SII-SWORD/CoKE huggingface dataset:
RNA binding protein HABP4/SERBP1-like (HABP4/SERBP1-like)
Type: Family

This entry includes proteins with a hyaluronan/mRNA-binding protein domain, including HABP4 hyaluronan-binding proteins, PAI-RBP1 (also known as SERBP1) and related sequences.

HABP4 binds hyaluronan (a glucosaminoglycan), but according to its intracellular localisation, it may not be relevant in vivo. It has binds RNA and regulates transcription and pre-mRNA splicing .

SERBP1 is a ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilised in an inactive state and preserved from proteasomal degradation . It acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilisation and storage in an inactive state and it may also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay . It seems to play a role in PML-nuclear bodies formation . The orthologue from S. pombe, oga-1, is a ribosome preservation factor that protects a small pool of nontranslating, vacant ribosomes in cells under nutrient starvation conditions. Under nutrient-limiting conditions, cells reduce ribosome biogenesis and degrade ribosomes via autophagy (ribophagy) or proteasomal degradation. It binds specifically G4 quadruplex (these are four-stranded right-handed helices, stabilised by guanine base quartets) and purine motif triplex (characterised by a third, antiparallel purine-rich DNA strand located within the major groove of a homopurine stretch of duplex DNA) nucleic acid structures. These structures may be present at telomeres or in rRNAs. Extends chronological lifespan when overexpressed .
Protein Yip5/YIPF1/YIPF2 (Yip5/YIPF1/YIPF2)
Type: Family

This entry includes Yip5 from yeasts and YIPF1/YIPF2 from animals. Yip5 interacts with Rab GTPase and is localized to late Golgi vesicles . Together with YIPF6, YIPF1 and YIPF2 play a role in the Golgi reassembly and glycan synthesis .
Vacuolar protein sorting-associated protein 53 (Vps53)
Type: Family

This entry represents Vps53 from eukaryotes. Vps53 is part of the of the GARP (Golgi-associated retrograde protein) complex involved in retrograde transport from early and late endosomes to late Golgi . Mutations in the human Vps53 gene cause pontocerebellar hypoplasia 2E (PCH2E), a neurodegenerative disorder characterised by progressive cerebello-cerebral atrophy, profound mental retardation, progressive microcephaly, spasticity, and early-onset epilepsy .
RalA-binding protein 1 (RALBP1)
Type: Family

RALBP1, also known as RLIP76, is a Ral-binding GTPase activating protein implicated in a number of cell processes, including receptor-mediated endocytosis, cell migration, mitochondrial division and metabolite transport . It transports glutathione-conjugates of electrophilic compounds and may contribute to the multidrug resistance . It has been shown to mediate ATP-dependent transport of glutathione-conjugates and doxorubicin in human erythrocytes .
Ribosomal export protein Nmd3 (Nmd3)
Type: Family

Nmd3 acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit . It may activate the circularly permuted GTPase Lsg1 during 60S ribosome biogenesis .
18S rRNA (guanine(1575)-N(7))-methyltransferase Bud23-like (Bud23-like)
Type: Family

This entry includes yeast Bud23 and its homologues from animals and plants. They are S-adenosyl-L-methionine-dependent methyltransferases that specifically methylates the N7 position of a guanine in 18S rRNA . Bud23 homologue in Arabidopsis, known as Rid2 (ROOT INITIATION DEFECTIVE 2), is also involved in pre-rRNA processing . This protein requires the methyltransferase adapter protein TRM112 for full rRNA methyltransferase activity .
Ribosome biogenesis protein Rpf2 (Rpf2)
Type: Family

Rpf2 is a conserved protein essential for the maturation of 25 S rRNA and the 60 S ribosomal subunit assembly . It is part of the complex (Rpf2/Rrs1/rpL5/rpL11) that functions in intermediate stages of 66S preribosome maturation and assembles into 90S preribosomes containing 35S pre-rRNA .
Exosome complex component Csl4 (Csl4)
Type: Family

This entry includes archaeal exosome complex component Csl4 and its homologues from eukaryotes (also known as exosome component 1 EXOSC1 in mammals). In budding yeast, Csl4 is also known as Ski4 due to its superkiller (SKI) phenotype first described as a more efficient ability to kill sensitive non-killer yeast strains . Later, it was found to be part of the yeast exosome complex involved in 3'-5' RNA processing and degradation in both the nucleus and the cytoplasm .

