SII-SWORD/CoKE huggingface dataset:
SIKE family (SIKE)
Type: Family

Suppressor of IKBKE 1 (SIKE) is a physiological suppressor of IKK-epsilon and TBK1 . IKKepsilon and TBK1 are two IKK-related kinases critically involved in virus- and TLR3-triggered activation of interferon regulatory factor 3 (IRF-3).

Other members of this family are circulating cathodic antigen (CCA), found in Schistosoma mansoni (Blood fluke) , and FGFR1 oncogene partner 2, which may be involved in wound healing pathway .
Alkaline phosphatase PhoX (PhoX)
Type: Family

This family consists of proteins predominantly found in bacteria, including Alkaline phosphatase PhoX from Pseudomonas fluorescens (

), a phosphomonoesterase with no phosphodiesterase activity. This protein adopts a six-bladed β-propeller fold, with the active site located at the bottom of the cavity at the centre of the propeller .
Minor capsid protein VP2, lagovirus (VP2_lagovirus)
Type: Family

This family includes minor capsid protein VP2 from Rabbit hemorrhagic disease virus and related lagoviruses. VP2 is a minor structural protein that forms a portal-like structure at a unique three-fold axis of symmetry, following binding to the host receptor. The channel formed by VP2 may allow the delivery of the viral genome through the host endosomal membrane.
Calcium load-activated calcium channel (TMCO1)
Type: Family

This entry includes TMCO1, a member of the Oxa1 superfamily which includes a group of proteins that function in different contexts as transmembrane domains (TMD) insertases and/or as intramembrane chaperones to facilitate membrane protein folding and assembly . TMCO1 has been recently described as a component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes . Previously, it has been reported that TMCO1 is a ER calcium load-activated calcium channel . TMCO1 is required for the normal development of corpus callosum as it plays a role in Ca2 homeostasis . Archaeal members may function as insertases of the archaeal plasma membrane .
Protein of unknown function DUF842, eukaryotic (DUF842_euk)
Type: Family

This family represents Protein FAM136A and similar uncharacterised proteins of unknown function from animals and plants. The sequences carry three sets of CxxxC motifs, which might suggest a type of zinc-finger formation. In humans, FAM136A has been related to Meniere's disease, a complex disorder of the inner ear .
Protein Ac76, baculovirus (Ac76_baculovir)
Type: Family

This family consists mainly of baculovirus proteins. The member from Autographa californica multiple nucleopolyhedrovirus (AcMNPV), protein Ac76, has been characterised, and is involved in intranuclear microvesicle formation .
Autographa californica nuclear polyhedrosis virus (AcMNPV), C42 (AcMNPV_C42)
Type: Family

This entry is represented by Autographa californica nuclear polyhedrosis virus (AcMNPV), Orf101 (also known as Protein C42) . It plays a role in host nuclear actin polymerization by recruiting p78/73 protein that is capable of activating an actin-related protein 2/3 complex to initiate nuclear actin polymerization .
Protein AC81, baculovirus (AcMNPV_AC81)
Type: Family

This family consists of Baculovirus proteins and includes Autographa californica multiple nucleopolyhedrovirus (AcMNPV) protein AC81, which is required for nucleocapsid envelopment .
Golgi apparatus membrane protein TVP23-like (TVP23-like)
Type: Family

Tvp23 is a Golgi membrane protein involved in vesicular trafficking .
TtsA-like, Glycoside hydrolase family 108 domain (TtsA-like_GH18_dom)
Type: Domain

This entry represents a domain that is frequently found at the N terminus of proteins containing a C-terminal

domain, predominantly in bacteria and virus, including Glycoside hydrolase family 108 protein from Salmonella typhi (TtsA,

). TtsA is a specific muramidase that facilitates toxin transport through the peptidoglycan layer. The N-terminal domain, which contains the lysozyme-like catalytic triad (Glu14, Asp19, Thr28), shows three short helices forming a defined globular domain .
Gammaherpesvirus protein of unknown function DUF848 (DUF848)
Type: Family

This family consists of several uncharacterised proteins from the Gammaherpesvirinae.
Beta-keto acid cleavage enzyme (BKACE)
Type: Family

This family represents a group of beta-keto acid cleavage enzymes (BKACE) mainly found in prokaryotes that show at least 14 slightly different potential enzymatic activities . In certain instances these enzymes catalyse the conversion of 3-keto-5-aminohexanoate and acetyl-CoA into acetoacetate and 3-aminobutyryl-CoA and are involved in the lysine fermentation pathway .
ER membrane protein complex subunit 3 (EMC3)
Type: Family

