the venom of red imported fire ant, is a powerful trigger of anaphylaxis. It causes production of IgE antibody in many individuals stung by fire ants. The closest structure homologue of Sol I 2 is the odorant binding protein and pheromone binding protein LUSH of the fruit fly Drosophila (

), suggesting a possible similar biological function .
EMC2, TPR-like domain (TPR_EMC2)
Type: Domain

This entry represents a TPR-like domain from the central region of EMC2 and its homolgoues.

ER membrane protein complex subunit 2 (EMC2, also known as tetratricopeptide repeat protein 35) is a tetratricopeptide repeat-containing protein, and a component of the ER membrane protein complex (EMC), which is required for efficient folding of proteins in the endoplasmic reticulum (ER). EMC2 is a cytosolic component of the complex . Purified recombinant EMC2 formed a stable complex with either EMC8 or EMC9 .
Amylosucrase, C-terminal domain (Amylosucrase_C)
Type: Domain

This entry represents a domain found C-terminal in Amylosucrase from Neisseria polysaccharea (Ams) and similar bacterial proteins. Ams catalyses the synthesis of alpha-glucan from sucrose . This domain follows the catalytic β/α barrel domain (

). It folds into a β-sandwich with a greek-key topology .
Septum site-determining protein MinC, N-terminal domain (MinC_N_1)
Type: Domain

This entry represents the N-terminal domain of Septum site-determining protein MinC and related proteins mainly found in firmicutes. MinC is a cell division inhibitor that blocks the formation of polar Z ring septums. It consists of two domains. The N-terminal domain interacts with FtsZ and inhibits FtsZ polymerisation, while the C-terminal interacts with MinD and inhibits the bundling of FtsZ filaments .
Spartan-like, zinc binding domain (SPRTN_ZBD)
Type: Domain

This zinc binding domain (ZBD) is found in DNA-dependent metalloprotease Spartan (SPRTN) and its homologues. SPRTN cleaves DNA-protein crosslinks (DPCs) and protects cells from DPC-induced genome instability. The zinc binding domain is located in close proximity to the catalytic domain and contributes to the ssDNA specificity of SPRTN .
DNA replication complex GINS protein PSF3, N-terminal domain (PSF3_N)
Type: Domain

This entry represents the GINS/PriA/YqbF domain, which is found in the N-terminal region of the GINS complex protein PSF3 . The GINS complex is crucial for the establishment of DNA replication forks and replisome progression in eukaryotes. The crystal structure of the human GINS complex reveals a heterotetrameric assembly with a pseudo symmetrical layered structure . The complex consists of two heterodimers that create four subunit-subunit interfaces . The subunit structures of the heterodimers consist of two alternating domains, an α-helix-rich (A) domain

and a β-strand-rich (B) domain (this entry).
PRISE-like, Rossmann-fold domain (PRISE-like_Rossmann-fold)
Type: Domain

This NAD(P)-binding Rossmann-fold-like domain is found in a number of enzymes with oxidoreductase activity from eukaryotes and uncharacterised bacterial sequences . Amongst them are the PRISEs (Progesterone 5beta-reductase and/or iridoid synthase-like 1,4-enone reductases) that are involved in cardenolide and iridoid biosynthesis. This domain is also found in the short chain dehydrogenase ausT, involved in the terpenoid biosynthesis pathway .
Fe(3+) ions import ATP-binding protein FbpC, regulatory domain (FbpC_RD)
Type: Domain

This entry represents the regulatory domain (RD) of Fe(3+) ions import ATP-binding protein FbpC, the nucleotide-binding domain of the iron-uptake ABC transporter FbpABC from Neisseria gonorrhoeae. This domain adopts two OB-folds per monomer . Members of this group are mainly found in Neisseria species.
MLPTv-like, winged helix-turn-helix domain (MLPTv-like_wHTH)
Type: Domain

This entry represents a winged helix-turn-helix (wHTH) domain present in MLPTv (MarR-like protein from Thermoplasma volcanium) .
DNAJC11-like, beta-barrel domain (DNAJC11-like_beta-barrel)
Type: Domain

This entry represents a large β-barrel domain found in the central region of DNAJC11 from humans and its orthologues. DNAJC11 is a mitochondrial outer membrane protein involved in mitochondrial biogenesis and in the response to microenvironment changes and requirements. The J-domain mediates its mitochondrial localisation, while the C-terminal domain is critical for protein-protein interactions . The function of this domain is believed to be involved in protein-protein interactions. However, its exact function is unknown .

