SII-SWORD/CoKE huggingface dataset:
Edg1, TPR repeats region (TPR_Edg1)
Type: Domain

This entry represents a region of tetratricopeptide-like repeats found in a group of animal proteins, including protein Edg-1 from Caenorhabditis elegans, which plays a role in regulating deps-1 cluster formation in the germline .
EDRF1, N-terminal (EDRF1_N)
Type: Domain

This entry represents the N-terminal domain of Erythroid differentiation-related factor 1 (EDRF1).

EDRF1 is a transcription factor involved in erythroid differentiation and in transcriptional activation of the globin gene .
EDRF1, TPR repeats region (EDRF1_TPR)
Type: Domain

This region of tetratricopeptide-like repeats (TPR) is found at the C-terminal end of human Erythroid differentiation-related factor 1 (EDRF1) and similar eukaryotic proteins.

EDRF1 is a transcription factor involved in erythroid differentiation and in transcriptional activation of the globin gene .
EF-hand (EF-hand_15)
Type: Domain

This entry represents a domain found in a group of fungal proteins that are likely possessing phosphoinositide phospholipase C activity. This domain shares significant similarity to EF-hand domains (

,

) and is predicted to adopt a similar structure.
Leprecan-like alpha-helical domain (Leprecan_dom)
Type: Domain

This entry represents the N-terminal α-helical domain of members of the leprecan family. Members of this family include Prolyl 3-hydroxylase 1/2/3 which often have an associated C-terminal enzymatic domain . This domain is also found in the Cartilage-associated protein CRTAP and in the Endoplasmic reticulum protein SC65 .

Leprecan proteins are involved in the hydroxylation of proline residues in collagen, an essential post-translational modification for the stability and assembly of collagen fibrils. Leprecan proteins form complexes with other enzymes to hydroxylate lysine residues in collagen alpha chains, which is crucial for the proper assembly and cross-linking of collagen fibrils in various tissues, including skin, bone, tendon, aorta, and cornea. Some Leprecan proteins also exhibit growth suppressive activity and may play a role in the secretory pathway of cells. Leprecan's enzymatic activity is particularly important for the structural integrity of type I, IV, and V collagens, contributing to normal bone density and skin stability.
PLCG1, EF-hand (EF-hand_PLCG1)
Type: Domain

This entry represents an EF-hand like domain found in animal 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma proteins (PLCG). PLCG1 plays a role in actin reorganisation and cell migration . PLGC1 has a critical role in maintaining immune homeostasis . PLCG2 is a crucial enzyme in transmembrane signalling. This protein has been associated with several disorders . PLCG structure comprises several key domains: an N-terminal PH domain, EF-hand motifs, catalytic X and Y domains forming a TIM-barrel, a C2 domain, a split PH domain, two SH2 domains (N-terminal and C-terminal), and an SH3 domain .

This domain is also found in the orthologue from C.elegans 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma plc-3, which regulates basal and ovulatory sheath cell contractions .
EFCAB10, C-terminal EF-hand (EF_EFCAB10_C)
Type: Domain

This is the second and C-terminal EF hand domain of EF-hand calcium-binding domain-containing protein 10 (EFCAB10) and similar proteins. The function of this protein is not known.
LRP2, EGF-like domain (EGF_LRP2)
Type: Domain

This EGF-like domain is found in human Low-density lipoprotein receptor-related protein 2 (LRP2) and similar animal proteins.

LRP2 is a multi-ligand endocytic receptor. It acts together with CUBN to mediate endocytosis of high-density lipoproteins . In the kidney, LRP2 mediates the tubular uptake and clearance of leptin .
Egal-1, winged helix domain (WH_Egal-1)
Type: Domain

This entry represents a winged-helix domain found in three copies in the C. elegans protein Egalitarian (Egal-1). This protein functions as part of a complex with BicaudalD (BicD) and dynein light chain (Dlc-1) to recruit the dynein motor complex to specific cargoes and regulate dynein activity. It interacts with both the BicD-1 and Dlc-1 proteins. Genetic disruption of egal-1 leads to defects in hyp7 nuclear migration, similar to defects seen when disrupting bicd-1 or components of dynein. The egal-1 phenotype is enhanced when combined with a nud-2 mutant, but not enhanced by bicd-1, suggesting egal-1 and bicd-1 function in the same genetic pathway. A model is proposed where BicD-1, Egal-1 and Dlc-1 form a complex that is recruited by the nuclear envelope protein UNC-83. This complex then helps recruit the dynein motor to the nuclear envelope to regulate nuclear migration .
Mua-3/Mup-4, EGF-like domain (Mua-3/Mup-4_EGF)
Type: Domain

