SII-SWORD/CoKE huggingface dataset:
MT-A70-like (MT-A70-like)
Type: Family

N6-methyladenosine (m6A) is present at internal sites in some mRNAs. m6A affects different aspects of mRNA metabolism, such as half-life, splicing, and translation .

MT-A70 (also known as METTL3) is the S-adenosylmethionine-binding subunit of human mRNA N6-adenosine-methyltransferase (MTase), an enzyme that sequence-specifically methylates adenines in pre-mRNAs. Proteins with sequence similarity to MT-A70 have been identified in eukaryotes and prokaryotes. The resulting family is defined by sequence similarity in the carboxyl-proximal regions of the respective proteins. The amino-proximal regions of the eukaryotic proteins are highly diverse, often Pro-rich, and are conserved only within individual subfamilies . Corresponding regions are not present in prokaryotic members of the family. MT-A70-like proteins contain examples of some of the consensus methyltransferase motifs that have been derived from mutational and structural studies of bacterial DNA methyltransferases, including the universally conserved motif IV catalytic residues and a proposed motif I (AdoMet binding) element . The MT-A70-like family comprises four subfamilies with varying degrees of interrelatedness. One subfamily is a small group of bacterial DNA: m6A MTases. The other three are paralogous eukaryotic lineages, two of which have not been associated with MTase activity but include proteins that regulate mRNA levels via unknown mechanisms apparently not involving methylation .

Some proteins known to belong to the MT-A70-like family are listed below:

Human N6-adenosine-methyltransferase 70kDa subunit (MT-A70 or METTL3) (

), the catalytic component of the METTL3-METTL14 heterodimer that forms the N6-methyltransferase complex that methylates adenosine residues at the N6 position of some RNAs .

Human N6-adenosine-methyltransferase non-catalytic subunit (METTL14), the non-catalytic component of the METTL3-METTL14 heterodimer.

Yeast N6-adenosine-methyltransferase IME4 (

), which is important for induction of sporulation.

Yeast karyogamy protein KAR4, a phosphoprotein required for expression of karyogamy-specific genes during mating and that it also acts during mitosis and meiosis . It has been suggested that KAR4 is inactive for methyltransfer and may not even bind AdoMet.
Nucleoporin, NSP1-like, C-terminal (Nucleoporin_NSP1_C)
Type: Domain

The NSP1-like protein appears to be an essential component of the nuclear pore complex, for example preribosome nuclear export requires the Nup82p-Nup159p-Nsp1p complex. The C-terminal of Nsp1 is involved in binding Nup82 , probably via coiled-coil formation . The family is related to the rotavirus nonstructural protein NSP1 which is the least conserved protein in the rotavirus genome. Its function in the replication process is not fully understood.
ASXL, HARE-HTH domain (Asxl_HARE-HTH)
Type: Domain

This domain, known as the HARE-HTH domain, adopts the winged helix-turn-helix fold and is predicted to bind DNA. It can be found at the N terminus of the ASXL protein. It can also be found in several other eukaryotic chromatin proteins (such as HB1 in plants), diverse restriction endonucleases and DNA glycosylases, the RNA polymerase delta subunit of Gram-positive bacteria and certain bacterial proteins that combine features of the RNA polymerase alpha-subunit and sigma factors . The genetic interaction of the HARE-HTH containing ASXL with the methyl cytosine hydroxylating Tet2 protein is suggestive of a role for the domain in discriminating sequences with DNA modifications such as hmC . Bacterial versions include fusions to diverse restriction endonucleases, and a DNA glycosylase where it may play a similar role in detecting modified DNA. Certain bacterial version of the HARE-HTH domain show fusions to the helix-hairpin-helix domain of the RNA polymerase alpha subunit and the HTH domains found in regions 3 and 4 of the sigma factors . These versions are predicted to function as a novel inhibitor of the binding of RNA polymerase to transcription start sites, similar to the Bacillus delta protein .

This domain consists of four α-helices (helices I-II-III-IV) and an antiparallel β-sheet composed of three short β-strands at the top of a "twisted tripod" formed by helices II, III, and IV .

The Asx-like (Asxl) proteins includes Asxl1-3. They are putative Polycomb group (PcG) proteins, which act by forming multiprotein complexes that are required to maintain the transcriptionally repressive state of homeotic genes throughout development. Asxl1 is involved in transcriptional regulation mediated by ligand-bound retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG) .

