SII-SWORD/CoKE huggingface dataset:
Histone methyltransferase, Tudor domain 2 (Tudor_4)
Type: Domain

This is the second TUDOR domain found in SETDB1 enzymes (

) from mammals, also known as Eggless in Drosophila . In Drosophila, SetdB1 (Egg) is important for oogenesis and the silencing of chromosome 4 . SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase (HMT) that methylates lysine 9 on histone H3 (H3K9). The enzymatic activity of SETDB1, in association with MBD1-containing chromatin-associated factor 1 (MCAF1), converts H3K9me2 to H3K9me3 and represses subsequent transcription. SETDB1 is amplified in cancers such as melanoma and lung cancer, and increased expression of SETDB1 promotes tumorigenesis in a zebrafish melanoma model. In addition, SETDB1 is required for endogenous retrovirus silencing during early embryogenesis, inhibition of adipocyte differentiation, and differentiation of mesenchymal cells into osteoblasts . The tandem Tudor domains in the N-terminal region are involved in protein-protein interactions .
Serine-tRNA ligase type 2, tRNA-binding domain (SerS_tRNA-bd)
Type: Domain

This is the N-terminal domain found in archeal type-2 serine-tRNA ligase (SerRS) (

). The SerRS N-terminal domain interacts with the extra-arm stem and the outer corner of tRNA specific to Selenocysteine (tRNA-Sec) .
Ankyrin ubiquitin-binding domain (AnkUBD)
Type: Domain

This is an Ankyrin repeat domain found in TRABID (also known as Ubiquitin thioesterase ZRANB1) (

). In TRABID, the first ankyrin repeat spans residues 260-290 and is connected to the second repeat residues 313-340 by a long linker that packs against what would correspond to the concave surface in an extended ankyrin-repeat structure. Ankyrin-repeat domains mediate protein interactions through a variety of surfaces. The ankyrin domain of TRABID interacts with ubiquitin, hence it is referred to as the ankyrin ubiquitin-binding domain, or AnkUBD .
MapZ, extracellular domain 1 (MapZ_EC1)
Type: Domain

This is the extracellular domain 1 (MapZextra1) found in Streptococcus pneumoniae cell division site positioning protein MapZ. MapZ ensures accurate placement of the bacterial division site. The domain is a rigid four α-helices with two flexible linkers. The N-terminal end of MapZextra1 is connected to the trans-membrane segment of MapZ whilst the C-terminal is linked to MapZextra2 via a serine rich linker (SRL). The highly conserved residues are not accessible at the surface but are directly involved in many inter-helices interactions allowing for rigidity .
ISP3, C-terminal (ISP3_C)
Type: Domain

This domain is found at the C-terminal of IPS3.

ISP3 protein plays a role in asexual daughter cell formation. The C-terminal domain consists of a seven-stranded antiparallel β-sandwich bordered on one end by a interstrand loop (open end) and capped at the other end by an amphipathic C-terminal helix (closed end). The loop between β5 and β6 is extended and variable. The domain adopts a pleckstrin homology (PH) fold, despite having negligible sequence similarity. PH domains are often found in proteins that support protein-lipid and play a role in mediating membrane localization through IP binding. However, the phospholipid binding properties of PH domains are not conserved in the ISP3. Unlike PH domains, ISP3 is cysteine rich. The cysteine-rich nature of the ISP3s and the number of surface-exposed cysteines may result in redox instability and may also facilitate higher order multimerization. There are no disulfide bonds in ISP3 unlike in ISP1. It is worth noting that ISP1 and ISP3 share low sequence identity but contain the same secondary core elements .
DNA repair protein Crb2, Tudor domain (Crb2_Tudor)
Type: Domain

