SII-SWORD/CoKE huggingface dataset:
RNA binding protein fox-1 homolog 1-3 (RBFOX1-3)
Type: Family

This entry represents RNA binding protein fox-1 homologue 1-3 (RBFOX1-3) and its homologues predominantly found in vertebrates. Members of this family regulate alternative splicing events by binding to 5'-UGCAUGU-3' elements .
Peptidase S1A, polyserase-2 (Pept_S1A_polyserase-2)
Type: Family

This entry represents serine peptidases that belong to MEROPS petidase family S1A (clan PA(S)). They are a novel enzyme with three tandem serine protease domains in a single polypeptide chain. Polyserase-2 (polyserine protease-2) is the second identified human enzyme with several tandem serine protease domains. The first serine protease domain contains all characteristic features of these enzymes, whereas the second and third domains lack one residue of the catalytic triad of serine proteases and are predicted to be catalytically inactive. Both full-length polyserase-2 and its first serine protease domain hydrolyse synthetic peptides used for assaying serine proteases. The activity of the isolated domain was greater than that of the entire protein, suggesting that the two catalytically inactive serine protease domains of polyserase-2 may modulate the activity of the first domain. Polyserase-2 is expressed in foetal kidney, adult skeletal muscle, liver, placenta, prostate, and heart, and tumour cell lines derived from lung and colon adenocarcinomas. In contrast to polyserase-1, this protein is a secreted enzyme whose three protease domains remain as an integral parts of a single polypeptide chain .
Peptidase S1A, TMPRSS13 (Peptidase_S1A_TMPRSS13)
Type: Family

This group represents type II transmembrane serine proteases or TTSPs that belong to MEROPS peptidase family S1A (clan PA(S)). They proteolytically activate membrane fusion activity of the hemagglutinin of highly pathogenic avian influenza viruses and induce their multicycle replication .
Sirtuin, class I (Sirtuin_class_I)
Type: Family

This entry represents eukaryotic type sirtuin-2 (Sir2, or silent information regulator) family of NAD-dependent deacetylases, which are nicotinamide adenine dinucleotide (NAD+)-dependent enzymes that hydrolyse one molecule of NAD+ for every lysine residue that is deacetylated . The sirtuins are phylogenetically conserved in eukaryotes, prokaryotes, and archeal species. Sir2 itself deacetylates Lys-40 of alpha-tubulin, and is involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton . Other members of this family could function in telomeric silencing, cell cycle progression, chromosome stability, and/or as a regulator of gene expression through the modification of chromatin.
Peptidase S1A, HAT/DESC1 (Pept_S1A_HAT/DESC1)
Type: Family

This entry represents the type II transmembrane serine proteases (TTSPs), which belong to MEROPS peptidase family S1A (clan PA(S)). They include the HAT/DEASC1-like (human airway trypsin-like protease/ differentially expressed in squamous cell carcinoma gene 1) serine peptidases. They are activated by cleavage and secreted . The entry includes the adrenal secretory serine peptidases, which are HAT peptidases that play an important role in airway physiology .
Sperm-associated antigen 7 (SPAG7)
Type: Family

The function of SPAG7 is not clear. It has been linked to an auto-inflammatory disease-periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome .
Peptidoglycan recognition protein, PGRP-S (Peptidoglycan_recognition)
Type: Family

PGRP-S (peptidoglycan recognition protein short, also known as peptidoglycan recognition protein 1) is a innate immunity pattern recognition protein conserved from insects to mammals, recognising bacterial cell wall peptidoglycan and activates two antimicrobial defense systems, prophenoloxidase cascade and antimicrobial peptides through Toll receptor .

