SII-SWORD/CoKE huggingface dataset:
Protein of unknown function DUF5570 (DUF5570)
Type: Family

This is a family of unknown function found in chordata. Family members contain a transmembrane region in the C-terminal and have been shown to be localized to the Golgi apparatus .
Beta-galactosidase, beta-sandwich domain (GHD)
Type: Domain

This entry corresponds to a β sandwich like domain found in glycosyl hydrolase family 35 beta galactosidase enzymes.
Sld3, N-terminal (Sld3_N)
Type: Domain

This entry represents the N-terminal domain of Sld3 which is shown to bind to the N-terminal domain of Sld7 . It adopts a Ku70-like β-barrel fold that in this protein is truncated, containing five β-strands .
Cthe_2314-like HEPN (HEPN_Cthe2314)
Type: Domain

This entry represents Cthe_2314-like HEPN .
McpB, third HAMP domain (McpB_HAMP_3rd)
Type: Domain

This entry represents the third of five HAMP domains of Methyl-accepting chemotaxis protein McpB from Pseudomonas aeruginosa and similar sequences mainly from gammaproteobacteria. McpB, also known as Aerotaxis transducer Aer2, is a chemoreceptor that plays a critical role in the virulence and pathogenesis of the bacteria in a variety of hosts. This domain adopts a conformation resembling Af1503, with only minor differences in helical tilt and orientation . The basic construction of each HAMP domain consists of a monomeric unit of two parallel α-helices (AS1 and AS2) joined by an elongated connector of 12-14 residues form a parallel four-helix bundle .
Cysteine-rich protective antigen 6 bladed domain (CyRPA)
Type: Domain

Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) is a 42.8kDa protein of 362 residues with a predicted N-terminal secretion signal. It is part of a multi-protein complex including the PfRH5-interacting protein PfRipr and the reticulocyte binding-like homologous protein PfRH5, which binds to the erythrocyte receptor basigin. PfRH5, PfCyRPA, and PfRipr colocalize during parasite invasion at the junction between merozoites and erythrocytes. The complex seems to be required both for triggering Ca2+ release and establishment of tight junctions. PfCyRPA adopts a 6-bladed β-propeller structure with similarity to the classic sialidase fold, but it has no sialidase activity and fulfills a purely non-enzymatic function. Each blade of the propeller is constructed by a four-stranded anti-parallel β-sheet .
ThiD2 (ThiD2)
Type: Domain

This domain functions as a ThiD protein and is called the ThiD2. The domain is associated with the ThiE domain in some proteins .
DdrB-like domain (DdrB_dom)
Type: Domain

Proteins containing this domain are members of the ParB/sulfiredoxin superfamily found in polyvalent proteins prototyped by the version in the phage P1 ddRB protein. These proteins are predicted to function as nucleases .
Large catalase, C-terminal domain (Catalase_large_C)
Type: Domain

The most conspicuous difference between small and large catalases is the presence in large catalases of an extra C-terminal domain. This domain is found at the C terminus of a variety of large catalase enzymes. Structurally it is related to class I glutamine amidotransferase domains . The precise molecular function of this domain is uncertain.
PARP16 N-terminal domain (PARP16_N)
Type: Domain

This is the N-terminal domain of poly ADP-ribose polymerase (PARP16 also known as ARTD15) present in homo sapiens. ARTDs catalyse the formation of branched or unbranched chains of ADP-ribose units on protein side chains. The N-terminal domain of ARTD15 does not share any obvious sequence similarity with the regulatory domains of ARTD1-4. The N-terminal domain arrangement in both ARTD15 and ARTD1-3 suggests a regulatory role through different mechanisms .
Cell wall elongation regulator TseB-like domain (TseB-like_dom)
Type: Domain

