SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF5556 (DUF5556)
Type: Family

This is a family of unknown function found in primates.
Pullulanase, N2 domain (Pullulanase_N2)
Type: Domain

This domain is found close to the N terminus of the Klebsiella starch debranching pullulanase enzyme . The structure of the domain is a β sandwich fold.
Large polyvalent protein associated domain 34 (LPD34)
Type: Domain

This is a predicted enzymatic α and β fold domain with a large, prominent helix with conserved glutamate residue and several additional conserved residues including the motifs HTxN and SN . The domain is associated with polyvalent proteins of firmicute conjugative elements .
CCDC81, HU domain 2 (CCDC81_HU_dom_2)
Type: Domain

This is the second of two HU domains found in the CCDC81-like proteins. CCDC81 has been experimentally linked to the centrosome; eukaryotic CCDC81 HU domains are predicted to function in protein-protein interactions in centrosome organization and potentially contribute to cargo-binding in conjunction with Dynein-VII. A striking lineage-specific expansion of the domain is observed in birds, where the HU domains could function in recognition of non-self molecules .
PvuRts1 I-like, SET and RING associated domain (PvuRts1I-like_SRA)
Type: Domain

This is the C-terminal domain found in the restriction endonuclease PvuRts1 I from Proteus vulgaris (

) and similar bacterial sequences. PvuRts1I a modification-dependent endonuclease with high selectivity for 5-hydroxymethylcytosine, an epigenetic marker that is crucial for multiple biological processes, over 5-methylcytosine and cytosine. This protein is organised into a nuclease domain (this entry) and a C-terminal SRA (SET and RING associated) domain (

) . This domain has the typical SRA domain fold .
E3 ubiquitin-protein ligase AMFR, Ube2g2-binding region (AMFR_Ube2g2-bd)
Type: Domain

The activity of RING finger ubiquitin ligases (E3) is dependent on their ability to facilitate transfer of ubiquitin from ubiquitin-conjugating enzymes (E2) to substrates. The G2BR domain within the E3 ubiquitin-protein ligase AMFR (also known as gp78) binds selectively and with high affinity to the E2 Ube2g2. Binding to the G2BR results in conformational changes in Ube2g2 that affect ubiquitin loading. The Ube2g2-G2BR interaction also causes a 50-fold increase in affinity between the E2 and RING finger. Hence, the Ube2g2-binding region (G2BR) is required for the function of gp78. In yeast, Ubc7p, the ortholog of Ube2g2, is recruited by Cue1p to the ER membrane. Cue1p directly binds Ubc7p through a stretch of 50 aa domain analogous to G2BR, i.e. suggesting that this domain which activates ERAD and Hrd1p stimulating ubiquitylation, might be the yeast equivalent of the G2BR domain .
Domain of unknown function DUF5641 (DUF5641)
Type: Domain

This presumed domain is found in a range of retrotransposon polyproteins.
Large polyvalent protein-associated domain 7 (LPD7)
Type: Domain

This domain contains conserved aspartate and phenylalanine residues. It is widely present in polyvalent proteins and gene neighbourhoods of conjugative elements . This domain is also known as PTox1 .
AbrB, C-terminal (AbrB_C)
Type: Domain

This is the C-terminal domain of AbrB protein from Bacillus subtilis. AbrB is a transition state regulator. Functions of AbrB include biofilm formation, antibiotic production, competence development, extracellular enzyme production, motility, and sporulation. The C-terminal domain is responsible for multimerization and, to a lesser extent than the N-terminal domain, also contributes in DNA binding .
PTX/LNS-Like (PLL) domain (PLL)
Type: Domain

Adhesion G protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. The N-terminal domain of GPR56 has low sequence identity and a fold that likely diverged from the PTX and LNS domains. It also has a conserved motif (HphiC91xxWxxxxG) that was identified among canonical PTX domains. Thus, it is termed the Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL) domain. Truncation-based analyses suggest that the regions of GPR56 responsible for binding TG2 and collagen III are within the PLL domain, most likely in the surface-exposed conserved patch. Furthermore, it is suggested that the conserved patch of the PLL domain mediates an essential function in CNS myelination .
Domain of unknown function DUF5643 (DUF5643)
Type: Domain

This is an immunoglobulin-like domain found in bacteria.
Cilia- and flagella-associated protein HOATZ-like (HOATZ-like)
Type: Family

This entry represents cilia- and flagella-associated protein, HOATZ, and related proteins, found in metazoa.

