SII-SWORD/CoKE huggingface dataset:
CXC chemokine receptor 4 N-terminal domain (Chemokine_CXCR4_N_dom)
Type: Domain

This entry represents the N-terminal region of the CXC type 4 chemokine receptor. CXCR4 and its ligand stromal cell-derived factor-1 (also known as CXCL12) are essential for proper fetal development. CXCR4 is also the major coreceptor for T-tropic strains of Human immunodeficiency virus 1, and SDF-1 inhibits HIV-1 infection. Additionally, SDF-1 and CXCR4 mediate cancer cell migration and metastasis. The N-terminal domain of most chemokine receptors is the ligand binding domain and so the N-terminal domain of CXCR4 is the binding site for SDF-1 .

The CXC chemokine receptors are a subfamily of chemokine receptors that specifically bind and respond to cytokines of the CXC chemokine family. There are currently seven known CXC chemokine receptors in mammals, CXCR1 through to CXCR7.

Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role . They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system , and endothelial cells, where they may act as either angiogenic or angiostatic factors .

The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).

Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors . Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells . Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).
Pupal cuticle protein C1 (Cuticle_C1)
Type: Family

Insect cuticles are composite structures whose mechanical properties are optimised for biological function. The major components are the chitin filament system and the cuticular proteins, and the cuticle's properties are determined largely by the interactions between these two sets of molecules. The proteins can be ordered by species.
Period circadian-like, C-terminal (Period_circadian-like_C)
Type: Domain

This domain is found in the family of Period circadian protein homologues (PER1, PER2, PER3) found in vertebrates. Sequences represented by this entry are found C-terminal to

.

PER proteins (PER 1-3) are transcriptional repressors which form the core component of the circadian clock. They play a critical role in rhythm generation, whereas delays imposed by post-translational modifications are important for determining the period of the rhythms. The core clock genes: PER1/2/3 and CRY1/2 form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression .
DAZ associated protein 2 (DAZ_assoc-2)
Type: Family

DAZ associated protein 2 has a highly conserved sequence throughout evolution including a conserved polyproline region and several SH2/SH3 binding sites. It occurs as a single copy gene with a four-exon organisation and is located on chromosome 12. It encodes a ubiquitously expressed protein and binds to DAZ and DAZL1 through DAZ repeats .
Dermaseptin domain (Dermaseptin_dom)
Type: Domain

This entry represents the dermaseptin domain found in dermaseptin precursor polypeptides and similar proteins from tree frogs.

Dermaseptin proteins are used in eukaryotes as an antimicrobial agent. Dermaseptins are typically between 30 to 76 amino acids in length. This domain is found associated with a propeptide (

). The full-length protein is almost completely defined in an α helical domain. It creates high levels of disorder at the level of the phospholipid head group of bacterial membranes suggesting that it partitions into the bilayer where it severely disrupts membrane packing.
Peptidase S54, GlpG peptidase, N-terminal (Peptidase_S54_GlpG_N)
Type: Domain

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes . They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence . Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases .

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base . The geometric orientations of the catalytic residues are similar between families, despite different protein folds . The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) .

This entry represents the N-terminal domain of membrane-bound serine endopeptidases belonging to MEROPS peptidase family S54 (rhomboid-1, clan ST). This domain contains a conserved ASW sequence motif and a single completely conserved residue F that may be functionally important.
DPUP/SUD, C-terminal, betacoronavirus (DPUP_SUD_C_bCoV)
Type: Domain

This domain is found in betacoronavirus non-structural protein NSP3, and is about 65 amino acids in length. It was originally thought to exist only in SARS-coronaviruses, and so was termed the SARS-unique domain (SUD), however this has since been shown to be incorrect. The domain is also known as DPUP (domain preceding Ubl2 and PL2pro).

NSP3 is the product of ORF1a and proteolytically released from the pp1a/1ab polyprotein . The SUD domain has three globular domains, SUD-N (N-terminal), SUD-M (middle region of SUD), and SUD-C (C-terminal). SUD-C adopts a fold consisting of seven β-strands arranged in an anti-parallel β-sheet, and two α-helices which are packed against the same side of the β-sheet. It adopts a frataxin like fold with structural similarities to DNA-binding domains. It has been shown that SUD-C binds to single-stranded RNA and recognises purine bases more strongly than pyrimidine bases, but these interactions are stabilised in the presence of SUD-M. The function of this domain is not clear but studies of structural homologues of SUD-C suggest that it could be related to metal, adenylate and nucleic acid binding .
Apolipoprotein M (ApoM)
Type: Family

ApoM is a 25kDa plasma protein associated with high-density lipoproteins (HDLs). ApoM is important in the formation of pre-ss-HDL and also in increasing cholesterol efflux from macrophage foam cells . Lipoproteins consist of lipids solubilized by apolipoproteins. ApoM lacks an external amphipathic motif and is uniquely secreted to plasma without cleavage of its terminal signal peptide .
bMERB domain (bMERB_dom)
Type: Domain

