SII-SWORD/CoKE huggingface dataset:
Delta-hexatoxin (Delta-hexatoxin)
Type: Family

Delta-hexatoxin (also known as delta-atracotoxin) is an arachnid toxin that produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels . Effects are an increase in resting tension, a muscle fasciculation and a decrease in indirect twitch tension. In vivo, it is lethal to both vertebrates and insects . Its structure comprises a core β-region containing a triple-stranded a thumb-like extension protruding from the β-region and a C-terminal helix. The β-region contains a cysteine knot motif, a feature seen in other neurotoxic polypeptides .
Bacteriophage tail attachment protein FII (Phage_tail_attach_FII)
Type: Family

The phage head-tail attachment protein is required for the joining of phage heads and tails at the last step of morphogenesis . FII is incorporated into the base vertex of DNA-filled heads to facilitate head-tail joining and may determine the specificity of tail attachment. There are 5-6 copies of protein FII per mature phage.
Apolipoprotein C-II (Apo-CII)
Type: Family

Apolipoprotein CII (apoC-II) is a surface constituent of plasma lipoproteins and the activator for lipoprotein lipase (LPL). It is therefore central for lipid transport in blood. Lipoprotein lipase is a key enzyme in the regulation of triglyceride levels in human serum . It is the C-terminal helix of apoC-II that is responsible for the activation of LPL . The active peptide of apoC-II occurs at residues 44-79 and has been shown to reverse the symptoms of genetic apoC-II deficiency in a human subject .

Micellar SDS, a commonly used mimetic of the lipoprotein surface, inhibits the aggregation of apoC-II and induces a stable structure containing approximately 60% α-helix. The first 12 residues of apoC-II are structurally heterogeneous but the rest of the protein forms a predominantly helical structure .
Capsid protein G8P (G8P)
Type: Family

This entry represents the class I phage major coat protein Gp8 or B. The coat protein is largely α-helix with a slight curve . It is inserted in the host inner membrane, where filamentous phages are assembled and then extruded across the cellular envelope, without killing the bacterial host .

The major coat protein in the capsid of filamentous bacteriophage forms a helical assembly of about 7000 identical protomers, with each protomer comprised of 46 amino acids, after the cleavage of the signal peptide. Each protomer forms a slightly curved helix that combines to form a tubular structure that encapsulates the viral DNA .
Attachment protein G3P, N-terminal (Attachment_G3P_N)
Type: Domain

The G3P protein (also known as attachment protein or coat protein A) of filamentous phage such as M13, phage fd and phage f1, is an essential coat protein for the infection of Escherichia coli. The G3P protein consists of three domains: two N-terminal domains (N1 and N2) with a similar β-barrel fold, and a C-terminal domain . The N-terminal domains protrude from the phage surface, while the C-terminal domain acts as an anchor embedded in the phage coat, together forming a horseshoe-like structure . The G3P protein exists as 3-5 copies at the tip of the phage particle.
DicB (DicB)
Type: Family

DicB is part of the dic operon, which resides on cryptic prophage Kim. Under normal
conditions, expression of dicB is actively repressed. When expression is induced, however, cell
division rapidly ceases, and this division block is dependent on MinC with which it interacts
.
Protein of unknown function DUF748 (DUF748)
Type: Family

This is a family of proteins of unknown function.
YiaAB two helix (YiaAB)
Type: Domain

This domain consists of two transmembrane helices and a conserved linking section.
CPI-17 (CPI-17)
Type: Family

Contractility of vascular smooth muscle depends on phosphorylation of myosin light chains, and is modulated by hormonal control of myosin phosphatase activity. Signaling pathways activate kinases such as PKC or Rho-dependent kinases that phosphorylate the myosin phosphatase inhibitor protein called CPI-17 (also known as protein phosphatase 1 regulatory subunit 14). Phosphorylation of CPI-17 at Thr-38 enhances its inhibitory potency 1000-fold, creating a molecular switch for regulating contraction .
Herpesvirus ICP47 (Herpes_ICP47)
Type: Family

ICP47 (US12) is a key factor in the evasion of cellular immune response against Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1)-infected cells. Specific inhibition of the transporter associated with antigen processing (TAP) by ICP47 prevents peptide transport into the endoplasmic reticulum and subsequent loading of major histocompatibility complex (MHC) class I molecules . ICP47 is comprised of three helices and is associated with cellular membranes .
Cytochrome b-c1 complex subunit 9 (QCR9)
Type: Family

