SII-SWORD/CoKE huggingface dataset:
DnaK suppressor protein DksA, N-terminal domain (DksA_N)
Type: Domain

DksA is a transcription factor that directly binds RNA polymerase and controls the bacteria response to stress and starvation. DksA is all helical . This is the N-terminal domain that consists of two helices arranged in an antiparallel α-hairpin with left-handed twist . It extends through the secondary channel toward the RNAP active site and serves as a conduit for the substrate NTPs.
Type III effector Xcv3220-like, C-terminal domain (XopL_C)
Type: Domain

This domain is found at the C-terminal end of the type III effector Xcv3220 (XopL) (

) from the plant pathogen Xanthomonas campestris and similar proteins from Xanthomonadales. XopL induces plant cell death, subverts plant immunity and shows E3 ubiquitin ligase activity, which is associated with this domain. This domain interacts with plant E2 ubiquitin conjugating enzymes and folds into a four-helical bundle, which can be subdivided into two uneven lobes almost perpendicular to each other giving the molecule an 'L' shape (

). A large cleft with a net negative charge is formed at the intersection of the two lobes .
XMAP215/Dis1/CLASP, TOG domain (XMAP215_CLASP_TOG)
Type: Domain

This is the tubulin-binding TOG domain of two related families of microtubules (MTs) regulatory proteins, XMAP215/Dis1 and Cytoplasmic Linker ASsociated Proteins CLASP . XMAP215/Dis1 family includes Stu2 from S. cerevisiae, S. pombe Alp14 and Dis1, A. thaliana MOR1, C. elegans Zyg9, D. melanogaster MiniSpindles (MSPS) and human ch-TOG (also known as Cytoskeleton-associated protein 5), which have conserved roles in promoting the assembly of microtubules . CLASP proteins promote MT rescue and suppress MT catastrophe events .
Stu2, C-terminal segment (Stu2_CTS)
Type: Domain

This entry represents the C-terminal segment of Stu2, which binds the four-way junction of the Ndc80 complex (Ndc80c). This interaction is crucial for association of Stu2 with kinetochores, that when it is compromised, there is impairment in cell viability, biorientation defects and delay in cell cycle progression . This Stu2 segment folds into a single α-helix that is enriched with hydrophobic residues essential for the interaction (

).
DUF1980, N-terminal domain (DUF1980_N)
Type: Domain

Members of this family are found in a set of prokaryotic hypothetical proteins. Their exact function has not, as yet, been defined. This entry represents the N-terminal three-transmembrane helical domain.
Dit-like phage tail protein, N-terminal domain (Dit-like_N)
Type: Domain

This entry represents a RIFT-like barrel domain found in a large family of proteins which is related to the Dit phage protein from SPP1.
Lincosamide nucleotidyltransferase-like, C-terminal domain (LinB-like_C)
Type: Domain

This domain is found at the C-terminal end of Lincosamide nucleotidyltransferase from Enterococcus faecium (LinB) and similar proteins from bacteria. LinB catalyses adenylylation of the lincosamide class of antibiotics. This domain folds into an α-helical bundle, which consists of five α-helices . It is involved in dimer formation.
DUF1846, N-terminal domain (DUF1846_N)
Type: Domain

This is the N-terminal domain found in the uncharacterised protein family DUF1846 (also known as UPF0371). Some members of the family are annotated as ATP-dependent peptidases. This is a P-loop-like domain PDBe:

.
Leukemia inhibitory factor receptor-like, Ig-like domain (LIF-R-like_Ig-like)
Type: Domain

This domain is found in Leukemia inhibitory factor receptor from mouse (LIF-R) and similar proteins from vertebrates. LIF-R binds a cytokine that acts on many cell types including embryonic stem cells, megakaryocytes, osteoblasts, and neuronal cells. The extracellular region of this protein shows a modular structure with two cytokine-binding modules (CBM, with

representing the second subdomain of CBM1, D2) separated by an Ig-like domain (this entry) and followed by three membrane-proximal fibronectin type-III (FNIII) domains (

) This domain interacts directly with site 3 of the Cilliary Neutrophic Factor (CNTF) .