In mice HOATZ is encoded by the gene designated 4833427G06Rik (C11orf88). Mouse Hoatz mRNA Is specifically expressed in tissues with motile cilia and flagella . Hoatz knockout mice developed hydrocephalus and male infertility, and the ependymal cilia frequently showed disorganized axonemes .
HscB, tetracysteine metal binding motif (HscB_4_cys)
Type: Domain

This is the N-terminal domain of human co-chaperone protein HscB (hHscB). This domain is capable of binding a metal ion through its tetracysteine metal binding motif. The metal atom is coordinated by a set of four cysteine residues (Cys41, Cys44, Cys58 and Cys61) on opposed β-hairpins. Although the N-domain lacks any recognizable secondary structure elements, it has several distant structural homologs including C-4 zinc finger domains and rubredoxin .
Surface adhesin CshA, non-repetitive domain 2 (CshA_NR2)
Type: Domain

The multifunctional fibrillar adhesin CshA, which mediates binding to both host molecules and other microorganisms, is an important determinant of colonization by Streptococcus gordonii, an oral commensal and opportunistic pathogen of animals and humans. CshA binds the high-molecular-weight glycoprotein fibronectin (Fn) via an N-terminal non-repetitive region, and this protein-protein interaction has been proposed to promote S. gordonii colonization at multiple sites within the host. This 259kDa polypeptide is organized in the form of a leader peptide (residues 1-41), a non-repetitive region (residues 42-778), 17 repeat domains (R1-R17, each about 101-aa residues), and a C-terminal cell wall anchor. The non-repetitive Fn-binding region of CshA in turn is composed of three distinct domains, designated as non-repetitive domain 1 (NR1, CshA(42-222)), non-repetitive domain 2 (NR2, CshA(223-540)), and non-repetitive domain 3 (NR3, CshA(582-814)). The NR2 domain of CshA is shown to adopt a globular structure with a lectin-like fold and a ligand-binding site on its surface with structural homologues identified as those involved in binding carbohydrates or glycoproteins .
5-hmdU DNA kinase, helical domain (HMUDK_hel)
Type: Domain

This entry represents an α-helical domain found in 5-hmdU DNA kinase (HMUDK), a P-loop nucleotide kinase that phosphorylates 5-hydroxymethyluracil (5hmdU) into 5-phosphomethyl-2'-deoxyuridine (5-PmdU) on DNA as a step in the pathway leading to thymidine hypermodifications in the viral genome . HMUDK also transfers glutamate to 5-pyrophosphoryloxymethyldeoxyuridine (5-PPmdU) to produce 5-Nalpha-glyutamylthymidine (Nalpha-GluT) . These modifications probably prevent degradation of viral genome by the host restriction-modification antiviral defense system . Members of this entry (formerly known as aGPT-Pplase1) are found in phages with hypermodified bases and eukaryotes such as fungi and stramenopiles .
Annexin-like domain (Annexin-like)
Type: Domain

This annexin-like domain can be found in astrotactin 2 (Astn-2), an integral membrane perforin-like protein linked to the planar cell polarity pathway in hair cells. The annexin-like domain is closest in fold to repeat three of human annexin V and similarly binds calcium, yet shares no sequence homology with it. Notably, this ASTN-2 annexin-like domain is closer in structure to human annexin repeat 3 than human annexin repeat 3 is to repeat 1. Annexin-like domains are known for their capacity to remodel membranes, triggered by calcium binding, and have also been suggested to be involved in the formation of pores in membranes both are possible biological roles of the ASTN-2 annexin-like domain .
Phosphoribosylaminoimidazole carboxylase, C-terminal domain (PurK_C)
Type: Domain

The novo purine biosynthesis proceeds by two divergent paths. In bacteria, yeasts, and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxy-AIR (CAIR) by two enzymes: N5-carboxy-AIR (N5-CAIR) synthetase (PurK) and N5-CAIR mutase (class I PurE) . In animals, the conversion of AIR to CAIR requires a single enzyme, AIR carboxylase (class II PurE).

