SII-SWORD/CoKE huggingface dataset:
Lens epithelium-derived growth factor, integrase-binding domain (LEDGF_IBD)
Type: Domain

Lens epithelium-derived growth factor (LEDGF), also known as transcriptional co-activator p75, is a chromatin-associated protein that protects cells from stress-induced apoptosis. It is the binding partner of HIV-1 integrase in human cells . The integrase binding domain (IBD) of LEDGF is a compact right-handed bundle composed of five α-helices. The residues essential for the interaction with the integrase are present in the inter-helical loop regions of the bundle structure. The integrase binding domain is not unique to LEDGF, as a second human protein, hepatoma-derived growth factor-related protein 2 (HRP2), contains a homologous sequence .
Ribonuclease III, archaeal (Ribonuclease_III_archaeal)
Type: Family

This is a family of archaeal ribonuclease_III proteins.
TUG ubiquitin-like domain (TUG-UBL1)
Type: Domain

This entry represents the N-terminal ubiquitin-like domain of the TUG protein. This domain in the similar protein, UBL1, appears to participate in protein-protein interactions . The region does have a area of negative electrostatic potential and increased backbone motility which leads to suggestions of a potential protein-protein interaction site . This domain is also found at the N terminus of yeast Ubx4 .

Proteins containing this domain include Ubx4 from budding yeast and TUG (also known as tether containing UBX domain for GLUT4) from mice.

Ubx4 is involved in Cdc48-dependent protein degradation through the ubiquitin/proteasome pathway .
LamB-type porin N-terminal domain (LamB-type_porin_N_dom)
Type: Domain

This entry represents an N-terminal extension found in some, though not all, of the LamB-type porins . The porin LamB family includes porin BglH, which may be a sugar porin with a broad carbohydrate specificity, and sucrose porin .
Protein of unknown function DUF3206 (DUF3206)
Type: Family

This bacterial family of proteins has no known function.
Leader peptide, picornavirus (Leader_pept_picornaV)
Type: Family

This is the N-terminal domain of a family of virion proteins which contains a zinc finger domain. Currently no function is known.
Sialyltransferase PMO188 (PM0188)
Type: Family

PMO188 is a sialyltransferase from P.multocida. It transfers sialic acid from cytidine 5'-monophosphonuraminic acid to an acceptor sugar . It has important catalytic residues such as Asp141, His311, Glu338, Ser355 and Ser356 .
RNA silencing suppressor P21, C-terminal (Suppressor_P21_C)
Type: Domain

P21 is produced by Beet yellows virus to suppress the antiviral silencing response mounted by the host. P21 acts by binding directly to siRNA which is a mediator in the process. P21 has an octameric ring structure with a large central cavity .
Protein of unknown function DUF3208 (DUF3208)
Type: Family

This bacterial family of proteins has no known function.
Protein of unknown function DUF3209 (DUF3209)
Type: Family

This family of proteins has no known function.
STK_08120-like (STK_08120-like)
Type: Family

This entry represents a family of proteins specific to thermoacidophile archaea that includes STK_08120 (

) from Sulfurisphaera tokodaii. This protein shows three α-helices and a seven-stranded β-sheet. It may function as a carrier of fatty acids in their biosynthesis, metabolism, and/or intracellular transport processes .
Protein of unknown function DUF3212 (DUF3212)
Type: Family

Members in this family of proteins are annotated as YfmB however currently no function for this protein is known.
Type II restriction enzyme SfiI (Restrct_endonuc_II_SfiI)
Type: Family

SfiI is a restriction enzyme that can cleave two DNA sites simultaneously to leave 3-base 3' overhangs. It acts as a homo-tetramer and recognises a specific eight base-paid palindromic DNA sequence. After binding two copies of its recognition sequence, SfiI becomes activated leading to cleavage of all four DNA strands. The structure of SfiI consists of a central twisted β-sheet surrounded by α-helices.
Transcription regulator LGE1, helical region (Tscrpt_reg_Lge1)
Type: Domain

This domain, comprising a single α-helix, is found in the Transcriptional regulatory protein Lge1 from S. cerevisiae and related proteins including the S. pombe homologue Shf1. It is involved in Bre1 binding.

