SII-SWORD/CoKE huggingface dataset:
Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (Plno_GlcNAc_GPI2)
Type: Family

This entry represents the subunit C of the phosphatidylinositol N-acetylglucosaminyltransferase (PIG-C) and its yeast homologue, Gpi2. It catalyses the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, the first step of GPI biosynthesis. This step involves products of three or four genes in both yeast (GPI1, GPI2 and GPI3) and mammals (GPI1, PIG A, PIG H and PIG C), respectively .
Amine dehydrogenase heavy chain (Metamine_DH_Hvc)
Type: Family

This entry represents a group of bacterial amine dehydrogenase heavy chains. They include methylamine and arylamine dehydrogenase heavy chains , which form heterotetramers with their respective light chains, and catalyse the oxidative deamination of amines to their corresponding aldehydes.
Pneumovirus matrix 2-1 (Pneumovirus_M2-1)
Type: Family

This family includes several Pneumovirus matrix glycoprotein M2-1 sequences. Family members function as transcription processivity factors that are essential for virus replication .
IMP-specific 5-nucleotidase (ISN1)
Type: Family

The Saccharomyces cerevisiae ISN1 (YOR155c) gene encodes an IMP-specific 5'-nucleotidase, which catalyses degradation of IMP to inosine as part of the purine salvage pathway.
Lipid transport, open beta-sheet (Lipid_transpt_open_b-sht)
Type: Domain

This entry represents a conserved open β-sheet domain found in several lipid transport proteins, including vitellogenin and apolipoprotein B-100 .

Vitellinogen precursors provide the major egg yolk proteins that are a source of nutrients during early development of oviparous vertebrates and invertebrates. Vitellinogen precursors are multi-domain apolipoproteins that are cleaved into distinct yolk proteins. Different vitellinogen precursors exist, which are composed of variable combinations of yolk protein components; however, the cleavage sites are conserved. In vertebrates, a complete vitellinogen is composed of an N-terminal signal peptide for export, followed by four regions that can be cleaved into yolk proteins: heavy chain lipovitellin (lipovitellin-1), phosvitin, light chain lipovitellin (lipovitellin-2), and a von Willebrand factor type D domain (YGP40) . In vitellinogen, this domain is often found as part of the lipovitellin-1 peptide product.
ATP synthase YMF19, uncharacterised, C-terminal (YMF19)
Type: Domain

This domain represents the C-terminal region of YMF19 of the F0 complex of mitochondrial F-ATPases from plants . This domain is found C-terminal to the plant mitochondrial ATPase subunit 8 domain

.
Moricin family (Moricin_fam)
Type: Family

Moricin is a antibacterial peptide that is highly basic. The structure of moricin reveals that it is comprised of a long α-helix. The N terminus of the helix is amphipathic, and the C terminus of the helix is predominately hydrophobic. The amphipathic N-terminal segment of the α-helix is mainly responsible for the increase in permeability of the bacterial membrane which kills the bacteria .
THH1/TOM1/TOM3 domain (THH1/TOM1/TOM3_dom)
Type: Domain

This domain is found in plant proteins including THH1/TOM1/TOM3 from Arabidopsis. TOM1 and TOM3 are transmembrane proteins necessary for the efficient multiplication of tobamoviruses . THH1 supports tobamovirus multiplication, but to a lesser extent than TOM1 and TOM3 . Members containing this domain are part of the GPCR superfamily and involved in stress tolerance .
Ectatomin (Ectatomin)
Type: Family

Ectatomin is a toxin from the venom of the ant Ectatomma tuberculatum. Ectatomin can efficiently insert into the plasma membrane, where it can form channels. Ectatomin was shown to inhibit L-type calcium currents in isolated rat cardiac myocytes . In these cells, ectatomin induces a gradual, irreversible increase in ion leakage across the membrane, which can lead to cell death.

Ectatomin is comprised of two subunits, A and B, which are homologous. The structure of ectatomin reveals that each subunit consists of two α helices with a connecting hinge region, which form a hairpin structure that is stabilised by disulphide bridges. A disulphide bridge between the hinge regions of the two subunits links the heterodimer together, forming a closed bundle of four helices with a left-handed twist .
MucBP domain (MucBP_dom)
Type: Domain

The MucBP (MUCin-Binding Protein) domain is found in a wide variety of bacterial proteins, in several repeats. The domain is found in bacterial peptidoglycan bound proteins.
Ryanodine Receptor TM 4-6 (Ryanrecept_TM4-6)
Type: Domain

The release of Ca
2+
ions from intracellular stores is a key step in a wide variety of cellular functions. In striated muscle, the release of Ca
2+
from the sarcoplasmic reticulum (SR) leads to muscle contraction. Ca
2+
release occurs through large, high-conductance Ca
2+
release channels, also known as ryanodine receptors (RyRs) because they bind the plant alkaloid ryanodine with high affinity and specificity .

