SII-SWORD/CoKE huggingface dataset:
Tumor necrosis factor receptor 19-like, N-terminal (TNFRSF19L_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 19-like (TNFRSF19L), also known as receptor expressed in lymphoid tissues (RELT), is especially abundant in hematologic tissues and can stimulate the proliferation of T-cells . It serves as a substrate for the closely related kinases, odd-skipped related transcription factor 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK) ; RELT binds SPAK and uses it to mediate p38 and JNK activation, rather than rely on the canonical TRAF pathways for its function. RELT is capable of stimulating T-cell proliferation in the presence of CD3 signaling, which suggests its regulatory role in immune response. It interacts with phospholipid scramblase 1 (PLSCR1), an interferon-inducible protein that mediates antiviral activity against DNA and RNA viruses; PLSCR1 is a regulator of hepatitis B virus X (HBV X) protein. RELT and PLSCR1 co-localize in intracellular regions of human embryonic kidney-293 cells, with RELT over-expression appearing to alter the localization of PLSCR1 .

This entry represents the N-terminal domain of TNFRSF19L. 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 25, N-terminal (TNFRSF25_N)
Type: Domain

TNFRSF25 (also known as death receptor 3 (DR3), death domain receptor 3 (DDR3), apoptosis-mediating receptor, lymphocyte associated receptor of death (LARD), apoptosis inducing receptor (AIR), APO-3, translocating chain-association membrane protein (TRAMP), WSL-1, WSL-LR or TNFRSF12) is preferentially expressed in thymocytes and lymphocytes, and may play a role in regulating lymphocyte homeostasis . Various death domain containing adaptor proteins mediate the signal transduction of this receptor; it activates nuclear factor kappa-B (NFkB) and induces cell apoptosis by associating with TNFRSF1A-associated via death domain (TRADD), which is known to mediate signal transduction of tumor necrosis factor receptors . DR3 associates with tumor necrosis factor (TNF)-like cytokine 1A (TL1A also known as TNFSF15) on activated lymphocytes and induces pro-inflammatory signals; TL1A also binds decoy receptor DcR3 (also known as TNFRSF6B) . DR3/DcR3/TL1A expression is increased in both serum and inflamed tissues in autoimmune diseases such as in several autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), allergic asthma, experimental autoimmune encephalomyelitis, type 1 diabetes, ankylosing spondylitis (AS), and primary biliary cirrhosis (PBC), making modulation of TL1A-DR3 interaction a potential therapeutic target .

This entry represents the N-terminal domain of TNFRSF25. 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 .
Tripeptidyl-peptidase II domain (TPP_II_domain)
Type: Domain

Tripeptidyl-peptidase II (MEROPS identifier S08.090) is a member of the peptidase S8 or subtilase family. Tripeptidyl-peptidase II removes tripeptides from the free N terminus of oligopeptides as well as having endoproteolytic activity. Some tripeptidyl-peptidases have been shown to cleave tripeptides and small peptides, e.g. angiotensin II and glucagon, while others are believed to be involved in MHC I processing .

Peptidases S8 (or subtilases serine endo- and exo-peptidase clan) have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinities. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular; some function at extreme temperatures and pH values .
Tumor necrosis factor receptor EDAR, N-terminal (EDAR_N)
Type: Domain

Ectodysplasin A receptor (EDAR, also known as DL, ED3, ED5, ED1R, EDA3, HRM1, EDA1R, ECTD10A, ECTD10B, EDA-A1R) binds the soluble ligand ectodysplasin A and can activate the nuclear factor-kappaB, JNK, and caspase-independent cell death pathways. It is required for the development of hair, teeth, and other ectodermal derivatives . Mutations in this gene result in autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia . Patients present defects in the development of ectoderm-derived structures resulting in sparse hair, too few teeth (oligodontia), the absence or reduction in the ability to sweat as well as problems with mucous and saliva and the production and formation of pigment cells .

This entry represents the N-terminal domain of EDAR.
Tumor necrosis factor receptor 5, N-terminal, teleost (TNFRSF5_N_teleost)
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. 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 .