This entry also includes Chaperone protein dnaJ 13 (also known as OWL1) from Arabidopsis thaliana, involved in perception of very low light fluences .
FilE, C-terminal domain (FilE_C)
Type: Domain

This entry represents a domain found C-terminal in FilE protein. FilE is found almost exclusively in Acinetobacter, and is assigned as a putative pilus system protein from local genomic contexts that include several additional putative pilus system proteins. It is predicted to adopt a globular structure similar to galactose-binding domains.
ATP-dependent helicase HRQ1, winged helix domain (HRQ1_WHD)
Type: Domain

This domain is found in ATP-dependent helicase HRQ1 from yeast and its homologues. HRQ1 is a helicase with 3'-5' helicase activity involved in genome stability . Hrq1 is able to unwind relatively long duplex DNA up to 120-bp and is significantly stimulated by a preexisting fork structure. This domain is predicted to form a globular structure with significant similarity to Winged helix HTH domains.
Cas9, RuvC domain (Cas9_RuvC)
Type: Domain

This entry represent a RuvC endonuclease domain found in CRISPR-Cas9 from Streptococcus pyogenes and related sequences, mainly from firmicutes . This domain, and the HNH (

) domain of Cas9, are used to cleave the DNA strands complementary (target) and non-complementary (non-target) to the crRNA, respectively . This domain is related to

.
VEGFR1-3, fifth immunoglobulin-like domain (VEGFR1-3_5th)
Type: Domain

This is the fifth immunoglobulin-like domain of human Vascular endothelial growth factor receptor 1, 2 and 3 (VEGFR1-3) and similar sequences mainly found in animals.

VEGFR-1 is a cell-surface receptor for VEGFA, VEGFB and PGF. It is a tyrosine-protein kinase that plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion . VEGFR2 is a receptor for VEGFA, VEGFC or VEGFD, and plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis . VEGFR3 is a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development .
Tiam1/2, second PH-like domain (PH_Tiam1/2)
Type: Domain

This entry represents the second PH domain found in TIAM1/2 proteins from human and its orthologues from Drosophila, SIF1/2. The TIAM family proteins are guanine nucleotide exchange factors (GEFs) that modulate the activity of RHO-like GTPases, linking extracellular signals to cytoskeletal dynamics. They are involved in various cellular processes, including cell adhesion, migration, and neurite outgrowth. TIAM family members activate GTPases such as RAC1 and CDC42, which are critical for actin cytoskeleton reorganisation, lamellipodial formation, and growth cone advancement in neurons. These proteins contribute to synaptic differentiation and are implicated in the development of the cerebral cortex and eye. The TIAM family is characterised by the presence of multiple domains, including PH domains, which are essential for membrane localisation and enhancing catalytic activity, and a TSS domain necessary for Rac1 activity and induction of neurite-like structures .
VPS15-like, helical domain (VPS15-like_hel)
Type: Domain

This entry represents the central domain of VPS15 proteins, which consists of armadillo repeats . VPS15 proteins in animals are known as Phosphoinositide 3-kinase regulatory subunit 4 (Pik3r4) . Vps15 associates and regulates Vps34, also called Class III phosphoinositide 3-kinase (PI3K), which the phosphorylation of D-myo-phosphatidylinositol (PtdIns). Vps34 is the only PI3K present in yeast. It plays an important role in the regulation of protein and vesicular trafficking and sorting, signalling, and phagocytosis . This domain forms 9 helical pairs arranged as a right-handed helical solenoid .
DIS3-like exonuclease 2, C-terminal (Dis32-like_C)
Type: Domain

This domain is found at the C-terminal of DIS3-like exonuclease 2 from Schizosaccharomyces pombe (Dis32) and related proteins from Schizosaccharomyces. Dis32, also known as Dis3l2, is a 3'-5'-exoribonuclease that specifically recognises RNAs polyuridylated at their 3' end and mediates their degradation. This domain shows three antiparallel β-strands that show OB-fold characteristics .
PaaX-like, ferredoxin-like domain (PaaX-like_ferredoxin-like)
Type: Domain

