SII-SWORD/CoKE huggingface dataset:
Proline-rich receptor-like protein kinase PERK1-13-like (PERK1-13-like)
Type: Family

This entry represents a family of plant proteins that includes Proline-rich receptor-like protein kinase PERK1-13 from Arabidopsis thaliana. Most members of this family show a protein kinase domain.
F-box only protein 7 (Fbxo7)
Type: Family

This family includes F-box only protein 7 from humans (Fbxo7) and similar animal proteins. Fbxo7 is the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It plays a role in the clearance of damaged mitochondria via selective autophagy (mitophagy). Mutations in this protein lead to Parkinson's disease .
Forkhead box protein N2/3-like (FOXN2/3-like)
Type: Family

This entry represents a protein family that includes the transcription factors Forkhead box protein N2, N3 and N4 from humans (FOXN2/3/4) and related proteins from animals . Putative forkhead-related transcription factor fkh-5 from Caenorhabditis elegans, is also included in this entry, which binds to DNA sequence motif 5'-CTGTTTCA-3' and regulates expression of a class of small RNAs, known as 21UR-NAs .
Prickle/Espinas/Testin (Pk/Esn/Tes)
Type: Family

This entry represents a family of proteins with a LIM-type zinc finger that are found in animals and some fungal species, including Protein prickle (Pk) and Protein espinas (Esn) from Drosophila melanogaster and human Testin (Tes).

Pk has been implicated in regulation of cell movement in the planar cell polarity (PCP) pathway , which requires the conserved Frizzled/Dishevelled (Dsh). Prickle interacts with Dishevelled , thereby modulating the activity of Frizzled/Dishevelled and the PCP signalling. Two forms of prickle have been identified, namely prickle 1 and prickle 2. These are differentially expressed; prickle 1 is found in fetal heart and haematological malignancies, while prickle 2 is expressed in fetal brain, adult cartilage, pancreatic islet, and some types of tumorous cells .

Esn binds to the seven-pass transmembrane cadherin Flamingo. The interplay elicits repulsion between dendritic branches of sensory neurons .

Tes is a cytoskeleton associated focal adhesion protein that localizes along actin stress fibres, at cell-cell contact areas, and at focal adhesion plaques . It plays a role in the regulation of cell proliferation; it may act as a tumour suppressor .
Uncharacterized protein YjlB-like (YjiB-like)
Type: Family

This family represents a group of bacterial and fungal sequences homologous to the uncharacterised protein YjlB from B. subtilis, whose function is not yet known. These proteins contain a conserved cupin domain.
Trans-enoyl reductase-like (Trans-enoyl_RdTase-like)
Type: Family

This family includes a group of trans-enoyl reductases predominantly found in fungi which are part of gene clusters that mediate the biosynthesis of secondary metabolites, including PoxP involved in the synthesis of the cytotoxic compound oxaleimide , TenC which mediates tenellin-type 2-pyridones synthesis, iron-chelating compounds involved in iron stress tolerance, competition with the natural competitor fungus Metarhizium robertsii and insect hosts infection . Lovastatin nonaketide synthase, enoyl reductase component lovC is also part of this family, which mediates the biosynthesis of lovastatin, a hypolipidemic inhibitor of HMG-CoA reductase . Members of this entry contain a GRoES-like fold at the N-terminal and a classical NAD- and NADP-binding domain with a Rossmann fold at the C-terminal.
Myeloid-associated differentiation marker-like (MYADM-like)
Type: Family

This entry represents a family of proteins from vertebrates, including Myeloid-associated differentiation marker from human (MYADM). MYADM regulates cell spreading and migration, and membrane condensation. It also mediates Rac1 targeting to ordered membranes . This protein regulates the connection between the plasma membrane and the cortical cytoskeleton, controlling the endothelial inflammatory response . Its expression has been associated with asthma severity . MYADM has been proposed as biomarker for non-small-cell lung cancer . Members of this group of proteins show two tandem Marvel domains (

).
Uracil-DNA glycosylase-like HI_0220.2 (HI_0220.2)
Type: Family

This family represents a group of bacterial proteins containing uracil-DNA glycosylase-like domain, including HI_0220.2 from Haemophilus influenzae whose exact function is currently unknown.
Dynactin subunit 5 (DCTN5)
Type: Family

