SII-SWORD/CoKE huggingface dataset:
Influenza RNA polymerase PB2, C-terminal domain (Flu_PB2_C)
Type: Domain

This entry represents the C-terminal domain of RNA-directed RNA polymerase subunit PB2 (also known as Polymerase basic protein 2) from Influenza A virus and similar proteins from influenzavirus (orthomyxoviridae).

Influenza virus encodes a large, multidomain RNA-dependent RNA polymerase that can both transcribe and replicate the viral RNA genome. In influenza virus, the polymerase is composed of three polypeptides: PB1, PB2 and PA/P3. PB1 houses the polymerase active site, whereas PB2 and PA/P3 contain, respectively, cap-binding and endonuclease domains required for transcription initiation by cap-snatching .
Tautomerase-like (Tautomerase-like)
Type: Family

This protein family includes

from Chloroflexus aurantiacus (Caur_1358), a 4-Oxalocrotonate tautomerase (4-OT). This protein adopts a β/α/β scaffold and forms part of a functional heterohexamer 4-OT (hh4-OT) that contains three heterodimer units, each composed of one α-subunit (

) and one β-subunit, which is represented in this entry (

) .
Pullulanase, all-beta domain (pulA_all-beta)
Type: Domain

This entry represents the all-β domain found at the C-terminal of pullulanase A proteins, members of the glycosyl hydrolase family 13 .
TBP-interacting protein, C-terminal domain (TBPIP_C)
Type: Domain

This entry represents the C-terminal domain of archaeal TATA-binding protein (TBP)-interacting proteins (TBPIPs). This domain contains two Cys and two His which coordinates a zinc ion. It forms an unusual Cys2His2-type zinc finger, not functional as a DNA-binding module .
Flagellar hook-associated protein 1, D2-like domain (FlgK_D2-like)
Type: Domain

This entry represents a β-sandwich domain from Flagellar hook-associated protein 1 (FlgK) and related bacterial proteins. The Salmonella typhimurium FlgK (

) has one β-sandwich domain, while FlgK from Burkholderia pseudomallei has two of them protruding from the α-helical core, referred to as D2 and D3 domains in , of which the first one, D2, is covered in this entry . FlgK has cytotoxic effects suggesting an important role in pathogenesis and is highly immunogenic. Domains D2 and D3 from B. pseudomallei have been identified as epitopes with increased immunogenic potential for vaccine development.

Flagellar hook-associated protein 1 (FlgK or HAP1) is one of three HAPs that form the hook-filament junction and has structural similarity to flagellin. FlgK is required for normal flagellum assembly. Proteins in this entry have a multidomain fold comprising an elongated α-helical scaffold core, and depending on the bacterial species, a variable number of smaller domains .
Alpha-2 macroglobulin, MG2 domain (A2M_bMG2)
Type: Domain

Bacterial alpha-2 macroglobulin (A2M) is located in the periplasm and may protect the cell by trapping external proteases through a covalent interaction with an activated thioester . Macroglobulin (MG) β-sandwich domains appear to play a structural role. This entry represents bacterial MG2 (bMG2) domain which, with MG1, plays the role of a linker associating the main body of A2M to the bilayer .
TdIF1, C-terminal (TdIF1_C)
Type: Domain

This domain is found in deoxynucleotidyltransferase terminal- interacting protein 1 from humans (TdIF1) (

) and similar proteins conserved from nematodes to mammals. TdIF1 is part of a histone deacetylase complex that is upregulated during mitosis and is associated with cyclin A. It is organised into two domains. This entry represents the C-terminal domain, which adopts a structure related to the SKI/SNO/DAC domain (

) (

) and is involved in the interaction with both DNA and nucleosomes .
A2MG, CUB domain (A2MG_CUB)
Type: Domain

This domain is found in a group of proteins predominantly found in beta and gammaproteobacteria, such as alpha-2-macroglobulin (A2MG) from Salmonella typhimurium, a protein that protects the bacterial cell from host peptidases. A2MG is composed of 13 domains, 12 of them folding as beta sandwiches. This entry represents the CUB (complement C1r/C1s, Uegf, Bmp1) domain, which is connected to the TED domain (

).
56B-like, ribbon-helix-helix (56B_RHH)
Type: Domain

This entry includes Sulfolobus virus proteins, including 56B from Sulfolobus virus SIRV1, which have a ribbon-helix-helix fold , very similar to that of bacterial RHH proteins. 56B binds DNA .
TAR DNA-binding protein 43, C-terminal (TDP-43_C)
Type: Domain

