SII-SWORD/CoKE huggingface dataset:
ATP-binding cassette transporter, PDR-like subfamily G, domain 1 (ABCG_PDR_1)
Type: Domain

This entry represents the first domain of the pleiotropic drug resistance-like subfamily G of ATP-binding cassette (ABC) transporters.

Pleiotropic drug resistance (PDR) is a well-described phenomenon occurring in fungi and shares several similarities with processes in bacteria and higher eukaryotes . This PDR subfamily represents domain I of its (ABC-IM)2 organization. ABC transporters are a large family of proteins involved in the transport of a wide variety of different compounds including sugars, ions, peptides, and more complex organic molecules . The nucleotide binding domain shows the highest similarity between all members of the family . ABC transporters are a subset of nucleotide hydrolases that contain a signature motif, Q-loop, and H-loop/switch region, in addition to, the Walker A motif/P-loop and Walker B motif commonly found in a number of ATP- and GTP-binding and hydrolyzing proteins .
Tumour necrosis factor receptor 8, N-terminal (TNFRSF8_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 8 (TNFRSF8), also known as CD30, Ki-1 or D1S166E, is expressed by activated T and B cells. It transduces signals that lead to the activation of NF-kappaB, mediated by the adaptor proteins TRAF2 and TRAF5 . This receptor has been shown to limit the proliferative potential of auto-reactive CD8 effector T cells and protect the body against autoimmunity . Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. CD30 is expressed in malignant Hodgkin and Reed-Sternberg cells on the surface of extracellular vesicles, facilitating CD30-CD30L interaction between cell types . This receptor is also associated with anaplastic large cell lymphoma. It is expressed in embryonal carcinoma, but not in seminoma, making it a useful marker in distinguishing between these germ cell tumors . Since CD30 has restricted expression in normal tissues, it is an optimal target for selectively eliminating CD30-expressing neoplastic cells by specific toxin-conjugated monoclonal antibodies (mAbs) .

This entry represents the N-terminal domain of TNFRSF8. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family .
ATP-binding cassette transporter, PDR-like subfamily G, domain 2 (ABCG_PDR_2)
Type: Domain

This entry represents the second domain of the pleiotropic drug resistance-like subfamily G of ATP-binding cassette (ABC) transporters.

Pleiotropic drug resistance (PDR) is a well-described phenomenon occurring in fungi and shares several similarities with processes in bacteria and higher eukaryotes . This PDR subfamily represents domain II of its (ABC-IM)2 organization. ABC transporters are a large family of proteins involved in the transport of a wide variety of different compounds including sugars, ions, peptides, and more complex organic molecules . The nucleotide binding domain shows the highest similarity between all members of the family . ABC transporters are a subset of nucleotide hydrolases that contain a signature motif, Q-loop, and H-loop/switch region, in addition to, the Walker A motif/P-loop and Walker B motif commonly found in a number of ATP- and GTP-binding and hydrolyzing proteins .
Pol I subunit A12, C-terminal zinc ribbon (Zn_ribbon_RPA12_C)
Type: Domain

The C-terminal zinc ribbon domain of subunit A12 in RNA polymerase (Pol) I (RPA12) is involved in intrinsic transcript cleavage . Eukaryote genomes are transcribed by three nuclear RNA polymerases (Pol I, II and III) that share some subunits. RPA12 in Pol I, RPB9 in Pol II, RPC11 in Pol III and TFS in archaea are distantly related to each other and to the TFIIS elongation factor of Pol II . RPA12 has two zinc-binding domains separated by a flexible linker .
Peptidyl-dipeptidase DCP (M3A_DCP)
Type: Family

