SII-SWORD/CoKE huggingface dataset:
Pesticidal crystal protein (Pest_crys)
Type: Family

The crystal proteins of Bacillus thuringiensis have been extensively studied because of their pesticidal properties and their high natural levels of production . When an insect ingests these proteins, they are activated by proteolytic cleavage. The N terminus is cleaved in all of the proteins and a C-terminal extension is cleaved in some members. Once activated, the endotoxin binds to the gut epithelium and causes cell lysis by the formation of cation-selective channels, which leads to death. The activated region (toxic core) of the toxin is composed of three distinct structural domains: an N-terminal helical bundle domain (

) involved in membrane insertion and pore formation; a β-sheet central domain involved in receptor binding; and a C-terminal β-sandwich domain (

) that interacts with the N-terminal domain to form a channel .
Serine/threonine-protein kinase ATM, plant (ATM_plant)
Type: Family

ATM acts as a DNA damage sensor upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA) . It regulate DNA damage response mechanism through recognising the substrate consensus sequence [ST]-Q and phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs) . On DNA damage, autophosphorylation dissociates ATM into monomers rendering them catalytically active . It can phosphorylate DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C . ATM is also required for telomere elongation . ATM also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes . It is also involved in signal transduction and cell cycle control and may function as a tumour suppressor .

This entry includes ATM (Ataxia Telangiectasia Mutated) from plants, including AtATM from Arabidopsis and its homologues from fungi. AtATM is an Arabidopsis homologue of the human ATM gene and plays a important role in the response to both stress-induced and developmentally programmed DNA damage .
Polyadenylate-binding protein-interacting protein 5/6 (CID5/CID6)
Type: Family

This entry represents a group of plant proteins, including CID5 (also known as IPD1) and CID6 from Arabidopsis. They contain a CUE-like domain. CID5 regulates the endocycle leading to hypocotyl elongation and this function is controlled by blue and far-red light .
NrpR repressor (NrpR)
Type: Family

NrpR is an transcriptional repressor of nitrogen assimilation genes found primarily in Euryarchaeota . In the thermophilic archaeon Methanocaldococcus jannaschii it consists of a putative N-terminal winged helix-turn-helix (wHTH) domain used for DNA binding followed by two NrpR regulatory domains (NRD1 and NRD2) that sense and bind 2-oxoglutarate . In different organisms, NrpR proteins can vary on how many NrpR regulatory domains they contain and in their configuration. They can contain two NrpR domains, or one NrpR domain with or without the N-terminal HTH motif .
C2 domain-containing protein 5 (C2CD5)
Type: Family

C2CD5, also known as CDP138 or KIAA0528, is a C2 domain-containing phosphoprotein. It is a substrate for protein kinase Akt2, and it may be involved in the regulation of GLUT4 vesicle-plasma membrane fusion in response to insulin. The C2 domain of C2CD5 was shown to be capable of binding Ca(2+) and lipid membranes . Other studies indicate that C2CD5 is a CDK5- and FIBP-interacting protein, forming a complex with these proteins that is involved in cell proliferation and migration .
OPENER-like (OPRN-like)
Type: Family

This entry represents a group of plant proteins, including At5g43822 from Arabidopsis. Their function is not clear. In Arabidopsis At5g43822 has been characterised as an essential protein renamed OPENER (OPNR), whose gene is expressed in rapidly dividing cells and may function in cell cycle progression. It is expressed in mitochondria and the nuclear envelope. Loss of function results in embryo lethality and reduced transmission through the female .
Cryptic loci regulator 2 (Clr2)
Type: Family

Clr2 (cryptic loci regulator) is a chromatin silencing protein, one of a quartet of proteins forming the core of SHREC, a multienzyme effector complex that mediates hetero-chromatic transcriptional gene silencing in fission yeast . Clr2 does not have any obvious well-conserved domains, but along with the other core proteins binds to the histone deacetylase Clr3. On its own it may also have a role in chromatin organisation at the cnt domain, the site of kinetochore assembly.
Molybdopterin biosynthesis protein MoeA-like (MoeA-like)
Type: Family

Eukaryotic and prokaryotic molybdoenzymes require a molybdopterin cofactor (MoCF or Moco) for their activity. The biosynthesis of this cofactor involves a complex multistep enzymatic pathway. In bacteria, The final step in MoCF synthesis is the attachment of mononuclear Mo to MPT, a process that requires MoeA and which is enhanced by MogA in an Mg2 ATP-dependent manner .

