SII-SWORD/CoKE huggingface dataset:
Histone-lysine N-methyltransferase EZH1/2-like (EZH1/2-like)
Type: Family

This entry represents a group of histone-lysine N-methyltransferases that belong to the Polycomb group (Pc-G), including:

Drosophila melanogaster Enhancer of zeste E(z).

Mammalian EZH-1 and EZH-2.

Arabidopsis thaliana CURLY LEAF (CLF), a transcriptional repressor of floral homeotic gene AGAMOUS.

Arabidopsis thaliana CLF-like.

Arabidopsis thaliana MEDEA (MEA), a suppressor of endosperm development.

Arabidopsis thaliana EZA1.

The Polycomb Repressive Complex 2 (PRC2) is a chromatin modifying complex that consists of three core components: EED, SUZ12 and one of the two histone H3K27 methyltransferases, EZH1 or EZH2 . The PRC2 complex catalyses di- and trimethylation of histone H3 lysine 27 (H3K37me2/3), which has a repressive role. Even though EZH1 and EZH2 form similar PRC2 complexes, they exhibit contrasting repressive roles. In terms of their expression in mice, EZH1 is more abundant in nonproliferative adult organs, while EZH2 expression is tightly associated with proliferation .
Potassium channel KAT/AKT (KAT/AKT)
Type: Family

Potassium (K+) is an essential nutrient for plant growth and development. This entry represents a group of potassium channel proteins from plants, including KAT1-3, SKOR, GORK and AKT1/2/5/6 from Arabidopsis . Together with AtHAK5, AKT1 mediates high-affinity K+ uptake into roots during seedling establishment and post-germination growth . KAT1 is required for guard cell K+ uptake during light-induced stomatal opening . AKT6, also known as SPIK, plays a role in K+ uptake in the growing pollen tube . AKT1 has been shown to be regulated by the CBL1-CIPK23 complex . SKOR and GORK are both outward-rectifying potassium channels .
Zinc finger protein JAGGED/STAMENLESS 1-like (JAGGED/SL1-like)
Type: Family

This entry represents a group of plant zinc finger proteins, including JAGGED, JAGGED-like from Arabidopsis and STAMENLESS 1 from rice. JAGGED is a transcription factor activated in the emerging organ primordia and in the distal region of immature organs . It controls growth anisotropy and coordination between cell size and cell cycle during plant organogenesis . JAGGED-like acts redundantly with JAGGED to define stamen and carpel shape . STAMENLESS 1 regulates floral organ identity and cell proliferation in the inner floral whorls. It may specify the identities of lodicule and stamen through positive regulation of MADS16 expression. May contribute to morphogenesis by suppressing OSH1 expression in the lateral organs .
Chitinase Cts1-like (Cts1-like)
Type: Domain

This entry represents a domain found in a group of chitinase-like proteins mostly form fungi and plants, including Cts1 from budding yeasts, CHIB1 from Arabidopsis and XIP-I from wheat and rice. Cts1 is required for cell separation during growth of S. cerevisiae . XIP-I is a xylanase inhibitor that does not exhibit chitinolytic activity but shows specificities towards fungal GH11 xylanases .
E3 ubiquitin-protein ligase HECTD1/TRIP12-like (HECTD1/TRIP12-like)
Type: Family

This entry includes a group of E3 ubiquitin-protein ligases, including HECTD1/TRIP12 from humans, Ufd4 from budding yeasts and UPL3/4 from Arabidopsis. HECTD1 regulates intracellular localisation and secretion of Hsp90 and is essential for the correct development of the cranial neural folds and neural tube closure .

TRIP12 is involved in the ubiquitin fusion degradation pathway and regulation of DNA repair

,

]. This protein plays an important role in nervous system development and function . UPL3 is involved in ubiquitination and subsequent proteasomal degradation of target proteins and in the repression of the endoreduplication process and the cell morphogenesis in the trichomes .
Coiled-coil domain-containing protein 34 (CCDC34)
Type: Family

CCDC34 promotes cell proliferation and invasive properties in human cancer .
Small multidrug resistance protein (Small_multidrug_res)
Type: Family

Members of this family are integral membrane proteins that belong to the small multidrug resistance (SMR) protein family. They confer resistance to a wide range of toxic compounds by removing them for the cells. The efflux is coupled to an influx of protons. An example is Escherichia coli EmrE (

