SII-SWORD/CoKE huggingface dataset:
L-talarate/galactarate dehydratase (L-talarate_dehydratase)
Type: Family

Enzymes in the L-talarate/galactarate dehydratase family catalyze the dehydration of L-talarate (also called L-altrarate), the dehydration of galactarate, and the epimerization of L-talarate to galactarate .
MINDY deubiquitinase domain (MINDY_domain)
Type: Domain

This domain represents the catalytic domain of a group of deubiquitinating (DUB) enzymes known as the MINDY family (MIU-containing novel DUB). Ubiquitin (Ub) is released one molecule at a time from the distal end of proteins with Lys48-linked polyubiquitin chains. Long polyubiquitin chains are preferred. The catalytic Cys and His residues have been identified by site-directed mutagenesis, as has the Gln that participates in formation of the oxyanion hole during catalysis. Despite the structural similarity to papain-like cysteine peptidases, a residue corresponding to the Asn that orientates the imidazolium ring of the catalytic His has not been identified. Members of the MINDY family of DUBs contain an MIU (motif interacting with Ub) motif, which is a helical motif that binds mono-Ub .
Mannosyl-3-phosphoglycerate phosphatase, thermophiles (MPG_Pase_thermophiles)
Type: Family

Members of this family are mannosyl-3-phosphoglycerate phosphatase (

). It acts sequentially after mannosyl-3-phosphoglycerate synthase (

) in a two-step pathway of biosynthesis of the compatible solute mannosylglycerate, a typical osmolyte of thermophiles .
Thiazole synthase ThiG (Thiazole_synthase_ThiG)
Type: Domain

This entry refers to a domain found in several bacterial thiazole biosynthesis protein G (ThiG) sequences. ThiG, together with ThiF and ThiH, is proposed to be involved in the synthesis of 4-methyl-5-(b-hydroxyethyl)thiazole (THZ) which is an intermediate in the thiazole production pathway .

This entry also includes domains found in triosephosphate isomerase and pyridoxal 5'-phosphate synthase subunit PdxS.
SusD-like, N-terminal (SusD-like_N)
Type: Domain

SusD is a secreted polysaccharide-binding protein with an N-terminal lipid moiety that allows association with the outer membrane. SusD probably mediates xyloglucan-binding prior to xyloglucan transport in the periplasm for degradation .

This domain is found N-terminal to

.
Clusterin, conserved site (Clusterin_CS)
Type: Conserved_site

Clusterin is a vertebrate glycoprotein that functionas as a extracellular chaperone and has been associated with programmed cell death .

Clusterin (Apo-J) is synthesized as a precursor polypeptide of about 400 amino acids which is post-translationally cleaved to form two subunits (of about 200 amino acids each). The two subunits are linked by five disulfide bonds to form an antiparallel ladder-like structure . In each of the mature subunits the five cysteines that are involved in disulfide bonds are clustered in domains of about 30 amino acids located in the central part of the subunits.

This entry represents two conserved sites for clusterin, found one in each of the two subunits. Both of them contain three cysteines.
Aggrecan/versican, C-type lectin-like domain (CSPG_CTLD)
Type: Domain

This entry represents a C-type lectin-like domain (CTLD) of the type found in chondroitin sulfate proteoglycan core proteins (CSPGs) in human and chicken aggrecan, frog brevican, and zebra fish dermacan. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins . In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA) . These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Xenopus brevican is expressed in the notochord and the brain during early embryogenesis . Zebra fish dermacan is expressed in dermal bones and may play a role in dermal bone development . CSPGs do contain LINK domain(s) which bind HA. These LINK domains are considered by one classification system to be a variety of CTLD, but are omitted from this hierarchical classification based on insignificant sequence similarity.
CEL-1-like C-type lectin-like domain (CEL1-like_CTLD)
Type: Domain

This entry represents the C-type lectin-like domain (CTLD) of the type found in CEL-1 from Cucumaria echinata, and Echinoidin from Anthocidaris crassispina amongst others. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins . The CEL-1 CTLD binds three calcium ions and has a high specificity for N-acteylgalactosamine (GalNAc) . CEL-1 exhibits strong cytotoxicity which is inhibited by GalNAc . This protein may play a role as a toxin defending against predation. Echinoidin is found in the coelomic fluid of the sea urchin and is specific for GalBeta1-3GalNAc . Echinoidin has a cell adhesive activity towards human cancer cells which is not mediated through the CTLD . Both CEL-1 and Echinoidin are multimeric proteins comprised of multiple dimers linked by disulfide bonds.
CD209-like, C-type lectin-like domain (CD209-like_CTLD)
Type: Domain

This entry represents the C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), also known as CD209 antigen, and the related receptor, DC-SIGN receptor (DC-SIGNR), also known as CD209 antigen-like protein 1 or C-type lectin domain family 4 member M. This group also contains proteins similar to hepatic asialoglycoprotein receptor (ASGP-R) and langerin (also known as CD207 or C-type lectin domain family 4 member K) in human. These proteins are type II membrane proteins with a CTLD ectodomain. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins .

DC-SIGN is thought to mediate the initial contact between dendritic cells and resting T cells, and may also mediate the rolling of DCs on epithelium . DC-SIGN and DC-SIGNR bind to oligosaccharides present on human tissues, as well as on pathogens including parasites, bacteria, and viruses. DC-SIGN and DC-SIGNR bind to HIV, enhancing viral infection of T cells . DC-SIGN and DC-SIGNR are homotetrameric, and contain four CTLDs stabilized by a coiled coil of α helices . The hepatic ASGP-R is an endocytic recycling receptor which binds and internalizes desialylated glycoproteins having a terminal galactose or N-acetylgalactosamine residues on their N-linked carbohydrate chains, via the clathrin-coated pit mediated endocytic pathway, and delivers them to lysosomes for degradation. It has been proposed that glycoproteins bearing terminals 'Sia (sialic acid) alpha2, 6GalNAc' and 'Sia alpha2, 6Gal' are endogenous ligands for ASGP-R, and that ASGP-R participates in regulating the relative concentration of serum glycoproteins bearing alpha 2,6-linked Sia . The human ASGP-R is a hetero-oligomer composed of two subunits, both of which are found within this group . Langerin is expressed in a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin induces the formation of Birbeck Granules (BGs) and associates with these BGs following internalization . Langerin binds, in a calcium-dependent manner, to glyco-conjugates containing mannose and related sugars mediating their uptake and degradation. Langerin molecules oligomerize as trimers with three CTLDs held together by a coiled-coil of α helices .
Collectin, C-type lectin-like domain (Collectin_CTLD)
Type: Domain

This entry represents the C-type lectin-like domain (CTLD) of the type found in human collectins including lung surfactant proteins A and D, mannose-binding lectin (MBL, also known as mannan-binding protein or MBP), and CL-L1 (collectin liver 1) . CTLD refers to a domain, homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins .

The CTLDs of these collectins bind carbohydrates on surfaces (e.g. pathogens, allergens, necrotic, or apoptotic cells) and mediate functions associated with killing and phagocytosis. MBPs recognize high mannose oligosaccharides in a calcium dependent manner, bind to a broad range of pathogens, and trigger cell killing by activating the complement pathway . MBP also acts directly as an opsonin . SP-A and SP-D in addition to functioning as host defense components, are components of pulmonary surfactant which play a role in surfactant homeostasis . Pulmonary surfactant is a phospholipid-protein complex which reduces the surface tension within the lungs. SP-A binds the major surfactant lipid: dipalmitoylphosphatidylcholine (DPPC). SP-D binds two minor components of surfactant that contain sugar moieties: glucosylceramide and phosphatidylinositol (PI). MBP and SP-A, -D monomers are homotrimers with an N-terminal collagen region and three CTLDs. Multiple homotrimeric units associate to form supramolecular complexes. MBL deficiency results in an increased susceptibility to a large number of different infections and to inflammatory disease .
Selectin, C-type lectin-like domain (Selectin_CTLD)
Type: Domain

This entry represents a C-type lectin-like domain (CTLD) of the type found in the type 1 transmembrane proteins: P(platelet), E(endothelial), and L(leukocyte) selectins (sels). CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins .

P- E- and L-sels are cell adhesion receptors that mediate the initial attachment, tethering, and rolling of lymphocytes on inflamed vascular walls, enabling subsequent lymphocyte adhesion and transmigration . L-sel is expressed constitutively on most leukocytes. P-sel is stored in the Weibel-Palade bodies of endothelial cells and in the alpha granules of platlets. E-sels are present on endothelial cells . Following platelet and/or endothelial cell activation, P-sel is rapidly translocated to the cell surface and E-sel expression is induced. The initial step in leukocyte migration involves interactions of selectins with fucosylated, sialylated, and sulfated carbohydrate moieties on target ligands displayed on glycoprotein scaffolds on endothelial cells and leucocytes. A major ligand of P- E- and L-sels is PSGL-1 (P-sel glycoprotein ligand) . Interactions of E- and P- sels with tumor cells may promote extravasation of cancer cells . Regulation of L-sel and P-sel function includes proteolytic shedding of the most extracellular portion (containing the CTLD) from the cell surface . Increased levels of the soluble form of P-sel in the plasma have been found in a number of diseases including coronary disease and diabetes . E- and P-sel also play roles in the development of synovial inflammation in inflammatory arthritis . Platelet P-sel, but not endothelial P-sel, plays a role in the inflammatory response and neointimal formation after arterial injury . Selectins may also function as signal-transducing receptors.
Natural killer cell receptor-like, C-type lectin-like domain (NKR-like_CTLD)
Type: Domain