This entry represents a domain found in the probable cell wall elongation regulator TseB from Bacillus subtilis and similar sequences from firmicutes. TseB is required for normal cell shape. It plays an important role in cell wall elongation during exponential phase and spore outgrowth . This domain shows an α-β structure.
Dextranase, beta solenoid repeat (B_solenoid_dext)
Type: Repeat

The crystal structures of Dex49A from Penicillium minioluteum and of ATCC9642 isopullulanase from Aspergillus niger include β-solenoid repeats, sharing structural similarities. This entry includes a single repeat unit of the repeat regions.
DUF4458 domain-containing protein, leucine-rich repeat (DUF4458_prot_LRR)
Type: Repeat

This entry represents the leucine-rich repeat (LRR) found in proteins that also contain the N-terminal DUF4458 domain.
Protein of unknown function DUF5588 (DUF5588)
Type: Family

This is a family of unknown function found in animals.
Type III R-M EcoP15I, C-terminal (T3RM_EcoP15I_C)
Type: Domain

This domain is found in the Type III restriction-modification EcoP15I complex, present in E. coli. The Mod subunits function as a dimer with ModA recognizing the DNA and ModB methylating the target adenine base. This domain is found in the C-terminal of the ModB subunit .
COP9 signalosome complex subunit 4, helix turn helix domain (CSN4_HTH)
Type: Domain

Cullin-RING E3 ubiquitin ligases (CRLs) are regulated by the eight-subunit COP9 signalosome (CSN). Enzymatically, CSN functions as an isopeptidase that removes the ubiquitin-like activator NEDD8 from CRLs, but it can also bind deneddylated CRLs and maintain them in an inactive state. The CSN subunits CSN1, CSN2, CSN3, CSN4, CSN7 and CSN8, share a common domain composition: an N-terminal array of tandem α-helical tetratricopeptide/-like repeats, a 34 residue motif, followed by a PCI domain, which encompasses a WH subdomain, a linker, and one or two α-helices at the C terminus.
MazG, C-terminal (MazG_C)
Type: Domain

This entry represents an α+β fold domain found C-terminal to the MazG pyrophosphatase domain. The domain has a conserved DxYRxHDxxH motif indicative of catalytic activity. Based on its broader context in DNA modification, it is proposed to function as a nucleotide kinase .
Hemolysin coregulated protein (Hcp) TssD (Hcp_Tssd)
Type: Family

This entry represents a family of proteins including Hemolysin coregulated protein, Hcp (also known as TssD).

Type VI secretion systems (T6SSs) are multiprotein complexes requiring numerous core proteins (Tss proteins) that function as a toxin delivery systems. The core Tss proteins include cytoplasmic, transmembrane, and outer membrane components. The toxin delivery apparatus includes a needle or tube structure which functions as a puncturing device. This is comprised of a phage-like complex, similar to the T4 contractile bacteriophage tail, which is thought to be anchored to the membrane by a trans-envelope complex. The inner tube is formed of Hcp (TssD), assembled as stacked hexamers . Hcp proteins have also been reported to function as chaperones, by binding to and stabilizing effectors .
Restriction endonuclease AspBHI, N-terminal (RE_AspBHI_N)
Type: Domain

This is the N-terminal domain found in modification-dependent restriction endonuclease proteins such as AspBHI, which can be found in Azoarcus sp. AspBHI is a homo-tetrameric protein that recognizes 5-methylcytosine in the double-strand DNA sequence context of (C/T) (C/G) (5mC) nucleotide (C/G) and cleaves the two strands at a fixed distance (N12/N16) 3 to the modified cytosine. The N-terminal domain is responsible for DNA-recognition and resembles an SRA-like 5-methylcytosine binding domain in structure and function .
STATa immunoglobulin-like domain (STATa_Ig)
Type: Domain

This domain is found in signal transducer and activator of transcription A protein (STATa) present in Dictyostelium discoideum (dd). STATa is responsible for transcriptionally regulating cellular differentiation in Dictyostelium discoideum. ddSTATa is the only non-metazoan known to employ SH2 domain signaling. This domain adopts an Immunoglobulin-like fold .
Linalool dehydratase/isomerase (Ldi)
Type: Domain