TNFRSF5/CD40 homologues have been identified in teleosts. The zebrafish CD40 is a type I membrane-bound protein with a sequence pattern of four cysteine-rich domains in its extracellular N-terminal region. The consensus TNFR-associated factor (TRAF)2- and TRAF6-binding motifs in mammalian CD40 are found in the cytoplasmic tail of zebrafish CD40, which indicates similar signal transduction mechanisms to higher vertebrates . Salmon CD40 and CD40L are widely expressed, particularly in immune tissues, and their importance for the immune response is indicated by their relatively high expression in salmon lymphoid organs and gills .

This entry represents the N-terminal domain of TNFRSF5 from teleosts.
PrcA catalytic domain (Pep_S8_PrcA)
Type: Domain

This entry includes the peptidase domain of the bacterial members of the peptidase subfamily S8B, which also includes dibasic processing peptidases from eukaryotes. The characterised bacterial peptidases have a trypsin-like specificity, cleaving lysyl or arginyl bonds. PrcA peptidase (MEROPS identifier S08.079) is a calcium-dependent peptidase isolated from Anabaena located in the cytoplasm and synthesised as a precursor . The HreP peptidase from Yersinia enterocolitica (MEROPS identifier S08.043) is also synthesised with a propeptide and processes itself by cleavage of a lysyl bond . It is essential for virulence, and the hreP gene is regulated by three genes, pypA, pypB and pypC .

Peptidases S8 (or subtilases serine endo- and exo-peptidase clan) have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinities. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular; some function at extreme temperatures and pH values .
Tumor necrosis factor receptor 6, N-terminal, teleost (TNFRSF6_N_teleost)
Type: Domain

This entry represents the N-terminal domain of TNFRSF6/Fas from teleosts. 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 superfamily member 6 (TNFRSF6), also known as Fas cell surface death receptor (FasR) or Fas, APT1, CD95, FAS1, APO-1, FASTM, ALPS1A, contains a death domain and plays a central role in the physiological regulation of programmed cell death . It has been implicated in the pathogenesis of various malignancies and diseases of the immune system . The receptor interacts with the Fas ligand (FasL), allowing the formation of a death-inducing signalling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10; autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, leading to apoptosis. This receptor has also been shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is involved in transducing the proliferating signals in normal diploid fibroblast and T cells .

In channel catfish and the Japanese rice fish medaka, homologues of Fas receptor (FasR), as well as FADD and caspase 8, have been identified and characterised, and likely constitute the teleost equivalent of the death-inducing signalling complex (DISC) . FasL/FasR are involved in the initiation of apoptosis and suggest that mechanisms of cell-mediated cytotoxicity in teleosts are similar to those used by mammals; presumably, the mechanism of apoptosis induction via death receptors was evolutionarily established during the appearance of vertebrates.
PatG/PatA-like domain (Pep_S8_PatG/PatA-like)
Type: Domain

This entry includes the subtilisin-like peptidase domain of the PatG peptidase (also known as the thiazoline oxidase/subtilisin-like protease; MEROPS identifier S08.146) which is produced by the symbiotic bacteria Prochloron spp. that inhabit didemnid family ascidians. The cyclic peptides of the patellamide class found in didemnid extracts are now known to be synthesized by the Prochloron spp. The prepatellamide is heterocyclized to form thiazole and oxazoline rings and the peptide is cleaved to form the two cyclic patellamides A and C . Two peptidases are required for the release of the active peptide from its precursor. PatA peptidase (MEROPS identifier S08.156) cleaves off the N-terminal propeptide, and the PatG peptidase releases the C-terminal propeptide and cyclizes the patellamide . Unusually, cleavage by PatG occurs at a cystinyl bond. The tertiary structure of the PatG peptidase domain shows a unique element not found in other subtilisin homologues that may be responsible for the N-C macrocyclization of the patellamide .

This domain is part of a family of domains found in serine peptidases belonging to the MEROPS peptidase families S8 (subfamilies S8A (subtilisin) and S8B (kexin)) and S53 (sedolisin), both of which are members of clan SB .

Peptidases S8 (or subtilases serine endo- and exo-peptidase clan) have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinities. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular; some function at extreme temperatures and pH values .
Tumor necrosis factor receptor 9, N-terminal, teleost (TNFRSF9_N_teleost)
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 .