This is the tudor domain found in DNA repair protein Crb2. Structural and functional studies of Crb2 and its mammalian homologue 53BP1 indicate that the conserved tandem-Tudor domain of 53BP1 and Crb2 preferentially interacts with H4K20me2, though it also binds to H4K20me1 . Furthermore, despite low amino acid sequence similarity, Crb2 is structurally related to 53BP1 in having two tudor domains and a conserved dimethyllysine-binding pocket, and that, like 53BP1, it directly binds H4-K20me2 .
DNA polymerase eta, ubiquitin-binding zinc finger (UBZ3)
Type: Domain

This entry represents type 3 UBZ found in DNA polymerase eta (

). It is important in the recruitment of the polymerase to the stalled replication machinery in translesion synthesis. The UBZ domain adopts a classical C2H2 zinc-finger structure characterised by a β-β-α fold .

The ubiquitin-binding zinc finger (UBZ) is a type of zinc-coordinating β-β-α fold domain found mainly in proteins involved in DNA repair and transcriptional regulation. UBZ domains coordinate a zinc ion with cysteine or histidine residues; depending on their amino acid sequence, UBZ domains are classified into several families . Type 1 UBZs are CCHH-type zinc fingers found in tandem UBZ domains of TAX1-binding protein 1 (TAX1BP1) , type 2 UBZs are CCHC-type zinc fingers found in FAAP20 which is a subunit of the Fanconi anemia (FA) core complex , type 3 UBZs are CCHH-type zinc fingers found only in the Y-family translesion polymerase eta , and type 4 UBZs are CCHC-type zinc fingers found in Y-family translesion polymerase kappa, Werner helicase-interacting protein 1 (WRNIP1), and Rad18 .
Chromatin remodeling factor Mit1, C-terminal Zn finger 1 (Znf-CCCH_7)
Type: Domain

The Snf2/Hdac Repressive Complex (SHREC) is the fission yeast nucleosome remodeling and deacetylation (NuRD) equivalent and plays a major role in transcriptional gene silencing (TGS) within S. pombe heterochromatin. SHREC consists of the chromatin remodeler Mit1, the HDAC Clr3, and Clr1 and Clr2 proteins. The Mit1 C terminus contains two zinc binding motifs (CCHC zinc fingers) at the C terminus onto which the α helices from both Clr1 and Mit1 pack. The Mit1 chromatin remodeler uses its C-terminal domain to intimately bind to the N-terminal half of Clr1 to integrate into the SHREC complex. This is entry represents the first C-terminal zinc-binding domain found on Mit-1 .
CxC7-like cysteine cluster associated with KDZ transposases (CxC7)
Type: Domain

A predicted Zinc chelating domain present C-terminal to the KDZ transposase domain in Xiphophorus maculatus .
Phage-Barnase-EndoU-ColicinE5/D-RelE like nuclease 3 (PBECR3)
Type: Domain

Polyvalent proteins are predicted to be transmitted by genomic parasites such as conjugative elements, plasmids, and phages during the initial phase of infection along with their DNA. They are typified by the presence of multiple domains with disparate activities .

This entry represents a predicted endoRNase of the Barnase-EndoU-ColicinE5/D-RelE like nuclease fold found in polyvalent proteins of phages and conjugative elements. The predicted active site contains a conserved histidine and threonine residues .
Ribonuclease inhibitor, leucine rich repeat cap (LRR_RI_cap)
Type: Repeat

Leucine-rich repeats are composed of a β-α unit. This repeat is found as capping unit (N- or C- terminal of the repeat region) of ribonuclease inhibitors .
Phage spike trimer 2 (Phage_spike_2)
Type: Repeat

This entry includes some phage spike repeats that fail to be detected

model.
AbiTii (AbiTii)
Type: Domain

This is an α + β domain. It is found fused to the N terminus of the c2405 family of HEPN domains, and in few cases to Ymh .
Interleukin-4 inducing immunoglobulin-binding domain (IL4_i_Ig)
Type: Domain