This domain is also found in human Oncostatin-M-specific receptor subunit beta (OSMR), which associates with IL31RA to form the IL31 receptor. It binds IL31 to activate STAT3 and possibly STAT1 and STAT5 and is capable of transducing OSM-specific signalling events .
USP8, WW domain (WW_USP8)
Type: Domain

This entry represents a divergent WW domain found in the USP8 protein, where it has been shown to be involved in auto-inhibition . USP8 is a hydrolase that removes a conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. This WW domain might interact with and inhibit the catalytic USP domain by binding the catalytic cleft, and narrowing the entrance to the ubiquitin-binding pocket. Release of autoinhibition may underlie Cushing's disease caused by USP8 mutations .
Dickkopf-related protein 1/2/4, C-terminal subdomain 2 (DIKK1/2/4_C-subdom2)
Type: Domain

Dickkopf-related proteins are cysteine-rich secretory proteins and highly conserved inhibitors of the canonical Wnt signalling pathway, which play key roles in many essential biological processes. The C-terminal domain is described as two subdomains, each consisting of three antiparallel β-strands that are connected by a long loop which contains a short α-helix. This domain is strongly conserved in Dkk1, Dkk2 and Dkk4, and directly contacts LRP6. This entry represents the second subdomain . In Dkk3 these residues differ and is consistent with studies indicating that Dkk3 is a divergent family member that does not inhibit Wnt signalling . This domain share significant sequence similarity to the colipase fold.
Dickkopf-related protein 1/2/4, C-terminal subdomain 1 (DIKK1/2/4_C-subdom1)
Type: Domain

Dickkopf-related proteins are cysteine-rich secretory proteins and highly conserved inhibitors of the canonical Wnt signalling pathway, which play key roles in many essential biological processes. This entry represents the C-terminal cysteine-rich domain which is strongly conserved in Dkk1, Dkk2 and Dkk4, and directly contacts LRP6 . This domain is described as two subdomains, each consisting of three antiparallel β-strands that are connected by a long loop which contains a short α-helix. This entry represents the first subdomain, the second is covered in

. In Dkk3 the residues differ and is consistent with studies indicating that Dkk3 is a divergent family member that does not inhibit Wnt signalling . This domain share significant sequence similarity to the colipase fold.
Legumain, prodomain (Legum_prodom)
Type: Domain

This domain is found in the proenzyme form of Vacuolar-processing enzyme (VPE), known as legumain. VPE is an asparagine-specific endopeptidase that plays important roles in many physiological processes, including the maturation of toll-like receptors 3/7/9. The mature active form of VPE is generated by autoproteolytic maturation at acidic pH. In the three-dimensional structure of the proenzyme, this prodomain is located on top of the protease domain, blocking access to the active site. It adopts an α-helical structure, with an activation peptide and a region that assembles into a death domain-like fold at its C-terminal end .
Peptidoglycan beta-N-acetylmuramidase NamZ, N-terminal (NamZ_N)
Type: Domain

NamZ is an exo-beta-N-acetylmuramidase which catalyses an exo-lytic cleavage of beta-1,4-acetylmuramic acid from from the non-reducing ends of peptidoglycan chains and it is a founding member of a new family of glycosidases (GH171). NamZ consists of a N-terminal catalytic domain with a Rossmann-like fold (represented in this entry) and a C-terminal auxiliary α/β domain (

) .
Peptidoglycan beta-N-acetylmuramidase NamZ, C-terminal (NamZ_C)
Type: Domain

NamZ is an exo-beta-N-acetylmuramidase which catalyses an exo-lytic cleavage of beta-1,4-acetylmuramic acid from from the non-reducing ends of peptidoglycan chains and it is a founding member of a new family of glycosidases (GH171). NamZ consists of a N-terminal catalytic domain with a Rossmann-like fold (

) and a C-terminal auxiliary α/β domain (represented in this entry).
Dicers-like, N-terminal domain (Dicers-like_N)
Type: Domain

This domain is found at the N-terminal of hypothetical proteins from yeast, that are thought to be the noncanonical Dicers found in these organisms. These proteins adopt a homodimer assembly similar to bacterial ribonuclease III but extended by a unique N-terminal domain that consists of five α-helices .
Dicers-like, N-terminal domain superfamily (Dicers-like_N_sf)
Type: Homologous_superfamily

This superfamily includes the N-terminal domain of hypothetical proteins from yeast, that are thought to be the noncanonical Dicers found in these organisms. These proteins adopt a homodimer assembly similar to bacterial ribonuclease III but extended by a unique N-terminal domain that consists of five α-helices .
LED repeat (LED_rpt)
Type: Repeat

This entry represents a six residue tandem repeat found in Cerebellar degeneration-related antigen 1 (CDR1) from human . It is rich in Glu and Asp and usually flanked at the N terminus by hydrophobic residues (Leu/Phe) and on the C terminus by an aliphatic residue followed by and Asp residue .
WKTW repeat (WKTW_rpt)
Type: Repeat