Mostly, CD137 in teleosts have not been characterised.

This entry represents the N-terminal domain of TNFRSF9/CD137 from teleosts. 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 .
TagA/B/C/D, peptidase domain (TagA/B/C/D_pept_dom)
Type: Domain

In Dictyostelium discoideum, unique members of the ABCB transporter subfamily, TagB and TagC, appear responsible for peptide signal export during development. These Tag proteins are required for cell differentiation in Dictyostelium and have the potential to carry out the processing and transport of peptide signals since they possess an N-terminal serine protease domain and a C-terminal transporter domain . Other family members include TagA, which is required for the specification of an initial population of prespore cells in which tagA is expressed .

This entry represents the N-terminal serine protease domain, which is is part of a family of domains found in serine peptidases belonging to the MEROPS peptidase families S8 (subfamilies S8A (subtilisin) and S8B (kexin)) and S53 (sedolisin), both of which are members of clan SB .

Peptidases S8 (or subtilases serine endo- and exo-peptidase clan) have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinities. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular; some function at extreme temperatures and pH values .
Tumor necrosis factor receptor, N-terminal, viral (TNFRSF_N_viral)
Type: Domain

Viral TNFR homologues include vaccinia virus (VACV) cytokine response modifier E (CrmE) , an encoded TNFR that shares significant sequence similarity with mammalian type 2 TNF receptors (TNFSFR1B, p75, TNFR type 2) , a cowpox virus encoded cytokine-response modifier B (CrmB) , which is a secreted form of TNF receptor that can contribute to the modification of TNF-mediated antiviral processes, and a myxoma virus (MYXV) T2 (M-T2) protein that binds and inhibits rabbit TNF-alpha . The CrmE structure confirms that the canonical TNFR fold is adopted, but only one of the two "ligand-binding" loops of TNFRSF1A is conserved, suggesting a mechanism for the higher affinity of poxvirus TNFRs for TNFalpha over lymphotoxin-alpha . CrmB protein specifically binds TNF-alpha and TNF-beta indicating that cowpox virus seeks to invade antiviral processes mediated by TNF. Intracellular M-T2 blocks virus-induced lymphocyte apoptosis via a highly conserved viral preligand assembly domain (vPLAD), which controls receptor signaling competency prior to ligand binding .

This entry represents the N-terminal domain of viral TNFRs. 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 27, N-terminal (TNFRSF27_N)
Type: Domain

This entry represents the N-terminal domain of TNFRSF27/XEDAR. 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 .

TNFRSF27 (also known as ectodysplasin-A2 receptor (EDA2R), X-linked ectodermal dysplasia receptor (XEDAR), EDAA2R, and EDA-A2R) is a member of the TNFR superfamily that is recognised by ectodysplasin-A2 (EDA-A2), which is generated by alternative splicing of the EDA receptor (EDAR) ligand EDA-A1 . It is highly expressed during embryonic development and binds to ectodysplasin-A2 (EDA-A2), playing a crucial role in the p53-signalling pathway. EDA2R is a direct p53 target that is frequently down-regulated in colorectal cancer tissues due to its epigenetic alterations or through the p53 gene mutations . Mutations in the EDA-A2/XEDAR signalling give rise to ectodermal dysplasia, characterised by loss of hair, sweat glands, and teeth . A non-synonymous SNP on EDA2R, along with genetic variants in human androgen receptor is associated with androgenetic alopecia (AGA) .
Autotransporter serine protease peptidase domain (Peptidases_S8_Autotransporter)
Type: Domain

This entry includes autotransporter serine proteases belonging to the peptidase S8 (subtilase). Autotransporters are outer membrane/secreted proteins of Gram-negative bacteria. The presence of these subtilisin-like domains in these autotransporters may enable them to be auto-catalytic and may also serve to allow them to act as a maturation protease cleaving other outer membrane proteins at the cell surface. Included in this entry are: the SphB1 peptidase from Bordetella pertussis, the causative agent of whooping cough, which is required for the maturation of filamentous hemagglutinin adhesin at the bacterial surface (FHA) ; an extracellular subtilisin SSP from Serratia (MEROPS identifier S08.094), which has a large C-terminal domain that forms a pore in the outer membrane through which the mature enzyme can pass ; and the AasP peptidase from Actinobacillus pleuropneumoniae (MEROPS identifier S08.144), the causative agent of porcine pleuropneumonia, which does not undergo autoproteolysis, but is still an active sheddase, releasing fragments of the OmlA protein .

