SII-SWORD/CoKE huggingface dataset:
Lysine-specific histone demethylase (Hist_Lys-spec_deMease)
Type: Family

This entry represents a histone demethylase (LSD1) that specifically demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a co-repressor . This enzyme acts by oxidising the substrate by FAD to generate the corresponding imine, which is subsequently hydrolysed. This enzyme demethylates both mono- and di-methylated 'Lys-4' of histone H3 and may play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3 'Lys-4' on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. It may also demethylate 'Lys-9' of histone H3, a specific tag for epigenetic transcriptional repression, thereby leading to derepression of androgen receptor target genes. It plays a role in developmental growth and lifespan regulation in response to ultraviolet-induced damage .

This histone demethylase is a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, AOF2/LSD1, RCOR1/CoREST and PHF21A/BHC80 . The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. In the complex, RCOR1/CoREST strongly enhances the demethylase activity and protects it from the proteasome while PHF21A/BHC80 inhibits the demethylase activity. Interacts with the androgen receptor (AR).
Peptidase M12A, nematode astacin 7/8, Caenorhabditis (Caenorhab_nas-7/8)
Type: Family

This family of metallopeptidases belongs to MEROPS peptidase family M12A (astacin, clan MA). In the nematode Caenorhabditis elegans, 40 genes code for astacin-like proteins (nematode astacins, NAS). The astacins are metalloproteases present in bacteria, invertebrates and vertebrates and serve a variety of physiological functions like digestion, hatching, peptide processing, morphogenesis and pattern formation .

This entry represents nas-7 and nas-8 from Caenorhabditis. Nas-7 has a role in pharynx development .
Peptidase M12A, nematode astacin 9/10/11 (Peptidase_M12A_astacin-9/10/11)
Type: Family

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation, which is usually zinc but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophilic role.

Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site . The HEXXH motif is relatively common but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases .

This family of metallopeptidases are found in Caenorhabditis elegans and belong to MEROPS peptidase family M12A (astacin, clan MA). They hydrolys peptide bonds in substrates containing five or more amino acids, preferentially with Ala in P1', and Pro in P2'.
SPAN protein/blastula protease 10 (SPAN/blastula_protease_10)
Type: Family

This group represents a SPAN protein/blastula protease 10.
Hatching enzyme, Uvs2-like (Hatching_enzyme_Uvs2-like)
Type: Family

This group represents zinc-dependent metalloproteases related to the hatching enzyme, including uvs.2 from Xenopus (MEROPS identifier M12.014) and Astacin-like metalloendopeptidases from quail (MEROPS identifier M12.324), which may play a role in the breaking down of the vitelline membrane (days 0-5) and possibly, in the digestion of the egg white (days 9-12) .
Tumour necrosis factor receptor 11B (TNFR_11B)
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 .

TNF receptors 11A and 11B mediate the effects of receptor activator for NF-kappa-B ligand (RANKL), an essential osteoclast regulatory factor. The receptors have opposing effects -activation of TNF receptor 11A by RANKL promotes osteoclast differentiation , while TNF receptor 11B acts as a soluble decoy receptor for the ligand, thus inhibiting differentiation .

TNF receptor 11B (also known as osteoprotegerin (OPG)) is a secreted protein that contains two death domains within its C-terminal region. Mutations in the TNF receptor 11B gene are associated with the autosomal recessive osteopathy juvenile Paget disease . The receptor may also be involved in vascular calcification, and high expression levels in serum are a risk factor for the progression of atherosclerosis and the onset of cardiovascular disease .
Glial cell line-derived neurotrophic factor receptor, alpha 1/2 (Glial_neurotroph_fac_rcpt_a1/2)
Type: Family

Glial cell line-derived neurotrophic factor (GDNF) and its related factors neurturin (NTN), artemin (ART) and persephin (PSP), are members of the GDNF family of neurotrophic factors. They form a sub-group in the transforming growth factor-beta (TGF-beta) superfamily. These factors are involved in the promotion of neurone survival, exerting their effects through specific receptors.