This region covers TM regions 4-6 of the ryanodine receptor 1 family.
Non-structural protein NSP16, coronavirus-like (NSP16_CoV-like)
Type: Domain

This domain covers the NSP16 region of the coronavirus polyprotein. It was originally named NSP13 and later changed to NSP16 to distinguish it from the helicase region . NSP16 is a 7-methylguanine-triphosphate-adenosine (m7GpppA)-specific, SAM-dependent 2'-O-MTase that has selective RNA binding properties and is a cap-0 binding protein. It contains a highly conserved catalytic tetrad (K-D-K-E) that is a hallmark of RNA 2'O-MTases . NSP16 plays a key role in viral replication as it is involved in immune response evasion through the 2'-O-methylation of coronavirus RNA, which is essential for preventing recognition by the host. It mimics the human protein CMTr1 and, unlike CMTr1, it requires NSP10 as a binding partner to activate its enzymatic activity . Structural analysis in NSP16 from SARS-CoV-2 identified a cryptic pocket (also present in other coronavirus such as SARS-CoV-1 and MERS) not present in human CMTr1, and the fact that NSP16 is one of the most conserved proteins of SARS-CoV-2 and related viruses, make it an interesting target for developing new antiviral treatment for COVID-19 and other diseases caused by coronaviruses .
CHD subfamily II, SANT-like domain (CHD_II_SANT-like)
Type: Domain

CHD proteins (name derived from the presence of a Chromodomain, SWI2/SNF2 ATPase/Helicase and a motif with sequence similarity to a DNA-binding domain) are ATP-dependent chromatin remodelers found in plant and animals. In eukaryotes, there are three subfamilies, I, II and III. This domain is found in members of subfamily II which play a role in repression of genes involved in developmental regulation, including Mi-2 from Drosophila melanogaster, CHD3/4/5 from animals and PICKLE (a CHD3/4-related protein) from Arabidopsis. Sequence analysis revealed that this domain has a considerable similarity to SANT domains suggesting that it fold into this type of domain and it is integral to the DNA binding domain of CHD remodelers in subfamily II .
Domain of unknown function DUF1087 (DUF1087)
Type: Domain

This domain is found in chromatin remodelling factors (CHDs) from subfamily II, including CHD3/4/5 from animals and PICKLE from Arabidopsis . The exact function is, as yet, unknown.
PCAF, N-terminal (PCAF_N)
Type: Domain

This region is spliced out of

isoform 2. It is predicted to be of a mixed α/β fold - though predominantly helical.
Spondin, N-terminal (Spondin_N)
Type: Domain

This conserved region is found in the N-terminal half of several Spondin proteins , also called FS domain. It is found in F-spondins (spondin-1), mindins (spondin-2). Its homology to a common Ca2+- and lipid-binding C2 domain suggests that the F-spondin FS domain is responsible for part of the membrane targeting of F-spondin in its regulation of axon development .

Spondins are multi-domain extracellular matrix (ECM) protein as well as contact-repellent molecules that directs axon outgrowth and cell migration during development. Spondins are involved in patterning axonal growth trajectory through either inhibiting or promoting adhesion of embryonic nerve cells .
Non-structural protein 14, coronavirus (NSP14_CoV)
Type: Domain

The unique coronavirus (CoV) transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. This entry represents NSP14, encoded as part of polyprotein pp1ab and excised by NSP5. Its N-terminal exoribonuclease (ExoN) domain plays a proofreading role for prevention of lethal mutagenesis, and the C-terminal domain functions as an S-adenosyl methionine (SAM)-dependent (guanine-N7) methyl transferase (N7-MTase) for mRNA capping . NSP14 forms the nsp14-nsp10 complex involved in RNA viral proofreading .
Putative glycolipid-binding protein (Glycolipid-bd_prot_put)
Type: Family

This family has a novel fold known as a spiral β-roll, consisting of a 15-stranded β sheet wrapped around a single α helix. It forms dimers. It has some structural similarity to the E. coli lipoprotein localisation factors LolA (

) and LolB (

). Its structure suggests that it may have a role in glycolipid binding. Its genomic context supports a role in glycolipid metabolism .
Protein of unknown function DUF1090 (DUF1090)
Type: Family