Peptidoglycan recognition proteins (PGRPs) are part of the host's innate immune system. In mammals, only four types of PGRPs, long PGRPs, intermediate PGRPs and short PGRPs have so far been identified .
Uncharacterised conserved protein UCP037948, zinc finger MYND-type (UCP037948_Znf-MYND)
Type: Family

This group represents an uncharacterised protein with a C-terminal zinc finger MYND domain.
Eukaryotic translation initiation factor 3 subunit G (eIF3_g)
Type: Family

At least eleven different protein factors are involved in initiation of protein synthesis in eukaryotes. Binding of initiator tRNA and mRNA to the 40S subunit requires the presence of the translation initiation factors eIF-2 and eIF-3, with eIF-3 being particularly important for 80S ribosome dissociation and mRNA binding . eIF-3 is the most complex translation inititation factor, consisting of about 13 putative subunits and having a molecular weight of between 550 - 700kDa in mammalian cells. Subunits are designated eIF-3a - eIF-3m; the large number of subunits means that the interactions between the individual subunits that make up the eIF-3 complex are complex and varied . Subunit G is required for eIF3 integrity.

Eukaryotic translation initiation factor 3 subunit G (eIF3g) 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 . eIF3g can bind 18S rRNA .
E3 ubiquitin-protein ligase RNF8 (RNF8)
Type: Family

This entry represents E3 ubiquitin-protein ligase RNF8, which may be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. This enzyme promotes the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer . Substrates that are poly-ubiquitinated at 'Lys-63' are usually not targeted for degradation. RNF8 acts following DNA double-strand break (DSB) formation, and is recruited to the sites of damage by ATM-phosphorylated MDC1, where it promotes the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF) . It may play a role in the regulation of RXRA-mediated transcriptional activity, but is not involved in RXRA ubiquitination by UBE2E2.

Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1,

), a ubiquitin-conjugating enzyme (E2,

), and a ubiquitin ligase (E3,

,

), which work sequentially in a cascade. There are many different E3 ligases, which are responsible for the type of ubiquitin chain formed, the specificity of the target protein, and the regulation of the ubiquitinylation process . Ubiquitinylation is an important regulatory tool that controls the concentration of key signalling proteins, such as those involved in cell cycle control, as well as removing misfolded, damaged or mutant proteins that could be harmful to the cell. Several ubiquitin-like molecules have been discovered, such as Ufm1 (

), SUMO1 (

), NEDD8, Rad23 (

), Elongin B and Parkin (

), the latter being involved in Parkinson's disease .
Snurportin-1 (Snurportin-1)
Type: Family

Snurportin-1 is a nuclear import receptor that contains an N-terminal importin beta binding domain which is essential for its function as an snRNP-specific nuclear import receptor . Snurportin-1 interacts with m3G-cap where it enhances the m3G-cap dependent nuclear import of U snRNPs in Xenopus laevis oocytes and digitonin-permeabilized HeLa cells .
Zinc finger Ran-binding domain-containing protein 2 (ZRANB2)
Type: Family

ZRANB2 is a splice factor required for alternative splicing of TRA2B/SFRS10 transcripts. It may interfere with constitutive 5'-splice site selection .
Lytic switch protein BZLF1, human herpesvirus 4 (BZLF1_HHV-4)
Type: Family

This family represents thelytic switch protein BZLF1 from Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4). It is a transcription factor that acts as a molecular switch to induce the transition from the latent to the lytic or productive phase of the virus cycle of infection in cells containing a highly methylated viral genome . It probably binds to silenced chromatin and recruits host chromatin-remodeling enzymes .
U1 small nuclear ribonucleoprotein C (U1_snRNP-C)
Type: Family

This group represents U1 small nuclear ribonucleoprotein C. It is a component of the U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA .
Membrane cofactor protein CD46 (CD46)
Type: Family

This entry represents a group of membrane cofactor proteins (also known as CD46 or TLX). Human CD46 acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue . Rat CD46 may be involved in the fusion of the spermatozoa with the oocyte during fertilization .
S-adenosyl-L-methionine dependent methionine synthase, predicted (S-AdoMet-dep_Met_synth_prd)
Type: Family

This entry represents proteins predicted to function as S-adenosyl-L-methionine dependent methionine synthases, such as the uncharacterised protein TM0269 from Thermotoga maritima.
Uncharacterised conserved protein UCP037987 (UCP037987)
Type: Family

This group represents an uncharacterised conserved protein.
Uncharacterised conserved protein UCP037988,TerD, trypsin (UCP037988)
Type: Family

This group represents an uncharacterised protein with partial TerD and trypsin domains.
Peptidase S1A, Tysnd1 (Pept_S1A_Tysnd1)
Type: Family

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This entry contains serine peptidases belonging to MEROPS peptidase subfamily S1A (chymotrypsin A, clan PA(s)). The type example is chymotrypsin A from Bos taurus (Bovine).