This entry represents the C-terminal domain of the PurK enzyme.
Protein of unknown function DUF5586 (DUF5586)
Type: Family

This is a family of unknown function found in animals, including C8orf34 from humans.
SMODS and SLOG-associating 2TM effector domain 2 (SLATT_2)
Type: Domain

The SLATT domain contains two transmembrane helices. SLATT domains are generally predicted to function as pore-forming effectors in a class of conflict systems which are reliant on the production of second messenger nucleotide or nucleotide derivatives. SLATT domains are predicted to initiate cell suicide responses upon their activation. This SLATT family is the only prokaryotic SLATT family to exist as a standalone domain, with no as-yet discernable genome associations .
SUVR5, C2H2-type Zinc finger, 3 repeats (SUVR5_Znf-C2H2_3rpt)
Type: Repeat

This entry includes three instances of the Zinc finger C2H2-type. They contain a short β hairpin and an α helix (β/β/α structure), where a single zinc atom is held in place by Cys(2)His(2) (C2H2) residues in a tetrahedral array. Proteins containing this repeats include SUVR5, a histone methyltransferase that functions together with its binding partner LDL1/SWP1 as one of the regulators of flower timing in Arabidopsis .
FtsX, extracellular domain (FtsX_ECD)
Type: Domain

This is the extracellular domain (ECD) found in FtsX, a homologue of the transmembrane PG-hydrolase regulator. The FtsX extracellular domain binds the PG peptidase Rv2190c/RipC N-terminal segment, causing a conformational change that activates the enzyme ileading to PG hydrolysis in Mycobacterium tuberculosis. Structural analysis of FtsX ECD reveals fold containing two lobes connected by a flexible hinge. Mutations in the hydrophobic cleft between the lobes showed reduction in RipC binding in vitro and inhibition of FtsX function in Mycobacterium smegmatis .
PexRD2, WYL domain (PexRD2_WYL)
Type: Domain

Many phytopathogens secrete and/or inject 'effector' proteins inside host cells to modulate cellular processes. Phytopathogens deliver effector proteins inside host plant cells to promote infection. Crystal structures of the effector domains from two oomycete RXLR proteins, Phytophthora capsici AVR3a11 and Phytophthora infestans PexRD2 reveal a core α-helical fold (termed the 'WY-domain') which enables functional adaptation of these fast evolving effectors through (i) insertion/deletions in loop regions between α-helices, (ii) extensions to the N and C termini, (iii) amino acid replacements in surface residues, (iv) tandem domain duplications, and (v) oligomerization. It is proposed that the core fold provides both a degree of molecular stability and plasticity that enables development/maintenance of effector virulence activities while allowing evasion of recognition by the plant innate immune system during rapid 'arms race' co-evolution .
UGGT, thioredoxin-like domain 3 (UGGT_TRXL_3)
Type: Domain

This is the third out of four TRXL (thioredoxin-like) domains found in UDP-glucose:glycoprotein glucosyltransferase (UGGT).
UGGT, thioredoxin-like domain 1 (UGGT_TRXL_1)
Type: Domain

This is one of four TRXL (thioredoxin-like) domains found in UDP-glucose:glycoprotein glucosyltransferase (UGGT) .
UGGT, thioredoxin-like domain 2 (UGGT_TRXL_2)
Type: Domain

This is the second out of four TRXL (thioredoxin-like) domains found in UDP-glucose:glycoprotein glucosyltransferase (UGGT).
EcpB, C-terminal (EcpB_C)
Type: Domain