This entry represents a ferredoxin-like domain in PaaX-like protein from Jannaschia sp. (

). PaaX-like is a putative transcriptional regulator. Members of this group are specific to Rhodobacterales.
Pheromone cCF10 receptor-like, TPR region (PrgX-like_TPR)
Type: Domain

This entry represents the C-terminal tetratricopeptide repeat region (TPR) of the pheromone cCF10 receptor from Enterococcus faecalis (PrgX,

), which serves as a molecular switch controlling expression of conjugation and virulence genes encoded by the conjugative plasmid pCF10. This region includes two domains: a large central dimerisation (and pheromone-binding) domain, and a C-terminal regulatory domain that is important for structural integrity .
Alpha-L-arabinofuranosidase 1, catalytic domain (ASD1_cat)
Type: Domain

This entry represents the catalytic domain of Alpha-L-arabinofuranosidase 1/2 from Arabidopsis thaliana (ASD1/2), Alpha-L-arabinofuranosidases from fungi and uncharacterised sequences from bacteria. ASD1 may be involved in the coordinated dissolution of the cell wall matrix during abscission and in the secondary cell wall formation in xylem vessels . This domain is often found associated to

.
PP4R3, EVH1-like domain (EVH1_PP4R3)
Type: Domain

The Serine/threonine-protein phosphatase 4 regulatory subunits 3 (PPP4R3) contain a conserved N-terminal Enabled/VASP Homology 1 (EVH1) domain . EVH1 domains are found in numerous proteins and bind to proline-rich sequences that adopt a left-handed PPII polyproline helix. Common to all EVH1 domains is a conserved tryptophan residue interacting with a proline residue in the ligand. This domain has been shown to bind an FXXP motif .
Cdc6, AAA+ ATPase-type lid domain (Cdc6_lid)
Type: Domain

This domain is found in ORC1-type DNA replication protein (also known as Cdc6) and related proteins found mainly in archaea. Cdc6 is a key protein involved in the pre-replication complex assembly. It contains AAA+ ATPase domain that is capped by a lid domain, represented by this entry .
VEGFR1-3, N-terminal Ig-like domain (VEGFR1-3_N_Ig-like)
Type: Domain

This entry represents the N-terminal Ig-like domain of Vascular endothelial growth factor receptor 1-3 (VEGFR1-3) from vertebrates . Members are tyrosine kinase receptors with seven Ig-like domains in its extracellular portion.
Trans-sialidase, C-terminal domain (TS_C)
Type: Domain

This domain is found C-terminal in Trans-sialidase (TS) from Trypanosoma cruzi and other similar proteins. Members of this group are specific to Trypanosoma. TS is involved in host cell invasion and parasite survival in the bloodstream. The parasite uses TS activity to sialylate its own surface molecules, allowing it to evade lysis by serum factors. This domain follows the catalytic domain and adopts a β-sandwich fold typical for Concanavalin-like lectin/glucanase superfamily. It is likely involved in binding glycan structures present on the surface of the Trypanosomes or host cells and in modulating the activity and biological function of TS .
Alpha-galactosidase, CBM13 domain (CBM13-like)
Type: Domain

This is a carbohydrate-binding module family 13 domain that is found in beta-L-Arabinopyranosidase from Streptomyces avermitilis and similar sequences

.
Armadillo-like repeats domain (Armadillo_rpt_dom)
Type: Domain

This entry represents a conserved region containing set of armadillo-like repeats found in uncharacterised plant proteins. Its function is not known.
Lmo2446-like, N-terminal (Lmo2446-like_N)
Type: Domain

This domain is found at the N-terminal end of a group of bacterial proteins, including Lmo2446 protein from Listeria monocytogenes, a functionally uncharacterised extracellular lipidated protein. Lmo2446 contains a glycoside hydrolase 31 family (GH31) catalytic domain (

) flanked by three structural β-domains. This domain folds into a carbohydrate binding module (CBM)-like β-sandwich .

