Module KB
Reusable biological module sketches rendered from YAML. Columns with numeric counts are derived by recursively walking each module document. Click a column header to sort; counts and concepts come straight from the YAML.
| Module | Type | Status | Concepts | Nodes | Annotons | Parts | Variant sets | Variants | Connections | Genes rev. | Leaf gaps | Module DR | Source |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Activin receptor signaling pathway moduleMODULE:activin_receptor_signalingActivin ligands signal through ACVR type I and type II serine/threonine kinase receptors to activate SMAD2/3-SMAD4 transcriptional programs controlling growth and differentiation. | Signaling Pathway | DRAFT | activin receptor signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 1/6 | 0 | ✓ | modules/activin_receptor_signaling.yaml |
| Alzheimer disease-relevant human pathway modulesMODULE:alzheimer_disease_relevant_pathwaysA project-level decomposition of normal human pathway modules represented by the Alzheimer disease review gene set. The module groups gene products by evolved biological roles in APP processing and amyloid-beta handling, lipid/lipoprotein transport, microglial lipid-debris sensing, tau/cytoskeletal kinase biology, and endocytic/adhesion adaptor systems. It is not a causal disease-progression model. | Module | DRAFT | Alzheimer disease-relevant pathway curation set |
6 | 21 | 5 | 0 | 0 | 4 | 0/0 | 0 | ✗ | modules/alzheimer_disease_pathways.yaml |
| Androgen receptor signaling pathway moduleMODULE:androgen_receptor_signalingAndrogen receptor signaling couples steroid ligand binding, chaperone release, nuclear receptor dimerization, and co-regulator recruitment to androgen-responsive transcriptional programs. | Signaling Pathway | DRAFT | androgen receptor signaling pathway |
4 | 8 | 3 | 0 | 0 | 2 | 1/6 | 0 | ✓ | modules/androgen_receptor_signaling.yaml |
| B cell receptor signaling pathway moduleMODULE:b_cell_receptor_signalingAntigen-bound B cell receptor complexes signal through CD79 ITAM subunits, SYK, BLNK, BTK, PLC-gamma, and PI3K to drive calcium, NF-kappaB, MAPK, and transcriptional responses. | Signaling Pathway | DRAFT | B cell receptor signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 1/7 | 0 | ✓ | modules/b_cell_receptor_signaling.yaml |
| BBSome ciliary trafficking complex moduleMODULE:bbsomeThe BBSome is a conserved octameric protein complex that acts as a coat-like adaptor for ciliary membrane-protein trafficking. It is built from eight core subunits (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9, and BBIP1/BBS18), assembled with the help of a dedicated chaperonin-like module (BBS6/MKKS, BBS10, BBS12 acting with the CCT/TRiC chaperonin). Once assembled, the BBSome is recruited to the ciliary membrane by the GTP-bound Arf-like GTPase ARL6/BBS3, where it polymerizes into a coat that recognizes signaling-receptor cargo (ciliary GPCRs and Hedgehog-pathway components) and couples them to the intraflagellar transport (IFT) machinery, mediating ciliary import and, especially, retrieval/export across the transition zone. LZTFL1/BBS17 and the accessory factor CCDC28B regulate BBSome ciliary trafficking. Loss of BBSome function causes Bardet-Biedl syndrome. This module models the BBSome as a cellular component / protein complex grounded in GO:0034464, capturing its composition, assembly, membrane recruitment, cargo trafficking, and regulation. | Protein Complex | DRAFT | BBSome intraciliary transport |
6 | 6 | 5 | 0 | 0 | 4 | 14/14 | 1 | ✗ | modules/bbsome.yaml |
| BMP signaling pathway moduleMODULE:bmp_signalingBMP ligands activate type I and type II serine/threonine kinase receptor complexes that phosphorylate SMAD1/5-family effectors and regulate developmental patterning and differentiation. | Signaling Pathway | DRAFT | BMP signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 0/6 | 0 | ✓ | modules/bmp_signaling.yaml |
| Biological nitrogen cycle moduleMODULE:nitrogen_cycleA taxon-neutral decomposition of the biological nitrogen cycle: the set of microbially driven redox transformations that interconvert dinitrogen, ammonia, hydroxylamine, nitrite, nitrate, nitric oxide, nitrous oxide, and hydrazine. The module is organized by transformation (fixation, nitrification, denitrification, DNRA, anammox, assimilatory reduction, and ammonification) rather than by organism, and uses variant sets where convergent enzyme chemistries (e.g. cd1 vs Cu nitrite reductase) implement the same step. Leaf steps are grounded to canonical reviewed Swiss-Prot exemplars where one exists; abstract function selectors are used where no reviewed exemplar is available (nitrite-oxidizer NXR). Companion to projects/NITROGEN_CYCLE.md and the GO:0071941 obsoletion project (projects/NITROGEN_CYCLE_OBSOLETION.md). | Metabolic Pathway | DRAFT | nitrogen cycle metabolic process |
26 | 19 | 19 | 3 | 6 | 11 | 0/25 | 1 | ✗ | modules/nitrogen_cycle.yaml |
| Budding yeast (S. cerevisiae) high-osmolarity (Ssk2-Pbs2-Hog1) MAPK cascade moduleMODULE:scer_hog1_cascadeA decomposition of the Saccharomyces cerevisiae high-osmolarity glycerol (HOG) MAP kinase cascade, the osmostress-activated fungal realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). High external osmolarity is sensed by two upstream branches - the Sln1 two-component phosphorelay (which derepresses the MAP3Ks Ssk2/Ssk22) and the Sho1 branch (which routes through Ste11) - both converging on the single MAP2K Pbs2, which dually phosphorylates the MAPK Hog1 on its TGY activation-loop motif. Active Hog1 translocates to the nucleus and activates transcription factors (Hot1, Msn2/Msn4, Sko1) that induce glycerol-biosynthesis and stress-response genes restoring osmotic balance. The kinase relay - Ssk2/Ssk22 -> Pbs2 -> Hog1 - is declared as an inner bundle that `conforms_to` mapk_relay, while the osmosensing input and the Hog1 transcriptional output are this cascade's free extensions around the conforming core. Grounded in GO:0007231 (osmosensory signaling pathway). | Signaling Pathway | DRAFT | osmosensory signaling pathway |
10 | 7 | 9 | 0 | 0 | 6 | 0/6 | 1 | ✗ | modules/scer_hog1_cascade.yaml |
| Budding yeast (S. cerevisiae) pheromone-response (Ste11-Ste7-Fus3) MAPK cascade moduleMODULE:scer_mating_fus3_cascadeA decomposition of the Saccharomyces cerevisiae pheromone-response (mating) MAP kinase cascade, the fungal realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). Mating pheromone (a-factor or alpha-factor) activates a G-protein-coupled receptor (Ste2/Ste3); the released G-protein beta-gamma dimer and the PAK kinase Ste20, organized on the scaffold Ste5, activate the MAP3K Ste11, which phosphorylates the MAP2K Ste7, which dually phosphorylates the MAPK Fus3 (and the partially redundant Kss1) on its TEY activation-loop motif. Active Fus3 phosphorylates the transcription factor Ste12 and the cell-cycle inhibitor Far1, driving the mating transcriptional program, G1 arrest, and polarized shmoo formation for conjugation. The kinase relay - Ste11 -> Ste7 -> Fus3 - is declared as an inner bundle that `conforms_to` mapk_relay, while the pheromone/GPCR input and the Ste12/Far1 output are this cascade's free extensions around the conforming core. Grounded in GO:0000750 (pheromone-dependent signal transduction involved in conjugation with cellular fusion). | Signaling Pathway | DRAFT | pheromone-dependent signal transduction involved in conjugation with cellular fusion |
7 | 5 | 6 | 0 | 0 | 4 | 0/4 | 2 | ✗ | modules/scer_mating_fus3_cascade.yaml |
| Canonical Hedgehog/Smoothened signaling pathway moduleMODULE:hedgehog_signalingA compact vertebrate Hedgehog signaling module. Secreted Hedgehog ligand binds Patched, relieving Patched-mediated inhibition of Smoothened. Activated Smoothened accumulates in the primary cilium and shifts GLI transcription factors from repressor processing toward activator output. The module is grounded in GO:0007224, with curated UniProt exemplars for ligand, receptor, transducer, inhibitor, and GLI output; PTN ancestry is recorded only for Smoothened and SUFU, where the local PAINT cache has matching IBD seed rows. | Signaling Pathway | DRAFT | smoothened signaling pathway |
4 | 5 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✗ | modules/hedgehog_signaling.yaml |
| Canonical JAK-STAT cytokine signaling pathway moduleMODULE:jak_stat_signalingA taxon-neutral decomposition of the canonical JAK-STAT signal transduction pathway, the principal route by which type I/II cytokines and many hormones convert an extracellular signal into a direct change in gene transcription. The module is phrased as an ordered set of functions rather than a fixed gene list so it can represent the many receptor/JAK/STAT combinations that share the same mechanistic core: (1) a cytokine ligand binds and reorganizes a single-pass transmembrane receptor so that its intracellular domains are brought together; (2) receptor-associated Janus kinases (JAK1, JAK2, JAK3, TYK2) are juxtaposed and trans-activate by reciprocal tyrosine phosphorylation; (3) activated JAKs phosphorylate tyrosines on the receptor tails, creating phosphotyrosine docking sites; (4) latent cytoplasmic STAT transcription factors (STAT1-4, STAT5A, STAT5B, STAT6) are recruited via their SH2 domains and phosphorylated by the JAKs; (5) phosphorylated STATs dimerize through reciprocal SH2-phosphotyrosine contacts and translocate to the nucleus; (6) STAT dimers bind GAS/ISRE elements and drive transcription of cytokine-response genes; and (7) the response is terminated and tuned by SOCS/CIS proteins, protein tyrosine phosphatases (SHP1/SHP2, PTPN2), and PIAS SUMO ligases. Which JAKs and STATs are used is set by the receptor, captured here as variant sets along a receptor-class axis. The pathway is grounded in GO:0007259 (cell surface receptor signaling pathway via JAK-STAT). | Signaling Pathway | DRAFT | cell surface receptor signaling pathway via JAK-STAT cytokine-mediated signaling pathway |