Cytochrome b-c1 complex subunit 9 (QCR9) is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. It may interact with cytochrome c1 . QCR9 contains the single transmembrane helix structure.
Sarcolipin (Sarcolipin)
Type: Family

This entry represents Sarcolipin (SLN) and similar proteins from vertebrates. SLN is a short integral membrane protein that regulates Ca-ATPase activity in skeletal muscle . It has also been shown to amplify calcineurin signalling, and is a potential therapeutic target for the management of muscular dystrophy, as it is upregulated in the skeletal muscle of the classical mouse model for Duchenne muscular dystrophy .
Bacteriophage T7, Gp3, endodeoxynuclease I (Phage_T7_Gp3_endoDNaseI)
Type: Family

Endonuclease I (

) is a junction-resolving enzyme encoded by bacteriophage T7, that selectively binds and cleaves four-way Holliday DNA junctions . The structure of the enzyme shows that it forms a symmetric homodimer arranged in two well-separated domains. Each domain, however, is composed of elements from both subunits, and amino acid side chains from both protomers contribute to the active site .
NmrA-like domain (NmrA-like)
Type: Domain

NmrA is a negative transcriptional regulator of various fungi, involved in the post-translational modulation of the GATA-type transcription factor AreA . NmrA lacks the canonical GXXGXXG NAD-binding motif and has altered residues at the catalytic triad, including a Met instead of the critical Tyr residue. NmrA may bind nucleotides but appears to lack any dehydrogenase activity. It lacks most of the active site residues of the SDR (short-chain dehydrogenases/reductases) family, but has an NAD(P)-binding motif similar to the extended SDR family, GXXGXXG .

This domain can also be found in other atypical SDRs, such as HSCARG (an NADPH sensor) and PCBER (phenylcoumaran benzylic ether reductase) .
Monomethylamine methyltransferase MtmB (MtmB_MeTrfase)
Type: Family

Monomethylamine methyltransferase of the archaebacterium Methanosarcina barkeri contains a novel amino acid, pyrrolysine, encoded by the termination codon UAG . The structure of the enzyme reveals a homohexamer comprised of individual subunits with a TIM barrel fold. MtmB initiates the metabolism of monomethylamine by catalysing the transfer of the methyl group from monomethylamine to the corrinoid cofactor of MtmC .
Protein of unknown function DUF749 (DUF749)
Type: Family

This is a family of unknown function found in archaebacterial proteins. The family has been solved via structural genomics techniques and comprises of segregated helical and anti-parallel β sheet regions. It is a putative metal-binding protein.
Delta-hemolysin (Delta_lysin)
Type: Family

Delta-hemolysin (also known as Delta-lysin) is a 26 amino acid, hemolytic peptide toxin secreted by Staphylococcus aureus. It is thought that delta-toxin forms an amphipathic helix upon binding to lipid bilayers . It possesses hemolytic/lytic and antimicrobial activity . It may slightly perturb the membrane or lead to cell lysis. Delta-hemolysin serves as a model in the study of peptides interacting with membranes .
L-proline 3-hydroxylase, C-terminal (Pro_3_hydrox_C)
Type: Domain

Iron (II)/2-oxoglutarate (2-OG)-dependent oxygenases catalyse oxidative reactions in a range of metabolic processes. Proline 3-hydroxylase hydroxylates proline at position 3, the first of a 2-OG oxygenase catalysing oxidation of a free alpha-amino acid. The structure contains conserved motifs present in other 2-OG oxygenases including a jelly roll strand core and residues binding iron and 2-oxoglutarate, consistent with divergent evolution within the extended family. The structure differs significantly from many other 2-OG oxygenases in possessing a discrete C-terminal helical domain .
Conotoxin, mu-type (Conotoxin_mu-typ)
Type: Family

This entry represents Mu-type conotoxins. Cone snail toxins, conotoxins, are small peptides with disulphide connectivity, that target ion-channels or G-protein coupled receptors. Based on the number and pattern of disulphide bonds and biological activities, conotoxins can be classified into several families . Omega, delta and kappa families of conotoxins have a knottin or inhibitor cystine knot scaffold. The knottin scaffold is a very special disulphide through disulphide knot, in which the III-VI disulphide bond crosses the macrocycle formed by two other disulphide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N terminus.