The GDNF family receptors (GFRs) are glycosyl-phosphatidylinositol-linked, cell surface receptors . Four receptor subtypes, termed GFRalpha-1 to 4, are currently recognised. GFRalpha-1 and 2 are activated by GDNF and NTN respectively, although some degree of ligand promiscuity is thought to occur . Homologues for these receptor subtypes have been cloned from mammalian and avian tissue. The principal ligand for GFRalpha-3 is artemin. This receptor subtype is currently described only in mammals . GFRalpha-4 is activated by persephin and has so far only been found in chicken . This entry is general for types 1 to 3.

Activation of GFR family members triggers their interaction with the membrane-bound receptor kinase Ret. This induces Ret homo-dimerisation, triggering a cascade of intracellular signalling events such as the activation of the Ras-mitogen-activated protein kinase (MAPK), phosphoinositol-3-kinase (PI3K), Jun N-terminal kinase (JNK) and phospholipase C gamma (PLC gamma) dependent pathways .
Sodium-dependent phosphate transport protein 4 , predicted (Na-dep_P-transpt_4_prd)
Type: Family

This group represents a predicted sodium-dependent phosphate transport protein 4.
Fringe (Fringe)
Type: Family

The Notch receptor is a large, cell surface transmembrane protein involved in a wide variety of developmental processes in higher organisms . It becomes activated when its extracellular region binds to ligands located on adjacent cells. Much of this extracellular region is composed of EGF-like repeats, many of which can be O-fucosylated. A number of these O-fucosylated repeats can in turn be further modified by the action of a beta-1,3-N-acetylglucosaminyltransferase enzyme known as Fringe . Fringe potentiates the activation of Notch by Delta ligands, while inhibiting activation by Serrate/Jagged ligands. This regulation of Notch signalling by Fringe is important in many processes .

Four distinct Fringe proteins have so far been studied in detail; Drosophila Fringe (Dfng) and its three mammalian homologues Lunatic Fringe (Lfng), Radical Fringe (Rfng) and Manic Fringe (Mfng). Dfng, Lfng and Rfng have all been shown to play important roles in developmental processes within their host, though the phenotype of mutants can vary between species eg Rfng mutants are retarded in wing development in chickens, but have no obvious phenotype in mice . Mfng mutants have not, so far, been charcterised. Biochemical studies indicate that the Fringe proteins are fucose-specific transferases requiring manganese for activity and utilising UDP-N-acetylglucosamine as a donor substrate . The three mammalian proteins show distinct variations in their catalytic efficiencies with different substrates.
Peroxisome assembly protein 12 (PEX12)
Type: Family

This group represents peroxisome assembly protein 12, also known as Peroxin-12 or PEX12. PEX12 is required for protein import into peroxisomes .
Herpesvirus UL49A (Herpes_UL49A)
Type: Family

This group represents an envelope protein, UL49A herpesvirus type.
Herpesvirus US8A (Herpes_US8A)
Type: Family

This entry represents the Herpesvirus US8.5 protein family found in herpesviruses, including Human herpesvirus 2. The protein localises to the host nucleus and nucleolus. The specific function of this protein remains unknown, but it is phosphorylated and contains a disordered region between residues 63-93.
Torsin 1/2 (Torsin_1/2)
Type: Family

This entry represents a number of torsins including types 1A, 1B and 2A. Some torsin-like proteins are also included. Torsion dystonia is an autosomal dominant movement disorder characterised by involuntary, repetitive muscle contractions and twisted postures. The most severe early-onset form of dystonia has been linked to mutations in the human DYT1 (TOR1A) gene encoding a protein termed torsinA. While causative genetic alterations have been identified, the function of torsin proteins and the molecular mechanism underlying dystonia remain unknown. Phylogenetic analysis of the torsin protein family indicates these proteins share distant sequence similarity with the large and diverse family of AAA ATPase, central region containing proteins (