25 | 28 | 14 | 2 | 10 | 12 | 8/10 | 9 | ✗ | modules/jak_stat_signaling.yaml |
| Canonical NF-kappaB signaling pathway moduleMODULE:nfkb_canonical_signalingA compact canonical NF-kappaB module. Pro-inflammatory receptors such as TNFR1 assemble adaptor/ubiquitin ligase complexes, activate the IKK complex, induce phosphorylation and proteasomal destruction of IkappaB inhibitors, and release NF-kappaB dimers to enter the nucleus and drive inflammatory, survival, and immune-response genes. The module is grounded in GO:0007249 and includes curated TNFR1, TRAF2, IKK, IkappaB, and NF-kappaB exemplars, with PTN anchors where PAINT seed rows support the role. | Signaling Pathway | DRAFT | canonical NF-kappaB signal transduction |
4 | 5 | 3 | 0 | 0 | 2 | 1/7 | 0 | ✗ | modules/nfkb_canonical_signaling.yaml |
| Canonical Notch signaling pathway moduleMODULE:notch_signalingA compact metazoan Notch signaling module. Notch is a contact-dependent juxtacrine pathway in which a Delta/Serrate/LAG-2 family ligand on one cell binds a Notch receptor on a neighboring cell, triggers ADAM/gamma-secretase proteolysis, releases the Notch intracellular domain, and converts CSL/RBPJ transcription complexes from repressors to activators of targets such as HES and HEY family genes. The trunk is grounded in GO:0007219 and annotated with curated UniProt exemplars plus PAINT ancestral nodes where the local PANTHER cache supports a function-by-descent claim. | Signaling Pathway | DRAFT | Notch signaling pathway |
4 | 4 | 3 | 0 | 0 | 2 | 2/3 | 1 | ✗ | modules/notch_signaling.yaml |
| Chemokine-mediated signaling pathway moduleMODULE:chemokine_signalingChemokines activate seven-transmembrane chemokine receptors and heterotrimeric G proteins, coordinating PI3K, calcium, and Rho-family pathways that direct leukocyte migration and positioning. | Signaling Pathway | DRAFT | chemokine-mediated signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 0/6 | 0 | ✓ | modules/chemokine_signaling.yaml |
| Creatine biosynthesis (vertebrate, two-step AGAT to GAMT)MODULE:creatine_biosynthesisDe novo biosynthesis of creatine, the two-step pathway that supplies the phosphocreatine/creatine system used for cellular energy buffering in tissues with high and fluctuating ATP demand (skeletal and cardiac muscle, brain). The pathway is short and committed: L-arginine and glycine are first condensed by L-arginine:glycine amidinotransferase (AGAT/GATM) to give guanidinoacetate (GAA) and L-ornithine, then guanidinoacetate is methylated by guanidinoacetate N-methyltransferase (GAMT) using S-adenosyl-L-methionine (SAM) as the methyl donor to yield creatine and S-adenosyl-L-homocysteine (SAH). The two activities are characteristically split both by subcellular compartment and, in mammals, by organ: AGAT/GATM is a mitochondrial intermembrane-space enzyme and catalyses the first, committed, feedback- regulated step (creatine represses GATM), whereas GAMT is a cytosolic enzyme and is the second, methylation step. The first step is most active in kidney and pancreas and the second predominates in liver, so guanidinoacetate is an inter-organ intermediate that is exported and taken up before methylation; finished creatine is distributed in the blood and imported into target tissues by the creatine transporter SLC6A8. GAMT is also the largest single consumer of SAM-derived methyl groups in the body, tying creatine synthesis to one-carbon / methionine-cycle metabolism. Inherited deficiency of either enzyme (and of the SLC6A8 transporter) causes cerebral creatine-deficiency syndromes. Creatine utilization by the creatine kinases (the phosphocreatine shuttle and the "futile creatine cycle") is downstream of this module and is not part of the biosynthetic pathway itself. | Metabolic Pathway | DRAFT | creatine biosynthetic process |
3 | 2 | 2 | 0 | 0 | 1 | 2/2 | 0 | ✗ | modules/creatine_biosynthesis.yaml |
| Creatine-phosphocreatine system (human)MODULE:creatine_phosphocreatine_systemA navigational grouping for the biology that Reactome bundles as "Creatine metabolism" (R-HSA-71288), assembled here as an explicit biological *system* rather than as a single GO metabolic process. The grouping is deliberately not called "creatine metabolism": GO keys metabolism on the chemical entity, and this system spans more than one entity. It comprises (1) de novo synthesis of the creatine molecule (creatine biosynthetic process, GO:0006601; the AGAT/GATM -> GAMT pathway), (2) the creatine kinase energy-buffer that interconverts creatine and phosphocreatine (phosphocreatine metabolic process, GO:0006603; including phosphocreatine biosynthesis GO:0046314 and the thermogenic futile creatine cycle GO:0140651), (3) inter-organ and cellular distribution of creatine by the SLC6A8 transporter, and (4) non-enzymatic disposal of creatine and phosphocreatine to creatinine for excretion (creatinine metabolic process, GO:0046449). In strict GO terms (2) is phosphocreatine metabolism, not creatine metabolism, so the canonical GO umbrella creatine metabolic process (GO:0006600) covers only (1) and the creatinine-forming arm of (4). This node carries both GO:0006600 and GO:0006603 to make that cross-branch span explicit. The detailed, protein-grounded logic lives in the dedicated modules referenced by each part; this document holds no annotons of its own and exists only to relate them. | Biological Process | DRAFT | creatine metabolic process phosphocreatine metabolic process creatinine metabolic process |
4 | 1 | 3 | 0 | 0 | 3 | 1/1 | 2 | ✗ | modules/creatine_phosphocreatine_system.yaml |
| Cuproptosis (copper-induced cell death) moduleMODULE:cuproptosisA decomposition of cuproptosis: the regulated cell-death program in which excess intracellular copper, reduced to Cu(I) by the mitochondrial ferredoxin FDX1, binds the lipoyl moieties of lipoylated tricarboxylic-acid-cycle enzymes (chiefly the pyruvate dehydrogenase E2 subunit DLAT), driving their disulfide-dependent oligomerization/aggregation while destabilizing iron-sulfur cluster proteins. The resulting proteotoxic stress kills the cell. Cuproptosis is mechanistically distinct from apoptosis, necroptosis, ferroptosis, and pyroptosis, and was defined in human/mammalian cells, so this module is framed for the mammalian implementation with concrete human gene products grounded to UniProt. Design intent: the module is organized as an upstream copper-homeostasis layer that sets the death threshold (importer, chaperone, exporters), a copper- reduction trigger (FDX1), the protein-lipoylation machinery that builds the copper "bait", the lipoylated TCA-cycle targets/effectors (the pyruvate dehydrogenase complex, with DLAT as the aggregation-prone effector), and the execution node (cuproptosis proper). Protective and modulatory regulators (MTF1, GLS, CDKN2A) and the non-substituting paralog FDX2 are kept as an optional regulatory sub-module. Genes are grounded to UniProt only where verified; GO ids are grounded only to verified, non-obsolete terms in the matching aspect (MF in function, BP in processes/concepts, CC in locations). | Biological Process | DRAFT | cuproptosis |
7 | 15 | 6 | 0 | 0 | 8 | 1/16 | 1 | ✗ | modules/cuproptosis.yaml |
| Death receptor apoptotic signaling pathway moduleMODULE:death_receptor_apoptotic_signalingDeath ligands activate death-domain receptors and FADD-containing DISC complexes, bringing initiator caspase-8 into proximity to trigger extrinsic apoptotic protease cascades. | Signaling Pathway | DRAFT | extrinsic apoptotic signaling pathway via death domain receptors |
4 | 6 | 3 | 0 | 0 | 2 | 2/5 | 0 | ✓ | modules/death_receptor_apoptotic_signaling.yaml |
| EGFR signaling pathway moduleMODULE:egfr_signalingEGF-family ligand binding activates EGFR/ERBB1 receptor tyrosine kinase dimers, creating phosphotyrosine docking sites that recruit GRB2/SOS, PI3K, PLCG, and STAT branches for proliferation and differentiation outputs. | Signaling Pathway | DRAFT | epidermal growth factor receptor signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 1/6 | 0 | ✓ | modules/egfr_signaling.yaml |
| ERBB2 signaling pathway moduleMODULE:erbb2_signalingERBB2/HER2 acts as a ligandless preferred dimerization partner for ERBB receptors, especially ERBB3 after neuregulin binding, producing potent PI3K-AKT and MAPK output. | Signaling Pathway | DRAFT | ERBB2 signaling pathway |
4 | 5 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✓ | modules/erbb2_signaling.yaml |
| ERK1/2 (Ras-RAF-MEK-ERK) MAPK cascade moduleMODULE:erk_cascadeA taxon-neutral decomposition of the canonical Ras-RAF-MEK-ERK mitogen-activated protein kinase cascade, the concrete ERK1/2 realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). The cascade converts receptor-proximal tyrosine-phosphorylation events into ERK1/ERK2 activity and a proliferative/differentiation transcriptional program, and is deployed downstream of many distinct receptor systems: receptor tyrosine kinases (EGFR, FGFR, PDGFR, insulin/IGF), cytokine receptors signaling through JAKs, G-protein-coupled receptors, and integrins. The module captures: (1) recruitment of SH2/SH3 adaptors (GRB2, SHC) to a receptor phosphotyrosine; (2) GRB2-mediated recruitment of the Ras guanine nucleotide exchange factor SOS; (3) the Ras nucleotide switch (SOS GEF -> Ras GTPase -> RasGAP), declared as an inner bundle that `conforms_to` gtpase_switch; (4) the conforming ERK kinase relay - Ras-driven RAF(MAP3K) -> MEK1/2(MAP2K) -> ERK1/2(MAPK) on the TEY motif - declared as an inner bundle that `conforms_to` mapk_relay; (5) ERK action on nuclear (ELK1/Ets, RSK, MSK) and cytoplasmic substrates to drive transcription, proliferation, and differentiation; and (6) DUSP/MKP negative feedback on ERK. Grounded in GO:0000165 (MAPK cascade) / GO:0070371 (ERK1 and ERK2 cascade). | Signaling Pathway | DRAFT | MAPK cascade ERK1 and ERK2 cascade |
