SII-SWORD/CoKE huggingface dataset:
Transcription initiation Spt4 (Spt4)
Type: Family

This family consists of several eukaryotic transcription initiation Spt4 proteins. Three transcription-elongation factors Spt4, Spt5, and Spt6 are conserved among eukaryotes and are essential for transcription via the modulation of chromatin structure. Spt4 and Spt5 are tightly associated in a complex, while the physical association of the Spt4-Spt5 complex with Spt6 is considerably weaker. It has been demonstrated that Spt4, Spt5, and Spt6 play roles in transcription elongation in both yeast and humans including a role in activation by Tat. It is known that Spt4, Spt5, and Spt6 are general transcription-elongation factors, controlling transcription both positively and negatively in important regulatory and developmental roles .
Gamma-glutamylcyclotransferase, AIG2-like domain (AIG2-like_dom)
Type: Domain

This entry represents a domain found in a group of gamma-glutamyl cyclotransferases (GGCTs), including AIG2 from Arabidopsis. GGCT is a ubiquitous enzyme found in bacteria, plants, and metazoans from Dictyostelium through to humans. It converts gamma-glutamylamines to free amines and 5-oxoproline .

AIG2 is an Arabidopsis protein that exhibit RPS2- and avrRpt2-dependent induction early after infection with Pseudomonas syringae pv maculicola strain ES4326 carrying avrRpt2 . Its structure consists of a five-stranded β-barrel surrounded by two α-helices and a small β-sheet. A long flexible α-helix protrudes from the structure at the C-terminal end. Conserved residues in a hydrophilic cavity, which are able to bind small ligands, may act as an active site in AIG2-like proteins .
Baculoviridae 8.2kDa (Baculo_8kDa)
Type: Family

Family of proteins from various Baculoviruses with undetermined function.
Radial spoke 3 (Radial_spoke_3)
Type: Family

This family consists of several radial spoke protein 3 (RSP3) sequences. Eukaryotic cilia and flagella present in diverse types of cells perform motile, sensory, and developmental functions in organisms from protists to humans. They are centred by precisely organised, microtubule-based structures, the axonemes. The axoneme consists of two central singlet microtubules, called the central pair, and nine outer doublet microtubules. These structures are well conserved during evolution. The outer doublet microtubules, each composed of A and B sub-fibres, are connected to each other by nexin links, while the central pair is held at the centre of the axoneme by radial spokes. The radial spokes are T-shaped structures extending from the A-tubule of each outer doublet microtubule to the centre of the axoneme. Radial spoke protein 3 (RSP3), is present at the proximal end of the spoke stalk and helps in anchoring the radial spoke to the outer doublet. It is thought that radial spokes regulate the activity of inner arm dynein through protein phosphorylation and dephosphorylation .
Vacuolar protein sorting-associated protein 62 (Vps62)
Type: Family

Vps62 is a vacuolar protein sorting (VPS) protein required for cytoplasm to vacuole targeting of proteins .
rRNA biogenesis protein RRP36 (RRP36)
Type: Family

RRP36 is involved in the early processing steps of the pre-rRNA .
Uncharacterised protein family UPF0478 (UPF0478)
Type: Family

This family consists of bacterial sequences several of which are thought to be general stress proteins.
Gamma-secretase subunit Aph-1 (Aph-1)
Type: Family

This family consists of several eukaryotic Aph-1 proteins. Aph-1 is an essential subunit of the gamma-secretase complex, an endoprotease complex that catalyses the intramembrane proteolysis of Notch, beta-amyloid precursor protein, and other substrates as part of a new signalling paradigm and as a key step in the pathogenesis of Alzheimer's disease . It is thought that the presenilin heterodimer comprises the catalytic site and that a highly glycosylated form of nicastrin associates with it. Aph-1 and Pen-2, two membrane proteins genetically linked to gamma-secretase, associate directly with presenilin and nicastrin in the active protease complex. Co-expression of all four proteins leads to marked increases in presenilin heterodimers, full glycosylation of nicastrin, and enhanced gamma-secretase activity .
S. aureus uracil DNA glycosylase inhibitor (SAUGI)
Type: Family