Tysnd1 acts in the peroxisomes, where beta-oxidation of fatty acids takes place. Tysnd1 is responsible both for the removal of the leader peptide from PTS2 proteins and for the specific processing of PTS1 proteins . PTS1 and PTS2 are peroxisomal signal targeting sequences. The N-terminal fragment of Tysnd1 is removed, suggesting that this fragment has an inhibitory function. The expression of Tysnd1 is induced by the proliferator-activated receptor alpha agonist bezafibrate, along with an increase in its substrates .
UBX domain-containing protein 2/7 (UBX_7/2)
Type: Family

This entry represents UBX domain-containing proteins 2 (Ubx2) and 7 (UBXN7).

VCP/p97 or Cdc48 is a eukaryotic ATPase involved in membrane fusion, protein transport, and protein degradation. Ubx2 interacts with Cdc48 in fission yeast . UBXN7 is a ubiquitin-binding adapter that links a subset of NEDD8-associated cullin ring ligases (CRLs) to VCP/p97 to regulate turnover of their ubiquitination substrates .
Heterogeneous nuclear ribonucleoprotein C (hnRNP_C)
Type: Family

This entry represents heterogeneous nuclear ribonucleoproteins C and C-like.
The physiologically active form of human heterogeneous nuclear ribonucleoprotein C (hnRNPC) is a tetramer of isoforms hnRNPC1 and C2. It binds pre-mRNA and nucleates the assembly of 40S hnRNP particles. Single hnRNPC tetramers bind 230-240 nucleotides. It may play a role in the early steps of spliceosome assembly and pre-mRNA splicing. It interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules .

Among the hnRNP C-like proteins is Raly, a protein described in mouse and humans .
Serine/threonine-protein kinase pim-1/2/3 (PIM1/2/3)
Type: Family

This entry represents serine/threonine-protein kinase Pim-1/2/3. They are a group of proto-oncogenes with serine/threonine kinase activity that can prevent apoptosis and promote cell survival and protein translation .
Tumour necrosis factor receptor 3 (TNFR_3_LTBR)
Type: Family

The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins. Family members are defined based on similarity in their extracellular domain - a region that contains many cysteine residues arranged in a specific repetitive pattern . The cysteines allow formation of an extended rod-like structure, responsible for ligand binding .

Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences . Activation of TNFRs can therefore induce a range of disparate effects, including cell proliferation, differentiation, survival, or apoptotic cell death, depending upon the receptor involved .

TNFRs are widely distributed and play important roles in many crucial biological processes, such as lymphoid and neuronal development, innate and adaptive immunity, and maintenance of cellular homeostasis . Drugs that manipulate their signalling have potential roles in the prevention and treatment of many diseases, such as viral infections, coronary heart disease, transplant rejection, and immune disease .
LIM and senescent cell antigen-like-containing domain protein 1-4-like (PINCH-1-4-like)
Type: Family

This group represents LIM and senescent cell antigen-like-containing domain protein 1 (LIMS1, also known as PINCH-1), and its homologues LIMS2-4, LIM domain-containing protein unc-97 and LIM domain-containing protein pin-2. LIMS1 is LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway . Unc-97 is part of the integrin containing attachment complex, which is required for muscle development and maintenance ; it may also function in adherens junction .
Methyl-CpG-binding domain protein 4 (MBD4)
Type: Family

Methyl-CpG-binding domain protein 4 (MBD4) is a mismatch-specific DNA N-glycosylase involved in DNA repair. It has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites .
Methyl-CpG binding protein MeCP2 (Me_CpG-bd_MeCP2)
Type: Family

Methyl-CpG-binding protein 2 (Mecp2) binds specifically to methylated DNA and represses transcription through the recruitment of chromatin remodeling complexes containing histone deacetylase activities . It is a multi-functional protein whose function depends on its protein partners and post-translational modifications . Mecp2 is required for proper mitotic spindle organisation and affects proliferation and apoptosis . Mutations in MeCP2 gene cause an X-linked neurodevelopmental disease known as Rett syndrome .