12 | 9 | 11 | 0 | 0 | 8 | 6/6 | 5 | ✗ | modules/erk_cascade.yaml |
| ERK5 (MEKK2/3-MEK5-ERK5) MAPK cascade moduleMODULE:erk5_cascadeA taxon-neutral decomposition of the ERK5 (big MAP kinase 1, BMK1) cascade, the MEF2-driven concrete realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). Growth factors, and oxidative and osmotic stress, signal through the MAP3Ks MEKK2 (MAP3K2) and MEKK3 (MAP3K3) to the dedicated dual-specificity MAP2K MEK5 (MAP2K5), which dually phosphorylates the MAPK ERK5 (MAPK7) on its TEY activation-loop motif. ERK5 is distinctive in carrying a large C-terminal transcriptional-activation domain in addition to its kinase domain, and its principal output is activation of MEF2-family transcription factors controlling proliferation, survival, and endothelial/cardiovascular development. The kinase relay - MEKK2/3 -> MEK5 -> ERK5 - is declared as an inner bundle that `conforms_to` mapk_relay, while the upstream input and the ERK5/MEF2 output are this cascade's free extensions around the conforming core. Grounded in GO:0070375 (ERK5 cascade). | Signaling Pathway | DRAFT | ERK5 cascade |
7 | 5 | 6 | 0 | 0 | 4 | 0/4 | 2 | ✗ | modules/erk5_cascade.yaml |
| Ephrin receptor signaling pathway moduleMODULE:ephrin_receptor_signalingMembrane-tethered ephrin ligands activate Eph receptor tyrosine kinases across cell-cell contacts, producing bidirectional signals that pattern adhesion, repulsion, migration, and vascular organization. | Signaling Pathway | DRAFT | ephrin receptor signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✓ | modules/ephrin_receptor_signaling.yaml |
| Erythromycin A biosynthesis (Saccharopolyspora erythraea)MODULE:erythromycin_biosynthesisRepresentative-species module for biosynthesis of the macrolide antibiotic erythromycin A in Saccharopolyspora erythraea, encoded by the ery cluster (MIBiG BGC0000055). It is grounded to the concrete S. erythraea gene set reviewed under genes/SACEN/. The module combines a modular type I polyketide synthase (DEBS) that builds the macrolactone, post-PKS cytochrome-P450 oxidations, two TDP-deoxysugar pathways feeding two glycosyltransferases, final O-methylation, and rRNA-methylation self-resistance. Companion prose/MIBiG-alignment notes are in terms/erythromycin_biosynthesis/. | Metabolic Pathway | DRAFT | erythromycin biosynthetic process |
9 | 20 | 8 | 0 | 0 | 6 | 20/20 | 0 | ✓ | modules/erythromycin_biosynthesis.yaml |
| Estrogen receptor signaling pathway moduleMODULE:estrogen_receptor_signalingEstrogen receptors act as ligand-regulated nuclear receptors and signaling scaffolds, recruiting co-regulators to control chromatin, transcription, and cell-type-specific hormone responses. | Signaling Pathway | DRAFT | estrogen receptor signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✓ | modules/estrogen_receptor_signaling.yaml |
| FGFR signaling pathway moduleMODULE:fgfr_signalingFGF ligands and heparan sulfate cofactor activate FGFR receptor tyrosine kinases, recruiting FRS2/GRB2/SOS, PI3K, PLCG, and MAPK outputs for development, angiogenesis, and tissue repair. | Signaling Pathway | DRAFT | fibroblast growth factor receptor signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 0/6 | 0 | ✓ | modules/fgfr_signaling.yaml |
| Fc-epsilon receptor signaling pathway moduleMODULE:fc_epsilon_receptor_signalingHigh-affinity IgE receptor signaling couples FCER1 antigen crosslinking to ITAM phosphorylation, SYK activation, BTK/PLC-gamma signaling, calcium mobilization, and mast-cell effector responses. | Signaling Pathway | DRAFT | Fc-epsilon receptor signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 1/7 | 0 | ✓ | modules/fc_epsilon_receptor_signaling.yaml |
| Fc-gamma receptor signaling pathway moduleMODULE:fc_gamma_receptor_signalingFc-gamma receptor signaling couples immune-complex binding to ITAM-containing receptor chains, SYK/BTK activation, PLC-gamma and PI3K branches, phagocytosis, and inflammatory effector functions. | Signaling Pathway | DRAFT | Fc-gamma receptor signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 1/7 | 0 | ✓ | modules/fc_gamma_receptor_signaling.yaml |
| Ferroptosis (iron-dependent lipid-peroxidation cell death) moduleMODULE:ferroptosisA decomposition of ferroptosis: the iron-dependent form of regulated cell death in which polyunsaturated-fatty-acid (PUFA) phospholipids in cellular membranes undergo iron-catalysed peroxidation to lipid hydroperoxides, ultimately rupturing the membrane. Ferroptosis is morphologically and biochemically distinct from apoptosis, necroptosis, and pyroptosis: there is no caspase cascade and no dedicated executioner enzyme. Instead the program is defined by the balance between (a) a driver arm that supplies the oxidisable substrate (PUFA phospholipids) and the redox-active iron that catalyses peroxidation, and (b) several biochemically independent defense arms that detoxify lipid hydroperoxides or quench the propagating radicals. Death occurs when the defenses are overwhelmed, so ferroptosis is best modelled as one execution node negatively regulated, in parallel and redundantly, by multiple suppressor systems. Design intent: the module is organized as a driver layer (PUFA-phospholipid supply and labile-iron supply) that provides input to a central execution node (GO:0097707 ferroptosis), opposed by four independent suppressor sub-modules that each NEGATIVELY_REGULATE the execution node: the canonical GPX4-glutathione axis, the FSP1-CoQ10 axis, the mitochondrial DHODH-CoQ10 axis, and the GCH1-BH4 (tetrahydrobiopterin) axis. A transcriptional/regulatory sub-module (NRF2/KEAP1, ATF4, p53) tunes the set point of these defenses and is kept optional. The module is framed for the human/mammalian implementation, where ferroptosis was defined, but the core chemistry (iron + O2 + PUFA membranes) and the principal defenses (GPX4, the CoQ system) are deeply conserved across eukaryotes, with ferroptosis-like death reported in plants, fungi, and protozoa. Genes are grounded to UniProt and GO ids taken from the matching per-gene reviews under genes/human/; GO ids are used only in their correct aspect (MF in function, BP in processes/concepts, CC in locations). | Biological Process | DRAFT | ferroptosis |
18 | 27 | 17 | 0 | 0 | 14 | 21/24 | 1 | ✗ | modules/ferroptosis.yaml |
| GPCR-PLC-calcium-PKC signaling pathway moduleMODULE:gpcr_plc_calcium_pkc_signalingA compact Gq/11-coupled GPCR signaling module. Agonist-bound GPCR activates G alpha q/11, which stimulates phospholipase C beta to cleave PIP2 into IP3 and DAG. IP3 releases calcium from intracellular stores, calcium/calmodulin activates calcium-sensitive effectors, and DAG plus calcium activates conventional PKC isoforms such as PRKCA. The pathway is grounded in GO:0007200 and includes PAINT ancestry where local seed rows support PRKCA and calmodulin roles. | Signaling Pathway | DRAFT | phospholipase C-activating G protein-coupled receptor signaling pathway |
5 | 6 | 4 | 0 | 0 | 3 | 2/6 | 0 | ✗ | modules/gpcr_plc_calcium_pkc_signaling.yaml |
| GPCR-cAMP-PKA signaling pathway moduleMODULE:gpcr_camp_pka_signalingA compact Gs-coupled GPCR signaling module. An agonist-occupied GPCR activates heterotrimeric Gs, G alpha s stimulates adenylyl cyclase, cAMP accumulates and activates PKA, and PKA phosphorylates cytosolic and nuclear substrates including CREB. The module is grounded in GO:0007188. ADRB2 is anchored to PAINT GPCR nodes; downstream GNAS, ADCY5, PRKACA, and CREB1 are curated UniProt exemplars without PTN ancestry claims in this first pass. | Signaling Pathway | DRAFT | adenylate cyclase-modulating G protein-coupled receptor signaling pathway |
4 | 5 | 3 | 0 | 0 | 2 | 2/5 | 0 | ✗ | modules/gpcr_camp_pka_signaling.yaml |
| Generic E1-E2-E3 ubiquitin transfer relay motifMODULE:ubiquitin_transfer_relayThe minimal, reusable ubiquitin-conjugation relay: an E1 ubiquitin-activating enzyme adenylates ubiquitin and forms a thioester with it in an ATP-dependent reaction; the activated ubiquitin is passed to the active-site cysteine of an E2 conjugating enzyme; and an E3 ligase brings the E2~ubiquitin together with a selected substrate to transfer ubiquitin onto a substrate lysine. Iteration builds polyubiquitin chains that mark substrates for proteasomal degradation or other fates. The same relay (with cognate activating/conjugating/ligase enzymes) is reused by the ubiquitin-like modifiers SUMO, NEDD8, and ISG15. The motif is gene-free and taxon-neutral, fixing only the E1/E2/E3 roles by molecular-function term and the activating transfer topology. Grounded in GO:0016567 (protein ubiquitination). | Biological Process | DRAFT | protein ubiquitination |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/ubiquitin_transfer_relay.yaml |
| Generic GTPase nucleotide switch motif (GEF / GTP / GAP)MODULE:gtpase_switchThe minimal, reusable nucleotide-switch motif shared by regulatory GTPases: a guanine-nucleotide exchange factor (GEF) loads GTP to flip the GTPase into its active conformation, where it engages downstream effectors; a GTPase-activating protein (GAP) then stimulates GTP hydrolysis to return the switch to its inactive GDP-bound state. The motif is deliberately gene-free and taxon-neutral: it fixes only the GEF/GTPase/GAP roles (by molecular-function term) and the load/hydrolyze topology. Concrete switches - the Ras, Rho/Rac/Cdc42, Rab, Arf, Ran, and heterotrimeric-Galpha families - embed this motif as an inner bundle through `conforms_to`, substituting their own GEF/GTPase/GAP and the specific effectors they activate. Grounded in GO:0007264 (small GTPase-mediated signal transduction). | Signaling Pathway | DRAFT | small GTPase-mediated signal transduction |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/gtpase_switch.yaml |