The delta protein is a dispensable subunit of Bacillus subtilis RNA polymerase (RNAP) that has major effects on the biochemical properties of the purified enzyme. In the presence of delta, RNAP displays an increased specificity of transcription, a decreased affinity for nucleic acids, and an increased efficiency of RNA synthesis because of enhanced recycling . The delta protein, contains two distinct regions, an N-terminal domain and a glutamate and aspartate residue-rich C-terminal region . It participates in both the initiation and recycling phases of transcription.
Manganese catalase (Mn_catalase)
Type: Family

Catalases (

) are antioxidant enzymes that catalyse the conversion of hydrogen peroxide to water and molecular oxygen. Hydrogen peroxide is produced as a consequence of oxidative cellular metabolism and can be converted to the highly reactive hydroxyl radical via transition metals, this radical being able to damage a wide variety of molecules within a cell, leading to oxidative stress and cell death. Catalases act to neutralise hydrogen peroxide toxicity, and are produced by all aerobic organisms ranging from bacteria to man. There are three structurally independent classes of catalases: ubiquitous mono-functional haem-containing catalases (

), bifunctional haem-containing catalase-peroxidases that are closely related to plant peroxidases (

), and non-haem manganese-containing catalases .

This entry represents the non-haem Mn-catalases, which are found in several bacterial species . The structure of the Mn catalase from Lactobacillus plantarum reveals a homo-hexamer, where each subunit contains a dimanganese active site that is accessed by a single substrate channel . The dimanganese active site performs a two-electron catalytic cycle that alternately oxidises and reduces the dimanganese atoms in a manner that is similar to its haem-counterpart found in other catalases.
Mannitol repressor MtlR-like (MtlR-like)
Type: Family

The mannitol operon of Escherichia coli, encoding the mannitol-specific enzyme II of the phosphotransferase system (MtlA) and mannitol phosphate dehydrogenase (MtlD) contains an additional downstream open reading frame which encodes the mannitol repressor (MtlR). Although it is involved in the repression of the expression of the mannitol operon it does not bind the operator/promoter regulatory region of this operon. MtlR and homologous protein YggD belong to a new class of transcription factors in bacteria that may regulate gene expression indirectly as a part of a larger transcriptional complex .
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 (NDUFA12)
Type: Family

This entry includes the NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 (NDUFA12) and the NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2 (NDUFAF2). NDUFA12 is an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) , not involved in catalysis . NDUFAF2 is a paralogue of the structural subunit NDUFA12. NDUFAF2 function is tightly associated with the attachment of the N module and NDUFA12, NDUFS4 and NDUFS6 work together to release the assembly factor in the final step of complex I biogenesis .
Herpesvirus UL43 (Herpes_UL43)
Type: Family

UL43 genes are expressed with true-late (gamma2) kinetics and have been identified as a virion tegument component . Studies suggest that the N-terminal sequences target UL43 to protein aggregates and that C-terminal sequences are important for incorporation into particles.
Baculovirus p24 capsid (Baculo_p24)
Type: Family

The Culex nigripalpus NPV (Culex nigripalpus nucleopolyhedrovirus) protein p24 is associated with nucleocapsids of budded and polyhedra-derived virions .
Protein of unknown function DUF684 (DUF684)
Type: Family

This family contains uncharacterised proteins from Caenorhabditis species.
Suppressor of fused (Suppressor_of_fused)
Type: Family

Sufu, encoding the human ortholog of Drosophila suppressor of fused, appears to have a conserved role in the repression of Hedgehog signalling . It is a repressor of the Gli and Ci transcription factors of the Hedgehog signalling cascade , and functions by binding these proteins and preventing their translocation to the nucleus. Sufu has been found to be a tumour-suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signalling pathway . Homologues of Sufu have been found in bacteria, though their function is not currently known.

