SII-SWORD/CoKE huggingface dataset:
SHC SH2 domain-binding protein 1-like (SHCBP1-like)
Type: Family

This entry includes SHC SH2 domain-binding protein 1 (Shcbp1) and related proteins, including protein nessun dorma (also known as Nesd) from Drosophila melanogaster. Shcbp1 is expressed in proliferating cells and is an important component of FGF (fibroblast growth factor) signalling in neural progenitor cells . Nesd is part of the centralspindlin complex, a key regulator of cytokinesis .
N-alpha-acetyltransferase 60-like (NAA60-like)
Type: Family

This entry includes NAA60 from animals and MCC1 from Arabidopsis. NAA60 (also known as NatF) is an N-alpha-acetyltransferase that specifically mediates the acetylation of N-terminal residues of the transmembrane proteins, with a strong preference for N termini facing the cytosol. It is localized in the Golgi apparatus . In Drosophila, NAA60 knockdown cells shows chromosomal segregation defects .

MCC1 may be a histone acetyltransferase involved in plant meiosis .
BCAS3-like (BCAS3-like)
Type: Family

This entry includes BCAS3 microtubule associated cell migration factor (BCAS3) from animals and AT18F/G/H from Arabidopsis. BCAS3 is a microtubule associated cell migration factor that has been linked to the development of breast cancer and angiogenesis . It forms a complex with PHAF1 and associates with the preautophagosomal structure during both non-selective and selective autophagy .

AT18F/G/H are linked to autophagy .
Kinetochore protein Spc25 (Spc25)
Type: Family

The Ndc80 complex is a conserved outer kinetochore protein complex consisting of Ndc80 (Hec1), Nuf2, Spc24 and Spc25. The Ndc80 complex is required for chromosome segregation and spindle checkpoint activity .
Transcription initiation factor TFIID component TAF4 (TAF4)
Type: Family

Accurate transcription initiation at protein-coding genes by RNA polymerase II requires the assembly of a multiprotein complex around the mRNA start site. Transcription factor TFIID is one of the general factors involved in this process. Yeast TFIID comprises the TATA binding protein and 14 TBP-associated factors (TAFIIs), nine of which contain histone-fold domains. The C-terminal region of the TFIID-specific yeast TAF4 (yTAF4) containing the HFD shares strong sequence similarity with Drosophila (d)TAF4 and human TAF4. A structure/function analysis of yTAF4 demonstrates that the HFD, a short conserved C-terminal domain (CCTD), and the region separating them are all required for yTAF4 function .
Chromatin assembly factor 1 subunit Cac2/CHAF1B/FAS2 (PTHR15271)
Type: Family

This entry includes chromatin assembly factor 1 subunit CHAF1B (also known as p60 subunit) from animals, and its homologues such as Cac2 from yeasts and FAS from Arabidopsis. They are a component of the chromatin assembly factor complex (CAF-1), an evolutionarily conserved heterotrimeric chaperone comprised of p150, p60 and p48 subunits, mediates DNA synthesis-coupled chromatin assembly in S-phase. It is also involved in chromatin assembly following DNA repair . In plants, the loss of activity of the CAF1 pathway causes delay and arrest of the cell cycle during pollen development . The CAF1 complex is also required for stable maintenance of telomeres and 45S rDNA in Arabidopsis .
Splicing factor 3A subunit 1 (SF3A1)
Type: Family

Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form . The 120kDa subunit (SF3a120) has a carboxy-terminal ubiquitin-like domain and two SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, at its amino-terminus .

This entry represents SF3a120 (also known as SF3A1) and its homologues such as Prp21 from budding yeasts and Sap114 from fission yeasts.
AT-rich interactive domain-containing protein 3 (ARI3A/B/C)
Type: Family

This entry represents a group of transcription factors, including ARID3A/B/C from humans and protein dead ringer (Retn) from Drosophila melanogaster. ARID3A (also known as E2FBP1 or Bright) is involved in the control of cell cycle progression by the RB1/E2F1 pathway and in B-cell differentiation . ARID3B has been linked to malignant neuroblastoma . Retn is regulator of the late development of longitudinal glia . Mutations in the Drosophila retn gene lead to female behavioral defects and alter a limited set of neurons in the CNS. Retn also affects a male behavioral pathway activated by fruM .
Transcription elongation regulator 1-like (TCRG1-like)
Type: Family

This entry includes TCRG1/TCRGL from human and related proteins from animals, fungi and plants. This entry also includes dre4 from fission yeast, URN1 from budding yeast and PRP40C from Arabidopsis. They are predicted to be involved in pre-mRNA splicing . The plant PRP40C binds the phosphorylated C-terminal domain of the largest subunit of RNA polymerase II and its two WW domains were shown to mediate this interaction .