In eukaryotes, MogA and MoeA are fused into a single polypeptide chain, such as in Drosophila protein cinnamon . The corresponding mammalian protein gephyrin has also been implicated in the anchoring of glycinergic receptors to the cytoskeleton at inhibitory synapses .
Something about silencing protein 4 (Sas4)
Type: Family

SAS4 is a fungal silencing regulator. In S. cerevisiae, Sas4 is a subunit of a histone acetyltransferase complex termed SAS complex, which consists of Sas2, Sas4 and Sas5 . The SAS complex acetylates both free histones and nucleosomes and is involved in transcriptional silencing. Both Sas4 and Sas5 are required for optimal Sas2 histone acetyltransferase activity .
Ubiquinone biosynthesis accessory factor UbiJ (UbiJ)
Type: Family

UbiJ is involved in ubiquinone (coenzyme Q) biosynthesis under aerobic conditions . It is an accessory protein that binds hydrophobic ubiquinone biosynthetic intermediates via its SCP2 domain and is essential for the stability of the Ubi complex .
LBH domain (LBH_dom)
Type: Domain

LBH (limb-bud and heart) protein may act as a transcriptional activator in mitogen-activated protein kinase signalling pathway to mediate cellular functions. It has been shown to regulate cardiac gene expression by modulating the combinatorial activities of key cardiac transcription factors, as well as their individual functions in cardiogenesis in mice .

Proteins containing this domain include Protein LBH, and LBH domain-containing protein 1 (LBHD1) from humans.
Caspase activity and apoptosis inhibitor 1 (CAAP1)
Type: Family

CAAP1, or caspase activity and apoptosis inhibitor 1, is a family of eukaryotic proteins involved in the regulation of apoptosis. It modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop .
Transmembrane protein 204 (TMEM204)
Type: Family

The function of TMEM204 is not clear.
Internal virion protein Gp15 (Gp15)
Type: Family

This entry includes Gp15 and related proteins. Gp15 is a component of the cylindrical core that assembles on the inner surface of the capsid during capsid formation and plays a role in viral DNA ejection into the host cell . Bacteriophage T7 proteins Gp15 and Gp16 form a spiral ring complex that binds to both the viral DNA and the host inner membrane .

T7 is a member of the Podoviridae, having short, noncontractile tails that are too short to span a bacterial cell envelope. Its internal core, consists of Gp14/ Gp15/Gp16, is essential for both virion morphogenesis and ejection of its genome .
Internal virion protein Gp16 (Gp16)
Type: Family

This entry includes Gp16 and related proteins . Gp16 is a component of the cylindrical core that assembles on the inner surface of the capsid during capsid formation and plays a role in viral DNA ejection into the host cell . Bacteriophage T7 proteins Gp15 and Gp16 form a spiral ring complex that binds to both the viral DNA and the host inner membrane .

T7 is a member of the Podoviridae, having short, noncontractile tails that are too short to span a bacterial cell envelope. Its internal core, consists of Gp14/ Gp15/Gp16, is essential for both virion morphogenesis and ejection of its genome .
Portal protein, Caudovirales (Portal_prot_Caudovirale)
Type: Family

Most bacterial viruses need the tail complex to inject their genomes inside the bacterial cytoplasm without disrupting the cellular integrity. The portal protein is part of the tail complex. BacteriophageT7 portal protein, also known as Gp8, serves as a connector in the tail complex .
Internal virion protein Gp14 (Gp14)
Type: Family

This entry includes Gp14 and related proteins from tailed bacteriophages and bacterial prophages. Gp14 is a component of the cylindrical core that assembles on the inner surface of the capsid during capsid formation and plays a role in viral DNA ejection into the host cell .

T7 is a member of the Podoviridae, having short, noncontractile tails that are too short to span a bacterial cell envelope. Its internal core, consists of Gp14/ Gp15/Gp16, is essential for both virion morphogenesis and ejection of its genome .
Major capsid protein, Myoviridae (CAPSID_Myoviridae)
Type: Family

This entry includes major capsid proteins from Myoviridae. Bacteriophage T4 major capsid protein, also known as Gp23, self-associates to form hexamers, building most of the capsid in association with pentons made of the capsid vertex protein and one dodecamer of the portal protein .
Highly immunogenic outer capsid protein (HOC)
Type: Family

HOC is a non-essential outer capsid protein that decorates the capsid surface .
Capsid vertex protein (CAPSP)
Type: Family

This entry represents capsid vertex proteins from Myoviridae, including Gp24 from bacteriophage T4. Gp24 can self-associate to form pentons, building the capsid in association with hexamers of the major capsid protein and one dodecamer of the portal protein .
ATP-dependent DNA helicase DinG (DinG_proteobact)
Type: Family