The disulphide bonding network as well as specific amino acids in inter-cysteine loops provide specificity of conotoxin . The cysteine arrangement is the same for omega, delta and kappa families, but omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels and kappa conotoxins are potassium channel blockers . Mu conotoxins have two types of cysteine arrangement, but the knottin scaffold is not observed. Conotoxin gm9a, a putative 27-residue polypeptide encoded by Conus gloriamaris, has been shown to adopt an inhibitory cystine knot motif constrained by three disulphide bonds . Mu conotoxins target the voltage-gated sodium channels , preferential skeletal muscle , and are useful probes for investigating voltage-dependent sodium channels of excitable tissues . They differ on the primary structure level which also affect their three-dimensional structures, explaining their sodium channel subtype specificities .
Pacifastin domain (Pacifastin_dom)
Type: Domain

Proteins containing this domain are proteinase inhibitors belonging to MEROPS inhibitor family I19 (clan IW) and sharing a pacifastin domain of ~35 residues, which contains a characteristic pattern of six conserved cysteine residues (C-x(9,12)-C-N-x-C-x-C-x(2,3)-G-x(3,6)-C-T-x(3)- C). The pacifastin domain consists of a twisted β-sheet composed of three antiparallel strands and stabilised by an identical pattern (C1-C4, C2-C6, C3-C5) of disulfide bridges .
Hydantoinase/oxoprolinase, N-terminal (Hydant_A_N)
Type: Domain

This domain is found at the N terminus of the hydantoinase/oxoprolinase

family.
Retrotransposon, Pao (Retrotrans_Pao)
Type: Family

This signature identifies members of the Pao retrotransposon family.
Bacteriophage lysin (Phage_lysin)
Type: Domain

This entry is represents bacteriophage lysins (Cell wall hydrolase;

). The Pal protein from the pneumococcal bacteriophage Dp-1 (

) has been shown to be an N-acetylmuramoyl-L-alanine amidase . According to the known modular structure of this and other peptidoglycan hydrolases from the pneumococcal system, the active site should reside within this domain while a C-terminal domain binds to the choline residues of the cell wall teichoic acids .
DNA replication licensing factor Mcm2 (MCM2)
Type: Family

The MCM2-7 complex consists of six closely related proteins that are highly conserved throughout the eukaryotic kingdom. In eukaryotes, Mcm2 is a component of the MCM2-7 complex (MCM complex), which consists of six sequence-related AAA + type ATPases/helicases that form a hetero-hexameric ring . MCM2-7 complex is part of the pre-replication complex (pre-RC). In G1 phase, inactive MCM2-7 complex is loaded onto origins of DNA replication . During G1-S phase, MCM2-7 complex is activated to unwind the double stranded DNA and plays an important role in DNA replication forks elongation .

The components of the MCM2-7 complex are:

DNA replication licensing factor MCM2,

DNA replication licensing factor MCM3,

DNA replication licensing factor MCM4,

DNA replication licensing factor MCM5,

DNA replication licensing factor MCM6,

DNA replication licensing factor MCM7,

In addition to its role in initiation of DNA replication, Mcm2 is able to inhibit the Mcm4,6,7 helicase. Studies on murine Mcm2 indicate that its C terminus is required for interaction with MCM4, as well as for inhibition of the DNA helicase activity of the Mcm4,6,7 complex. The N-terminal region, which contains an H3-binding domain and a region required for nuclear localisation, is required for the phosphorylation by CDC7 kinase.
DNA replication licensing factor Mcm3 (Mcm3)
Type: Family

The MCM2-7 complex consists of six closely related proteins that are highly conserved throughout the eukaryotic kingdom. In eukaryotes, Mcm3 is a component of the MCM2-7 complex (MCM complex), which consists of six sequence-related AAA + type ATPases/helicases that form a hetero-hexameric ring . MCM2-7 complex is part of the pre-replication complex (pre-RC). In G1 phase, inactive MCM2-7 complex is loaded onto origins of DNA replication . During G1-S phase, MCM2-7 complex is activated to unwind the double stranded DNA and plays an important role in DNA replication forks elongation .