This entry represents the eukaryotic suppressor of fused proteins and their bacterial homologues.
Poxvirus A19 (Poxvirus_A19)
Type: Family

This entry represents Protein A19 from Vaccinia virus, also known as Protein OPG146, and similar sequences from poxvirus. A19 plays a role in the maturation of immature virions to infectious particles. It may also participate in viral transcription .
Protein DMP (DMP)
Type: Family

This entry includes plant protein DMP, including Arabidopsis AtDMP1-10. DMP1 is a membrane protein that may be involved in membrane fission during breakdown of the ER and the tonoplast during leaf senescence and in membrane fusion during vacuole biogenesis in roots . DMP8 and DMP9 have been shown to facilitate gamete fusion during double fertilization in flowering plants .
Protein of unknown function DUF680 (DUF680)
Type: Family

This family contains several uncharacterised proteins which seem to be found exclusively in Rhizobiales.
Beak and feather disease virus (BFDV), Orf5 (BFDV_Orf5)
Type: Family

This entry is represented by Beak and feather disease virus (BFDV), Orf5; it is a family of uncharacterised viral proteins.
Autographa californica nuclear polyhedrosis virus (AcMNPV), P18 (AcMNPV_P18)
Type: Family

This entry is represented by Autographa californica nuclear polyhedrosis virus (AcMNPV), P18; it is a family of uncharacterised viral proteins.
Putative nitrogen fixation protein (Put_N_fixation)
Type: Family

This family contains several uncharacterised bacterial proteins. These proteins are found in nitrogen fixation operons, so are likely to play some role in this process. They consist of two α helices which are joined by a four residue linker. The helices form an antiparallel bundle and cross towards their termini. They are likely to form a rod-like dimer . They have structural similarity to the regulatory protein Rop (

).
Leukocyte-specific transcript 1, LST-1 (Leukocyte-sp_tscrpt_1_LST1)
Type: Family

B144/LST1 is a gene encoded in the human major histocompatibility complex that produces multiple forms of alternatively spliced mRNA and encodes peptides fewer than 100 amino acids in length. B144/LST1 is strongly expressed in dendritic cells. Transfection of B144/LST1 into a variety of cells induces morphologic changes including the production of long, thin filopodia .

A possible role in modulating immune responses. Induces morphological changes including production of filopodia and microspikes when overexpressed in a variety of cell types and may be involved in dendritic cell maturation. Isoform 1 and isoform 2 have an inhibitory effect on lymphocyte proliferation .
Protein of unknown function DUF685 (DUF685)
Type: Family

This family consists of uncharacterised proteins from Borrelia species. There is some evidence to suggest that the proteins may be outer surface proteins.
Dictyostelium REP (Dict_REP)
Type: Family

This family consists of REP proteins from a number of Dictyostelium species (Slime molds). REP protein is probably involved in transcription regulation and control of DNA replication, specifically the amplification of plasmid at low copy numbers. The formation of homomultimers may be required for their regulatory activity .
Rotavirus VP2 (Rotavirus_VP2)
Type: Family

Rotavirus particles consist of three concentric proteinaceous capsid layers. The innermost capsid (core) is made of VP2. The genomic RNA and the two minor proteins VP1 and VP3 are encapsidated within this layer . The N terminus of rotavirus VP2 is necessary for the encapsidation of VP1 and VP3 .
NAD-glutamate dehydrogenase, bacteria (NAD_Glu_DH_bac)
Type: Family

This family consists of several bacterial proteins which are closely related to NAD-glutamate dehydrogenase found in Streptomyces clavuligerus. Glutamate dehydrogenases (GDHs) are a broadly distributed group of enzymes that catalyse the reversible oxidative deamination of glutamate to ketoglutarate and ammonia .
Alpha-N-acetylglucosaminidase (NAGLU)
Type: Family

Alpha-N-acetylglucosaminidase is a lysosomal enzyme required for the stepwise degradation of heparan sulphate . Mutations on the alpha-N-acetylglucosaminidase (NAGLU) gene can lead to Mucopolysaccharidosis type IIIB (MPS IIIB; or Sanfilippo syndrome type B) characterised by neurological dysfunction but relatively mild somatic manifestations .
Vitamin K-dependent gamma-carboxylase (VKG_COase)
Type: Family

Using reduced vitamin K, oxygen, and carbon dioxide, gamma-glutamyl carboxylase post-translationally modifies certain glutamates by adding carbon dioxide to the γ position of those amino acids. In vertebrates, the modification of glutamate residues of target proteins is facilitated by an interaction between a propeptide present on target proteins and the gamma-glutamyl carboxylase .
Eukaryotic translation initiation factor 3 subunit D (eIF3d)
Type: Family

Eukaryotic translation initiation factor 3 subunit D (eIF3d) is a component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome . The gene coding for the protein has been implicated in cancer in mammals .
Per os infectivity factor (PIR)
Type: Family

