SII-SWORD/CoKE huggingface dataset:
PheRS, DNA binding domain 3 (PheRS_DBD3)
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 tRNAPhe binding and recognition, i.e., from the drastic reduction of aminoacylation activity seen upon removal of the N-terminal domains .
Halobacterial output domain 2 (HalOD2)
Type: Domain

HalOD2 (Halobacterial output domain 2) is a protein domain that is found in haloarchaea in combination with the response regulator receiver domain (

) .
Nicotinate phosphoribosyltransferase, N-terminal domain (NAPRTase_N)
Type: Domain

Nicotinate phosphoribosyltransferase (

) is the rate limiting enzyme that catalyses the first reaction in the NAD salvage synthesis. This is the N-terminal domain of the enzyme .
Domain of unknown function DUF5635 (DUF5635)
Type: Domain

This is a domain of unknown function which is found C-terminal to

in actinobacteria.
Kazal-type serine protease inhibitor domain (Kazal_3)
Type: Domain

This Kazal domain is found in the factor I-like modules (FIMs) region on the C terminus of complement component C7 proteins. Complement component C7 is a subunit of the membrane attack complex (MAC), a fundamental machinery in the mammalian innate immunity. KAZAL domains are common in serine protease inhibitors .
Hexapeptide repeat including loop (Hexapep_loop)
Type: Repeat

This entry contains a single hexapeptide repeat unit including a loop between two strands.
Metal-independent restriction enzyme BfiI, DNA binding domain (BfiI_DBD)
Type: Domain

This domain is found in the metal-independent restriction enzyme BfiI present in Bacillus firmus. This domain is found at the C terminus of the protein and is responsible for DNA binding. The domain exhibits a β-barrel-like structure similar to the effector DNA-binding domain of the Mg2+ dependent restriction enzyme EcoRII and to the B3-like DNA-binding domain of plant transcription factors .
Zyg-1, polo box domain 1 (Zyg-1_PB1)
Type: Domain

In metazoans, Plk4 kinases control daughter centriole assembly. Plk4 homologues have an N-terminal kinase domain, a C-terminal polo box, and a central domain termed the 'cryptic polo box' (CPB) that has been shown to dimerize, to be sufficient for centriole localization and to be required for Plk4 to promote centriole assembly. Probable serine/threonine-protein kinase zyg-1 (

) (ZYG-1) is a Plk4 homlogue found in C. elegans. Crystal structure for the CPB of C. elegans ZYG-1, reveals that it forms a Z-shaped dimer containing an intermolecular β-sheet with an extended basic surface patch. Electrostatic interactions between the basic patch on the ZYG-1 CPB dimer and the SPD-2 acidic region dock ZYG-1 onto centrioles to promote new centriole assembly. ZYG-1 CPB contains two tandem polo boxes (PB1 and PB2), each containing a six-stranded β-sheet with an α-helix packed against one side . This entry represents PB1.
Zyg-1, polo box domain 2 (Zyg-1_PB2)
Type: Domain

In metazoans, Plk4 kinases control daughter centriole assembly. Plk4 homologs have an N-terminal kinase domain, a C-terminal polo box, and a central domain termed the 'cryptic polo box' (CPB) that has been shown to dimerize, to be sufficient for centriole localization and to be required for Plk4 to promote centriole assembly. Probable serine/threonine-protein kinase zyg-1 (

) (ZYG-1) is a Plk4 homlog found in C. elegans. Crystal structure for the CPB of C. elegans ZYG-1, reveals that it forms a Z-shaped dimer containing an intermolecular β-sheet with an extended basic surface patch. Electrostatic interactions between the basic patch on the ZYG-1 CPB dimer and the SPD-2 acidic region dock ZYG-1 onto centrioles to promote new centriole assembly. ZYG-1 CPB contains two tandem polo boxes (PB1 and PB2), each containing a six-stranded β-sheet with an α-helix packed against one side . This entry represents PB2.
Protein of unknown function DUF5583 (DUF5583)
Type: Family