This family includes dynactin 5 (DCTN5, also known as subunit p25). Dynactin is a major component of the activator complex that stimulates dynein-mediated vesicle transport . Dynactin is a heterocomplex of at least eight subunits, including a 150,000-MW protein called Glued, the actin-capping protein Arp1, and dynamatin . In vitro binding experiments show that dynactin enhances dynein-dependent motility, possibly through interaction with microtubules and vesicles. DCTN5 is part of the pointed-end subcomplex in dynactin that also includes p26, p27 (also known as dynactin 6), and Arp11. This subcomplex interacts with membranous cargoes. DCTN5 plays a dual role in cargo binding and dynactin regulation, being critical for this process . DCTN5 contains imperfect tandem repeats of a hexapeptide repeat motif (X-[STAV]-X-[LIV]-[GAED]-X), indicating a left-handed parallel β-helix (LbH) structural domain . Proteins containing hexapeptide repeats are often enzymes showing acyltransferase activity.
RING finger protein 141-like (RNF141-like)
Type: Family

This entry represents RING finger protein 141 from human (RNF141, also known as ZNF230) and similar RING-type zinc finger containing proteins predominantly found in eukaryotes. RNF141 may be involved in spermatogenesis .
Mutator MutT-like (MutT-like)
Type: Family

This family includes mutator MuT (also known as 8-oxo-dGTP diphosphatase) and similar proteins such as CTP pyrophosphohydrolase NudG from E.coli.

MutT is a 7,8-dihydro-8-oxoguanine triphosphatase converting 8-oxoguanine triphosphatase to the monophosphate with high efficiency. It acts both on 8-oxoGTP as well as 8-oxodGTP. It also can convert, less efficiently, the GDP and dGDP forms to the monophosphates . Consequently it reduces the availability of 8-oxoGTP and the rate of mutation.

NudG (also referred to as Orf135 protein), is a MutT-type enzyme that hydrolyzes 5-Me-dCTP with high activity, but also dCTP, 2-OH-dATP and 8-OH-dGTP with lower activity .
Phytanoyl-CoA dioxygenase (PhyH)
Type: Family

This entry represents Phytanoyl-CoA dioxygenase from human (PhyH) and similar proteins found in animals, bacteria and some fungal species. PhyH catalyses the 2-hydroxylation of not only racemic phytanoyl-CoA and the isomers of 3-methylhexadecanoyl-CoA, but also a variety of other mono-branched 3-methylacyl-CoA esters (with a chain length of at least seven carbon atoms) and straight-chain acyl-CoA esters (with a chain length longer than four carbon atoms) . PhyH deficiency causes Refsum's disease (RD) which is an inherited neurological syndrome biochemically characterised by the accumulation of phytanic acid in plasma and tissues .
Serine/Threonine protein phosphatase PP2A-like (PPA2-like)
Type: Family

This entry represents PP2A-like family of phosphoprotein phosphatases (PPPs) which includes PP2A, PP4 and PP6, which are more closely related in sequence to one another than they are to the other PPPs . PP2A (Protein phosphatase 2A) is a critical regulator of many cellular activities, and together with protein phosphatase 1 (PP1), accounts for more than 90% of all serine/threonine phosphatase activities in most cells and tissues. The PP2A subunit has a catalytic domain homologous to PP1 and a unique C-terminal tail, containing a motif that is conserved in the catalytic subunits of all PP2A-like phosphatases including PP4 and PP6, and has an important role in PP2A regulation. The PP2A-like family of phosphatases all share a similar heterotrimeric architecture, that includes: a 65kDa scaffolding subunit (A), a 36kDa catalytic subunit (C), and one of 18 regulatory subunits (B). The PPP (phosphoprotein phosphatase) family, to which PP2A belongs, is one of two known protein phosphatase families specific for serine and threonine. PP2A is the major phosphatase for microtubule-associated proteins (MAPs) .

PP4 (also known as protein phosphatase X) is a phosphatase involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumour necrosis factor (TNF)-alpha signalling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signalling, NF-kappa-B activation and cell migration. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated on Ser-140 (gamma-H2AX) generated during DNA replication and required for DNA double strand break repair .

PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL2 receptor stimulation . It also regulates innate immunity by acting as a negative regulator of the cGAS-STING pathway as it mediates dephosphorylation and inactivation of CGAS and STING1 .
Serpentine type 7TM GPCR chemoreceptor Srsx, nematodes (7TM_GPCR_Srsx_nematod)
Type: Family

This entry represents a protein family specific to nematodes.

