species	gene	uniprot_id	hf_model	hf_organism	generation_sha256	functional_summary
AGKCO	fibrolase	P28891	SFT	Agkistrodon contortrix contortrix (Southern copperhead)	6524e59ea0cf3b02b965cd2935109ee2a3c1b051f817b31453177839563251cd	A secreted zinc-dependent endopeptidase from snake venom that dissolves blood clots by cleaving the alpha and beta chains of fibrinogen, thereby dismantling the fibrin network and exerting strong fibrinolytic effects. The same catalytic machinery liberates bradykinin from high-molecular-weight kininogen, producing vasodilatory and pain-modulating signals. The enzyme’s compact reprolysin fold coordinates a catalytic metal and additional cations that stabilize the active site, enabling efficient proteolysis in the extracellular milieu.
ARATH	BRI1	O22476	SFT	Arabidopsis thaliana (Mouse-ear cress)	71b3e54072b2ff3ebd51fa8c3cd71f5e6875fa8c01cc26077aee3738b55fc1b9	A single-pass plasma membrane receptor kinase in Arabidopsis that uses an extracellular leucine-rich repeat scaffold with a specialized steroid-binding pocket to capture brassinosteroids and trigger receptor dimerization. Ligand engagement relieves autoinhibition of the cytosolic kinase, enabling autophosphorylation and phosphorylation of downstream kinases to drive growth programs, seedling and leaf development, promotion of flowering, anther tapetum differentiation, and pollen wall formation, while tempering cell death and modulating UV-B responses. Signaling is initiated at the cell surface and continues from endosomal pools through assembly with co-receptors and inhibitory regulators.
ARATH	COP1	P43254	SFT	Arabidopsis thaliana (Mouse-ear cress)	4fdaa68478671c2d7a898b5dd89f8a824ae85cb3a7eb824512ebd0d39dbf5014	A nuclear, light-gated RING E3 ubiquitin ligase that assembles with repressors in darkness to ubiquitinate and promote the degradation of photomorphogenesis-promoting transcription factors, thereby enforcing skotomorphogenic development. Upon illumination, photoreceptor binding inhibits the ligase, allowing transcriptional activation that drives photomorphogenesis, shapes circadian entrainment, and modulates flowering time, stomatal behavior, UV-B responses, DNA repair programs, and flavonoid metabolism. The enzyme concentrates in nuclear bodies and dynamically redistributes within the nucleoplasm, using a C‑terminal beta-propeller to recruit substrates and adaptors while the N‑terminal RING domain catalyzes ubiquitin transfer.
ARATH	ETR1	P49333	SFT	Arabidopsis thaliana (Mouse-ear cress)	0fcdbf2b37402697b2f6f0b298b3180880468092dce15de3a40dedbbd5560f68	An endoplasmic reticulum membrane ethylene sensor that uses an extracellular ethylene-binding module and a cytosolic hybrid histidine kinase core to switch the ethylene signaling state. In the absence of ethylene, its kinase relay maintains repression of the pathway; ligand binding blocks this repression, enabling downstream activation. Through this switch, it governs seed dormancy and seedling development, modulates cell division and vascular tissue formation, regulates stomatal movement, and coordinates extensive hormone and stress crosstalk, including abscisic acid, auxin, gibberellin, cytokinin metabolism, heat and salt responses, defense against microbes with callose deposition and hydrogen peroxide production, and insect responses. It likely functions as a homodimer at the ER, engaging a Raf-like kinase and the ethylene phosphorelay to control transcriptional outputs.
BACSU	amyE	P00691	SFT	Bacillus subtilis (strain 168)	aa0f6d141c496d1d1c34379b0bf66a78dc715c1e5e9a8f732a4bc309ee066a85	A secreted endo-acting glucan hydrolase that initiates extracellular starch breakdown by cleaving internal alpha-1,4 linkages to generate malto-oligosaccharides, with ancillary activity on glycogen and soluble dextrins. A catalytic core performs hydrolysis, an all‑beta C-terminal domain stabilizes the active site and supports processivity, and a terminal starch-binding module concentrates the enzyme on insoluble granules. The resulting oligosaccharides are routed to partner exo- and phosphorolytic enzymes to complete carbon acquisition from environmental polysaccharides.
BACSU	aprE	P04189	SFT	Bacillus subtilis (strain 168)	4b7ef158762d283642214c99da3cdf4758f7a92c67dcaaa705e23f3b26e948fb	A secreted subtilisin-like serine endopeptidase from Bacillus subtilis that is produced as an autoinhibited zymogen and activated outside the cell. Once activated, it cleaves diverse extracellular proteins such as casein and gelatin and likely remodels host factors to dampen clot formation. Its activity contributes to nutrient acquisition and extracellular matrix turnover within a coordinated secretome regulated by environmental sensing and transcriptional control.
BACSU	comK	P40396	SFT	Bacillus subtilis (strain 168)	732c7142c6d6286756fa6899aa1e926745a04ea920e59c56c0fbea0e0c4b610d	An ATP-driven competence ATPase in Bacillus subtilis that self-assembles into higher-order rings to power uptake of exogenous DNA during natural transformation. By coupling ATP binding and hydrolysis to conformational cycling, it engages membrane DNA receptors and channels to energize DNA translocation, while also acting as a transcriptional activator that promotes expression of competence genes during the transition state. Its assemblies and partners are organized at the endospore core, where it coordinates with membrane translocation components and regulatory factors to integrate DNA acquisition with developmental programs.
BACSU	divIVA	P71021	SFT	Bacillus subtilis (strain 168)	ea2299531b76c8444d696b0141cd4047831f46ff4405c9ccbff3937ab178b5ef	A polar, cell wall-associated scaffold that self-assembles into coiled-coil filaments to create an assembly hub at bacterial cell poles. By providing a multivalent platform, it recruits and stabilizes the Z-ring components and their adaptors to initiate polar septation, and it also nucleates and promotes the early steps of basal body formation for flagella. Through these coordinated assemblies, it links cell division with flagellar biogenesis and supports surface swarming motility, with regulatory input likely modulating its polymerization and client recruitment.
BACSU	fliY	P24073	SFT	Bacillus subtilis (strain 168)	65304b0ba40f1084b82a46092d1b87ad74e15051d576321dc9781aac9ff6610f	A cytoplasmic, basal-body–attached switch scaffold that builds the C-ring of the flagellar motor and accelerates adaptation by promoting dephosphorylation of the response regulator that controls motor direction. Its N-terminal recognition modules capture phosphorylated chemotaxis proteins and present them to the associated phosphatase for rapid hydrolysis, resetting motor bias and enabling chemotactic navigation. Its C-terminal oligomerization and anchoring region assembles the switch complex, couples it to the export machinery, and coordinates hook and filament assembly, thereby linking signal resetting to construction of the motility apparatus and supporting both swimming and swarming behaviors.
BACSU	ftsZ	P17865	SFT	Bacillus subtilis (strain 168)	4012ffb3ef93b232a3c054c53503aed8f8249a2cfbfda1c28fb6dcc98e39661e	A bacterial tubulin-like cytokinetic scaffold that binds GTP, self-associates into dynamic filaments, and assembles into a Z ring at mid-cell to initiate and position division. Its N-terminal nucleotide-binding core drives polymerization and hydrolysis-dependent turnover, while its C-terminal interaction platform recruits and regulates partner proteins at the cytoplasmic membrane, thereby coordinating septum formation and constriction during cell division.
BACSU	secA	P28366	SFT	Bacillus subtilis (strain 168)	712d18ed3393068b861415b7c5a00525b230b0fc2f862a77f96f701654d0071b	An ATP-driven peripheral membrane motor in Bacillus subtilis that binds preproteins via a dedicated substrate-gripping module and uses cycles of ATP binding and hydrolysis to push substrates through the Sec translocon at the cytoplasmic face of the cell membrane. By docking to the channel through a wing/scaffold platform and a C‑terminal acidic tail, it couples chemical energy to vectorial translocation, enabling post-translational export of secretory and membrane proteins. Its selective engagement of regulatory substrates, including an anti-sigma factor, links protein export to activation of sporulation-specific transcriptional programs.
BACSU	sigF	P07860	SFT	Bacillus subtilis (strain 168)	b858be7d1fd3b7bd46c7107a3febe2af15ceb025aa94a44d95644247665b1d50	A sigma-70 family initiation factor that selects and activates sporulation-specific promoters by binding both the core RNA polymerase and defined promoter elements, thereby initiating transcriptional programs that drive the transition from vegetative growth to spore formation. Its activity is gated by an anti-sigma/anti-anti-sigma regulatory circuit at the membrane interface, which releases the factor under appropriate stress or developmental cues. Through this switch-like control, it promotes expression of genes for cell wall remodeling and extracellular protease production that support spore coat assembly and maturation.
BACSU	sigG	P19940	SFT	Bacillus subtilis (strain 168)	c1b18611f32c9c6bc7b77e9e1eea444b0450857db6c73e6810e2eacac9ce1f52	A cytoplasmic sporulation-specific initiation factor that assembles with the core RNA polymerase to direct promoter-specific transcription during late stages of spore development. After proteolytic maturation, it recognizes -10, -12, and -35 promoter elements, drives open-complex formation, and activates genes required for endospore wall remodeling and lysis, thereby enabling extracellular dissemination. Its activity is gated by a phosphorylation–serine protease control axis and coordinated with other sporulation sigma factors to sequence the transcriptional program.
BACSU	sigK	P12254	SFT	Bacillus subtilis (strain 168)	566b7e40d7919737f095d52d8b4fee5929fa39db047af90862be4bcc8c71d787	A primary transcription initiation factor in Bacillus subtilis that binds the core RNA polymerase and promoter DNA to direct assembly of the holoenzyme at specific -35/−10 elements. Its N-terminal module engages the core enzyme and recognizes the −10 region to promote DNA melting, while its C-terminal helix–turn–helix binds the −35 element to confer promoter specificity. By dynamically partitioning the core enzyme and being modulated by regulatory partners, it both activates its regulon and can suppress initiation at competing promoters, operating within the nucleoid-associated transcription machinery.