DinG is a DNA damage-inducible protein that functions as a helicase which translocates on single-stranded DNA (ssDNA) in the 5'-3' direction . The ATP-dependent DNA helicase activity of DinG requires divalent cations (Mg2+, Ca2+, and Mn2+) but is not observed in the presence of Zn2+ .
Peptidoglycan-associated lipoprotein (Pal)
Type: Family

Peptidoglycan-associated lipoprotein (Pal or OprL) is part of the Tol-Pal system. The system appears to be involved both in the maintenance of outer membrane integrity and in outer membrane invagination during cell division . The Tol-Pal system is also required for polar localization of chemoreceptor clusters . Pal contains a hydrodrophobic lipoprotein signal sequence, a conserved N-terminal cleavage and modification site, a poorly conserved low-complexity region, together comprising about 65 amino acids, and a well-conserved C-terminal domain.
Hydrogenase maturation factor HybF (HybF)
Type: Family

Bacterial membrane-bound nickel-dependent hydrogenases require a number of accessory proteins which are involved in their maturation . Escherichia coli has two accessory proteins that share protein sequence similarity, HypA and HybF . This entry represents HybF, which is involved in the maturation of isoenzymes 1 and 2 .
Carnitine monooxygenase reductase subunit (Carnitine_monoox_B)
Type: Family

Two-component Rieske-type oxygenase/reductase contains CntA, a Rieske-type oxygenase protein, and CntB, a predicted reductase with a plant-type ferridoxin domain. CntAB is essential in carnitine degradation to trimethylamine (TMA). This entry represents CntB .
Carnitine monooxygenase oxygenase subunit (Carnitine_monoox_A)
Type: Family

Two-component Rieske-type oxygenase/reductase contains CntA, a Rieske-type oxygenase protein, and CntB, a predicted reductase with a plant-type ferridoxin domain. CntAB is essential in carnitine degradation to trimethylamine (TMA). This entry represents CntA .
CSPG repeat (CSPG_rpt)
Type: Repeat

The CSPG (chondroitin sulfate proteoglycan) repeat is a cadherin-like and tumor-relevant protein module which is thought to mediate interactions between cells and the extracellular matrix (ECM) in species as divergent as cyanobacteria, fly, worm, sea urchin and human. The phyletic distribution of the CSPG repeats suggests that horizontal gene transfer contributed in their evolutionary history. The CSPG domain occurs in 1-15 tandem copies per protein. In some proteins the CSPG repeat is combined with Laminin G domains and EGF-like domains .

The CSPG repeat is likely to obtain an all-β fold, possibly comprising eight β-strands. The sixth β-strand starts with a conserved aromatic residue, which is followed by a conserved serine or threonine. Conserved acidic residues are present in the subsequent loop regions between strands 6 and 7, as well as between 7 and 8. For most β-strands one can observe a typical alternating pattern of hydrophobic and non-hydrophobic residues. Hydrophobic side chains that point to the same side of the β-sheet are probably buried in the interior of the CSPG domain .
Rho GTPase-activating protein, pG2 domain (RhoGAP_pG2)
Type: Domain

GTPases bind to guanosine triphosphate (GTP), hydrolyze gamma-phosphate, release guanosine diphosphate (GDP) and then rebind GTP, a process termed 'GTPase cycling'. GTPases are regulated by GTPase activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs). The Ras superfamily of small GTPases consists of five subgroups (Ras, Rho, Rab, Ran and Arf) that act as molecular switches in broad and diverse cellular pathways and processes. The Ras superfamily members contain five highly conserved sequence motifs, termed 'G-motifs', required for nucleotide-binding and catalytic activity. PseudoGTPases by definition would consist of a GTPase fold lacking one or more of these G motifs .

The p190RhoGAP proteins, p190RhoGAP-A (ARHGAP35) and p190RhoGAP-B (ARHGAP5), are key regulators of Rho GTP hydrolysis and are highly important for maintenance of proper Rho signaling. They share a domain organization containing a GTP-binding GTPase domain, four FF domains, two GTPase-like folds (pG1 and pG2) and a C-terminal GAP domain. Their pG1 (pseudoGTPase1) and pG2 (pseudoGTPase2) domains lack conserved GTPase motifs and don't have nucleotide-binding activity .