TCRG1 (also known as CA150) contains three N-terminal WW domains and six consecutive FF domains (

). WW and FF domains are versatile modules that mediate protein-protein interactions . TCRG1 is a transcription elongation factor that interacts with the splicing factor SF1 and with the phosphorylated C-terminal repeat domain (CTD) of RNA polymerase II (RNAPII) through its WW and FF domains, respectively . It regulates transcription elongation in a TATA box-dependent manner . They bind the phosphorylated C-terminal of RNA polymerase II and mediate interactions with other proteins such as HTATSF1.
Protein OS-9-like (OS-9-like)
Type: Family

OS9 is conserved among eukaryotes and shows similarities with mannose-6-phosphate receptors (MPRs). Proteins in this family are lectins that functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD) . Proteins in this entry also include endoplasmic reticulum lectin 1 (ERLEC1, also known as XTP3-B), which may function in endoplasmic reticulum quality control and endoplasmic reticulum-associated degradation (ERAD) of both non-glycosylated proteins and glycoproteins .
Transmembrane reductase CYB561D1/2 (CYB561D1/2)
Type: Family

This entry includes CYB561D1/2 from humans. CYB561D2 (also known as 101F6), a cytochrome b561 homologue, is a transmembrane reductase that may use ascorbate as an electron donor in the cytoplasm and transfer electrons across endoplasmic reticulum membranes to reduce monodehydro-L-ascorbate radical and iron cations Fe3 in the lumen of that compartment . The function of CYB561D1 is not clear. This entry also includes cytochrome b561 domain-containing proteins such as At4g18260 and At2g30890 from Arabidopsis .
DDB1- and CUL4-associated factor 8-like (DCAF8)
Type: Family

This entry represents a group of WD and tetratricopeptide repeats proteins, including DCAF5/6/8 and DCAF8L1/DCAF8L2/WDTC1 from humans. They may function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex .

Proteins in this entry also include protein ALTERED SEED GERMINATION 2 (ASG2) from Arabidopsis. It is a negative regulator of ABA signalling .
Enhancer of mRNA-decapping protein 4-like (EDC4-like)
Type: Family

Ge-1, also known as EDC4 (enhancer of mRNA-decapping protein 4), is a regulator of mRNA decapping to function in the mRNA P-bodies within the cytoplasm. It has been shown to interact with mTORC1 , coenzyme A synthase and MARF1 . It is also involved in the regulation of immune system .

This entry also includes EDC4 homologues from fungi and plants .
Est1/Ebs1-like (Est1/Ebs1-like)
Type: Family

This entry includes Est1/Esl1/Ebs1 from budding yeasts and Est1A/SMG6/SMG7 from humans. Est1 is a TLC1 RNA-associated factor involved in telomere length regulation . Ebs1, an Est1 paralogue and human Smg7 orthologue, is involved in translation inhibition and nonsense-mediated decay . Esl1 is not involved in nonsense-mediated mRNA decay or telomere maintenance pathways, instead, it regulates adaptive gene expression responses of environmental sensing pathways .
Protein PCF11-like (PCF11-like)
Type: Family

This entry includes Pcf11 and related proteins from animals, fungi and plants.

Pcf11 is a subunit and essential component of cleavage and polyadenylation factor IA (CF IA), involved in pre-mRNA 3' end processing and in transcription termination . It has been reported that Pcf11-mediated termination is essential for vertebrate development and its own levels are maintained by an auto-regulatory mechanism involving premature termination of its transcript . Human Pcf11, also referred to as pre-mRNA cleavage complex 2 protein Pcf11, has been shown to enhance degradation of RNAP II-associated nascent RNA and transcriptional termination. Pcf11 binds to Clp1, another subunit of CFIA whose interaction is responsible for maintaining a tight coupling between the Clp1 nucleotide binding subunit and the other components of the polyadenylation machinery .
Beta-lactamase class A, catalytic domain (Beta-lactam_cat)
Type: Domain

This entry represents the catalytic domain of class A beta-lactamases .

