SII-SWORD/CoKE huggingface dataset:
Multiple myeloma tumor-associated protein 2-like (MMTAG2-like)
Type: Family

Multiple myeloma tumor-associated protein 2 (MMTAG2) is an uncharacterised protein initially identified in the human multiple myeloma cell line ARH-77. The protein contains phosphorylation sites, N-myristoylation sites and nuclear localisation signals . Proteins in this entry contain a kinase phosphorylation domain.
C2 calcium-dependent domain-containing protein 4 (C2_Ca-dependent_4)
Type: Family

C2 calcium-dependent domain-containing protein 4A (NLF1) and 4B (NLF2) are nuclear factors highly expressed in endothelial cells and induced by acute inflammation. They may have a role in regulating genes that control cellular architecture and adhesion .
ORC ubiquitin ligase 1 (OBI1)
Type: Family

This family describes ORC ubiquitin ligase 1 (previously known as RING finger protein 219 or RNF219). ORC ubiquitin ligase 1 is an E3 ubiquitin ligase essential for DNA replication origin activation during S phase. It functions as a replication origin selector and catalyzes the multi-mono-ubiquitination of a subset of chromatin-bound ORC3 and ORC5 during S-phase .
2-oxoglutarate and iron-dependent oxygenase domain-containing protein 3 (OGFOD3)
Type: Family

2-Oxoglutarate and iron-dependent oxygenase domain-containing protein 3 (OGFOD3) is an uncharacterised protein predominantly found in animals and SAR supergroup organisms. It is a type II transmembrane protein with a short N-terminal cytoplasmic section and the bulk of the protein in the lumen. It contains a Fe(2+) and 2-oxoglutarate (2OG)-dependent dioxygenase domain and is assumed to be an enzyme that catalyses the oxidation of an organic substrate using a dioxygen molecule.
Ribosome-binding factor A, mitochondrial (RBFA_mitochondrial)
Type: Family

This entry represents ribosome-binding factor A (RBFA) from human and its homologues. it is a mitochondrial RNA-binding protein that exerts crucial roles in mitoribosome biogenesis . The structure has been solved by NMR (

) and cryo_EM (

).
FAM90 (FAM90)
Type: Family

This mammalian protein family is known as FAM90, and it is functionally uncharacterised.
Lymphocyte antigen 96 (LY96)
Type: Family

Lymphocyte antigen 96 (LY96 or MD-2) is a glycoprotein essential for the innate response to lipopolysaccharide (LPS), binds to both LPS and the extracellular domain of Toll-like receptor 4 (TLR4) . LY96 also associates with TLR2, enabling a response to LPS and peptidoglycan from both Gram-positive and Gram-negative bacteria . The structure of LPS-bound LY96 has been solved, showing that the LPS binds in a deep hydrophobic cavity sandwiched by two β sheets and that the phosphorylated glucosamine moieties are located at the entrance to the cavity .
REM family (REM_fam)
Type: Family

This entry represents a group of plant proteins, known as REM. They are B3 domain-containing proteins. AtREM1 contains several repeats of a B3-related domain and may be involved in the organisation of reproductive meristem .
FAM3 family (FAM3)
Type: Family

Family with sequence similarity 3 (FAM3) members are designated as FAM3A, FAM3B, FAM3C and FAM3D. There is increasing evidence that FAM3A, FAM3B and FAM3C are important regulators of glucose and lipid metabolism, which makes this family a promising therapeutical target for non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes .
Protein AATF/Bfr2 (AATF/Bfr2)
Type: Family

Apoptosis antagonizing transcription factor (AATF, also known as Che-1) is a adaptor that connects transcriptional regulation, cell-cycle progression, checkpoint control, and apoptosis . It contains a leucine zipper-containing domain . AATF has been shown to inhibit the aberrant production of the amyloid beta peptide 1-42 by direct interaction with Par4; this interaction occurs via the leucine zipper. . AATF has also been shown to form a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis .

This entry also includes the yeast protein Bfr2, which is a component of the SSU processome and 90S preribosomes .
Transcription factor Gibbin (AHDC1)
Type: Family

Transcription factor Gibbin, also known as AT-hook DNA-binding motif-containing protein 1 (AHDC1), is a transcription factor required for the proper patterning of the epidermis, which plays a key role in early epithelial morphogenesis . It directly binds promoter and enhancer regions and acts by maintaining local enhancer-promoter chromatin architecture. It interacts with many sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes that wire surface ectoderm stratification . Truncating mutations in the gene lead to a syndrome in which patients suffered hypotonia, intellectual disability, global developmental delay, mildly dysmorphic facial features and in some cases sleep apnea .
Ski3/TTC37 (Ski3/TTC37)
Type: Family

This entry includes superkiller protein 3 (Ski3) from yeasts and plants and tetratricopeptide repeat protein 37 (TTC37/SKI3) from animals. They are a component of the Ski complex required for exosome-mediated RNA surveillance .

In budding yeasts, the SKI complex (Ski2-Ski3-Ski8) is a helicase complex functioning with the RNA-degrading exosome to mediate the 3'-5' messenger RNA (mRNA) decay in turnover and quality-control pathways . Ski3 has also been shown to repress dsRNA virus propagation by specifically blocking translation of viral mRNAs .
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 (GNG13)
Type: Family

A guanine nucleotide-binding protein (G protein) is involved in transmembrane signaling systems and is a complex of alpha, beta and gamma subunits. The beta and gamma subunits are required for GTPase activity. The entry includes the G protein gamma subunit GNG13. GNG13 associates with the alpha subunit of gustducin, a transducin-like G protein selectively expressed in taste receptor cells . The equivalent subunit in
Drosophila melanogaster
is known as guanine nucleotide-binding protein subunit gamma-e (Ggamma30A).
SUZ domain-containing protein 1 (SZRD1)
Type: Family

The function of SZRD1 is not clear. It may act as a tumour suppressor in cervical cancer . Homologues are found in metazoa and fungi. Homologues contain a SUZ domain, which is a conserved RNA-binding domain enriched in positively charged amino acids and first characterised in the Caenorhabditis elegans protein SZY-20 where it has been shown to bind RNA and allow their localization to the centrosome .
Tubulin polyglutamylase complex subunit 2 (TPGS2)
Type: Family

TPGS2 is part of the neuronal tubulin polyglutamylase complex, which plays a role in post-translational addition of glutamate residues to C-terminal tubulin tails .
Tubulin polyglutamylase complex subunit 1 (TPGS1)
Type: Family

Tubulin polyglutamylase complex subunit 1-like TPGS1 (also known as PGs1) is part of the tubulin polyglutamylase complex, which plays a role in post-translational addition of glutamate residues to C-terminal tubulin tails . It is required for sperm axoneme assembly and normal animal behaviour .
Gastrin (GAST)
Type: Family

Gastrin is a hormonal regulator of various digestive processes and feeding behaviours. It induces gastric secretion, stimulates pancreatic secretion, increases blood circulation and water secretion in the stomach and intestine, and stimulates smooth muscle contraction. Originally found in the gut, it has since been shown to be present in various parts of the nervous system. Like many other active peptides gastrin is synthesized as a larger protein precursor that is enzymatically converted to its mature form. It is found in several molecular forms due to tissue-specific post-translational processing. The biological activity of gastrin is associated with the last five C-terminal residues. One or two positions downstream, there is a conserved sulphated tyrosine residue . Cionin, a neuropeptide from the protochordate Ciona intestinalis, belongs to this family.
Lymphocyte antigen 6 complex locus protein G6c (LY6G6C)
Type: Family

The function of LY6G6C is not clear . It is a GPI-anchored cell surface protein, highly expressed at the leading edges of cells, on filopodia, which are normally involved in cell adhesion and migration . Homologues are found only in mammals.
Adherens junction-associated protein 1 (AJAP1)
Type: Family

