BioReason Chat Export

Exported on March 22, 2026 at 01:33 AM

Organism: Mus musculus

Sequence:

MTAMEESQSDISLELPLSQETFSGLWKLLPPEDILPSPHCMDDLLLPQDVEEFFEGPSEALRVSGAPAAQDPVTETPGPVAPAPATPWPLSSFVPSQKTYQGNYGFHLGFLQSGTAKSVMCTYSPPLNKLFCQLAKTCPVQLWVSATPPAGSRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNLYPEYLEDRQTFRHSVVVPYEPPEAGSEYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEVLCPELPPGSAKRALPTCTSASPPQKKKPLDGEYFTLKIRGRKRFEMFRELNEALELKDAHATEESGDSRAHSSYLKTKKGQSTSRHKKTMVKKVGPDSD

Thinking Trace

I begin by dissecting the InterPro architecture. The protein is classified broadly by IPR002117 (p53 tumour suppressor family, residues 6–362), immediately suggesting a transcriptional regulator that orchestrates stress and checkpoint pathways. Near the N-terminus sits IPR013872 (p53, transactivation domain, residues 9–32), a low-complexity activation module that recruits coactivators and corepressors. The central core comprises IPR011615 (p53, DNA-binding domain, residues 97–286), reinforced by two overlapping superfamily signatures—IPR012346 (p53/RUNT-type transcription factor, DNA-binding domain superfamily, residues 92–292) and IPR008967 (p53-like transcription factor, DNA-binding domain superfamily, residues 94–284)—which together define a structured site-recognition fold that binds specific DNA elements and couples sequence-specific contacts to regulatory responses. Embedded within this core is IPR057064 (p53, central conserved site, residues 234–246), a hallmark motif that stabilizes the DNA-binding architecture and coordinates allosteric communication. At the C-terminus, IPR010991 (p53, tetramerisation domain, residues 316–353) and its higher-order envelope IPR036674 (p53-like tetramerisation domain superfamily, residues 316–357) enforce assembly into a homotetramer. This ordered layout—an N-terminal activation region, a central site-specific DNA-binding core with a conserved stabilization motif, and a C-terminal oligomerization hub—causally dictates a sequence-specific DNA-binding transcription factor that operates as a tetrameric switch.

From these domains, the molecular function follows directly. The presence of a dedicated transactivation domain (IPR013872) coupled to the structured DNA-binding core (IPR011615 and its superfamilies) establishes RNA polymerase II-dependent transcriptional regulation. The tetramerisation module (IPR010991/IPR036674) amplifies affinity and specificity by cooperative assembly, a common strategy for high-fidelity transcriptional control. This architecture yields DNA-binding transcription factor activity with sequence specificity and supports both activation and repression depending on cofactor recruitment. Therefore, the molecular function is best captured by GO:0003700 DNA-binding transcription factor activity, sequence-specific DNA binding.

Biological process emerges as a consequence of this regulatory capacity. A p53-family transcriptional hub that binds and modulates promoter/enhancer activity is poised to govern checkpoints and stress responses. The conserved central site and tetrameric assembly ensure robust control over gene networks that halt cell cycle progression and promote repair or apoptosis when genomic integrity is compromised. This causal chain aligns with control of the cell cycle and apoptosis and situates the protein at the heart of stress-responsive transcriptional programs. Accordingly, the most defensible process annotations are GO:0051726 regulation of cell cycle and GO:0006915 apoptotic process.

Cellular location follows from function and architecture. A DNA-binding transcriptional regulator must access chromatin; the presence of a transactivation domain and a canonical DNA-binding core necessitate nuclear residence, consistent with a soluble nuclear regulator. Thus, the cellular component is the nucleus (GO:0005634).