BACSU	spo0A	P06534	SFT	Bacillus subtilis (strain 168)	3559ed4ec71a504a3e27de59b067b4ab0ca251eb3c8aab720ae465d4ad859e70	A cytoplasmic, phosphorylation-activated transcription factor that senses environmental and physiological cues through a two-component phosphorelay, dimerizes upon receiver-domain phosphorylation, and uses a C-terminal winged-helix to bind specific promoter elements. By activating early developmental and matrix-production genes, it initiates sporulation, drives asymmetric division and septum formation, and promotes biofilm development, functioning as a central regulator of transcriptional programs at the bacterial nucleoid.
BACSU	spoIIE	P37475	SFT	Bacillus subtilis (strain 168)	20dc36e4d74b4ad97edc007bf641d8e237a85373387c918724e2f83771730807	A forespore-localized regulatory scaffold that is exported from the mother cell and accumulates in the forespore core during sporulation stage II. It uses a PP2C-like regulatory module to bind and modulate phosphorylation-dependent partners within the sporulation signaling network, thereby activating transcriptional programs that promote assembly of the flagellar apparatus and enable swarming motility during spore development.
BACSU	spoIIGA	P13801	SFT	Bacillus subtilis (strain 168)	fb648e83b935876a6467a0cb2c4f1619e80f2fd7935e88065ed5c21e2e62209c	A membrane-embedded aspartic endopeptidase that oligomerizes to cleave the inhibitory propeptide from the forespore-derived sigma factor precursor, thereby releasing an active sigma factor that assembles with RNA polymerase to drive mother-cell gene expression during sporulation. Its multi-pass topology positions the catalytic core at the cytosolic face of the membrane, where substrate presentation and timing are coordinated with upstream phosphoregulation and envelope remodeling modules.
DROME	Akt1	Q8INB9	SFT	Drosophila melanogaster (Fruit fly)	2f90f202b76cdbbbc25ad77bb1fde4a68cedf740c8ebce4e00e0bb1746945e71	A membrane-recruited AGC-family serine/threonine kinase that is activated by binding 3-phosphoinositides and subsequent phosphorylation by upstream kinases. Once engaged at the plasma membrane and cortex, it phosphorylates key effectors to promote cell and organ growth, support survival, and remodel neuronal architecture, while also tuning lipid metabolism, immune tone, epithelial morphogenesis, and tissue repair. Its activity integrates insulin/IGF and PI3K signals with mTOR complexes and is restrained by lipid phosphatases, enabling precise control of proliferation, migration, and synaptic plasticity in diverse tissues, including neurons and the ovary.
DROME	CRY	O77059	SFT	Drosophila melanogaster (Fruit fly)	31a8e0605fb2a82ae891efab2b7a963b3c44c29e2f3f5befb114e5dc9281f816	A soluble blue-light sensor in fruit fly that binds an antenna chromophore and a flavin cofactor to convert photon energy into a conformational and redox signal that resets the circadian transcriptional feedback loop. By engaging core clock proteins, it promotes the stability and nuclear activity of key repressors and dampens activator-driven transcription of clock genes, thereby aligning daily rhythms in gene expression with environmental light. The protein shuttles between cytosol and nucleoplasm, where light-triggered states enable transcriptional repression and propagation to organismal outputs such as locomotor rhythms and sleep–wake behavior.
DROME	Hsp83	P02828	SFT	Drosophila melanogaster (Fruit fly)	b00dff1f16a5a003f795851088a8d751930e658c2bffc5b475b4ab909f354847	An ATP-dependent molecular chaperone in fruit fly that cycles between open and closed conformations to bind, remodel, and release client proteins. By partnering with co-chaperones, it stabilizes kinases and receptor complexes, promotes folding and assembly of large machines such as the proteasome and RNA-silencing factors, and supports centrosome dynamics and localized ribonucleoprotein assembly. Its activity buffers proteome stress during heat and cold, modulates insulin signaling and circadian sleep–wake behavior, and contributes to germline patterning and cell proliferation control. It operates primarily in the cytoplasm with dynamic engagement of perinuclear ER chaperone hubs, the plasma membrane, centrosomes, and chromatin-associated interband regions.
DROME	LysB	Q08694	SFT	Drosophila melanogaster (Fruit fly)	e6d4a2e466d9d609382579bbd5d7e8e6ba01600eb76754aef348d1a02820d81b	An extracellular antibacterial enzyme in fruit fly that hydrolyzes β-1,4 linkages in bacterial peptidoglycan, lysing cells including E. coli and shaping humoral immunity. By degrading microbial cell wall polymers in the hemolymph or other extracellular fluids, it directly contributes to defense against Gram-negative bacteria and modulates immune signaling intensity, likely by clearing peptidoglycan fragments that sustain inflammatory pathways. Its mechanism relies on a compact lysozyme-like fold that binds the glycan chain and catalyzes bond scission via a conserved acid–base pair, with potential low-level activity on chitinous substrates in contexts where the same glycosidic linkage is presented.
DROME	Nmnat	Q9VC03	SFT	Drosophila melanogaster (Fruit fly)	981caed0cd719c8842920458e811623e84d3b393f33706e6057978d623dc1a8d	A cytosolic, neuronally enriched adenylyltransferase that builds NAD+ from NMN and ATP and also provides a holdase-like surface that binds unfolded proteins. By supplying NAD+ directly at presynaptic terminals and neuronal cell bodies, it fuels NAD-dependent deacylases to tune synaptic transmission and stabilize dendritic spine structure, thereby supporting photoreceptor integrity and neuromuscular function. Its activity is organized at presynaptic active zones and neuromuscular junctions, where it forms a local metabolic–chromatin hub with NAD consumers and NAD biosynthetic enzymes while transiently buffering stress-exposed synaptic proteins.
DROME	Git	Q95RG8	SFT	Drosophila melanogaster (Fruit fly)	6901043e2226a3623d4fd6c185ba0c531e3a6da37a42d9c203bcda8cdbc8715d	A cytoskeletal and membrane-proximal scaffold that combines an ARF GTPase-activating module with ankyrin repeats and GIT-specific interaction motifs to coordinate small GTPase signaling, adhesion, and trafficking. By accelerating ARF-dependent cycles at membranes and assembling Rac1/Cdc42 activators with PAK kinases, it tunes actin and microtubule dynamics at leading edges and presynaptic active zones. This coordination supports growth cone guidance, synaptic protein positioning and vesicle recycling, and contributes to morphogenesis of the nervous system and somatic muscle. Through scaffolded contacts with adhesion proteins and Hippo pathway components, it promotes pathway activity that restrains organ growth, and it likely modulates myosin II–dependent contractility via a PAK–ROCK–myosin II axis.
ECOLI	CnoX	P77395	SFT	Escherichia coli (strain K12)	7444e7c6b8887dc360c629f3dfaecced710cb54c22ea9766047c470835402578	A cytosolic redox-chaperone that binds non-native polypeptides via a helical repeat scaffold and reduces their disulfide bonds through an N-terminal thioredoxin module. By coupling holdase activity with thiol–disulfide exchange, it stabilizes unfolded proteins, promotes their refolding, and protects the proteome during oxidative stress, operating in concert with the cellular thioredoxin system and core chaperone-protease networks to maintain protein quality.
ECOLI	CpxP	P0AE85	SFT	Escherichia coli (strain K12)	c497e7289e0de864e13b8926d893da88e9cc65808d3187bb08551ad343d9eab6	A periplasmic holdase chaperone that binds non-native envelope proteins to prevent aggregation and promote productive folding, while simultaneously tuning the activity of the periplasmic sensor of a two-component system. By capturing misfolded clients generated during envelope stress, it stabilizes them for refolding or handoff to proteases and couples client occupancy to signaling through the stress pathway, thereby enhancing resistance to protease exposure and other envelope challenges.
ECOLI	DnaJ	P08622	SFT	Escherichia coli (strain K12)	6afecd14298a50b8c2a910555f3b04dec9109463a405fd3a46c9ca03b60643ec	A cytosolic J-domain co-chaperone that captures non-native polypeptides, stimulates Hsp70 ATPase activity, and uses a cysteine-rich zinc-binding module to stabilize client engagement and perform thiol–disulfide remodeling when needed. By coordinating client transfer to Hsp70 and collaborating with disaggregases and chaperonins, it promotes refolding, suppresses heat-induced growth arrest, and supports recovery of core processes such as DNA replication. Its regulatory binding to the heat-shock sigma factor tempers the stress response as proteostasis improves, and transient membrane-proximal assemblies likely form during quality-control triage.
ECOLI	DnaK	P0A6Y8	SFT	Escherichia coli (strain K12)	028e7732359570f8549683f41206f29b2bf4c0e5f16d19d45fc1574a7d3767da	A cytosolic ATP-dependent chaperone that cycles between nucleotide-bound states to capture, stabilize, and release non-native polypeptides, thereby preventing aggregation, promoting folding of newly synthesized proteins, and remodeling aggregates during stress. It cooperates with J-domain cochaperones to stimulate ATP hydrolysis and with nucleotide exchange factors to reset the cycle, and it hands clients to downstream systems such as Hsp90 and the GroEL–GroES chaperonin for late-stage maturation. During recovery from heat shock, it antagonizes the heat shock sigma factor to temper stress-responsive transcription. It assembles into dynamic complexes in the cytosol and concentrates at aggregate surfaces, including inclusion bodies, to drive disaggregation and refolding.
ECOLI	GroEL	P0A6F5	SFT	Escherichia coli (strain K12)	e2631e774e3ea8fbe4d67805f3f49b31be09e663b60dd40300d47fd88a9636f2	An ATP-dependent cytosolic chaperonin that assembles into a double-ring complex and, together with its small co-chaperonin cap, forms a sealed chamber that captures non-native polypeptides, sequesters them from the cytosol, and uses cycles of ATP binding, hydrolysis, and product release to drive productive folding. It collaborates with upstream Hsp70/DnaJ and Hsp90 systems, disaggregases, trigger factor, and proteases to triage clients during stress, thereby restoring proteome integrity and supporting folding of viral structural proteins required for capsid assembly. The machine operates through allosteric coupling between an ATPase equatorial base, a hinge-like intermediate connector, and a substrate-binding apical head, with magnesium coordinating the nucleotide and conserved residues near the apical–intermediate interface stabilizing the allosteric network.