This domain is found also in isomaltosyltransferase CtsY, which together with CtsZ, is involved in the conversion of alpha-1,4-glucan into a cyclic tetrasaccharide (CTS) constructed from four alpha-glucopyranosyl residues .
Negative regulator of ofd1, C-terminal (Nro1_C)
Type: Domain

This entry represents the C-terminal region of fission yeast Negative regulator of ofd1 (Nro1), whose α-helices are grouped in six helical hairpins. This protein is a positive regulator of the stability of the N-terminal transcription factor domain (Sre1N) of sre1 which is released from the membrane and enters the nucleus to activate hypoxic gene expression. It also fuctions as a direct inhibitor of ofd1, probably by inhibiting the ability of the ofd1 to accelerate Sre1N degradation in absence of oxygen .
DNA double-strand break repair protein Mre11, C-terminal Rad50-binding domain, archaea (Mre11_C_arc)
Type: Domain

Communication between Mre11 and Rad50 in the MR complex is critical for the sensing, damage signalling, and repair of DNA double-strand breaks. Mre11 protein consists of an N-terminal core domain and a C-terminal domain linked by an extended connecting loop. The C-terminal domain of Mre11 (this entry) is composed of three α-helices and binds to the C-terminal part of the Rad50 coiled-coil

.
Winged helix-turn-helix domain, proteobacterial-type (HTH_proteobacteria)
Type: Domain

This winged helix-turn-helix domain is often found in proteobacteria and some phage proteins. It is likely to be involved in DNA-binding.
Topoisomerase V, HHH domain (TopoV_HHH)
Type: Domain

This entry represents a helix-hairpin-helix (HHH) domain of topoisomerase V (Topo-V,

), the only member of a novel topoisomerase subtype. Topo-V is unique as it is a bifunctional enzyme carrying both topoisomerase and DNA repair lyase activities within the same protein . This protein contains a topoisomerase domain at the N-terminal, followed by twelve tandem helix-hairpin-helix (HhH)2 domains.
Insertion element IS150 protein InsJ-like, helix-turn-helix domain (InsJ-like_HTH)
Type: Domain

This entry represents a helix-turn-helix (HTH) domain found in Insertion element IS150 protein InsJ from Escherichia coli and similar sequences from cellular organisms, mainly bacteria. It is likely to be DNA-binding.
PSV, transcriptional regulator domain (PSV_trans_reg_dom)
Type: Domain

This domain is found in Transcriptional regulator

from Pyrobaculum spherical virus (PSV) and similar viral proteins. It shows a winged-helix configuration .
Crb2, Tudor domain, schizosaccharomyces (Crb2_Tudor_schizosaccharomyces)
Type: Domain

This entry represents a Tudor domain in the DNA repair protein Crb2 from Schizosaccharomyces pombe . Crb2 possesses tandem Tudor domains which interact with histone H4 dimethylated at Lys20 (H4-K20me2).
SOS1/NGEF-like, PH domain (SOS1_NGEF_PH)
Type: Domain

This is a PH domain found in a diverse group of animal proteins such as human Ephexin-1 (NGEF) and Son of sevenless homolog 1 (SOS1) and related RhoGEFs .
Class III superoxide reductase, N-terminal (SOR_N)
Type: Domain

This short domain is found at the N-terminal of class III superoxide reductase from Treponema pallidum (SOR,

), a small protein that catalyses the one-electron reduction of superoxide to hydrogen peroxide, having rubredoxin as their putative electron donor. It is organised into two distinct domains: an N-terminal domain that shows four β-strands and a C-terminal one that harbours the catalytic site and displays an immunoglobulin-like fold .
Argonaute, N-terminal domain, thermococcales (Ago_N_thermococcales)
Type: Domain

This domain is found at the N-terminal of Protein argonaute from Pyrococcus furiosus (Ago), a component of the RNAi effector complex (RISC). Ago is organised into four domains: N (this entry), PAZ (

), middle and PIWI (

). This domain shows a small four-stranded β-sheet, three α-helices and a β-hairpin . Members of this group are specific to thermococcales.
pPIWI_RE three-gene island, domain Z (pPIWI_RE_Z)
Type: Domain

This entry represents a poorly-understood bacterial domain observed N-terminal to DinG-type helicase, which is part of a conserved three-gene island also containing a REase domain and the pPIWI_RE module. This three gene island is predicted to form a conflict system which targets R-loop formation of invasive plasmids during plasmid replication .
Reticulophagy regulator 1, N-terminal reticulon-homology domain (RETR1_RHD)
Type: Domain

This entry represents the N-terminal reticulon-homology domain (RHD) of RETREG1/FAM134B, which shows sequence similarity to ADP-ribosylation factor-like 6 binding factor 1 (Arl6IP1 or Arl6ip-1), an ER protein that has an important role in cell conduction and material transport. This domain may function in inducing membrane curvature . Members of this group are specific to vertebrates.