This is a family of unknown function found in chordata.
Mex67, RNA recognition motif (Mex67_RRM)
Type: Domain

The Mex67-Mtr2 complex (TAP-p15 or NXF1-NXT1 in metazoans) is the principal mRNA export factor in Saccharomyces cerevisiae. Mex67 is a member of the NXF family of proteins and has conserved homologs through eukaryotes from yeasts to humans. Although sequence conservation is poor between S. cerevisiae Mex67 and Homo sapiens NXF1, they do show functional complementarity. Mex67 and TAP/NXF1 are modular proteins that contain four structural domains: an N-terminal RNA recognition motif (RRM), a leucine rich repeat (LRR) domain, a nuclear transport factor 2-like domain (NTF2L) and an ubiquitin-associated domain (UBA). This entry describes the N-terminal RNA recognition motif (RRM) found in Mex67 proteins .
Domain of unknown function DUF5638 (DUF5638)
Type: Domain

This is a domain of unknown function found in Legionella.
Large polyvalent protein associated domain 22 (LPD22)
Type: Domain

This is a predicted enzymatic α-helical domain with highly conserved aspartate residues . The domain is found in polyvalent proteins of phage and prophage genes and is often the immediate neighbour of a lysozyme gene .
RlmM ferredoxin-like domain (RlmM_FDX)
Type: Domain

This domain is found in Ribosomal methyltransferase RlmM (YdgE) present in E. coli. RlmM catalyzes the S-adenosyl methionine (AdoMet)-dependent 2'O methylation of C2498 in 23S ribosomal RNA. The domain is ferredoxin-like and forms part of the THUMP domain which binds RNA. THUMP domains typically have low sequence similarity .
MglB-2, periplasmic binding protein domain (MglB-2_Peripla_BP)
Type: Domain

Treponema pallidum, the bacterium that causes syphilis, is an obligate human parasite. T. pallidum lacks the machinery for the de novo synthesis of many key nutrients therefore it acquires these nutrients from its human host. MglB-2 from T. pallidum has been shown to act as the ligand-binding element of an ABC transporter for D-glucose. The overall fold of MglB-2 resembles those of LBPs (Ligand-binding proteins sometimes called 'Periplasmic Binding Proteins') that serve as receptors for nutrients and cofactors in bacterial ABC transporters. Furthermore, structural analysis of MglB-2 found in Treponema pallidum shows it to be one of the founding member of a family of proteins related to the 'Type I' or 'Cluster B' LBPs .
Amino acid:DNA transferase (ADDT)
Type: Domain

This entry represents the α-helical domain of the glycinyl, putrescine and serinyltransferases (grouped as amino acid:DNA transferases, formerly known as alpha-putrescinyl/glutamylthymidine pyrophosphorylases (aGPT-Pplases) ) which catalyse thymidine hypermodifications in the viral genome , transferring glycine, putrescine or serine to 5-phosphomethyl-2'-deoxyuridine (5-PmdU) to produce Nalpha-GlyT, Nalpha-PutT and O-SerT, respectively. These modifications probably prevent degradation of viral genome by the host restriction-modification antiviral defense system .
Peptidoglycan hydrolase LytB, WW-like domain (LytB_WW-like)
Type: Domain

Structural analysis revealed that the catalytic domain of LytB consists of three structurally independent modules: SH3b, WW domain-like, and the glycoside hydrolase family 73 (GH73). This entry is the WW like domain found in endo-beta-N-acetylglucosaminidase LytB from Streptococcus pneumoniae. Functional analysis show that the deletion of both SH3b and WW modules almost completely abolished the activity of LytB. Furthermore, it was shown that the SH3b and WW modules are indispensable for LytB in cell separation .
DNA methylase N-terminal domain (DNA_meth_N)
Type: Domain

This N-terminal domain is found in some DNA methylases, including Type II methyltransferase M.EcoRII (