ECOLI	RidA	P0AF93	SFT	Escherichia coli (strain K12)	4c4fe8744e287354959a5df19995d733a602a1d3d2f34c659727dd01e1354898	A trimeric cytosolic enzyme that hydrolytically deaminates 2-iminopropanoate, thereby draining a reactive intermediate that would otherwise nitrosate heme and other cellular targets. By positioning a catalytic water within a conserved pocket at the subunit interface, it converts the imine to acetate and ammonia, protecting the cell during nitrosative stress. The trimeric surface likely moonlights as a holdase for non-native polypeptides under stress and assembles into larger protein complexes; a fraction of these complexes is recruited to the membrane, where proximity to transport and metabolic machinery helps prevent damage from reactive nitrogen species.
ECOLI	SecB	P0AG86	SFT	Escherichia coli (strain K12)	fadbe463533baa06478494bb73165822b86d37095585a1b7f0ae5609d87306d7	A cytosolic dimeric holdase that captures unfolded secretory precursors via hydrophobic grooves, stabilizes them against premature folding, and delivers them to the translocation machinery for export. By coordinating client binding with the membrane translocon and associated targeting factors, it promotes efficient secretion and membrane insertion while safeguarding proteostasis during the transit from synthesis to export.
ECOLI	Skp	P0AEU7	SFT	Escherichia coli (strain K12)	c859ea2ca1abaff03163d90c05110aa5b125a201314dfac792f27b65f94dd37f	A periplasmic chaperone that forms a small, likely dimeric cradle to bind and stabilize unfolded segments of nascent outer-membrane proteins, preventing their aggregation and keeping them in an assembly-competent state. By holding clients such as the C-terminal region of a major outer-membrane porin in a soluble conformation, it coordinates their handoff to the outer-membrane assembly machinery for insertion and contributes to envelope biogenesis and stress resilience at the cell periphery.
ECOLI	SlyD	P0A9K9	SFT	Escherichia coli (strain K12)	67011e1a09a2e34b298e05865c037866f3fba54fdd6195dabce6ecd685c46591	A cytosolic FKBP-type peptidyl-prolyl isomerase and chaperone that accelerates protein folding by catalyzing cis–trans isomerization of proline bonds and, through a metal-binding insertion, acts as a holdase under non-stress conditions and as a metal-buffering isomerase during severe stress. Its metal-coordination pocket likely transiently binds nickel and other divalent metals to stabilize and deliver them to metalloenzyme assembly factors, particularly those required for hydrogenase maturation, while cooperating with general chaperone systems and ribosome-proximal folding to refold and stabilize non-native proteins.
ECOLI	Spy	P77754	SFT	Escherichia coli (strain K12)	85a66ab0341b72f5b113759fcaa5a6dd2e04f4dcc9c9e9b8b16aae8f13e22b85	A periplasmic holdase chaperone that binds non-native polypeptides to prevent aggregation and promote their productive handling during envelope stress. By stabilizing misfolded or nascent periplasmic and membrane-proximal proteins, it supports quality control of envelope biosynthetic and transport machinery and integrates with stress-sensing pathways to bolster survival under antibiotic and other organic cyclic compound challenges. Its activity likely couples client capture to refolding or proteolytic routes at the inner membrane–periplasm interface and coordinates with efflux systems to maintain envelope integrity.
ECOLI	ftsI	P0AD68	SFT	Escherichia coli (strain K12)	a413b0c3e2de6a77751f9c1ba61471dc7e70e792fe38099891a2849a8f4b19ad	An inner-membrane, septum-localized peptidoglycan cross-linking enzyme that drives cell division by forming 4→3 peptide cross-links during synthesis of new cell wall. A periplasmic catalytic core containing a penicillin-trapping serine executes transpeptidation on septal peptidoglycan, while an N-terminal dimerization module organizes contacts within the divisome to concentrate activity at the constricting ring. Its susceptibility to beta-lactam antibiotics links it directly to xenobiotic stress responses that modulate division and envelope biogenesis.
ECOLI	mrdA	P0AD65	SFT	Escherichia coli (strain K12)	a90e1d8e216809f656097f16cc6c3b783e068588751a175a182803b27647ee01	A single-pass inner-membrane enzyme in E. coli that presents a periplasmic catalytic head to forge 4-3 cross-links in peptidoglycan during lateral wall growth. Its N-terminal scaffold domain organizes interactions with the elongation machinery, positioning the serine-dependent transpeptidase core to acyl-transfer between stem peptides. This activity supports cell wall assembly and rod-shape maintenance, and it is susceptible to acylation by penicillins, which explains antibiotic sensitivity. The enzyme likely operates within the elongasome alongside glycan polymerases, flippases, and partner transpeptidases to coordinate substrate flow and cross-linking.
ECOLI	surA	P0ABZ6	SFT	Escherichia coli (strain K12)	f42abd58faf151cf2041eb3e3f99620b1eeb5012f8a7b5b4e91022a82264ce07	A periplasmic chaperone–isomerase that binds unfolded outer-membrane protein precursors and accelerates their productive folding by catalyzing proline bond isomerization. Its N-terminal cradle captures exposed hydrophobic segments to prevent aggregation, while tandem catalytic modules drive conformational equilibration at prolines to reduce kinetic traps. After folding, clients are delivered to the beta-barrel assembly machinery for membrane insertion, integrating with periplasmic quality-control factors to stabilize substrates and ensure robust outer membrane biogenesis.
PSEPK	pedH	Q88JH0	SFT	Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440)	d960d0f164107dafc77dce6cbb463190efb72411cad6219ce5cbc526184bcdc5	A periplasmic, membrane-proximal quinoprotein alcohol dehydrogenase that uses a PQQ cofactor and a calcium-stabilized beta-propeller to oxidize short-chain primary alcohols, including ethanol, 1-propanol, and 1-butanol, and can also act on glycerol in vitro. The enzyme transfers electrons from the reduced PQQ to external acceptors such as NAD or periplasmic cytochromes/quinones, thereby feeding aerobic respiration. Under aerobic conditions it can oxidize lactate to pyruvate, integrating short-chain alcohol and lactate metabolism with the electron transport chain. It likely operates as part of a periplasmic cytochrome-containing redox assembly, handing aldehydes off to aldehyde dehydrogenases to complete catabolic flux and limit aldehyde toxicity.
SCHPO	Epe1	O94603	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	1abbdb6d316b33d2f3be3518d2a2b1fed95a50025427ca96af981a77c10d1aed	A nuclear chromatin regulator in fission yeast that uses an Fe(II)- and 2-oxoglutarate-dependent catalytic core to remove di- and tri-methyl groups from lysine 9 of histone H3, thereby counteracting the accumulation of repressive marks at the periphery of silent domains. By erasing H3K9 methylation at domain edges, it limits recruitment of heterochromatin readers and deacetylases, stabilizes boundaries between silent and active chromatin, and supports proper gene repression and genome stability within heterochromatin.
SCHPO	SPAC8E11.10	Q9Y6Z9	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	8403629c20c2f3d17db863dc01a1de4876b66b394b7ee1e67f2964f7d48739a8	A soluble mitochondrial oxidoreductase in fission yeast that uses a Rossmann-like cofactor-binding fold and a short-chain dehydrogenase/reductase active site to oxidize linear sugar alcohols. It converts D-arabitol to D-xylulose, D-xylose to D-xylulose, and D-galactose to D-gulose, but does not act on the branched polyol D-galactitol. The enzyme likely binds NADP+ in its binding groove and employs a Tyr–Lys catalytic pair to abstract the substrate hydroxyl proton and transfer a hydride to the nicotinamide, generating NADPH and a ketose product that feeds into mitochondrial polyol–ketose interconversion pathways.
SCHPO	SPCC16C4.02c	O74447	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	087185d081cef87c70e1bb8748bb5d250748c20128ff2f1a5d10ee1600619708	A cytoplasmic adaptor that concentrates at the spindle pole body and the cell division site to organize cytoplasmic microtubules during mitosis and cytokinesis. Built from armadillo-like repeats, it functions as a multivalent scaffold that assembles nucleators, motors, and regulatory enzymes to control microtubule nucleation, anchoring, and remodeling at the microtubule-organizing center and at the equatorial ring, thereby coordinating spindle function with cell division.
SCHPO	Shu1	Q92340	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	7b67557407f0af27a43c0b583cb94fd159571ff16adc36b9ec63ad9ba813224e	An ER-resident single-pass type I membrane adaptor that uses protein-binding interfaces on its luminal domain and short cytosolic tail to organize plasma membrane microdomains and ensure proper delivery and localization of a key lipid flippase. By coupling luminal client handling with recruitment of actin-remodeling machinery at the cell surface, it maintains normal plasma membrane organization and supports the distribution of the flippase required for membrane lipid asymmetry.
SCHPO	tim10	Q9UTE9	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	330259a9750849f871fe739db8e4c9f7c6b65191a52f55a8bcde65af61cf97a2	A small mitochondrial intermembrane space chaperone that assembles into a Tim10-like hexameric ring to bind and shield hydrophobic segments of multi-pass carrier precursors as they traverse from the outer membrane into the intermembrane space. By stabilizing these clients and docking to the inner-membrane carrier translocase, it delivers them for lateral insertion into the inner membrane, thereby supporting protein transport and maintaining mitochondrial organization. Its fold is oxidative-folding stabilized in the intermembrane space and it operates loosely associated with the inner membrane.
SCHPO	alo1	Q9HDX8	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	e303baa6fd0216803e86c8636b3825d35da6209b30904c74df1d791d7d61fe47	A mitochondrial FAD-dependent oxidase that completes the L-gulonate route to vitamin C by oxidizing L-gulono-1,4-lactone to the corresponding lactone that spontaneously isomerizes to ascorbate. Its N-terminal FAD-binding core accepts hydride from the substrate’s C1 alcohol, and the C-terminal VAO-like module positions molecular oxygen to reoxidize the flavin, producing hydrogen peroxide. Operating in the mitochondrial matrix, it supports local redox homeostasis and couples ascorbate production to mitochondrial metabolic demands.
SCHPO	atg101	O13978	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	81b49d8302a8ebafd5136fb6db32d4154f1b8f7aa98b4037493648cff55626f2	A cytosolic autophagy adaptor that assembles and stabilizes the initiation machinery at the phagophore assembly site. By binding the Atg1/ULK1 kinase module and organizing early factors, it promotes kinase activation and coordinates recruitment of the class III phosphatidylinositol 3-kinase complex to generate phosphatidylinositol 3-phosphate, thereby driving autophagosome formation. It likely interfaces with membrane-delivery components and ubiquitin-like conjugation enzymes to couple signaling with membrane growth, and can transit to the nucleus to align autophagy initiation with cellular state.