This entry represents an EGF-like domain found in a variety of nematode cell surface proteins, including Transmembrane cell adhesion receptor mua-3 and Transmembrane matrix receptor MUP-4 from Caenorhabditis elegans. Mua-3 is involved in cell adhesion and required for organ positioning and attachment . Mup-4 is essential for enclosure of the embryo by the hypodermis, hypodermal integrity, embryo elongation, and maintenance of hypodermal morphology in fully elongated embryos and is required for junctional attachments between hypodermis and muscle .
ELP3-like, N-terminal domain (ELP3-like_N)
Type: Domain

This domain is found N-terminal in Elongator complex protein 3 (ELP3) and related proteins. ELP3 is required for multiple modifications of tRNA. In the elongation complex, it acts as a tRNA uridine(34) acetyltransferase . It may also act as a lysine acetyltransferase by mediating acetylation of target proteins . The domain represented by this entry is predicted to fold into a globular structure consisting of two nearly orthogonal α-helical hairpins.
F-box protein At3g26010-like, beta-propeller domain (Beta-prop_At3g26010-like)
Type: Domain

This entry represents the C-terminal β-propeller domain of F-box protein At3g26010 from Arabidopsis thaliana and similar plant proteins. It has been shown that this domain has a strong specificity for ASK13 . Members of this family contain an F-box domain (

).
LRRK2, ANK repeat domain (ANK_LRRK2)
Type: Domain

This entry represents the ankyrin repeat (ANK) found towards the N-terminal end of the Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) from eukaryotes, between the ARM repeat domain (

) and the LRR domain (

). The ANK domain plays a key role in this process, as conserved leucine residues within the ANK domain are required for Rab29 binding, which mediates Golgi recruitment and kinase activation .

LRRK2 is a serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, primary ciliogenesis, autophagy, and vesicle trafficking . Mutations in LRRK2 are the most common genetic cause of Parkinson's disease . LRRK2 phosphorylates a group of Rab GTPase proteins, including Rab29.
F-box protein AT5G49610-like, beta-propeller domain (AT5G49610-like_b-prop)
Type: Domain

This entry includes a group of plant proteins containing an F-box domain at the N-terminal, followed by a β-propeller-like domain. The F-box motif is a key component of the SCF (SKP1-cullin-F-box) complex, which functions as an E3 ligase . Members of this family are likely to play a role in the ubiquitination pathway, where they are responsible for targeting specific substrates for proteasomal degradation. The F-box domain facilitates the recognition and binding of substrate proteins, while the FBD (F-box associated domain) may contribute to the specificity and functionality of the SCF complex. This entry also includes uncharacterised single domain plant proteins.
FACT complex subunit SPT16, PH-like domain (Fact-SPT16_PH)
Type: Domain

This domain is found in FACT complex subunit SPT16 and related eukaryotic proteins. It shows similarity to known PH domains.

SPT16 is a component of the FACT (facilitator of chromatin transcription) complex, a general chromatin factor that acts to reorganise nucleosomes . In budding yeasts, the N-terminal domain (NTD) of SPT16 includes a smaller N-terminal lobe (residues 1-175) and a larger C-terminal lobe (residues 176-447).
FAD synthase, middle domain (FLAD1_M)
Type: Domain

This domain is found centrally located in FAD synthase (FLAD1) and similar sequences mainly found in animals. FLAD1 catalyses the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme . In FLAD1, this domain is found C-terminal to

and N-terminal to

.

This domain, which is predicted to show an α-β configuration, is also found C-terminal in plant and fungal uncharacterised proteins such as YMR178W from Saccharomyces cerevisiae and prokaryotic sequences like AF_2251 from Archaeoglobus fulgidus. The function of these proteins is unknown.
LRRK2, ARM repeat domain (ARM_LRRK2)
Type: Domain

This entry represents the armadillo repeat (ARM) found at the N-terminal end of Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) from eukaryotes. The domain adopts an ARM-like fold, consisting of a right-handed superhelix formed by two curved layers of repeated helical structural units . A patch of negatively charged residues within the ARM domain has been pointed to contribute to complex formation by binding a positive residue in Rab switch 1 region . ARM domain is also suggested to form connections between adjacent microtubules . Also included in this entry is the armadillo repeat domain of Protein aardvark from Dictyostelium discoideum, a component of the junctional complex, both involved in cell adhesion and signalling .