Chemoreception is mediated in Caenorhabditis elegans by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs) of proteins which are of the serpentine type . Srsx is a solo family amongst the superfamilies of chemoreceptors. Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf' .
RNA binding protein fox-1 homolog 1-like (RBFOX1-like)
Type: Family

In mammals, there are three Fox-1 homologues, RBFOX1-3 (RNA binding protein Fox-1 homologue 1-3). RBFOX1 is predominantly expressed in neurons, skeletal muscle and heart . RBFOX1 binds to the C terminus of ataxin-2 and forms an ataxin-2/A2BP1 complex involved in RNA processing . RBFOX2 is expressed in ovary, whole embryo, and human embryonic cell lines in addition to neurons and muscle . RBFOX2 activates splicing of neuron-specific exons . RBFOX3 is a nuclear RNA-binding protein that regulates alternative splicing of the RBFOX2 pre-mRNA, producing a message encoding a dominant negative form of the RBFOX2 protein. Its message is detected exclusively in post-mitotic regions of embryonic brain . RBFOX3 modulates brain and muscle-specific splicing of exon EIIIB of fibronectin, exon N1 of c-src, and calcitonin/CGRP .
Olfactory receptor subfamily 6C-like (Olfact_rcpt_6C-like)
Type: Family

This family includes human olfactory receptor proteins from subfamily 6C and similar proteins such as 6X, 6J, 6T, 6V, as well as related proteins from other vertebrates. Olfactory receptors (ORs) play a central role in olfaction. ORs belong to the class A rhodopsin-like family of G protein-coupled receptors and constitute the largest multigene family in mammals of approximately 1,000 genes. More than 60% of human ORs are non-functional pseudogenes compared to only about 20% in mouse. Each OR can recognize structurally similar odorants, and a single odorant can be detected by several ORs .
Small integral membrane protein 5 (SMIM5)
Type: Family

This is a small family of proteins found in vertebrates, including the small integral membrane protein 5 (SMIM5) from human, whose function is not yet clear. This protein has been reported as a variant of the Cancer-Associated Small Integral Membrane Open reading frame 1 (CASIMO1), a small open reading frame (sORF)-encoded protein (also known as a microprotein). CASIMO1 controls cell proliferation and interacts with squalene epoxidase (SQLE) modulating lipid droplet formation .
E3 ubiquitin-protein ligase RNF4 (RNF4)
Type: Family

This family represents E3 ubiquitin-protein ligase RNF4, a SUMO-targeted E3 ubiquitin-protein ligase with a pivotal function in the DNA damage response (DDR) through interacting with the deubiquitinating enzyme ubiquitin-specific protease 11 (USP11), a known DDR-component, and further facilitating DNA repair . It plays a novel role in preventing the loss of intact chromosomes and ensures the maintenance of chromosome integrity. Moreover, RNF4 is responsible for the UbcH5A-catalyzed formation of K48 chains that target SUMO-modified promyelocytic leukemia (PML) protein for proteasomal degradation in response to arsenic treatment . It also interacts with telomeric repeat binding factor 2 (TRF2) in a small ubiquitin-like modifiers (SUMO)-dependent manner and preferentially targets SUMO-conjugated TRF2 for ubiquitination through SUMO-interacting motifs (SIMs) . Furthermore, RNF4 can form a complex with a Ubc13-ubiquitin conjugate and Ube2V2. It catalyzes K63-linked polyubiquitination by the Ube2V2-Ubc13 (ubiquitin-loaded) complex . Meanwhile, RNF4 negatively regulates nuclear factor kappa B (NF-kappaB) signaling by down-regulating transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1)-TAK1-binding protein2 (TAB2) .
Uncharacterized transporter YisQ (YsiQ)
Type: Family

This family represents a group of poorly characterised bacterial transporters, such as YisQ from Bacillus subtilis.
Adenylosuccinate lyase PurB, bacteria (PurB_bact)
Type: Family

This family represents adenylosuccinate lyase (ASL) mainly from bacteria . ASL, PurB in Escherichia coli, catalyses the cleavage of succinylaminoimidazole carboxamide ribotide to aminoimidazole carboxamide ribotide and fumarate and the cleavage of adenylosuccinate to adenylate and fumarate . It also catalyses the conversion of 2-amino-2'-deoxyadenylo-succinate to dZMP and fumarate, when the bacterium is infected by a phage that produces the substrate of this reaction, a step in the synthesis of dZTP (2-amino-2'-deoxyadenosine 5'-triphosphate), which is a nucleotide then used by the phage as a DNA polymerase substrate .
Polyketide cyclase/dehydrase-like ORF3 (ORF3)
Type: Family