This entry includes the following members of peptidase subfamily M3A: peptidyl dipeptidase DCP (EC 3.4.15.5; MEROPS identifier M03.005; also known as dipeptidyl carboxypeptidase) and oligopeptidase A (OpdA; EC 3.4.24.70; MEROPS identifier M03.004). DCP releases dipeptides from the C-termini of various peptides and proteins, the smallest substrate being N-blocked tripeptides and unblocked tetrapeptides. DCP from E. coli is inhibited by the anti-hypertensive drug captopril, an inhibitor of the mammalian angiotensin converting enzyme (ACE, also called peptidyl dipeptidase A) . Oligopeptidase A (OpdA) may play a specific role in the degradation of signal peptides after they are released from precursor forms of secreted proteins. It can also cleave N-acetyl-L-Ala .
Oligopeptidase F type 2 (M3B_PepF_2)
Type: Family

Oligopeptidase F (PepF; Pz-peptidase B; MEROPS identifier M03.010) is mostly bacterial and includes oligoendopeptidase F from Lactococcus lactis. This enzyme hydrolyzes peptides containing between 7 and 17 amino acids with fairly broad specificity. The PepF gene is duplicated in L. lactis on the plasmid that bears it, while a shortened second copy is found in Bacillus subtilis. Most bacterial PepFs are cytoplasmic endopeptidases; however, the PepF Bacillus amyloliquefaciens oligopeptidase is a secreted protein and may facilitate the process of sporulation . Specifically, the yjbG gene encoding the homologue of the PepF1 and PepF2 oligoendopeptidases of Lactococcus lactis has been identified in Bacillus subtilis as an inhibitor of sporulation initiation when over expressed from a multicopy plasmid .
C-type lectin-like domain, bacterial (CTLD_bac)
Type: Domain

This is a bacterial subgroup of the C-type lectin-like (CTLD) domain, a subgroup of bacterial protein domains homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Many CTLDs are calcium-dependent carbohydrate-binding modules; other CTLDs bind protein ligands, lipids, and inorganic surfaces, including CaCO3 and ice. Bacterial CTLDs within this group are functionally uncharacterised. Animal C-type lectins are involved in such functions as extracellular matrix organisation, endocytosis, complement activation, pathogen recognition, and cell-cell interactions. CTLDs may bind a variety of carbohydrate ligands, including mannose, N-acetylglucosamine, galactose, N-acetylgalactosamine, and fucose. CTLDs associate with each other through several different surfaces to form dimers, trimers, or tetramers from which ligand-binding sites project in different orientations. In some CTLDs a loop extends to the adjoining domain to form a loop-swapped dimer .
TC14-like, C-type lectin-like domain (TC14-like_CTLD)
Type: Domain

This entry represents a C-type lectin-like domain (CTLD) of the type found in lectins TC14, TC14-2, TC14-3, and TC14-4 from the budding tunicate Polyandrocarpa misakiensis and PfG6 from the Acorn worm. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. TC14 is homodimeric. The CTLD of TC14 binds D-galactose and D-fucose . TC14 is expressed constitutively by multipotent epithelial and mesenchymal cells and plays in role during budding, in inducing the aggregation of undifferentiated mesenchymal cells to give rise to epithelial forming tissue . TC14-2 and TC14-3 shows calcium-dependent galactose binding activity. TC14-3 is a cytostatic factor which blocks cell growth and dedifferentiation of the atrial epithelium during asexual reproduction . It may also act as a differentiation inducing factor. Galactose inhibits the cytostatic activity of TC14-3 . The gene for Acorn worm PfG6 is gill-specific; PfG6 may be a secreted protein .
Oligopeptidase F type 4 (M3B_PepF_4)
Type: Family

This is a cluster of sequences from uncharacterised proteins that are most closely related to oligopeptidase F.
DGCR2-like, C-type lectin-like domain (DGCR2-like_CTLD)
Type: Domain

This C-type lectin-like domain (CTLD) is found in DGCR2, an integral membrane protein deleted in DiGeorge Syndrome (DGS). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. DGS is also known velo-cardio-facial syndrome (VCFS). DGS is a genetic abnormality that results in malformations of the heart, face, and limbs and is associated with schizophrenia and depressive disorders. DGCR2 is a candidate for involvement in the pathogenesis of DGS since the DGCR2 gene lies within the minimal DGS critical region (MDGRC) of 22q11, which when deleted gives rise to DGS, and the DGCR2 gene is in close proximity to the balanced translocation breakpoint in a DGS patient having a balanced translocation .
Attractin-like, C-type lectin-like domain (Attractin-like_CTLD)
Type: Domain