Mechanistically, I hypothesize a tetrameric transcriptional switch that senses intracellular stress and enforces checkpoints. The N-terminal activation domain recruits chromatin-modifying coactivators (e.g., acetyltransferases) or corepressors, while the central domain binds specific promoter elements and transmits signals through the conserved site to tune transcriptional output. The tetramerisation domain concentrates binding interfaces to stabilize higher-order assemblies on DNA. Likely partners include E3 ubiquitin ligases that set protein turnover thresholds, chromatin remodelers that gate promoter accessibility, and checkpoint kinases that phosphorylate and modulate its activity. Together, these interactions allow dynamic repression or activation of genes governing cell cycle arrest and apoptosis within the nucleus.

Functional Summary

A nuclear, tetramer-forming transcriptional regulator that uses an N‑terminal activation module and a central site-recognition core to control RNA polymerase II–dependent gene programs. By assembling into a cooperative homotetramer, it binds specific promoter elements, recruits chromatin-modifying cofactors, and toggles between activation and repression to enforce checkpoint pathways that govern cell cycle control and trigger apoptosis under stress.

UniProt Summary

Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activating protein that acts downstream of a signal mediated by a DNA damage-stress pathway. Appears to regulate at least two distinct pathways: the mediation of apoptotic pathways by p53/TP53, and repression of cell cycle progression by impeding the G2/M transition (By similarity).

InterPro Domains

• p53 tumour suppressor family (IPR002117, family) — residues 6-362
• p53, transactivation domain (IPR013872, domain) — residues 9-32
• p53/RUNT-type transcription factor, DNA-binding domain superfamily (IPR012346, homologous_superfamily) — residues 92-292
• p53-like transcription factor, DNA-binding domain superfamily (IPR008967, homologous_superfamily) — residues 94-284
• p53, DNA-binding domain (IPR011615, domain) — residues 97-286
• p53, central conserved site (IPR057064, conserved_site) — residues 234-246
• p53, tetramerisation domain (IPR010991, domain) — residues 316-353
• p53-like tetramerisation domain superfamily (IPR036674, homologous_superfamily) — residues 316-357

GO Terms

Molecular Function: molecular_function (GO:0003674), molecular function regulator activity (GO:0098772), binding (GO:0005488), transcription regulator activity (GO:0140110), enzyme regulator activity (GO:0030234), DNA-binding transcription factor activity, sequence-specific DNA binding (GO:0003700), organic cyclic compound binding (GO:0097159), heterocyclic compound binding (GO:1901363), chromatin binding (GO:0003682), protein binding (GO:0005515), nucleic acid binding (GO:0003676), DNA-binding transcription activator activity (GO:0001216), enzyme binding (GO:0019899), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), ubiquitin-like protein ligase binding (GO:0044389), transcription regulatory region nucleic acid binding (GO:0001067), DNA binding (GO:0003677), ubiquitin protein ligase binding (GO:0031625), sequence-specific DNA binding (GO:0043565), transcription cis-regulatory region binding (GO:0000976), double-stranded DNA binding (GO:0003690), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)