EMC3 is a subunit if the ER Membrane protein Complex (EMC), which is required for efficient folding of proteins in the endoplasmic reticulum (ER). Loss of the EMC leads to accumulation of misfolded membrane proteins .
Protein of unknown function DUF851 (DUF851)
Type: Family

Proteins in this family have no known function and only seem to occur in Chromadorea.
ESCRT-II complex, Vps25 subunit (ESCRT-II_cplx_Vps25-sub)
Type: Family

This entry represents the Vps25 subunit (vacuolar protein sorting-associated protein 25) of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs) . ESCRT-II recruits the transport machinery for protein sorting at MVB . In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo .

ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps35 .
Helicase HerA-like (HerA-like)
Type: Family

This entry includes helicase HerA from archaea and some putative helicases from bacteria. HerA is a DNA helicase able to utilise either 3' or 5' single-stranded DNA extensions for loading and subsequent DNA duplex unwinding . It forms a complex with NurA nuclease, this complex has the 5'-3' DNA end resection activity and is essential for cell viability in the crenarchaeon Sulfolobus islandicus .
Baculovirus U-box/Ring-like (Baculovirus_U-box/Ring-like)
Type: Family

This family consists of several Baculovirus proteins of around 130 residues in length. The function of members of this family is unknown, but appear to be related to the U-box and ring finger domain by profile-profile comparison. In the Autographa californica multiple nucleopolyhedrovirus, ac53 (also known as orf53) is essential for production of infectious budded virus. Initially distributed in the cytoplasm and nucleus, ac53 accumulates near the nucleus-cytoplasm boundary. Deletion does not affect the levels of viral DNA replication but does affect nucleocapsid assembly .
Interactor of ZYG-11, nematodes (Nematodes_ZYG-11_interact)
Type: Family

This entry represents the protein product of the gene W03D8.9 (

) and similar sequences from nematodes. This protein has been identified as an interactor of ZYG-11. ZYG-11 is the substrate-recognition subunit for a CUL-2 based complex that regulates cell division and embryonic development .
Alpha-N-methyltransferase NTM1 (MeTrfase_NTM1)
Type: Family

All fungal and animal N-terminally methylated proteins contain a unique N-terminal motif, Met-(Ala/Pro/Ser)-Pro-Lys. Alpha-N-methyltransferase methylates the N terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. It catalyses mono-, di- or tri-methylation of the exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif . Some of the substrates may be primed by NTMT2-mediated monomethylation .
Putative viral structural protein (DUF859) (DUF859)
Type: Family

This family consists of several uncharacterised proteins from a number of the Siphoviruses as well as some bacterial proteins from Streptococcus species. Some of the members of this family are described as putative minor structural proteins.
(S)-ureidoglycine aminohydrolase, cupin domain (UGlyAH_Cupin_dom)
Type: Domain

This is the conserved barrel domain of the 'cupin' superfamily found in (S)-ureidoglycine aminohydrolase (UGlyAH or UGHY) from E.coli, with a conserved jelly roll-like β-barrel fold capable of homodimerization. This enzyme is involved in the anaerobic nitrogen utilization via the assimilation of allantoin and catalyses the second stereospecific hydrolysis reaction (deamination) of the allantoin degradation pathway, producing S-ureidoglycolate and ammonia from S-ureidoglycine .

This domain is also present in EutQ family from the eut operon, involved in ethanolamine degradation. EutQ is essential during anoxic growth and has acetate kinase activity . The cupin domain from EutQ does not possess the His residues responsible for metal coordination in other classes of cupins .
PPPDE peptidase domain (PPPDE_dom)
Type: Domain

The PPPDE superfamily (after Permuted Papain fold Peptidases of DsRNA viruses and Eukaryotes), consists of thiol peptidases with a circularly permuted papain-like fold. They contain a PPPDE domain which is a cysteine isopeptidase that exhibits a deSUMOylase activity in PPPDE2 (DeSI-1) and a deubiquinating activity in PPPDE1 (DeSI-2) and is described as a mixed α/β-fold composed of six β-strands and six α-helices. The catalytic dyad is formed by a conserved N-terminal histidine residue on beta2-strand and a conserved C-terminal cysteine residue on the following alpha3-helix (the H-C configuration). This catalytic dyad is invariably conserved in the PPPDE family of proteins .
Protein of unknown function DUF863, plant (DUF863_pln)
Type: Family