) proteins. It has been suggested that torsins play a role in effectively managing protein folding and that possible breakdown in a neuroprotective mechanism that is, in part, mediated by torsins may be responsible for the neuronal dysfunction associated with dystonia .
PDZ domain-containing protein GIPC1/2/3 (GIPC1/2/3)
Type: Family

Gipc1/2/3 are a group of PDZ domain-containing proteins. They contain a central PDZ domain and GIPC homology (GH1 and GH2) domains . They are involved in trafficking, signaling and recycling of RTKs, GPCRs, integrins and other transmembrane proteins. Gipc1 and Gipc2 have been linked to cancer, while mutations in the Gipc3 gene cause nonsyndromic hearing loss .
Histone acetyltransferase type B, catalytic subunit (Hist_AcTrfase_B-typ_cat-su)
Type: Family

This entry represents the catalytic subunit of histone acetyltransferase type B (

) (also known as HAT1), which is the catalytic component of the histone acetylase B (HAT-B) complex . The HAT-B complex is composed of at least HAT1 and HAT2. In the cytoplasm, this complex binds to the histone H4 tail. In the nucleus, the HAT-B complex has an additional component, the histone H3/H4 chaperone HIF1.

This enzyme acetylates soluble but not nucleosomal H4 at Lys-12, which is required for telomeric silencing. HAT1 has intrinsic substrate specificity that modifies lysine in recognition sequence GXGKXG. It is involved in DNA double-strand break repair .
Leukocyte cell-derived chemotaxin 2, chordata (LECT2_chordata)
Type: Family

This group represents a leukocyte cell-derived chemotaxin 2.
Actin-related protein 2/3 complex subunit 1 (ARPC1)
Type: Family

Arp2/3 binds to pre-existing actin filaments and nucleates new daughter filaments, and thus becomes incorporated into the dynamic actin network at the leading edge of motile cells and other actin-based protrusive structures . In order to nucleate filaments, Arp2/3 must bind to a member of the N-WASp/SCAR family protein . Arp2 and Arp3 are thought to be brought together after activation, forming an actin-like nucleus for actin monomers to bind and create a new actin filament. In the absence of an activating protein, Arp2/3 shows very little nucleation activity. Recent research has focused on the binding and hydrolysis of ATP by Arp2 and Arp3 , and crystal structures of the Arp2/3 complex have been solved .

The human Arp2/3 complex composed of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. This family represents the ARPC1/p41-ARC subunit.
NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex subunit 1 (NADH_Ub_cplx-1_asu_su-1)
Type: Family

This group represents a NADH dehydrogenase [ubiquinone] (complex I), alpha subcomplex subunit 1 . Complex I functions in the transfer of electrons from NADH to the respiratory chain.
ATPase, V0 complex, subunit e1/e2, metazoa (ATPase_V0-cplx_e1/e2_su_met)
Type: Family

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra-and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release . V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins .

This entry represents subunit e (or subunit M9.2) found in the V0 complex of certain V-ATPases. The V0 complex contains subunit c (proton-conducting pore), as well as accessory subunits that function in assembly, targeting or regulation of the V-ATPase complex. Subunit e is an extremely hydrophobic protein of approximately 9kDa, which may be required for assembly of vacuolar ATPases . The amino terminal domain of subunit E interacts with the H subunit and is required fo V-ATPase function . Different isoforms of this subunit exist sometimes annotated as e1 and e2 also a neuron-specific isoform, NM9.2 has been identified .
Transcription factor SOX-12/11/4 (SOX-12/11/4)
Type: Family

SYR-related high mobility group (HMG) box (SOX) family proteins are a conserved group of transcriptional regulators defined by the presence of a highly conserved HMG box domain that mediates DNA binding . This group represents the redundantly acting transcription factor SOX-12/11/4 proteins, which belong to the subgroup C of the SOX gene family. These proteins have almost identical DNA-binding domains that bind to the DNA sequence 5'-AACAAT-3' and have a highly conserved transactivation domain at their C-terminal . They play an essential role in several developmental pathways including neurogenesis and skeletogenesis, affecting maintenance, proliferation and differentiation of progenitor cells in developing tissues such as the neural tube, branchial arches and somites .
Testis-specific TEX28 (Testis-specific_TEX28)
Type: Family