Beta-lactamase catalyses the opening and hydrolysis of the beta-lactam ring of beta-lactam antibiotics such as penicillins and cephalosporins. There are four groups, classed A, B, C and D according to sequence, substrate specificity, and kinetic behaviour. Class A (penicillinase-type) is the most common . The genes for class A beta-lactamases are widely distributed in bacteria, frequently located on transmissible plasmids in Gram-negative organisms, although an equivalent chromosomal gene has been found in a few species . Class A, C and D beta-lactamases are serine-utilising hydrolases, while class B enzymes utilise a catalytic zinc centre instead. The 3 classes of serine beta-lactamase are evolutionarily related and belong to a superfamily that also includes DD-peptidases and other penicillin-binding proteins . All these proteins contain an S-x-x-K motif, the Ser being the active site residue . Although clearly related, however, the sequences of the 3 classes of serine beta-lactamases vary considerably outside the active site.

This entry represents the Group 2 beta-lactamases, which correspond to the penicillinases and cephalosporinases, which are inhibited by clavulanic acid. They corresponding to the molecular classes A and D reflecting the original TEM and SHV genes. However, because of the increasing number of TEM and SHV derived beta-lactamases, they have been divided into two subclasses, 2a and 2b:

The 2a subgroup contains just penicillinases.

The 2b subgroup contains broad spectrum beta-lactamases, meaning that they are capable of inactivating penicillins and cephalosporins at the same rate. Furthermore, new subgroups were segregated from subgroup 2b based on their activity against certain antibiotics and resistance to clavulanic acid.

Molecular Class D or A Subgroup 2d enzymes inactivate cloxacillin more than benzylpenicillin, with some activity against carbenicillin; these enzymes are poorly inhibited by clavulanic acid, and some of them are extended spectrum beta-lactamases (ESBLs).

The class A and D beta-lactamases belong to MEROPS peptidase family S11 (D-Ala-D-Ala carboxypeptidase A family, clan SE).
Vacuolar protein 8 (Vac8)
Type: Family

This family includes vacuolar protein 8 (Vac8), an armadillo repeat-containing protein that functions in both vacuole inheritance and protein targeting from the cytoplasm to vacuole . Its structure has a N-terminal flexible H1 helix followed by 12 armadillo repeats that form a right-handed superhelical structure . The cationic triad (Arg276, Arg317, and Arg359) motifs in this protein are critical for the interaction with the nuclear membrane protein Nvj1 to form a nucleus-vacuole junction (NVJ) and for the recognition of Atg13, a key component of the cytoplasm-to-vacuole targeting (CVT) pathway .
CagA, N-terminal (CagA_N)
Type: Domain

The Helicobacter pylori type IV secretion effector CagA is a major bacterial virulence determinant and critical for gastric carcinogenesis . X-ray crystallographic analysis of the N-terminal CagA fragment (residues 1-876) revealed that the region has a structure comprised of three discrete domains. Domain I constitutes a mobile CagA N terminus, while domain II tethers CagA to the plasma membrane by interacting with membrane phosphatidylserine. Domain III interacts intramolecularly with the intrinsically disordered C-terminal region, and this interaction potentiates the pathogenic scaffold/hub function of CagA .

This entry represents the CagA N-terminal domain, containing domain I, II and III.
K(+) efflux antiporter 4/5/6-like (KEA4/5/6-like)
Type: Family

This entry includes a group of K(+) efflux antiporters, including KEA4/5/6 from Arabidopsis and TMCO3 from animals. They are homologues of bacterial K+/H+ antiporters, plays potential roles in K+ homeostasis and osmotic adjustment .
WD repeat-containing protein DCAF7-like (DCAF7-like)
Type: Family

This entry represents a group of WD repeat-containing proteins, including DCAF7 from animals, LWD1/2/TTG1 from Arabidopsis and YPL247C from budding yeasts. In general, WD40 repeat domain-containing proteins are scaffolding elements for the assembly of multi-subunit protein complexes. DCAF7, also known as WDR68, interacts with Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A, a Down's syndrome-associated protein kinase) and is required for Endothelin-1 (EDN1) signalling . It also acts as a DDB1- and CUL4-associated factor . Mutations in the DCAF7 gene have been linked to cleft lip with or without cleft palate (CL/P) . In Arabidopsis, LWD1 and LWD2 serve as clock proteins involved in photoperiod flowering control . TRANSPARENT TESTA GLABRA 1 (TTG1) is a regulator of early developmental traits and is also involved in flowering time regulation .
Autophagy-related protein 16 (ATG16)
Type: Family

Macroautophagy is a bulk degradation process induced by starvation in eukaryotic cells. In yeast, 15 Atg proteins coordinate the formation of autophagosomes. The pre-autophagosomal structure contains at least five Atg proteins: Atg1p, Atg2p, Atg5p, Aut7p/Atg8p and Atg16p, found in the vacuole . The C-terminal glycine of Atg12p is conjugated to a lysine residue of Atg5p via an isopeptide bond. During autophagy, cytoplasmic components are enclosed in autophagosomes and delivered to lysosomes/vacuoles. Autophagy protein 16 (Atg16) has been shown to bind to Atg5 and is required for the function of the Atg12p-Atg5p conjugate . Autophagy protein 5 (Atg5) is directly required for the import of aminopeptidase I via the cytoplasm-to-vacuole targeting pathway .