This is an immunoglobulin like domain found at the C-terminal region of EcpB. It is a periplasmic chaperone which along with EcpE help assemble the E. coli common pilus (ECP) EcpA and EcpD subunits. The C-terminal domain is predicted to contain residues that might be involved in binding a C-terminal carboxylate anchor .
Large polyvalent protein associated domain 23 (LPD23)
Type: Domain

This is an α-helical domain that is usually N-terminal to a metallopeptidase domain. The domain is found in both in polyvalent proteins of conjugative elements and phages/prophages .
Pullulanase, N1 domain (PulA_N1)
Type: Domain

This is the N-terminal domain found in debranching enzymes such as Pullulanase (PulA) from Anoxybacillus sp. LM18-11. The PulA structure comprises four domains (N1, N2, A, and C). This is the N1 domain which has been identified as a carbohydrate-binding motif. Two maltotriose or maltotetraose molecules were found between the N1 domain and a loop of the A domain in the PulA-maltotriose or PulA-maltotetraose structures. These carbohydrates are bound in a parallel binding mode close to each other and form hydrogen bonds. The sugar moieties bound to the N1 domain are not immediately adjacent to the active site, but the enzyme might use N1 binding to attract and grab the substrate. Functional analysis indicate that N1 is important for catalytic activity and thermostability in addition to assisting substrate binding. The structure of the N1 domain reveals a classic distorted β-jelly roll fold consisting of two anti-parallel β-sheets, forming a concave and a convex surface. On the concave side of N1 domain there is a cleft to accommodate two molecules of maltotriose or maltotetraose .
Hydrazine synthase alpha subunit, middle domain (HZS_alpha_mid)
Type: Domain

The crystal structure of hydrazine synthase multiprotein complex isolated from the anammox organism Kuenenia stuttgartiensis implies a two-step mechanism for hydrazine synthesis: a three-electron reduction of nitric oxide to hydroxylamine at the active site of the gamma-subunit and its subsequent condensation with ammonia, yielding hydrazine in the active centre of the alpha-subunit. The alpha-subunit consists of three domains: an N-terminal domain which includes a six-bladed β-propeller, a middle domain binding a pentacoordinated c-type haem (haem alphaI) and a C-terminal domain which harbours a bis-histidine-coordinated c-type haem (haem alphaII). This entry represents the middle domain of subunit alpha of hydrazine synthase (HZS) .
DNA 3'-5' translocase XPB, damage recognition domain (XPB_DRD)
Type: Domain

This domain is found in the N-terminal region of DNA 3'-5' translocase XPB helicase present in Archaeoglobus fulgidus. XPB is essential for transcription, nucleotide excision repair, and TFIIH functional assembly . The domain is a damage recognition domain (DRD) which allows XPB to unwind damaged DNA as needed for nucleotide excision repair .
ZNRF-3, ectodomain (ZNRF-3_ecto)
Type: Domain

This domain is found in ZNRF-3 protein present in Danio rerio. ZNRF-3 is a transmembrane E3 ubiquitin ligase that antagonizes Wnt signalling, the signalling system used to mediate Rspo protein actions. ZNFR3 and RNF43, alongside the Rspo proteins, have emerged as a system with therapeutic potential for a number of pathological processes. This domain is known as the ectodomain .
Bacterial archaeo-eukaryotic release factor family 2 (Bact_RF_family2)
Type: Family

This entry represents the bacterial family of the archaeo-eukaryotic release factor superfamily. It is likely to play roles in biological conflicts or regulation under stress conditions at the ribosome. This family contains a well-conserved 'FP' motif in the catalytic loop .
Limiting CO2-inducible protein B/C, beta carbonyic anhydrase domain (LCIB/C_CA)
Type: Domain

Limiting CO2-inducible B protein (LCIB)-LCIC complex plays an important role in the microalgal CO2-concentrating mechanisms (CCMs). LCIB and homologues (LCIB1-4 and LCIC) structurally resemble beta carbonyic anhydrases (b-CAs) with striking similarities in overall fold, zinc-binding motif, and especially putative active site architecture .
HEPN, AbiU2-like (HEPN_AbiU2)
Type: Domain