A variety of different effector proteins interact specifically with GTP-bound Rab proteins and mediate their versatile roles in membrane trafficking, including budding of vesicles from a donor membrane, directed transport through the cell and finally tethering and fusion with a target membrane. The "bivalent Mical/EHBP Rab binding" (bMERB) domain is a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. The bMERB domain displays a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and at least some of the bMERB domains contain two separate binding sites for Rab-proteins, allowing Micals and EHBPs to bind two Rabs simultaneously. The strong similarity between the two binding sites within one bMRB domain strongly suggests an evolutionarily development via duplication of a common ancestor supersecondary structure element .

The bMERB domain has a completely α-helical fold consisting of a central helix and N- and C-terminal helices folding back on this central helix .
Non-structural protein NS6, betacoronavirus (NS6_bCoV)
Type: Family

This entry represents the non-structural protein NS6 (also known as ORF6, accessory protein 6, or X3 protein), which is highly conserved among SARS-related coronaviruses (this is distinct from NSP6 which is encoded on the replicase polyprotein). NS6 is located in the endoplasmic reticulum . It has been reported that NS6 can increase the cellular gene synthesis and it can also induce apoptosis through Jun N-terminal kinase and Caspase-3 mediated stress. This protein can modulate host antiviral responses by inhibiting synthesis and signalling of interferon-beta (IFN-beta) via two complementary pathways. One involves NS6 interaction with host N-Myc (and STAT) interactor (Nmi) protein inducing its degradation via ubiquitin proteasome pathway, suppressing Nmi enhanced IFN signalling. The other pathway suppresses the translocation of signal transducer and activator of transcription 1 (STAT1) and downstream IFN signalling .

This protein interacts with Rae1 and Nup98 to prevent both nuclear import and export, which renders host cells incapable of responding to SARS-CoV-2 infection .
RNA polymerase recycling, bacterial, C-terminal (RapA_C)
Type: Domain

This domain is found in bacteria. This domain is about 360 amino acids in length. This domain is found associated with

,

. The function of this domain is not known, but structurally it forms an α-β fold in nature with a central β-sheet flanked by helices and loops, the β-sheet being mainly antiparallel and flanked by four α helices, among which the two longer helices exhibit a coiled-coil arrangement.
Adenylylsulphate reductase, beta subunit, C-terminal (AprB_C)
Type: Domain

During dissimilatory sulphate reduction and sulphur oxidation, adenylylsulphate (APS) reductase catalyzes reversibly the two-electron reduction of APS to sulphite and AMP. Found in several bacterial lineages and in Archaeoglobales, APS reductase is a heterodimer composed of an alpha subunit containing a noncovalently bound FAD, and a beta subunit containing two [4Fe-4S] clusters. This entry describes the C-terminal domain of the beta subunit of APS reductase.
Polyphenol oxidase, central domain (Polyphenol_oxidase_cen)
Type: Domain

This domain is found in bacteria and eukaryotes and is approximately 50 amino acids in length. It is found in association with

and

. Most members are annotated as being polyphenol oxidases, and many are from plants or plastids. There is a conserved DWL sequence motif.
Polyphenol oxidase, C-terminal (Polyphenol_oxidase_C)
Type: Domain

This domain represents the C terminus of polyphenol oxidases. This region is primarily found in eukaryotes, although a few bacterial members also exist. It is typically between 138 and 152 amino acids in length and the family is found in association with

and

. Many members are plant or plastid polyphenol oxidases, and there is a highly conserved KFDV sequence motif.
Bacteriophage B103, Gp8, head fibre (Phage_B103_Gp8)
Type: Family

This entry is represented by Bacteriophage B103, Gp8. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.

Gp8 (Gene locus 8.5 in contig X99260_GR) is a structural head protein in phage and is dispensable.
Serine aminopeptidase, S33 (Hydrolase_4)
Type: Domain

This domain is found in bacteria and eukaryotes and is approximately 110 amino acids in length. The majority of the members in this entry carry the exopeptidase active-site residues of Ser-122, Asp-239 and His-269 as in

.
Methyltransferase domain, putative (MeTrfase_dom_put)
Type: Domain

This domain is predominantly found in bacterial proteins and is approximately 110 amino acids in length. It shows some similarity to methyltransferase domains.
Eukaryotic translation initiation factor 4G1, eIF4E-binding domain (eIF4G1_eIF4E-bd)
Type: Domain

The eukaryotic initiation factor 4G (eIF4G) is the core of a multicomponent switch controlling gene expression at the level of translation initiation. It interacts with the small ribosomal subunit interacting protein, eIF3, and the eIF4E/cap-mRNA complex in order to load the ribosome onto mRNA during cap-dependent translation.