LRRK2 is a serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, primary ciliogenesis, autophagy, and vesicle trafficking . Mutations in LRRK2 are the most common genetic cause of Parkinson's disease . LRRK2 phosphorylates a group of Rab GTPase proteins, including Rab29.
FK506-binding protein 15-like domain (FKBP-15_dom)
Type: Domain

This domain is found in human FK506-binding protein 15 (FKBP15) and similar animal proteins. FKBP15 is involved in the transport of early endosomes and probably in the cytoskeletal organisation of neuronal growth cones . This domain, predicted to show a long α-helix, is often found C-terminal to

.
AAA+ ATPase lid domain, fungi (AAA_lid_fung)
Type: Domain

This is the lid domain found C-terminal to the AAA domain (

) in a group of fungal proteins. This domain is predicted to adopt an α-helical configuration.

AAA ATPases (ATPases Associated with diverse cellular Activities) form a large protein family and play a number of roles in the cell including cell-cycle regulation, protein proteolysis and disaggregation, organelle biogenesis and intracellular transport. Some of them function as molecular chaperones, subunits of proteolytic complexes or independent proteases (FtsH, Lon). They also act as DNA helicases and transcription factors .

AAA ATPases belong to the AAA+ superfamily of ringshaped P-loop NTPases, which act via the energy-dependent unfolding of macromolecules . There are six major clades of AAA domains (proteasome subunits, metalloproteases, domains D1 and D2 of ATPases with two AAA domains, the MSP1/katanin/spastin group and BCS1 and it homologues), as well as a number of deeply branching minor clades .

They assemble into oligomeric assemblies (often hexamers) that form a ring-shaped structure with a central pore. These proteins produce a molecular motor that couples ATP binding and hydrolysis to changes in conformational states that act upon a target substrate, either translocating or remodelling it .

They are found in all living organisms and share the common feature of the presence of a highly conserved AAA domain called the AAA module. This domain is responsible for ATP binding and hydrolysis. It contains 200-250 residues, among them there are two classical motifs, Walker A (GX4GKT) and Walker B (HyDE) .
T9SS-like, galactose binding domain-like (GBD_T9SS_assoc)
Type: Domain

This entry represents a galactose binding domain-like that is found up to six times in a variety of bacterial cell surface proteins that usually have a C-terminal type 9 secretion signal domain. The domain contains four conserved cysteines. AlphaFold models suggest that the first and third form one disulphide bond and the second and fourth form a second disulphide bond.
Galaxin-like repeats domain (Galaxin_dom)
Type: Domain

This entry represents a repetitive region found in galaxins and related proteins.

Galaxins are characterised by their role in biomineralization processes . These proteins are typically involved in the formation of calcium carbonate skeletons in marine organisms, such as corals. They may function by influencing the nucleation and growth of calcium carbonate crystals, contributing to the structural integrity and resilience of coral skeletons. Galaxins are also of interest for their potential applications in biomimetic materials science and understanding the impact of environmental changes on coral reef ecosystems.
LRRK2, beta-propeller (Beta-prop_LRRK2)
Type: Domain

This entry represents the β-propeller found at the C-terminal end of the Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) from eukaryotes. The β-propeller domain is suggested to mediate LRRK2 dimerisation and autophosphorylation, and plays an important role in neurotoxicity associated to LRRK2 PD mutations .

LRRK2 is a serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, primary ciliogenesis, autophagy, and vesicle trafficking . Mutations in LRRK2 are the most common genetic cause of Parkinson's disease . LRRK2 phosphorylates a group of Rab GTPase proteins, including Rab29.
GATOR1 complex protein NPRL3, C-terminal HTH domain (HTH_NPRL3)
Type: Domain

This domain is found at the C-terminal end of GATOR1 complex protein NPRL3 (NPRL3) and similar proteins, mainly found in animals and fungi. As a component of the GATOR1 complex, NPRL3 functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. This domain shows an helix-turn-helix (HTH) configuration .
GBF1-like, tetratricopeptide repeats domain (GBF1-like_TPR)
Type: Domain

This region of predicted tetratricopeptide repeats (TPR) are found at the C-terminal end of Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) and similar eukaryotic proteins. GBF1 is involved in trafficking in the early secretory pathway and required for the assembly of the Golgi apparatus . This entry is often found associated with

and

.
LTI65/LTI78, N-terminal domain (LTI65_LTI78_N)
Type: Domain

This entry represents a disordered region found at the N-terminal of LTI65/LTI78 (

) from Arabidopsis thaliana and similar sequences from plants . This domain is enriched in V/K/H/E/D amino acids.