This group represents a testis-specific protein TEX28.
Nucleoporin, NUP53 (Nucleoporin_NUP53)
Type: Family

The nuclear pore complex (NPC) mediates the transport of macromolecules across
the nuclear envelope (NE). The NPC is composed of a relatively small number of
proteins (~30), termed nucleoporins or Nups. The vertebrate nuclear pore
protein Nup35, the orthologue of Saccharomyces cerevisiae Nup53p, is suggested to interact with the NE membrane and to be required for nuclear morphology .

This entry also includes Asm4 (a paralogue of Saccharomyces cerevisiae Nup53p) from Saccharomyces cerevisiae and Nup40 from Schizosaccharomyces pombe.
Ubiquitinyl hydrolase, UCH37 type (Ubiquitinyl_hydrolase_UCH37)
Type: Family

This group represents an ubiquitin carboxyl-terminal hydrolase, UCH37 (also known as UCHL5) type.

Human UCH37 is a protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. It is also a deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome .

This entry also includes fission yeast Uch2, which is an ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins .
AP2/ERF transcription factor ERF/PTI6 (AP2/ERF-transcript_factor)
Type: Family

This entry represents a group of plant AP2/ERF transcription factors, including pathogenesis-related genes transcriptional activator PTI6 and ethylene-responsive transcription factor ERF . PTI6 binds to the GCC-box pathogenesis-related promoter element and activates the defense genes of plants .
Chromatin-remodeling complex component Sfh1/SNF5 (Sfh1/SNF5)
Type: Family

This entry includes Sfh1 from fungi and SNF5 from animals. They are components of chromatin-remodeling complex. In animals, SNF5 is a component of the BAF (hSWI/SNF) complex, which is an ATP-dependent nucleosome-remodelling complex that plays important roles in cell proliferation and differentiation . In budding yeasts, Sfh1 is a component of the chromatin structure-remodeling complex (RSC), which is involved in transcription regulation and nucleosome positioning .
LOB domain-containing protein 18/20 (LOB_18/20)
Type: Family

This group of proteins contain a lateral organ boundaries (LOB) domain and are restricted to plants.

The lateral organ boundaries (LOB) gene is expressed at the adaxial base of initiating lateral organs and encodes a plant-specific protein of unknown function. The N-terminal one half of the LOB protein contains a conserved approximately 100-amino acid domain (the LOB domain) that is present in 42 other Arabidopsis thaliana proteins and in proteins from a variety of other plant species. Genes encoding LOB domain (LBD) proteins are expressed in a variety of temporal- and tissue-specific patterns, suggesting that they may function in diverse processes
The LOB domain contains conserved blocks of amino acids that identify the LBD gene family. In particular, a conserved C-x(2)-C-x(6)-C-x(3)-C motif, which is defining feature of the LOB domain, is present in all LBD proteins. It is possible that this motif forms a new zinc finger .
Chlorophyllase-like (Chlorophyllase-like)
Type: Family

This entry includes Chlorophyllases (Chlase) from plants and uncharacterised bacterial proteins which share the same PET hydrolase fold.