This entry represents the eIF4E-binding domain superfamily of eIF4G . Binding of this domain to its substrate triggers a coupled folding transition where it forms a right-handed helical ring that wraps around the N terminus of eIF4E.
Cathelicidin, antimicrobial peptide, C-terminal (Cathlecidin_C)
Type: Domain

This entry represents the cathlecidin antimicrobial C-terminal peptides. The C terminus is cleaved from the cathlecidin precursor, and is approximately 30 amino acids in length with a helical structure. This entry is found in association with

. The C terminus peptides possess antimicrobial activity by virtue of their binding to bacterial lipopolysaccharides .
Salmonella outer protein D (SopD)
Type: Family

The proteins in this entry are also known as secreted effector proteins. Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. They contribute to the formation of Salmonella-induced filaments (Sifs) in infected epithelial cells and to replication in macrophages .

SopD is a type III virulence effector protein whose structure consists of 38% α-helix and 26% β-strand .
NADH dehydrogenase subunit 2, N-terminal (NADH_DH_su2_N)
Type: Domain

This domain is found in eukaryotes, and is approximately 90 amino acids in length. It is found N-terminal to

. All members are annotated as being NADH dehydrogenase subunit 2.
N6 adenine-specific DNA methyltransferase, N-terminal domain (D12N6_MeTrfase_N)
Type: Domain

This domain is found at the N-terminal of the methylase subunit of Type I DNA methyltransferases. This domain is found in bacteria and archaea, and is typically between 123 and 138 amino acids in length. It is found in association with

. Mutations in this region of EcoKI methyltransferase

abolish the normally strong preference of this system for methylating hemimethylated substrate . The structure of this domain has been shown to be all α-helical.
Interferon regulatory factor 2-binding protein 1/2-like, zinc finger (IRF-2BP1_2-like_Znf)
Type: Domain

Interferon regulatory factor 2-binding protein 1 and 2 (IRF-2BP1/2) and their homologue IRF-2BP-like (also known as IRF-2BPL or C14orf4) (

) are nuclear transcriptional repressor proteins that bind to the C-terminal repression domain of IRF-2 and can inhibit both enhancer-activated and basal transcription. They contain N-terminal zinc finger and C-terminal RING finger domains . Mutations in IRF2BP2 are responsible for a Familial Form of Common Variable Immunodeficiency Disorder (CVID), one of the most frequently diagnosed forms of primary immunodeficiency characterised by low quantity of IgG and IgA and poor specific antibody production . IRF2BPL may play a role in the development of the central nervous system and in neuronal maintenance .

This entry represents the N-terminal zinc finger domain of IRF-2BP1 and IRF-2BP2.
Alpha-mannosyltransferase (Alpha_mannosyltransferase)
Type: Family

Alpha-mannosyltransferase is responsible for the addition of residues to the outer chain of core N-linked polysaccharides and to O-linked mannotriose. It is implicated in late Golgi modifications . The proteins matching this entry are conserved in fungi and also found in some phototrophic organisms.
Signal transducer and activation of transcription 1, TAZ2 binding domain, C-terminal (STAT1_TAZ2-bd_C)
Type: Domain

This entry represents the C-terminal domain of STAT1, which selectively binds the TAZ2 domain of CRB (CREB-binding protein) . This group of eukaryotic proteins is approximately 20 amino acids in length, and is found in association with

,

,

,

. By binding to CRB, it becomes a transcriptional activator and can initiate transcription of certain genes.
Type IV pilus biogenesis PilP (T4SS_pilus_biogen_PilP)
Type: Family

Type IV pili are required for auto-agglutination, twitching motility, biofilm formation, adherence and DNA uptake during transformation . PilP is an inner membrane protein, required for pilus expression and transformation . PilP interacts with PilQ which suggests that the two proteins may have coordinated activity in functions such as pilus extrusion/retraction .
DNA polymerase III, gamma subunit, domain III (DNA_pol_III_gamma-3)
Type: Domain

This domain is found in bacteria and eukaryotes, and is approximately 110 amino acids in length. It is found in association with

. This domain is also present in the tau subunit before it undergoes cleavage. Domains I-III are shared between the tau and the gamma subunits, while most of the DnaB-binding Domain IV and all of the alpha-interacting Domain V are unique to tau.
Zinc finger, double-stranded RNA binding (Znf_C2H2_jaz)
Type: Domain

This zinc finger is mainly found in eukaryotic sequences, and is approximately 30 amino acids in length. The mammalian members of this group occur multiple times along the protein, joined by flexible linkers, and are referred to as JAZ - dsRNA-binding ZF protein - zinc-fingers. The JAZ proteins are expressed in all tissues tested and localise in the nucleus, particularly the nucleolus . JAZ preferentially binds to double-stranded (ds) RNA or RNA/DNA hybrids rather than DNA. In addition to binding double-stranded RNA, these zinc-fingers are required for nucleolar localisation.
Signal transducer and activation of transcription 2, C-terminal (STAT2_C)
Type: Domain