This entry represents the pG2 domain.
Rho GTPase-activating protein, pG1 domain (pG1)
Type: Domain

GTPases bind to guanosine triphosphate (GTP), hydrolyze gamma-phosphate, release guanosine diphosphate (GDP) and then rebind GTP, a process termed 'GTPase cycling'. GTPases are regulated by GTPase activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs). The Ras superfamily of small GTPases consists of five subgroups (Ras, Rho, Rab, Ran and Arf) that act as molecular switches in broad and diverse cellular pathways and processes. The Ras superfamily members contain five highly conserved sequence motifs, termed 'G-motifs', required for nucleotide-binding and catalytic activity. PseudoGTPases by definition would consist of a GTPase fold lacking one or more of these G motifs .

The p190RhoGAP proteins, p190RhoGAP-A (ARHGAP35) and p190RhoGAP-B (ARHGAP5), are key regulators of Rho GTP hydrolysis and are highly important for maintenance of proper Rho signaling. They share a domain organization containing a GTP-binding GTPase domain, four FF domains, two GTPase-like folds (pG1 and pG2) and a C-terminal GAP domain. Their pG1 (pseudoGTPase1) and pG2 (pseudoGTPase2) domains lack conserved GTPase motifs and don't have nucleotide-binding activity .

This entry represents the pG1 domain.
Intermediate filament, rod domain (IF_rod_dom)
Type: Domain

Intermediate filaments (IF) are proteins which are primordial components of the cytoskeleton and the nuclear envelope. They generally form filamentous structures 8 to 14 nm wide. IF proteins are members of a very large multigene family of proteins which has been subdivided in six types:

Type I: Acidic cytokeratins.

Type II: Basic cytokeratins.

Type III: Vimentin, desmin, glial fibrillary acidic protein (GFAP), peripherin, and plasticin.

Type IV: Neurofilaments L, H and M, alpha-internexin and nestin.

Type V: Nuclear lamins A, B1, B2 and C.

Type VI: 'Orphan' IF proteins, which are more distant in terms of their amino acid sequences.

All IF proteins are structurally similar in that they consist of: a central rod domain comprising some 300 to 350 residues which is arranged in coiled- coiled α-helices, with at least two short characteristic interruptions; a N-terminal non-helical domain (head) of variable length; and a C-terminal domain (tail) which is also non-helical, and which shows extreme length variation between different IF proteins.

While IF proteins are evolutionary and structurally related, they have limited sequence homologies except in several regions of the rod domain. The IF rod domain is approximately 310 residues long in all cytoplasmic IF proteins and close to 350 residues in the nuclear ones. The IF rod domain exhibits an interrupted α-helical conformation and reveals a pronounced seven-residue periodicity in the distribution of apolar residues. The heptad periodicity within the rod domain is interrupted in several places, which generates four consecutive α-helical segments: 1A and 1B, which together form the so-called coil 1, and 2A and 2B, which form coil 2. The four α-helical segments are interconnected by relatively short, variable linkers L1, L12 and L2 .

IF proteins have a very strong tendency to dimerize via the formation of an α-helical coiled coil (CC) by their rod domains .
Capsid Gp10A/Gp10B domain (Capsid_Gp10A/Gp10B_dom)
Type: Domain

This entry describes a domain found in capsid proteins, such as Gp10A (also known as Major capsid protein,

) and Gp10B (also known as Minor capsid protein,

) from bacteriophage T7 and T3 and similar sequences from tailed bateriophages. Gp10A subunits adopt an HK97-like conformation to form the viral shell. They incorporate into the capsid in about a 90/10 ratio .
Synaptotagmin, SMP domain (Synaptotagmin_SMP)
Type: Domain

SMP is a proposed lipid-binding module, ie a synaptotagmin-like mitochondrial-lipid-binding domain found in eukaryotes. The SMP domain has a β-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerises to form an approximately 90-Angstrom-long cylinder traversed by a channel lined entirely with hydrophobic residues. The following two C2 domains then form arched structures flexibly linked to the SMP domain. The SMP domain is a lipid-binding domain that links the ER with other lipid bilayer-membranes within the cell .