Chlase (

) is an enzyme involved in chlorophyll degradation and catalyses the hydrolysis of the ester bond to yield chlorophyllide and phytol . It is found in higher plants, green algae and diatoms . It is important for de-greening processes such as fruit ripening, leaf senescence and flowering, as well as in the turnover and homeostasis of chlorophyll .
WRKY transcription factor, group IIc (TF_WRKY_IIc)
Type: Family

This entry represents a subset of group IIc probable WRKY transcription factors from plants. Plant WRKY transcription factors are known to regulate various biotic and abiotic stress responses .
WD repeat protein DCAF11/LEC14B (DCAF11/LEC14B)
Type: Family

This entry includes a group of WD repeat proteins, including DDB1- and CUL4-associated factor 11 (DCAF11) from animals and LEC14B from plants. DCAF11 may function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex . The function of LEC14B from plants is not clear.
Eukaryotic elongation factor 2 kinase (eEF-2K)
Type: Family

This entry represents elongation factor 2 kinase (eEF-2 kinase), a highly specific kinase that phosphorylates and inactivates eukaryotic elongation factor-2 (eEF-2), and thus can modulate the rate of polypeptide chain elongation during translation. eEF-2 kinase is part of the family of alpha-kinases, whose catalytic domains display no sequence homology to conventional eukaryotic protein kinases . This family also includes Dictyostelium myosin heavy chain kinases A, B, and C, and several mammalian putative protein kinases.
Protein phosphatase 1 regulatory subunit 12A/B/C (MYPT1/MYPT2/Mbs85)
Type: Family

This group represents protein phosphatase 1 regulatory subunits 12A/B/C (also known as MYPT1/MYPT2/Mbs85) from animals. They are key regulators of protein phosphatase 1C (PPP1C). They modulates Ca
2+
-dependent phosphorylation of myosin light chain by myosin light chain kinase, which is essential for smooth muscle contraction . MYPT2 have similar features as MYPT1, such as: a specific interaction with the catalytic subunit of type 1 phosphatase, delta isoform (PP1cdelta); interaction of MYPT2 with the small heart-specific MP subunit; interaction of the C-terminal region of MYPT2 with the active form of RhoA; phosphorylation by Rho-kinase at an inhibitory site, Thr646 and thiophosphorylation at Thr646 inhibited activity of the MYPT2-PP1cdelta complex . Mbs85 has been shown to regulate myosin phosphatase activity .
Proteorhodopsin (Proteorhodopsin)
Type: Family

This entry represents blue-light-absorbing and green-light absorbing proteorhodopsins, as well as predicted bacterial type rhodopsins. Proteorhodopsins (PRs), the recently discovered light-driven proton pumps, play a major role in supplying energy for microbial organisms of oceans and belong to the archaeal/bacterial/fungal opsin family . Blue-light absorbing proteorhodopsin may have a regulatory rather than energy harvesting function, based on light-induced opening of proton channels, to modulate cell physiology depending on light intensity variations, and could be a sensory rhodopsin, potentially associated with a transducer component. Blue-light absorbing proteorhodopsin presents a much slower photocycle than that of the green-absorbing proteorhodopsin. Green-light absorbing proteorhodopsin generates photothrophic energy, with a fast proton release and an alkaliphilic photocycle.
Podocalyxin (PODXL)
Type: Family

Podocalyxin is involved in the regulation of both adhesion and cell morphology and cancer progression. It functions as an anti-adhesive molecule that maintains an open filtration pathway between neighbouring foot processes in the podocyte by charge repulsion .
Ladinin 1 (Ladinin_1)
Type: Family

Ladinin 1 is an anchoring filament protein which is a component of the basement membrane zone.1 .
Citron Rho-interacting kinase (Citron_Rho-interacting_kinase)
Type: Family

Citron Rho-interacting kinase (CRIK) is a dual specificity protein kinase, which catalyses the autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues . It plays an important role in the regulation of cytokinesis and the development of the central nervous system. It is required for KIF14 localization to the central spindle and mid-body. It is also a putative RHO/RAC effector that binds to the GTP-bound forms of RHO and RAC1.
Serine/threonine-protein kinase Rio3 (Ser/Thr_kinase_Rio3)
Type: Family

This entry represents serine/threonine-protein kinases (

) such as Rio3. RIO kinases are atypical members of the protein kinase family that are required for ribosome biogenesis and cell cycle progression . Rio3 has only been found in multicellular organisms.