In yeast, the Lge1 protein facilitates co-transcriptional H2B ubiquitination . Multiple roles were attributed to Lge1. In S. cerevisiae, Rad6 and Bre1 are present in a complex, also containing Lge1. Bre1 is the H2B ubiquitin ligase that interacts with acidic activators, such as Gal4, and recruits Rad6 and its binding partner Lge1 to target promoters . Recent reports invoke a role for Lge1 in liquid-liquid phase separation and formation of a structure that concentrates Bre1 in a shell that surrounds a Lge1 scaffolding core and allows the recruitment of Rad6 and nucleosomes . There is no Lge1 homologue in humans but the WAC protein is thought to be its functional analogue .
Altered inheritance of mitochondria protein 21 (Aim21)
Type: Family

This is a family of proteins conserved in yeasts. Saccharomyces cerevisiae Aim21 may be involved in mitochondrial migration along actin filament . It may also interact with ribosomes .
Protein of unknown function DUF3213 (DUF3213)
Type: Family

The backbone structure of this family of proteins has been determined however the function remains unknown. The protein has an α and β structure with a ferredoxin-like fold .
Thylakoid soluble phosphoprotein TSP9 (TSP9)
Type: Family

The plant-specific protein, TSP9 is phosphorylated and released in response to changing light conditions from the photosynthetic membrane. The protein resembles the characteristics of transcription/translation regulatory factors. The structure of the protein is predicted to consist of a random coil .
Ta0938 (Ta0938)
Type: Family

Ta0938 is a protein of unknown function however the structure has been determined. The protein has a novel fold and a putative Zn-binding motif. The structure has two different parts, one region contains a β sheet flanked by two α helices and the other contains a bundle of loops which contain all cysteines in the protein .
Transcription regulator TrmB, C-terminal (Tscrpt_reg_TrmB_C)
Type: Domain

This domain is found at the C-terminal end of HTH-type sugar sensing transcriptional regulator TrmB from the hyperthermophilic archaea Thermococcus litoralis and Pyrococcus furiosus and in similar prokaryotic sequences. TrmB is an alpha-glucoside sensing transcriptional regulator. The protein is the transcriptional repressor for a gene cluster encoding trehalose/maltose ABC transporter . A nonreducing glucosyl residue is shared by all substrates bound to TrmB which suggests that its a common recognition motif .
Transcription activator LAG-3 (Transcription_activator_LAG-3)
Type: Family

The C.elegans Notch pathway, involved in the control of growth, differentiation and patterning in animal development, relies on either of the receptors GLP-1 or LIN-12 . Both these receptors promote signalling by the recruitment of LAG-3 to target promoters, where it then acts as a transcriptional activator. LAG-3 works as a ternary complex together with the DNA binding protein, LAG-1 .
Spindle pole body-associated protein cut12 (Cut12)
Type: Domain

This is the central coiled-coil region of cut12 also found in other fungi, barring S. cerevisiae. The full protein has two predicted coiled-coil regions, and one consensus phosphorylation site for p34cdc2 and two for MAP kinase. During fission yeast mitosis, the duplicated spindle pole bodies (SPBs) nucleate microtubule arrays that interdigitate to form the mitotic spindle. Cut12 is localised to the SPB throughout the cell cycle, predominantly around the inner face of the interphase SPB, adjacent to the nucleus . Cut12 associates with Fin1 and is important in this context for the activity of Plo1 .
NSP1, globular domain, betacoronavirus (NSP1_glob_bCoV)
Type: Domain

This entry represents the globular domain of NSP1 from betacoronavirus lineage B and C.