Uracil-DNA glycosylase inhibitors are DNA mimic proteins that prevent the DNA binding sites of UDGs (Uracil DNA glycosylase) from interacting with their DNA substrate. SSP0047 or SAUGI (for Staphylococcus aureus uracil-DNA glycosylase inhibitor) (

) acts as a uracil-DNA glycosylase inhibitor that breaks the uracil-removing activity of S. aureus uracil-DNA glycosylase (SAUDG,

) . The SAUGI/SAUDG complex has been determined, and shows that SAUGI binds to the SAUDG DNA binding region via several strong interactions, by using a hydrophobic pocket to hold SAUDG's protruding residue (i.e. SAUDG Leu184, E. coli UDG Leu191 and B. subtilis UDG Phe191). By binding to SAUDG in this way, SAUGI thus prevents SAUDG from binding to its DNA substrate and performing DNA repair activity .
Protein of unknown function DUF951 (DUF951)
Type: Family

This family consists of several short hypothetical bacterial proteins of unknown function.
Protein of unknown function DUF952 (DUF952)
Type: Family

This family consists of several hypothetical bacterial and plant proteins of unknown function.
Gammaherpesvirus capsid (Herpes_capsid)
Type: Family

This family includes the small capsomere-interacting protein (SCP) from Gammaherpesviruses. By analogy with SCP from human herpesvirus 1, SCP forms a complex with the major capsid protein in the cytoplasm which is translocated to the nucleus. SCP decorates the outer surface of the capsid shell during capsid assembly, forming a layer between the capsid and the tegument.
Transcription activator RinB (Transcription_activator_RinB)
Type: Family

This family consists of several Staphylococcus aureus bacteriophage RinB proteins and related sequences from their host. The int gene of staphylococcal bacteriophage phi 11 is the only viral gene responsible for the integrative recombination of phi 11. rinA and rinB, are both required to activate expression of the int gene .
Tail length tape measure (Tail_length_tape_measure)
Type: Domain

This entry consists of the tail length tape measure protein from Bacteriophage HK97 and related sequences from Escherichia coli.
Protein of unknown function DUF960 (DUF960)
Type: Family

This family consists of several hypothetical proteins from several species of bacteria. The function of this family is unknown.
Herpesvirus Latent membrane 2 (Herpes_LAMP2)
Type: Family

This is a family of Kaposi's sarcoma-associated herpesvirus (HHV8) latent membrane protein. It includes protein K15, which plays a role in the modulation of host signaling pathways .
2-hydroxy-palmitic acid dioxygenase Mpo1-like (Mpo1-like)
Type: Family

Budding yeast Mpo1 is a dioxygenase that catalyzes the alpha-oxidation of a 2-hydroxy fatty acid in an Fe2+-dependent manner .

This entry also includes Mpo1 homologues from bacteria, fungi and plants. Their function is not clear.
Protein of unknown function DUF963 (DUF963)
Type: Repeat

This family consists of a series of repeated sequences from one hypothetical protein (

) found in Schizosaccharomyces pombe. The function of this family is unknown.
Bacterial microcompartment shell protein EutS/PduU/CutR (EutS/PduU/CutR)
Type: Family

Bacterial microcompartments (BCMs) function as organelles by sequestering particular metabolic processes within the cell. The shells of varied microcompartments are built primarily from small proteins belonging to the BMC domain family.

This family represents Bacterial microcompartment shell protein EutS, PduU and CutR, all of them components of the BMC.

PduU is minor shell protein of the BMC dedicated to the coenzyme B12-dependent degradation of 1,2-propanediol (1,2-PD) . This protein exists as a hexamer which might further assemble into the flat facets of the polyhedral outer shell of the pdu microcompartments . The core of PduU is related to the typical bacterial BMC domain and its natural oligomeric state is a cyclic hexamer. Unlike other typical BMC domain proteins, the 3D topology of PduU reveals a circular permuted variation on the typical BMC fold which leads to several unique features. The exact functions related to those unique features are still not clear. Another difference is the presence of a deep cavity on one side of the hexamer as well as an intermolecular six-stranded β barrel that seems to block the central pore that is present in other BMC domain proteins.