This domain is part of a family of domains found in serine peptidases belonging to the MEROPS peptidase families S8 (subfamilies S8A (subtilisin) and S8B (kexin)) and S53 (sedolisin), both of which are members of clan SB .

Peptidases S8 (or subtilases serine endo- and exo-peptidase clan) have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinities. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular; some function at extreme temperatures and pH values .
Tumor necrosis factor receptor 26, N-terminal (TNFRSF26_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 26 (TNFRSF26), also known as tumor necrosis factor receptor homologue 3 (TNFRH3) or TNFRSF24, is predominantly expressed in embryos and lymphoid cell types, along with its closely related TNFRSF22 and TNFRSF23 orthologues, and is developmentally regulated. These three
TNFSFRs genes are present in the mouse and rat, but absent in humans . Unlike TNFRSF22/23, TNFRSF26 does not serve as a TRAIL decoy receptor; it remains an orphan receptor .

This entry represents the N-terminal domain of TNFRSF26 and the TNFRSF22 and TNFRSF23 orthologues. 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 .
Fervidolysin domain (Fervidolysin_dom)
Type: Domain

This entry refers to a domain found in fervidolysin as well as other serine peptidases.

Fervidolysin (MEROPS identifier S08.021) which is found in the thermophilic bacterium Fervidobacterium pennivorans is an extracellular subtilisin-like keratinase . It contains a signal peptide, a propeptide, and a catalytic region. The tertiary structure of fervidolysin is similar to that of subtilisin .

It contains a Asp/His/Ser catalytic triad and is a member of the peptidase S8 (subtilisin and kexin) family. The catalytic triad is similar to that found in trypsin-like proteases, but it does not share their three-dimensional structure and are not homologous to trypsin. Serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base. The S53 family contains a catalytic triad Glu/Asp/Ser with an additional acidic residue Asp in the oxyanion hole, similar to that of subtilisin. The serine residue here is the nucleophilic equivalent of the serine residue in the S8 family, while glutamic acid has the same role here as the histidine base. However, the aspartic acid residue that acts as an electrophile is quite different. In S53, it follows glutamic acid, while in S8 it precedes histidine. The stability of these enzymes may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinity. There is a great diversity in the characteristics of their members: some contain disulfide bonds, some are intracellular while others are extracellular, some function at extreme temperatures, and others at high or low pH values .
All0781-like, domain (All0781-like_dom)
Type: Domain

This entry refers to a domain found in uncharacterised subtilisin homologues, including the All0781 protein from the cyanobacterium Nostoc.

This domain is part of a family of domains found in serine peptidases belonging to the MEROPS peptidase families S8 (subfamilies S8A (subtilisin) and S8B (kexin)) and S53 (sedolisin), both of which are members of clan SB .

Peptidases S8 (or subtilases serine endo- and exo-peptidase clan) have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinities. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular; some function at extreme temperatures and pH values .
Serine protease KerA-like, domain (Serine_protease_KerA-like_dom)
Type: Domain

This entry refers to a domain found in uncharacterised subtilisin homologues from bacteria, including KerA from Streptomyces.

This domain is part of a family of domains found in serine peptidases belonging to the MEROPS peptidase families S8 (subfamilies S8A (subtilisin) and S8B (kexin)) and S53 (sedolisin), both of which are members of clan SB .

Peptidases S8 (or subtilases serine endo- and exo-peptidase clan) have an Asp/His/Ser catalytic triad similar to that found in trypsin-like proteases, but do not share their three-dimensional structure and are not homologous to trypsin. The stability of subtilases may be enhanced by calcium; some members have been shown to bind up to 4 ions via binding sites with different affinities. Some members of this clan contain disulfide bonds. These enzymes can be intra- and extracellular; some function at extreme temperatures and pH values .