Nonstructural protein 1 (NSP1) is a critical virulence factor of coronaviruses (CoV) and plays key roles in suppressing host gene expression, which facilitates viral replication and immune evasion. NSP1 is a characteristic feature of alpha and betacoronavirus, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses . NSP1 binds to the 40S ribosomal subunit and inhibits host translation, and it also induces a template-dependent endonucleolytic cleavage of host mRNAs , while viral mRNAs are less susceptible to NSP1-mediated inhibition of translation, because of their 5'-end leader sequence . NSP1 also suppresses the host innate immune functions by inhibiting type I interferon expression and host antiviral signalling pathways. The C-terminal domain binds to the mRNA entry tunnel interfering with mRNA binding (

) . NSP1 consists of a globular domain arranged in a mixed parallel/antiparallel 6-stranded β-barrel with an α-helix covering one end of the barrel and another helix alongside the barrel . In addition to the globular domain, bCoV NSP1s have a C-terminal domain .
YNR034W-A/EGO2 (YNR034W-A/EGO2)
Type: Family

This family of proteins is predominantly found in Saccharomycetales, including YNR034W-A (also known as EGO4) and YCR075W-A (EGO2) from Saccharomyces cerevisiae. EGO2 is a component of the yeast EGO complex (EGOC), which is responsible for the amino acid-dependent activation of the target of rapamycin complex 1 (TORC1), a central controller of cell growth, metabolism, proliferation, and differentiation in response to environmental cues. EGO2 adopts a Roadblock domain fold that consists of a central core β-sheet of five anti-parallel β-strands flanked by a long α-helix on the bottom side. EGO4 shows a similar αββαββ configuration. It interacts with the GTPase Gtr2, but its specific function remains unknown .
Protein of unknown function DUF3218 (DUF3218)
Type: Family

This family of proteins with unknown function appears to be restricted to Pseudomonas.
Thermoplasma acidophilum protein TA0956 (TA0956)
Type: Family

TA0956 is a protein from Thermoplasma acidophilum which currently has no known function however the structure has been determined. The protein has a two-layered α/β-sandwich topology and is a putative Elongation factor 1-alpha binding motif .
Protein of unknown function DUF3219 (DUF3219)
Type: Family

This family of proteins with unknown function appears to be restricted to Bacillaceae. Some members in this family of proteins are annotated as YkvR however this cannot be confirmed.
Protein of unknown function DUF3220 (DUF3220)
Type: Family

This family of proteins with unknown function appears to be restricted to Bordetella.
Protein of unknown function DUF3221 (DUF3221)
Type: Family

This family of proteins with unknown function appears to be restricted to Bacillus. Some members in this family of proteins are annotated as YobA however this cannot be confirmed. YobA is a protein with unknown function.
Protein of unknown function DUF3222 (DUF3222)
Type: Family

This family of proteins with unknown function appears to be restricted to Rhodopseudomonas.
Transcription factor TFIIE alpha subunit, C-terminal (TFIIE_asu_C)
Type: Domain

TFIIE is compiled of two subunits, alpha and beta. This entry represents the C-terminal domain of the alpha subunit. The alpha subunit is the largest and contains several functional domains which are important for basal transcription and cell growth. The C-terminal end of the protein binds directly to the amino-terminal PH domain of p62/Tfb1 (of IIH) which is involved in the recruitment of the general transcription factor IIH to the transcription preinitiation complex. p53 competes for the same binding site as TFIIE alpha, which shows their structural similarity. Like p53, the C terminus of TFIIE alpha (residues 336-439) can activate transcription in vivo .
Phosphatidylinositol 4-kinase, Pik1, fungi (Phosphatidylino_kinase_fungi)
Type: Family

Pik1 is a regulator of membrane traffic and participates in the mating-pheromone signal-transduction cascade. The protein is localised to the nucleus and cytoplasm in the Golgi. Pik1 is thought to have an actin-independent role in membrane transport .
Selenium-binding protein, archaea (SeBP_arc)
Type: Family