) and DNA-cytosine methyltransferase .
Npun R1517 (Npun_R1517)
Type: Domain

This domain belongs to Npun R1517 which is found in Nostoc punctiforme. Studies indicate that Npun R1517 is encoded by orphan gene 29. Npun R1517 adopts a sleigh-shaped structure with a two-stranded antiparallel β-sheet forming the floor of the sleigh, a HTH forming the seat and a HTH forming the front of the sleigh .
Ankyrin, UPA domain (Ankyrin_UPA)
Type: Domain

The UPA domain is conserved in UNC5, PIDD, and Ankyrins. It has a β sandwich structure . This entry represents the UPA domain in ankyrins.
THO1_MOS11, C-terminal domain (THO1_MOS11_C)
Type: Domain

This is the C-terminal domain found in THO1 and Modifier of SNC1, 11 (MOS11).

THO is a multi-protein complex involved in the formation of messenger ribonucleoproteins (mRNPs) by coupling transcription with mRNA processing and export. Some studies show that Tho1, like Sub2, can assemble onto the nascent mRNA during transcription and that Tho1 and Sub2 can provide alternative pathways for mRNP biogenesis in the absence of a functional THO complex . The C-terminal region of Tho1 from Saccharomyces cerevisiae, adopts a helical fold similar to that of the WHEP RNA-binding domains of metazoan aminoacyl-tRNA synthetases .

MOS11 contributes to the transfer of mature mRNA from the nucleus to the cytosol . In Arabidospis, the THO/TREX component TEX1 interacts with MOS11 and modulates mRNA export and alternative splicing events .
BILBO1, N-terminal domain (BILBO1_N)
Type: Domain

This is the N-terminal domain of BIBLO1 present mostly in Trypanosomatidae. BILBO1 is a flagella pocket collar component. Depletion of BIBLO1 prevents flagella pocket and flagella pocket collar biogenesis and leads to cell death. This domain has a ubiquitin-like fold and has a conserved patch of four aromatic residues (Phe-12, Trp-71, Tyr-87, and Phe-89) and three basic residues (Lys-15, Lys-60, and Lys-62) .
HP0268 (HP0268)
Type: Domain

HP0268 is a small, characterised protein that is conserved in H. pylori strains and consists of 80 amino acid residues with a molecular weight of approximately 9.5kDa. HP0268 has nicking endonuclease and RNase activities, both of which are specific for a single-strand of nucleotides. It is structurally similar to small MutS-related (SMR) domains, that can be categorised roughly into three subfamilies according to their arrangement in the domain architecture. HP0268 falls into subfamily 3 that is found as stand-alone type proteins. It is proposed that HP0268 has become an evolutionary intermediate between RNases and nicking endonucleases during H. pylori adaptation to the extremely acidic environment of the stomach .
BRCC36, C-terminal helical domain (BRCC36_C)
Type: Domain

This is the C-terminal domain of BRCC36, a Zn2+ dependent deubiquitinating enzyme, present in Camponotus floridanus. BRCC36 hydrolyzes lysine linked ubiquitin chains as part of macromolecular complexes that participate in either interferon signalling or DNA-damage recognition. The domain consists of 2 non canonical helices. The domain interacts hydrophobically with helices alpha 4 and alpha 5 of KIAA0157 in the form of a coiled coil helical bundle. This interaction helps establish the association of BRCC36 with KIAA0157, a pseudo-DUB MPN-protein that is essential for the activity of BRCC36 .
eIF3 subunit M, C-terminal helix domain (eIF3m_C_helix)
Type: Domain

This is the C-terminal helix domain found in Eukaryotic translation initiation factor 3 subunit M (eIF3m). In mammalian eIF3a, the C-terminal helix following the PCI domain is involved in interactions with other core subunits .
S-layer protein SbsC, C-terminal domain (SbsC_C)
Type: Domain