SCHPO	atg13	O36019	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	0fdc651dfd5bba612eaf096cb98a7c690f30787ef69bca8c3f9ce2639803a370	A cytosolic scaffold that assembles and regulates the autophagy initiation kinase complex at the phagophore assembly site. Its N-terminal conformational module creates a switchable binding platform that captures autophagy factors and couples nutrient signaling to kinase activation, while the extended scaffold stabilizes the initiation complex and coordinates membrane supply and selective cargo pathways, including turnover of mitochondria.
SCHPO	atg16	O94656	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	13108fce605c02e281e6a22bcc8a8ac2aaace4f44bb2a806e3adb40fb5785793	A ubiquitin-like modifier that is proteolytically matured and then activated by an E1-like enzyme, transferred to an E2-like enzyme, and finally conjugated to a target scaffold by an E3-like complex to form a core autophagy assembly. This conjugate organizes autophagosome biogenesis and membrane remodeling at cytosolic sites, the division plane, and the spindle pole body, with a minor nuclear pool supporting chromosome segregation. The protein’s activity relies on high-affinity binding to its activating, conjugating, and scaffolding partners, enabling dynamic cycles of conjugation and deconjugation that coordinate cell division and meiosis.
SCHPO	atg2	O94649	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	8ec11c176a12a9d5b190f1e20616682b54b64cbf7c365d3074f395cb3c3bee15	A large peripheral membrane lipid transporter in fission yeast that bridges the endoplasmic reticulum and the edge of the nascent isolation membrane to supply phospholipids for autophagosome biogenesis. Its elongated, hydrophobic conduit extracts lipids from the ER and delivers them to the growing phagophore, while a C-terminal docking module targets the phagophore rim. The same mechanism likely supports nuclear envelope expansion during mitosis by channeling ER-derived lipids to the nuclear membranes. It operates at the preautophagosomal structure and ER interfaces and coordinates with core autophagy factors to couple membrane input with autophagosome growth.
SCHPO	atg38	O94427	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	d9175c4e70e2189a3e69094d28d993bf6b95cdd0412f6439dc6d83d3bd6d2d20	A membrane-proximal adaptor that assembles the autophagy-specific class III phosphatidylinositol 3-kinase complex to generate phosphatidylinositol-3-phosphate on nascent isolation membranes. By using an N-terminal helical docking module to capture partner subunits, it positions the kinase and cofactors at the phagophore assembly site to promote membrane expansion and recruitment of downstream effectors, thereby driving autophagosome formation. It cycles from the cytoplasm to the preautophagosomal structure during initiation and subsequently relocalizes to the vacuole after autophagosome–lysosome fusion, coordinating initiation with maturation.
SCHPO	atg5	O74971	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	0979103e83e0472945aaf12423bfebfea7a218e8f001b03f017575f2a2e0f00e	A cytosolic scaffold that becomes peripherally associated with the preautophagosomal structure to drive autophagosome biogenesis. It forms a covalent conjugate with a ubiquitin-like modifier and, together with an additional subunit, assembles an E3-like complex that stimulates lipidation of a membrane receptor on nascent autophagic membranes. This activity promotes membrane expansion and closure during bulk and selective autophagy, including turnover of mitochondria and endoplasmic reticulum, and it likely contributes to meiotic programs by coordinating organelle remodeling and stress-responsive membrane dynamics.
SCHPO	bst1	Q9UT41	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	72860aa88c4e4626f80e1504d1f8e67858dd0f71484e5b6b90653da6277fd41e	A multi-pass membrane serine hydrolase in fission yeast that removes the inositol-linked acyl chain from newly GPI-anchored proteins in the endoplasmic reticulum. By deacylating the inositol lipid moiety at the lumenal membrane interface, it licenses subsequent remodeling and cargo recognition, thereby promoting efficient ER-to-Golgi trafficking of GPI-anchored clients. The enzyme likely operates adjacent to the GPI transamidase and p24 cargo receptors, using an alpha/beta hydrolase catalytic core to cleave the inositol O-acyl ester and facilitating maturation within the secretory pathway.
SCHPO	cps1	O13968	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	270c321e6b1456e28b7b453c8d765f5b871b4c1b3d3e1e1e48c59d625b081db0	A metallo-dependent exopeptidase that functions as a dimeric aminopeptidase to trim N-terminal residues from diverse peptides, thereby completing peptide breakdown and recycling amino acids. It likely assembles in the cytoplasm before being delivered to the vacuole, where it collaborates with other hydrolases to finalize proteolysis, and may also act at peroxisomes to process peptides arising from organelle turnover. Through this activity it supports cellular nitrogen economy and feeds amino acid pools into biosynthetic pathways, with vacuolar sorting machinery ensuring proper targeting and maturation.
SCHPO	cts2	Q9C105	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	b281e0a46f846df9910611bef0298b294150ef5123ea5ece723a8e4bdb63d4a5	A secreted fungal chitinase that targets the primary septum to hydrolyze chitin during cell separation. It is trafficked through the secretory pathway to the cell wall, concentrates at the septal interface, and degrades the chitin scaffold into oligomers to enable daughter cells to disperse. A vacuolar pool likely supports storage, maturation, and turnover of the enzyme. Its activity is coordinated with membrane and wall remodeling, potentially integrating with lipid-modifying enzymes to synchronize septum digestion with final separation.
SCHPO	gaa1	Q9US48	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	0a746733a6cfd1cc1a8d2b7986c994f0299674f357cdbd736fb14bf1b5d64ee1	A multi-pass ER membrane subunit of the GPI transamidase that enables the complex to cleave the C-terminal signal peptide of nascent proteins and transfer a preassembled GPI lipid to create mature GPI-anchored proteins. It acts as a membrane-embedded organizer and substrate-handling module that aligns the protein substrate and the GPI donor for efficient amide-bond formation, thereby driving the key transamidation step in GPI anchor attachment within the ER.
SCHPO	pmp20	O14313	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	2d701d885011bfb66d5327b31db91ade2ae9d0653170a2920db8617a13edf2f2	A soluble thiol-dependent peroxidase in fission yeast that uses a thioredoxin-like fold to reduce hydrogen peroxide and organic hydroperoxides, thereby protecting the cytosolic and nuclear proteome from oxidative damage. By lowering peroxide levels and engaging transiently with non-native polypeptides, it promotes refolding of stress-labile proteins. Electrons are supplied primarily by thioredoxins, with auxiliary support from the glutathione system and catalase, and its activity likely scales with cellular redox metabolism and proteostasis control.
SCHPO	pol5	O60094	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	2306c90d9f0bf77f8c547722a5d22801f3797a91b5212b7ff19e56451d3744f1	A nucleolar scaffold that binds rDNA regulatory elements and organizes transcriptional and biogenesis factors to promote ribosomal RNA production. Its elongated repeat architecture provides multivalent protein-binding surfaces, while a short polymerase-related motif stabilizes DNA engagement. By anchoring the rRNA-transcribing machinery and recruiting small subunit processome components, it couples initiation at ribosomal DNA with early pre-rRNA processing. A cytosolic pool likely supports assembly and regulated nuclear import, and contacts with RNA-silencing factors may tune rRNA output under specific conditions.
SCHPO	ral2	P15258	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	473e32cd84dcc3db7986c14a569240eaa3eb237d7ecb49ef2b79e7c19a6fa8ef	A modular adaptor that uses an N-terminal beta-propeller to capture signaling components and a C-terminal BTB/POZ-like interface to dock onto ubiquitin ligase or large structural platforms, thereby assembling and stabilizing the MAPK module that drives the pheromone response. By positioning at the endoplasmic reticulum and spindle pole body, and engaging Ras-like and Rho-pathway factors, it promotes efficient signal transmission required for mating and cell fusion, likely by scaffolding and locally remodeling kinase complexes without intrinsic enzymatic activity.
SCHPO	snx41	O60107	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	43e2e790c03e36e51b1136c8a5e81c865bf713f752321a3a9d6707540aeba947	A PI3P-targeted, curvature-sensing sorting nexin that assembles protein complexes on endosomal and autophagic membranes to drive selective autophagy. By binding PI3P via its PX module and stabilizing curved membranes through a BAR-like region, it scaffolds retromer and other adaptors to capture cargo and promote sequestration of mitochondria and ER subdomains. It cycles between the cytosol and PI3P-enriched membranes, where its membrane remodeling and protein-binding activities coordinate cargo selection and autophagosome initiation.
SCHPO	tam10	G2TRQ9	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	7f250a58c85da9fb9989799c7df0bf07c207f76845e1cd040ee903583df91c85	A nuclear, nucleolus-enriched splicing factor that uses an acidic interaction module to bind basic spliceosomal proteins and SR-like factors on pre-mRNA, promoting assembly and stabilization of spliceosome subcomplexes. By acting as a non-enzymatic adaptor, it likely coordinates factor recruitment and remodeling steps that drive intron removal, with nucleolar residence supporting factor storage or pre-assembly before deployment to active splicing sites.
SCHPO	tpx1	O74887	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	f3f23761b96b2511c2449923881c9cf9f6817ad3f6fdac7368afd197780ce23a	A soluble thiol-dependent peroxidase in fission yeast that reduces hydrogen peroxide and organic hydroperoxides using electrons ultimately supplied by NADPH via the thioredoxin system. Its thioredoxin-like fold and peroxiredoxin C-terminal tail enable catalytic cycling between reduced and disulfide states and confer a chaperone-like ability to bind unfolded proteins during stress. By buffering and relaying hydrogen peroxide signals, it maintains cellular redox balance, collaborates with parallel peroxide-removal enzymes, and modulates transcriptional programs in the cytosol and, under stress, in the nucleus.