TDP43 is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, which is involved in RNA processing and in stress granule response. It is linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It is the main component of intraneuronal inclusion bodies (IBs), a pathological hallmark of ALS. This entry represents the C-terminal Gly-rich region of TAR DNA-binding protein 43 (TDP-43) , which is an intrinsically disordered prion-like domain, capable of assembling into dynamic oligomers rich in β-sheet structures [(pdbe:7Q3U]), being responsible of TDP-43 aggregation .
Fanconi-associated nuclease 1-like, winged-helix domain (FAN1-like_WH)
Type: Domain

This entry represents the WH domain of FAN1 and similar proteins mainly from eukaryotes and proteobacteria.

Fanconi-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). It maintains genomic stability and prevents tissue decline in several organs. This protein possesses preferential endonuclease activity toward 5' flap structures. FAN1 is present in most eukaryotes and some bacterial sequences. It consists of four characterised domains: UBZ, SAP, TPR and VRR nuclease (

). However, monocellular eukaryote and bacterial homologues lack the UBZ domain . The N-terminal helical domain of FAN1 can be subdivided in a winged-helix (WH) DNA-binding domain, represented in this entry, and a SAP domain (bacterial

and eukaryotic

) .
Fanconi-associated nuclease 1-like, TPR domain (FAN1-like_TPR)
Type: Domain

This entry represents the TPR domain from Fanconi-associated nuclease 1 (FAN1) and similar sequences from eukaryotes. FAN1 mediates inter-domain interactions and is part of the dimerisation interface . This protein is a DNA structure-specific nuclease involved in processing DNA interstrand crosslinks. FAN1 maintains genomic stability and prevents tissue decline in multiple organs . It mediates cancer drug resistance in several cancer subtypes.
TECR-like, N-terminal domain (TECR-like_N)
Type: Domain

This entry represents the ubiquitin-like domain found at the N-terminal of Very-long-chain enoyl-CoA reductase (also known as TECR or synaptic glycoprotein SC2) from animals. TECR is a synaptic glycoprotein that catalyses the fourth reaction in the synthesis of very long-chain fatty acids (VLCFA).

This domain is also found in the trans-2,3-enoyl-CoA reductase-like (TECRL) protein, also known as steroid 5-alpha-reductase 2-like 2 protein (SRD5A2L2). TECRL is associated with life-threatening inherited arrhythmias displaying features of both long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT).
Ribonucleases P/MRP subunit Pop8-like domain (Pop8-like_dom)
Type: Domain

This entry represents the structural domain of Pop8 from yeast, which is a component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends. It is also a component of Ribonuclease MRP, which cleaves pre-rRNA sequences . Ribonuclease P consists of an RNA moiety and at least 9 protein subunits including POP1, POP3, POP4, POP5, POP6, POP7, POP8, RPP1 and RPR2. Ribonuclease MRP complex consists of an RNA moiety and at least 10 protein subunits including POP1, POP3, POP4, POP5, POP6, POP7, POP8, RMP1, RPP1 and SNM1, many of which are shared with the Ribonuclease P complex . Pop8 interacts with Pop5 and Rpp1 to form the Pop5-Pop8-(Rpp1)2 heterotetramer, which is part of the arm module of the protein hook . This domain can be found in multidomain protein sequences from fungi.
Poxvirus, 2L, N-terminal domain (2L_N_poxvirus)
Type: Domain

This domain is found at the N-terminal of 2L protein from Yaba-like disease virus (YLDV) and similar proteins from poxvirus. 2L binds tumour necrosis factor-alpha (TNFalpha) to inhibit host antiviral and immune responses. This entry represents the α1-α2 superdomain which consists of an antiparallel β-sheet that is topped by two α-helices. It shows similarity with the same domain in classical class I MHC molecules and MHC homologues (

) .
Paraneoplastic antigen-like protein 8A, C-terminal (PNM8A_C)
Type: Domain

This entry represents a conserved helical region found at the C-terminal of paraneoplastic antigen-like protein 8A (PNM8A), a protein whose function is still unknown.
Fanconi-associated nuclease 1-like, eukaryotes (FAN1-like_euk)
Type: Family

Fanconi-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). It maintains genomic stability and prevents tissue decline in several organs. This protein possesses preferential endonuclease activity toward 5' flap structures. FAN1 is present in most eukaryotes and some bacterial sequences. It consists of four characterised domains: UBZ, SAP, TPR and VRR nuclease (