This C-type lectin-like domain (CTLD) is found in human and mouse attractin (AtrN) and attractin-like protein (ALP). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins. Mouse AtrN (the product of the mahogany gene) has been shown to bind Agouti protein and to function in agouti-induced pigmentation and obesity . Mutations in AtrN have also been shown to cause spongiform encephalopathy and hypomyelination in rats and hamsters . The cytoplasmic region of mouse ALP has been shown to bind to melanocortin receptor (MCR4) . Signaling through MCR4 plays a role in appetite suppression. Attractin may have therapeutic potential in the treatment of obesity . Human attractin (hAtrN) has been shown to be expressed on activated T cells and released extracellularly. The circulating serum attractin induces the spreading of monocytes that become the focus of the clustering of non-proliferating T cells .
Pol II subunit B9, C-terminal zinc ribbon (Zn_ribbon_RPB9_C)
Type: Domain

The C-terminal zinc ribbon domain of subunit B9 in RNA polymerase (Pol) II (RPB9) is involved in intrinsic transcript cleavage . Eukaryote genomes are transcribed by three nuclear RNA polymerases (Pol I, II and III) that share some subunits. RPB9 is homologous to RPA12 of Pol I and RPC11 of Pol III subunits but its intrinsic cleavage activity is weaker for Pol II . RPB9 C-terminal zinc ribbon is homologous to Pol II elongation factor TFIIS domain III . The very weak cleavage activity of Pol II is stimulated by TFIIS. RPB9 has two zinc-binding domains separated by a flexible linker .
Pol III subunit C11, C-terminal zinc ribbon (Zn_ribbon_RPC11_C)
Type: Domain

The C-terminal zinc ribbon domain of subunit C11 in RNA polymerase (Pol) III (RPC11) is required for intrinsic transcript cleavage. RPC11 is also involved in Pol III termination . Eukaryote genomes are transcribed by three nuclear RNA polymerases (Pol I, II and III) that share some subunits. RPC11 is homologous to RPB9 of Pol II and RPA12 of Pol I. RPC11 C-terminal zinc ribbon is homologous to Pol II elongation factor TFIIS domain III . RPC11 has two zinc-binding domains separated by a flexible linker .
Aminopeptidase, leukotriene A4 hydrolase-like (M1_LTA4H)
Type: Family

This entry includes leukotriene A4 hydrolase (LTA4H;

; MEROPS identifier M01.004) and the close homologues cold-active aminopeptidase (
Colwellia psychrerythraea
-type peptidase; ColAP; MEROPS identifier M01.031), and arginyl aminopeptidase-like 1 (also known as aminopeptidase RNPEPL1, MEROPS identifier M01.022), all members of the aminopeptidase M1 family. LTA4H, is a bifunctional enzyme possessing an aminopeptidase as well as an epoxide hydrolase activity . The two activities occupy different, but overlapping sites . The activity and physiological relevance of the aminopeptidase is as yet unknown while the epoxide hydrolase converts leukotriene A4 (LTA4) into leukotriene B4 (LTB4), a potent chemotaxin that is fundamental to the inflammatory response of mammals . It accepts a variety of substrates, including some opioid, di- and tripeptides, as well as chromogenic aminoacyl-p-nitroanilide derivatives. The aminopeptidase activity of LTA4H is possibly involved in the processing of peptides related to inflammation and host defense. Kinetic analysis shows that LTA4H hydrolyzes arginyl tripeptides with high efficiency and specificity, indicating its function as an arginyl aminopeptidase . LTA4H is overexpressed in certain human cancers, and has been identified as a functionally important target for mediating anticancer properties of resveratrol, a well known red wine polyphenolic compound with cancer chemopreventive activity .
Tumour necrosis factor receptor 18, N-terminal (TNFRSF18_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as activation-inducible TNF receptor (AITR), glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), CD357, or GITR-D, has increased expression upon T-cell activation, and is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells . In inflammatory cells, GITR expression indicates a possible molecular link between steroid use and complicated acute sigmoid diverticulitis; increased MMP-9 expression by GITR signaling might explain morphological changes in the colonic wall in diverticulitis . Its ligand, GITRL, activates GITR which could then influence the activity of effector and regulatory T cells, participating in the development of several autoimmune and inflammatory diseases, including autoimmune thyroid disease and rheumatoid arthritis . In systemic lupus erythematosus (SLE) patients, serum GITRL levels are increased compared with healthy controls . GITR and its ligand, GITRL, are possibly involved in the pathogenesis of primary Sjogren's syndrome (pSS) .