This (α,α)6 barrel fold domain is found in linalool dehydratase/isomerase (Ldi,

) and linalool isomerase (Lis) from the betaproteobacterium Castellaniella defragrans 65Phen and Thauera linaloolentis 47Lol , respectively. Ldi mineralizes monoterpenes coupled to anaerobic denitrification. The periplasmic enzyme reversibly catalyses the isomerisation from the primary alkenol geraniol into the tertiary alkenol (S)-linalool and its dehydration to beta-myrcene. Each monomer is built up of a classical (α,α)6 barrel fold composed of six inner helices. Structural data of Ldi revealed the terpene binding site between two monomers inside a hydrophobic channel, and three catalytic clusters involved in catalysis .
Xrn1, helical domain (Xrn1_helical)
Type: Domain

This helical domain is part of the Xrn1 catalytic core . Xrn1 is a cytoplasmic 5'-3' exonuclease that degrades decapped mRNAs. This domain can also be found in Xrn2 .
MmyB-like transcription regulator ligand binding (MLTR_LBD)
Type: Domain

This entry represents the ligand binding domain found in the C-terminal portion of a family of actinobacterial transcription factors. Studies of the crystal structure indicate that the domain has fold similar to the Per-Arnt-Sim (PAS) domain .
RACo-like, middle region (Raco-like_middle)
Type: Domain

This entry represents the middle region of the reductive activator of CoFeSP (RACo) proteins (

). This region contains residues in their α-helices (H6 and H7) that mediate dimerization with subdomain I of the C-terminal domain. Structure analysis of RACo indicate that it contains 4 regions: N-terminal region (residues 3-94) binding the [2Fe-2S] cluster, a linker region (residues 95-125), the middle region (residues 126-206), and the large C-terminal domain (residues 207-630) .
BclA, C-terminal domain (BclA_C)
Type: Domain

This is the C-terminal domain of BclA (Bacillus collagen-like protein of anthracis) which is expressed on spores of Bacillus species. Trimers of the C-terminal domain (CTD) form the tips of the spore's hair-like nap and are the immunodominant target of vertebrate antibodies and drive trimerization . Structure analysis indicate the C-terminal region of the peptide folding into an all-β structure with a jelly-fold topology, similar to the first human complement C1q, a member of the tumor necrosis factor (TNF)-like family. The C-terminal globular domain has been shown to be located on the exterior of the exosporium, and therefore is critical in determining the immunogenicity of the spore in a mammalian host .
IL-1Ra-like, immunoglobulin domain (IL-1RAcP-like_ig)
Type: Domain

This is an immunoglobulin domain which can be found in Interleukin-1 receptors and Interleukin 1 receptor accessory proteins (IL-1RAcP).

IL-1RAcP is a member of the Ig superfamily and has a limited homology throughout the protein to both Type I and Type II IL-1 receptors. IL-1RAcP is a transmembrane protein required for IL-1 signal transduction . It increases the binding affinity of the recombinant Type I IL-1R for IL-1 beta when the two receptor proteins are co-expressed . It has been suggested to play a role in the formation of the active receptor complex .
Probable aminopeptidase NPEPL1, N-terminal (NPEPL1_N)
Type: Domain

This domain is found in the N-terminal region of NPEPL1 from mammals and Lap-1 from C. elegans. NPEPL1 and Lap-1 belong to the M17 aminopeptidase family, whose members are Zn-dependent exopeptidases that catalyse the removal of unsubstituted amino acid residues from the N terminus of peptides .
SAM domain (SAM_3)
Type: Domain