) which plays a role in pH and osmotic stress response and biofilm formation. It confers resistance to a wide range of toxic compounds, including ethidium, methyl viologen , benzalkonium, propidium, dequalinium, different aromatic cation antibiotics, being also involved in ethidium bromide efflux . It simultaneously binds and co-transports proton and drug . Structural studies of EmrE revealed that the transmembrane (TM) helices undergo a complex reorientation to bind and transport diverse substrates. It may function not only as a proton-coupled antiporter but also as a proton-coupled symporter or uncoupled uniporter that potentially confers susceptibility rather than resistance, because the inward proton motive force and negative-inside membrane potential in bacteria would lead to concentrative uptake of toxic cations .
TMEM70/TMEM186/TMEM223 protein family (TMEM70/TMEM186/TMEM223)
Type: Family

This entry represents the TMEM70/TMEM186/TMEM223 protein family. TMEM70 is a family of proteins essential for assembly of the mitochondrial proton-transporting ATP synthase complex within the inner mitochondrial membrane. TMEM70 functions in the assembly of complexes I and V .
Autophagy protein ATG17-like domain (ATG17-like_dom)
Type: Domain

This domain is found in the autophagy-related proteins ATG17 and ATG11, conserved across eukaryotes . ATG17 forms a complex with ATG29 and ATG31, critical for both PAS (preautophagosomal structure) formation and autophagy. Together with ATG13, it is required for ATG1 kinase activation [

, CITE:23219485]]. ATG11 is a scaffold protein required for the cytoplasm-to-vacuole targeting (Cvt) pathway during starvation and to recruit ATG proteins to the pre-autophagosome. It is also required for ATG1 kinase activation. In many eukaryotes, ATG11 (the orthologue in mammals is RB1-inducible coiled-coil protein 1 (RB1CC1) and in S. pombe is Taz1-interacting factor 1 (taf1)) is essential for bulk autophagy, except in S.cerevisiae . ATG17 and ATG11 are large similar proteins, both predicted to be almost entirely helical, containing conserved coiled-coil regions and lack obvious functional motifs .
Protein of unknown function DUF5881 (DUF5881)
Type: Family

This is a family of uncharacterised proteins predominantly found in viruses.
Yeast cell wall synthesis Kre9/Knh1 (Kre9/Knh1)
Type: Family

This entry includes a group of cell wall synthesis proteins, such as Knh1 and Kre9 from budding yeasts, involved in cell wall beta 1,6-glucan synthesis. Kre9 is involved involved in cell wall beta-glucan assembly . In Saccharomyces cerevisiae, a kre9 null mutation has been shown to lead to severe growth defects, aberrant multi-budded morphology, and mating defects . Over-expression of Knh1 suppresses growth defects of a kre9 null mutant . Moreover, Knh1 is required for propionic acid resistance .
Leucine zipper putative tumor suppressor (LZTS)
Type: Family

The leucine zipper tumor suppressor (LZTS) family members are thought to play roles in cell growth modulation, mitosis and cancer cell growth suppression . This entry includes the protein families LZTS 1-3 from animals.

LZTS1 (also known as FEZ1) plays a role in mitosis . It is associated with assembled microtubules and is involved in the stabilisation of active p34CDC2 (Cdk1) . LZTS2 (LAPSER1) interacts with p80 katanin and regulates katanin-mediated microtubule severing. It alters cell proliferation by regulating cytokinesis. It is localised to the centrosome and the midbody in mitotic cells and modulates beta-catenin signalling and localisation . LZTS3 (ProSAP-interacting protein 1, ProSAPiP1) interacts with the PDZ domain of ProSAP2/Shank3, a scaffolding protein for components of the postsynaptic density (PSD) of excitatory brain synapses . It also interacts with the postsynaptic protein Sipa1l3/SPAR3 .
TRM3/TARBP1 (TRM3/TARBP1)
Type: Family

This entry includes a group of putative methyltransferases, including TARBP1 from humans and Trm3 from Saccharomyces cerevisiae. TARBP1 (TAR RNA-binding protein 1) plays a role in HIV-1 infection by binding to the loop region of TAR RNA, a region also bound by RNA polymerase II . Its dimerization may have a critical role in its activity . Trm3 catalyses a specific methylation of the guanosine nucleotide at position 18 of the tRNAs. It is involved in the cellular response to oxidative stress, and its activity may play a role on innate response .
MITD1, N-terminal domain (MITD1_N)
Type: Domain

The MIT domain forms an asymmetric three-helix bundle. It is found in vacuolar sorting proteins, spastin (probable ATPase involved in the assembly or function of nuclear protein complexes), and a sorting nexin, which may play a role in intracellular trafficking.

MIT domain-containing protein 1, together with components of the ESCRT-III complex, is required for efficient abscission at the end of cytokinesis .
ARMET, N-terminal (ARMET_N)
Type: Domain

This entry represents the N-terminal domain of ARMET.