GITR is inactivated during tumor progression in Multiple Myeloma (MM); restoration of GITR expression in GITR deficient MM cells leads to inhibition of MM proliferation and induction of apoptosis, thus playing a pivotal role in MM pathogenesis and disease progression . Regulatory T-cells (Tregs) in liver tumor up-regulate the expression of GITR compared with Tregs in tumor-free liver tissue and blood . Regulatory single nucleotide polymorphisms (SNPs) in the promoter regions of the TNFRSF18 gene have been identified in a group of male Gabonese individuals exposed to a wide array of parasitic diseases such as malaria, filariasis and schistosomiasis, and may serve as a basis to study parasite susceptibility in association studies .

This entry represents the N-terminal domain of TNFRSF18. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family .
Tumour necrosis factor receptor 9, N-terminal (TNFRSF9_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD137, ILA or 4-1BB, plays a role in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of tumor-infiltrating lymphocytes. It can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells . In addition, CD137 expression is found on dendritic cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation . It transduces signals that lead to the activation of NF-kappaB, mediated by the TRAF adaptor proteins. CD137 contributes to the clonal expansion, survival, and development of T cells . It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. CD137 is modulated by SAHA treatment in breast cancer cells, suggesting that the combination of SAHA with this receptor could be a new therapeutic approach for the treatment of tumors .

This entry represents the N-terminal domain of TNFRSF9. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family .
Tumour necrosis factor receptor 5, N-terminal (TNFRSF5_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 5 (TNFRSF5), commonly known as CD40 and also as CDW40, p50 or Bp50, is widely expressed in diverse cell types including B lymphocytes, dendritic cells, platelets, monocytes, endothelial cells, and fibroblasts . It is essential in mediating a wide variety of immune and inflammatory responses, including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal centre formation . Its natural immunomodulating ligand is CD40L, and a primary defect in the CD40/CD40L system is associated with X-linked hyper-IgM (XHIM) syndrome . It is also involved in tumorigenesis; CD40 expression is significantly higher in gastric carcinomas and it is associated with the lymphatic metastasis of cancer cells and their tumor node metastasis (TNM) classification . Upregulated levels of CD40/CD40L on B cells and T cells may play an important role in the immune pathogenesis of breast cancer . Consequently, the CD40/CD40L system serves as a link between tumorigenesis, atherosclerosis, and the immune system, and offers a potential target for drug therapy for related diseases, such as cancer, atherosclerosis, diabetes mellitus, and immunological rejection .

This entry represents the N-terminal domain of TNFRSF5. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family .
Tumour necrosis factor receptor 4, N-terminal (TNFRSF4_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as OX40, ACT35, CD134, IMD16 or TXGP1L, activates NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5 . It also promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis . It is primarily expressed on activated CD4+ and CD8+ T cells, where it is transiently expressed and upregulated on the most recently antigen-activated T cells within inflammatory lesions. This makes it an attractive target to modulate immune responses, i.e. TNFRSF4 (OX40) blocking agents to inhibit adverse inflammation or agonists to enhance immune responses . An artificially created biologic fusion protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Some single nucleotide polymorphisms (SNPs) of its natural ligand OX40 ligand (OX40L, CD252), which is also found on activated T cells, have been associated with systemic lupus erythematosus .