Methylation at CpG dinucleotide, the most common DNA modification in eukaryotes, has been correlated with gene silencing associated with various phenomena such as genomic imprinting, transposon and chromosome X inactivation, differentiation, and cancer. Effects of DNA methylation are mediated through proteins which bind to symmetrically methylated CpGs. Such proteins contain a specific domain of ~70 residues, the methyl-CpG-binding domain (MBD), which is linked to additional domains associated with chromatin, such as the bromodomain, the AT hook motif, the SET domain, or the PHD finger. MBD-containing proteins appear to act as structural proteins, which recruit a variety of histone deacetylase (HDAC) complexes and chromatin remodelling factors, leading to chromatin compaction and, consequently, to transcriptional repression. The MBD of MeCP2, MBD1, MBD2, MBD4 and BAZ2 mediates binding to DNA, in case of MeCP2, MBD1 and MBD2 preferentially to methylated CpG. In case of human MBD3 and SETDB1 the MBD has been shown to mediate protein-protein interactions .
Vasodilator-stimulated phosphoprotein/ENA/VASP-like (VASP/EVL)
Type: Family

Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity, such as axon guidance and lamellipodial and filopodial dynamics in migrating cells . Ena/VASP proteins possess a modular domain organization, including a conserved tetramerization domain (TD) mediates the formation of Ena/VASP tetramers . In vertebrates there are three Ena-VASP family members: Mena (Mammalian enabled), VASP, and EVL (Ena-VASP like).

This entry includes VASP and Ena/VASP-like (EVL) proteins.
Tumour necrosis factor ligand 10/11 (TNF_ligand_10/11)
Type: Family

This group represents a tumour necrosis factor ligand superfamily member, 10/11 types.
Chimaerin (CHN1/CHN2)
Type: Family

Chimaerin is a family of GTPase activating proteins for the small G-protein Rac. Chimaerin family members have been implicated in development, neuritogenesis and cancer .

This entry includes alpha-chimaerin (Chn1) and beta-chimaerin (Chn2) from animals.
Telomeric repeat-binding factor 1/2 (TERF1/2)
Type: Family

This group represents telomeric repeat-binding factors 1 (TERF1, also known as TRF1).

Telomeres function to shield chromosome ends from degradation and end-to-end fusions, as well as preventing the activation of DNA damage checkpoints. Telomeric repeat binding factor (TRF) proteins TRF1 and TRF2 are major components of vertebrate telomeres required for regulation of telomere stability. TRF1 and TRF2 bind to telomeric DNA as homodimers. Dimerisation involves the TRF homology (TRFH) subdomain contained within the dimerisation domain. The TRFH subdomain is important not only for dimerisation, but for DNA binding, telomere localisation, and interactions with other telomeric proteins. The dimerisation domains of TRF1 and TRF2 show the same multi-helical structure, arranged in a solenoid conformation similar to TPR repeats, which can be divided into an α-α superhelix and a long α hairpin .