This domain is found in Interleukin-4 inducing protein alpha-1 (IPSE/alpha-1) present in Schistosoma mansoni, a parasite of humans. IPSE/alpha-1 triggers the release of IL-4 from basophils in the liver which is a major site of egg deposition during S. mansoni infection. This domain adopts a beta-gamma-crystallin fold that is stabilised by three disulfide bonds within the domain (23/26, 59/93, and 111/121). The domain is involved in immunoglobulin binding .
NSD, Cys-His rich domain (C5HCH)
Type: Domain

This is an NSD-specific Cys-His rich region (C5HCH) domain. Proteins containing this domain include NSD (nuclear receptor SET domain-containing) proteins. This domain is located on the C-terminal of NSD1, 2 and 3 proteins. C5HCH domain lies adjacent to the fifth plant homeodomain (PHD5). The PHD5-C5HCH module of NSD3 (PHD5-C5HCHNSD3) recognises the H3 N-terminal peptide containing unmodified K4 and trimethylated K9. Moreover, it has been reported that the PHD5-C5HCH module of NSD1 (PHD5-C5HCH) was the sole region required for tight binding of the NUP98-NSD1 fusion protein to the HoxA9 gene promoter, implicating that PHD5-C5HCH might have chromatin targeting ability .
Polysaccharide biosynthesis enzyme WcbI (WcbI)
Type: Domain

Capsular polysaccharides (CPSs) are protective structures on the surfaces of many Gram-negative bacteria. WcbI is one of several genes in the CPS biosynthetic cluster whose deletion leads to significant attenuation of the pathogen. Structural analysis and biophysical assays suggest that WcbI functions as an acetyltransferase enzyme but it requires another functional module to carry out this function. WcbI adopts a predominantly helical fold where the N-terminal 100 amino acids form a ligand-binding domain and binds tightly to coenzyme A and its derivative acetyl-CoA .
Xer recombinase, N-terminal (Xer_N)
Type: Domain

Xer recombinases are members of the tyrosine site-specific recombinase superfamily, a large group of enzymes that catalyze DNA breakage and rejoining using a conserved tyrosine nucleophile. Tyrosine recombinases promote various programmed DNA rearrangements including the monomerization of phage, plasmid and chromosome multimers, resolution of hairpin telomeres, and the movement of virulence and antibiotic resistance carrying integrative mobile genetic elements. Structural analysis of Helicobacter pylori XerH indicates that this N-terminal domain consisting of six α-helices contacts the DNA using a four-helix bundle .
TANK-binding kinase 1, coiled-coil domain 1 (TBK1_CC1)
Type: Domain

This is a coiled-coil domain found in TANK-binding kinase 1 (TBK1), it comprises one of two coiled-coil domains found in the scaffold dimerization region. TBK1 is a serine/threonine kinase and a noncanonical member of the IKK family implicated in diverse cellular functions, including innate immune response as well as tumorigenesis and development . Deletion of the coiled-coil 1 region in TBK1 lead to a severe impairment in TBK1 function even upon over-expression .
TNF receptor-associated factor 6, zinc finger 2 (TRAF6_Z2)
Type: Domain

This domain is the second of three zinc fingers of Homo sapiens TNF receptor associated factor 6 (TRAF6). TRAF6 mediates Lys63 (K63)-linked polyubiquitination for Necrosis Factor-kappaB activation. The first three residues and the last Cys of finger 1 form a classical type I β-turn .
Large polyvalent protein associated domain 29 (LPD29)
Type: Domain

This is an α and β fold domain with conserved polar residues that is found in polyvalent proteins of conjugative elements .
CHIP, N-terminal tetratricopeptide repeat domain (CHIP_TPR_N)
Type: Domain

This is N-terminal tetratricopeptide repeat (TPR) domain found in CHIP, the C terminus of Hsp70 interacting proteins. The TPR domain of CHIP binds directly to EEVD motifs located at the C termini of Hsc/Hsp70 and Hsp90 .
Domain of unknown function DUF5642 (DUF5642)
Type: Domain

This is a domain of unknown function found in actinobacteria.
PlcR, tetratricopeptide repeat (PlcR_TPR)
Type: Repeat