Adherens junction-associated protein 1 (AJAP1, also known as shrew-1) was first discovered as a transmembrane protein of adherent junctions in epithelial cells. Later, it was found to act as a tumour suppressor in gliomas. It may affect cell motility, migration, invasion and proliferation . Homologues are found only in chordates.
Ribosomal RNA-processing protein Rrp9-like (Rrp9-like)
Type: Family

This entry includes Rrp9 from budding yeasts and its homologue, U3 small nucleolar RNA-interacting protein 2 (also known as U3-55K) from animals. Rrp9 interacts with U3 snRNP and is involved in pre-rRNA processing . Human U3-55 protein has also been shown to bind to U3 snoRNA .
Mediator of RNA polymerase II transcription subunit 9, metazoan (MED9_metazoa)
Type: Family

This entry represents subunit Med9 of the Mediator complex. Subunit Med9 is part of the middle module of the Mediator complex ; this associates with the core polymerase subunits to form the RNA polymerase II holoenzyme.

Med9 alternatively known as the chromosome segregation protein, CSE2 (

) is required, along with CSE1 (

) for accurate mitotic chromosome segregation in Saccharomyces cerevisiae (Baker's yeast) .

This entry includes Med9 from metazoa.
Leucine-rich repeat-containing protein 25 (LRRC25)
Type: Family

Leucine-rich repeat-containing protein 25 (LRRC25) is an inhibitor of signalling pathways. In the RLR-mediated type I interferon signaling pathway, LRRC25 targets DDX58/RIG-I for autophagic degradation . Similarly, the NF-kappa-B signaling pathway and the inflammatory response are inhibited by targeting p65/RELA for degradation . LRRC25 is a type I transmembrane protein with an N-terminal lumenal domain, a single transmembrane domain and a larger cytoplasmic domain. The leucine-rich repeats are in the N-terminal, lumenal domain.
Galanin-like peptide (GALP)
Type: Family

The galanin-like peptide (GALP) exists in two isoforms which have different physiological functions. Isoform 1 is a neuropeptide from the hypothalamus that binds to the G-protein-coupled galanin receptors and is required for regulation of gonadotropin-releasing hormone secretion amongst other central nervous system homeostatic processes . Isoform 2 (also known as alarin), produced by alternative splicing and sharing only the N-terminal pentapeptide with mature isoform 1, is a vasoconstrictor in the microvasculature of the skin and does not bind to G-protein-coupled galanin receptors. It also has antimicrobial activity against Gram-negative bacteria .
Peroxisomal/glyoxysomal leader peptide-processing protease (TYSND1/DEG15)
Type: Family

The peroxisomal leader peptide-processing protease (TYSND1, trypsin domain-containing 1) removes the N-terminal transit peptide from proteins containing a PTS2 target sequence . The plant glyoxysomal processing protease (DEG15) performs a similar function in the glyoxysome, a specialized peroxisome. DEG15 exists as a homodimer or as a monomer; as a dimer it is a processing enzyme, as a monomer it degrades denatured proteins . These peptidases are trypsin homologues and members of MEROPS family S1 and subfamily S1B. Cleavage requires a cysteine residue in P1 or P2 .
Flagellar protein FlgA (Flagellar_FlgA)
Type: Family

FlgA is essential for flagellar biosynthesis and motility, and plays a significant role in biofilm formation in Campylobacter . It functions as a flagellar chaperone in P-ring assembly .
RNA-binding protein KhpB (KhpB)
Type: Family

This entry represents the RNA-binding protein KhpB, also known as RNA-binding protein Jag/EloR, a RNA chaperone that forms a complex with KhpA and binds to cellular RNA, controlling its expression. It plays a role in peptidoglycan (PG) homeostasis and cell length regulation, cell division and maintenance of cell shape . Bacillus subtilis KhpB/Jag is associated with SpoIIIJ, a gene necessary for the third stage of sporulation . These proteins consist of an N-terminal Jag-domain of unknown function and two RNA-binding domains, a type II KH domain (KH-II) and R3H, at the C-terminal end.
Phosphatase RsbX (Ptase_RsbX)
Type: Family