| Generic PI3K-AKT-mTOR signaling moduleMODULE:pi3k_akt_mtorA taxon-neutral decomposition of the class I PI3K-AKT-mTOR signaling axis, the reusable survival/growth/metabolism arm deployed downstream of many receptor systems. Like the Ras-MAPK cascade it is a "sidecar" module: the same PI3K->PIP3->AKT->mTOR core is engaged by receptor tyrosine kinases (insulin/IGF, EGFR, PDGFR), by insulin-receptor-substrate (IRS) adaptors, by cytokine receptors signaling through JAKs, by GPCRs (class IB PI3K-gamma), and by active Ras. The module captures: (1) recruitment and activation of class I PI3K (p110 catalytic + p85 regulatory subunits) at a receptor phosphotyrosine, via IRS, or by Ras; (2) PI3K conversion of PIP2 to the second messenger PIP3; (3) PIP3-dependent membrane recruitment of PH-domain proteins PDK1 and AKT; (4) AKT activation by dual phosphorylation (PDK1 on Thr308, mTORC2 on Ser473); (5) AKT-driven activation of mTORC1 via inhibition of the TSC1/2 GAP and consequent Rheb-GTP accumulation; (6) downstream outputs - mTORC1 activation of S6K and 4E-BP1 (translation/growth) and AKT inhibition of FOXO and GSK3 (survival, metabolism); and (7) negative regulation, principally the lipid phosphatase PTEN (which removes the 3-phosphate from PIP3), plus PHLPP (AKT dephosphorylation) and the TSC complex. Grounded in GO:0043491 (phosphatidylinositol 3-kinase/protein kinase B signal transduction) and GO:0031929 (TOR signaling). | Signaling Pathway | DRAFT | phosphatidylinositol 3-kinase/protein kinase B signal transduction TOR signaling |
7 | 7 | 6 | 0 | 0 | 5 | 2/2 | 4 | ✗ | modules/pi3k_akt_mtor.yaml |
| Generic SNARE-mediated membrane fusion cycle motifMODULE:snare_fusion_cycleThe minimal, reusable membrane-fusion motif: cognate vesicle (v-/R-) and target (t-/Q-) SNAREs zipper into a four-helix trans-SNARE complex that pulls the two bilayers together; the resulting force drives membrane fusion and cargo delivery; and the ATPase NSF, with its SNAP cofactors, then disassembles the cis-SNARE complex to recycle the SNAREs for another round. This cycle underlies essentially all intracellular vesicular fusion (ER-Golgi, endosomal, synaptic-vesicle, etc.). The motif is gene-free and taxon-neutral, fixing only the SNARE-pairing and fusion roles and the pair -> fuse -> recycle topology. Grounded in GO:0006906 (vesicle fusion). | Transport Step | DRAFT | vesicle fusion |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/snare_fusion_cycle.yaml |
| Generic Wnt signaling pathway moduleMODULE:generic_wnt_signalingA generic, taxon-neutral decomposition of Wnt signaling as a module. Wnt signaling is an ancient metazoan cell-cell communication system in which secreted, lipid-modified Wnt glycoproteins act on neighboring cells to control proliferation, cell-fate specification, polarity, and stem-cell maintenance. The module is phrased as a set of conserved functions and pathway segments rather than a fixed gene list, so it can represent invertebrate and vertebrate implementations and the multiple paralogous family members at each step. It captures the shared upstream events (Wnt acylation, secretion, and receptor engagement) and then branches into the canonical beta-catenin-dependent pathway and the beta-catenin-independent (planar-cell-polarity and calcium) pathways. The canonical branch is modeled with both its ligand-off state (the beta-catenin destruction complex driving beta-catenin turnover) and its ligand-on state (signalosome assembly, destruction-complex inhibition, beta-catenin stabilization, nuclear entry, and TCF/LEF-dependent transcription). | Signaling Pathway | DRAFT | Wnt signaling pathway |
14 | 18 | 8 | 2 | 5 | 9 | 2/13 | 5 | ✗ | modules/wnt_signaling.yaml |
| Generic coat-mediated vesicle budding motifMODULE:vesicle_coat_buddingThe minimal, reusable vesicle-budding motif: a membrane-associated small GTPase (Arf or Sar1, switched on by its GEF) nucleates assembly of a protein coat on the donor membrane; coat adaptors capture transmembrane cargo and concentrate it into the forming bud; polymerization of the coat deforms the membrane and drives scission of a coated vesicle; and the coat is then shed (uncoating, often on GTP hydrolysis) to yield a transport-competent vesicle. The same motif is reused by the COPII (ER exit), COPI (Golgi-to-ER), and clathrin (post-Golgi/ endocytic) systems. The motif is gene-free and taxon-neutral, fixing only the coat, adaptor, and budding roles and the recruit -> capture -> bud -> uncoat topology. Grounded in GO:0006900 (vesicle budding from membrane). | Transport Step | DRAFT | vesicle budding from membrane |
5 | 4 | 4 | 0 | 0 | 3 | 0/0 | 4 | ✗ | modules/vesicle_coat_budding.yaml |
| Generic ferroptosis-defense-factor abundance/activity switch motifMODULE:ferroptosis_defense_factor_switchThe minimal, reusable motif for set-point control of a ferroptosis-defense factor: a defense node - a suppressor whose activity is part_of negative regulation of ferroptosis (GO:0110076) - is held between two opposed arms. A destabilizer arm lowers the suppressor's abundance or activity (it directly negatively regulates the defense node and is itself part_of positive regulation of ferroptosis, GO:0160020), and a stabilizer arm preserves or restores it (it directly positively regulates the defense node and is part_of negative regulation of ferroptosis). The net ferroptosis set-point is the balance of the two arms acting on the shared defense node. Unlike molecular-function-tiered motifs (e.g. the MAPK relay, where every realization shares the MAP3K/MAP2K/MAPK function terms), the tiers of THIS motif are unified by causal role and topology, NOT by a shared molecular function. Two curated GO-CAM realizations make this explicit with completely different machinery: SLC7A11 is destabilized by a CRL3 ubiquitin ligase (CUL3-KCTD10-RBX1) and rescued by a deubiquitinase (USP18); GPX4 is destabilized by chaperone-mediated autophagy (HSPA8-LAMP2) and stabilized by EGLN3/PHD3 prolyl hydroxylation. Concrete realizations therefore embed this motif through `conforms_to` with status WITH_DEVIATIONS - matching the destabilizer/stabilizer topology while substituting instance-specific tier functions - rather than the EXACT status used by shared-function cascades. | Regulatory Step | DRAFT | negative regulation of ferroptosis positive regulation of ferroptosis |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/ferroptosis_defense_factor_switch.yaml |
| Generic gluconeogenesis moduleMODULE:generic_gluconeogenesisA generic, taxon-neutral decomposition of gluconeogenesis as a module. The module is intentionally phrased as a set of functions and pathway segments rather than as a fixed list of genes, so it can represent bacterial, fungal, plant, and animal implementations. | Metabolic Pathway | DRAFT | gluconeogenesis |
11 | 6 | 5 | 2 | 5 | 4 | 0/0 | 8 | ✗ | modules/gluconeogenesis.yaml |
| Generic kinase / phosphatase reversible-phosphorylation toggle motifMODULE:kinase_phosphatase_toggleThe minimal, reusable reversible-phosphorylation switch: a protein kinase phosphorylates a substrate to set one functional state, and an opposing protein phosphatase removes the phosphate to reset it. This antagonistic kinase/ phosphatase pair acting on a shared substrate is the most pervasive regulatory toggle in biology (cell-cycle CDK/phosphatase pairs, the DUSP/MKP feedback in MAPK cascades, receptor kinase/phosphatase balance, etc.). The motif is gene-free and taxon-neutral: it fixes only the kinase and phosphatase roles by molecular-function term and their opposing action on one substrate state. Concrete switches embed it through `conforms_to`, substituting their own kinase, phosphatase, and substrate. Grounded in GO:0006468 (protein phosphorylation) and GO:0006470 (protein dephosphorylation). | Regulatory Step | DRAFT | protein phosphorylation protein dephosphorylation |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/kinase_phosphatase_toggle.yaml |
| Generic phosphotyrosine-adaptor recruitment motifMODULE:phosphotyrosine_adaptor_recruitmentThe minimal, reusable receptor-proximal recruitment motif: an activated receptor (or receptor-associated kinase) presents a phosphotyrosine docking site; an SH2- or PTB-domain adaptor recognizes that phosphotyrosine; and the adaptor, through a second interaction surface (e.g. an SH3 domain), recruits a downstream effector to the membrane. This pTyr -> adaptor -> effector wiring is the generic interface by which receptor tyrosine kinases, cytokine-receptor- associated JAKs, and other tyrosine-phosphorylation events launch downstream pathways - it is the recruitment step that precedes the Ras switch in MODULE:erk_cascade. The motif is gene-free and taxon-neutral, fixing only the phosphotyrosine-binding and adaptor roles and the recruitment topology. Grounded in GO:0007169 (cell surface receptor protein tyrosine kinase signaling pathway). | Signaling Pathway | DRAFT | cell surface receptor protein tyrosine kinase signaling pathway |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/phosphotyrosine_adaptor_recruitment.yaml |