EutS proteins included in this family are sequence homologues of PduU. They are encoded within eut operon and may be required for the formation of the outer shell of bacterial eut polyhedral organelles which are involved in the cobalamin-dependent degradation of ethanolamine .

CutR is a minor shell protein of the choline degradation-specific BMC. It may play a key role in conferring heterogeneity and flexibility in this BMC .
Rhamnose isomerase (Rhamnose_isomerase)
Type: Family

This family consists of several bacterial L-rhamnose isomerase proteins (

). This enzyme interconverts L-rhamnose and L-rhamnulose. In some species, including Escherichia coli, this is the first step in rhamnose catabolism. Sequential steps are catalysed by rhamnulose kinase (rhaB), then rhamnulose-1-phosphate aldolase (rhaD) to yield glycerone phosphate and (S)-lactaldehyde. Bifunctional enzyme RhaA/RhaB from Bacillus clausii is also included in this entry. It contains both rhamnulokinase and L-rhamnose isomerase domains.
IreB regulatory phosphoprotein (IreB)
Type: Family

IreB is a cytosolic 10.5kDa protein that is highly conserved among low-GC Gram-positive bacteria. Studies of E. faecalis mutants lacking ireB revealed that IreB acts downstream of IreK as a negative regulator of cephalosporin resistance in E. faecalis. IreB can be modified by phosphorylation in vivo, and mutations that prevent modification at the known sites of phosphorylation (T4 and T7) influence the ability of IreB to modulate cephalosporin resistance. Furthermore, mutations that impair dimerization abolish the regulation of cephalosporin resistance .
BphX-like (BphX)
Type: Family

This is a family of bacterial proteins located in the phenyl dioxygenase (bph) operon. The function of this family is unknown.
Interferon alpha-inducible protein IFI6/IFI27-like (IFI6/IFI27-like)
Type: Family

This entry represents interferon alpha-inducible proteins IFI6 (also known as IFI-6-16) and IFI27-like (also known as ISG12) which play a role in the apoptotic process and also have pro-apoptotic activity . ISG12a is a mitochondrial protein that contributes to IFN-induced apoptosis through perturbation of normal mitochondrial function .
Minor tail protein U-like (Phage_lambda_GpU-like)
Type: Family

This entry represents bacteriophage lambda, GpU, a minor tail protein. GpU plays an essential role in tail assembly by capping the rapidly polymerizing tail once it has reached its requisite length and serving as the interaction surface for the completion protein . GpU forms a hexameric ring within the tail structure since it spontaneously forms such rings in the presence of Mg2+ that match the size of the hexameric rings of gpV that comprise the bulk of the tail tube. However, prior to tail assembly, gpU remains monomeric . The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
Baculovirus 11kDa (Baculo_11_kDa)
Type: Family

This is a family of uncharacterised Baculovirus proteins that are all about 11kDa in size.
Coronavirus nonstructural NS1 (Corona_NS1)
Type: Family

One of the members of this family is a 4.9kDa proteins, encoded by Bovine coronavirus NS1 .
Phosphate-starvation-induced PsiE (P_starv_induced_PsiE)
Type: Family

Phosphate-starvation-inducible E (PsiE) expression is under direct positive and negative control by PhoB and cAMP-CRP, respectively . PsiE is an integral membrane protein with four transmembrane helices. The second α helix contains a conserved glutamic acid residue and the third helix contains a conserved arginine residue. The function of PsiE remains to be determined.
COG complex component, COG2 (COG2)
Type: Family

The COG complex comprises eight proteins COG1-8. The COG complex plays critical roles in Golgi structure and function and it is necessary for retrograde trafficking in the Golgi apparatus and for protein glycosylation .
ChaB (ChaB)
Type: Family

This family of proteins contain a conserved 60 residue region. This protein is known as ChaB in Escherichia coli and is found next to ChaA, which is a cation transporter protein . ChaB may regulate ChaA function in some way.
Gustatory receptor (Gustatory_rcpt)
Type: Family