The components of the MCM2-7 complex are:

DNA replication licensing factor MCM2,

DNA replication licensing factor MCM3,

DNA replication licensing factor MCM4,

DNA replication licensing factor MCM5,

DNA replication licensing factor MCM6,

DNA replication licensing factor MCM7,
Mini-chromosome maintenance complex protein 4 (MCM_4)
Type: Family

The MCM2-7 complex consists of six closely related proteins that are highly conserved throughout the eukaryotic kingdom. In eukaryotes, Mcm3 is a component of the MCM2-7 complex (MCM complex), which consists of six sequence-related AAA + type ATPases/helicases that form a hetero-hexameric ring . MCM2-7 complex is part of the pre-replication complex (pre-RC). In G1 phase, inactive MCM2-7 complex is loaded onto origins of DNA replication . During G1-S phase, MCM2-7 complex is activated to unwind the double stranded DNA and plays an important role in DNA replication forks elongation .

The components of the MCM2-7 complex are:

DNA replication licensing factor MCM2,

DNA replication licensing factor MCM3,

DNA replication licensing factor MCM4,

DNA replication licensing factor MCM5,

DNA replication licensing factor MCM6,

DNA replication licensing factor MCM7,

Mcm4 is thought to play a pivotal role in ensuring DNA replication occurs only once per cell cycle. Phosphorylation of Mcm4 dramatically reduces its affinity for chromatin - it has been proposed that this cell cycle-dependent phosphorylation is the mechanism that inactivates the MCM complex from late S phase through mitosis, thus preventing illegitimate DNA replication during that period of the cell cycle .
DNA replication licensing factor Mcm5 (MCM5)
Type: Family

The MCM2-7 complex consists of six closely related proteins that are highly conserved throughout the eukaryotic kingdom. In eukaryotes, Mcm5 is a component of the MCM2-7 complex (MCM complex), which consists of six sequence-related AAA + type ATPases/helicases that form a hetero-hexameric ring . MCM2-7 complex is part of the pre-replication complex (pre-RC). In G1 phase, inactive MCM2-7 complex is loaded onto origins of DNA replication . During G1-S phase, MCM2-7 complex is activated to unwind the double stranded DNA and plays an important role in DNA replication forks elongation .

The components of the MCM2-7 complex are:

DNA replication licensing factor MCM2,

DNA replication licensing factor MCM3,

DNA replication licensing factor MCM4,

DNA replication licensing factor MCM5,

DNA replication licensing factor MCM6,

DNA replication licensing factor MCM7,
DNA replication licensing factor Mcm6 (MCM6)
Type: Family

In eukaryotes, Mcm6 is a component of the MCM2-7 complex (MCM complex), which consists of six sequence-related AAA + type ATPases/helicases that form a hetero-hexameric ring . MCM2-7 complex is part of the pre-replication complex (pre-RC). In G1 phase, inactive MCM2-7 complex is loaded onto origins of DNA replication . During G1-S phase, MCM2-7 complex is activated to unwind the double stranded DNA and plays an important role in DNA replication forks elongation .

The components of the MCM2-7 complex are:

DNA replication licensing factor MCM2,

DNA replication licensing factor MCM3,

DNA replication licensing factor MCM4,

DNA replication licensing factor MCM5,

DNA replication licensing factor MCM6,

DNA replication licensing factor MCM7,
DNA replication licensing factor Mcm7 (MCM7)
Type: Family

The MCM2-7 complex consists of six closely related proteins that are highly conserved throughout the eukaryotic kingdom. In eukaryotes, Mcm7 is a component of the MCM2-7 complex (MCM complex), which consists of six sequence-related AAA + type ATPases/helicases that form a hetero-hexameric ring . MCM2-7 complex is part of the pre-replication complex (pre-RC). In G1 phase, inactive MCM2-7 complex is loaded onto origins of DNA replication . During G1-S phase, MCM2-7 complex is activated to unwind the double stranded DNA and plays an important role in DNA replication forks elongation .