This entry represents a C-type lectin-like domain (CTLD) of the type found in natural killer cell receptors (NKRs), including proteins similar to oxidized low density lipoprotein (OxLDL) receptor (LOX-1), CD94, CD69, NKG2-A and -D, osteoclast inhibitory lectin (OCIL), dendritic cell-associated C-type lectin-1 (dectin-1), human myeloid inhibitory C-type lectin-like receptor (MICL), mast cell-associated functional antigen (MAFA), killer cell lectin-like receptors: subfamily F, member 1 (KLRF1) and subfamily B, member 1 (KLRB1), and lys49 receptors. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins .

NKRs are variously associated with activation or inhibition of natural killer (NK) cells. Activating NKRs stimulate cytolysis by NK cells of virally infected or transformed cells; inhibitory NKRs block cytolysis upon recognition of markers of healthy self cells. Most Lys49 receptors are inhibitory; some are stimulatory. OCIL inhibits NK cell function via binding to the receptor NKRP1D. Murine OCIL in addition to inhibiting NK cell function inhibits osteoclast differentiation . MAFA clusters with the type I Fc epsilon receptor (FcepsilonRI) and inhibits the mast cells secretory response to FcepsilonRI stimulus . CD72 is a regulator of B cell receptor signaling . NKG2D is an activating receptor for stress-induced antigens; human NKG2D ligands include the stress induced MHC-I homologs, MICA, MICB, and ULBP family of glycoproteins. Several NKRs have a carbohydrate-binding capacity which is not mediated through calcium ions (e.g. OCIL binds a range of high molecular weight sulfated glycosaminoglycans including dextran sulfate, fucoidan, and gamma-carrageenan sugars) . Dectin-1 binds fungal beta-glucans and is involved in the innate immune responses to fungal pathogens . MAFA binds saccharides having terminal alpha-D mannose residues in a calcium-dependent manner. LOX-1 is the major receptor for OxLDL in endothelial cells and thought to play a role in the pathology of atherosclerosis . Some NKRs exist as homodimers (e.g.Lys49, NKG2D, CD69, LOX-1) and some as heterodimers (e.g. CD94/NKG2A). Dectin-1 can function as a monomer in vitro.
Tumor necrosis factor receptor 1A, N-terminal (TNFRSF1A_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A, also known as type I TNFR, TNFR1, DR1, CD120a, p55) binds TNF-alpha, through the death domain (DD), and activates NF-kappaB, mediates apoptosis and activates signaling pathways controlling inflammatory, immune, and stress responses. It mediates signal transduction by interacting with antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRAF2 and TRADD that play regulatory roles .

The human genetic disorder called tumor necrosis factor associated periodic syndrome (TRAPS), or periodic fever syndrome, is associated with germline mutations of the extracellular domains of this receptor, possibly due to impaired receptor clearance . TNFRSF1A polymorphisms rs1800693 and rs4149584 are associated with elevated risk of multiple sclerosis . Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder, and high levels are also associated with cognitive impairment and dementia . Patients with idiopathic recurrent acute pericarditis (IRAP), presumed to be an autoimmune process, have also been shown to carry rare mutations (R104Q and D12E) in the TNFRSF1A gene .

This entry represents the N-terminal domain of TNFR1A. 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 1A, death domain (TNFRSF1A_death)
Type: Domain

This entry represents the death domain (DD) found in tumour necrosis factor receptor-1 (TNFR-1). TNFR-1 has many names, including TNFRSF1A, CD120a, p55, p60, and TNFR60. It activates two major intracellular signalling pathways that lead to the activation of the transcription factor NF-kB and the induction of cell death. Upon binding of its ligand TNF, TNFR-1 trimerises, which leads to the recruitment of an adaptor protein named TNFR-associated death domain protein (TRADD) through a DD/DD interaction . Mutations in the TNFRSF1A gene causes TNFR-associated periodic syndrome (TRAPS), a rare disorder characterised recurrent fever, myalgia, abdominal pain, conjunctivitis and skin eruptions .

DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily, including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
Tumor necrosis factor receptor superfamily member 1A, N-terminal, teleost (TNFRSF1A_N_teleost)
Type: Domain

This subfamily of tumor necrosis factor receptor 1A (TNFRSF1, also known as type I TNFR, TNFR1, DR1, TNFRSF1A, CD120a, p55) is found in teleosts. It binds TNF-alpha, through the death domain (DD), and activates NF-kappaB, mediates apoptosis and activates signaling pathways controlling inflammatory, immune, and stress responses. It mediates signal transduction by interacting with antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRAF2 and TRADD that play regulatory roles .