This repeat is found in five copies at the C terminus of Cerebellar degeneration-related antigen 1 (CDR1) from human (

) and related chordate proteins. It has the conserved sequence motif WKTWI.
Alpha-galactosyl binding lectin (LDL)
Type: Family

This protein family includes Alpha-galactosyl-binding lectin from Lyophyllum decastes (LDL) and similar proteins from fungi. This protein forms a compact structure with a five-stranded anti-parallel β-sheet and two α-helices packed against one side of the β-sheet . Two β-sheets pack nearly orthogonal against each other to form a homodimeric structure.
Transmembrane protein 106, C-terminal domain (TMEM106_C)
Type: Domain

This entry represents the C-terminal domain of TMEM106A/B/C and similar animal proteins.

This family includes Transmembrane protein 106A/B/C, type II transmembrane proteins which have homology to the late embryogenesis abundant-2 (LEA-2) domain . TMEM106A has been identified as a key factor to regulate macrophage activation and a tumour suppressor in gastric, renal cancer and non small-cell lung carcinoma (NSCLC) . TMEM106B localises to late endosomes and lysosomes, and it is involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with MAP6 . Its overexpression is associated with familial frontotemporal lobar degeneration . It has also been identified as a protein required for productive SARS-CoV-2 . Structural analysis of LEA-2 domains revealed that they have a long, conserved lipid-binding groove, implying that TMEM106B and its homologues Vac7 and Tag1 from yeast, may all be lipid transfer proteins in the lumen of late endocytic organelles .
WsaF, N-terminal domain (WsaF_N)
Type: Domain

This entry represents a domain found N-terminal in WsaF from Geobacillus stearothermophilus (

) and related bacterial proteins. WsaF catalyses the formation of beta-1-2-linkage of rhamnose sugars in the carbohydrate polymer. It consists of two domains, the N-terminal which binds the acceptor (the growing rhamnan chain), and a C-terminal domain which binds the substrate (dTDP-beta-l-rhamnose) (

) .
Transmembrane protein 106, N-terminal (TMEM106_N)
Type: Domain

This entry represents the N-terminal region of TMEM106A/B/C and similar animal proteins.

This family includes Transmembrane protein 106A/B/C, type II transmembrane proteins which have homology to the late embryogenesis abundant-2 (LEA-2) domain . TMEM106A has been identified as a key factor to regulate macrophage activation and a tumour suppressor in gastric, renal cancer and non small-cell lung carcinoma (NSCLC) . TMEM106B localises to late endosomes and lysosomes, and it is involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with MAP6 . Its overexpression is associated with familial frontotemporal lobar degeneration . It has also been identified as a protein required for productive SARS-CoV-2 . Structural analysis of LEA-2 domains revealed that they have a long, conserved lipid-binding groove, implying that TMEM106B and its homologues Vac7 and Tag1 from yeast, may all be lipid transfer proteins in the lumen of late endocytic organelles . This entry represents the N-terminal region of TMEM106 family.
Dicer, platform domain (Dicer_platform)
Type: Domain

This entry represents the platform domain in Dicer proteins from animals, which sits on the top of the L-shaped Dicer structure and shows a phosphate pocket .

Dicer endoribonuclease plays a central role in short dsRNA-mediated post-transcriptional gene silencing. It cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs . Dicer shows two N-terminal helicase domains (

), a dimerisation domain (

), a platform domain (

), a PAZ domain (

), two RNase III a/b domains (

) and a dsRNA-binding domain in its C-terminal region (

).
Dicer, partner-binding domain (Dicer_PBD)
Type: Domain

This domain is found in endoribonuclease Dicer from animals. This entry represents the partner-binding domain (PBD), which folds into a four-helical bundle. It is is responsible for the interactions with the dsRNA-binding proteins that support the enzymatic activity of Dicer .

Dicer endoribonuclease plays a central role in short dsRNA-mediated post-transcriptional gene silencing. It cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs . Dicer shows two N-terminal helicase domains (

), a dimerisation domain (

), a platform domain (

), a PAZ domain (

), two RNase III a/b domains (

) and a dsRNA-binding domain in its C-terminal region (

).
DWD hypersensitive to UV-B 1, N-terminal domain (DHU1_N)
Type: Domain

This entry represents the N-terminal domain of DWD hypersensitive to UV-B 1 from Arabidopsis thaliana and related plant sequences, which may act as a substrate receptor of a CUL4-RING E3 ubiquitin-protein ligase (CRL4) complex involved in the negative regulation of cellular responses to ultraviolet-B (UV-B) illumination, likely in coordination with RUP1 . It interacts with COP1 and probably prevents the formation of active UVR8-COP1 complex thus avoiding UVR8-COP1-mediated positive regulation of UV-B responses . DHU1 consists of two domains, LRR included in this entry and WD40 (