In Drosophila, taste is perceived by gustatory neurons located in sensilla distributed on several different appendages throughout the body of the animal. This family represents the taste receptor sensitive to trehalose .
Lactococcus phage , Structural protein (Phage_A118_VSP1)
Type: Family

This entry represents Structural protein from Lactococcus phage and similar proteins from tailed bacteriophages and bacterial prophages.
Antitoxin CbeA (Antitoxin_CbeA)
Type: Family

This is a family of cognate antitoxins to the CbtA toxins that act by inhibiting the polymerisation of cytoskeletal proteins (see

). These are classified as a type IV toxin-antitoxin system . The family includes three proteins from E. coli YagB, YeeU and YfjZ, which act not by forming a complex with CbtA but through acting as antagonists to the CbtA toxicity, by stabilising the CbtA target proteins. For example, YeeU binds directly to both MreB and FtsZ and enhances the bundling of their filaments in vitro. YeeU is also able to neutralise the toxicity caused by other MreB and FtsZ inhibitors, such as A22 [S-(3, 4-dichlorobenzyl)isothiourea] for MreB, and SulA and DicB for FtsZ . Thus CbeA, for cytoskeleton bundling-enhancing factor A, is proposed as a general name for all of these antitoxin proteins.
Protein of unknown function DUF973 (DUF973)
Type: Family

This family consists of proteins of unknown function.
Protein of unknown function DUF979 (DUF979)
Type: Family

This family consists of several putative bacterial membrane proteins. The function of this family is unclear.
Protein of unknown function DUF981 (DUF981)
Type: Family

This is a family of uncharacterised proteins found in bacteria and archaea.
Protein of unknown function DUF983 (DUF983)
Type: Family

This family consists of several bacterial proteins of unknown function.
Protein of unknown function DUF984 (DUF984)
Type: Family

This is a family of bacterial proteins with unknown function. This entry includes the uncharacterised protein YhfF from Bacillus subtilis.
Cupin domain of unknown function DUF985 (Cupin_DUF985)
Type: Domain

This cupin domain is found in uncharacterised protein YML079W, from budding yeast. Its structure has been solved .
Protein of unknown function DUF986 (DUF986)
Type: Family

This family consists of several bacterial putative membrane proteins of unknown function.
Protein of unknown function DUF987 (DUF987)
Type: Family

This is a family of bacterial proteins that are related to the hypothetical protein YeeT.
Lipopolysaccharide core heptose(II) kinase (LipoPS_heptP_kinase)
Type: Family

This family consists of several bacterial lipopolysaccharide core biosynthesis proteins (WaaY or RfaY). The waaY, waaQ, and waaP genes are located in the central operon of the waa (formerly rfa) locus on the chromosome of Escherichia coli. This locus contains genes whose products are involved in the assembly of the core region of the lipopolysaccharide molecule. WaaY is the enzyme that phosphorylates HepII in this system .
Oligogalacturonate-specific porin (Oligogalacturonate-sp_porin)
Type: Family

This family consists of several bacterial proteins which are homologous to the oligogalacturonate-specific porin protein KdgM (

) from Erwinia chrysanthemi. The phytopathogenic Gram-negative bacteria E. chrysanthemi secretes pectinases, which are able to degrade the pectic polymers of plant cell walls, and uses the degradation products as a carbon source for growth. KdgM is a major outer membrane protein, whose synthesis is strongly induced in the presence of pectic derivatives. KdgM behaves like a voltage-dependent porin that is slightly selective for anions and that exhibits fast block in the presence of trigalacturonate. In contrast to most porins, KdgM seems to be monomeric .
Mediator of RNA polymerase II transcription subunit 22 (Med22)
Type: Family

The Mediator complex is a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. On recruitment the Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins.

The Mediator complex is composed of at least 31 subunits: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11.