Csl4 is a non-catalytic component of the exosome, a complex involved in RNA processing and degradation . The exact composition of the exosome varies, depending on the organism or the subcellular localization, but in all cases it is composed of a ring-shaped core made of three heterodimers (Rrp41p/Rrp45p, Rrp43p /Rrp46p, Rrp42p/Mtr3p) stabilized by the presence of three other proteins (Csl4/Ski4, Rrp4p, Rrp40p) . The presence of different proteins in the cap may enable interactions with different substrates. It has been shown that the archaeal DnaG protein needs Csl4 for binding to the exosome. DnaG is a poly(A)-binding protein and enhances the degradation of adenine-rich transcripts by the Csl4-exosome .
RNA methyltransferase Bin3-like (Bin3-like)
Type: Family

Proteins in this entry contain a Bin3-type S-adenosyl-L-methionine binding domain, proteins include:

Drosophila melanogaster 7SK snRNA methylphosphate capping enzyme bin3, interacting with bicoid/bcd , probable RNA methyltransferase CG1239 and CG11342

7SK snRNA methylphosphate capping enzyme (MePCE) or Bicoid-interacting protein 3 homologue (Bin3 homolog), a S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5'-end of 7SK snRNA, leading to stabilise it

RNA 5'-monophosphate methyltransferase BCDIN3D

Arabidopsis thaliana probable RNA methyltransferase At5g51130

Schizosaccharomyces pombe probable RNA methyltransferase C2A9.10

Caenorhabditis elegans probable methyltransferase Y17G7B.18
Molecular chaperone regulator BAG (BAG_chaperone_regulator)
Type: Family

BAG domains are present in Bcl-2-associated athanogene 1 and silencer of death domains. The BAG proteins are modulators of chaperone activity; they bind to HSP70/HSC70 proteins and promote substrate release. The proteins have anti-apoptotic activity and increase the anti-cell death function of BCL-2 induced by various stimuli. BAG-1 binds to the serine/threonine kinase Raf-1 or Hsc70/Hsp70 in a mutually exclusive interaction. BAG-1 promotes cell growth by binding to and stimulating Raf-1 activity. The binding of Hsp70 to BAG-1 diminishes Raf-1 signalling and inhibits subsequent events, such as DNA synthesis, as well as arrests the cell cycle. BAG-1 has been suggested to function as a molecular switch that encourages cells to proliferate in normal conditions but become quiescent under a stressful environment .

BAG-family proteins contain a single BAG domain, except for human BAG-5, which has four BAG repeats . The BAG domain is a conserved region located at the C-terminal of the BAG-family proteins that binds the ATPase domain of Hsc70/Hsp70. The BAG domain is evolutionarily conserved, and BAG domain containing proteins have been described and/or proven in a variety of organisms, including Mus musculus (Mouse), Xenopus spp., Drosophila spp., Bombyx mori (Silk moth), Caenorhabditis elegans, Saccharomyces cerevisiae (Baker's yeast), Schizosaccharomyces pombe (Fission yeast), and Arabidopsis thaliana (Mouse-ear cress).

The BAG domain has 110-124 amino acids and is comprised of three anti-parallel α-helices, each approximately 30-40 amino acids in length. The first and second helices interact with the serine/threonine kinase Raf-1, and the second and third helices are the sites of the BAG domain interaction with the ATPase domain of Hsc70/Hsp70. Binding of the BAG domain to the ATPase domain is mediated by both electrostatic and hydrophobic interactions in BAG-1 and is energy-requiring.
Transcriptional regulatory protein Sin3-like (Sin3-like)
Type: Family

Proteins in this entry contain N-terminal PAH (paired amphipathic helix) repeats, a histone deacetylase interacting domain, and a Sin3, C-terminal domain. Sin3 proteins have at least three PAH domains (PAH1, PAH2, and PAH3). They are components of a co-repressor complex that silences transcription, playing important roles in the transition between proliferation and differentiation. Sin3 proteins are recruited to the DNA by various DNA-binding transcription factors such as the Mad family of repressors, Mnt/Rox, PLZF, MeCP2, p53, REST/NRSF, MNFbeta, Sp1, TGIF and Ume6 . Sin3 acts as a scaffold protein that in turn recruits histone-binding proteins RbAp46/RbAp48 and histone deacetylases HDAC1/HDAC2, which deacetylate the core histones resulting in a repressed state of the chromatin . The PAH domains are protein-protein interaction domains through which Sin3 fulfils its role as a scaffold. The PAH2 domain of Sin3 can interact with a wide range of unrelated and structurally diverse transcription factors that bind using different interaction motifs. For example, the Sin3 PAH2 domain can interact with the unrelated Mad and HBP1 factors using alternative interaction motifs that involve binding in opposite helical orientations . The Sin3, C-terminal domain forms interactions with histone deacetylases .
Homeodomain containing protein PHTF1/2 (PHTF1/2)
Type: Family