SAM domains are found in a diverse set of proteins, which include scaffolding proteins, transcription regulators, translational regulators tyrosine kinases and serine/threonine kinases. Structures of SAM domains reveal a common five helical structure. The SAM domain is involved in a variety of functions. The most widespread function is in domain-domain interactions. This SAM (sterile alpha motif) domain is found in epidermal growth factor receptor kinase substrate (EPS8) and other proteins.
TnsE, C-terminal (TnsE_C)
Type: Domain

The bacterial transposon Tn7 facilitates horizontal transfer by directing transposition into actively replicating DNA with the element-encoded protein TnsE. Structural analysis of the C-terminal domain of TnsE identified a central V-shaped loop that toggles between two distinct conformations. It is suggested that a conformational change within the C-terminal domain of TnsE underlies target site selection by regulating stable engagement of the target DNA while providing a signal for activating transposition .
Phage-Barnase-EndoU-ColicinE5/D-RelE like nuclease 4 (PBECR4)
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 residue .
Ubl4, C-terminal TUGS domain (Ubl4_C_TUGS)
Type: Domain

This is the C-terminal domain of Ubiquitin-like protein 4A, an orthologue of yeast Get5. In budding yeasts, Get proteins directly mediate the insertion of newly synthesized TA proteins into endoplasmic reticulum membranes. Similarly, mammalian BAG6, Ubl4a, and SGTA make up a trimeric complex that binds TA proteins post-translationally and then loads them onto the cytosolic ATPase TRC40, which in turn targets them to the endoplasmic reticulum. Structural studies show that this C-terminal TUGS domain of Ubl4a is essential for BAG6 tethering. Given that BAG6 mediates oligomeric complex formation of Ubl4a, TRC35, and TRC40 (mammalian counterparts of Get5, Get4, and Get3, respectively), the C-terminal TUGS domain might be crucial for supporting BAG6-mediated Ubl4a-TRC35 complex formation in humans as an alternative to the direct Get5-Get4 interaction in yeast .
Protein of unknown function DUF5545 (DUF5545)
Type: Family

This is a family of unknown function found in primates.
DNA gyrase subunit B insert domain (GyrB_insert)
Type: Domain

This is the insert domain found in DNA gyrase B subunit proteins. Studies indicate that the insert has two functions, acting as a steric buttress to pre-configure the primary DNA-binding site, and serving as a relay that may help coordinate communication between different functional domains .
CinA, KH domain (CinA_KH)
Type: Domain

This domain is found in competence-induced protein A (CinA) present in Thermus thermophiles. CinA is important in the horizontal transfer of genes via competence and may also participate in the pyridine nucleotide cycle, which recycles products formed by non-redox uses of NAD. This domain has a KH-type fold and contains the absolutely conserved Glu-187, which stabilizes the binding of Mg2+ and hence polarizes the P=O bond for hydrolysis. A major feature of the CinA in T. thermophiles structure is the asymmetry in the dimer, which is caused by contact between a KH-type domain on the opposite chain and the bound ADP-ribose. This has the effect of closing the active site, allowing additional recognition of ADP-ribose by residues from the KH-type domain .
Complement C3/4/5, macroglobulin domain MG1 (C3/4/5_MG1)
Type: Domain

This entry represents the N-terminal macroglobulin domain, MG1, found in complement proteins C3, C4 and C5 , and their homologues such as Cobra venom factor, and other venom factor proteins.
Mos1 transposase, HTH domain (Mos1_HTH)
Type: Domain

The N-terminal domain of the Mos1 Mariner transposase comprises two HTH domains . This HTH domain binds in the DNA major groove to the transposons inverted repeats.
AbiJ-NTD3 (AbiJ-NTD3)
Type: Domain

AbiJ_NTD3(for AbiJ N-terminal domain) is an alpha beta domain>It is found fused to AbiJ-like HEPN domains and to other domains presumably involved in defense .
Syntrophin, split Pleckstrin homology (PH) domain (PHsplit_syntrophin)
Type: Domain