). However, monocellular eukaryote and bacterial homologues lack the UBZ domain . The N-terminal helical domain of FAN1 can be subdivided in a winged-helix (WH) DNA-binding domain, represented in this entry, and a SAP domain (bacterial

and eukaryotic

) .
2B protein, soluble domain (2B_soluble)
Type: Domain

This domain is found in the membrane-targeting protein 2B from Human hepatitis A virus. This protein, which is the soluble region of the virus, plays a key role in the rearrangement of host intracellular membranes, part of the viral infection process of this picornavirus. This entry represents the soluble domain of this protein, which is organised into two subdomains: the N-terminal adopts a pseudo-β-barrel shape with five β-strands that fold into a curved antiparallel β-sheet, and two β-strands prolonged by a β-hairpin; the C-terminal consists of four α-helices forming an helical bundle. This structure shows great similarity to the β-barrel domain of enteroviral 2A proteins .
Mucolipin, extracytosolic domain (MCLN_ECD)
Type: Domain

Mucolipins 1-3 are ion channel proteins that belong to the transient receptor potential (TRP) superfamily of cation channels and are the major Ca2-permeable channels on late endosomes and lysosomes (LEL).

This entry represents the extracytosolic domain (ECD), which consists of two β-sheets and two extracytosolic helices that tetramerize into a ring that caps the extracytosolic side of the channel .
TEP1, second CUB domain (TEP1_CUB2)
Type: Domain

Thioester-containing protein 1 (TEP1) is a central component in the innate immune response of Anopheles gambiae to Plasmodium infection. TEP1 has a series of eight macroglobulin (MG) domains and the β-sheet CUB domain which is flanking the α-helical TED domain. The CUB domain can be divided in two sections, one at the N-terminal and the second at the C-terminal of the TED domain. This entry represents the second part of the CUB domain .
Phage G20C small terminase, N-terminal domain (TerS_N)
Type: Domain

This entry represents the N-terminal helix-turn-helix domain of the terminase small subunit (TerS) from Thermus phage G20c (

) , which oligomerises into a nonamer that binds DNA, stimulates terminase large subunit (TerL) ATPase activity, and inhibits TerL nuclease activity (

) .
Rudivirus, ORF117-like (ORF117-like_Rudivir)
Type: Family

This protein family represents a group of viral proteins, including

from Sulfolobus islandicus rod-shaped virus 1 (117) .
Fanconi-associated nuclease 1, SAP subdomain, metazoa (Fan1_SAP_met)
Type: Domain

This domain is found in Fanconi-associated nuclease 1 from humans (Fan1) (

) and similar proteins mainly from chordates. Fan1 is involved in the processing of DNA interstrand crosslinks (ICLs) and therefore in the maintenance of genomic stability and prevention of tissue decline in multiple organs. FAN1 consists of an SAP-containing N-terminal domain, a middle tetratricopeptide repeat domain (TPR) and a C-terminal viral replication and repair nuclease domain (VRR_nuc domain,

). This entry represents the SAP subdomain, part of the N-terminal domain. It consists of four α-helices .
Telomerase reverse transcriptase, C-terminal extension (TERT_C)
Type: Domain

This domain is found at the C-terminal of Telomerase reverse transcriptase (TERT), a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. This entry represents the C-terminal extension (also known as the thumb domain), which forms an α-helical bundle (

). There are three conserved motifs in this domain involved in nucleic acid binding. In humans, single mutations localised within this portion of telomerase are associated with several bone marrow failure syndromes .
10-bladed beta-propeller domain (10_blade)
Type: Domain

This entry represents a domain consisting of β-propeller repeats identified in metagenomics data. They have 10 blades in an arrangement similar to the sortilin protein (

).
Mechanosensitive ion channel, transmembrane helices 2/3 (MS_channel_1st)
Type: Domain

This entry includes small conductance mechanosensitive channels (MscS), which assembles to a homoheptameric complex . Each monomer consists of an N-terminal transmembrane region and a large cytoplasmic segment composed of a five-stranded antiparallel β-sheet (middle/second) domain and a C-terminal α/β-domain . The N-terminal region consists of three membrane spanning helices (TM1, TM2 and TM3), TM2 and TM3 are represented in this entry. In the heptamer, the permeation pathway is formed by the packing of TM3s, flanked by TM1-TM2 helical hairpins .
Tertiapin (Tertiapin)
Type: Family