Selenium is an important nutrient which needs to be regulated since lack of the nutrient leads to cell abnormalities and high concentrations are toxic. The selenium binding protein (SeBP) regulates the level of free selenium in the cell by sequestering the nutrient during transport. SeBP acts as a pentamer and delivers the selenium to the selenophosphate synthetase enzyme . Each subunit is composed of an α helix on top of a four stranded twisted ss sheet, stabilised by hydrogen bonds . Proteins in this entry are restricted to the archaeal Methanococcales.
Copper resistance protein K (CopK)
Type: Family

Copper resistance protein K (CopK) is a periplasmic dimeric protein which is strongly up-regulated in the presence of copper, leading to a high periplasmic accumulation . CopK has two different binding sites for Cu(I), each with a different affinity for the metal. Binding of the first Cu(I) ion (CuI) induces a conformational change of CopK which involves dissociation of the dimeric apo-protein. Binding of a second Cu(I) (CuII) further increases the plasticity of the protein. The binding of CuI greatly enhances the specific affinity for CuII and, in turn, CuII binding increases the specific affinity for CuI, although to a lesser extent. This type of cooperative behaviour is unprecedented in copper binding proteins . CopK has features that are common with functionally related proteins such as a structure consisting of an all-β fold and a methionine-rich Cu(I) binding site .
Pcf11, Clp1-ID (Pcf11_Clp1-ID)
Type: Domain

This entry represents the Clp1-interacting domain of Pcf11 (Clp1-ID), found towards the C-terminal end of these proteins.

Pcf11 is a subunit and essential component of cleavage and polyadenylation factor IA (CF IA), involved in pre-mRNA 3' end processing and in transcription termination . It has been reported that Pcf11-mediated termination is essential for vertebrate development and its own levels are maintained by an auto-regulatory mechanism involving premature termination of its transcript . Human Pcf11, also referred to as pre-mRNA cleavage complex 2 protein Pcf11, has been shown to enhance degradation of RNAP II-associated nascent RNA and transcriptional termination. Pcf11 binds to Clp1, another subunit of CFIA whose interaction is responsible for maintaining a tight coupling between the Clp1 nucleotide binding subunit and the other components of the polyadenylation machinery .
Protein of unknown function DUF3224 (DUF3224)
Type: Family

This family of predominantly bacterial proteins has no known function.
Melampsora lini avirulence protein AvrL567 (AvrL567)
Type: Family

AvrL567 is a protein from the fungal pathogen Melampsora lini which induces plant disease resistance in flax plants . Avirulence proteins trigger the resistance response in plants by interacting with plant disease-resistance proteins . The protein has a novel β-barrel-like fold .
Nitrosopumilus output domain 5 (NitrOD5)
Type: Domain

NitrOD5 (Nitrosopumilus output domain 5) is found in thaumarchaea, either in stand-alone form or in combination with the signal transduction response regulator, receiver domain (

) .
Protein of unknown function DUF3228 (DUF3228)
Type: Family

This family of proteins has no known function.
Spindle pole body component Spc42 (Spc42)
Type: Family

Spc42 is a central plaque component of spindle pole body (SPB), which is the microtubule organising centre (MTOC) in the yeast Saccharomyces. Spc42 is involved in SPB duplication and facilitates the attachment of the SPB to the nuclear membrane .
Staphylococcal complement inhibitor SCIN (SCIN)
Type: Family

SCIN is released by Staphylococcus aureus to counteract the host immune defense. The protein binds to and inhibits C3 convertases on the bacterial surface, reducing phagocytosis and blocking downstream effector functions by C3b deposition on its surface . An 18 residue stretch 31-48 is crucial for SCIN activity .
Protein-tyrosine phosphatase receptor IA-2 ectodomain (Receptor_IA-2_dom)
Type: Domain