This family includes a group poorly characterised sequences predominantly found in bacteria, such as ORF3 protein (also known as Uncharacterized 17.2 kDa protein in melC2-rnhH intergenic region) from Streptomyces lincolnensis. They contain a START domain found in polyketide cylcases/dehydrases.
Rhophilin-1/2 (RHPN1_2)
Type: Family

This entry represents Rhophilin-1/2 (RHPN1/2) and similar proteins predominantly found in vertebrates. RHPN1/2 bind specifically to GTP-Rho and regulate the actin cytoskeleton through interactions with various downstream effector molecules . RHPN1 is a key regulator of the podocyte cytoskeleton and is essential for glomerular filtration . The isolated Bro1-like domain of Rhophilin-1 (

) binds human immunodeficiency virus type 1 (HIV-1) nucleocapsid . RHPN2 limit stress fibre formation and/or increase the turnover of F-actin structures in the absence of high levels of RhoA activity .
tRNA endonuclease ANKZF1/VMS1 (ANKZ1/VMS1)
Type: Family

This entry represents a group of proteins predominantly found in eukaryotes, including Ankyrin repeat and zinc finger domain-containing protein 1 from human (ANKZF1) and VMS1 from Saccharomyces cerevisiae which belong to the VLRF1 (Vms1-Like Release Factor-1) clade . They have been identified as peptidyl-tRNA hydrolases that release nascent chains from stalled ribosomes . ANKZF1, VMS1 orthologue in human, plays a role in the cellular response to hydrogen peroxide and in the maintenance of mitochondrial integrity under conditions of cellular stress . VMS1 is a component of an evolutionarily conserved system for ubiquitin-mediated mitochondria-associated protein degradation (MAD), which is necessary to maintain mitochondrial, cellular, and organismal viability. It is involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway .
Low amplitude and bright protein LabA (LabA)
Type: Family

This family represents a group of bacterial and archaeal proteins, which are poorly characterised. They contain a NYN domain

. This entry includes low amplitude and bright protein LabA from Synechococcus elongatus PCC 7942 (

) which participates in cyanobacterial circadian timing. It is required for negative feedback regulation of the autokinase/autophosphatase KaiC, a central component of the circadian clock system, and appears to be necessary for KaiC-dependent repression of gene expression.
Stealth family (Stealth)
Type: Family

This entry represents a group of mono/polysaccharide phosphotransferases from animal, fungi and bacteria, including N-acetylglucosamine-1-phosphotransferase subunits alpha/beta from humans (GNPTAB) and Capsular polysaccharide phosphotransferase WcwK from Streptococcus pneumoniae. Family members were first identified in microbes as proteins that help pathogens to elude the host innate immune system. Microbial stealth proteins are involved in the biosynthesis of exopolysaccharides . GNPTAB catalyses the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. MP6 residues mediate the vesicular transport of lysosomal enzymes to the endosomal/prelysosomal compartment .

This entry also includes 3-O-alpha-D-mannopyranosyl-alpha-D-mannopyranose xylosylphosphotransferase from Cryptococcus neoformans, which functions in the O-glycosylation of proteins en route through the secretory pathway .
Oryzines biosynthesis cluster protein J/Cupin-domain-containing oxidoreductase virC-like (OryJ/VirC-like)
Type: Family

This family includes bacterial and fungal sequences which contain a cupin domain. This family includes oryzines biosynthesis cluster protein J (OryJ) which is part of the gene cluster that mediates the biosynthesis of oryzines, natural products with an unusual maleidride backbone , VirC, which is part of the gene cluster that mediates the biosynthesis of virensols and trichoxide, fungal natural products that contain or are derived from a salicylaldehyde core .
G-protein coupled estrogen receptor 1-like (GPER1-like)
Type: Family

This family represents a group of proteins from vertebrates that belong to the G-protein coupled receptor 1 family, including G-protein coupled estrogen receptor 1 (GPER1, also known as G-protein coupled receptor 30), the atypical chemokine receptor 3 and orphan receptors such as GP182 and GP146. GPER1 has been described as an atypical GPCR whose physiological and/or pathological roles remain to be determined. It was first described that it binds 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signalling pathways, however, evidence confirming this is still lacking . In vitro studies suggest that E2 could bind GPER1 to trigger various intracellular signalling pathways, and in vivo studies do not exclude GPER1 as an ER in mediating estrogenic responses, but further investigation is needed to confirm this .
BCL-6 corepressor-like (BCOR-like)
Type: Family