This entry represents subunit Med22 of the Mediator complex. It contains several eukaryotic Surfeit locus protein 5 (SURF5) sequences. The human Surfeit locus has been mapped on chromosome 9q34.1. The locus includes six tightly clustered housekeeping genes (Surf1-6), and the gene organisation is similar in human, mouse and chicken Surfeit loci .
Protein of unknown function DUF992 (DUF992)
Type: Family

This entry consists of several hypothetical bacterial proteins of unknown function.
Protein of unknown function DUF993 (DUF993)
Type: Family

This entry consists of several hypothetical bacterial proteins of unknown function.
Type III secretion system HrpE /V-type ATP synthase subunit E (T3SS_HrpE/ATPase_suE)
Type: Family

This family consists of several bacterial HrpE proteins, which are believed to function on the type III secretion system, specifically the secretion of HrpZ (harpinPss) . This family also includes V-type proton ATPase subunit E proteins. This subunit appears to form a tight interaction with subunit G in the F0 complex. Subunits E and G may act together as stators to prevent certain subunits from rotating with the central rotary element .

also contains V-type ATPase subunit E proteins.
Protein of unknown function DUF995 (DUF995)
Type: Family

This is a family of uncharacterised Proteobacteria proteins.
Protein of unknown function Orf51 (Orf51)
Type: Family

This entry is represents a family of predicted proteins found in bacteriophages and prophages.
Protein of unknown function DUF998 (DUF998)
Type: Family

This is a family of proteins with no known function.
Protein of unknown function DUF999 (DUF999)
Type: Family

This is a family of conserved Schizosaccharomyces proteins with unknown function.
Protein of unknown function DUF1002 (DUF1002)
Type: Family

This protein family has no known function. Its members are about 300 amino acids in length. It has so far been detected in Firmicute bacteria and some archaebacteria.
Borna disease virus G (BDV_G)
Type: Family

This family consists of Borna disease virus G glycoprotein sequences. Borna disease virus (BDV) infection produces a variety of clinical diseases, from behavioural illnesses to classical fatal encephalitis . G protein is important for viral entry into the host cell .
BMP and activin membrane-bound inhibitor (BAMBI)
Type: Family

This entry consists of several eukaryotic BMP and activin membrane-bound inhibitor (BAMBI) proteins. Members of the transforming growth factor-beta (TGF-beta) superfamily, including TGF-beta, bone morphogenetic proteins (BMPs), activins and nodals, are vital for regulating growth and differentiation. BAMBI is related to TGF-beta-family type I receptors but lacks an intracellular kinase domain .

BAMBI is an essential regulator of cell proliferation and differentiation that represses TGF-beta and enhances Wnt/beta-catenin signalling in various cell types . Thus, it is involved in a high number of physiological and pathological processes . It stably associates with TGF-beta-family receptors and inhibits BMP and activin as well as TGF-beta signalling .
GRIM-19 (GRIM-19)
Type: Family

This family consists of several eukaryotic gene associated with retinoic-interferon-induced mortality 19 (GRIM-19) proteins. GRIM-19, was reported to encode a small protein primarily distributed in the nucleus and was able to promote cell death induced by IFN-beta and RA. A bovine homologue of GRIM-19 was co-purified with mitochondrial NADH:ubiquinone oxidoreductase (complex I) in bovine heart. Therefore, its exact cellular localisation and function are unclear. It has now been discovered that GRIM-19 is a specific interacting protein which negatively regulates Stat3 activity .
Rice tungro bacilliform virus P46 (RTBV_P46)
Type: Family

This family consists of several Rice tungro bacilliform virus P46 proteins (also known as P4). The function of this family is unknown.
Nitrogen permease regulator 2-like (NPR2-like)
Type: Family

This family of regulators are involved in post-translational control of nitrogen permease. In mammals, members may act as a tumour suppressor that suppresses cell growth and enhances sensitivity to various anticancer drugs .
TRIP4/RQT4, C2HC5-type zinc finger (TRIP4/RQT4_C2HC5_Znf)
Type: Domain

This entry represents a C2HC5-type zinc finger found in human activating signal cointegrator 1 (ASC-1, also known as TRIP4) and its orthologue from yeast RQC trigger complex subunit RQT4 which function as part of the RQC trigger (RQT) complex that activates the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation . TRIP4 has also been described as a transcription coactivator which associates with nuclear receptors and transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription .

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few . Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.