This family consists of several bacterial proteins of unknown function and is known as YqjC in Escherichia coli.
RNA-dependent RNA polymerase, N-terminal, coronavirus (RdRp_N_CoV)
Type: Domain

RNA-directed RNA Polymerase corresponds to the nonstructural protein 12 (NSP12) produced by cleavage of ORF1b. NSP12 contains a polymerase domain that assumes a structure resembling a cupped 'right hand', similar to other polymerases, containing a fingers domain, a palm domain and a thumb domain. Coronavirus (CoV) NSP12 also contains a nidovirus-unique N-terminal extension (nidovirus RdRp-associated nucleotidyltransferase (NiRAN)) that possesses a kinase-like fold allowing the binding of NSP12 to NSP7 and NSP8 which is followed by an interface domain (IF). NSP12 possesses some minimal activity on its own, but the addition of the NSP7 and NSP8 co-factors greatly stimulates polymerase activity .

This domain represents the N-terminal region of the coronavirus RNA-directed RNA Polymerase, which includes the NiRAN and interface domains . The function of the NiRAN domain is not clear and its target is yet unknown, but it has enzymatic activity that is essential for viral propagation. Structure from SARS-CoV-2 revealed that this domain binds ADP-Mg+2, which may constitute a new pocket for anti-viral treatment development .
Chitinase, C-terminal (Chi_C)
Type: Domain

This ~170 aa region is found at the C-terminal to the catalytic domain (

) found in members of glycoside hydrolase family 18.
Teneurin intracellular, N-terminal (Ten_N)
Type: Domain

This domain is found in the intracellular N-terminal region in Teneurin proteins.

Teneurins are a family of phylogenetically conserved transmembrane glycoproteins expressed during pattern formation and morphogenesis . Originally discovered as ten-m and ten-a in Drosophila melanogaster, the teneurin family is conserved from Caenorhabditis elegans (ten-1) to vertebrates, in which four paralogs exist (teneurin-1 to -4 or odz-1 to -4). Their distinct domain architecture is highly conserved between invertebrate and vertebrate teneurins, particularly in the extracellular part. The intracellular domains of Ten-a, Ten-m/Odz and C. elegans Ten-1 are significantly different, both in size and structure, from the comparable domains of vertebrate teneurins, but the extracellular domains of all of these proteins are remarkably similar.

The large C-terminal extracellular domain consists of eight EGF-like repeats (see

), a region of conserved cysteines and unique YD-repeats. The N-terminal intracellular domain of vertebrate teneurins contains two EF-hand-like calcium-binding motifs and two polyproline regions involved in protein-protein interactions, followed by a single-span transmembrane domain. The intracellular domain is linked to the cytoskeleton through its interaction with the adaptor protein CAP/ponsin and can be cleaved near (or possibly in) the transmembrane domain and transported to the nucleus , giving teneurins the potential to act as transcription factors

,

]. There is considerable divergence between intracellular domains of invertebrate and vertebrate teneurins as well as between different invertebrate proteins .

Teneurin proteins are involved in the development and function of the nervous system . They are ancient cell-cell adhesion receptors that play a vital role in establishing precise connectivity within the nervous system, including the formation of topographic projections, dendrite morphogenesis, and axon targeting . These proteins mediate both homophilic and heterophilic cell-cell adhesion, which is essential for synapse assembly and the formation of neural circuits. They also act as ligands for specific receptors, contributing to axon guidance and intracellular signal transduction. Additionally, certain members are implicated in gene transcription regulation, cytoskeleton reorganisation, and neuroplasticity. Teneurins may also contribute to the differentiation of specific cell types, and play roles in stress response and neuroprotection. Their functions are fundamental to neural development and the establishment of proper nervous system connectivity .
Tab2-like (Tab2-like)
Type: Family

Tab2 was first identified in Chlamydomonas reinhardtii as a RNA binding protein required for translation of the chloroplast PsaB photosystem I subunit . Later, the Tab2 homologue from Arabidopsis was found involved in the signalling pathway of light-controlled synthesis of photosystem proteins during early plant development, that probably functions as an activator of translation with targets at PSI and PSII . Proteins in this entry are from photosynthetic organisms including plants and cyanobacteria.
Orthopoxvirus A49 (Orthopox_A49)
Type: Family

This family consists of several Orthopoxvirus A49 proteins. The function of this family is unknown.
Bacilliredoxins BrxB/BrxA (BrxB/BrxA)
Type: Family

S-bacillithiolation is the formation of mixed disulfide bonds between protein thiols and the general thiol reductant bacillithiol (BSH) under oxidative stress. BSH is an equivalent of glutathione (GSH) in Firmicutes .