This entry represents BCL-6 corepressor from humans (BCOR) and similar proteins from animals. BCOR is a transcriptional corepressor that may specifically inhibit gene expression when recruited to promoter regions by sequence-specific DNA-binding proteins such as BCL6 and MLLT3. This repression may be mediated at least in part by histone deacetylase activities which can associate with this corepressor. It functions as a negative regulator of osteo-dentinogenic capacity in adult stem cells through the repression of AP-2alpha, which implies inhibition of methylation on histone H3 'Lys-4' (H3K4me3) and 'Lys-36' (H3K36me2) .
FERM domain-containing protein 6-like (FRMD6-like)
Type: Family

This family includes FERM domain-containing protein 6 (FRMD6, also known as willin and hEx/human expanded), its homologue from Drosophila, Expanded (Ex) and FERM domain-containing protein 1 (FRMD1). Ex, is a regulator of the Hippo/SWH (Sav/Wts/Hpo) signalling pathway, which plays a pivotal role in organ size control and is tumour suppression by restricting proliferation and promoting apoptosis . Human FRMD6 was first thought to function independently of the Hippo pathway as it lacks the C-terminal domain of Ex that allows it to directly interact with various downstream Hippo signalling components . However, it has been shown to act as an upstream regulator of Hippo signalling that modulates actin cytoskeleton dynamics and mechanical phenotype of neuronal cells through ERK signalling . FRMD6 is widely distributed in various tissues and cell types; in the nervous system is involved in neuronal differentiation, myelination, nerve injury repair, and vesicle exocytosis. It has been implicated in the progression of Alzheimer's disease (AD) and positioned as a novel AD risk gene .

There is not much information about FRMD1 to date. Both FRMD1 and FRMD6 contain a single FERM domain, which is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin.
F-box only protein 5/43 (FBX5_43)
Type: Family

This entry represents F-box only protein 5 and 43 (FBX5/43, also known as Emi1/Emi2, respectively ) from human and similar proteins from animals. FBX5 is a regulator of the anaphase-promoting complex (APC) activity during mitotic and meiotic cell cycle . It promotes migration and osteogenic differentiation of mesenchymal stem cells . FBX43 is required to establish and maintain the arrest of oocytes at the second meiotic metaphase until fertilization. This protein acts by inhibiting the APC/cyclosome ubiquitin ligase. It probably recognises and binds to some phosphorylated proteins and promotes their ubiquitination and degradation .
85/88 kDa calcium-independent phospholipase A2 (PLPL9)
Type: Family

This family includes 85/88 kDa calcium-independent phospholipase A2 (PLPL9/PNPLA9, also known as Patatin-like phospholipase domain-containing protein 9, PLA2G6 (phospholipase A2 group VI) or iPLA2beta) and related animal sequences. PNPLA9 is a Ca-independent phospholipase that catalyses the hydrolysis of glycerophospholipids at the sn-2 position, being involved in phospholipid remodelling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction. It is stimulated by ATP and inhibited by bromoenol lactone (BEL). In humans, PNPLA9 in expressed ubiquitously and is involved in signal transduction, cell proliferation, and apoptotic cell death. It plays a critical role in membrane homeostasis.

Mutations in human PNPLA9 leads to infantile neuroaxonal dystrophy (INAD) and idiopathic neurodegeneration with brain iron accumulation (NBIA) .
Kinesin-like protein KIF11-like (KIF11-like)
Type: Family

This entry includes a group of kinesin-like proteins, including human Eg5/KIF11, its orthologue from Drosophila Klp61F, BimC from Emericella nidulans and CIN8 from Saccharomyces cerevisiae. These are spindle pole proteins, which participate in spindle assembly and chromosome segregation during cell division, required for spindle body separation .
SGT (SGT)
Type: Family

This entry represents the SGT family, which includes Small glutamine-rich tetratricopeptide repeat-containing protein alpha/beta (SGTA/B) from humans and similar sequences spread in eukaryotes and prokaryotes. SGT is a co-chaperone that binds misfolded and hydrophobic patches-containing client proteins in the cytosol. It mediates their targeting to the endoplasmic reticulum but also regulates their sorting to the proteasome when targeting fails . SGT binds directly to HSC70 and HSP70 and regulates their ATPase activity . Most members of this family contain tetratricopeptide repeats.