IA-2 (also known as PTPRN or ICA512) and phogrin (also known as PTPRN2, IA-2b, IAR or ICAAR) are homologous protein-tyrosine phosphatase (PTP) receptors. They have a signal peptide, an ectodomain, a single-pass transmembrane region, and a single intracellular PTP domain. Processing of pro IA-2 by furin-like hormone convertases produces mature IA-2, which lacks the signal peptide and an adjacent fragment (residues 1-448). Upon exocytosis, the cytoplasmic domain of IA-2 is cleaved and moves to the nucleus where it enhances transcription of the insulin gene . The mature ectodomain of IA-2 participates in adhesion to the extracellular matrix and is self-proteolysed in vitro by reactive oxygen species, which may be a new shedding mechanism .
Protein transport protein SEC31 (Sec31)
Type: Family

Sec31 is involved in COPII coat formation as it forms through the sequential binding of three cytoplasmic proteins: Sar1, Sec23/24 and Sec13/31. Sec13/31 is recruited by the pre-budding complex and polymerisation of Sec13/31 occurs to form an octahedral cage that is the outer shell of the COPII coat . Sec13/31 is a hetero-tetramer which is organised as a linear array of α-solenoid and β-propeller domains to form a rod in which twenty-four copies assemble to form the COPII cub-octahedron .
Outer membrane protein Omp28 (Omp28)
Type: Family

Omp28 is a 28kDa outer membrane protein from Porphyromonas gingivalis. Omp28 is thought to be a surface adhesion/receptor protein. Omp28 is expressed in a wide distribution of P.gingivalis strains .
Protein of unknown function DUF3231 (DUF3231)
Type: Family

This bacterial family of proteins has no known function.
Protein of unknown function DUF3232 (DUF3232)
Type: Family

This bacterial family of proteins has no known function.
Mig-6 domain (Mig-6)
Type: Domain

When the kinase domain of EGFR binds to segment one of Mitogen induced gene 6 (Mig-6), EGFR becomes inactive due to the conformation it adopts which is Src/CDK like. The binding of the two proteins prevents EGFR acting as a cyclin-like activator for other kinase domains . The structure of Mig-6(1) consists of α-helices-G and -H with a polar surface and hydrophobic residues for interactions with EGFR. A critical step for the activation of EGFR is the formation of an asymmetric dimer involving the kinase domains of the protein. Since Mig-6 binds to the kinase domain it blocks this process and EGFR becomes inactive .
Erythrocyte binding antigen 175, C-terminal (EBA-175_C)
Type: Domain

EBA-175 is involved in the formation of a tight junction, a necessary step in invasion. This entry represents the C-terminal region VI which is a cysteine rich domain essential for EBA-175 trafficking. The structure is a homodimer that contains a five-α-helical core stabilised by four disulphide bridges .
Solitary outer membrane autotransporter-like, beta-barrel domain (Omp_AT)
Type: Domain

This entry represents the β-barrel domain in putative Solitary outer membrane autotransporte in Gram-negative Gamma-proteobacteria. Secondary structure prediction indicates a β-barrel domain of 12 β-strands. with an N-terminal helix running along the central barrel axis perpendicular to the 12 antiparallel strands that form the barrel. Autotransporter translocation units defined by a β-barrel of 12 to 14 antiparallel strands with an N-terminal helix perpendicular to the barrel .
Afadin/alpha-actinin-binding (Afadin/alpha-actinin-bd)
Type: Family

This family is found in mammals where it is localised at cell-cell adherens junctions , and in Sch. pombe and other fungi where it anchors spindle-pole bodies to spindle microtubules . It is a coiled-coil structure, and in pombe, it is required for anchoring the minus end of spindle microtubules to the centrosome equivalent, the spindle-pole body. The name ADIP derives from the family being composed of Afadin- and alpha Actinin-Binding Proteins Localised at Cell-Cell Adherens Junctions.
Lamina-associated polypeptide 2 alpha, C-terminal (LAP2alpha_C)
Type: Domain