SCHPO	ura7	O42644	SFT	Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast)	c6f9244af50d23472f7420a857bdb85ed165f503b579383ad55062079e97511b	An ATP-dependent enzyme in fission yeast that converts UTP to CTP using glutamine as the nitrogen source, thereby supplying the cell with CTP for RNA, lipid, and other cytidine-dependent biosyntheses. Its N-terminal module activates UTP with ATP, while its C-terminal glutamine-hydrolyzing module generates ammonia that is channeled to the activation site to complete C–N bond formation. The protein assembles into cytosolic filaments whose formation modulates catalytic output, aligning CTP production with cellular demand and integrating with broader nucleotide and nitrogen metabolism.
human	BCL2	P10415	SFT	Homo sapiens (Human)	1b64e120b4568994242adedd4bdc5316aaf53b1e5e0c397fda6b63a3f5b2c9d0	A multi-pass membrane-anchored regulator that uses an N-terminal regulatory module and a canonical BH1–BH3 groove to bind BH3 motifs, assemble dimers and higher-order complexes, and modulate membrane permeabilization and ion homeostasis. By acting as a molecular adaptor at mitochondria, endoplasmic reticulum, and nuclear membranes—and transiently within the nucleoplasm—it restrains caspase activation, stabilizes mitochondrial potential, suppresses autophagy initiation, and coordinates stress and damage responses. Its scaffolded interfaces recruit proteases, ubiquitin ligases, and transcriptional regulators to tune survival, immune, and growth programs across diverse stimuli.
human	CYCS	P99999	SFT	Homo sapiens (Human)	cbfab0d076c74963cc2346d681d50759e6a2c673d8364d72e859c9c139f52159	A small, soluble mitochondrial heme protein that ferries single electrons between the cytochrome b-c1 complex and cytochrome c oxidase to sustain oxidative phosphorylation. Its positively charged surface and conserved docking grooves enable rapid, transient binding to respiratory partners on the intermembrane-space side of the inner membrane. Upon mitochondrial permeabilization, it is released to the cytosol, where it binds the apoptosome scaffold to trigger initiator and effector caspase activation; fragments or complexes can also access the nucleus. This dual role integrates electron transfer in respiration with execution-phase control of apoptosis.
human	FXN	Q16595	SFT	Homo sapiens (Human)	07422d74655b8304fc1148d9ab7da9ea7d218e1195129f70da4a08e78d8084b4	A small mitochondrial matrix protein that oligomerizes into an acidic scaffold to capture ferrous iron, transiently ligate nascent iron–sulfur intermediates, and deliver them to the ISC assembly machinery. By presenting iron and sulfur to the ISCU scaffold while oxidizing excess ferrous ions, it promotes [2Fe–2S] cluster formation, protects Fe–S enzymes from oxidative damage, and couples iron handling to heme synthesis. Autoprocessing yields a stable C-terminal fragment that sustains these activities. Through iron buffering and support of mitochondrial redox metabolism, it limits cytochrome c release, thereby fostering cell growth and proliferation.
human	GAPDH	P04406	SFT	Homo sapiens (Human)	8767153583ce72c9bb5538847ada86be4107d648a960acc55d53283d5e5b339c	A tetrameric, NAD-dependent dehydrogenase that catalyzes the oxidation of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate in glycolysis and moonlights as a regulatory scaffold. Its Rossmann fold binds NAD+ and positions the catalytic cysteine to drive hydride transfer, while flexible surface loops enable binding to intrinsically disordered regions of partner proteins and RNA. In the cytosol it assembles with other glycolytic enzymes to channel intermediates; in the nucleus it binds RNA to repress translation; and at membranes and signaling hubs it organizes innate immune complexes that enhance NF-κB and type I interferon responses, modulates protease activity, and influences autophagy. These activities collectively couple metabolic state to immune and proteostatic control.
human	KEAP1	Q14145	SFT	Homo sapiens (Human)	507b1a0b6e88e3d19abfac822649fd80bb6fe0148f6c52b4c5154da26a9d2de9	A BTB–BACK–Kelch scaffold that assembles a CUL3–RBX1 ubiquitin ligase and uses a C-terminal Kelch β-propeller to capture degron motifs on transcription factors and other clients. Under non-stressed conditions it targets the NRF2 pathway for proteasomal turnover, thereby restraining antioxidant gene expression. During electrophilic or nitrosative stress, modifications on the scaffold disengage NRF2 and promote autophagic routing of the adaptor, enabling NRF2 accumulation and transcriptional activation. The same ligase adaptor activity extends to additional substrates, including KEAP1, SIAH1, MYOD1, PML, and ZNF252, coordinating ubiquitin-dependent proteolysis across cytosolic and nuclear compartments and at centriolar satellites and midbody structures.
human	MYC	P01106	SFT	Homo sapiens (Human)	818d8a729bbc6eecd98dd9054281d4a00a60c3f5ed9d626bbd769b298f2832c7	A dimeric, sequence-specific transcription factor that binds E-box motifs through a C‑terminal basic helix–loop–helix–leucine zipper module and uses an N‑terminal transactivation region to recruit chromatin-modifying cofactors. It activates and represses RNA polymerase II transcription programs that drive cell-cycle entry, biomass accumulation, and lineage decisions, while integrating signals from growth factors, hypoxia, DNA damage, xenobiotics, and UV. By assembling with coactivators or repressors, it remodels chromatin, modulates DNA methylation and checkpoint pathways, and influences apoptosis and noncoding RNA production. It resides primarily on nuclear chromatin and nucleolar compartments but can redistribute to the cytoplasm, cytoskeleton, and peripheral endoplasmic reticulum in response to stress and signaling, thereby coupling environmental cues to transcriptional outputs that determine proliferation, differentiation, and survival.
human	NFE2L2	Q16236	SFT	Homo sapiens (Human)	5aae9bc0ebfb1a919c2ff699f47ff10028703a3de78aad5e2a056260918868df	A redox-regulated transcription factor that dimerizes with small Maf proteins to bind antioxidant response elements and activate cytoprotective gene expression. In the cytosol it is held in an inactive state by a KEAP1-centered complex; oxidative or proteostatic stress disrupts this restraint, enabling nuclear accumulation and engagement of the RNA polymerase II transcriptional machinery. The resulting program elevates detoxifying enzymes, chaperones, and proteostasis factors, coordinates with unfolded protein response pathways, and promotes ubiquitin- and ubiquitin-independent ER-associated degradation, thereby maintaining redox balance, limiting oxidative apoptosis, and enhancing cellular resilience to hydrogen peroxide, inflammatory cues, and mechanical stress.
human	PTEN	P60484	SFT	Homo sapiens (Human)	f10ccf799e6cff6ca88bf2cedf472d92dd6fc7d60028979c9d8b720b8ddb8a22	A membrane-targeted, dual-specificity phosphatase that uses a C2 domain to dock at acidic phospholipid surfaces and a catalytic pocket to remove the 3-phosphate from key phosphoinositides, thereby antagonizing PI3K–AKT signaling and dampening MAPK outputs. By reshaping local PIP3/PIP2 pools and directly dephosphorylating protein substrates, it restrains proliferation, enforces checkpoints, promotes apoptosis, and remodels adhesion and cytoskeletal dynamics. Scaffolding via PDZ adaptors positions it at apical and junctional membranes and within cytosolic and nuclear compartments, enabling integration of electrical and Wnt cues and coordination with ubiquitin-system regulators to stabilize select proteins and tune turnover.
human	TARDBP	Q13148	SFT	Homo sapiens (Human)	47c6f4672984c9c88e363344dc095388055898a456a95f90e396422e01b7a124	A nucleoplasmic RNA-binding regulator that uses an N-terminal dimerization module and tandem RNA-recognition motifs to bind GU-rich and YGCY-containing elements in pre-mRNAs and 3'UTRs, assembling multivalent ribonucleoprotein condensates that direct splicing, mRNA stability, and translation. Its prion-like C-terminus drives self-association and phase separation, enabling formation of dynamic granules and, under stress, amyloidogenic assemblies. Through selective engagement of transcripts encoding cell-cycle, apoptotic, and synaptic factors, it modulates proliferation, survival, and neuronal plasticity, while its condensates interface with nuclear envelope organization and host–symbiont control of nucleic acid fate.
human	VEGFA	P15692	SFT	Homo sapiens (Human)	c5b1633e046c4d14d8d0ba544a425a76838470a7a49c5dfaf4116daac9f58bff	A secreted, matrix-tetherable growth factor that forms disulfide-stabilized homodimers and binds high-affinity receptors on endothelial cells to drive angiogenic sprouting, proliferation, migration, survival, and increased vascular permeability. Its basic C-terminal region binds heparin and extracellular matrix components such as fibronectin, concentrating the ligand at the cell surface and within perivascular niches. This positioning promotes receptor dimerization and activation, triggering downstream kinase cascades that remodel adherens junctions, enhance permeability, and coordinate tissue homeostasis and wound repair, with additional roles in immune cell chemotaxis and developmental vascular branching.
mouse	Akt1	P31750	SFT	Mus musculus (Mouse)	4efd59b3b59943af044e623b6e7b6836aafe0aeb0984347f53be078e011cbf95	A lipid-gated serine/threonine kinase that is recruited to membranes by phosphoinositide binding, activated by upstream kinases and TORC2, and then phosphorylates a broad set of metabolic, transcriptional, cytoskeletal, and survival regulators to coordinate growth, metabolism, survival, motility, and stress adaptation. It promotes glucose uptake and storage, inhibits apoptosis, modulates transcription factors and chaperones, and shapes cell cycle and cytoskeletal dynamics. The enzyme operates in cytosol, nucleus, and at membrane-associated signaling sites, assembling with chaperones, scaffolds, and phosphatases to tune pathway output across development, stress responses, and neuronal and muscle contexts.
mouse	Bcl2	P10417	SFT	Mus musculus (Mouse)	df0c51665e8b6759e0f547bf45321bdac1d7844492e6320474fbd7029a8763cd	An anti-apoptotic, membrane-anchored regulator that uses a BH4-stabilized helical bundle and a BH1–BH3 groove to bind BH3-only ligands and antagonize pore-forming effectors at organelle membranes. By occupying the mitochondrial surface, it prevents cytochrome c release and caspase activation, thereby promoting cell survival during stress and development. Its cytosolic and membrane pools also tune calcium and reactive oxygen balance, modulate protein stability through phosphatase recruitment, and interface with autophagy and viral latency pathways. Dynamic localization across mitochondria, endoplasmic reticulum, nuclear envelope, and cytosol enables context-dependent control of proliferation, differentiation, immune homeostasis, and tissue morphogenesis.