This entry includes ATG16-1 and ATG16-2 .
U3 small nucleolar RNA-associated protein 18 (Utp18)
Type: Family

Utp18 is a small-subunit (SSU) processome protein involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly .
Serine/threonine-protein kinase Vps15-like (Vps15-like)
Type: Family

This entry represents the Vps15 family of proteins. In animals, proteins part of this family are known as Phosphoinositide 3-kinase regulatory subunit 4 (Pik3r4).

Vps15 associates and regulates Vps34, also called Class III phosphoinositide 3-kinase (PI3K), which catalyses the phosphorylation of D-myo-phosphatidylinositol (PtdIns) . Vps34 is the only PI3K present in yeast. It plays an important role in the regulation of protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signalling, and phagocytosis .
Focadhesin/RST1 (Focadhesin/RST1)
Type: Family

This entry includes Focadhesin from animals and RST1 (RESURRECTION 1) from plants. Focadhesin (FOCAD) is a focal adhesion protein with potential tumour suppressor function in gliomas . RST1 was originally identified in a genetic screen for factors involved in the biosynthesis of epicuticular waxes . Later, RST1 and RST1 INTERACTING PROTEIN (RIPR) have been shown to act as cofactors of the cytoplasmic exosome and the Ski complex in plants . RST1 is involved in the suppression of siRNA-mediated silencing of transgenes and certain endogenous transcripts .
RNA-binding region-containing protein RBM41/RNPC3 (RBM41/RNPC3)
Type: Family

RNPC3 serves as a bridging factor between the U11 and U12 snRNPs. It contains two RNA recognition motifs (RRMs), connected by a linker that includes a proline-rich region. It binds to the U11-associated 59K protein via its RRM1 and employs the RRM2 to bind hairpin III of the U12 small nuclear RNA (snRNA). The proline-rich region might be involved in protein-protein interactions . RBM41 contains only one RRM. Its biological function remains unclear.
Nitrobindin family (Nitrobindin)
Type: Family

Nitrobindins (Nbs) are evolutionary conserved all-β-barrel heme-proteins displaying a highly solvent-exposed heme-Fe(III) atom. Mycobacterium tuberculosis Nb (Mt-Nb(III) and the C terminus of Homo sapiens Nb (Hs-Nb(III)) share this β-barrel structure, suggesting that Nb may act as a sensor possibly modulating the THAP4 transcriptional activity residing in the N-terminal region . Ferric nitrobindin-like proteins that lack the conserved His residue which binds heme iron are also included in the Nb family.

Mt-Nb(III) is a peroxynitrite isomerase that converts peroxynitrite to nitrate. It may be required to scavenge reactive nitrogen and oxygen species produced by the host during the immunity response .

In humans THAP4 catalyses the heme-based conversion of peroxynitrite into nitrate/NO3 in vitro . At1g79260 is a nitrophorin-like heme-binding protein that may reversibly bind nitric oxide (NO) and be involved in NO transport . This entry also includes Caenorhabditis elegans protein male abnormal 7 (Mab-7) which plays an important role in determining body shape and sensory ray morphology .
Pre-mRNA-splicing factor Spp2-like (Spp2-like)
Type: Family

Spp2 is a yeast G-patch protein and spliceosome component that interacts with the ATP-dependent DExH-box splicing factor Prp2 . This interaction involves the G-patch sequence in Spp2 and is required for the recruitment of Prp2 to the spliceosome before the first catalytic step of splicing. It has been proposed that Spp2 might be an accessory factor that confers spliceosome specificity on Prp2 .