This entry represents a group of dsDNA Baculovirus proteins. It is required for the infectivity of the OBs or occlusion bodies. It is a structural protein of the ODV envelope required only in the first steps of per os larva infection, as viruses being produced in cells expressing the gene for this protein but not containing it in their genomes are able to produce successful infections. Baculoviruses are large DNA viruses that infect arthropods, mainly members of the order Lepidoptera. In their life cycle, they produce two kinds of particles, a budded, non-occluded virus (BV), which buds out of the infected cell and is responsible for the cell-to-cell transmission of the virus, and an occluded form, the occlusion body (OB), which is responsible for protecting the virus between encounters with larvae. A variable number of virions are included in the para-crystalline structure of the OB, mainly constituted by the virus-encoded polyhedrin protein; these virions are called occlusion body-derived virions or ODVs .
Anamorsin (Anamorsin)
Type: Family

Anamorsin (also named CIAPIN1 for cytokine-induced anti-apoptosis inhibitor 1), is the human homologue of yeast Dre2, a conserved soluble eukaryotic Fe-S cluster protein, that functions in cytosolic Fe-S protein biogenesis . It is found in both the cytoplasm and in the mitochondrial intermembrane space (IMS) . Anamorsin is found to be up-regulated in hepatocellular cancer, is considered to be a downstream effector of the receptor tyrosine kinase-Ras signalling pathway, and is essential in mouse definitive haematopoiesis . In addition, it mediates the anti-apoptotic effects of various cytokines .
Late expression factor 9 (LEF-9)
Type: Family

The baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) encodes a DNA-dependent RNA polymerase that is required for transcription of viral late genes. This polymerase is composed of four equimolar subunits, LEF-8, LEF-4, LEF-9, and p47. LEF-9 is homologous to the largest beta-subunit of prokaryotic DNA-directed RNA polymerase .
Protein of unknown function DUF687 (DUF687)
Type: Family

This family contains uncharacterised Chlamydia proteins.
Glutaminyl-peptide cyclotransferase (QCT)
Type: Family

QCT converts glutamine and N-terminal glutamyl residues in peptides to 5-oxoproline and 5-oxoproline residues .
Protein of unknown function DUF688 (DUF688)
Type: Family

This entry consists of uncharacterised proteins.
Late expression factor 4 (LEF-4)
Type: Family

The baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) virus encodes a DNA-dependent RNA polymerase that is required for transcription of viral late genes. This polymerase is composed of four equimolar subunits, LEF-8, LEF-4, LEF-9, and p47. LEF-4 carries out all the enzymatic functions related to mRNA capping .
Co-chaperone DjlA, N-terminal (DjlA_N)
Type: Domain

This entry represents the N-terminal of the DjlA protein. This domain can also be found in the tellurium resistance protein TerB.
Type IV secretion system, VirB3 / TrbD / AvhB (T4SS_VirB3/TrbD/AvhB)
Type: Family

This entry represents type IV secretion system proteins VirB3, TrbD and AvhB. Type IV secretion systems are found in plant and animal pathogens, as well as in symbiotic bacteria. The tumour-inducing (Ti) plasmid of Rhizobium radiobacter (Agrobacterium tumefaciens) encodes two DNA transfer systems: VirB and Trb, where the virB operon is required for the transfer DNA to the plant host, and the trb system is required for the conjugal transfer of the Ti plasmid between cells of Agrobacterium . In addition, VirB3 is found associated with bacterial inner and outer membranes and assists T pilus formation as an assembly factor . The conjugal transfer protein TrbD contains a nucleotide binding motif and may provide energy for the export of DNA or the export of other Trb proteins . This entry also includes avhB (Agrobacterium virulence homologue virB), which is most similar to the VirB type IV secretion system of Bartonella henselae (Rochalimaea henselae) .
DivIVA family (DivIVA_fam)
Type: Family

The Bacillus subtilis divIVA1 mutation causes misplacement of the septum during cell division, resulting in the formation of small, circular, anucleate minicells . Inactivation of divIVA produces a minicell phenotype, whereas overproduction of DivIVA results in a filamentation phenotype . These proteins appear to contain coiled-coils.