The components of the MCM2-7 complex are:

DNA replication licensing factor MCM2,

DNA replication licensing factor MCM3,

DNA replication licensing factor MCM4,

DNA replication licensing factor MCM5,

DNA replication licensing factor MCM6,

DNA replication licensing factor MCM7,

The human MCM7 gene has been localised to chromosome 7q21.3-q22.1. Increased expression of Mcm7 RNA and protein in MYCN-amplified neuroblastoma tumour and cell lines has been reported . Furthermore, The Mcm7 protein has been shown to form complexes with the retinoblastoma protein . These findings suggest Mcm7- directed DNA replication contributes to neoplastic transformation.
Voltage gated sodium channel, alpha-1 subunit (Na_channel_a1su)
Type: Family

Voltage-dependent sodium channels are transmembrane (TM) proteins responsible for the depolarising phase of the action potential in most
electrically excitable cells . They may exist in 3 states : the resting state, where the channel is closed; the activated state, where the channel is open; and the inactivated state, where the channel is closed and refractory to opening. Several different structurally and functionally distinct isoforms are found in mammals, coded for by a multigene family, these being responsible for the different types of sodium ion currents found in excitable tissues.

There are nine pore-forming alpha subunit of voltage-gated sodium channels consisting of four membrane-embedded homologous domains (I-IV), each consisting of six α-helical segments (S1-S6), three cytoplasmic loops connecting the domains, and a cytoplasmic C-terminal tail. The S6 segments of the four domains form the inner surface of the pore, while the S4 segments bear clusters of basic residues that constitute the channel's voltage sensors .

The SCN1A gene encodes the NaB1 channel and is particularly expressed in the brain, but is also found in a variety of other tissues, ranging from the retina to the olfactory bulb. Epilepsy, a disorder of neuronal hyperexcitability, has been associated with altered kinetics of SCN1A, as well as delayed inactivation of SCN2A .

This entry represents the alpha 1 subunits of the voltage-gated Na+ channel superfamily. For entries containing other members of this superfamily see

,

,

.
Voltage gated sodium channel, alpha-4 subunit, mammalian (Na_channel_a4su_mammal)
Type: Family

Voltage-dependent sodium channels are transmembrane (TM) proteins responsible for the depolarising phase of the action potential in most
electrically excitable cells . They may exist in 3 states : the resting state, where the channel is closed; the activated state, where the channel is open; and the inactivated state, where the channel is closed and refractory to opening. Several different structurally and functionally distinct isoforms are found in mammals, coded for by a multigene family, these being responsible for the different types of sodium ion currents found in excitable tissues.

There are nine pore-forming alpha subunit of voltage-gated sodium channels consisting of four membrane-embedded homologous domains (I-IV), each consisting of six α-helical segments (S1-S6), three cytoplasmic loops connecting the domains, and a cytoplasmic C-terminal tail. The S6 segments of the four domains form the inner surface of the pore, while the S4 segments bear clusters of basic residues that constitute the channel's voltage sensors .

This entry represents the voltage-gated sodium channel alpha-4 subunits (Nav1.4, also known as SCN4A) from mammals.Nav1.4 is expressed in skeletal muscle . Mutations in Nav1.4 gene cause several diseases in humans, such as Paramyotonia congenita of von Eulenburg (PMC), Myotonia SCN4A-related (MYOSCN4A) and Periodic paralysis hyperkalemic (HYPP) .
Voltage gated sodium channel, alpha-5 subunit (Na_channel_a5su)
Type: Family

Voltage-dependent sodium channels are transmembrane (TM) proteins responsible for the depolarising phase of the action potential in most
electrically excitable cells . They may exist in 3 states : the resting state, where the channel is closed; the activated state, where the channel is open; and the inactivated state, where the channel is closed and refractory to opening. Several different structurally and functionally distinct isoforms are found in mammals, coded for by a multigene family, these being responsible for the different types of sodium ion currents found in excitable tissues.

There are nine pore-forming alpha subunit of voltage-gated sodium channels consisting of four membrane-embedded homologous domains (I-IV), each consisting of six α-helical segments (S1-S6), three cytoplasmic loops connecting the domains, and a cytoplasmic C-terminal tail. The S6 segments of the four domains form the inner surface of the pore, while the S4 segments bear clusters of basic residues that constitute the channel's voltage sensors .

The SCN5A gene encodes the NaH1 channel and is expressed in cardiac muscle, foetal skeletal muscle and denervated adult skeletal muscle. Mutations in the SCN5A gene affect the function of NaH1 channels in the heart and are one of the three causes of Long QT syndrome, an inherited cardiac arrhythmia that can cause abrupt loss of consciousness, seizures and sudden death ; it is also associated with Brugada syndrome and conduction system disease .