This entry also includes the plant MOS2 protein required for innate and induced resistance to pathogens, and MOS2 homologues from Metazoa .
Hobbit (Hobbit)
Type: Family

This entry includes Hobbit protein from Drosophila melanogaster and its homologues such as Bridge-like lipid transfer protein family member 2 from human (BLTP2/KIAA0100) and FMP27 from yeast, referred to the Hob proteins . These proteins are localised to endoplasmic reticulum-plasma membrane (ER-PM) contact sites described as conserved lipid-binding proteins. They are tube-forming transport proteins which bind to phosphatidylinositols and affect phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) distribution , that have a long hydrophobic groove and can mediate bulk transport of lipids between organelles. This entry also includes maize protein APT1 and Arabidopsis homologues SABRE and KIP . The Hob family belongs to the repeating β-groove (RBG) superfamily together with VPS13, ATG2, SHIP164, Csf1/BLTP1, which are all conserved lipid transfer proteins containing long hydrophobic grooves . They all share the same structure consisting of multiple repeating modules consisting of five β-sheets followed by a loop.
YTH domain containing protein (YTH_prot)
Type: Family

The YTH (YT521-B homology) domain has been suggested to be an evolutionarily conserved m6A-dependent RNA binding domain . Proteins containing this domain includes mammalian YTHD and YTDC proteins, Arabidopsis CPSF30 (At1g30460), and budding yeast Pho92. These proteins recognise and bind N6-methyladenosine (m6A)-containing mRNAs, and regulate their stability . YTHD acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex . The YTHDF paralogues (YTHDF1, YTHDF2 and YTHDF3) shares m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation .

In Saccharomyces cerevisiae, Pho92 is a post-transcriptional regulator that regulates Pho4 mRNA stability by binding to the 3'-UTR in a phosphate-dependent manner. Its YTH domain exhibits RNA-binding activity . Its orthologue from S. pombe, Mmi1, is an
RNA-binding protein that recognises and binds N6-methyladenosine (m6A)-containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs. It functions alone and as part of the erh1-mmi1 complex, to recruit the CCR4-NOT complex and the NURS complex to target RNAs .
Nitrite and sulphite reductase 4Fe-4S domain containing protein (NO2/SO3_Rdtase_4Fe4S_prot)
Type: Family

Sulphite reductases (SiRs) and related nitrite reductases (NiRs) catalyse the six-electron reduction reactions of sulphite to sulphide, and nitrite to ammonia, respectively. The Escherichia coli SiR enzyme is a complex composed of two proteins, a flavoprotein alpha-component (SiR-FP) and a hemoprotein beta-component (SiR-HP), and has an α(8)β(4) quaternary structure . SiR-FP contains both FAD and FMN, while SiR-HP contains a Fe(4)S(4) cluster coupled to a sirohaem through a cysteine bridge. Electrons are transferred from NADPH to FAD, and on to FMN in SiR-FP, from which they are transferred to the metal centre of SiR-HP, where they reduce the siroheme-bound sulphite.
MTOX family (MTOX)
Type: Family

MTOX family consists of a group of FAD dependent oxidoreductases, including monomeric sarcosine oxidase (MSOX), pipecolate oxidase (PIPOX), heterotetrameric sarcosine oxidase (TSOX), D-amino acid oxidase (DAAO) and possibly two mitochondrial enzymes, sarcosine dehydrogenase (SDH) and dimethylglycine dehydrogenase (DMGDH) .

N-methyltryptophan oxidase (MTOX) catalyses the oxidative demethylation of N-methyl-L-tryptophan , while Monomeric sarcosine oxidase (MSOX) catalyses the oxidative demethylation of sarcosine . PIPOX is involved in the lysine degradation pathway where it oxidizes L-pipecolate, a neuromodulator of the GABA receptor complex . Peroxisomal DAAO degrades D-serine, a modulator of neurotransmission in the brain. DMGDH and SDH are flavoproteins which catalyse the oxidative demethylation of dimethyl glycine to sarcosine and sarcosine to glycine, respectively .
Tubulin-folding cofactor B, ubiquitin-like domain (TBCB_Ubl)
Type: Domain

Tubulin-folding cofactor B (TBCB) is one of the protein cofactors A through E that is required for the folding of tubulins prior to their incorporation into microtubules and heterodimer assembly . These cofactors are involved in the biogenesis and degradation of alpha and beta tubulins to maintain concentrated soluble pools, required for cell homeostasis . TBCB comprises an N-terminal ubiquitin-like (Ubl) domain and a C-terminal cytoskeleton-associated protein with glycine-rich segment (CAP-Gly) domain. The Ubl domain of TBCB is essential for proper folding and assembly of tubulin alpha. It has a β-grasp Ubl fold, a common structure involved in protein-protein interactions. Ubiquitin (Ub) is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. TBC-A through E are necessary for the biogenesis of microtubules and for cell viability .