This region is found in the mammalian signal transducer and activation of transcription (STAT) 2 protein, and is approximately 60 amino acids in length. The family is found in association with

,

,

,

. There is a conserved DLP sequence motif. STATs are involved in transcriptional regulation and are the only regulators known to be modulated by tyrosine phosphorylation. STAT2 forms a trimeric complex with STAT1 and IRF-9 (Interferon Regulatory Factor 9), on activation of the cell by interferon, which is called ISGF3 (Interferon-stimulated gene factor 3). The C-terminal domain of STAT2 contains a nuclear export signal (NES) which allows export of STAT2 into the cytoplasm along with any complexed molecules.
Glucose signalling factor 2 (Gsf2)
Type: Family

This entry represents fungal Glucose singalling factor 2. Gsf2 is localised to the ER and functions to promote the secretion of certain hexose transporters .
ATP-dependent helicase Sgs1 (Helicase_Sgs1)
Type: Domain

This entry represents a domain found in the fungal Sgs1 protein.
Antirestriction protein Ral (Antirestriction_protein_Ral)
Type: Family

Ral alleviates restriction and enhances modification by the E.coli restriction and modification system .
Fumarate lyase, N-terminal (Fumarate_lyase_N)
Type: Domain

A number of enzymes, belonging to the lyase class, for which fumarate is a substrate, have been shown to share a short conserved sequence around a methionine which is probably involved in the catalytic activity of this type of enzymes . This entry represents the N-terminal region of fumarate lyase family.
Peptidase S54, rhomboid domain (Peptidase_S54_rhomboid_dom)
Type: Domain

This entry represents a six transmembrane helix rhomboid domain.

This domain is found in serine peptidases belonging to the MEROPS peptidase family S54 (Rhomboid, clan ST). They are integral membrane proteins related to the Drosophila melanogaster (Fruit fly) rhomboid protein

. Members of this family are found in archaea, bacteria and eukaryotes.

The rhomboid protease cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine. The active site is embedded within the membrane and the active site residues are on different transmembrane regions. From the tertiary structure of the Escherichia coli homologue GlpG it was shown that hydrolysis occurs in a fluid filled cavity within the membrane. Initially, a catalytic triad including a highly conserved asparagine had been proposed, but this residue has been shown not to be essential . Drosophila rhomboid cleaves the transmembrane proteins Spitz, Gurken and Keren within their transmembrane domains to release a soluble TGFalpha-like growth factor. Cleavage occurs in the Golgi, following translocation of the substrates from the endoplasmic reticulum membrane by Star, another transmembrane protein. The growth factors are then able to activate the epidermal growth factor receptor .

Few substrates of mammalian rhomboid homologues have been determined, but rhomboid-like protein 2 has been shown to cleave ephrin B3 . Parasite-encoded rhomboid enzymes are also important for invasion of host cells by Toxoplasma and the malaria parasite. Invasion of host cells first requires their recognition and this is achieved by parasite transmembrane adhesins interacting with host cell receptors. Before the parasite can enter a host cell the adhesins must be released by cleavage. In Toxoplasma rhomboid TgROM5 cleaves the adhesins, and in Plasmodium, which lacks a TgROM5 orthologue, PfROMs 1 and 4 cleave the diverse array of malaria parasite adhesins .

This entry also includes catalytically inactive rhomboid protease homologues, iRhom1/2, which are metazoan-specific and play crucial roles within the secretory pathway, including protein degradation, trafficking regulation, and inflammatory signaling . They regulate ADAM17 protease, acting as trafficking factors that escort ADAM17 from the ER to the later secretory pathway. They are required for the cleavage and release of a variety of membrane-associated proteins . iRhombs have been linked to the development and progression of several autoimmune diseases including rheumatoid arthritis, lupus nephritis, as well as hemophilic arthropathy and also in neurological disorders such as Alzheimer's and Parkinson's diseases, inflammation, cancer and skin diseases .
Dna2/Cas4, domain of unknown function DUF83 (Dna2/Cas4_DUF83)
Type: Domain

This entry represents an uncharacterised domain found in several proteins, including DNA replication helicase Dna2, clustered regularly interspaced short palindromic repeats (CRISPR)-associated exonuclease Cas4 and putative RecB family exonuclease proteins.

Dna2 is a DNA replication factor with single-stranded DNA-dependent ATPase, ATP-dependent nuclease, (5'-flap endonuclease) and helicase activities. Cas4 has been shown to be a 5' to 3' single stranded DNA exonuclease in Sulfolobus solfataricus .