The bacterial PIcR helix-turn-helix transcription factor includes five TPR units of different lengths . This entry represents the central, medium-sized TPR repeat.
ISP1 C-terminal (ISP1_C)
Type: Domain

This is the C-terminal domain of ISP1 protein, which plays a role in asexual daughter cell formation, such as in Toxoplasma gondii. The domain consists of a seven-stranded antiparallel β-sandwich bordered on one end by an inter-strand loop (open end) and capped at the other end by an amphipathic C-terminal helix (closed end). The domain adopts a pleckstrin homology (PH) fold, despite having negligible sequence similarity. PH domains are often found in proteins that support protein-lipid and play a role in mediating membrane localization through IP binding. However, the phospholipid binding properties of PH domains are not conserved in the TgISP1. Unlike PH domains, ISP1 is cysteine rich. The cysteine-rich nature of the ISPs and the number of surface-exposed cysteines may result in redox instability and may also facilitate higher order multimerization. A disulfide bond between beta 2 and beta 3 is likely a structural feature of the ISP1, as both cysteines appear broadly conserved .
RET, cadherin-like domain 4 (RET_CLD4)
Type: Domain

RET is a single transmembrane-spanning receptor tyrosine kinase (RTK) that plays critical roles in the development of vertebrates. Structural analysis indicate that the ligand-binding RET ectodomain (RET-ECD) contains four consecutive cadherin-like domains (CLD1-CLD4) followed by a membrane-proximal cysteine-rich domain (CRD). This entry relates to CLD4 which is required for CRD folding .
pEK499_p136 HEPN domain (pEK499_p136)
Type: Domain

This is a pEK499_p136-like HEPN domain .
Protein of unknown function DUF5543 (DUF5543)
Type: Family

This is a family of unknown function found in primates.
CxC1-like cysteine cluster associated with KDZ transposases (CxC1)
Type: Domain

This entry represents a predicted zinc chelating domain present N-terminal to the KDZ transposase domain .
Lpg0393, helical bundle domain (Lpg0393_HBD)
Type: Domain

Lpg0393 is a Legionella pneumophila effector protein. Structure analysis reveals that it has two domains, the N-terminal domain is a Vps9-like domain, which is structurally most similar to the catalytic core of human Rabex-5 that activates the endosomal Rab proteins Rab5, Rab21 and Rab22. The C-terminal domain is a helical bundle domain. The C-terminal helical bundle of Lpg0393 corresponds to the N-terminal helical bundle of Rabex-5, it lacks an obvious region that corresponds to the membrane-binding motif of Rabex-5. One possibility may be that Lpg0393 localization to endosomes depends on an unknown Legionella effector .
Synaptonemal complex protein 2, armadillo-repeat-like domain (SYCP2_ARLD)
Type: Domain

Synaptonemal complex protein 2 (SYCP2) N-terminal region contains two separate subdomains an ARLD (armadillo-repeat-like domain) and an SLD (Spt16M-like domain). The ARLD domain belongs to the armadillo-repeat protein family. Armadillo-repeat units often form a superhelix, which typically provides a platform for many protein partners that transduce Wnt signaling, such as beta-catenin. The ARLD of mouse SYCP2 was found to associate with different protein partners, including CENP J and CENP F. ARLD structure is highly similar to that of the 'required for cell differentiation (RCD-1)' protein .
HEPN-like integron domain (HEPN-like_int)
Type: Domain

This is a domain found in HEPN-like nucleases. It is part of mobile integron element. The integron cassettes are known to be activated by stress conditions, thereby allowing swapping of genetic material that might be of adaptive value. Hence it is hypothesized that the HEPN domains present in some integron cassettes contribute to the stress response by functioning as RNases that induce dormancy by probably inhibiting translation and thus enabling survival of harsh conditions .
Antigen I/II, N-terminal (AgI/II_N)
Type: Domain

This entry describes an N-terminal domain found in Antigen I/II (also known antigen B, PAc or adhesin P1).