This protein family includes the bacilliredoxins BrxA and BrxB (previously known as YphP and YqiW, respectively) and uncharacterised proteins from bacteria. BrxA and BrxB debacillithiolate (remove BSH) the S-bacillithiolated OhrR (OhrR-SSB) and in vivo NaOCl-generated S-bacillithiolated MetE (MetE-SSB). Both proteins are involved in maintaining redox homeostasis in response to disulfide stress conditions . The crystal structure of BrxA shows similarity with a thioredoxin fold. It has a CXC motif that plays a key role in catalytic activity .
Protein of unknown function DUF1096 (DUF1096)
Type: Family

This family of unknown function consists of several proteins found in Caenorhabditis.
Protein of unknown function DUF1097 (DUF1097)
Type: Family

This family consists of several bacterial putative membrane proteins, including inner membrane protein YcdZ (

) from Salmonella typhimurium.
Baculovirus Ac102 (Baculo_Ac102)
Type: Family

This family of baculovirus proteins is represented by Autographa californica nuclear polyhedrosis virus (AcMNPV) Ac102. Nuclear actin is critical for AcMNPV progeny production, and Ac102 plays an essential role in actin translocation to the nucleus . It plays a role in regulating nuclear actin polymerization as well as the morphogenesis and spatial distribution of viral capsid structures in the host nucleus .
Human herpesvirus U55 (Herpes_U55)
Type: Family

This family consists of several human herpesvirus U55 proteins. The function of this family is unknown.
Equine infectious anaemia virus S2 (Equine_IAV_S2)
Type: Family

This family consists of several equine infectious anaemia virus S2 proteins. The function of this family is unknown.
Protein of unknown function DUF1102 (DUF1102)
Type: Family

This family consists of proteins of unknown function.
Type III secretion systems tip complex component IpaD/BipD/SipD (IpaD/BipD/SipD)
Type: Family

This family consists of several invasion plasmid antigen IpaD proteins found in Shigella as well as homologues such as SipD from Salmonella and BipD from Burkholderia . Gram-negative bacteria use type III secretion systems (T3SSs) as protein transport devices for injecting virulence effector proteins into eukaryotic cells during infection. T3SSs consist of a needle complex (NC) and a tip complex (TC). In Shigella the TC is composed of two proteins, each essential to host cell sensing: IpaD and IpaB. IpaD is hydrophilic and required for tip recruitment of the hydrophobic proteins IpaB and IpaC, which later form the pore in host cell membranes .
Protein of unknown function DUF1103 (DUF1103)
Type: Repeat

This family consists of several repeats of around 30 residues in length which are found specifically in mature-parasite-infected erythrocyte surface antigen proteins from Plasmodium falciparum. This family often found in conjunction with

.
Borna disease virus P10 (BDV_P10)
Type: Family

This family consists of several Borna disease virus P10 (or X) proteins. Borna disease virus (BDV) is unique among the non-segmented negative-strand RNA viruses of animals and man because it transcribes and replicates its genome in the nucleus of the infected cell. It has been suggested that the p10 protein plays a role in viral RNA synthesis or ribonucleoprotein transport .
Purine nucleoside permease (Pur_nuclsid_perm)
Type: Family

This family consists of several purine nucleoside permease from both bacteria and fungi . They are nucleoside permeases that transports adenosine and guanosine and does not show any transport activities towards cytidine, adenine, guanine, uridine, and uracil
Orthopoxvirus A43R (Orthopox_A43R)
Type: Family

This family consists of several Orthopoxvirus A43R proteins. The function of this family is unknown.
Protein of unknown function DUF1104 (DUF1104)
Type: Family

This family consists of several hypothetical proteins of unknown function which appear to be found mainly in Helicobacter pylori. The structure of HP0721 protein consists of a bundle of four α-helices connected by loops and stabilised by hydrophobic interactions. It has been suggested that this protein might represent a novel H. pylori .
PAR1 (PAR1)
Type: Family

This family consists of several plant specific PAR1 proteins from Nicotiana tabacum (Common tobacco) and Arabidopsis thaliana (Mouse-ear cress). The function of this family is unknown.
Protein of unknown function DUF1106 (DUF1106)
Type: Family

This family consists of several hypothetical bacterial proteins found in Enterobacterales. The function of this family is unknown.
Protein of unknown function DUF1107 (DUF1107)
Type: Family

This family consists of several short, hypothetical bacterial proteins of unknown function.
TniQ (TniQ)
Type: Family