This family consists of a number of hypothetical proteins from plants. The function of this family is unknown.
CXXC motif containing zinc binding protein, eukaryotic (CXXC_Zn-binding_euk)
Type: Family

This family consists of a number of eukaryotic proteins including CXXC motif containing zinc binding protein (previously known as UPF0587 protein C1orf123). The crystal structure reveals that the protein binds a Zn2+ ion in a tetrahedral coordination with four Cys residues from two CxxC motifs.
Poly-gamma-glutamate hydrolase (Gamma_PGA_hydro)
Type: Family

This family consists of a number of bacterial and phage proteins that function as gamma-PGA hydrolase enzymes . Structurally the protein in this family adopted an open α/β mixed core structure with a seven-stranded parallel/anti-parallel β-sheet. This structure shows similarity to mammalian carboxypeptidase A and related enzymes.
Protein of unknown function DUF868, plant (DUF868_pln)
Type: Family

This family consists of several hypothetical proteins from plants. The function of this family is unknown.
Filament-like plant protein (FPP_plant)
Type: Family

This entry represents the filament-like plant proteins. In Arabidopsis thaliana, there are 7 filament-like plant proteins. They are coiled-coil proteins with unknown function .
Protein of unknown function DUF870, Caenorhabditis species (DUF870_CAE_spp)
Type: Family

This family consists of proteins of unknown function found in Caenorhabditis species.
6-phospho-N-acetylmuramidase (MupG)
Type: Family

This family consists of 6-phospho-N-acetylmuramidase, involved in the recycling pathway of the cell wall turnover product MurNAc-GlcNAc in S.aureus. It catalyses the hydrolysis of MurNAc 6-phosphate-GlcNAc, the disaccharide product of MurP-uptake and phosphorylation, yielding MurNAc 6-phosphate and GlcNAc .
Transmembrane protein 230/134 (TMEM_230/134)
Type: Family

This entry represents the eukaryotic transmembrane proteins 230 and 134 (TMEM230 and 134). TMEM134 function is unknown, but it has been shown to interact with E virus ORF2 . TMEM 230 is involved in trafficking and recycling of synaptic vesicles .
GINS complex subunit Sld5 (GINS_Sld5)
Type: Family

GINS is a key component of eukaryotic replicative forks. It is part of the CMG (Cdc45-MCM-GINS) complex, the eukaryotic replicative helicase that unwinds double-stranded DNA at replication forks . Beside its role as a key component of the CMG complex, GINS mediates a interactions with many replication factors .

GINS is composed of four subunits: Sld5, Psf1, Psf2, and Psf3 . The four subunits are structurally related and are likely to derive from a single protein. They share a common fold made up of an α-helical A domain and a β-rich B domain. Sld5 and Psf1 possess the A domain at the N terminus and the B domain at the C terminus, whereas these two domains are swapped in Psf2 and Psf3 . All subunits are essential for DNA replication.

This family of proteins represents the Sld5 subunit.
Protein of unknown function DUF874 (DUF874)
Type: Family

This family consists of several hypothetical proteins, mainly from Helicobacter pylori. The function of this family is unknown.
DNA N-6-adenine-methyltransferase (Dam_MeTrfase)
Type: Family

This family consists of several bacterial and phage DNA N-6-adenine-methyltransferase (Dam) like sequences . Dam methylates adenine residues in the ssDNA and dsDNA sequence 5'-GATC-3' .
Scavenger mRNA decapping enzyme DcpS/DCS2 (DcpS/DCS2)
Type: Family

This entry represents scavenger mRNA decapping enzymes, such as Dcp2 and DcpS. DcpS is a scavenger pyrophosphatase that hydrolyses the residual cap structure following 3' to 5' mRNA degradation. DcpS uses cap dinucleotides or capped oligonucleotides as substrate to release m(7)GMP (N7-methyl GMP), while Dcp2 uses capped mRNA as substrate in order to hydrolyse the cap to release m(7)GDP (N7-methyl GDP) . The association of DcpS with 3' to 5' exonuclease exosome components suggests that these two activities are linked and there is a coupled exonucleolytic decay-dependent decapping pathway. The family contains a histidine triad (HIT) sequence with three histidines separated by hydrophobic residues . The central histidine within the DcpS HIT motif is critical for decapping activity and defines the HIT motif as a new mRNA decapping domain, making DcpS the first member of the HIT family of proteins with a defined biological function. This family is related to (