The cariogenic bacterium Streptococcus mutans uses adhesin P1 to adhere to tooth surfaces, extracellular matrix components, and other bacteria. The N terminus forms a stabilizing scaffold by wrapping behind the base of P1's elongated stalk and physically 'locking' it into place. It is suggested that the N-terminal has a pronounced impact on P1 immunogenicity, antigenicity, folding, stability, and adherent function .

This domain can also found in aggregation substance (Asa1) from Enterococcus faecalis. It is a structural homologue of Streptococcus mutans Antigen I/II. It acts as an adhesin mediating cell-cell contact between different E. faecalis strains and also binding of E. faecalis to eukaryotic cells .
Protein glutaminase (Gln_deamidase_2)
Type: Domain

Protein glutaminase (PG,

) can deamidate glutamine residues in proteins to glutamate residues. This entry represents the mature PG enzyme which bears partial homology to factor XIII-like Transglutaminase (TG), especially its Cys-His-Asp catalytic triad. A similar triad (Cys-His-Asn) is also shared by some cysteine proteases such as papain and actinidin. The mature PG is a monomer enzyme consisting of 185 amino acid residues .
Tk-SP N-propeptide domain (Tk-SP_N-pro)
Type: Domain

This is the N-propeptide domain found in Tk-SP, a subtilisin-like serine protease from Thermococcus kodakaraensis. The β sheet of this domain packs tightly to the two nearly parallel α helices 2 and 3 located at the surface of the subtilisin domain. Gln105 and Asp107 of the N-propeptide domain also bind to the N-termini of these two α-helices to form helix caps .
ATP nucleosidase Cap17-like, N-terminal domain (Cap17-like_N)
Type: Domain

This entry represents a domain found at the N-terminal of ATP nucleosidase Cap17 from E.coli and related sequences. Cap17 is likely an effector protein with (d)ATP degrading activity of a CBASS (cyclic oligonucleotide-based antiphage signaling system) antivirus system, which provides immunity against bacteriophages . Members of this entry often co-occur genomically with the bacterial HORMA and Pch2/TRIP13 domains .
ResE, histidine kinase sensor domain (HisK_sensor)
Type: Domain

The Bacillus subtilis ResD-ResE two-component (TC) regulatory system activates genes involved in nitrate respiration in response to oxygen limitation or nitric oxide (NO). The sensor kinase ResE activates the response regulator ResD through phosphorylation, which then binds to the regulatory region of genes involved in anaerobiosis to activate their transcription. In other words, ResE is involved in sensing signals related to the redox state of the cells. ResE is composed of an N-terminal signal input domain and a C-terminal catalytic domain. The N-terminal domain contains two transmembrane subdomains and a large extra-cytoplasmic loop. Mutational analysis indicate that cytoplasmic ResE lacking the transmembrane segments and the extra-cytoplasmic loop retains the ability to sense oxygen limitation and NO, which leads to transcriptional activation of ResDE-dependent genes. However, it is also proposed that the extra-cytoplasmic region may serve as a second signal-sensing subdomain. This suggests that the extracytoplasmic region could contribute to amplification of ResE activity leading to the robust activation of genes required for anaerobic metabolism in B. subtilis .
YubB, ferredoxin-like domain (YubB_C)
Type: Domain

This domain has a ferredoxin like fold. It can be found in the YubB protein from E. coli. Its function is not clear.
KN17, SH3-like domain (KN17_SH3)
Type: Domain

This domain can be found at the C terminus of the human KIN17 protein and its homologues. In human cells, over-expression of KIN17 modifies the nuclear morphology and inhibits S-phase progression, thus blocking cell growth as part of the response to genotoxics. The C-terminal domain exhibits an all-β structure consisting of two tightly packed SH3-like subdomains, the first one represented in this entry. This domain has structural similarity with various SH3-like domains, although it lacks similarities in both primary sequence and charge distribution .
Bacterial alpha amylase, C-terminal domain (Bac_A_amyl_C)
Type: Domain