Abortive infection (Abi) systems are anti-bacteriophage systems that limit the spread of infection. The primary components of 6 Abi systems define distinct groups of HEPN domains, namely the AbiA-C-terminal domain (AbiA-CTD), AbiD (including AbiD1), AbiF, AbiJ, AbiU2 and AbiV . This entry represents the AbiU2-like HEPN domain.
MYST, zinc finger domain (Zf-MYST)
Type: Domain

This zinc finger domain is found in the MYST family of histone acetyltransferases .
Phosphoribosylformylglycinamidine synthase, N-terminal (FGAR-AT_N)
Type: Domain

This is the N-terminal domain found in formylglycinamide ribonucleotide amidotransferase (FGAR-AT), also known as phosphoribosylformylglycinamidine synthase (

), PurL and formylglycinamidine ribonucleotide (FGAM) synthase. This enzyme catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide and glutamine to formylglycinamidine ribonucleotide, ADP, Pi, and glutamate in the fourth step of the purine biosynthetic pathway .
Domain of of unknown function DUF5636 (DUF5636)
Type: Domain

This is a domain of unknown function, mostly found in gammaproteobacteria.
Importin 13, repeat 1 (Importin_rep_1)
Type: Repeat

Importin 13 has a spiralic structure containing repeats structurally similar to HEAT repeats . It serves as receptor for nuclear localization signals (NLS) in cargo substrates , mediating docking of the importin/substrate complex to the nuclear pore complex (NPC). It contains several repeats structurally similar to the HEAT repeat . This entry represents a single repeat unit.
Immunomodulating metalloprotease N-terminal domain (IMPa_N_2)
Type: Domain

PA0572 of P. aeruginosa is an inhibitor of PSGL-1, also known as an immunomodulating metalloprotease of P. aeruginosa (IMPa). IMPa prevents neutrophil extravasation and thereby protects P. aeruginosa from neutrophil attack . It belongs to the peptidase M60 family. This entry represents the N-terminal α/β-fold domain .
Phosphofructokinase, N-terminal domain (Pfk_N)
Type: Domain

This is a phosphofructokinase (Pfk) N-terminal domain found in yeast ATP-dependent 6-phosphofructokinase subunit alpha. ATP-dependent 6-phosphofructokinases (Pfks,

) catalyze the phosphorylation of fructose 6-phosphate (F-6-P) to fructose 1,6-bisphosphate, a key control step of glycolysis in most organisms. The N-terminal domain contains the active site and is related to glyoxalase I (

) .
Domain of unknown function DUF5611 (DUF5611)
Type: Domain

This is a domain of unknown function. Studies of the TA0095 gene product indicate that this 96-residue hypothetical protein from Thermoplasma acidophilum is a member of the COG4004 orthologous group of unknown function found in Archaea bacteria. The structure displays an α/β two-layer sandwich architecture formed by three α-helices and five β-strands. Furthermore, structural homologs indicate that the TA0095 structure belongs to the TBP-like fold .
RAP80, N-terminal (RAP80_UIM)
Type: Domain

This is the N-terminal domain found in RAP80 protein present in Homo sapiens. RAP80 is fundamental for protein recruitment in the DNA damage response. The N-terminal domain is a ubiquitin-interacting motif (UIM). RAP80 is involved in multivalent recognition of polyUb chains through N-terminal domain .
Kinetoplastid DICER, KptA ADP-ribosyltransferase domain (KptA_kDICER)
Type: Domain

This is a KptA ADP-ribosyltransferase domain observed in kinetoplastid DICER-like (DCL) enzymes. It appears to have lost most residues required for catalysing phospho-transfer to NAD; however, several positively-charged residues implicated in RNA end recognition remain well-conserved .
Outer-membrane lipoprotein Wza, C-terminal domain (Wza_C)
Type: Domain