).
Sensor DegS (DegS)
Type: Domain

This is a group of Bacillus DegS proteins. The DegS-DegU two-component regulatory system of Bacillus subtilis controls various processes that characterise the transition from the exponential to the stationary growth phase, including the induction of extracellular degradative enzymes, expression of late competence genes and down-regulation of the sigma D regulon . The entry also contains one sequence

from Thermoanaerobacter tengcongensis which is described as a sensory transduction histidine kinase.
Accessory protein p30II (P30II)
Type: Family

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1)-encoded P30II is a nuclear-resident protein that inhibits virus expression by reducing Tax and Rex protein expression .
Invertebrate-type lysozyme (Invert_lysozyme)
Type: Family

This is a family of invertebrate-type lysozymes . It includes Destabilase (

), an endo-epsilon(gamma-Glu)-Lys isopeptidase, which cleaves isopeptide bonds formed by transglutaminase (Factor XIIIa) between glutamine gamma-carboxamide and the ε-amino group of lysine .
Di19, zinc-binding domain (Di19_Zn-bd)
Type: Domain

This zinc-binding domain is found in Di19 proteins, animal E3 ubiquitin-protein ligases (RNF114/KCMF1/RNF138/RNF125/RNF166) and transcriptional repressors (ZEB1/ZEB2). KCMF1 and RNF114 are E3 ubiquitin-protein ligases , while ZEB1 represses transcription by binding to the E box (5'-CANNTG-3') . In RNF114, this domain has been shown to be essential for mono-ADPr-dependent recruitment to DNA lesions .

Protein dehydration-induced19 (Di19) increases the sensitivity of plants to environmental stress, such as salinity, drought, osmotic stress and cold. The protein is also induced by an increased supply of stress-related hormones such as abscisic acid ABA and ethylene . Di19 has been found to be strongly expressed in both the roots and leaves of Arabidopsis thaliana during progressive drought . It is phosphorylated by AtCPK11 in a Ca(2+)-dependent manner
Putative sugar diacid recognition (Diacid_rec)
Type: Domain

This region is found in several proteins characterised as carbohydrate diacid regulators (e.g.

). An HTH DNA-binding motif is found at the C terminus of these proteins suggesting that this region includes the sugar recognition region.
Cell-cell adhesion (Dicty_CAD)
Type: Family

Most members of this group of proteins are found in Dictyostelium discoideum (Slime mould) and are essential in early development .

and

are located on the cell surface and mediate cell-cell adhesion.
Duffy-antigen binding domain (Duffy-antigen-binding)
Type: Domain

This entry contains several Plasmodium Duffy binding proteins. Plasmodium vivax and Plasmodium knowlesi merozoites invade Homo sapiens erythrocytes that express Duffy blood group surface determinants . The Duffy receptor family is localised in micronemes, an organelle found in all organisms of the phylum Apicomplexa .
Dynactin subunit 4 (DCTN4)
Type: Family

DCTN4 (also known as dynactin subunit p62) is a subunit of the dynactin that may have a dual role in dynein targeting and in ACTR1A/Arp1 subunit of dynactin pointed-end capping. It could be involved in ACTR1A pointed-end binding and in additional roles in linking dynein and dynactin to the cortical cytoskeleton . It also interacts with the N terminus of P-type ATPase ATP7B .
Microtubule-associated protein 7 family (MAP7_fam)
Type: Family

MAP7 (also known as E-MAP-115 or Ensconsin) is a microtubule-stabilising protein that may play an important role in microtubule reorganisation during polarisation and differentiation of epithelial cells . It may play a role in the formation of intercellular contacts .

The MAP7 family has three other members: MAP7 domain containing proteins 1 (MAP7D1), 2 (MAP7D2) and 3 (MAP7D3) . MAP7D3 has been identified as a critical regulator of microtubule stability, probably through its binding to tubulin and microtubules, as well as its regulation of histone deacetylase 6 activity .
Extracellular matrix protein 1 (ECM1)
Type: Family

This family consists of several eukaryotic extracellular matrix protein 1 (ECM1) sequences. ECM1 has been shown to regulate endochondral bone formation, stimulate the proliferation of endothelial cells and induce angiogenesis . Mutations in the ECM1 gene can cause lipoid proteinosis, a disorder which causes generalised thickening of skin, mucosae and certain viscera. Classical features include beaded eyelid papules and laryngeal infiltration leading to hoarseness .
Eukaryotic translation initiation factor 4E binding (EIF4EBP)
Type: Family