| Generic three-tier MAP kinase relay (MAP3K -> MAP2K -> MAPK)MODULE:mapk_relayThe minimal, reusable core motif shared by all mitogen-activated protein kinase cascades: a three-tier protein kinase relay in which a MAP kinase kinase kinase (MAP3K) phosphorylates and activates a MAP kinase kinase (MAP2K), which in turn dually phosphorylates the activation loop of a MAP kinase (MAPK). The motif is deliberately gene-free and taxon-neutral: it fixes only the three tier identities (by molecular-function term) and the activating phosphotransfer topology that connects them. Concrete cascades - ERK1/2, p38, JNK, ERK5, the fungal Fus3/Kss1/Hog1 pathways, and plant MPK cascades - embed this motif as an inner bundle through `conforms_to`, substituting their own kinase families and adding their own upstream activation and downstream effector steps before and after the relay. Grounded in GO:0000165 (MAPK cascade). | Signaling Pathway | DRAFT | MAPK cascade |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/mapk_relay.yaml |
| Generic two-component / phosphorelay signal transduction motifMODULE:two_component_relayThe minimal, reusable phosphorelay motif of two-component signal transduction: a sensor histidine kinase autophosphorylates on a conserved histidine in response to a stimulus, then transfers the phosphoryl group to a conserved aspartate on a cognate response regulator, which effects the output (often transcriptional). An optional histidine-phosphotransfer (Hpt) step inserts a His->Asp->His->Asp multistep relay between the sensor and the terminal response regulator. The motif is gene-free and taxon-neutral: it fixes the sensor-kinase / (phosphotransfer) / response-regulator roles by molecular-function term and the His->Asp phosphotransfer topology. Bacterial, archaeal, plant, and fungal two-component systems embed it through `conforms_to` (e.g. the Sln1->Ypd1->Ssk1 phosphorelay upstream of MODULE:scer_hog1_cascade). Grounded in GO:0000160 (phosphorelay signal transduction system). | Signaling Pathway | DRAFT | phosphorelay signal transduction system |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/two_component_relay.yaml |
| Generic zymogen protease-activation cascade motifMODULE:protease_activation_cascadeThe minimal, reusable proteolytic-activation motif: an active protease cleaves an inactive zymogen at a specific site, converting it into the next active protease, which in turn activates the following zymogen (and acts on effector substrates). Iterating this step builds the self-amplifying proteolytic cascades of the caspase apoptosis pathway, the complement system, and the coagulation cascade. The motif is gene-free and taxon-neutral: it fixes only the protease and zymogen-substrate roles and the cleavage-activates-the-next topology. Concrete cascades embed it through `conforms_to`, substituting their own protease family and zymogen substrates. Grounded in GO:0031638 (zymogen activation). | Biological Process | DRAFT | zymogen activation |
4 | 3 | 3 | 0 | 0 | 2 | 0/0 | 3 | ✗ | modules/protease_activation_cascade.yaml |
| Glucocorticoid receptor signaling pathway moduleMODULE:glucocorticoid_receptor_signalingGlucocorticoid receptor signaling couples steroid ligand binding, HSP90/co-chaperone regulation, nuclear translocation, and co-regulator exchange to anti-inflammatory and metabolic transcriptional programs. | Signaling Pathway | DRAFT | nuclear receptor-mediated glucocorticoid signaling pathway |
4 | 8 | 3 | 0 | 0 | 2 | 1/6 | 0 | ✓ | modules/glucocorticoid_receptor_signaling.yaml |
| Gluconeogenesis (human) with precursor-entry routesMODULE:gluconeogenesis_human_substratesExtension of the human gluconeogenesis module that makes the choice of non-carbohydrate precursor explicit. The three physiological precursors enter the pathway at different points: lactate (via lactate dehydrogenase) and the glucogenic amino acid alanine (via alanine aminotransferase) are converted to pyruvate and so require the pyruvate carboxylase / phosphoenolpyruvate carboxykinase backbone, whereas glycerol enters lower down — glycerol kinase and cytosolic glycerol-3-phosphate dehydrogenase feed dihydroxyacetone phosphate directly into the triose-phosphate pool, bypassing pyruvate carboxylase and PEPCK entirely. All routes converge on the shared fructose-1,6-bisphosphatase step and the terminal endoplasmic-reticulum glucose-6-phosphatase system (G6PC1 plus the SLC37A4 antiporter). Because glycerol bypasses the carboxylation arm, pyruvate carboxylase is no longer required by every route: the only steps common to all precursor routes are the terminal G6PC1·SLC37A4 system, which is therefore the single universal gate of free-glucose output. The module is built to be evaluated against tissue expression so that, per tissue, one can ask not just whether gluconeogenesis is possible but which precursors a tissue is equipped to use. | Metabolic Pathway | DRAFT | gluconeogenesis |
23 | 13 | 10 | 6 | 12 | 0 | 0/13 | 0 | ✗ | modules/gluconeogenesis_human_substrates.yaml |
| Gluconeogenesis (human, tissue- and compartment-resolved)MODULE:gluconeogenesis_humanHuman gluconeogenesis: the synthesis of free glucose from non-carbohydrate precursors (lactate, glucogenic amino acids such as alanine, and glycerol). Unlike the taxon-neutral gluconeogenesis template, this module is grounded to specific human isozymes and is organised around the fact that in a metazoan the pathway is not uniformly active: every cell carries the genes, but free-glucose output is restricted to a few tissues. Three control points are encoded as variant sets over human isozymes that differ by tissue and subcellular compartment: the phosphoenolpyruvate-forming step (cytosolic PCK1 vs mitochondrial PCK2), the fructose-1,6-bisphosphatase step (gluconeogenic FBP1 vs muscle FBP2), and the terminal glucose-releasing step, which is a two-component endoplasmic-reticulum system requiring both a catalytic subunit and the glucose-6-phosphate antiporter SLC37A4. The terminal step is the physiological gate: only tissues expressing the gluconeogenic catalytic subunit G6PC1 together with SLC37A4 can release free glucose, which is why liver, kidney cortex, and intestine are gluconeogenic while skeletal muscle and brain are not. This module is designed to be evaluated against tissue expression data: each isozyme atom is an expressed/not-expressed predicate per context, so the realised route through the pathway can be resolved per tissue. | Metabolic Pathway | DRAFT | gluconeogenesis |
12 | 7 | 7 | 2 | 4 | 4 | 0/7 | 1 | ✗ | modules/gluconeogenesis_human.yaml |
| HGF-MET signaling pathway moduleMODULE:hgf_met_signalingHepatocyte growth factor activates the MET receptor tyrosine kinase, recruiting multisite docking adaptors that coordinate motility, invasive growth, survival, and epithelial morphogenesis. | Signaling Pathway | DRAFT | hepatocyte growth factor receptor signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✓ | modules/hgf_met_signaling.yaml |
| Hippo-YAP/TAZ signaling pathway moduleMODULE:hippo_signalingA compact Hippo pathway module. Upstream polarity, junctional, mechanical, and stress inputs activate the MST1/2 kinase tier, which activates LATS1/2 kinases through scaffolded phosphorylation. Active LATS1/2 phosphorylate YAP/TAZ, causing cytoplasmic retention or degradation and suppressing TEAD-dependent growth programs. When the kinase cassette is inactive, YAP/TAZ enter the nucleus and coactivate TEAD transcription factors. The module is grounded in GO:0035329, with PAINT anchors for STK4/MST1 and LATS1 where local seed rows support the kinase-pathway roles. | Signaling Pathway | DRAFT | hippo signaling |
4 | 5 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✗ | modules/hippo_signaling.yaml |
| Histidine biosynthesis (GapMind-derived DRAFT)MODULE:gapmind_his_biosynthesisAuto-converted DRAFT module for Histidine biosynthesis, mined from the GapMind amino-acid pathway definition 'his.steps' and grounded against ModelSEED. Generated by a feasibility-spike importer; GO molecular-function term assignments and biological prose are intentionally left for human/deep-research review and must not be treated as curated. | Metabolic Pathway | DRAFT | 12 | 11 | 11 | 0 | 0 | 0 | 0/0 | 9 | ✗ | modules/experimental/gapmind-mining/his-from-gapmind.yaml | |
| IL-1 signaling pathway moduleMODULE:il1_signalingIL-1 cytokines activate IL1R1/IL1RAP receptor complexes and MyD88-IRAK-TRAF6 signaling assemblies to induce NF-kappaB and inflammatory transcriptional responses. | Signaling Pathway | DRAFT | interleukin-1-mediated signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 1/6 | 0 | ✓ | modules/il1_signaling.yaml |
| IL-6 signaling pathway moduleMODULE:il6_signalingIL-6 engages IL6R and gp130/IL6ST receptor complexes, activating JAK kinases and STAT3-centered transcriptional programs that control inflammation, acute-phase responses, and differentiation. | Signaling Pathway | DRAFT | interleukin-6-mediated signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 2/6 | 0 | ✓ | modules/il6_signaling.yaml |
| Insulin receptor signaling pathway moduleMODULE:insulin_receptor_signalingA compact insulin receptor signaling module. Insulin binding activates the receptor tyrosine kinase INSR, which autophosphorylates and phosphorylates IRS adaptors. IRS phosphotyrosines recruit PI3K and route the signal into PIP3-AKT signaling, controlling FOXO-dependent transcription, glucose uptake, glycogen metabolism, growth, and survival. The module is grounded in GO:0008286 and uses PAINT PTN anchors for the insulin receptor and AKT-family signaling roles where local IBD seed rows support them. | Signaling Pathway | DRAFT | insulin receptor signaling pathway |
4 | 5 | 3 | 0 | 0 | 2 | 1/5 | 0 | ✗ | modules/insulin_receptor_signaling.yaml |