This entry represents a group of homeodomain containing proteins from animals, including PHTF1/2 from mammals. In rat PHTF1 is an integral membrane protein abundantly expressed in testis . It is localised in the endoplasmic reticulum saccules applied to the trans face of the Golgi system .
Sister chromatid cohesion protein Pds5 (Pds5)
Type: Family

This entry includes sister chromatid cohesion protein Pds5 and its homologues. In budding yeasts, Pds5 is required for both sister chromatid cohesion and condensation . It forms the Pds5-Wapl complex that unloads cohesin from chromosomes .
Interferon-related developmental regulator (IFRD)
Type: Family

Interferon-related developmental regulator (IFRD1) is the human homologue of the Rattus norvegicus early response protein PC4 and its murine homologue TIS7 . IFRD1 is a transcriptional coactivator/repressor controlling patterns of gene expression by interacting with transcription factors or histone deacetylase (HDAC) complexes . This entry also contains IFRD2 and its murine equivalent SKMc15, which are highly expressed soon after gastrulation and in the hepatic primordium, suggesting an involvement in early hematopoiesis . Members of this group are generally described as transcriptional regulators implicated in cellular differentiation and various human diseases .
Programmed cell death protein 4 (PDCD4)
Type: Family

Programmed cell death protein 4 (PDCD4) binds to eukaryotic initiation factor 4A (eIF4A), inhibits translation initiation, and acts as a tumour suppressor. It contains two C-terminal MA3 domains that bind specifically to the eIF4A N-terminal domain (eIF4A-NTD) .

This entry also includes MRF1/2/3/4 from plants. They are involved in target of rapamycin (TOR)-egulated translation control, especially under energy-deficient conditions .
RFX-like DNA-binding protein (RFX-like)
Type: Family

This entry includes Rfx1 from budding yeasts, Sak1 from fission yeasts and RFX1-8 from humans . They are transcription factors that contain a RFX DNA binding domain and a conserved C-terminal region .

Mutations in the RFX5 gene cause Bare lymphocyte syndrome 2 (BLS2), a severe combined immunodeficiency disease with early onset . Mutations in the RFX6 gene cause Mitchell-Riley syndrome (MTCHRS), a disorder characterised by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, and absent gallbladder .
CCR4-NOT transcription complex subunit 4 (Mot2)
Type: Family

NOT4, also known as CNOT4 or MOT2, is a component of the CCR4-NOT complex, a global negative regulator of RNA polymerase II transcription . It associates with polysomes and contributes to the negative regulation of protein synthesis . NOT4 functions as an E3 ubiquitin-protein ligase that interacts with a specific E2, Ubc4/5 in yeast, and the orthologue UbcH5B in humans, and ubiquitinates a wide range of substrates, including ribosome-associated factors . Thus, it plays a role in cotranslational quality control (QC) through ribosome-associated ubiquitination and degradation of aberrant peptides. NOT4 contains a C4C4-type RING finger motif, whose overall folding is similar to that of the C3HC4-type RING-HC finger, a central RNA recognition motif (RRM), and a C-terminal domain predicted to be unstructured .
Rad21/Rec8-like protein (Rad21/Rec8-like)
Type: Family

Rad21/Rec8 like proteins mediate sister chromatid cohesion during mitosis and meiosis, as part of the cohesin complex . Cohesion is necessary for homologous recombination (including double-strand break repair) and correct chromatid segregation. These proteins may also be involved in chromosome condensation. Dissociation at the metaphase to anaphase transition causes loss of cohesion and chromatid segregation .
Intermembrane lipid transfer protein VPS13B (VPS13B)
Type: Family

Intermembrane lipid transfer protein VPS13B (also known as Vacuolar protein sorting-associated protein 13B) may be involved in protein sorting in post Golgi membrane traffic. Mutations of the VPS13B gene cause Cohen syndrome (COH1), a rare autosomal recessive disorder characterised by obesity, hypotonia, intellectual deficit, characteristic craniofacial dysmorphism and abnormalities of the hands and feet .
Deubiquitinating enzyme MINDY-3/4 (MINY3/4)
Type: Family

Deubiquitinating enzymes (DUBs) remove ubiquitin (Ub) from Ub-conjugated substrates to regulate the functional outcome of ubiquitylation. This entry includes MINDY-3/4. They belong to the MINDY (motif interacting with Ub-containing novel DUB) family (peptidase family C121), whose members are deubiquitinating enzymes releasing Lys48-linked ubiquitin .
Protein EFR3 (EFR3)
Type: Family