This domain is found in the crystalline bacterial cell-surface layer (S-layer) protein SbsC present in Geobacillus stearothermophilus. S-layers are a common feature of archaeal cell envelopes. SbsC is an oblique lattice forming protein. This domain, termed Domain 9, is located at the C-terminal region of SbsC. The C-terminal region comprises the self-assembly domain responsible for the formation of the crystalline array .
DNA mismatch repair protein HSM3, C-terminal domain (HSM3_C)
Type: Domain

Hsm3 is a proteasome-dedicated chaperone that forms a base precursor, Hsm3-Rpt1-Rpt2-Rpn1 . Hsm3 consists of 23 α-helices forming 11 repeats similar to HEAT repeats. This entry include the last 5 repeats at the C terminus.
Domain of unknown function DUF5620 (DUF5620)
Type: Domain

This is a domain of unknown function predicted to be a carbohydrate binding module .
Pre ATP-grasp domain (PreAtp-grasp)
Type: Domain

This is a preATP grasp domain found in Pheganomycin (PGM1) .
Interleukin receptor mimic protein A (IrmA)
Type: Family

The E. coli interleukin [IL] receptor mimic protein A (IrmA), is a small (13kDa) Uropathogenic E. coli (UPEC) protein that was originally identified in a large reverse genetic screen as a broadly protective vaccine antigen. It has a fibronectin III (FNIII)-like fold that forms a domain-swapped dimer with structural mimicry to the binding domain of the IL-2 receptor (IL-2R), the IL-4 receptor (IL-4R) and, to a lesser extent, the IL-10 receptor (IL-10R). IrmA binds to all three cytokines, with the greatest affinity observed for IL-4. It is suggested that IrmA may contribute to manipulation of the innate immune response during UPEC infection .
Peptidase M61, N-terminal domain (Peptidase_M61_N)
Type: Domain

This domain is found at the N terminus of

and has a β-sandwich-like fold with similarity to the baculovirus p35 protein.
Endoribonuclease Regnase 1/ZC3H12, C-terminal domain (Regnase_1/ZC3H12_C)
Type: Domain

This is the C-terminal domain found in regnase-1, an RNase that directly cleaves mRNAs of inflammatory genes such as IL-6 and IL-12p40, and negatively regulates cellular inflammatory responses. The C-terminal domain is composed of three α helices and resembles ubiquitin associated protein 1 in structure .
Release factor glutamine methyltransferase, N-terminal domain (PrmC_N)
Type: Domain

This entry corresponds to the N-terminal α helical domain of the PrmC/HemK protein. PrmC/HemK is a methyltransferase enzyme that carries out the methylation of the N5 nitrogen of the glutamine found in the conserved GGQ motif of class-1 release factors .
Regulator of G-protein signalling, DHEX domain (RGS_DHEX)
Type: Domain

This domain is found in a diverse group of multifunctional proteins that regulate cellular signalling events downstream of G-protein coupled receptors (GPCRs). They belong to the R7 (Neuronal RGS) subfamily, which includes RGS6, RGS7, RGS9, and RGS11, all of which, in humans, are expressed predominantly in the nervous system . They form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes . In addition, R7 proteins were found to bind many other proteins outside of the G protein signalling pathways including: m-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, guanylyl cyclase, among others. They have an RGS domain, which is an essential part of the R7 protein subfamily. These proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis . This entry also includes egl-10, an orthologue of human RGS7 from C. elegans.

This domain is referred to as DEP helical extension (DHEX) because it is located next to N-terminal Dishevelled/Egl-10/Pleckstrin homology (DEP) domain . Both the DEP and DHEX domains are necessary, but not sufficient, to bind anchoring proteins such as RGS9 anchor protein. These constitute a site of major allosteric regulation of the complex via association with GPCRs and small SNARE-like membrane proteins. DHEX has no close structural homologues .
Testis-specific expressed protein 55 (Tex55)
Type: Family

This family includes testis-specific expressed protein 55 (also known as TSCPA in human) from animals, which is involved in normal spermatogenesis .
Tle cognate immunity protein 4, N-terminal domain (Tli4_N)
Type: Domain