This is tertiapin (

), a honeybee peptide identified as a presynaptic neurotoxin that blocks the inwardly rectifying Kir1.1/KCNJ1 and Kir3.1/3.4 (KCNJ3/KCNJ5) potassium channels with high affinity. It can prevent dose-dependently acetylcholine(ACh)-induced atrioventricular blocks in mammalian hearts, as KCNJ3/KCNJ5 channels (also named I(KACh), because these channels are activated by ACh) are found in mammalian myocytes. Interacts specifically with calmodulin in the presence of calcium (

)
FAM186A/B, N-terminal (FAM186A_B_N)
Type: Domain

This is a helical region found at the N-terminal of FAM186A/B from human and similar proteins from vertebrates. The function of members in this entry is not clear.
FAM186A/B, C-terminal (FAM186A_B_C)
Type: Domain

This is the C-terminal helical domain found in FAM186A/B and similar proteins from vertebrates. The function of FAM186A/B is not known.
FAM186A, PQQAQ repeat (FAM186A_PQQAQ)
Type: Repeat

This entry represents a short repeat found in protein FAM186A from human (

) and related sequences from vertebrates. These repeats form a long α-solenoid structure, in which each repeat forms a single α-helix, characterised by PQQAQ sequence.
Phosphoserine phosphatase, ACT domain (PSP_ACT)
Type: Domain

This entry includes the second of the two ACT domains found N-terminal of phosphoserine phosphatase (PSP, SerB) . PSPs belong to the L-2-haloacid dehalogenase-like protein superfamily. PSP is involved in serine metabolism; serine is synthesized from phosphoglycerate through sequential reactions catalyzed by 3-phosphoglycerate dehydrogenase (SerA), 3-phosphoserine aminotransferase (SerC), and SerB.
TetR/AcrR type transcriptional regulator-like, C-terminal domain (TetR/AcrR_C)
Type: Domain

This domain is found at the C-terminal of bacterial transcriptional regulators. It is usually found associated with

.
EFR3 protein, HEAT-like repeat region (EFR3_HEAT-like_rpt)
Type: Repeat

This entry represents the HEAT-like repeat region found in a group of fungal sequences, including the EFR3 protein .

Protein EFR3 homologue A (EFR3A) is a component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and FAM126 (FAM126A or FAM126B). This complex is required for the attachment of phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. EFR3A is palmitoylated at its N terminus, anchoring the protein to the plasma membrane, and probably acts as the membrane-anchoring component in the complex. In yeast, the Efr3p protein is a main regulator of the Stt4p phosphatidylinositol 4-kinase at contact sites between the endoplasmic reticulum and the plasma membrane.
CsgD-like, receiver domain (CsgD-like_REC)
Type: Domain

This domain is found at the N-terminal of the CsgBAC operon transcriptional regulatory protein (CsgD) from Escherichia coli (

) and other proteins predominantly found in proteobacteria. CsgD is responsible for the curli fibers production that promotes biofilm formation and can modulate cellulose biosynthesis through activation of the yoaD gene. It is organised into two domains: an N-terminal regulatory receiver domain (REC) and a C-terminal helix-turn-helix domain (

). This entry represents the REC domain which consists of five α-helices and five β-strands, with the β-strands stabilising as a parallel β-sheet surrounded by the α-helices (

) .
EFR3-like, armadillo repeat (EFR3-like_ARM)
Type: Repeat

This entry represents the N-terminal armadillo repeats of a group of animal and plant EFR3-like proteins.

EFR3 protein form a complex with Ypp1/TTC7 which is required to localise phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. EFR3 acts as a regulator of the Stt4p phosphatidylinositol 4-kinase at contact sites between the endoplasmic reticulum and the plasma membrane . EFR3 consists of armadillo repeats at its N terminus, which act as a scaffold and a basic patch binds acidic phospholipids that anchors the complex to the plasma membrane .
Pol beta superfamily nucleotidyltransferase in conflict systems (NTase-conflict)
Type: Domain

This is a Pol beta superfamily nucleotidyltransferase domain found in bacterial conflict systems and predicted to function as an effector .
ExoU toxin, C-terminal domain (ExoU_C)
Type: Domain

This domain is found in the toxin ExoU from Pseudomonas aeruginosa (

) and similar sequences mainly found in Gammaproteobacteria. ExoU, an effector of the type III secretion system of the bacteria, is a patatin-like phospholipase that binds to the host membranes and induces cytotoxic effects leading to rapid necrotic cell death. This protein shows four domains: a putative chaperone binding domain. a patatin-like domain (