), which mediate protein-protein interactions.
DHH-CID domain (DHH_CID)
Type: Domain

DHH-CID (CMG Interacting Domain) domain is found in proteins that are members of DHH phosphatase family. This domain is located between the catalytic domains and consists of array of four helices with two 'kissing' loops. The DHH-CID domain contains H2TH motif and is structurally very similar to proteins members of S13-like H2TH superfamily.
DGC-associated coil (DGCcoil)
Type: Domain

This entry represents the DGC-associated coil (DGCcoil) domain found widespread in gammaproteobacteria . This is an α-helical cytoplasmic domain found N-terminal of the GGDEF domain .
DENR, N-terminal domain (DENR_N)
Type: Domain

The density regulated protein (DENR) forms a stable heterodimer with malignant T-cell-amplified sequence 1 (MCT-1) which interacts with the 40S ribosomal subunit during initiation, reinitiation and recycling stages, playing a role in regulation of non-canonical translation initiation and ribosomal recycling . This entry represents the N-terminal domain of DENR, containing a zinc ion-binding site, which preserves the structure of DENR's MCT-1-binding interface that is essential for the dimerisation . DENR likely coordinates the Zn ion mainly via three rather than four cysteines .
Ice-binding protein, beta roll (IBP_b_roll)
Type: Repeat

The grass Lolium perenne produces an ice-binding protein (LpIBP) that helps this perennial tolerate freezing by inhibiting the recrystallization of ice . Ice-binding proteins (IBPs) are also produced by freeze-avoiding organisms to halt the growth of ice and are better known as antifreeze proteins (AFPs) . The ice-binding site (IBS) is formed by a flat β-sheet on one surface of the β-roll . This region folds as a left-handed β-helix. Each of the eight beta-helical coils is composed of two seven-residue tandem repeats with a consensus sequence XXNXVXG where X is a solvent-exposed residue, typically with a polar side chain .
Gfd2/YDR514C-like, C-terminal domain (Gfd2/YDR514C-like_C)
Type: Domain

This entry represents a domain found at the C-terminal end of fungal proteins, including Gfd2 and YDR514C from yeasts and QDE-2-interacting protein from the filamentous fungi Neurospora crassa (

) , which are related to DNA polymerase III subunit epsilon and similar proteins that belong to the DnaQ-like (or DEDDh) exonuclease superfamily. These proteins catalyse the excision of nucleoside monophosphates at the DNA or RNA termini in the 3'-5' direction. Most DEDDh exonucleases are the proofreading subunits (epsilon) or domains of bacterial DNA polymerase III, the main replicating enzyme in bacteria, which functions as the chromosomal replicase. This domain shows an α-β configuration .
Lactate racemase, C-terminal domain (LarA_C)
Type: Domain

This entry represents the C-terminal domain of the nickel-dependent lactate racemase enzyme (LarA) and related proteins found in archaea and bacteria. LarA is part of a superfamily containing many different enzymes . These include malate racemases, phenyllactate racemase, one alpha-hydroxyglutarate racemase, D-gluconate 2-epimerase, a short-chain aliphatic alpha-hydroxyacid racemase .
WipA-like, phosphatase domain (WipA_Phos)
Type: Domain

This entry represents the phosphatase domain of WipA from Legionella pneumophila (

) and related bacterial proteins. WipA is one of the effector proteins involved in pathogenesis and targets tyrosine-phosphorylated peptides. The structure of WipA consists of two domains, an N-terminal coiled-coil and a C-terminal catalytic phosphatase domain (

). The latter has a serine/threonine phosphatase fold that unexpectedly targets tyrosine-phosphorylated peptides .
Death domain, fish (Death_3_fish)
Type: Domain

This entry represents a death domain found in proteins containing tandem TNFR/NGFR cysteine-rich (

) domains. This domain is largely found in fish proteins.
Protein LANA1-like, DNA-binding domain (LANA1_DNA-bd)
Type: Domain

Latency-associated nuclear antigen (LANA) is a multifunctional protein that plays a role in the replication and long-term persistence of the viral episomal genome in dividing cells. It binds to mitotic chromosomes via its N-terminal region and to a 16-bp imperfect palindrome within the origin of replication (oriP) located in the viral terminal repeat (TR) through its C-terminal. It also plays a role in the repression of host NF-kappa-B activity upon TNF-alpha stimulation by promoting the proteasomal degradation of host RELA . This entry represents the DNA-binding domain of LANA from murine gammaherpesvirus 68, which is homologous to that of Kaposi's sarcoma-associated herpesvirus (KSHV) .
Lysosome-associated membrane glycoprotein 2-like, transmembrane domain (Lamp2-like_TM)
Type: Domain