| Integrin-FAK-SRC signaling pathway moduleMODULE:integrin_fak_src_signalingA compact integrin signaling module. Extracellular-matrix engagement clusters integrins, talin/kindlin link cytoplasmic integrin tails to actin, FAK/PTK2 and SRC-family kinases are recruited and activated at focal adhesions, and adaptor scaffolds such as paxillin route the signal to Rho GTPase, MAPK, PI3K, migration, survival, and mechanotransduction outputs. The module is grounded in GO:0007229 and includes PAINT PTN anchors for the FAK/SRC tyrosine kinase tier where local IBD rows support the role. | Signaling Pathway | DRAFT | integrin-mediated signaling pathway |
4 | 5 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✗ | modules/integrin_fak_src_signaling.yaml |
| Intrinsic apoptotic signaling pathway moduleMODULE:intrinsic_apoptotic_signalingCell-intrinsic stress signals regulate BCL2-family mitochondrial permeabilization, cytochrome c release, apoptosome assembly, and initiator caspase-9 activation. | Signaling Pathway | DRAFT | intrinsic apoptotic signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 3/5 | 0 | ✓ | modules/intrinsic_apoptotic_signaling.yaml |
| Isoleucine biosynthesis (GapMind-derived DRAFT)MODULE:gapmind_ile_biosynthesisAuto-converted DRAFT module for Isoleucine biosynthesis, mined from the GapMind amino-acid pathway definition 'ile.steps' and grounded against ModelSEED. Generated by a feasibility-spike importer; GO molecular-function term assignments and biological prose are intentionally left for human/deep-research review and must not be treated as curated. | Metabolic Pathway | DRAFT | 18 | 13 | 14 | 1 | 3 | 0 | 0/0 | 10 | ✗ | modules/experimental/gapmind-mining/ile-from-gapmind.yaml | |
| JNK (c-Jun N-terminal kinase) stress-activated MAPK cascade moduleMODULE:jnk_cascadeA taxon-neutral decomposition of the JNK (c-Jun N-terminal kinase) cascade, the stress- and cytokine-activated concrete realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). Environmental stress and inflammatory cytokines signal through upstream MAP3Ks (MEKK1/MAP3K1, ASK1, MLK family) to the dual-specificity MAP2Ks MKK4 (MAP2K4) and MKK7 (MAP2K7), which dually phosphorylate the JNK MAPKs (JNK1/2/3) on their TPY activation-loop motif. Active JNK phosphorylates the transcription factor c-Jun (and JunD, ATF2), assembling the AP-1 transcriptional program that controls stress responses, apoptosis, and proliferation. The kinase relay - MAP3K -> MKK4/7 -> JNK - is declared as an inner bundle that `conforms_to` mapk_relay, while the stress/cytokine input and the JNK/AP-1 output and DUSP-mediated feedback are this cascade's free extensions around the conforming core. Grounded in GO:0007254 (JNK cascade) / GO:0051403 (stress-activated MAPK cascade). | Signaling Pathway | DRAFT | JNK cascade stress-activated MAPK cascade |
8 | 6 | 7 | 0 | 0 | 5 | 0/4 | 3 | ✗ | modules/jnk_cascade.yaml |
| Ketone body oxidation (ketolysis)MODULE:ketone_body_oxidationMitochondrial oxidation of the ketone bodies D-3-hydroxybutyrate and acetoacetate to acetyl-CoA for entry into the TCA cycle, the route by which extrahepatic tissues (heart, brain, skeletal muscle, renal cortex) use ketone bodies as fuel during fasting. The pathway is three obligate steps: D-3-hydroxybutyrate dehydrogenase (BDH1) oxidises 3-hydroxybutyrate to acetoacetate; succinyl-CoA:3-oxoacid CoA-transferase (OXCT1/SCOT) activates acetoacetate to acetoacetyl-CoA; and acetyl-CoA acetyltransferase (ACAT1, mitochondrial thiolase) thiolytically cleaves acetoacetyl-CoA to two acetyl-CoA. The SCOT step is the committed, irreversible activation step and the metabolic switch that distinguishes ketone-consuming tissues from the liver: the liver produces ketone bodies but does not express OXCT1, so it cannot re-oxidise them and instead exports them. This module is built to be evaluated against tissue expression so that the tissues capable of ketone-body oxidation, and the basis of the liver's inability, can be resolved directly. | Metabolic Pathway | DRAFT | ketolysis |
4 | 3 | 3 | 0 | 0 | 2 | 0/3 | 0 | ✗ | modules/ketone_body_oxidation.yaml |
| L-histidine biosynthesis (microbial)MODULE:histidine_biosynthesisDe novo biosynthesis of L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) and ATP. This is an ancient, largely linear pathway of ten enzymatic activities that is broadly conserved across bacteria, archaea, fungi, and plants, and is the canonical microbial route. The pathway is metabolically unusual in that its purine-like intermediates connect it to nucleotide metabolism: the imidazole-glycerol-phosphate synthase step releases AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), a purine-biosynthesis intermediate, recycling the adenine ring of ATP back into the nucleotide pool. Several activities are commonly fused or bifunctional in microbes (e.g. the HisIE pyrophosphohydrolase/cyclohydrolase, and the HisB dehydratase fused to a histidinol-phosphate phosphatase domain in enteric bacteria), and the terminal HisD histidinol dehydrogenase performs two successive NAD+-dependent oxidations through a histidinal intermediate. The pathway is energetically expensive and is tightly regulated, classically by feedback inhibition of the first committed enzyme (ATP phosphoribosyltransferase, HisG) by L-histidine. | Metabolic Pathway | DRAFT | L-histidine biosynthetic process |
11 | 11 | 10 | 0 | 0 | 9 | 0/0 | 10 | ✗ | modules/histidine_biosynthesis.yaml |
| L-methionine biosynthesis (from homoserine)MODULE:methionine_biosynthesisDe novo biosynthesis of L-methionine from L-homoserine, modelled as a species-agnostic pathway template with alternative routes at three steps, so the same logic can be evaluated across genomes (a eukaryote-to-prokaryote test of the module satisfiability engine). Homoserine is first activated by acylation, for which bacteria use either an O-succinyltransferase (metA) or an O-acetyltransferase (metX). Sulfur is then incorporated to give homocysteine by one of two routes: trans-sulfuration (cystathionine gamma-synthase metB plus cystathionine beta-lyase metC, drawing sulfur from cysteine) or direct sulfhydrylation (an O-acyl-homoserine sulfhydrylase, metY/metZ, using free sulfide in a single step). Finally homocysteine is methylated to methionine by either the cobalamin-independent synthase (metE) or the cobalamin-dependent synthase (metH). Because every step has alternatives, no single enzyme is universally required; an organism makes methionine if it encodes at least one option at each of the three steps. This mirrors GapMind-style pathway reconstruction: the template defines steps and route alternatives, and a per-genome oracle decides which candidates are present. | Metabolic Pathway | DRAFT | methionine biosynthesis |
12 | 7 | 5 | 3 | 6 | 2 | 0/0 | 0 | ✗ | modules/methionine_biosynthesis.yaml |
| L-tryptophan biosynthesis (microbial)MODULE:tryptophan_biosynthesisDe novo biosynthesis of L-tryptophan from chorismate, the branch-point precursor of the aromatic amino acids. Five enzymatic activities convert chorismate to L-tryptophan, drawing in L-glutamine (amide nitrogen), PRPP (5-phospho-alpha-D-ribose 1-diphosphate), and L-serine, and releasing pyruvate, CO2 and glyceraldehyde 3-phosphate along the way. The pathway is the classic textbook microbial operon (the trp operon) and is notable for extensive enzyme fusion and channeling: anthranilate synthase is a glutamine amidotransferase built from a synthase component (TrpE) and a glutaminase component (TrpD/TrpG), the latter frequently fused to anthranilate phosphoribosyltransferase in enteric bacteria; phosphoribosylanthranilate isomerase (TrpF) is often fused to indole-3-glycerol-phosphate synthase (TrpC); and the terminal tryptophan synthase is an alpha-2-beta-2 complex in which indole produced at the TrpA (alpha) active site is channeled through an intramolecular tunnel to the TrpB (beta) active site, where it condenses with L-serine, so free indole is not released. The pathway is feedback-regulated by L-tryptophan, classically at anthranilate synthase and, in many bacteria, also transcriptionally via attenuation and the TrpR repressor. | Metabolic Pathway | DRAFT | L-tryptophan biosynthetic process |
8 | 8 | 5 | 1 | 2 | 4 | 0/0 | 6 | ✗ | modules/tryptophan_biosynthesis.yaml |
| Methionine (S-adenosylmethionine) cycle moduleMODULE:methionine_cycleA taxon-neutral decomposition of the methionine / S-adenosylmethionine (SAM) cycle, the core methyl-group-cycling pathway that interconverts methionine, S-adenosyl-L-methionine, S-adenosyl-L-homocysteine, and homocysteine, with exits to transsulfuration (via cystathionine beta-synthase) and remethylation inputs from folate (via methionine synthase) and choline/betaine (via BHMT). This module is intentionally structured in two layers. The CATALYTIC layer (enzymatic steps) grounds each step to a GO molecular-function term, the same EC <-> GO MF alignment used by the gluconeogenesis module. The REGULATORY layer is captured as connections of type POSITIVELY_REGULATES / NEGATIVELY_REGULATES whose predicate is grounded to a Systems Biology Ontology (SBO) term that distinguishes the MECHANISM (competitive vs allosteric), with the effector represented as a ChEBI-grounded metabolite-pool node. This regulatory wiring (small-molecule effector -> enzyme, with mechanism and sign) is information GO cannot express: GO annotations attach to gene products, the effectors here are metabolites, and GO has no competitive-vs-allosteric distinction. The regulatory structure is transcribed from the biosustain Maud kinetic model `data/methionine/methionine_cycle.toml`. A notable showcase is METAT, where two isozyme forms of methionine adenosyltransferase catalyse the SAME reaction but are OPPOSITELY regulated by SAM: MAT-I is competitively product-inhibited by SAM, whereas MAT-III is allosterically activated by SAM. Isozyme-specific regulation of this kind is the central thing GO flattens away. | Metabolic Pathway | DRAFT | methionine cycle |
17 | 9 | 11 | 2 | 5 | 20 | 0/0 | 11 | ✗ | modules/methionine_cycle.yaml |