Protein EFR3 homologue A (EFR3A) is a component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and FAM126 (FAM126A or FAM126B) . This complex is required for the attachment of phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. EFR3A is palmitoylated at its N terminus, anchoring the protein to the plasma membrane, and probably acts as the membrane-anchoring component in the complex . In yeast, the Efr3p protein is a main regulator of the Stt4p phosphatidylinositol 4-kinase at contact sites between the endoplasmic reticulum and the plasma membrane .
Poly(U)-specific endoribonuclease (ENDOU)
Type: Family

This entry represents endoribonucleases, mainly uridylate and poly(U)-specific, found predominantly in eukaryotes.

The founding member of this family, XendoU, is a uridylate-specific, divalent cation-dependent enzyme that produces molecules with 2',3'-cyclic phosphate ends . The human Endou, known as PP11, has endoribonuclease activity with placental tissue specificity .

This entry also includes Endoribonuclease Arlr which has a broad specificity and preferentially cleaves single stranded RNA at sites with AU, UC and less efficiently poly-U sites .
Nucleolar protein 4 family (NOL4/NOL4L)
Type: Family

NOL4 has been identified as a methylation target for cervical and head and neck cancer . NOL4L was first identified in acute myeloid leukaemia and was shown to be involved in cell progression in neuroblastoma . NOL4L effects gene expression in the PI3K/AKT pathway and is critical for tumor progression and metastasis in ovarian cancer cells .
CYFIP-related Rac1 interactor (CYRI)
Type: Family

This entry includes CYRI (CYFIP-related Rac interactor) from Dictyostelium and its homologues, CYRIA/CYRIB, from animals. CYRI binds activated Rac1 via a domain of unknown function (DUF1394). It plays important roles in cell migration, chemotaxis and pathogen entry into cells. It controls actin dynamics through Rac1, the Scar/WAVE Complex and the Arp2/3 Complex . In mice, CYRIB (also known as CYRI or FAM49B) negatively regulates RAC1-driven cytoskeletal remodelling and plays a role in restricting infection mediated by Mycobacterium tuberculosis and Listeria monocytogenes .
Cysteine and histidine-rich domain-containing protein 1 (CHRD1)
Type: Family

This entry includes Cysteine and histidine-rich domain-containing protein 1 (CHRD1) and its orthologue from Drosophila, morgana, which contain a CHORD (cysteine- and histidine-rich) domain. CHRD1/Morgana regulate centrosome duplication and mitotic spindle dynamics and it also involved in controlling the size of dendritic arbors . Morgana may act as co-chaperone for Hsp83 , while CHRD1 may act as co-chaperone for HSP90 . CHRD1 plays a role in ensuring the localisation of the tyrosine kinase receptor EGFR to the plasma membrane, and thus ensures the subsequent regulation of EGFR activity and EGF-induced actin cytoskeleton remodeling . This entry also includes Integrin beta-1-binding protein 2, also known as Melusin and CHORDC3, which may play a role during maturation and/or organisation of muscles cells .

CHORDs are 60-amino acid modules that bind two zinc ions. They are usually arranged in tandem and are found in all tested eukaryotes, with the exception of yeast, where they are involved in processes ranging from pressure sensing in the heart to maintenance of diploidy in fungi, and exhibit distinct protein-protein interaction specificity. Six cysteine and two histidine residues are invariant within the CHORD domain. Three other residues are also invariant and some positions are confined to positive, negative, or aromatic amino acids .
Chorion-specific transcription factor GCM (GCM)
Type: Family

GCM transcription factors are a family of proteins which contain a GCM motif. They bind specific sequences on gene promoters and activate their transcription. Human GCM1 is involved in the control of expression of placental growth factor (PGF) and other placenta-specific genes . Fruit fly GCM determines the choice between glial and neuronal fates .
Uroporphyrinogen-III synthase (UROS/Hem4)
Type: Family

Uroporphyrinogen-III synthase (U3S) catalyses the cyclisation of the linear hydroxymethylbilane (HMB) to uroporphyrinogen III (uro'gen III), the cyclic tetrapyrrole and physiologic precursor of haem, chlorophyl, and corrin . Uncharacterised homologues are also known from bacteria.
Glucosidase II beta subunit-like (Gtb1-like)
Type: Family

This entry includes glucosidase II beta subunit from eukaryotes and N-acetylglucosamine-1-phosphotransferase subunit gamma from animals. They share a conserved N-terminal domain.