Reticulophagy regulator 1 (RETREG1), also called FAM134B (family with sequence similarity 134, member B), is an endoplasmic reticulum (ER)-anchored autophagy receptor that regulates the size and shape of the ER. It regulates turnover of the ER by selective phagocytosis, mediating ER delivery into lysosomes through sequestration into autophagosomes. It promotes membrane remodelling and ER scission through its membrane bending activity, and targets the fragments into autophagosomes by interacting with ATG8 family modifier proteins such as MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2 . Loss of function of FAM134B is associated with diseases and cancer, including hereditary sensory and autonomic neuropathy type IIB (HSAN IIB), colorectal adenocarcinoma, and oesophageal squamous cell carcinoma, and other progressive neuronal degenerative diseases . FAM134B is also implicated in the suppression of viral replication during Ebola, Dengue, Zika, and West Nile viral infections .
KHDC4/BBP-like, KH-domain type I (KH_1_KHDC4/BBP-like)
Type: Domain

This entry represents an eukaryotic type I KH domain found in a group of proteins involved in pre-mRNA splicing, such as KH domain-containing BBP from fungi, KH homology domain-containing protein 4 (KHDC4, also known as BLOM7) and Splicing factor 1 from animals, animal quaking proteins such as human QKI, and homologues from plants, including RIK.

BBP/SF1 family members include the branchpoint binding proteins (BBP) from yeast and their mammalian homologue, splicing factor 1 (SF1). They are required for pre-spliceosome formation, which is the first step of pre-mRNA splicing . BBP binds the conserved RNA sequence UACUAAC, called the branchpoint motif, found near the 3' end of yeast introns . Besides its function in pre-mRNA splicing, BBP is also involved in nuclear retention of pre-mRNA . Mammalian SF1, also known as ZFM1, may act as transcription repressor .

KHDC4 interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. It binds preferentially RNA with A/C rich sequences and poly-C stretches. KHDC4 contains two type I K homology (KH) RNA-binding domains . RIK1 interacts with rough sheath2 (RS2), which is a myb domain protein required to repress knox genes during leaf development .

Human QKI is involved in various cellular processes, such as mRNA storage into stress granules, apoptosis, lipid deposition, interferon response, glial cell fate and development .

The core KH domain is accompanied by additional α-helix and β-sheet motifs at the C terminus.
Reticulophagy regulator 2, N-terminal reticulon-homology domain (RETR2_RHD)
Type: Domain

This entry represents the N-terminal reticulon-homology domain (RHD) of RETREG2/FAM134A, which shows sequence similarity to ADP-ribosylation factor-like 6 binding factor 1 (Arl6IP1 or Arl6ip-1), an endoplasmic reticulum protein that has an important role in cell conduction and material transport. The RHD may function in inducing membrane curvature . Members of this group are specific to vertebrates.

Reticulophagy regulator 2 (RETREG2), also called FAM134A (family with sequence similarity 134, member A), interacts with ATG8 family modifier proteins MAP1LC3A, MAP1LC3B, GABARAP, and GABARAPL1
Reticulophagy regulator 3, N-terminal reticulon-homology domain (RETR3_RHD)
Type: Domain

This entry represents the N-terminal reticulon-homology domain (RHD) of RETREG3/FAM134C, which shows sequence similarity to ADP-ribosylation factor-like 6 binding factor 1 (Arl6IP1 or Arl6ip-1), an endoplasmic reticulum protein that has an important role in cell conduction and material transport. The RHD may function in inducing membrane curvature . Members of this group are specific to vertebrates.

Reticulophagy regulator 3 (RETREG3), also called FAM134C (family with sequence similarity 134, member C), mediates NRF1-enhanced neurite outgrowth. It interacts with ATG8 family modifier proteins MAP1LC3A, MAP1LC3B, GABARAP, and GABARAPL1 .