| NLR signaling pathway moduleMODULE:nlr_signalingNucleotide-binding leucine-rich-repeat receptors detect intracellular perturbations and assemble RIPK-, ASC-, or caspase-containing signaling platforms for inflammatory and antimicrobial responses. | Signaling Pathway | DRAFT | nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✓ | modules/nlr_signaling.yaml |
| Neurotrophin TRK receptor signaling pathway moduleMODULE:neurotrophin_trk_signalingNeurotrophins activate TRK receptor tyrosine kinases, engaging Ras-MAPK, PI3K-AKT, and PLC-gamma branches that regulate neuronal survival, differentiation, and plasticity. | Signaling Pathway | DRAFT | neurotrophin TRK receptor signaling pathway |
4 | 8 | 3 | 0 | 0 | 2 | 0/6 | 0 | ✓ | modules/neurotrophin_trk_signaling.yaml |
| Nicotine biosynthesis module (Nicotiana / Solanaceae)MODULE:nicotine_biosynthesisA plant-scoped, recursively decomposable decomposition of nicotine biosynthesis as it operates in Nicotiana (tobacco / wild tobacco). Nicotine is an alkaloid built by condensing two separately made rings: a PYRIDINE ring supplied by the aspartate-derived NAD/quinolinate (pyridine nucleotide) branch, and a PYRROLIDINE ring (the N-methyl-Delta1-pyrrolinium cation) supplied by the polyamine/ornithine branch. The module separates these two upstream supply branches from the late "nicotine synthase" cascade that joins the rings, and from the vacuolar transport/metabolon step. This module is intentionally NOT a flat gene list (that lives in the per-gene NICAT reviews and the NICOTINE_BIOSYNTHESIS project). Its purpose is to capture the pathway-level structure that the individual gene reviews cannot: the two-branch convergence, the recently revised late steps, and the co-clustered transport component. The late steps are phrased to reflect the 2025-2026 revision of the pathway. In the classical model the N-methylpyrrolinium cation condensed with a nicotinic acid derivative directly. The new model ("complete biosynthesis of nicotine", Cell 2026, PMID:41928514; "nicotine biosynthesis completed by cryptic activating glucosylation", Nat Commun 2026, PMID:42151135) routes nicotinic acid through a hidden N-glucosylation/reduction/condensation/deglucosylation relay: a UDP-glucosyltransferase (UGT1/NaGT) glucosylates nicotinic acid to nicotinic acid N-glucoside, an A622/NaGR reductase and a BBL oxidase act on the activated glucoside during condensation with the pyrrolidine ring, and a beta-glucosidase (beta-GD1/NicGH) removes the sugar to release nicotine. A vacuolar-membrane MATE transporter (MATE1) co-clusters with A622 and beta-GD1 and is required for high heterologous production. This activating-glucosylation relay and the A622-MATE1-beta-GD1 metabolon are the parts of the pathway that GO biological-process and molecular-function terms flatten away. | Metabolic Pathway | DRAFT | nicotine biosynthetic process |
21 | 14 | 14 | 3 | 6 | 11 | 13/13 | 1 | ✗ | modules/nicotine_biosynthesis.yaml |
| Nitric oxide-cGMP signaling pathway moduleMODULE:nitric_oxide_cgmp_signalingNitric oxide activates soluble guanylate cyclase to raise cGMP, engaging PRKG and cyclic nucleotide phosphodiesterases that control vascular smooth muscle tone and other cGMP-dependent outputs. | Signaling Pathway | DRAFT | nitric oxide-cGMP-mediated signaling |
4 | 5 | 3 | 0 | 0 | 2 | 0/5 | 0 | ✓ | modules/nitric_oxide_cgmp_signaling.yaml |
| Nodal signaling pathway moduleMODULE:nodal_signalingNodal/TGF-beta family ligands use EGF-CFC co-receptors and activin-class receptors to activate SMAD2/3 transcriptional programs for embryonic axis formation and cell-fate decisions. | Signaling Pathway | DRAFT | nodal signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 1/7 | 0 | ✓ | modules/nodal_signaling.yaml |
| Oxidative phosphorylation (OXPHOS) moduleMODULE:oxidative_phosphorylationA taxon-neutral decomposition of oxidative phosphorylation: the coupled process by which a respiratory electron transport chain (ETC) oxidizes reduced cofactors and uses the released free energy to pump protons across a coupling membrane, and an F1Fo-ATP synthase uses the resulting proton-motive force to phosphorylate ADP. The module is deliberately phrased in terms of functional modules, protein complexes, and pathway segments rather than a fixed gene list, so it can represent the mitochondrial inner-membrane chain of eukaryotes and the plasma-membrane respiratory chains of aerobic bacteria. Design intent for complexes (the central modelling question): each respiratory complex is represented as a single PROTEIN_COMPLEX node whose emergent, complex-level catalytic activity is carried by ONE complex-level annoton (the redox half-reaction it performs), with its functionally important subunits exposed as `active_units` on the complex descriptor rather than as separate per-subunit annotons. This mirrors the GO `contributes_to` philosophy: an individual subunit contributes to but does not independently enable the complex activity. Large, internally modular complexes (Complex I; the F1Fo-ATP synthase) are additionally decomposed with `parts` into their functional sub-modules (the N/Q/proton-pumping arms of Complex I; the F1 catalytic head and Fo proton turbine of ATP synthase) — this recursive decomposition is the payoff of the module representation over a flat subunit list. Lineage- and chemistry-specific alternatives that bypass the proton-pumping complexes (type-II NADH dehydrogenase, the alternative oxidase, bacterial bd-type oxidases) are captured as `variant_sets` along explicit axes, so OXPHOS reads as one conserved energy-conservation plan with multiple implementations. Complex assembly/biogenesis is treated as a distinct process from chain operation and kept as an optional sub-module. | Biological Process | DRAFT | oxidative phosphorylation aerobic respiration generation of precursor metabolites and energy |
24 | 23 | 18 | 2 | 5 | 9 | 0/0 | 19 | ✗ | modules/oxphos.yaml |
| Oxygenic photosynthesis moduleMODULE:oxygenic_photosynthesisA taxon-neutral decomposition of oxygenic photosynthesis as a recursively decomposable module. The module separates the thylakoid light reactions (light harvesting, water oxidation at photosystem II, the cytochrome b6f complex, photosystem I, mobile electron carriers, ferredoxin-NADP+ reductase, and the ATP synthase) from carbon fixation by the Calvin-Benson-Bassham reductive pentose-phosphate cycle, and adds optional photoprotection/electron balancing, the inorganic carbon-concentrating mechanism, and chlorophyll supply. It is phrased as functions, complexes, and pathway segments rather than a fixed gene list so it can represent cyanobacterial, algal, and plant implementations. Anoxygenic photosynthesis (single reaction center, non-water electron donors) is explicitly out of scope. | Biological Process | DRAFT | oxygenic photosynthesis |
25 | 22 | 17 | 3 | 7 | 9 | 3/6 | 14 | ✓ | modules/photosynthesis.yaml |
| PDGFR signaling pathway moduleMODULE:pdgfr_signalingPlatelet-derived growth factor ligands activate PDGFR receptor tyrosine kinases, recruiting SH2 adaptors and lipid-kinase branches that control mesenchymal proliferation, migration, and survival. | Signaling Pathway | DRAFT | platelet-derived growth factor receptor signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 1/5 | 0 | ✓ | modules/pdgfr_signaling.yaml |
| Peroxisome lifecycle and matrix protein import moduleMODULE:peroxisome_lifecyclePeroxisomes are maintained by coordinated membrane-protein delivery, matrix cargo recognition, receptor docking and translocation at the importomer, ubiquitin-dependent receptor recycling, membrane growth and division, and import of resident metabolic enzymes. This module captures the conserved peroxin roles and the major route variants that support peroxisome assembly, inheritance, and function across eukaryotes. | Organelle Lifecycle | DRAFT | peroxisome organization peroxisome |
20 | 14 | 9 | 5 | 10 | 8 | 16/18 | 5 | ✓ | modules/peroxisome-lifecycle.yaml |
| Phosphocreatine shuttle / creatine kinase system (human)MODULE:phosphocreatine_shuttleThe creatine kinase (CK) / phosphocreatine energy-buffer system, which uses the creatine produced by creatine biosynthesis (see MODULE:creatine_biosynthesis) as a spatial and temporal buffer of ATP. This module covers creatine *utilization*, not its synthesis. A single reversible reaction, creatine kinase activity (ATP + creatine <=> ADP + phosphocreatine, GO:0004111), is run in two cellular locations by compartment-specific isozymes to form a shuttle: mitochondrial CK isozymes (CKMT1A/B ubiquitous, CKMT2 sarcomeric) sit in the mitochondrial intermembrane space and use ATP exported from oxidative phosphorylation to phosphorylate creatine, producing phosphocreatine; phosphocreatine, being small and diffusible, moves through the cytosol to sites of high ATP turnover, where cytosolic CK isozymes (CKB brain-type, CKM muscle-type; assembled as CK-BB, CK-MB, and CK-MM dimers) regenerate ATP from phosphocreatine and ADP exactly where it is consumed. The net effect is to shuttle high-energy phosphate from mitochondria to ATPases and to buffer the cytosolic ATP/ADP ratio in tissues with high, fluctuating energy demand (skeletal and cardiac muscle, brain, photoreceptors, spermatozoa). The same enzymes also support a thermogenic "futile creatine cycle" (GO:0140651) in some adipocytes, in which phosphocreatine is hydrolysed back to creatine (releasing heat) rather than donating phosphate to ADP. The catalytic species are oligomers, and the participants here are modelled as protein complexes mirroring Reactome: the mitochondrial limb as alternative homo-octamers and the cytosolic limb as the CK-MM, CK-BB, and CK-MB dimers (the heterodimer being a genuine two-gene-product catalytic unit). This module is distinct from, and downstream of, creatine biosynthesis: it consumes creatine, it does not make it. | Metabolic Pathway | DRAFT | phosphocreatine biosynthetic process |