), and two domains that form the membrane localization domain (MLD). This entry represents the C-terminal domain, which folds into a four-helical bundle with a conserved arginine exposed. This residue seems to be essential for localisation .
ExoU toxin, middle helical domain (ExoU_mid_dom)
Type: Domain

Many pathogenic Gram-negative bacteria use type III secretion systems (T3SS) to deliver effector proteins into the host cell cytosol and facilitate the infectious process. The effector protein ExoU from Pseudomonas aeruginosa, one of the most aggressive toxins injected by a T3SS, has four distinct domains. The chaperone-binding domain consists of two separate regions, a N-terminal region and a middle subdomain (this entry). The latter shows a mostly α-helical structure .
Phage tail assembly spiral chaperone protein TAC-like (Phage_chap_TAC_15-like)
Type: Family

This family includes represents phage tail assembly chaperone proteins that are required for the morphogenesis of long-tailed phages .
PfEMP1, CIDRalpha1 domain (PfEMP1_CIDRalpha1_dom)
Type: Domain

This domain is found in the surface protein PfEMP1 from Plasmodium falciparum. PfEMP1 is essential for the virulence of this organism. This protein interacts with the endothelial protein C receptor (EPCR) through its cysteine-rich interdomain region (CIDRalpha1), represented in this entry. This domain show binding surfaces that are conserved in shape and bonding potential, despite dramatic sequence diversity. The domain is built around a long three-helical core bundle, with a four-stranded β-sheet on one side and two α-helices on the opposite side .
PF0610-like, winged HTH, N-terminal (PF0610-like_wHTH_N)
Type: Domain

This domain is found in PF0610 protein from Pyrococcus furiosus (

) and related prokaryotic proteins. This protein has a Zn-ribbon embedded in a winged HTH fold. This entry represents the N-terminal domain, which is composed of three helices . This domain is also found in some arsenical resistance operon repressor (ArsR)

and similar metal-regulated homodimeric repressors, which also accquires a winged helix topology

The function of PF0610 has not been fully chracterized. wHTH domains containing proteins are believed to serve as DNA- or RNA-binding domains

. A large number of wHTH proteins are transcriptional regulators, while others are involved in chromosome packing. Because of its apparent sequence-independent interaction with DNA, PF0610 could be a part of the chromatin system of P. furiosus. The numerous basic residues in PF0610 ensure strong DNA interactions. The Zn ribbon motif could help improve the structural stability of the protein at a high temperature. Another possibility is that PF0610 is a metal-dependent transcription factor. This is based on DNA microarray data. However, further research is needed to conclude if PF0610 is an iron-containing protein
PI4KB/PIK1, accessory domain (PI4KB-PIK1_PIK)
Type: Domain

Phosphatidylinositol 4-kinase beta (PI4KB) is one of four mammalian PI4K enzymes that phosphorylate phosphatidylinositol to generate phosphatidylinositol 4-phosphate (PI4P). It localizes at the Golgi and is essential for Golgi formation and function. PI4KB consists of two domains, a right-handed helical solenoid at the N-terminal, also referred to as accessory (PIK) domain, and a C-terminal kinase domain . This entry represents the N-terminal PIK domain from mammalian PI4KB and the yeast orthologue Pik1 , which may be involved in substrate presentation.
Glycosyl hydrolase family 59, catalytic domain (GH59_cat)
Type: Domain

This entry represents the catalytic domain found in a group of proteins from animals, fungi and bacteria that belong to the Glycoside hydrolase family 59

. This family comprises enzymes with only one known activity: galactocerebrosidase (

).

Globoid cell leukodystrophy (Krabbe disease) is a severe, autosomal recessive disorder that results from deficiency of galactocerebrosidase (GALC) activity . GALC is responsible for the lysosomal catabolism of certain galactolipids, including galactosylceramide and psychosine .

O-Glycosyl hydrolases (

) are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families . This classification is available on the CAZy (CArbohydrate-Active EnZymes) website.
Glycosyl hydrolase family 59, C-terminal lectin domain (GH59_C)
Type: Domain

This domain is found at the C-terminal end of a group of glycosyl hydrolase family 59 (GH59) members from animals and bacteria, including Galactocerebrosidase from Mus musculus (GALCERase) (

). GH59

comprises enzymes with only one known activity: galactocerebrosidase (

). GALCERase is responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon. This protein is organised into three domains, all of them contributing residues to the substrate-binding pocket. This entry represents the lectin domain, which is not present in other lysosomal enzymes, is likely to be be involved in processes that are not found in related enzymes. Mutations in this domain lead to Krabbe disease .