This entry represents the N-terminal domain of TNFRSF4. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number of modules can vary in number and type in different members of the family .
Tumor necrosis factor receptor 6B, N-terminal (TNFRSF6B_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) is also known as decoy receptor 3 (DcR3), M68, or TR6. This protein is a soluble receptor secreted by cells, that does not contain a death domain and cytoplasmic domain. It acts as a decoy receptor that competes with death receptors for ligand binding. It is a pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases, and cancer . Over-expression of this gene has been noted in several cancers, including pancreatic carcinoma, and gastrointestinal tract tumors. It can neutralize the biological effects of three tumor necrosis factor superfamily (TNFSF) members: TNFSF6 (Fas ligand/FasL/CD95L) and TNFSF14 (LIGHT) which are both involved in apoptosis and inflammation, and TNFSF15 (TNF-like molecule 1A/TL1A), which is a T cell co-stimulator and involved in gut inflammation . DcR3 is a novel inflammatory marker; higher DcR3 levels strongly correlate with inflammation and independently predict cardiovascular and all-cause mortality in chronic kidney disease (CKD) patients on hemodialysis . Increased synovial inflammatory cells infiltration in rheumatoid arthritis and ankylosing spondylitis is also associated with the elevated DcR3 expression . In cartilaginous fish, mRNA expression of DcR3 in the thymus and leydig, which are the representative lymphoid tissues of elasmobranchs, suggests that DcR3 may act as a modulator in the immune system. Interestingly, in banded dogfish (Triakis scyllia), DcR3 mRNA is strongly expressed in the gill, compared with human expression in the normal lung; both are respiratory organs, suggesting potential relevance of DcR3 to respiratory function .

This entry represents the N-terminal domain of TNFRSF6B. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family .
Tumor necrosis factor receptor 10, N-terminal (TNFRSF10_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 10 (TNFRSF10) family contains TNFRSF10A (also known as DR4, Apo2, TRAIL-R1, CD261), TNFRSF10B (also known as DR5, KILLER, TRICK2A, TRAIL-R2, TRICKB, CD262), TNFRSF10C (also known as DcR1, TRAIL-R3, LIT, TRID, CD263), and TNFRSF10D (also known as DcR2, TRUNDD, TRAIL-R4, CD264). Tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL) binds to all 4 receptors.

DR4 (TRAIL-R1) and DR5 (TRAIL-R2) are membrane-bound and contain a death domain in their intracellular portion, which is able to transmit an apoptotic signal, thus often called death receptors. In contrast, DcR1 (TRAIL-R3), which lacks the complete intracellular portion and DcR2 (TRAIL-R4), which has a truncated cytoplasmic death domain, do not transmit an apoptotic signal, thus known as decoy receptors . Apoptosis mediated by DR4 and DR5 requires Fas (TNFRSF6)-associated via death domain (FADD), a death domain containing adaptor protein . DcR1 appears to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis; DcR2 has been shown to play an inhibitory role in TRAIL-induced cell apoptosis . The membrane expression of all of these receptors (DR4, DR5, DcR1, and DcR2) is greater in normal endometrium (NE) than in endometrioid adenocarcinoma (EAC) . In EAC patients, membrane expression of these receptors are not independent predictors of survival. DcR1 and DcR2 expression is critical in cell growth and apoptosis in cutaneous or uveal melanoma ; DcR1 and DcR2 are frequently methylated in both, leading to loss of gene expression and melanomagenesis. On the other hand, DR4 and DR5 methylation is rare in cutaneous melanoma and frequent in uveal melanoma; their expression is wholly independent of the promoter methylation status. DcR1 and DcR2 genes are also reported to be hyper-methylated in prostate cancer . The TRAIL ligand, a potent and specific inducer of apoptosis in cancer cells, has been explored as a therapeutic drug; experimental data has shown that DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer .

This entry represents the N-terminal domain of TNFRSF10. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number and type of modules can vary in different members of the family .