8 | 5 | 2 | 2 | 5 | 2 | 4/4 | 0 | ✗ | modules/phosphocreatine_shuttle.yaml |
| Plant cellulose biosynthesis moduleMODULE:plant_cellulose_biosynthesisA taxon-neutral decomposition of plant cellulose biosynthesis as a recursively decomposable module. Cellulose is synthesized at the plasma membrane by the cellulose synthase complex (CSC, the "rosette"), which polymerizes UDP-glucose into (1->4)-beta-D-glucan chains that coalesce into crystalline microfibrils in the apoplast. The module separates (1) UDP-glucose substrate supply, (2) glucan polymerization by the CSC with distinct primary- and secondary-cell-wall CESA isoform sets, (3) guidance of CSC trajectory by the cortical microtubule cytoskeleton, (4) accessory enzymes/proteins required for productive synthesis (KORRIGAN endoglucanase, COBRA), and (5) microfibril assembly and organization. It is phrased as functions, complexes, and pathway segments rather than a fixed gene list so it can represent angiosperm, grass, and (with substitution) algal implementations. Concrete UniProt members are Arabidopsis exemplars, not species-restricting claims. Cellulose synthase-like (CSL) backbones of hemicelluloses, lignin biosynthesis, and the bacterial BcsA-type machinery are out of scope. As a bioenergy module, the polymerization step and its CESA isoform composition are the principal determinants of biomass recalcitrance and the main engineering targets for improved lignocellulosic saccharification. | Metabolic Pathway | DRAFT | plant-type cell wall cellulose biosynthetic process cellulose biosynthetic process |
12 | 9 | 7 | 2 | 4 | 4 | 0/9 | 3 | ✗ | modules/cellulose_biosynthesis.yaml |
| RIG-I signaling pathway moduleMODULE:rig_i_signalingRIG-I detects viral RNA and signals through MAVS to activate TBK1/IKK-family kinases and IRF transcription factors that induce type I interferon responses. | Signaling Pathway | DRAFT | RIG-I signaling pathway |
4 | 5 | 3 | 0 | 0 | 2 | 2/5 | 0 | ✓ | modules/rig_i_signaling.yaml |
| Retinoic acid receptor signaling pathway moduleMODULE:retinoic_acid_receptor_signalingRetinoic acid synthesis and transport feed RAR/RXR nuclear receptor complexes that switch chromatin-associated co-repressor/co-activator states to control developmental and differentiation genes. | Signaling Pathway | DRAFT | retinoic acid receptor signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 1/5 | 0 | ✓ | modules/retinoic_acid_receptor_signaling.yaml |
| Rho protein signal transduction pathway moduleMODULE:rho_gprotein_signalingRho-family GTPase signaling uses GEFs, GAPs, and GTP-bound Rho switches to regulate actomyosin organization, adhesion, polarity, migration, and cytokinesis. | Signaling Pathway | DRAFT | Rho protein signal transduction |
4 | 6 | 3 | 0 | 0 | 2 | 0/4 | 0 | ✓ | modules/rho_gprotein_signaling.yaml |
| Streptococcus pyogenes FbaB covalent surface-adhesin module (CnaB2 isopeptide domain; SpyTag/SpyCatcher origin)MODULE:spytag_spycatcherThis module describes the multidomain group A Streptococcus (Streptococcus pyogenes) surface adhesin FbaB (gene fba2; UniProtKB:Q8G9G1) and, in particular, its CnaB2 / SpaA-like prealbumin-fold domain, which autocatalytically forms an intramolecular Lys-Asp isopeptide bond. FbaB is a major virulence factor of invasive M3/M18 GAS strains: it is covalently anchored to the peptidoglycan cell wall via a C-terminal LPXTG sortase motif, binds host fibronectin through C-terminal fibronectin-binding repeats to mediate adhesion to and invasion of host cells, carries an N-terminal thioester (TED) domain of the kind that covalently captures host proteins in related streptococcal adhesins, and uses the CnaB2 isopeptide bond to gain the mechanical, thermal and chemical stability inferred to be needed for force-bearing engagement of host fibronectin during invasion. The CnaB2 domain (residues ~462-541; the region crystallized in PDB 9OJ3 and earlier FbaB-CnaB2 structures) is the natural scaffold that was split and engineered into the widely used SpyTag/SpyCatcher covalent protein-conjugation system (SpyTag = reactive Asp-bearing peptide; SpyCatcher = Lys-bearing protein partner; catalytic Glu), with SpyTag003/SpyCatcher003 being the third-generation variant in PDB 9OJ3. The module is grounded in a single natural gene product, FbaB; SpyTag and SpyCatcher are engineered fragments of this one protein, not separate genes. | Module | DRAFT | fibronectin binding adhesion of symbiont to host cell |
5 | 4 | 4 | 0 | 0 | 3 | 1/1 | 0 | ✗ | modules/spytag_spycatcher.yaml |
| T cell receptor signaling pathway moduleMODULE:t_cell_receptor_signalingA compact T cell receptor (TCR) signaling module. Antigen-bound TCR/CD3 complexes are phosphorylated by Src-family kinases such as LCK, recruit and activate ZAP70, phosphorylate LAT/SLP76 adaptor scaffolds, and split into PLC gamma/calcium/NFAT, Ras-MAPK/AP-1, and PKC/NF-kappaB outputs. The module is grounded in GO:0050852 and uses PAINT PTN anchors for the LCK/ZAP70 non-receptor tyrosine kinase tier where the local cache supports them. | Signaling Pathway | DRAFT | T cell receptor signaling pathway |
4 | 6 | 3 | 0 | 0 | 2 | 0/7 | 0 | ✗ | modules/t_cell_receptor_signaling.yaml |
| TGF-beta receptor-SMAD signaling pathway moduleMODULE:tgfb_smad_signalingA compact TGF-beta/SMAD signaling module. A dimeric TGF-beta family ligand binds type II and type I serine/threonine kinase receptors, the type II receptor activates the type I receptor, the type I receptor phosphorylates receptor-regulated SMADs, and SMAD complexes accumulate in the nucleus to regulate transcription. The module is grounded in GO:0007179. TGFB1 is anchored to PAINT TGF-beta-family nodes; receptors and SMADs are included as curated UniProt exemplars without PTN ancestry where local seed rows were not available. | Signaling Pathway | DRAFT | transforming growth factor beta receptor signaling pathway |
4 | 4 | 3 | 0 | 0 | 2 | 1/6 | 0 | ✗ | modules/tgfb_smad_signaling.yaml |
| TNF-mediated signaling pathway moduleMODULE:tnf_signalingTNF binding to TNF receptor complexes nucleates TRADD, RIPK, and TRAF signaling assemblies that balance NF-kappaB activation, inflammatory gene expression, survival, and death decisions. | Signaling Pathway | DRAFT | tumor necrosis factor-mediated signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 1/5 | 0 | ✓ | modules/tnf_signaling.yaml |
| Toll-like receptor innate immune signaling pathway moduleMODULE:toll_like_receptor_signalingA compact Toll-like receptor (TLR) signaling module. Ligand-bound TLRs recruit TIR-domain adaptors such as MYD88, activate IRAK kinases and TRAF6 ubiquitin ligase scaffolds, and route the signal through TAK1/IKK and MAPK branches to NF-kappaB, AP-1, and inflammatory gene expression. The module is grounded in GO:0002224 and includes PTN anchors for TRAF6-family ubiquitin-ligase and innate-immune roles where local PAINT seed rows support them. | Signaling Pathway | DRAFT | toll-like receptor signaling pathway |
4 | 5 | 3 | 0 | 0 | 2 | 1/5 | 0 | ✗ | modules/toll_like_receptor_signaling.yaml |
| Type I interferon signaling pathway moduleMODULE:type_i_interferon_signalingType I interferons engage IFNAR receptor complexes and JAK1/TYK2 kinases to activate STAT1-STAT2-IRF9 transcriptional complexes that induce antiviral gene programs. | Signaling Pathway | DRAFT | type I interferon-mediated signaling pathway |
4 | 8 | 3 | 0 | 0 | 2 | 3/8 | 0 | ✓ | modules/type_i_interferon_signaling.yaml |
| Type II interferon signaling pathway moduleMODULE:type_ii_interferon_signalingInterferon-gamma engages IFNGR receptor complexes and JAK1/JAK2 kinases to activate STAT1-dependent transcriptional programs for macrophage activation and cell-mediated immunity. | Signaling Pathway | DRAFT | type II interferon-mediated signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 2/6 | 0 | ✓ | modules/type_ii_interferon_signaling.yaml |
| VEGFR signaling pathway moduleMODULE:vegfr_signalingVEGF ligands activate endothelial VEGF receptor tyrosine kinases, coupling receptor phosphorylation to PLC-gamma, PI3K, and migration programs that drive vascular growth and permeability. | Signaling Pathway | DRAFT | vascular endothelial growth factor receptor signaling pathway |
4 | 7 | 3 | 0 | 0 | 2 | 1/6 | 0 | ✓ | modules/vegfr_signaling.yaml |
| p38 stress-activated MAPK cascade moduleMODULE:p38_cascadeA taxon-neutral decomposition of the p38 mitogen-activated protein kinase cascade, the stress- and cytokine-activated concrete realization of the generic three-tier MAP kinase relay (MODULE:mapk_relay). Environmental stresses (UV, osmotic and oxidative stress) and inflammatory cytokines (TNF, IL-1) signal through upstream MAP3Ks (ASK1/MAP3K5, TAK1/MAP3K7, MLK family) to the dual-specificity MAP2Ks MKK3 (MAP2K3) and MKK6 (MAP2K6), which dually phosphorylate the p38 MAPKs (p38 alpha/beta/gamma/delta) on their TGY activation-loop motif. Active p38 phosphorylates substrate kinases (MK2/MAPKAPK2) and transcription factors (ATF2, MEF2), driving stress-response and inflammatory gene programs. The RAF-analogous kinase relay - MAP3K -> MKK3/6 -> p38 - is declared as an inner bundle that `conforms_to` mapk_relay, while the stress/cytokine input and the p38 effector output and DUSP-mediated feedback are this cascade's free extensions around the conforming core. Grounded in GO:0038066 (p38MAPK cascade) / GO:0051403 (stress-activated MAPK cascade). | Signaling Pathway | DRAFT | p38MAPK cascade stress-activated MAPK cascade |
8 | 6 | 7 | 0 | 0 | 5 | 1/4 | 3 | ✗ | modules/p38_cascade.yaml |