This entry represents the SMP domain found in plant synaptotagmins and extended synaptotagmins from metazoa. The extended synaptotagmins transport glycerolipids between the two bilayers via their lipid-harboring SMP domains and Ca2 + regulates their membrane tethering and lipid transport function .
Inorganic triphosphatase YgiF (YgiF)
Type: Family

YgiF from E. coli is a specific inorganic triphosphatase (PPPase). Inorganic pyrophosphatase (PPase) is the main enzyme responsible for hydrolysis of PPPi, whereas YgiF contributes only marginally to the total PPPase activity in this organism. PPPi could be cytotoxic because of its high affinity for calcium ion, thereby interfering with calcium signaling .
Protein myomixer (Myomixer)
Type: Family

Protein myomixer, also known as minion or myomerger, is a myoblast-specific protein that mediates myoblast fusion and is required for muscle development. It associates with Myomaker, a fusogenic membrane protein, and together they can also induce fibroblast-fibroblast fusion and fibroblast-myoblast fusion .
Endonuclease domain-containing 1 protein (ENDOD1)
Type: Family

ENDOD1 may act as a DNase and a RNase . It acts as a tumour suppressor in prostate cancer .
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK)
Type: Family

Reck is a GPI-anchored membrane protein that negatively regulates matrix metalloproteinase-9 (MMP-9) by suppressing MMP-9 secretion and by direct inhibition of its enzymatic activity . It also regulates two other MMPs, MMP-2 and MT1-MMP, known to be involved in cancer progression . Reck and the orphan receptor Gpr124 interact to activate Wnt7a/Wnt7b signalling in CNS vascular development . Reck interacts specifically with the disordered linker region of Wnt7, which confers ligand selectivity for Wnt7 .
ATP synthase protein 8, mammals (ATP8_mammal)
Type: Family

ATP synthase (F1F0 ATPase), also called complex V, is an enzyme that uses a stream of protons passing through the inner membrane of the mitochondria to synthesize ATP. It consists of a part located on the mitochondrial membrane (F0) and containing a proton channel, and a catalytic component (F1) connected to F0 and locating on the side of the mitochondrial matrix . The F0 component contains 3-9 protein subunits (9 in humans) including subunits 6 and 8, encoded by the mtDNA genes ATP6 and ATP8, respectively .

This entry represents ATP8 from mammals.
Endonuclease VapC20-like (VapC20-like)
Type: Family

VapC20 is a toxin from the type II toxin-antitoxin (TA) system of Mycobacterium tuberculosis; its cognate antitoxin is known as VapB20 . VapC20 inhibits translation by cleavage of the sarcin-ricin loop of 23S rRNA .
Cation channel sperm-associated auxiliary subunit zeta (CATSPERZ)
Type: Family

CatSperZ is a subunit of 9-subunit CatSper ion channel complex, involved in sperm cell hyperactivation . Disruption of CatSperZ resulted in male subfertility; fewer calcium ions were able to pass through the channels to enter the cell, affecting the proximal flagellum flexibility and preventing sperm from migrating efficiently. CatSperZ may represent an evolutionary adaptation to maximize fertilization inside the mammalian female reproductive tract . Together with EFCAB9, CatSperZ associates with the CatSper channel pore and is required for the two-row structure of each single CatSper channel .
Terpene cyclase PaxB-like (PaxB-like)
Type: Family

This entry matches terpene cyclases, such as PaxB from Penicillium paxilli. PaxB is part of the ATM2 gene cluster that mediates the biosynthesis of paxilline, a mycotoxin that acts as an inhibitor of mammalian maxi-K channels .
Circadian clock protein KaiB-like (KaiB-like)
Type: Family

The cyanobacterial circadian clock protein KaiB is encoded in the kaiABC operon that controls circadian rhythms. It is a component of the KaiABC clock protein complex, which constitutes the main circadian regulator in cyanobacteria . KaiB has homologues of unknown function in some Archaea and Proteobacteria, and paralogs in some Cyanobacteria. KaiB forms homodimers, homotetramers, and multimeric complexes with KaiA and/or KaiC .
Succinate dehydrogenase membrane subunit SdhC, prokaryotes (SdhC_prok)
Type: Family

In Escherichia coli and many other bacteria, two small, hydrophobic, mutually homologous subunits of succinate dehydrogenase (a TCA cycle enzyme) are SdhC and SdhD. Both SdhC and SdhD participate in anchoring the complex. This entry represents SdhC, the cytochrome b subunit, also called b556 in bacteria.

Mycobacterium contains two operons which are predicted to encode succinate dehydrogenase enzymes (Sdh-1 and Sdh-2). SdhC is encoded in the operon sdhCDAB for Sdh-2. Sdh1 (and not Sdh2) seems to be the primary aerobic succinate dehydrogenase of M. tuberculosis .
Restriction of telomere capping protein 4 (RTC4)
Type: Family

Proteins in this family are known as RTC4 (restriction of telomere capping protein 4) as deletion of RTC4 in Saccharomyces cerevisiae affects the cell response to telomere uncapping .