SII-SWORD/CoKE huggingface dataset:
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha, PX domain (PX_PI3K_C2_alpha)
Type: Domain

This entry represents the PX domain found in phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3K-C2alpha). The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others . PI3K-C2alpha, the class II alpha isoform of PI3K, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis . The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction .

The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis . PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C terminus .
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta, PX domain (PX_PI3K_C2_beta)
Type: Domain

This entry represents the PX domain found in phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (PI3K-C2beta). The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signalling, vesicular trafficking, protein sorting, and lipid modification, among others . PI3K-C2beta, the class II beta isoform of PI3K, contributes to the migration and survival of cancer cells . It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion .

The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis . PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C terminus .
SNX5, PX domain (PX_SNX5)
Type: Domain

This entry represents the PX domain found in Sorting nexin-5 (SNX5). The PX domain of SNX5 binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,4)P2. SNX5 is localized to a subdomain of early endosome and is recruited to the plasma membrane following EGF stimulation and elevation of PI(3,4)P2 levels .

The Phox Homology (PX) domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds phosphoinositides (PIs) and targets the protein to PI-enriched membranes . SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway .
SNX6, PX domain (PX_SNX6)
Type: Domain

This entry represents the PX domain found in Sorting nexin-6 (SNX6).

SNX6 was found to interact with members of the transforming growth factor-beta family of receptor serine/threonine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation
in vivo
of oligomeric complexes. SNX6 is localized in the cytoplasm where it is thought to target proteins to the
trans
-Golgi network . In addition, SNX6 was found to be translocated from the cytoplasm to nucleus by Pim-1, an oncogene product of serine/threonine kinase. This translocation is not affected by Pim-1-dependent phosphorylation, but the functional significance is unknown .

The Phox Homology (PX) domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds phosphoinositides (PIs) and targets the protein to PI-enriched membranes . SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway .
Vertebrate SNX3, PX domain (PX_SNX3_Vert)
Type: Domain

This entry represents the PX domain found in Sorting nexin-3 (SNX3) from vertebrates. In budding yeasts, Snx3 homologue has been shown to associate with early endosomes through a PX domain-mediated interaction with phosphatidylinositol-3-phosphate (PI3P) . It associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer. SNX3 is required for the formation of multivesicular bodies, which function as transport intermediates to late endosomes . It also promotes cell surface expression of the amiloride-sensitive epithelial Na+ channel (ENaC), which is critical in sodium homeostasis and maintenance of extracellular fluid volume .

The Phox Homology (PX) domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds phosphoinositides (PIs) and targets the protein to PI-enriched membranes . SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway .
Fungal SNX3, PX domain (PX_Grd19_PX)
Type: Domain

This entry represents the PX domain found in SNX3 (also known as Grd19) from fungi. Grd19 has been shown to associate with early endosomes through a PX domain-mediated interaction with phosphatidylinositol-3-phosphate (PI3P) . Grd19 is involved in the localization of late Golgi membrane proteins in yeast. It associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer .

The Phox Homology (PX) domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds phosphoinositides (PIs) and targets the protein to PI-enriched membranes . SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway .
Rho GTPase-activating protein 32, PX domain (PX_ARHGAP32)
Type: Domain

This entry represents the PX domain found in Rho GTPase-activating protein 32 (ARHGAP32, also known as RICS). RICS is a Rho GTPase-activating protein for cdc42 and Rac1. It is implicated in the regulation of postsynaptic signaling and neurite outgrowth. An N-terminal splicing variant of RICS containing additional PX and Src Homology 3 (SH3) domains, also called PX-RICS, is the main isoform expressed during neural development. PX-RICS is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development . The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction . The PX domain of PX-RICS specifically binds phosphatidylinositol 3-phosphate (PI3P), PI4P, and PI5P .
CARD10, CARD domain (CARD_CARD10)
Type: Domain