ARMET, also known as mesencephalic astrocyte-derived neurotrophic factor (MANF) or arginine-rich protein, is a small protein of approximately 170 residues which contains four di-sulphide bridges that are highly conserved from nematodes to humans. It is a soluble protein resident in the endoplasmic reticulum and induced by ER stress. It appears to be involved with dealing with mis-folded proteins in the ER, thus in quality control of ER stress . ARMET from Rattus norvegicus (Rat) selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. It modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra, and enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons .

Proteins containing this domain includes the related neurotrophic factor CDNF (cerebral dopamine neurotrophic factor) .
ARMET-like (ARMET-like)
Type: Family

ARMET, also known as mesencephalic astrocyte-derived neurotrophic factor (MANF) or arginine-rich protein, is a small protein of approximately 170 residues which contains four di-sulphide bridges that are highly conserved from nematodes to humans. It is a soluble protein resident in the endoplasmic reticulum and induced by ER stress. It appears to be involved with dealing with mis-folded proteins in the ER, thus in quality control of ER stress . ARMET from Rattus norvegicus (Rat) selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. It modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra, and enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons .

This entry also includes the related neurotrophic factor CDNF (cerebral dopamine neurotrophic factor) .
Integrator complex subunit 3 (INTS3)
Type: Family

The Integrator complex is involved in small nuclear RNA (snRNA) U1 and U2 transcription, and in their 3'-box-dependent processing. This complex associates with the C-terminal domain of RNA polymerase II largest subunit and is recruited to the U1 and U2 snRNAs genes .

This entry represents integrator complex subunit 3 (Ints3). It is also a component of the sensor of single-stranded DNA complex (SOSS), which associates with single-stranded DNA, important for DNA repair and efficient homologous recombination . This subunit serves as a central adaptor for SOSS complex assembly and stability, and facilitates the accumulation of the complex to the sites of DNA damage. Its N-terminal region acts as a scaffold for SOSSB1 and SOSSC interaction and it is not essential for ssDNA binding .
Cell division protein FtsQ, C-terminal (FtsQ_C_sf)
Type: Homologous_superfamily

FtsQ is an essential cell division protein. It may link together the upstream cell division proteins, which are predominantly cytoplasmic, with the downstream cell division proteins, which are predominantly periplasmic . FtsQ may control the correct divisome assembly .

FtsQ has a short N-terminal cytoplasmic domain and a larger C-terminal periplasmic domain . This entry represents the C-terminal region of FtsQ.
MmgE/PrpD, N-terminal (MmgE_PrpD_N)
Type: Domain

This entry represents the N-terminal domain of 2-methylcitrate dehydratase PrpD.

PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle . This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an α/β domain . Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family . CAD is essential for itaconic acid production in Aspergillus terreus . Citrate/2-methylcitrate dehydratase from Bacillus subtilis is involved in the tricarboxylic acid (TCA) and methylcitric acid cycles as it has both 2-methylcitrate dehydratase and citrate dehydratase activities .
MmgE/PrpD, C-terminal (MmgE_PrpD_C)
Type: Domain

This entry represents the C-terminal domain of 2-methylcitrate dehydratase PrpD.

PrpD is required for propionate catabolism, catalysing the third step of the 2-methylcitric acid cycle . This enzyme consists of two domains: a large domain with an all-helical fold and a smaller domain that folds into an α/β domain . Cis-aconitic acid decarboxylase (CAD) shares high identity with proteins of the MmgE/PrpD family . CAD is essential for itaconic acid production in Aspergillus terreus . Citrate/2-methylcitrate dehydratase from Bacillus subtilis is involved in the tricarboxylic acid (TCA) and methylcitric acid cycles as it has both 2-methylcitrate dehydratase and citrate dehydratase activities .
Domain of unknown function DUF6535 (DUF6535)
Type: Domain

This entry represents an integral membrane region of a large family of fungal proteins. This region likely contains three transmembrane helices. Some proteins contain two copies of this region. The function of these proteins is unknown.
Domain of unknown function DUF6534 (DUF6534)
Type: Domain

This entry represents a domain found in a large family of fungal integral membrane proteins.
Domain of unknown function DUF6533 (DUF6533)
Type: Domain

This entry represents a short conserved region found in a large family of fungal integral membrane proteins.
Domain of unknown function DUF6532 (DUF6532)
Type: Domain

This entry represents a domain found in a group of uncharacterised fungal proteins.
Septation protein Etd1 (Etd1)
Type: Family

This family includes the Septation protein Etd1 from Schizosaccharomyces pombe, which activates the GTPase Spg1 to trigger signaling through the septum initiation network (SIN) pathway and onset of cytokinesis. The proper regulation of Etd1 is crucial for both activation of Spg1 in anaphase and inactivation of Spg1 when cytokinesis is complete . It was suggested that Etd1 is the functional homologue of budding yeast Lte1 as they have the same function but a very low sequence similarity .
VpsR domain (VpsR)
Type: Domain

This entry represents a domain found at the N terminus of VpsR from Vibrio cholerae.