mouse	Calm1	P0DP26	SFT	Mus musculus (Mouse)	08272bb4f921216119226255f54597d7386215b0d0c3d7c9ab466161e1301ce9	A small, bilobal calcium sensor that uses paired EF-hand motifs to bind Ca2+ and undergo a conformational switch that enables high-affinity engagement of basic amphipathic helices in diverse targets. By coupling Ca2+ transients to the activity of enzymes, ion channels, and trafficking factors, it modulates signaling pathways that promote entry into mitosis and enhances the DNA-binding capacity of select transcriptional regulators. It is a soluble protein that dynamically associates with membranes, vesicles, and specialized domains such as the myelin sheath and voltage-gated potassium channel assemblies, where it tunes channel gating, kinase and phosphatase activities, and local trafficking responses.
mouse	Egfr	Q01279	SFT	Mus musculus (Mouse)	f837efe6289bb47610a68878f325fbfec1573839560bd52e4fc8b264dd0ebe02	A single-pass cell-surface receptor tyrosine kinase in mouse that binds EGF-family ligands via a modular extracellular domain, dimerizes with ERBB family partners, and activates its intracellular kinase to autophosphorylate and recruit SH2/PTB adaptors and enzymes. This triggers RAS–MAPK, PI3K–AKT, PLCγ, and STAT signaling to drive proliferation, migration, and morphogenesis across epithelial and neural contexts, influences neurite outgrowth and synaptic plasticity, and can transactivate other receptors. Ligand-induced endocytosis and trafficking to perinuclear and nuclear compartments modulate transcriptional outputs, while phosphatase docking and phospholipase recruitment fine-tune signal amplitude.
mouse	Fyn	P39688	SFT	Mus musculus (Mouse)	88f6f8ca5a329376a11b59cf906adfc09a0115f47d8e5f47f04e05f2a10f4629	A lipid-anchored, raft-enriched non-receptor tyrosine kinase that uses an SH3–SH2–catalytic domain assembly to dock onto phosphorylated receptors and proline-rich adaptors at the plasma membrane and postsynaptic specializations. Upon recruitment, it autophosphorylates to activate and then phosphorylates nearby substrates to control immune receptor signaling, cytoskeletal remodeling, receptor trafficking, and synaptic plasticity. Its activity modulates NF-κB and MAPK pathways, shapes neuronal development and function, and tunes responses to growth factors and mechanical or environmental cues, with dynamic partitioning between the plasma membrane, membrane rafts, postsynaptic density, and associated cytoskeletal structures.
mouse	Myc	P01108	SFT	Mus musculus (Mouse)	136cc8a3368127f1b1a62bdf37d9427d50cf0c78a52ef921286bcf227ca40799	A dimeric transcription factor that binds E-box DNA elements to activate or repress RNA polymerase II and I–driven gene expression programs. Its N-terminal activation region recruits chromatin-modifying and remodeling complexes, while its C-terminal basic helix–loop–helix leucine zipper mediates heterodimerization and high-affinity DNA recognition. By assembling coactivators, corepressors, kinases, and ubiquitin ligase adaptors, it drives cell proliferation, differentiation, and apoptosis, coordinates organ development and tissue-specific programs, and integrates cytokine, DNA damage, xenobiotic, and kinase signals. It predominantly resides in euchromatin within nuclear bodies and the RNA polymerase II regulator complex, but dynamically shuttles through the perinuclear cytoplasm and can localize to the spindle and axons depending on cell state and partner interactions.
mouse	Pten	O08586	SFT	Mus musculus (Mouse)	f6379630c98e578ecdc15d517ea674b3eaf7ab33435e6a68d0698cd5d0c0ac63	A dual-specificity phosphatase that couples a membrane-targeted catalytic core to a C2 lipid-binding module to dephosphorylate both phosphoinositide lipids and protein phosphomonoesters. By removing the 3-phosphate from phosphatidylinositol-3,4,5-trisphosphate at the plasma membrane, it antagonizes PI3K–AKT signaling to restrain growth, proliferation, survival, and migration, while its protein-directed activity edits kinase and scaffold phosphorylation to refine pathway timing. Dynamic pools in the cytoplasm, nucleus, neuron projections, and myelinated regions enable it to tune synaptic plasticity, dendritic spine remodeling, oligodendrocyte differentiation and myelination, immune cell expansion, vascular growth and migration, and organismal behaviors including learning, circadian and locomotor rhythms, and parental and social behaviors. Mechanistically, it assembles with PI3K subunits, synaptic scaffolds, focal adhesion kinases, and p53 to create localized push–pull signaling hubs that terminate lipid signals and reset protein phosphorylation states.
mouse	Trp53	P02340	SFT	Mus musculus (Mouse)	2fa6c5557d01078f73032a40e5636829209fef068510b713a458263756677617	A stress-responsive transcription factor that assembles as a tetramer to bind specific DNA elements and recruit chromatin-modifying coactivators, thereby reprogramming gene expression to coordinate checkpoint arrest, DNA repair, and apoptosis. Its N-terminal activation region engages acetyltransferases and ubiquitin-system regulators to modulate chromatin accessibility and protein stability, while the central DNA-binding core confers high-affinity recognition of response elements and the C-terminal oligomerization domain enforces cooperative binding. It shuttles between cytosol, nucleus, nucleolus, replication forks, and DNA damage foci, and can signal to mitochondria to prime intrinsic apoptosis. Through these mechanisms it restrains proliferation, shapes developmental and immune programs, tunes circadian outputs, and orchestrates metabolic and proteostasis responses under genotoxic and environmental stress.
rat	Akt1	P47196	SFT	Rattus norvegicus (Rat)	a0e14f1ac3b3d5b37b54e1e489c1c48514bfa403a6b82a5a301e568dbc1112e2	A lipid-gated serine/threonine kinase that is recruited to membranes by binding phosphoinositides, becomes activated through phosphorylation of its activation loop and C-terminal regulatory motifs, and then phosphorylates metabolic enzymes, transcription factors, and cytoskeletal regulators to drive anabolic growth, survival, and controlled migration. It promotes insulin- and receptor-tyrosine-kinase–driven signaling, enhances translation and glycogen synthesis, tunes mitochondrial function and membrane potential, modulates stress and DNA-damage responses, and shapes ion transport and membrane excitability. The protein cycles between cytosol, plasma membrane, Golgi, mitochondria, and nucleus, where it engages phosphatases, kinases, and scaffolds to coordinate protein localization and pathway crosstalk.
rat	Casp3	P55213	SFT	Rattus norvegicus (Rat)	b18cc2230afafee43fe068e48e610b278643646fddec5a946516784e6d3b728b	An executioner cysteine protease that is synthesized as a cytosolic zymogen and activated by initiator caspases or death-receptor signaling to drive the execution phase of apoptosis. Upon activation, it dimerizes and cleaves substrates after aspartate residues, dismantling cytoskeletal and nuclear structures, inactivating survival and transcriptional regulators, and promoting inflammatory lipid signaling by activating phospholipases. It operates in the cytosol and can access the nucleus during apoptosis, associates with death-receptor signaling assemblies, and integrates diverse stress and hormonal cues to regulate proteolysis, protein stability, and tissue remodeling.
rat	Hspa5	P06761	SFT	Rattus norvegicus (Rat)	fbb235185680f73a68d2e4b46a7c8e7ce0a2952d2ed9b4f60d444ba8f9bf92d1	An endoplasmic reticulum–resident Hsp70 chaperone that uses an ATP-driven capture-and-release cycle to bind unfolded and misfolded polypeptides, promote their folding, and prevent aggregation during secretory pathway stress. By coordinating with J-domain cochaperones, oxidoreductases, and nucleotide exchange factors, it triages clients across the ER quality-control network and relays them to downstream chaperones. This activity maintains proteostasis during diverse insults, tunes the unfolded protein response, and modulates cell survival pathways, including a complex with BAG3 that suppresses apoptosis. It associates peripherally with the cytoplasmic face of the ER membrane and can redistribute under stress, with additional roles in shaping neuronal and endocrine responses through its control of secretory and stress-sensing pathways.
rat	Mapk1	P63086	SFT	Rattus norvegicus (Rat)	00ea6cde7b6a77f949fa1b750ca7301be0b75a15172a43af26227821caf7b79c	A versatile serine/threonine kinase that functions as a central node in the MAPK/ERK signaling cascade. It is activated by dual phosphorylation within its activation loop, recruited to receptor-proximal scaffolds including caveolin-rich microdomains and endosomal platforms, and then phosphorylates a wide spectrum of cytoplasmic and nuclear substrates to coordinate transcription, translation, cytoskeletal remodeling, endosomal trafficking, and organelle organization. It promotes nuclear entry of specific regulators, modulates chromatin and transcription factor activity, influences Golgi fragmentation, and contributes to cell migration, proliferation, stress responses, and specialized physiological programs such as pain signaling and decidualization. Its activity is tuned by upstream MAP2Ks and counteracted by dual-specificity phosphatases, enabling rapid, spatially organized signaling within cytosolic, nuclear, endosomal, Golgi, mitochondrial, and neuronal compartments.
rat	Prkaa2	Q09137	SFT	Rattus norvegicus (Rat)	92c13cf306fa1dc862dfe1b64335ae50d5105cc30e9c43cb8bee2a2f5328855b	A serine/threonine kinase catalytic subunit that senses cellular energy via adenylate-regulated control within a heterotrimeric complex and converts nutrient and stress signals into widespread phosphorylation of metabolic enzymes, transcriptional regulators, and components of growth control. It activates energy-producing pathways (glycolysis, gluconeogenesis, fatty acid oxidation) while suppressing energy-consuming biosynthesis, restrains protein, carbohydrate, and lipid synthesis, and modulates autophagy and the cell cycle. It promotes glucose uptake in myotubes and influences insulin sensitivity, contributes to cellular responses to glucose, calcium, activity, and caffeine, and coordinates lipid metabolism including inhibition of lipogenesis. It regulates mTORC1 by phosphorylating TSC2 to promote activity and RPTOR to inhibit it depending on nutrient status, and it can phosphorylate HSF4. The enzyme operates in the cytoplasm and nucleus and is targeted to membrane subdomains, including apical surfaces and neuronal dendrites and axons, where scaffolded interactions position it near substrates and upstream regulators.