LTI78 and LTI65 are involved in responses to abiotic stress .
Elapor1/2, C-terminal domain (Elapor1/2_C)
Type: Domain

This domain is found at the C-terminal of Endosome/lysosome-associated apoptosis and autophagy regulator family members 1/2 (Elapor1/2) and similar sequences predominantly found in vertebrates. It is predicted to adopt a predominantly β structure.

Human Elapor1, also known as EIG121 and KIAA1324, is a type I transmembrane protein induced by estrogen. It is associated with the endosome-lysosome compartments and may play an important role in autophagy and cell proliferation .

Mouse Elapor2 (Eig121l) functions as a regulator of the BMP signalling pathway and may be involved in epidermal differentiation .
Elapor1/2, mannose 6-phosphate receptor homology domain (Elapor1/2_MRH)
Type: Domain

The mannose 6-phosphate receptor homology (MRH) domain is found in Endosome/lysosome-associated apoptosis and autophagy regulator family members 1/2 (Elapor1/2) and similar sequences predominantly found in vertebrates. This domain is predicted to form two orthogonally oriented β-sheets that compose a β-barrel.

Human Elapor1, also known as EIG121 and KIAA1324, is a type I transmembrane protein induced by estrogen. It is associated with the endosome-lysosome compartments and may play an important role in autophagy and cell proliferation .

Mouse Elapor2 (Eig121l) functions as a regulator of the BMP signalling pathway and may be involved in epidermal differentiation .
Elapor1/2, galactose binding domain (Elapor1/2_GBD)
Type: Domain

This domain is found in Endosome/lysosome-associated apoptosis and autophagy regulator family members 1/2 (Elapor1/2) and similar sequences predominantly found in vertebrates. It is predicted to form a β-sandwich with a jelly roll topology typical of a galactose binding domain (GBD).

Human Elapor1, also known as EIG121 and KIAA1324, is a type I transmembrane protein induced by estrogen. It is associated with the endosome-lysosome compartments and may play an important role in autophagy and cell proliferation .

Mouse Elapor2 (Eig121l) functions as a regulator of the BMP signalling pathway and may be involved in epidermal differentiation .
Elapor1-like, galactose binding domain (Elapor1-like_3rd)
Type: Domain

This domain is found in Endosome/lysosome-associated apoptosis and autophagy regulator family member 1/2 (Elapor1/2) and similar sequences predominantly found in vertebrates. It is predicted to form a β sandwich with a jelly roll topology typical of a galactose binding domain (GBD).

Human Elapor1, also known as EIG121 and KIAA1324, is a type I transmembrane protein induced by estrogen. It is associated with the endosome-lysosome compartments and may play an important role in autophagy and cell proliferation .

Mouse Elapor2 (Eig121l) functions as a regulator of the BMP signalling pathway and may be involved in epidermal differentiation .
Elapor1/2, TNF receptor-like (Elapor1/2_TNFR-like)
Type: Domain

This domain is found in Endosome/lysosome-associated apoptosis and autophagy regulator family members 1/2 (Elapor1/2) and similar sequences predominantly found in vertebrates. This domain, which contain several conserved cysteines, is predicted to adopt a TNF-receptor (TNFR) fold.

Human Elapor1, also known as EIG121 and KIAA1324, is a type I transmembrane protein induced by estrogen. It is associated with the endosome-lysosome compartments and may play an important role in autophagy and cell proliferation .

Mouse Elapor2 (Eig121l) functions as a regulator of the BMP signalling pathway and may be involved in epidermal differentiation .
Ecto-NOX disulfide-thiol exchanger 1/2 domain (ENOX1/2_dom)
Type: Domain

This domain is found in human Ecto-NOX disulfide-thiol exchanger 1/2 (ENOX1/2) and similar sequences mainly found in animals. ENOX1/2 probably act as terminal oxidases of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface, playing a role in control of the ultradian cellular biological clock . This domain is predicted to form a long α-helix.
Fibulin-2 domain (FIBL-2_dom)
Type: Domain

This domain is found at the N-terminal region of Fibulin-2 (FIBL-2) and similar proteins from vertebrates. FIBL-2 binds to fibronectin and some other ligands in a calcium dependent manner. It may act as an adapter that mediates the interaction between FBN1 and ELN .
Protein of unknown function DUF7287 (DUF7287)
Type: Family