This entry represents DivIVA and related proteins, including cell cycle protein GpsB.
Ribosome receptor lysine/proline rich (Rib_rcpt_KP)
Type: Domain

The ribosome receptor is an integral endoplasmic reticulum protein that has been suggested to be involved in secretion. This highly conserved region is found towards the C terminus of the transmembrane domain . The function is unclear.
Type VII secretion system EccB (T7SS_EccB)
Type: Family

The proteins in this family are found in Actinobacteria and are part of type VII secretion system (T7SS) . This entry represents the transmembrane protein EccB of actinobacterial type VII secretion systems. EccB (ESX conserved component B) is a core component of the T7SS architecture. Species such as Mycobacterium tuberculosis have several instances of this system per genome, designated EccB1, EccB2, etc. Mycobacterium tuberculosis EccB1 has been shown to be an ATPase .

This entry does not identify functionally related proteins in the Firmicutes such as Staphylococcus aureus and Bacillus anthracis.
Envelope glycoprotein GP350, N-terminal, A domain, herpervirus (GP350_N_A_dom_herpes)
Type: Domain

This entry represents domain A of the N-terminal region of GP350. This domain is located in the middle of the "L-shape" structure adopted by the N-terminal, bridging domain B on one side and domain C on the other .

This entry includes Envelope glycoprotein GP350 from Epstein-Barr virus (also known as BLLF1 viral late glycoprotein), the most abundantly expressed glycoprotein in the viral envelope of Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies
in vivo
. It is a 907 residues long gp350 polypeptide containing an 18-residue peptide at the C terminus that is located inside the viral membrane, a membrane-spanning domain and a large N-terminal segment (860 residues) predicted to extend outside the viral membrane. The extreme N-terminal region (1-470) is sufficient to bind receptor CR2 (also known as CD21) and fold into three distinct domains (denoted as A (

), B (

) and C (

)) that organise into an "L-shape" structure.

The binding of the viral major glycoprotein BLLF1 to the CD21 cellular receptor is responsible for viral attachment to the cell surface during infection of B lymphocytes by the Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4) .
AF4/FMR2 family (AF4/FMR2)
Type: Family

The AFF (AF4/FMR2) family includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. All AFF proteins are localized in the cell nucleus and are involved in regulation of gene expression .

In humans, AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs) .

This entry also includes Drosophila AF4 protein homologue Lilliputian which contains an AT-hook domain. Lilliputian represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis in Drosophila .

This family also includes a Drosophila AF4 protein homologue Lilliputian which contains an AT-hook domain. Lilliputian represents a novel pair-rule gene that acts in cytoskeleton regulation, segmentation and morphogenesis in Drosophila .
Ameloblastin precursor (Amelin)
Type: Family

This family consists of mammalian Ameloblastin precursor (Amelin) proteins. Matrix proteins of tooth enamel consist mainly of amelogenin but also of non-amelogenin proteins, which, although their volumetric percentage is low, have an important role in enamel mineralization. One of the non-amelogenin proteins is ameloblastin, also known as amelin and sheathlin. Ameloblastin (AMBN) is one of the enamel sheath proteins which is thought to have a role in determining the prismatic structure of growing enamel crystals .
Baculovirus p47 (Baculo_p47)
Type: Family

This family consists of several baculoviral p47 proteins which is one of the primary components of Autographa californica nuclear polyhedrosis virus (AcMNPV) encoded RNA polymerase, which initiates transcription from late and very late promoters .
Protein of unknown function DUF693 (DUF693)
Type: Family

This family consists of uncharacterised proteins from Borrelia burgdorferi.
RiPP precursor modification enzyme MbnB/TglH/ChrH (MbnB/TglH/ChrH)
Type: Family

This entry represents a family of multinuclear iron-containing proteins which are post-translational modification enzymes involved in the biosynthesis of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products, including the precursor modification enzymes MbnB, TglH, and ChrH, formerly known as DUF692 .
Cytochrome b6-f complex subunit 6 (Cyt_b6/f_cplx_su6)
Type: Family

This family consists of several Cytochrome B6-F complex subunit VI (PetL) proteins found in a number of plant species. PetL is one of the small subunits which make up the cytochrome b(6)f complex. PetL is not absolutely required for either the accumulation or for the function of cytochrome b6f; in its absence, however, the complex becomes unstable
in vivo
in aging cells and labile
in vitro
. It has been suggested that the N terminus of the protein is likely to lie in the thylakoid lumen .