Knockout studies in zebrafish embryos have shown that a signaling balance between TNFRSF1A and TNFRSF1B is required for endothelial cell integrity. TNFRSF1A signals apoptosis through caspase-8, whereas TNFRSF1B signals survival via NF-kappaB in endothelial cells. Thus, this apoptotic pathway seems to be evolutionarily conserved, as TNFalpha promotes apoptosis of human endothelial cells and triggers caspase-2 and P53 activation in these cells via TNFRSF1A .

This entry represents the N-terminal domain of TNFR1A 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 1B, N-terminal (TNFRSF1B_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 1B (TNFRSF1B, also known as TNFR2, type 2 TNFR, TNFBR, TNFR80, TNF-R75, TNF-R-II, p75, CD120b) binds TNF-alpha, but lacks the death domain (DD) that is associated with the cytoplasmic domain of TNFRSF1A (TNFR1) . It is inducible and expressed exclusively by oligodendrocytes, astrocytes, T cells, thymocytes, myocytes, endothelial cells, and in human mesenchymal stem cells . TNFRSF1B protects oligodendrocyte progenitor cells (OLGs) against oxidative stress, and induces the up-regulation of cell survival genes . While pro-inflammatory and pathogen-clearing activities of TNF are mediated mainly through activation of TNFRSF1A, a strong activator of NF-kappaB, TNFRSF1B is more responsible for suppression of inflammation . Although the affinities of both receptors for soluble TNF are similar, TNFRSF1B is sometimes more abundantly expressed and thought to associate with TNF, thereby increasing its concentration near TNFRSF1A receptors, and making TNF available to activate TNFRSF1A (a ligand-passing mechanism) .

This entry represents the N-terminal domain of TNFR1B. 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 3, N-terminal (TNFRSF3_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 3 (TNFRSF3, also known as lymphotoxin beta receptor, LTbetaR, CD18, TNFCR, TNFR3, D12S370, TNFR-RP, TNFR2-RP, LT-BETA-R, TNF-R-III) plays a role in lipid metabolism, immune response, programmed cell death, and in signaling during development of lymphoid and other organs . Its ligands include lymphotoxin (LT) alpha/beta membrane form (heterotrimer) and tumor necrosis factor ligand superfamily member 14 (also known as LIGHT) . TNFRSF3 agonism by these ligands initiates canonical, as well as non-canonical nuclear factor-kappaB (NF-kappaB) signaling, and preferentially results in the translocation of p52-RELB complexes into the nucleus . While these ligands are often expressed by T and B cells, TNFRSF3 is conspicuously absent on T and B lymphocytes and NK cells, suggesting that signaling may be unidirectional for TNFRSF3 . Activity of this receptor has also been linked to carcinogenesis; it helps trigger apoptosis and can also lead to release of the interleukin 8 (IL8) . Alternatively spliced transcript variants encoding multiple isoforms have been observed.

This entry represents the N-terminal domain of TNFRSF3. 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 .
Fas receptor, death domain (TNFRSF6_death)
Type: Domain

This entry represents the death domain (DD) found in the FS7-associated cell surface antigen (FAS). FAS, also known as TNFRSF6 (TNF receptor superfamily member 6), APT1, CD95, FAS1, or APO-1, together with FADD (Fas-associating via Death Domain) and caspase 8, is an integral part of the death inducing signalling complex (DISC), which plays an important role in the induction of apoptosis and is activated by binding of the ligand FasL to FAS . FAS also plays a critical role in self-tolerance by eliminating cell types (autoreactive T and B cells) that contribute to autoimmunity .

DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
Fas receptor, N-terminal (TNFRSF6_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 6 (TNFRSF6), also known as Fas cell surface death receptor (FasR), Fas, APT1, CD95, FAS1, APO-1, FASTM, or 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 signaling 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 .

This entry represents the N-terminal domain of FasR. 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 7, N-terminal (TNFRSF7_N)
Type: Domain

Tumor necrosis factor receptor superfamily member 7 (TNFRSF7), also known as CD27, T14, S152, Tp55, S152 or LPFS2, has a key role in the generation of immunological memory via effects on T-cell expansion and survival, and B cell development . It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. CD27 transduces signals that lead to the activation of NF-kappaB and MAPK8/JNK, and mediates the signaling process through adaptor proteins TRAF2 and TRAF5. CD27-binding protein (SIVA), a pro-apoptotic protein, can bind to CD27 and may play an important role in the apoptosis induced by this receptor . The potential role of the CD27/CD70 pathway in the course of inflammatory diseases, such as arthritis, and inflammatory bowel disease, suggests that CD70 may be a target for immune intervention. The expression of CD27 and CD44 molecules correlates with the differentiation stage of B cell precursors and has been shown to have a biological significance in acute lymphoblastic leukemia .

This entry represents the N-terminal domain of TNFRSF7. 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 .