This entry includes uncharacterised archaeal proteins including Uncharacterized protein AF_0763 from Archaeoglobus fulgidus [

].
Flagellar attachment zone protein 1, conserved domain (FAZ1_cons)
Type: Domain

This entry represents a conserved domain found twice in FAZ1 from Trypanosoma brucei and similar sequences mainly from trypanosomatids . This domain is found near the central region and at the very C-terminal of FAZ1. At least 50% of the T. cruzi genome is repetitive sequence, consisting mostly of large gene families of surface proteins, retrotransposons, and subtelomeric repeats .
FAZ1, C-terminal region (FAZ1_C)
Type: Domain

The entry represents a repeats-containing region found towards the C-terminal end of FAZ1 from Trypanosoma brucei brucei and related proteins mainly found in lower eukaryotes. FAZ1 is a component of FAZ filament that is required for correct FAZ assembly and attachment . These repeats consist of 36x14aa repeats in T.brucei and T.cruzi while in the Leishmania major LmjF34.0690 orthologue there are 70x14aa repeats .
MIT1, chromo domain (Chromo_MIT1)
Type: Domain

This domain is found in the Chromatin remodeling factor mit1 (MIT1) from fission yeast and related proteins from fungi. MIT1 is required for proper positioning of the nucleosomes at heterochromatic loci and for transcriptional gene silencing function of the multienzyme effector complex SHREC . The domain represented by this entry is predicted to fold into a globular structure with significant similarity to Chromo domain (

).
Microtubule-associated protein 1B/S, N-terminal domain (MAP1B/S_N)
Type: Domain

This entry represents the N-terminal domain of Microtubule-associated protein 1B (MAP1B) which, when phosphorylated is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension . According to the structure predictions and comparisons, this domain may adopt a P-loop fold closely similar to that found in small GTPases, such as Arf6.

This domain is also found in the Microtubule-associated protein 1S (MAP1S) which mediates aggregation of mitochondria resulting in cell death and genomic destruction . MAP1S also plays a role in anchoring the microtubule organising centre to the centrosomes .

This domain isn't present in MAP1A.
Membrane-bound transcription factor PTM, chromo domain-like (Chromo_PTM)
Type: Domain

This is a putative chromo domain-like domain found in the membrane-bound transcription factor PTM (also known as DDP1) and similar plant sequences. PTM is required for the plastid-to-nucleus retrograde signalling, which plays an important role in the coordinated expression of both nuclear- and chloroplast-localised genes that encode photosynthesis-related proteins .
Mucin-4-like, C8-3 domain (C8-3_MUC4)
Type: Domain

This domain is found in human Mucin-4 (MUC4) and related proteins, including SUSD2 and MESH. It is usually found next to VWD domain (

). Despite lack of sequence similarity, it is predicted to adopt similar structure to the C8-3 domain of MUC2, consisting of three α-helical bundle. This domain contains two highly conserved cysteine residues and these may engage in disulfide bond formation. MUC4 is a membrane-bound mucin which belongs to a family of highly glycosylated proteins that constitute the major component of the mucus .
HTH domain upstream PIN-TPR-GreABC (HTH_next_PIN-TPR-GreABC)
Type: Domain

This is a HTH domain found next to the double PIN in the TPR-GreAB-C-PIN type conflict system (

) .
IL27B, N-terminal Fn3 domain (FN3_IL27B_N)
Type: Domain

This entry represents the Fibronectin type III (FN3) domain found at the N-terminal end of Interleukin-27 subunit beta (IL27B), from animals. This domain is found in association with a C-terminal FN3 (

). Also known as EBI3, IL27B binds p28 to form the heterodimeric cytokine IL-27, which plays an important role in innate immunity by inducing naive CD4+ T cells proliferation . IL-27 binds GP130 and IL-27Ra, acting as a bridge, to activate the JAK/STAT signalling cascade. EBI3 stabilises the complex by binding a positively charged surface of IL-27Ra and Domain 1 of GP130 .
FBXO47, ARM repeats region (ARM_FBXO47)
Type: Domain

This is the C-terminal region of human F-box only protein 47 (FBXO47) and similar metazoan sequences. This region is predicted to consist of armadillo (ARM)-like repeats.

The function of FBXO47 is not clear. It may play a role in carcinogenesis .
MLLE-like domain (MLLE_2)
Type: Domain

This entry represents a domain related to the MLLE domain found in a set of plant proteins. This domain is likely to function as a peptide binding domain.