This family consists of several eukaryotic translation initiation factor 4E binding proteins (EIF4EBP1, -2 and -3). Translation initiation in eukaryotes is mediated by the cap structure (m7GpppN, where N is any nucleotide) present at the 5' end of all cellular mRNAs, except organellar. The cap is recognised by eukaryotic initiation factor 4F (eIF4F), which consists of three polypeptides, including eIF4E, the cap-binding protein subunit. The interaction of the cap with eIF4E facilitates the binding of the ribosome to the mRNA. eIF4E activity is regulated in part by translational repressors, 4E-BP1, 4E-BP2 and 4E-BP3 which bind to it and prevent its assembly into eIF4F .
Ectropic viral integration site 2A protein (Ectropic_vir_integratn_site_2A)
Type: Family

This family contains several mammalian ectropic viral integration site 2A (EVI2A) proteins. The function of this protein is unknown although it is thought to be a membrane protein and may function as an oncogene in retrovirus induced myeloid tumours .
Ebola nucleoprotein (Ebola_NP)
Type: Family

This family consists of Ebola virus sp., Lake Victoria marburgvirus nucleoproteins. These proteins are responsible for encapsidation of genomic RNA. It has been found that nucleoprotein DNA vaccines can offer protection from the virus .
Eukaryotic rRNA processing (Ebp2)
Type: Family

This family consists of several eukaryotic rRNA processing protein EBP2 sequences. Ebp2p is required for the maturation of 25S rRNA and 60S subunit assembly. Ebp2p may be one of the target proteins of Rrs1p for executing the signal to regulate ribosome biogenesis .
SPI-2 type 3 secretion system translocon protein SctB-like (SctB2-like)
Type: Family

This entry represents a protein family that includes SPI-2 type 3 secretion system translocon protein SctB from Salmonella typhimurium (SctB2) and similar bacterial sequences. SctB2 is required for the translocation of SPI-2 effector proteins and for systemic Salmonella infection of the mouse . It is also essential for SpvB-induced actin depolymerisation in the host cell cytoplasm .
Mating pheromone, Euplotes octocarinatus (Mating_pheromone_EUPOC)
Type: Family

This family consists of several mating pheromone proteins from Euplotes octocarinatus. Cells of the ten mating types of the ciliate E. octocarinatus communicate by pheromones before they enter conjugation. The pheromones induce homotypic pairing when applied to mating types that do not secrete the same pheromone(s). Heterotypic pairs (i.e., those between cells of different mating types) are formed only when both mating types in a mixture secrete a pheromone that the other does not. The genetics of mating types is based on four codominant mating type alleles, each allele determining production of a different pheromone. The pheromones not only induce pair formation but also attract cells .
Excalibur calcium-binding domain (Excalibur_Ca-bd_domain)
Type: Domain

Extracellular Ca
2+
-dependent nuclease YokF from Bacillus subtilis and several other surface-exposed proteins from diverse bacteria are encoded in the genomes in two paralogous forms that differ by a ~45 amino acid fragment, which comprises a novel conserved domain. Sequence analysis of this domain revealed a conserved DxDxDGxxCE motif, which is strikingly similar to the Ca
2+
-binding loop of the calmodulin-like EF-hand domains, suggesting an evolutionary relationship between them. Functions of many of the other proteins in which the novel domain, named Excalibur (extracellular calcium-binding region), is found, as well as a structural model of its conserved motif are consistent with the notion that the Excalibur domain binds calcium. This domain is but one more example of the diversity of structural contexts surrounding the EF-hand-like calcium-binding loop in bacteria. This loop is thus more widespread than hitherto recognised and the evolution of EF-hand-like domains is probably more complex than previously appreciated .
Acidic fibroblast growth factor intracellular-binding protein (FIBP)
Type: Family

Acidic fibroblast growth factor (aFGF) intracellular binding protein (FIBP) is a protein found mainly in the nucleus that is thought to be involved in the intracellular function of aFGF .
FNIP (FNIP)
Type: Repeat

This short repeat is predominantly found in proteins from mimivirus and lower eukaryotes, including Calmodulin-binding protein CmbB from Dictyostelium discoideum (Social amoeba). It appears to be related to

. The alignment consists of two tandem repeats. It is termed the FNIP repeat after the pattern of conserved residues.
Uncharacterised protein family, YcgJ (Uncharacterised_YcgJ)
Type: Family

The function of these proteins is unknown.
Protein S10 (S10)
Type: Family

This family consists of several Fijivirus Protein S10.