This entry represents the caspase activation and recruitment domain (CARD) found in CARD10, also known as CARMA3. The CARMA3-BCL10-MALT1 signalosome plays a role in the GPCR-induced NF-kB activation . CARMA3 is more widely expressed than CARMA1, which is found only in hematopoietic cells. In endothelial and smooth muscle cells, CARMA3-mediated NF-kB activation induces pro-inflammatory signals within the vasculature and is a key factor in atherogenesis . In bronchial epithelial cells, CARMA3-mediated NF-kB signaling is important for the development of allergic airway inflammation .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
CARD11, CARD domain (CARD_CARD11)
Type: Domain

This entry represents the CARD domain found in CARD11, also known as CARMA1. CARMA1, together with BCL10 (B-cell lymphoma 10) and Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1), form the L-CBM signalosome (CBM complex in lymphoid immune cells) which mediates activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. CARMA1 associates with BCL10 via a CARD-CARD interaction .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
CARD9, CARD domain (CARD_CARD9)
Type: Domain

This entry represents the CARD domain found in CARD9, which is a central regulator of innate immunity and is highly expressed in dendritic cells and macrophages . Together with BCL10 (B-cell lymphoma 10) and Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1), it forms the M-CBM signalosome (the CBM complex in myeloid immune cells), which mediates activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. CARD9 associates with BCL10 via a CARD-CARD interaction .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
BCL10, CARD domain (CARD_BCL10)
Type: Domain

This entry represents the CARD domain found in B-cell lymphoma/leukemia 10 (BCL10). BCL10 and Malt1 (mucosa-associated lymphoid tissue-lymphoma-translocation gene 1) are the integral components of CBM signalosomes. They associate with CARD9 to form M-CBM (CBM complex in myeloid immune cells) and with CARMA1 to form L-CBM (CBM complex in lymphoid immune cells), to mediate activation of NF-kB and MAPK by ITAM-coupled receptors expressed on immune cells. Both CARMA1 and CARD9 associate with BCL10 via a CARD-CARD interaction .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
IPS1, CARD domain (CARD_IPS1)
Type: Domain

This entry represents the CARD domain found in IPS1, also known as mitochondrial antiviral-signaling protein (MAVS). IPS1 is an adaptor protein that plays an important role in interferon induction in response to viral infection. It is crucial in triggering innate immunity and in developing adaptive immunity against viral pathogens. The CARD of IPS-1 associates with the CARDs of two RNA helicases, RIG-I and MDA5, which bind viral DNA in the cytoplasm during the initial stage of intracellular antiviral response, leading to the induction of type I interferons .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
RIG-I, CARD domain repeat 2 (CARD_RIG-I_r2)
Type: Domain

This entry represents the CARD domain, repeat 2, found in RIG-I (also known as DDX58). RIG-I is a cytoplasmic RNA helicase that plays an important role in host antiviral response by sensing incoming viral RNA. RIG-I contains two N-terminal CARD domains and a C-terminal RNA helicase . Upon activation, the signal is transferred to downstream pathways via the adaptor molecule IPS-1 (MAVS, VISA, CARDIF), leading to the induction of type I interferons. Although very similar in sequence, RIG-I recognizes different sets of viruses compared to MDA5, a related RNA helicase. RIG-I associates with IPS-1 through a CARD-CARD interaction .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
BinCARD, CARD domain (CARD_BinCARD)
Type: Domain

This entry represents the CARD domain found in BinCARD, also known as CARD19. BinCARD interacts with apoptosis inducer CARD protein Bcl10 through CARD. It inhibits Bcl10-mediated activation of NF-kappa B and to suppress Bcl10 phosphorylation .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
CASP9, CARD domain (CARD_CASP9)
Type: Domain

This entry represents the CARD domain found in Caspase-9 (CASP9), which is the initiator caspase associated with the intrinsic or mitochondrial pathway of apoptosis, induced by many pro-apoptotic signals. Together with APAF-1, it forms the heptameric 'apoptosome' in response to the release of cytochrome c from mitochondria . Activated caspase-9 cleaves and activates downstream effector caspases, like caspase-3, caspase-6, and caspase-7, resulting in apoptosis .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
RAIDD, CARD domain (CARD_RAIDD)
Type: Domain