Glucosidase II catalyses the sequential removal of two alpha-1,3-linked glucose residues in the second step of N-linked oligosaccharide processing. It is a heterodimer whose alpha subunit bears the glycosyl hydrolase active site, while its beta subunit role is controversial. The beta subunit has been reported to be involved in the solubility and stability of the heterodimeric enzyme, and in retaining the enzyme within the endoplasmic reticulum . Other studies suggest that the beta subunit modulates N-Glycan trimming in both fission yeast and mammals .

N-acetylglucosamine-1-phosphotransferase subunit gamma (GNPTG) is a non-catalytic component of the N-acetylglucosamine-1-phosphotransferase complex. The complex is lysoosomal and a heterohexamer consisting of two alpha, two beta and two gamma subunits, and is required for the first step in the synthesis of the mannose 6-phosphate recognition marker on lysosomal acid hydrolases. The gamma subunit facilitates the addition of a second GlcNAc-P to the high mannose oligosaccharides of the substrates . Mutations in the gene for the gamma subunit are associated with mucolipidosis type III complementation group C (MLIIIC), an autosomal recessive disease of lysosomal hydrolase trafficking .
E3 ubiquitin-protein ligase listerin (LTN1/Rkr1)
Type: Family

This entry represents a group of E3 ubiquitin-protein ligases, including Rkr1 from budding yeasts and listerin (LTN1) from animals. LTN1/Rkr1 is a component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation .
MIP18 family (MIP18)
Type: Family

MIP18 is a component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins . This entry includes MIP18 and its homologues, such as YHR122W from S. cerevisiae and AE7 from plants .
Protein Pecanex (Pecanex)
Type: Family

Pecanex is a multi-pass transmembrane protein. Its function is not clear. In fruit flies, it is a maternal neurogenic gene and is involved in notch (N) signaling . In rat, it is expressed in spermatocytes and probably functions in the testes .
Sulfhydryl oxidase (Sulfhydryl_oxidase)
Type: Family

This entry contains sulfhydryl oxidases that are flavin-dependent . Sulfhydryl oxidase 1 (QSOX1 or quiescin Q6) oxidizes sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide, permitting disulfide bond formation. QSOX1 is predominantly found in the Golgi . Sulfhydryl oxidase 2 (QSOX2) is predominantly located in the plasma and in the nuclear membrane and regulates the sensitization of neuroblastoma cells for interferon-gamma-induced apoptosis .
Sulfhydryl oxidase ALR/ERV (ALR/ERV)
Type: Family

This entry contains FAD-dependent sulfhydryl oxidases, including ALR from animals and Erv from plants and fungi. ALR generates the disulfide bonds in CHCHD4/MIA40, which in turn is a chaperone required for disulfide bond formation and protein folding in the mitochondrial intermembrane space . ERV1 from Arabidopsis is required for the import and folding of small cysteine-containing proteins in the mitochondrial intermembrane space . Erv2 from
Saccharomyces cerevisiae
catalyzes disulfide bond formation in the endoplasmic reticulum lumen .
Calcium uptake protein 1/2/3 (MICU1/2/3)
Type: Family

This entry represents a group of calcium uptake proteins, including MICU1/2/3 from humans. They contain the conserved EF-hand Ca2+-binding domains. MICU1 and MICU2 are the main regulators of the mitochondrial Ca(2+)-uniporter (MCU) . MICU2 forms a heterodimer with MICU1 to modulate MCU channel activity . MICU3 a tissue-specific enhancer of mitochondrial calcium uptake .
Epidermal growth factor receptor kinase substrate 8-like (EPS8-like)
Type: Family

This entry includes EPS8 and EPS8L1-3 from animals.

Epidermal growth factor receptor kinase substrate 8 (EPS8) is a signalling adapter that possesses actin binding, bundling, and barbed-end capping activities . It forms a complex with Sos-1, Abi1 and the lipid kinase phosphoinositide 3-kinase (PI3-K) to regulate Rac activation that leads to actin cytoskeletal remodeling . It is critical for dendritic cell migration . It is involved in the initial growth of stereocilia in both inner hair cells and outer hair cells . It also regulates axonal filopodia in hippocampal neurons in response to brain-derived neurotrophic factor (BDNF) . It has been linked to proliferation, metastasis and prognosis of many malignant tumours .

Similarly to EPS8, EPSLs interact with Abi1 and Sos-1. However, only EPS8L1 and EPS8L2 activate the Rac-GEF activity of Sos-1, and bind to actin in vivo . Eps8L2 null-mutant mice has been shown to exhibit a late-onset, progressive hearing loss that is directly linked to a gradual deterioration in hair bundle morphology .