This entry consists of several bacterial TniQ proteins. TniQ along with TniA and B is involved in the transposition of the mercury-resistance transposon Tn5053 that carries the mer operon. It has been suggested that the tni genes are involved in the dissemination of integrons . This entry also includes TnsD from E. coli. TnsD is required for Tn7 transposition .
Escherichia phage P2, Tail assembly protein E' (P2_GpE')
Type: Family

This family represents Tail assembly protein E' from Escherichia phage P2 and closely related proteins from Proteobacteria and tailed bacteriophages. GpE' essential for the lytic growth of P2 virus .
Protein of unknown function DUF1108 (DUF1108)
Type: Family

This entry includes Bacteriophage 92, Orf49. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

This family consists of several bacterial proteins from Staphylococcus aureus as well as a number of phage proteins. The function of this family is unknown.
Anti-sigma-F factor NrsF (NrsF)
Type: Family

This entry includes anti-sigma-F factor NrsF from
Caulobacter crescentus
, which is thought to be an anti-sigma factor for sigma F.
Caulobacter crescentus
survives where nutrients are low and where the concentration of heavy metals are high, and it is able to do so by altering the expression of a large number of genes. Sigma factor F is involved in the control of the transcriptional response to chromium and cadmium, controlling at least eight genes, all of which are in the sigma F regulon. NrsF is also in this regulon, and is released into the cytoplasm during chromium stress. Substitution of two conserved cysteines abrogate the ability of NrsF to maintain the expression of sigma F-dependent genes at basal levels .
Repulsive guidance molecule, C-terminal (RGM_C)
Type: Domain

This entry represents the C-terminal domain of repulsive guidance molecule (RGM) mainly found in animals. This domain is responsible for neogenin (NEO1) binding . This domain contains a β-sandwich structure. In some proteins, this domain encompasses the entire protein.

RGM is a GPI-linked axon guidance molecule of the retinotectal system, and controls cell motility, adhesion, immune cell regulation and systemic iron metabolism . RGM is repulsive for a subset of axons, those from the temporal half of the retina. Temporal retinal axons invade the anterior optic tectum in a superficial layer, and encounter RGM expressed in a gradient with increasing concentration along the anterior-posterior axis. Temporal axons can receive posterior-dependent information by sensing gradients or concentrations of guidance cues. Thus, RGM will likely provide positional information for temporal axons invading the optic tectum in the stratum opticum .
Regulator protein, PHA-1 (Regulator_protein_PHA-1)
Type: Family

This family represents the protein product of the gene pha-1 which coordinates with lin-35 Rb during animal development. The protein is expressed during embryonic development and functions in the cytoplasm. PHA-1 acts in a parallel pathway with UBC-18 to regulate the activity of a common cellular target .
Bacteriophage 4268, Orf1, C-terminal (Phage_4268_Orf1_C)
Type: Domain

This entry represents the C terminus of various Lactococcus bacteriophage repressor proteins.
Oxamate carbamoyltransferase subunit AllG-like (AllG-like)
Type: Family

This entry, previously known ad DUF1116, represents Oxamate carbamoyltransferase subunit AllG and related bacterial proteins. AllG is a component of a carbamoyltransferase involved in the anaerobic nitrogen utilisation via the assimilation of allantoin . It is catalyses the conversion of oxalurate (N-carbamoyl-2-oxoglycine) to oxamate and carbamoyl phosphate.
Protein of unknown function DUF1118 (DUF1118)
Type: Family

This family consists of several hypothetical plant proteins of unknown function.
Uncharacterised conserved protein UCP020269 (UCP020269)
Type: Family

This family consists of several hypothetical proteins from bacteria and from Dictyostelium discoideum (Slime mold). The function of this family is unknown.
Secretion monitor (SecM)
Type: Family

This family consists of several bacterial Secretion monitor precursor (SecM) proteins. SecM is known to regulate SecA expression by translational coupling of the secM secA operon. Translational pausing at a specific Pro residue 5 residues before the end of the protein may allow disruption of a mRNA repressor helix that normally suppresses secA translation initiation. The eubacterial protein secretion machinery consists of a number of soluble and membrane associated components. One critical element is SecA ATPase, which acts as a molecular motor to promote protein secretion at translocation sites that consist of SecYE, the SecA receptor, and SecG and SecDFyajC proteins, which regulate SecA membrane cycling .
Protein of unknown function DUF1125 (DUF1125)
Type: Family

This family consists of several short proteins from Lactococcus species and bacteriophages. The function of this family is unknown.