Phosphatase RsbX from Bacillus subtilis is a negative regulator of sigma-B activity, a transcription factor that controls the general stress response. The activity of SigB is directly regulated under stress conditions by a signalling cascade composed of seven Rsb proteins (regulators of sigma B) . RsbX halts the stress response by dephosphorylation of RsbS and/or RsbR .
G patch domain-containing protein 11 (GPATCH11)
Type: Family

G patch domain-containing protein 11 (GPATCH11) is an uncharacterised protein containing a G-patch domain. Homologues are known from eukaryotes.
CREBL2/REPTOR-BP (CREBL2/REPTOR-BP)
Type: Family

The cAMP-responsive element-binding protein-like 2 (CREBL2) is an uncharacterised protein containing a basic-leucine zipper (bZip) domain. Because of the location of the gene in a region frequently deleted in cancers, it has been suggested that CREBL2 is a tumour repressor .

This entry also includes REPTOR-BP from fruit flies. It is a transcriptional regulator that acts in the TORC1 signaling pathway to regulate energy homeostasis and promote survival during nutrient deprivation .
Oxidoreductase-like domain-containing protein 1 (OXLD1)
Type: Family

This entry contains uncharacterised oxidoreductase-like domain-containing proteins including mammalian oxidoreductase-like domain-containing protein 1 (OXLD1), and the mitochondrial proteins P31B10.02 and YPL107W from the yeasts
Schizosaccharomyces pombe
and
Saccharomyces cerevisiae
.
Protein RALF-like 27 (RALFL27)
Type: Family

The plant RAPID ALKALINIZATION FACTOR (RALF) family consists of extracellular peptides that serve as extracellular signals . This entry represents RALF-like 27, whose exact function is not known.
Aprataxin and PNK-like factor (APLF)
Type: Family

The protein APLF (aprataxin and PNK-like factor or Xip1;

) is a nuclease involved in single-strand and double-strand DNA break repair . It has endo- and exonuclease activities and contains a FHA (forkhead-associated) domain and zinc-finger-like CYR motifs . APLF interacts with XRCC1 and XRCC4 via its FHA domain .
Protein Rds1 (Rds1)
Type: Family

This entry represents the Rds1 protein from Schizosaccharomyces pombe (

) and related fungal proteins. Rds1 from Schizosaccharomyces pombe may have a function in stress-related responses of the cell .
Large ribosomal RNA subunit accumulation protein YceD, bacteria (YceD_bac)
Type: Family

YceD is believed to play a role in synthesis, processing and/or stability of 23S rRNA, as gene knockout in Escherichia coli leads to significant reduction of 23S rRNA .
Ketosteroid isomerase (Ketosteroid_isomerase)
Type: Family

Many biological reactions proceed by enzymatic cleavage of a C-H bond adjacent to carbonyl or a carboxyl group, leading to an enol or a enolate intermediate that is subsequently re-protonated at the same or an adjacent carbon. Ketosteroid isomerases (

) are important members of this class of enzymes which are the most proficient of all enzymes known and have served as a paradigm for enzymatic enolizations since their discovery in 1954. This entry includes members of this class that calalyze the isomerization of various beta,gamma-unsaturated isomers at nearly a diffusion-controlled rate. These enzymes are widely distributed in bacteria .
B- and T-lymphocyte attenuator (BTLA)
Type: Family

BTLA is a lymphocyte inhibitory receptor belonging to the immunoglobulin superfamily . The BTLA ligand is a tumour necrosis factor receptor named herpesvirus-entry mediator (HVEM) . BTLA-HVEM interactions have been shown to regulate responses in several pathogen and autoimmune settings .
Zinc finger protein 511 (ZNF511)
Type: Family