rat	Rgn	Q03336	SFT	Rattus norvegicus (Rat)	10eab8c8db84f9aed7b715106d3946d55d0b8a65fa4bf915e12e70026951600c	A calcium-responsive cytosolic and nuclear regulator that combines a six-bladed beta-propeller catalytic core with conserved SMP-30/Regucalcin surfaces to hydrolyze sugar lactones while buffering calcium and assembling signaling complexes. By coupling calcium binding to lactonase activity and to protein–protein interactions, it modulates kinase and phosphatase pathways, small GTPase circuits, and redox enzymes, thereby shaping metabolic programs including glucose, fatty acid, and triglyceride biosynthesis, tuning calcium transport, and restraining proliferation and DNA synthesis. These activities extend to developmental contexts such as spermatogenesis, kidney formation, and liver regeneration, and contribute to organismal aging through sustained redox and calcium homeostasis.
rat	Slc5a1	P53790	SFT	Rattus norvegicus (Rat)	02242c85045c19b7f67a575a8b4460333583310463fd23048aed7c600dec7e45	A multi-pass epithelial membrane transporter that uses the inward sodium gradient to drive concentrative uptake of monosaccharides across the apical surface. In the intestine, it resides predominantly at the brush border to absorb dietary sugars from the lumen; in kidney proximal tubules, it supports glucose reclamation from filtrate. The transport cycle binds one sodium ion and one hexose (such as glucose, galactose, or xylose), occludes both within a transmembrane core, and releases them cytosolically to accumulate sugars against their gradients. Its activity and surface abundance are likely tuned by local signaling and trafficking machinery within apical microdomains.
rat	St13	P50503	SFT	Rattus norvegicus (Rat)	a3d6e4892caf06da1d420964325b64a08d3b3fec98a2ce6c865fbcfb43e45ebe	A soluble co-chaperone that organizes Hsp70–Hsp90 cycles to control client protein fate. Its N-terminal module grips the ATPase domain of Hsp70, a central array of tetratricopeptide repeats docks the C-terminal motifs of Hsp70 and Hsp90, and a C-terminal regulatory module stimulates Hsp70’s ATP hydrolysis. By accelerating ATP turnover and coordinating client transfer, it enhances folding efficiency and can route unstable substrates toward degradation. Operating in both cytoplasm and nucleus, it assembles large chaperone complexes that mature signaling proteins and transcriptional regulators.
rat	Tp53	P10361	SFT	Rattus norvegicus (Rat)	656c6cb72db492c4e33f9950521be7d747c759e5b9649a540ff41a969a1a23ee	A stress-responsive transcription factor in rat that assembles as a tetramer to bind specific DNA elements and recruit coactivators or corepressors, thereby switching between cell-cycle arrest and apoptosis in response to DNA damage and diverse physiological stresses. Its N-terminal activation region engages chromatin modifiers and ubiquitin pathway regulators to tune stability and activity, while the central DNA-binding core selects target genes and the C-terminal oligomerization domain stabilizes high-avidity chromatin binding. Dynamic shuttling between nucleus and cytoplasm, concentration in PML nuclear bodies, and transient association with mitochondria enable integration of checkpoint signals, modulation of cation and pH homeostasis via transporter-linked programs, and broad control over wound healing, proliferation, migration, and aging phenotypes.
rat	Uggt1	Q9JLA3	SFT	Rattus norvegicus (Rat)	473d3747325e5e48d3938a5b11b7db50ace2e017fc43c9691048074320c17e7a	An endoplasmic reticulum–lumenal quality-control enzyme that recognizes non-native glycoproteins and transfers a glucose from UDP-glucose onto the terminal diols of their N-linked glycans. By reglucosylating these glycans, it re-engages lectin chaperones to promote additional folding cycles and prevents premature trafficking of misfolded proteins. Its N-terminal chaperone-like modules bind incompletely folded regions, while the C-terminal catalytic core performs the glucosyl transfer, thereby sustaining iterative folding in the early secretory pathway and at the ER–Golgi interface.
worm	atfs-1	Q23272	SFT	Caenorhabditis elegans	22d26c1fc72f0cfcab1551a9dc228bf49ec25a475c4086e77298cb297fcc6fd5	A dual-localized regulatory factor that dimerizes through a C‑terminal bZIP module to bind promoters and reprogram transcription while its N‑terminal region engages mitochondrial proteostasis machinery. In the nucleus, it activates genes that elevate mitochondrial small-RNA levels and broader transcriptional output, thereby boosting mitochondrial function to support larval development. In the mitochondrial matrix, it associates with chaperones and proteases to sense protein-folding status; under amino acid starvation, this sensing converges with stress signaling to promote autophagy and mobilize stored lipids from lipid droplets.
worm	cmd-1	O16305	SFT	Caenorhabditis elegans	2fe0c40fd06d47b884b65e9f18062de35ab8af643dc87146baa8d79b73af1853	A Ca2+-sensor that uses paired EF-hand motifs to bind calcium and undergo a conformational switch, exposing hydrophobic pockets that clamp onto diverse target proteins. By activating or inhibiting kinases, phosphatases, ion channels, and cytoskeletal regulators, it coordinates meiotic progression, spindle orientation, cell migration and chemotaxis, regulation of protein localization, control of the cell cycle and apoptotic pathways, and efficient clearance of apoptotic corpses. Its activity is distributed across centrosomes, the mitotic spindle, the phagocytic cup, the cell periphery, and the nuclear envelope, reflecting dynamic recruitment to signaling hubs where calcium transients are decoded into precise cellular outcomes.
worm	drp-1	Q8WQC9	SFT	Caenorhabditis elegans	ea229bb954698a31a794bc87dcbac6ae68833de0815b8fd6c1becd2bc02fdc71	A peripheral mitochondrial mechanoenzyme that assembles into helical polymers on the outer membrane to drive mitochondrial division. Its N-terminal nucleotide-binding engine binds and hydrolyzes GTP, the central stalk mediates self-assembly and membrane tethering, and the C-terminal effector domain couples polymerization to catalytic activation. Through cycles of GTP-driven constriction, it executes mitochondrial fission, thereby shaping organelle morphology, contributing to developmental programs, and priming apoptotic remodeling. Recruitment by dedicated fission adaptors and regulation by mitochondrial stress pathways integrate its activity with quality control and organelle homeostasis.
worm	hlh-30	H2KZZ2	SFT	Caenorhabditis elegans	bd8964abffcffddb4cc27caa39f53c2cc8a5088413faaedc47e3692aca1b50d7	A dimeric basic helix–loop–helix transcription factor that binds E-box motifs to activate RNA polymerase II–dependent transcription programs controlling autophagy, lipid metabolism, and stress defense. By inducing autophagy genes, including the Atg8/LC3 ortholog, it promotes clearance of protein aggregates and contributes to organismal longevity. It also regulates triglyceride and sphingolipid pathways that influence plasma membrane organization. The factor operates primarily in the nucleus but undergoes cytoplasmic regulation and turnover, integrating nutrient and stress signals to fine-tune gene expression and autophagic flux.
worm	hsf-1	G5EFT5	SFT	Caenorhabditis elegans	dd3c5fbeb09a015978eef18fa1a33d6cbeccb9fd3285830e0f5c379ff18d2c4e	A nuclear transcriptional regulator that uses a winged-helix DNA-binding core to recognize heat shock elements at promoters and assemble stress-activated transcriptional complexes. It oligomerizes on DNA, engages chromatin, and is modulated by calmodulin and chaperone systems to switch between inactive and active states. By activating chaperones and proteostasis genes and selectively repressing targets in specific tissues, it coordinates responses to heat and misfolded proteins, shapes innate immunity and defense against Gram-negative bacteria, and integrates sensory and hormonal cues to influence development, metabolism, autophagy, and lifespan. Dynamic partitioning between nucleus, chromatin, nuclear bodies, cytoplasm, and stress granules supports this multifaceted control.
worm	hsp-90	Q18688	SFT	Caenorhabditis elegans	856622c1c318cf0e765a78eadbaa8b90d200293baf972352b902e3158305d900	An ATP-driven molecular chaperone that cycles between open and closed states to remodel client proteins, stabilize signaling factors, and coordinate their trafficking. It assembles with a defined set of co-chaperones to receive clients from Hsp70, stimulate ATP hydrolysis, and regulate associated kinases and phosphatases, thereby promoting protein folding, stability, and nuclear export of regulatory factors. By maintaining receptor and kinase homeostasis, it supports neuronal function, organismal locomotion and chemotaxis, developmental decisions such as dauer formation, and ultimately influences adult lifespan. It operates within chaperone assemblies concentrated near the nuclear envelope and at membrane raft microdomains, where receptor and kinase signaling are organized.
worm	ire-1	Q09499	SFT	Caenorhabditis elegans	bf29054d793bf3be67a810dcd1c22335ea444ceb20ba69d8399cf2ad1a044825	An endoplasmic reticulum–anchored, single-pass stress sensor that uses a luminal beta-propeller scaffold to monitor protein-folding conditions and, upon clustering, activates a cytosolic serine/threonine kinase that in turn switches on a site-specific endoribonuclease. This RNase cleaves selected mRNAs to drive a transcriptional program and remove ER-targeted transcripts, thereby rebalancing folding load and restoring proteostasis. Chaperone binding in the ER lumen modulates activation, while a bZIP transcription factor serves as a key downstream effector.
worm	lgg-1	Q09490	SFT	Caenorhabditis elegans	c3755f49f58e33aa3a25bc882876e83ec032c59c0cbefc9f11bd6d73a28c3bb0	A ubiquitin-like, lipid-anchored autophagy modifier that becomes conjugated to phosphatidylethanolamine on nascent autophagic membranes, where it scaffolds LIR-containing receptors and effectors to drive autophagosome assembly and selective cargo sequestration. By organizing aggrephagy and mitophagy, it supports membrane repair, maintains neuronal integrity, and modulates stress responses that influence developmental transitions and lifespan. It localizes to the autophagosome membrane and also associates with the mitochondrial surface during organelle turnover, with enrichment in neuronal compartments and detectable presence in the nucleus under stress.
worm	pgl-1	Q9TZQ3	SFT	Caenorhabditis elegans	a3fc12f671afe869dc4d1ee17231339879402c8d4a960e303a66f3dff40e044a	An ER-anchored, single-pass membrane adaptor in C. elegans germ cells that uses a cytosolic surface to bind and organize RNA-silencing factors at the ER. By recruiting helicases, P-body components, and Argonaute-family effectors, it assembles and stabilizes post-transcriptional repression complexes that remodel or degrade target mRNAs, thereby shaping gene expression programs required for late spermatogenesis and sperm individualization.