LAPs are components of the nuclear lamina which supports the nuclear envelope. LAP2alpha is a non-membrane-associated member of the LAP family which is unique. This entry represents the C-terminal domain of LAP2alpha which consists of residues 459-693 and constitutes a dimeric structure with an antiparallel coiled coil. LAP2alpha is involved in cell-cycle regulation and chromatin organisation and preferentially binds to lamin A/C .
Single-strand annealing weakened protein 1 (Saw1)
Type: Family

Saw1 is a structure-specific DNA binding protein with high affinity for splayed arm and 3'-flap DNAs . It is required for single-strand annealing (SSA) DNA double-strand break (DSB) repair. It recruits Rad1-Rad10 to SDSA (Synthesis-Dependent Strand Annealing) sites, but departs the repair site in advance of Rad1-Rad10 .
PI31 proteasome regulator, N-terminal (PI31_Prot_N)
Type: Domain

PI31 is a regulatory subunit of the immunoproteasome which is an inhibitor of the 20S proteasome in vitro. PI31 is also an Fbxo7.Skp1 binding partner. Fbxo7 is an F-box protein, which are the substrate-recognition components of the Skp1-Cul1-F box protein (SCF) E3 ubiquitin ligases. The interaction between PI31 and Fbxo7.Skp1 occurs via the β sheets of a N-terminal domain present in both proteins and known as FP(Fbxo7/PI31) domain. The structure of PI31 FP domain contains a novel α/β-fold and two intermolecular contact surfaces .

This entry represents the N-terminal domain of the PI31 proteasome regulator.
Plasmodium falciparum UIS3 membrane protein (PfUIS3)
Type: Family

UIS3 is a membrane protein essential for sporozoite development in infected hepatocytes. This family is 130-229 of the Plasmodium falciparum UIS3 protein which is compact and has an all α-helical structure. PfUIS3(130-229) interacts with lipids, phospholipid lysosomes, the human liver fatty acid-binding protein and with the lipid phosphatidylethanolamine. The interaction with liver fatty acid-binding protein provides the parasite with a method to import essential fatty acids/lipids during rapid growth phases of sporozoites .
Mediator complex, subunit Med27 (Mediator_Med27)
Type: Family

Mediator is a large complex of up to 33 proteins that is conserved from plants to fungi to humans - the number and representation of individual subunits varying with species. It is arranged into four different sections, a core, a head, a tail and a kinase-activity part, and the number of subunits within each of these is what varies with species. Overall, Mediator regulates the transcriptional activity of RNA polymerase II but it would appear that each of the four different sections has a slightly different function . Mediator exists in two major forms in human cells: a smaller form that interacts strongly with pol II and activates transcription, and a large form that does not interact strongly with pol II and does not directly activate transcription. The ubiquitous expression of Med27 mRNA suggests a universal requirement for Med27 in transcriptional initiation. Loss of Crsp34/Med27 decreases amacrine cell number, but increases the number of rod photoreceptor cells .
Protein of unknown function DUF3234 (DUF3234)
Type: Family

This bacterial family of proteins has no known function. Some members in this family of proteins are annotated as TTHA0547 however this cannot be confirmed.
Mediator complex, subunit Med23 (Mediator_Med23)
Type: Family

Med23 is one of the subunits of the Tail portion of the Mediator complex that regulates RNA polymerase II activity. Med23 is required for heat-shock-specific gene expression, and has been shown to mediate transcriptional activation of E1A in mice.
Resuscitation-promoting factor Rpf1, C-terminal (Rpf1_C)
Type: Domain

This entry represents the C-terminal domain of Resuscitation-promoting factor Rpf1 from Corynebacterium glutamicum, a factor that stimulates resuscitation or dormant cells . The function of this domain is not known.