This is a bacterial alpha amaylase C-terminal domain found mostly in bacilli.
Pan3 pseudokinase domain (Pan3_PK)
Type: Domain

This is a pseudokinase (PK) domain found in PAB-dependent poly(A)-specific ribonuclease subunit PAN3. PAN3 proteins contain three prominent regions: an unstructured N-terminal region (N-term), a central PK domain, and a highly conserved C-terminal domain (C-term). The PAN3 PK domain has retained its ATP binding capacity, and this function is required for mRNA degradation in vivo. Analysis of Pan3 amino acids sequences show that, despite of retaining the general structural characteristics of protein kinases, the PK domain has substitutions in all the conserved motifs that are critical for kinase activity, such as in the catalytic VAIK and HRD motifs and in the Mg2+ binding DFG motif. However, the PAN3 PK domain has been shown to bind ATP. Furthermore, similar to other kinases, the ATP-binding site is located in the cleft between the N- and C-lobes of the kinase fold, however, the ATP-binding pocket is wider than that of typical kinases .
Peptidase M60, C-terminal (M60_C)
Type: Domain

This is C-terminal domain (CTD) of M60-peptidases . It can also be found at the C-terminal region of gingipain B (RgpB) from P. gingivalis. It was found to possess a typical Ig-like fold encompassing seven antiparallel β-strands organized in two β-sheets, packed into a β-sandwich structure that can spontaneously dimerise through C-terminal strand swapping. Translocation of gingipains from the periplasm across the OM is dependent on the conserved CTD, which appears to be important for secretion of the proteins and in particular, truncation of the last few C-terminal residues of this domain leads to accumulation of gingipains in the periplasm. Subsequently, the T9SS targeting signal was demonstrated to reside within the last 22 residues at the C terminus of the CTD. During gingipain translocation across the OM, the CTD is cleaved off by PorU .
SAV2148-like HEPN domain (HEPN_SAV2148)
Type: Domain

This is a SAV2148-like HEPN nuclease domain .
DNA mismatch repair protein HSM3, N-terminal domain (HSM3_N)
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 the HEAT repeats. This entry includes the first 5 repeats at the N terminus.
DNA mitochondrial polymerase, exonuclease domain (DNApol_Exo)
Type: Domain

This domain belongs to human mitochondrial DNA polymerase (Pol-gamma). Pol-gamma has a catalytic subunit, Pol gamma-A, which possesses both polymerase and proofreading exonuclease activities and an accessory subunit, Pol gamma-B, which accelerates polymerization rate and suppresses exonuclease activity. This domain is the exonuclease domain of the catalytic subunit, Pol gamma-A .
Heterogeneous nuclear ribonucleoprotein Q acidic domain (hnRNP_Q_AcD)
Type: Domain

This is an acidic sequence segment domain found in the splicing factor SYNCRIP (hnRNP Q) which is involved in viral replication, neural morphogenesis, modulation of circadian oscillation and the regulation of the cytidine deaminase APOBEC1. This domain is a self-folding globular domain with an all α-helix architecture with negatively charged surface areas. Additionally it contains a large hydrophobic cavity and a positively charged surface area as potential epitopes for inter-molecular interactions .
OSBS, enolase-like N-terminal domain (OSBS_N)
Type: Domain

This is the N-terminal domain found in o-succinylbenzoate synthase (OSBS) enzymes (

). Like other members of the enolase superfamily, OSBS enzymes are composed of a C-terminal catalytic (β/α)7β-barrel domain (

) and an N-terminal capping domain with an α+β fold that is found in the enolase superfamily . This actino-bacterial N-terminal domain lacks the prototypical first two helices of the enolase capping domains. Structural analysis of T. fusca OSBS reveals that this is compensated for with an extra helix appended to the C terminus .
Cell-surface Ig-like, bacterial (Ig-like_bac)
Type: Domain

This presumed domain is found repeated in bacterial cell surface proteins.