This entry represents the CARD domain found in RAIDD (RIP-associated ICH-1 homologous protein with a death domain), also known as CRADD (Caspase and RIP adapter with death domain). RAIDD is an adaptor protein that, together with the p53-inducible protein PIDD and caspase-2, forms the PIDDosome complex, which is required for caspase-2 activation and plays a role in mediating stress-induced apoptosis. RAIDD contains an N-terminal CARD, which interacts with the caspase-2 CARD, and a C-terminal Death domain (DD), which interacts with the DD of PIDD .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
RIP2, CARD domain (CARD_RIP2)
Type: Domain

This entry represents the CARD domain found in Receptor Interacting Protein 2 (RIP2). RIP2 harbours a C-terminal CARD domain and functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR)-family, NOD1 and NOD2, which recognizes bacterial peptidoglycans released upon infection. This cascade is implicated in inflammatory immune responses and the clearance of intracellular pathogens. RIP2 associates with NOD1 and NOD2 via CARD-CARD interactions .

In general, CARDs are death domains (DDs) found associated with caspases . They are known to be important in the signaling pathways for apoptosis, inflammation, and host-defense mechanisms . 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 PYRIN and DED (Death Effector Domain). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes .
CAAX prenyl protease 2, MmRce1-like (MmRce1-like)
Type: Family

Methanococcus maripaludis Rce1, MmRce1, is a type II CAAX prenyl endopeptidase. MmRce1 cleaves the CAAX motif C-terminal to both P1 and P1' positions. Similarly to its eukaryotic orthologues, hydrolysis depends on a farnesylated cysteine residue; but unlike human Rce1, it does not show activity towards geranylgeranylated peptides . This entry contains MmRce1 homologues from bacteria and archaea.
IRAK2, death domain (Death_IRAK2)
Type: Domain

This entry represents the death domain found in interleukin-1 receptor-associated kinase-like 2 (IRAK2) . IRAK2 is an essential component of several signaling pathways, including NF-kappaB and the IL-1 signaling pathways. It is an inactive kinase that participates in septic shock mediated by TLR4 and TLR9 . It plays a redundant role with IRAK1 in early NF-kB and MAPK responses, and remains present at later stages whereas IRAK1 disappears .

Interleukin-1 receptor-associated kinases (IRAKs) are essential components of innate immunity and inflammation in mammals and other vertebrates . They are involved in signal transduction pathways involving IL-1 and IL-18 receptors, Toll-like receptors, nuclear factor-kappaB (NF-kB), and mitogen-activated protein kinases (MAPKs). IRAKs contain an N-terminal death domain (DD) and a C-terminal kinase domain .

Death domains (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 .
Uncharacterized protein Y4yA-like (Y4yA-like)
Type: Family

This entry includes the hypothetical Rhizobium sp. protein Y4yA and similar uncharacterised bacterial proteins. These proteins are homologous to eukaryotic ornithine decarboxylase (ODC) and diaminopimelate decarboxylase (DapDC). ODC and DapDC are fold type III PLP-dependent enzymes that contain an N-terminal PLP-binding TIM-barrel domain and a C-terminal β-sandwich domain, similar to bacterial alanine racemases. ODC participates in the formation of putrescine by catalyzing the decarboxylation of ornithine, the first step in polyamine biosynthesis. DapDC participates in the last step of lysine biosynthesis, the conversion of meso-2,6-diaminoheptanedioate to L-lysine. Proteins in this entry may function as PLP-dependent decarboxylases .
VDR, DNA-binding domain (DBD_VDR)
Type: Domain

This entry represents the DNA-binding domain of vitamin D receptors (VDR). It is composed of two C4-type zinc fingers. Each zinc finger contains a group of four Cys residues which coordinates a single zinc atom. VDR interacts with a VDR response element, a direct repeat of GGTTCA DNA site with 3 bp spacer upstream of the target gene, and modulates the rate of transcriptional initiation .