T6SS bacteria employ toxic effectors to inhibit rival cells and concurrently use effector cognate immunity proteins to protect their sibling cells. The effector and immunity pairs (E-I pairs) endow the bacteria with a great advantage in niche competition. This is the C-terminal domain of Tli4 (PA1509 in Pseudomonas aeruginosa). The Tle cognate immunity proteins (Tlis) can directly disable the transported Tle protein and thereby mediate the self-protection process. The Tle-Tli effector-immunity (E-I) pairs confer substantial advantage to the donor cell during interbacterial competition. Tli4 displays a two-domain conformation (domains I and II) and contains 17 β-strands and four helices. These two domains pack into a crab claw-like conformation functioning as an inhibitor of Tle4. Both domains adopt an α+β architecture. Domain I features a central antiparallel β-sheet sandwiched by two helices and a short antiparallel β-sheet. This entry comprises the N-terminal domain I found in Tli4 proteins .
Ribonucleotide reductase, alpha-helical domain (RNR_alpha_hel)
Type: Domain

This is the α helical domain of ribonucleotide reductases. Family members include Ribonucleotide reductase (RNR,

) which catalyse the reductive synthesis of deoxyribonucleotides from their corresponding ribonucleotides. It provides the precursors necessary for DNA synthesis. RNRs divide into three classes on the basis of their metallocofactor usage. This domain is found in Class II. Class II RNRs, found in bacteria, bacteriophage, algae and archaea, use coenzyme B12 (adenosylcobalamin, AdoCbl). Many organisms have more than one class of RNR present in their genomes. Ribonucleotide reductase is an oligomeric enzyme composed of a large sub-unit (700 to 1000 residues) and a small sub-unit (300 to 400 residues) - class II RNRs are less complex, using the small molecule B12 in place of the small chain . Some family members carry ATP cone domain which acts as a functional regulator. Competitive binding of ATP and dATP to an N-terminal ATP-cone domain determines enzyme activity. As the ratio of dATP to ATP increases above a certain threshold, the enzyme activity is turned off. Substrate nucleotides are recognised by relatively simple H-bonding interactions at the N terminus of one or more α helices. In the monomeric class II RNR, the effector binds in a pocket formed by helices in a 130 amino acid insertion which constitutes this domain .
Conserved virulence factor B-like, winged helix domain (CvfB_WH)
Type: Domain

This winged helix domain is found in RNA-binding proteins such as CvfB .
RapA, N-terminal Tudor like domain 1 (Tudor_1_RapA)
Type: Domain

This is one of two Tudor-like domains found in the N-terminal region of RapA proteins. RapA is an abundant RNAP-associated protein of 110kDa molecular weight with ATPase activity. It forms a stable complex with the RNAP core enzyme, but not with the holoenzyme. The ATPase activity of RapA increases upon its binding to RNAP . The N-terminal region of RapA contains two copies of a Tudor-like domains, both folded as a highly bent antiparallel β-sheet. This fold is also found in transcription factor NusG , ribosomal protein L24, human SMN (survival of motor neuron) protein, mammalian DNA repair factor 53BP1, putative fission yeast DNA repair factor Crb2 and bacterial transcription-repair coupling factor known as Mfd. The functional roles of the N-terminal region homologs in these proteins suggest that the Tudor-like domains of RapA may interact with both nucleic acids and RNAP .
RapA, N-terminal Tudor-like domain 2 (Tudor_2_RapA)
Type: Domain

This is the second of two Tudor-like domains found in the N-terminal region of RapA proteins. RapA is an abundant RNAP-associated protein of 110kDa molecular weight with ATPase activity. It forms a stable complex with the RNAP core enzyme, but not with the holoenzyme. The ATPase activity of RapA increases upon its binding to RNAP . The N-terminal region of RapA contains two copies of a Tudor-like domains, both folded as a highly bent antiparallel β-sheet. This fold is also found in transcription factor NusG , ribosomal protein L24, human SMN (survival of motor neuron) protein, mammalian DNA repair factor 53BP1, putative fission yeast DNA repair factor Crb2 and bacterial transcription-repair coupling factor known as Mfd. The functional roles of the N-terminal region homologs in these proteins suggest that the Tudor-like domains of RapA may interact with both nucleic acids and RNAP .
Diphteria toxin repressor/Iron-dependent repressor IdeR, SH3 domain (DtxR/IdeR_SH3)
Type: Domain