The two related human TRF proteins hTRF1 and hTRF2 form homodimers and bind directly to telomeric TTAGGG repeats via the myb DNA binding domain

at the carboxy terminus . TRF1 is implicated in telomere length regulation and TRF2 in telomere protection . Other telomere complex associated proteins are recruited through their interaction with either TRF1 or TRF2. The fission yeast protein Taz1p (telomere-associated in Schizosaccharomyces pombe (Fission yeast) has similarity to both hTRF1 and hTRF2 and may perform the dual functions of TRF1 and TRF2 at fission yeast telomeres .
Ras-related small G protein, RGK family (RGK)
Type: Family

This entry includes Rad, Rem, and Gem/Kir. They belong to the Ras superfamily of monomeric G-proteins. They are the most potent known intracellular inhibitors of high-voltage-activated Ca2+(Ca(V)1 and Ca(V)2) channels . Similar to other Ras superfamily proteins, RGKs contain a guanine nucleotide binding domain (G-domain). However,
they have non-conservative substitutions in the G-domain of residues critical for GTP binding and hydrolysis .
Phomoidride biosynthesis cluster protein F-like (Phi-like)
Type: Family

This entry represents a family of animal and fungal proteins, including Phomoidride biosynthesis cluster protein F (PhiF), part of the gene cluster that mediates the biosynthesis of the antihypercholesterolemic agents phomoidrides which are dimeric anhydrides . Many members of this group have a N-terminal RWD domain (

).
Anthrax toxin receptor (Anthrax_toxin_rcpt)
Type: Family

Anthrax is an acute disease in humans and animals, which is caused by the bacterium Bacillus anthracis. While the disease can be lethal, there are effective vaccines against anthrax, and some forms of the disease respond well to antibiotic treatment.

The anthrax toxin consists of the proteins protective antigen (PA), lethal factor (LF) and oedema factor (EF). The first step of toxin entry into host cells is the recognition by PA of a receptor on the surface of the target cell. The subsequent cleavage of receptor-bound PA enables EF and LF to bind and form a heptameric PA63 pre-pore, which triggers endocytosis. PA has been shown to bind to two cellular receptors, termed anthrax toxin receptor 1 (ANTXR1/TEM8) and 2 (ANTXR2). Both bind to PA with high affinity and are capable of mediating toxicity , and both are type 1 membrane proteins that include an approximately 200-aa extracellular von Willebrand factor A (VWA) domain with a metal ion-dependent adhesion site (MIDAS) motif .

This entry represents the anthrax toxin receptors. Their physiologic function is unclear. ANTXR1/TEM8 seems to have a role in arteriogenesis .
Bifunctional phosphatidylinositol trisphosphate phosphatase/dual specificity phosphatase PTEN (Bifunc_PIno_P3_Pase/Pase_PTEN)
Type: Family

This entry represents the magnesium-dependent bifunctional phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase/dual-specificity protein phosphatase PTEN (

;

;

), which possesses the following catalytic activities:

Phosphatidylinositol 3,4,5-trisphosphate + H(2)O = phosphatidylinositol 4,5-bisphosphate + phosphate.

A phosphoprotein + H(2)O = a protein + phosphate.

Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.

This protein acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine-and threonine-phosphorylated proteins . It also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate. The lipid phosphatase activity is critical for its tumour suppressor function . PTEN antagonizes the PI3K-AKT/PKB signalling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form of PTEN cooperates with AIP1 to suppress AKT1 activation. PTEN dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion form .
DNA-binding, RFXANK (DNA-bd_RFXANK)
Type: Family

This group represents the DNA-binding protein RFXANK which activates transcription from class II MHC promoters, requiring the activity of the MHC class II transactivator/CIITA. Deficiency is the commonest cause of bare lymphocyte syndrome (the absence of MHC class II transcription and humoral- and cellular-mediated immune responses to foreign antigens) .
Cdc42 effector protein 2 (Cdc42_effector_prot_2)
Type: Family

This entry represents Cdc42 effector protein 2 (also known as Binder of Rho GTPases 1). It is probably involved in the organisation of the actin cytoskeleton .
Gem-associated protein 2 (GEMIN2)
Type: Family

This entry represents Gem-associated protein 2 (GEMIN2, also known as SIP1). GEMIN2 is part of the SMN complex, which plays an essential role in spliceosomal snRNP assembly in the cytoplasm and is required for pre-mRNA splicing in the nucleus .
Protein lin-7 (LIN7)
Type: Family

There are three mammalian LIN7 homologues, LIN7A/B/C . LIN7 contains single L27 and PDZ domains.