This is the C-terminal domain found in Wza, an integral outer membrane lipoprotein, which is essential for group 1 capsule export in Escherichia coli. The domain is exposed on the cell surface and is suggested to mimic antimicrobial peptide pore formation .
P-loop nucleotide kinase 3 (Ploop_nt_kinase3)
Type: Family

This is a a P-loop nucleotide kinase predicted to be involved in modified base biosynthesis .
LnmK, N-terminal (LnmK_N_HDF)
Type: Domain

This domain is found in LnmK and is present in Streptomyces atroolivaceus. LnmK is a bifunctional acyltransferase/decarboxylase (AT/DC) that catalyzes first self-acylation using methylmalonyl-CoA as a substrate and subsequently trans-acylation of the methylmalonyl group to the phosphopantetheinyl group of the LnmL acyl carrier protein. LnmK is a homodimer composed of two monomeric double-hot-dog folds (DHDF). This domain is the N-terminal hot dog fold .
Domain of unknown function DUF5597 (DUF5597)
Type: Domain

This is the C-terminal domain of xyloglucan utilization locus (XyGUL) present in Cellvibrio japonicas. XyGUL is required for xyloglucan utilization .
Glycosyl hydrolase family 81, C-terminal domain (GH81_C)
Type: Domain

The glycosyl hydrolase family 81 comprises beta-1,3-glucanases which includes Eng1/Eng2 from fission yeast. Proteins in this entry hydrolyse linear beta-1,3-glucan chains . Eng1 is required for the degradation of the primary septum after completion of cytokinesis . Eng2 plays a role in coupling the endocytic coat to the actin cytoskeleton and, independently of this activity, it is required to establish bipolar cell growth by promoting localization of the scaffold protein scd2 to cell poles and thereby, the activation of cdc42 . The endo-beta-1,3-glucanase activity is essential for efficient spore release .

This entry represents the helical C-terminal domain.
Protein of unknown function DUF5520 (DUF5520)
Type: Family

This is a family of unknown function proteins found in mammals.
Hit1, C-terminal (Hit1_C)
Type: Domain

This domain is found in Hit1 protein (Hit1p) present in Saccharomyces cerevisiae. Hit1p contributes to C/D small nucleolar RNPs (snoRNPs) stability and pre-RNA maturation kinetics by associating with U3 snoRNA precursors and influencing its 3'-end processing. Snu13p-Rsa1p-Hit1p heterotrimer binds C/D snoRNAs. C/D snoRNAs are essential for the biogenesis of ribosomes and spliceosomes. The domain adopts a Pac-Hit fold that forms a claw which locks the α1 helix of Rsa1p, while the Rsa1p α2 helix packs against the exposed surface of the Hit1p Pac-Hit domain α3 helix .
Cytosolic phospholipases A2, C2-domain (cPLA2_C2)
Type: Domain

Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. In humans, the cPLA2 family contains six isoforms. Structural information of full length cPLA2alpha apo form, shows that it is composed of two domains; an N-terminal Ca2 + binding C2 domain and a C-terminal alpha/beta hydrolase core. This entry describes the N-terminal Ca2+ binding C2 domain which is composed of an eight-stranded antiparallel β-sandwich consisting of two four-stranded β-sheets. C2 domains are present in many lipid-binding proteins including Copines, CAPRI and Rabphilin-3A all of which are involved in membrane trafficking .
PheRS, DNA binding domain 1 (PheRS_DBD1)
Type: Domain

This is a DNA-binding fold domain found in Phenylalanyl-tRNA Synthetase (

) N-terminal region. This domain belongs to a superfamily of 'winged helix' DNA-biding domains. The topology of DBD-1 and DBD-3 closely resembles the topology of the Z-DNA-binding domain Zalpha of double-stranded RNA (dsRNA) adenosine deaminase and other domains from DNA-binding proteins. Mutational analysis indicate that DBD-1, 2 and 3 play critical roles in tRNA-Phe binding and recognition, i.e., from the drastic reduction of aminoacylation activity seen upon removal of the N-terminal domains .