This is an SH3 domain which can be found in diphtheria toxin repressor (DtxR) and the closest homologue Iron-dependent repressor IdeR, iron-responsive metalloregulators that control iron uptake . DtxR from Corynebacterium diphtheriae regulates the expression of the gene on corynebacteriophages that encodes diphtheria toxin (DT). Other genes regulated by DtxR include those that encode proteins involved in siderophore-mediated iron uptake .
Vid27, PH-like domain (Vid27_PH)
Type: Domain

This region has been predicted to contain a PH-like domain . It is found in Vid27, a cytoplasmic protein that possibly regulates import of fructose-1,6-bisphosphatase into Vacuolar Import and Degradation (Vid) vesicles, but is not essential for proteasome-dependent degradation of fructose-1,6-bisphosphatase (FBPase) .
Phosphoinositide phosphatase insertion domain (PI_PP_I)
Type: Domain

This domain is found in the effector protein SidP present in Legionella longbeachae. SidP functions as a Phosphoinositide-3-phosphatase specifically hydrolyzing Phosphoinositide(3)P, referred to as PI(3)P, and PI(3,5)P2. The domain is inserted into the N-terminal portion of the catalytic domain and is referred to as the appendage or insertion (I) domain .
Rtt106, pleckstrin homology domain (Rtt106_PH)
Type: Domain

This is a Pleckstrin Homology (PH) domain found on the N-terminal region of the histone chaperone Rtt106 in yeast. Rtt106 binds histone H3 acetylated at lysine 56 (H3K56ac) and facilitates nucleosome assembly during several molecular processes and this N-PH domain is shown to mediate histone binding .
Thiolase-like protein type 1, additional C-terminal domain (TLP1_add_C)
Type: Domain

This domain is found in thiolase-like protein type 1 (TLP1) present in Mycobacterium smegmatis. Thiolase enzymes are acetyl-coenzyme A acetyltransferases which convert two units of acetyl-CoA to acetoacetyl CoA in the mevalonate pathway. This domain is deemed an additional C-terminal region, much like the SPC2-thiolase present in mammals which has an additional C-terminal domain termed the sterol carrier protein-2 (SPC2). However, the additional C-terminal domain in TLP1 folds differently to the traditional SCP2-fold observed in mammalian SPC2-thiolase. The topology of the C-terminal domain of TLP1 is reminiscent of single strand nucleic acid binding proteins .
C19orf47, SAM domain (C19orf47_SAM)
Type: Domain

This entry corresponds to a SAM domain that is found at the N terminus of the human C19orf47 protein.
26S proteasome regulatory subunit Rpn6, N-terminal (Rpn6_N)
Type: Domain

This is the N-terminal domain found in Rpn6 proteins (26S proteasome regulatory subunit). The 26S proteasome holocomplex consists of a 28-subunit barrel-shaped core particle (CP) in the centre capped at the top and bottom by 19-subunit regulatory particles (RPs). The CP forms the catalytic chamber and the RP is formed from two subcomplexes known as the lid and the base . The lid comprises nine Rpn subunits in yeast (Rpn3/5/6/7/8/9/11/12/15) and the base comprises three Rpn subunits (Rpn1/2/13) and six ATPases (Rpt1-6) . Phosphorylation of Rpn6 enhances proteasome ATPase activity and promotes the formation of doubly capped (30S) proteasome, hence accelerating the degradation of short-lived proteins .
Protein of unknown function DUF5580 (DUF5580)
Type: Family

This family of proteins with unknown function can be found in metazoa.