VpsR appears superficially to be a response regulator, based on extension of its alignment to response regulators AlgB and NrtC all the way to the N terminus. Instead of being a response regulator with a histidine kinase partner, the sigma-54-dependent transcription factor VpsR directly binds to cyclic-di-GMP. Its regulon includes genes for the biosynthesis of the biofilm matrix component called Vibrio polysaccharide (VPS) .
C-JID domain (C-JID)
Type: Domain

C-terminal jelly roll/Ig-like domain (C-JID) was defined in cryogenic electron microscopy (cryoEM) structures of plant intracellular immune receptors containing Toll/interleukin-1 receptor (TIR), nucleotide-binding (NB-ARC) and leucine-rich repeat (LRR) domains (TIR-NLRs) . Structurally, the C-JID core is represented by a β-sandwich made up of 8 to 9 β-strands. C-JID matches the so-called post-LRR or C-terminal non-LRR domain detected earlier via MEME and BLAST searches . The domain showed a strong distribution bias towards TIR-NLRs of dicotyledonous plant species despite broader taxonomic distribution of TIR-NLR in plant groups . Structure-function analyses of cryoEM structures suggest that C-JID domains play a role in substrate recognition, such as binding to effector proteins from pathogens, and thus are involved in the initiation of signalling by TIR-NLR receptors . Presence of C-JID (or post-LRR) and its importance for the function of Arabidopsis TIR-NLR RPS4 that partners with RRS1 for effector recognition suggest that C-JID has additional functions .
Retroviral nucleocapsid Gag protein p24, C-terminal domain (Gag_p24_C)
Type: Domain

The Gag protein from retroviruses, also known as p24, forms the inner protein layer of the nucleocapsid. It is composed of two domains, the N-terminal domain (NTD), which contributes to viral core formation, and the C-terminal domain (CTD), which is required for capsid dimerisation, Gag oligomerization and viral formation . This protein performs highly complex orchestrated tasks during the assembly, budding, maturation and infection stages of the viral replication cycle. During viral assembly, the proteins form membrane associations and self-associations that ultimately result in budding of an immature virion from the infected cell. Gag precursors also function during viral assembly to selectively bind and package two plus strands of genomic RNA. ELISA tests for p24 is the most commonly used method to demonstrate virus replication both
in vivo
and
in vitro
.

This is the C-terminal domain of retroviral p24 nucleocapsid protein, which contains a highly conserved region across retroviruses, the major homology region (MHR). The MHR is essential for the stability and folding of the monomer and hence for viral assembly, maturation and infectivity. This is a globular domain, composed of four helices and an extended N-terminal strand that forms a dimer through parallel packing of helix 2. The MHR dimer is a target for the development of anti-HIV drugs .
Ermin (Ermin)
Type: Family

Ermin is an oligodendrocyte-specific protein that plays a role in cytoskeletal rearrangements during the late wrapping and/or compaction phases of myelinogenesis as well as in maintenance and stability of myelin sheath in the adult. It is expressed exclusively in oligodendrocytes in human brain and has been shown to bind and induce the reorganization of F-actin . It may also be essential in late-stage oligodendroglia maturation, myelin/Ranvier node formation during CNS development, and in the maintenance and plasticity of related structures in the mature CNS . In humans, it has been linked to epilepsy and multiple sclerosis .
HIND motif (HIND)
Type: Conserved_site

The Hub1 interacting motif (HIND) is a short conserved motif found in 1 to 3 copies in spliceosomal proteins such as SART1 from animals and Snu66 in yeast (both components of the U4/U6-U5 tri-snRNP complex). The motif is bound by the Hub1 protein, playing a key role in the splicing process .
CPSF complex subunit CPSF4-like (CPSF4/Yth1)
Type: Family

This entry includes CPSF4/CPSF4L from humans and Yth1 from yeasts. Most members have several CCCH type zinc finger domains, which are responsible for the nucleotide recognition .