This entry includes the uncharacterised zinc finger protein 511 (ZNF511) which contains C2H2-type zinc fingers. The gene for a homologue from the fruit fly
Drosophila melanogaster
, known as protein lethal(2)k10201, is vital and a component of the wunen locus which guides migrating germ cells from the lumen of the developing gut towards the overlying mesoderm .
Protein maelstrom (Protein_maelstrom)
Type: Family

Maelstrom is a germ-plasm component protein that is involved in the piRNA pathway, though its precise function is not known. This protein contains a novel domain, known as the Maelstrom domain, which adopts the RNaseH fold. Maelstrom is essential for Piwi-mediated silencing and acts downstream of or in parallel to H3K9me3 in Drosophila .
Chondroitin proteoglycan 3 (Cpg-3)
Type: Family

Each chondroitin proteoglycan (CPG) consists of a protein core and one or more covalently attached chondroitin chains. Nine chondroitin core proteins have been identified in C. elegans (CPG-1 to CPG-9) . This family includes proteins known as chondroitin proteoglycan 3 (CPG-3) and is found in nematodes from the class Chromadorea.
Ferredoxin-NADP reductase (FNR), nucleotide-binding domain (FNR_nucleotide-bd)
Type: Homologous_superfamily

This entry represents the nucleotide-binding domain found in ferredoxin-NADP reductases (FNRs).
DTW domain-containing protein DTWD2/TAPT (DTWD2/TAPT)
Type: Family

Proteins in this entry contain a DTW domain (with the presence of a central DTXW motif). DTW domain containing protein may have a SAM-dependent acp transferase activity . This entry includes DTWD2, also known as tRNA-uridine aminocarboxypropyltransferase 2, from humans, DTWD2A from Arabidopsis and TAPT (also known as YfiP) from Escherichia coli. TAPT is a tRNA-uridine aminocarboxypropyltransferase that catalyses the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 47 of tRNAs .
Tellurite resistance protein TehA (TehA)
Type: Family

This entry represents tellurite resistance protein TehA. TehA belongs to the C4-dicarboxylate transporter/malic acid transport (TDT) protein family and is a homologue of plant Slow Anion Channel-Associated 1 (SLAC1) . The tehA gene encodes an integral membrane protein that has been shown to have efflux activity on quaternary ammonium compounds. TehA protein of Escherichia coli functions as a tellurite-resistance uptake permease .
Putative lipid-transfer protein DIR1-like (DIR1-like)
Type: Family

This entry represents a group of plant proteins, including DIR1 (At5g48485) from Arabidopsis. AtDIR1 is an acidic lipid transfer protein essential for systemic acquired resistance (SAR), which is a defence mechanism that induces protection against a wide range of pathogens in distant, pathogen-free parts of plants after a primary inoculation . Upon SAR induction, DIR1 moves from locally infected to distant uninfected leaves to activate defense priming .
Autonomous transposable element EN-1 mosaic protein (EN-1/SPM)
Type: Family

This entry represents a group of plant proteins, including EN-1 (also known as SPM) from maize. EN-1 is a autonomous transposable element controlled by interacting epigenetic and autoregulatory mechanisms .
U7 snRNA-associated Sm-like protein Lsm11 (Lsm11)
Type: Family

The eukaryotic Sm and Sm-like (Lsm) proteins associate with RNA to form the core domain of the ribonucleoprotein particles involved in a variety of RNA processing events including pre-mRNA splicing, telomere replication, and mRNA degradation. Members of this family share a highly conserved Sm fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel β-sheet .
Ankyrin repeat and fibronectin type-III domain-containing protein 1 (ANKFN1)
Type: Family

Ankyrin repeat and fibronectin type-III domain-containing protein 1 (ANKFN1) contains two ANK repeats and a fibronectin type-III domain and may play a role in neuronal function . Homologues are known from metazoa.
Zinc finger protein 469 (ZNF469)
Type: Family