Syntrophins are scaffold proteins that associate with associate with the Duchenne muscular dystrophy protein dystrophin and the dystrophin-related proteins, utrophin and dystrobrevin to form the dystrophin glycoprotein complex (DGC). There are 5 members: alpha, beta1, beta2, gamma1, and gamma2) all of which contains a split (also called joined) PH domain and a PDZ domain (PHN-PDZ-PHC). The split PH domain of alpha-syntrophin adopts a canonical PH domain fold and together with PDZ forms a supramodule functioning synergistically in binding to inositol phospholipids. The alpha-syntrophin PH-PDZ supramodule showed strong binding to phosphoinositides PI(3,5)P2 and PI(5)P, modest binding to PI(3,4)P2 and PI(4,5)P2, and weak binding to PI(3)P, PI(4)P, and PI(3,4,5)P. There are a large number of signaling proteins that bind to the PDZ domain of syntrophins: nitric oxide synthase (nNOS), aquaporin-4, voltage-gated sodium channels, potassium channels, serine/threonine protein kinases, and the ATP-binding cassette transporter A1 .
Inositol-tetrakisphosphate 1-kinase, N-terminal (ITPK1_N)
Type: Domain

This entry represents the N-terminal domain of inositol-tetrakisphosphate 1-kinase (ITPK1), which is a kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3 .
ATRX, ADD domain (ADD_ATRX)
Type: Domain

This is a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in ATRX proteins. Chromatin-associated human protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation called ATR-X syndrome. Mutations or knockdown of ATRX expression cause diverse effects, including altered patterns of DNA methylation, a telomere-dysfunction phenotype, aberrant chromosome segregation, premature sister chromatid separation and changes in gene expression. ATRX localizes predominantly to large, tandemly repeated regions (such as telomeres, centromeres and ribosomal DNA) associated with heterochromatin, and studies show that it directs H3.3 deposition to pericentric and telomeric heterochromatin. The ADD domain of ATRX, in which most syndrome-causing mutations occur, engages the N-terminal tail of histone H3 through two rigidly oriented binding pockets, one for unmodified Lys4 and the other for di- or trimethylated Lys9. Mutations in the ATRX ADD domain cause mislocalization of ATRX protein to heterochromatin, and this may contribute to understanding the underlying etiology of ATRX syndrome. Structure analysis of the ADD domain of ATRX revealed that it contains a PHD zinc-finger domain packed against a GATA-like zinc finger. Same structure is also found in the DNMT3 DNA methyltransferases and DNMT3L .
Mvd1, C-terminal (Mvd1_C)
Type: Domain

Mvd1, also known as mevalonate-5-diphosphate decarboxylase (

), catalyzes the ATP dependent decarboxylation of mevalonate 5-diphosphate (MVAPP) to form isopentenyl 5-diphosphate. The reaction is required for production of polyisoprenoids and sterols from acetyl-CoA. This entry represents the C-terminal domain of Mvd1, which is a member of the GHMP kinase superfamily.
Ubiquitinyl hydrolase, variant UBP zinc finger (UBP13_Znf-UBP_var)
Type: Domain

This domain is found at the C terminus of the ubiquitin hydrolases and is related to the UBP-type zinc finger domain (

). However, it has an altered pattern of zinc binding residues.
26S proteasome non-ATPase regulatory subunit RPN1, C-terminal (RPN1_C)
Type: Domain

This is the C-terminal domain found in RPN1 proteins (26S proteasome non-ATPase regulatory subunit 2). 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) .
Domain of unknown function DUF5637 (DUF5637)
Type: Domain

This is a domain of unknown function found in predicted cysteine knot peptides.
Protein of unknown function DUF5552 (DUF5552)
Type: Family

This is a family of unknown function found in primates.
Bacterial CdiA-CT RNAse A domain (RNAse_A_bac)
Type: Domain

Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition found in many Gram-negative pathogens. CDI+ cells express cell-surface CdiA proteins that bind neighbouring bacteria and deliver C-terminal toxin domains (CdiA-CT) to inhibit target-cell growth. Structure analysis of CdiA-CT shows that it adopts the same fold (with two β-sheets forming an overall kidney shape) as angiogenin and other RNase A paralogs, but the toxin does not share sequence similarity with these nucleases and lacks the characteristic disulfide bonds of the superfamily. Furthermore, structural comparison analysis identified human angiogenin, Rana pipiens protein P-30 (onconase) and mouse pancreatic ribonuclease (RNase 1) as the closest structural homologs of CdiA-CT .
Gylcosyl hydrolase 115 C-terminal domain (GH115_C)
Type: Domain

This domain is found at the C terminus of glycosyl hydrolase family 115 proteins . This domain has a β-sandwich fold .
Carbohydrate-binding module 64 (CBM64)
Type: Domain

Spirochaeta thermophila secretes seven glycoside hydrolases for plant biomass degradation that carry a carbohydrate-binding module 64 (CBM64) appended at the C terminus. CBM64 adsorbs to various beta1-4-linked pyranose substrates and shows high affinity for cellulose. Structure analysis indicates a jelly-roll-like fold corresponding to a surface-binding type A CBM .
Rv3651-like, middle domain (Rv3651-like_middle)
Type: Domain

This domain is found in Rv3651 from Mycobacterium tuberculosis (

) and similar proteins from Actinobacteria. Rv3651 adopts a three-domain configuration. This entry represents the middle domain, a PAS domain that shows a central antiparallel β-sheet of five β-strands .
HypF, Kae1-like domain (HypF_C)
Type: Domain

This domain is found in carbamoyltransferase HypF. In the structure it is one of the two subdomains of the Kae1 domain .
Pih1, Ascomycota, CS domain (Pih1_CS_Ascomycota)
Type: Domain

This entry represents the CS domain found in Pih1 from Ascomycota. Pih1 is part of the R2TP complex . The CS domain of Pih1 binds to the unstructured region of Tah1 . The C-terminal domain of Pih1 consists of a seven-stranded β sandwich with the topology of a CS domain, a structural motif also found in Hsp90 cochaperones such as p23/Sba1 and Sgt1.
PIH1D1/2/3, CS-like domain (PIH1D1/2/3_CS-like)
Type: Domain

This domain is found in animal PIH1 domain-containing protein 1/2/3 (PIH1D1/2/3) and its homologues . PIH1D1 is part of the HSP90 co-chaperone R2TP complex involved in the assembly process of many molecular machines . This domain consists of a seven-stranded β sandwich with the topology of a CS domain, a structural motif also found in Hsp90 co-chaperones such as p23/Sba1 and Sgt1 . Proteins containing this domain also includes Kintoun from animals and uncharacterised proteins from fungi and plants.

Kintoun (also known as ktu or dynein assembly factor 2, axonemal) is a cytoplasmic protein conserved from ciliated unicellular organisms to mammals. It is required for cytoplasmic pre-assembly of axonemal dynein arm complexes before intraflagellar transport loads them for the ciliary compartment. Its homologue in single-celled alga Chlamydomonas is known as PF13. A mutation in Ktu/PF13 has been identified in some patients with primary ciliary dyskinesia (PCD). In the absence of Ktu/PF13, both dynein arms (inner and outer) are missing or defective in the axoneme, leading to a loss of motility .
ExoP, galactose-binding-like domain (Exop_C)
Type: Domain

This is the C-terminal domain found in ExoP (exo-1,3/1,4-beta-glucanase) from Pseudoalteromonas. This domain contains a β-sandwich fold which is common in glycosyl hydrolases (GH7, 11, 12 and 16) and in some 23 carbohydrate-binding modules. It is suggested that the main role of this domain is to provide structural stability necessary for ExoP activity, however no substrate-binding role has been shown .