In animals, the CPSF complex is the central complex of the cleavage and polyadenylation (CP) reaction. It carries the catalytic activity for pre-mRNA cleavage, and its interaction with the AAUAAA sequence is essential for cleavage and the AAUAAA dependence of polyadenylation . It is composed of five subunits: CPSF160, CPSF100, CPSF73 and CPSF30 (also known as CPSF4) and Fip1. CPSF4 has been shown to bind RNA polymers with a preference for poly(U) . In humans, CPSF4 has also been shown to interact with influenza A virus NS1 and block processing of pre-mRNAs, thereby preventing nuclear export of host cell mRNAs .
SLC41A divalent cation transporter (SLC41A1-3)
Type: Family

This entry includes the SLC41A family members mostly from eukaryotes and archaea. Some proteins are from bacteria. The SLC41A family of divalent cation transporters includes SLC41A1, SLC41A2 and SLC41A3 and MgtE . MgtE, the SLC41A1 orthologue found in prokaryotes, consists of a homodimer architecture with five transmembrane domains at the C terminus and the cytosolic domains at the N terminus. Structural and functional analyses showed MgtE conserved acidic side-chains play a key role as part of its selectivity filter .

In humans, SLC41A1 is a Na+/Mg2+ ion exchanger that acts as a predominant Mg2+ efflux system at the plasma membrane. The transporter activity is driven by the inwardly directed electrochemical gradient for Na+ ions, thus directly depends on the extracellular Na+ ion concentration set by the Na+/K+ pump. In this way, it generates circadian cellular Mg2+ fluxes that feed back to regulate clock-controlled gene expression and metabolism and facilitate higher energetic demands during the day. This protein is located in the cell membrane . Its expression level has been linked to diverse disorders such as preeclampsia in pregnant woman, nephronophthisis, Parkinson's disease and bone mass loss. Hence, it has been suggested this protein might be a great therapeutic target .
Protein of unknown function DUF5968 (DUF5968)
Type: Family

This entry represents a member of a biosynthetic gene cluster (BGC). This BGC (BGC0000566) is described by MIBiG as an example of the following biosynthetic class, RiPP (ribosomally synthesised and post-translationally modified peptide).
Domain of unknown function DUF6531 (DUF6531)
Type: Domain

This putative domain is found in a range of RHS proteins.
Protein of unknown function DUF6530 (DUF6530)
Type: Family

This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria. Proteins in this family are approximately 160 amino acids in length.
LAIKA domain (LAIKA)
Type: Domain

This presumed domain can be found in CCRA1/CCRA2 from animals and RSA1 from plants.

Cell division cycle and apoptosis regulator protein 1 (CCRA1, also known as CARP-1) is a transcriptional coactivator for nuclear receptors which may contribute to cell growth and apoptosis . It can act as a both a coactivator and corepressor of the transcription dependent on the androgen receptor (AR), thereby playing an important role in the growth and tumorigenesis of prostate cancer cells . Cell cycle and apoptosis regulator protein 2 (CCRA2, also known as DBC-1) is a core component of the DBIRD complex, which regulates alternative splicing . It is also involved in p53-mediated apoptosis , genomic stability and cellular integrity following UV-induced genotoxic stress , tumour suppression and BRCA1 activity .

In Arabidopsis thaliana, SHORT ROOT IN SALT MEDIUM 1 (RSA1, also known as EMB1579) is required for salt tolerance and sodium (Na) homeostasis after salt stress . RSA1 is localised to the nucleus and the loss of function of RSA1 affects global transcription and mRNA splicing .
Poly(A) polymerase catalytic subunit (PolyA_pol_cat_su)
Type: Domain

This family represents the Poly(A) polymerase catalytic subunit found in viruses .
Protein of unknown function DUF5882 (DUF5882)
Type: Family

This is a family of uncharacterised proteins of unknown function predominantly found in Marseillevirus.
Aminopeptidase N-like , N-terminal domain (Aminopeptidase_N-like_N)
Type: Domain

Aminopeptidase N from Escherichia coli is a broad specificity zinc exopeptidase belonging to aminopeptidase clan MA, family M1. The enzyme is composed of four domains: an N-terminal β-domain, a catalytic domain, a middle β-domain and a C-terminal α-domain .
Ty3 transposon capsid-like protein (Ty3_capsid)
Type: Domain

This entry corresponds to the capsid protein found in the Ty3 transposons of yeast as well as other transposable elements present in eukaryotes . These long terminal repeat (LTR) retrotransposons share similarities with the envelope protein in retroviruses like HIV-1 .
Protein of unknown function DUF5903 (DUF5903)
Type: Family

This is a family of proteins of unknown function mostly found in Prasinovirus.