Zinc finger protein 469 (ZNF469) is found in chordates and is uncharacterised. Mutations in the ZNF469 gene are associated with brittle cornea syndrome, an autosomal-recessive disorder characterised by a thin cornea that tends to perforate, causing progressive visual loss and blindness . The protein contains several C2H2-type zinc fingers.
Kiwellin-like (Kiwellin-like)
Type: Family

Kiwellin was identified as a kiwi fruit allergenic protein. It can be processed into an N-terminal 4kDa peptide known as Kissper, which can form an anion-selective pore . KWL1 specifically blocks the catalytic activity of the chorismate mutase Cmu1 . KWL1 binds in proximity to the Cmu1 active site and thus likely blocking the substrate access. It adopts a double psi β-barrel fold . This entry also includes Kiwellin-like proteins from rice and other plants.
CLEC16A/TT9 (CLEC16A/TT9)
Type: Family

CLEC16A (C-Type Lectin Domain Containing 16A) an evolutionarily conserved endosomal membrane protein required for trafficking of fluid-phase and receptor-mediated endocytic cargos. It is required for mitophagy, autophagy and endosome maturation . This protein has been identified as a susceptibility gene for autoimmune diseases like type 1 diabetes, multiple sclerosis and adrenal dysfunction . It has an inhibitory role in autophagy, probably by activating the mTOR pathway .

GFS9/TT9 (TRANSPARENT TESTA 9) is a protein from Arabidopsis required for vacuolar development through membrane fusion at vacuoles. It contributes to intracellular membrane trafficking and flavonoid accumulation .
AP-4 complex accessory subunit Tepsin (TEPSIN)
Type: Family

Tepsin associates with the adapter-like complex (AP-4) complex, which forms a non-clathrin coat around cytoplasmic vesicles in plants and animals . Mutagenesis studies have identified two phylogenetically conserved peptide motifs within the C-terminal of tepsin that interact with the C-terminal ear (or appendage) domains of the beta4 and epsilon subunits of AP-4 . The homologue from Arabidopsis thaliana is known as MTV1 (At3g16270), which mediates clathrin-dependent trafficking of vacuolar cargo from the trans-Golgi network .
Flowering-promoting factor 1 (FPF1)
Type: Family

This entry includes flowering-promoting factor 1 (FPF1) and related proteins from plants. They are involved in flowering time control .
PDZ domain-containing protein 8 (PDZD8)
Type: Family

PDZ domain-containing protein 8 (PDZD8) is a molecular tether, connecting endoplasmic reticulum (ER) and mitochondria membranes. This tethering is required for transfer of Ca
2+
ions between the ER and mitochondrion, which is particularly important in neurones . PDZD8 is a membrane protein containing a single transmembrane region and contains SMP-LTD (synaptotagmin-like mitochondrial-lipid binding protein) and PDZ domains and a phorbol-ester/DAG-type zinc finger. Homologues are found in metazoa.
Protein SAWADEE HOMEODOMAIN HOMOLOG 1/2 (SHH1/2)
Type: Family

This entry includes SAWADEE HOMEODOMAIN HOMOLOGS 1 and 2 (SHH1 and SHH2) from plants. In Arabidopsis, SHH1 is a homeodomain protein required for DNA methylation and for the accumulation of siRNAs at specific loci . It interacts with Pol-IV and acts upstream in the RdDM (RNA-directed DNA methylation) pathway. Its SAWADEE domain is a chromatin-binding module that functions as a dual lysine reader, probing for both unmethylated K4 and methylated K9 modifications on the histone 3 (H3) tail . The function of SHH2 is not clear.
Transcription factor VOZ1/VOZ2 (VOZ1/VOZ2)
Type: Family

This entry represents a group of plant transcription factors, including VOZ1 and VOZ2 from Arabidopsis. They are phytochrome B interacting factors that regulate flowering . They interact with CONSTANS and promote photoperiodic flowering transition . They also regulate the abiotic and biotic stress-responsive pathways .