This domain is found in Lysosome-associated membrane glycoprotein 2 from humans (Lamp2) and similar proteins from vertebrates. Lamp2 is an integral membrane protein that plays an important role in chaperone-mediated autophagy (CMA), targeting pertinent proteins for lysosomal degradation. This protein is organised into two conserved luminal domains (

), a single transmembrane (TM) domain (this entry) and a short C-terminal cytosolic tail. It adopts a trimeric configuration, and the transmembrane domains of the three monomers form a three-helical bundle structure .
Discoidin domain-containing receptor 1/2, DS-like domain (DDR1-2_DS-like)
Type: Domain

Discoidin domain-containing receptor 1/2 (DDR1/2) are receptor tyrosine kinases (RTKs) whose activating ligands are various collagens and consist of extracellular domains comprising the N-terminal discoidin domain (DS,

) followed by a DS-like domain and the cytoplasmic kinase domain (

) . Impairment in signalling by DDR1 and DDR2 is associated with the progression of various human diseases, including fibrosis, atherosclerosis and cancer, therefore, inhibition of signalling using monoclonal antibodies (mAbs) may be an useful therapy.

This entry represents the DS-like domain, which mediates binding to triple-helical collagen together with the DS domain and contains the epitopes of all mAbs .
WipA, alpha-helical hairpin (WipA_N)
Type: Domain

This entry represents the α-helical hairpin of WipA protein, from Legionella pneumophila (

) and related bacterial proteins, which adopts a coiled-coil structure. WipA is one of the effector proteins that is involved in its pathogenicity. This domain interacts with the phosphatase domain of another WipA molecule to form a dimer (

). It has been suggested that it mediates protein-protein interactions with a tyrosine- phosphorylated host target .
Cellulose-binding Sde182, C-terminal domain (Sde182_C)
Type: Domain

This domain is found at the C-terminal end of Cellulose-binding protein Sde0182 from Saccharophagus degradans

, which seems to have capacity to bind plant carbohydrates. This region shows a β-sandwich fold that consists of two β-sheets with seven β-strands in total. It has structural similarity to a polycystic kidney domain (PKD,

) and lacks the solvent exposed aromatic residues typically associated with an ability to bind carbohydrates . This domain is also found in other uncharacterised bacterial and fungal proteins.
Lysosome-associated membrane glycoprotein 2-like, luminal domains (Lamp2-like_luminal)
Type: Domain

This domain is found in a group of animal proteins that includes Lysosome-associated membrane glycoprotein 2 from humans (Lamp2). Lamp2 is an integral membrane protein that plays an important role in chaperone-mediated autophagy (CMA), targeting pertinent proteins for lysosomal degradation. This protein is organised into two conserved luminal domains (this entry), a single transmembrane (TM) domain (

), and a short C-terminal cytosolic tail. It adopts a trimeric configuration .
GP38, nairovirus (GP38_nairovirus)
Type: Domain

This entry represents the GP38 secreted glycoprotein from nairoviruses, including CCHFV and Dugbe virus. It is encoded in the glycoprotein precursor complex (GPC) from the M segment of nairovirus genome. It has a novel fold composed of a three-helix bundle and a β-sandwich . Although its function is unknown, it is known to be immunogenic in humans and, therefore, an interesting vaccine target .
FAM171, N-terminal (FAM171_N)
Type: Domain

This entry represents a domain found at the N-terminal of a family of proteins that includes FAM171A1/A2 and FAM171B. FAM171A1 is a type 1 transmembrane glycoprotein also known as astroprincin (APCN) due to abundant expression in astrocytes. APCN is also expressed in placental trophoblasts, skeletal and heart muscle, kidney and pancreas . APCN is involved in the regulation of the cytoskeletal dynamics, playing a role in actin stress fibre formation.
Protein ea8.5-like (ea8_5-like)
Type: Family

This entry includes Protein ea8.5 from Bacteriophage lambda (

) and similar sequences mostly from tailed bacteriophages and bacterial prophages. It ranges from around 45 to 90 residues in length and is associated with nucleic acid binding function, playing an essential role in the inhibition of the initiation of DNA synthesis in the phage host. NMR analysis shows it adopts a hybrid homeodomain/zinc-finger fold, which suggests a regulatory role .