worm	pink-1	Q09298	SFT	Caenorhabditis elegans	a4e2e5ad035c1804a64b9bfad5bfd34b0bdc4b67c8df58b15b1e0fd44ea37d8e	A mitochondria-focused serine/threonine kinase that senses organelle status and writes regulatory phosphorylation marks to control mitochondrial dynamics and quality. When the organelle is healthy and import is active, the enzyme resides in the matrix. When membrane potential collapses, import stalls and the kinase accumulates on the outer membrane, where it phosphorylates the fission GTPase to promote division and phosphorylates a cytosolic ubiquitin ligase to boost its activity. This dual action enhances ubiquitin tagging of mitochondrial surface proteins and drives selective autophagic removal of damaged organelles. Through these activities it supports oxidative and ER stress responses and is essential for neuronal development, including axon extension and guidance.
worm	pmk-1	Q17446	SFT	Caenorhabditis elegans	02c08a60df1f93e585643ee32c716e3da983a282422e820c2b9c405fb939c83f	A stress-activated MAP kinase in C. elegans that becomes activated by dual phosphorylation and then phosphorylates serine/threonine sites on downstream kinases and transcription factors to reprogram gene expression during innate immune and environmental stress. It shuttles from the cytosol to the nucleus to promote antimicrobial peptide transcription, modulate ER and oxidative stress responses, and shape developmental cell death and neuronal survival programs. Upstream MAP2Ks turn it on, while dual-specificity phosphatases turn it off, enabling precise control of defense against Gram-negative bacteria and adaptation to osmotic, heat, and toxic challenges.
worm	skn-1	P34707	SFT	Caenorhabditis elegans	129f5ba0855a66add6fbcefa3fd58d6f5dff7458cf5f5168cff451112d2d6f4a	A CNC-type bZIP transcription factor in C. elegans that dimerizes through its leucine zipper, binds specific promoter elements, and activates RNA polymerase II transcription to mount oxidative, ER, and heat-stress defenses. Its N-terminal regulatory region engages chaperones and ubiquitin–ligase machinery for stability control, causing cytoplasmic sequestration and turnover under basal conditions and nuclear accumulation during stress. By inducing detoxification enzymes and proteostasis programs, it enhances neuronal resilience, shapes developmental cell fate decisions, and contributes to organismal lifespan, with activity tuned by stress-activated and growth-control kinases and coordinated with translational control.
yeast	CAT2	P32796	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	627ef7a38968eaddb16f093ccc88f6b9c2214c0c6713f72aa91cd545286a533a	A soluble matrix acetyltransferase in baker’s yeast that catalyzes the reversible transfer of an acetyl group between acetyl‑CoA and carnitine, generating acetylcarnitine for inter-organelle shuttling and regenerating acetyl‑CoA for metabolism. In peroxisomes, it couples β‑oxidation to acetyl export; in mitochondria, it reconstitutes acetyl‑CoA to support the TCA cycle and anaplerotic routes. Its bilobal acyltransferase fold forms a catalytic cleft that binds acetyl‑CoA and carnitine to drive a ping‑pong acyl‑transfer mechanism, coordinating with carnitine transporters and acetyl‑handling enzymes to balance acetyl flux across organelles.
yeast	CDC37	P06101	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	7e42a96cf924d33f480e1ef597a59713420b28b09e502c7ae8fb98d1a90a3b96	A cytosolic Hsp90 co-chaperone that captures immature protein kinases, stabilizes them, and delivers them to the Hsp90 folding cycle to achieve activation. By coordinating auxiliary factors such as ATPase-stimulating and isomerase cofactors, it promotes maturation of kinase clients that drive osmoadaptation, MAPK signaling, and cell-cycle and spindle pole body organization, thereby safeguarding protein stability under stress and ensuring timely signaling outputs.
yeast	HSP104	P31539	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	90815e60e72986fdd515a710fcde152082636f4e0f5107c043db7fd3532cc2f1	An ATP-driven cytosolic disaggregase that assembles into a hexameric motor to extract polypeptides from heat-induced aggregates, cooperate with Hsp70/Hsp40 and small heat shock proteins for client triage, and hand substrates to Hsp70 for refolding. By forcibly remodeling protein assemblies, it promotes recovery from heat stress, disassembles stress granules to release specific RNA-binding factors, and supports proteostasis pathways that include folding of secretory-pathway clients and trehalose-linked acclimation mechanisms. It operates primarily in the cytosol with transient activity at the nuclear periphery within the dedicated Hsp70–Hsp40–Hsp104 complex.
yeast	HSP60	P19882	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	fb37f6560e3ab7c967fec64b50113b1976b4697138ab1f9ae4dc0ceb6c08531b	An ATP-driven mitochondrial folding machine that assembles into a double-ring cage and, together with a small cochaperonin lid, encapsulates non-native polypeptides to promote their productive folding, refolding, and stabilization. It operates primarily in the matrix, receiving newly imported precursors from the inner-membrane translocases and assisting their maturation, while also supporting assembly of multi-subunit complexes and stabilizing factors associated with mitochondrial DNA and nucleoids. Its equatorial ATPase core powers conformational cycles that reposition an apical substrate-binding lid, enabling selective capture and release of clients and integration with upstream Hsp70/GrpE delivery and downstream disaggregation pathways.
yeast	IRE1	P32361	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	797baae330e55c66994e5f7e588bc0b963c90204b60148bcba9d012b1cfc02cb	An endoplasmic reticulum membrane receptor-enzyme that senses unfolded proteins via a lumenal beta-propeller–like sensor, dimerizes, and activates a cytosolic serine/threonine kinase that autophosphorylates to switch on an adjacent endoribonuclease. The nuclease cleaves a structured cytoplasmic mRNA to generate a spliced leader that becomes a potent transcriptional activator, driving a gene program that expands ER folding capacity, enhances ER-associated degradation, promotes trafficking to the Golgi, and supports cell wall and inositol metabolism. The protein functions as a single-pass type I membrane receptor, assembles into kinase and endoribonuclease complexes, and exerts its effects from the ER with downstream action in the nucleus.
yeast	KAR2	P16474	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	3a04b3c9608e586f5caf1ba79a655aabcfd0c21c8179363bdf39da5416d06035	An endoplasmic reticulum lumenal Hsp70 chaperone that uses an ATP-driven cycle to bind and release exposed hydrophobic segments in nascent and misfolded polypeptides. By coupling ATP hydrolysis to lid closure on its peptide-binding site, it stabilizes translocating chains at the translocon, promotes folding and assembly of secretory and membrane proteins, and retains terminally misfolded glycoproteins for degradation. It collaborates with J-domain co-chaperones and nucleotide-exchange factors to reset the cycle, coordinates with lectin and disulfide isomerization pathways for quality control, and engages the ER-associated degradation machinery to route defective clients to the dislocation-ubiquitination pipeline. Through these actions it supports cotranslational and post-translational targeting to the ER, maintains ER proteostasis, influences the unfolded protein response via binding to luminal domains of signaling factors, and sustains processes such as cell wall biogenesis and mating-associated karyogamy that depend on robust secretory function.
yeast	PDI1	P17967	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	40f9c60aaf3416199562966b0b298c5a0a811ac7ec288a9a19df6dc264ea3e6c	An endoplasmic reticulum lumenal redox chaperone that catalyzes disulfide bond formation, isomerization, and reduction in secretory and membrane proteins while holding non-native polypeptides to prevent aggregation. It cooperates with oxidases, lectin chaperones, and Hsp70/Hsp40 systems to promote productive folding; when folding fails, it engages glycan-dependent quality control and channels clients into degradation. By improving folding throughput and triaging misfolded glycoproteins, it supports ER proteostasis and can enhance the unfolded protein response. It also contributes to the maturation of specific clients such as the a-factor pheromone and the a1 subunit of the plasma-membrane ATPase.
yeast	RAS2	P01120	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	067ff0591ef27c2ea243535b9f200705709dd2d848659d57a5fe7b5f6247fc36	A Ras-like small GTPase in baker’s yeast that cycles between GTP- and GDP-bound states to control nutrient-responsive signaling. When GTP-loaded at the cytoplasmic face of the plasma membrane via lipid anchoring, it engages adenylate cyclase to elevate cAMP and activate protein kinase A. This signaling axis modulates transcription during carbon catabolite conditions, promotes pseudohyphal growth, and tunes protein localization, while also influencing autophagy, P-body dynamics, and sporulation. Its activity is turned on by a guanine nucleotide exchange factor and turned off by a GTPase-activating protein, with additional regulatory crosstalk through kinases and transcriptional regulators that implement the cellular responses.
yeast	SIR2	P06700	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	22608fa6026483cc7a7cd9974808059a114cd4e5e847e347dfeb92fd837cb730	A nuclear NAD-dependent histone deacetylase that removes acetyl groups from lysines on histones H3 and H4 to compact chromatin and establish repressive domains at telomeres, silent mating-type loci, and rDNA. By assembling with chromatin-silencing factors and nucleolar tethers, it positions deacetylation at specific chromosomal regions to enforce heterochromatin, restrain recombination, modulate replication fork behavior, and influence sister chromatid cohesion and DNA repair pathway choice. Its activity is tightly coupled to cellular NAD supply, linking nutrient status to gene silencing and contributing to chronological aging, with inducible expression under nutrient deprivation reinforcing long-term cellular lifespan.
yeast	SSA1	P10591	SFT	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	b1bc12a151e67d244310476bd3b6949d9834db324ae969f627a110fa1b678728	A cytosolic heat-shock chaperone that uses an ATP-driven clamp to capture, stabilize, and refold non-native polypeptides, while also directing terminally misfolded clients toward ubiquitination and proteasomal degradation. It associates with translating ribosomes to support co-translational folding and to influence translation termination, and it powers targeting of nascent and preproteins to mitochondria and the endoplasmic reticulum. It escorts transcription factors into the nucleus and can moonlight at the cell surface and vacuolar membrane during stress. Mechanistically, ATP binding and hydrolysis in the N-terminal nucleotide-binding domain allosterically regulate a substrate-binding cleft and C-terminal lid, with cochaperones accelerating hydrolysis or promoting nucleotide exchange to switch between high- and low-affinity client states. It collaborates with Hsp90/Hsp40 systems and disaggregases to balance refolding, disaggregation, and degradation.