Biological Process: biological_process (GO:0008150), localization (GO:0051179), signaling (GO:0023052), biological regulation (GO:0065007), response to stimulus (GO:0050896), biological process involved in interspecies interaction between organisms (GO:0044419), growth (GO:0040007), negative regulation of biological process (GO:0048519), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), multicellular organismal process (GO:0032501), rhythmic process (GO:0048511), developmental process (GO:0032502), cellular process (GO:0009987), metabolic process (GO:0008152), immune system process (GO:0002376), cellular localization (GO:0051641), anatomical structure development (GO:0048856), negative regulation of signaling (GO:0023057), immune response (GO:0006955), cell cycle process (GO:0022402), pattern specification process (GO:0007389), cellular component organization or biogenesis (GO:0071840), regulation of multicellular organismal process (GO:0051239), anatomical structure formation involved in morphogenesis (GO:0048646), negative regulation of metabolic process (GO:0009892), regulation of biological quality (GO:0065008), regulation of cellular process (GO:0050794), regulation of response to stimulus (GO:0048583), cellular response to stimulus (GO:0051716), multicellular organism growth (GO:0035264), process utilizing autophagic mechanism (GO:0061919), negative regulation of cellular process (GO:0048523), cellular developmental process (GO:0048869), response to abiotic stimulus (GO:0009628), biosynthetic process (GO:0009058), regulation of metabolic process (GO:0019222), establishment of localization (GO:0051234), catabolic process (GO:0009056), macromolecule localization (GO:0033036), negative regulation of gene silencing by RNA (GO:0060967), immune effector process (GO:0002252), negative regulation of post-transcriptional gene silencing (GO:0060149), cell communication (GO:0007154), positive regulation of cellular process (GO:0048522), response to external stimulus (GO:0009605), developmental growth (GO:0048589), anatomical structure morphogenesis (GO:0009653), response to chemical (GO:0042221), leukocyte activation (GO:0045321), cell population proliferation (GO:0008283), nitrogen compound metabolic process (GO:0006807), negative regulation of multicellular organismal process (GO:0051241), regulation of developmental process (GO:0050793), response to biotic stimulus (GO:0009607), cell death (GO:0008219), response to endogenous stimulus (GO:0009719), regulation of signaling (GO:0023051), negative regulation of developmental process (GO:0051093), response to other organism (GO:0051707), signal transduction (GO:0007165), multicellular organism development (GO:0007275), cell activation (GO:0001775), determination of adult lifespan (GO:0008340), regulation of circadian rhythm (GO:0042752), circadian rhythm (GO:0007623), cell cycle (GO:0007049), organic substance metabolic process (GO:0071704), cellular metabolic process (GO:0044237), small molecule metabolic process (GO:0044281), positive regulation of metabolic process (GO:0009893), response to stress (GO:0006950), negative regulation of response to stimulus (GO:0048585), primary metabolic process (GO:0044238), behavior (GO:0007610), negative regulation of post-transcriptional gene silencing by RNA (GO:1900369), neural precursor cell proliferation (GO:0061351), negative regulation of cellular component organization (GO:0051129), response to external biotic stimulus (GO:0043207), reactive oxygen species metabolic process (GO:0072593), response to radiation (GO:0009314), regulation of response to stress (GO:0080134), stem cell proliferation (GO:0072089), regulation of tissue remodeling (GO:0034103), animal organ development (GO:0048513), regulation of signal transduction (GO:0009966), regulation of macromolecule metabolic process (GO:0060255), cellular aromatic compound metabolic process (GO:0006725), carbohydrate metabolic process (GO:0005975), negative regulation of cell cycle process (GO:0010948), establishment of protein localization (GO:0045184), autophagy (GO:0006914), response to inorganic substance (GO:0010035), intracellular transport (GO:0046907), cardiac septum morphogenesis (GO:0060411), negative regulation of macromolecule metabolic process (GO:0010605), organic acid metabolic process (GO:0006082), embryo development (GO:0009790), negative regulation of cell cycle (GO:0045786), cellular macromolecule metabolic process (GO:0044260), regulation of cell cycle process (GO:0010564), positive regulation of nitrogen compound metabolic process (GO:0051173), regulation of membrane permeability (GO:0090559), negative regulation of nitrogen compound metabolic process (GO:0051172), organic substance biosynthetic process (GO:1901576), small molecule catabolic process (GO:0044282), positive regulation of macromolecule metabolic process (GO:0010604), heterocycle metabolic process (GO:0046483), negative regulation of cell population proliferation (GO:0008285), regulation of cellular response to stress (GO:0080135), glial cell proliferation (GO:0014009), hindbrain development (GO:0030902), establishment of localization in cell (GO:0051649), cellular biosynthetic process (GO:0044249), monosaccharide metabolic process (GO:0005996), cellular nitrogen compound metabolic process (GO:0034641), regulation of protein stability (GO:0031647), macromolecule metabolic process (GO:0043170), positive regulation of biosynthetic process (GO:0009891), negative regulation of carbohydrate metabolic process (GO:0045912), innate immune response (GO:0045087), defense response to other organism (GO:0098542), regulation of multicellular organismal development (GO:2000026), cellular response to environmental stimulus (GO:0104004), regulation of cell population proliferation (GO:0042127), regulation of cell death (GO:0010941), somitogenesis (GO:0001756), regionalization (GO:0003002), positive regulation of cellular metabolic process (GO:0031325), cellular response to stress (GO:0033554), negative regulation of cell differentiation (GO:0045596), transport (GO:0006810), cellular macromolecule localization (GO:0070727), regulation of cellular metabolic process (GO:0031323), negative regulation of catabolic process (GO:0009895), negative regulation of biosynthetic process (GO:0009890), regulation of primary metabolic process (GO:0080090), generation of precursor metabolites and energy (GO:0006091), rhythmic behavior (GO:0007622), regulation of cellular response to growth factor stimulus (GO:0090287), negative regulation of signal transduction (GO:0009968), positive regulation of cell death (GO:0010942), response to hypoxia (GO:0001666), programmed cell death (GO:0012501), negative regulation of cell death (GO:0060548), cell development (GO:0048468), leukocyte activation involved in immune response (GO:0002366), response to xenobiotic stimulus (GO:0009410), cell differentiation (GO:0030154), negative regulation of nervous system development (GO:0051961), cellular catabolic process (GO:0044248), system development (GO:0048731), response to oxygen levels (GO:0070482), cardiac septum development (GO:0003279), response to growth factor (GO:0070848), cellular response to endogenous stimulus (GO:0071495), lymphocyte activation (GO:0046649), neuron death (GO:0070997), regulation of cell cycle (GO:0051726), regulation of catabolic process (GO:0009894), cerebellum development (GO:0021549), animal organ morphogenesis (GO:0009887), organic cyclic compound metabolic process (GO:1901360), leukocyte proliferation (GO:0070661), cellular response to abiotic stimulus (GO:0071214), apoptotic signaling pathway (GO:0097190), regulation of nitrogen compound metabolic process (GO:0051171), negative regulation of small molecule metabolic process (GO:0062014), regulation of cell differentiation (GO:0045595), cellular component organization (GO:0016043), cell surface receptor signaling pathway (GO:0007166), organic substance catabolic process (GO:1901575), regulation of cellular component organization (GO:0051128), organic hydroxy compound metabolic process (GO:1901615), negative regulation of cell communication (GO:0010648), mitotic cell cycle process (GO:1903047), intracellular signal transduction (GO:0035556), response to oxidative stress (GO:0006979), defense response (GO:0006952), response to osmotic stress (GO:0006970), circadian behavior (GO:0048512), cardiac chamber development (GO:0003205), negative regulation of cellular metabolic process (GO:0031324), metencephalon development (GO:0022037), response to organic substance (GO:0010033), necrotic cell death (GO:0070265), fibroblast proliferation (GO:0048144), cell fate commitment (GO:0045165), embryonic morphogenesis (GO:0048598), nucleobase-containing compound metabolic process (GO:0006139), head development (GO:0060322), regulation of cell communication (GO:0010646), tissue development (GO:0009888), cellular response to chemical stimulus (GO:0070887), cell activation involved in immune response (GO:0002263), regulation of biosynthetic process (GO:0009889), regulation of small molecule metabolic process (GO:0062012), entrainment of circadian clock (GO:0009649), cardiac chamber morphogenesis (GO:0003206), response to ischemia (GO:0002931), mitotic cell cycle (GO:0000278), nitrogen compound transport (GO:0071705), monosaccharide catabolic process (GO:0046365), T cell lineage commitment (GO:0002360), regulation of macromolecule biosynthetic process (GO:0010556), cellular response to oxygen levels (GO:0071453), regulation of protein metabolic process (GO:0051246), oxoacid metabolic process (GO:0043436), negative regulation of neural precursor cell proliferation (GO:2000178), negative regulation of reactive oxygen species metabolic process (GO:2000378), regulation of cellular carbohydrate metabolic process (GO:0010675), positive regulation of necrotic cell death (GO:0010940), regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090092), regulation of glial cell proliferation (GO:0060251), organic substance transport (GO:0071702), mitotic cell cycle checkpoint signaling (GO:0007093), regulation of gene expression (GO:0010468), entrainment of circadian clock by photoperiod (GO:0043153), regulation of neural precursor cell proliferation (GO:2000177), positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus (GO:1901522), intracellular protein transport (GO:0006886), negative regulation of autophagy (GO:0010507), circulatory system development (GO:0072359), response to decreased oxygen levels (GO:0036293), regulation of DNA-templated transcription in response to stress (GO:0043620), negative regulation of mitotic cell cycle (GO:0045930), intrinsic apoptotic signaling pathway (GO:0097193), negative regulation of fibroblast proliferation (GO:0048147), energy derivation by oxidation of organic compounds (GO:0015980), carbohydrate catabolic process (GO:0016052), cytokine-mediated signaling pathway (GO:0019221), cellular component disassembly (GO:0022411), negative regulation of gene expression (GO:0010629), B cell activation (GO:0042113), heart development (GO:0007507), mitochondrial transport (GO:0006839), positive regulation of neuron death (GO:1901216), cellular response to radiation (GO:0071478), cellular response to hypoxia (GO:0071456), response to transforming growth factor beta (GO:0071559), response to light stimulus (GO:0009416), hexose metabolic process (GO:0019318), lymphocyte proliferation (GO:0046651), leukocyte differentiation (GO:0002521), enzyme-linked receptor protein signaling pathway (GO:0007167), regulation of reactive oxygen species metabolic process (GO:2000377), regulation of DNA metabolic process (GO:0051052), cellular response to DNA damage stimulus (GO:0006974), cellular response to organic substance (GO:0071310), signal transduction in response to DNA damage (GO:0042770), aromatic compound biosynthetic process (GO:0019438), establishment of protein localization to organelle (GO:0072594), regulation of cell development (GO:0060284), negative regulation of protein metabolic process (GO:0051248), regulation of glucose metabolic process (GO:0010906), regulation of autophagy (GO:0010506), regulation of neuron death (GO:1901214), response to salt stress (GO:0009651), regulation of response to DNA damage stimulus (GO:2001020), macroautophagy (GO:0016236), response to endoplasmic reticulum stress (GO:0034976), positive regulation of macromolecule biosynthetic process (GO:0010557), neurogenesis (GO:0022008), negative regulation of organelle organization (GO:0010639), regulation of generation of precursor metabolites and energy (GO:0043467), positive regulation of RNA metabolic process (GO:0051254), neuron apoptotic process (GO:0051402), apoptotic process (GO:0006915), regulation of cellular biosynthetic process (GO:0031326), regulation of stem cell proliferation (GO:0072091), regulation of nucleobase-containing compound metabolic process (GO:0019219), regulation of organelle organization (GO:0033043), cellular nitrogen compound biosynthetic process (GO:0044271), protein localization (GO:0008104), regulation of cellular response to transforming growth factor beta stimulus (GO:1903844), epithelium development (GO:0060429), negative regulation of cell development (GO:0010721), positive regulation of cellular biosynthetic process (GO:0031328), lymphocyte activation involved in immune response (GO:0002285), cellular response to growth factor stimulus (GO:0071363), embryo development ending in birth or egg hatching (GO:0009792), negative regulation of cell cycle phase transition (GO:1901988), macromolecule biosynthetic process (GO:0009059), organic cyclic compound biosynthetic process (GO:1901362), regulation of mitotic cell cycle (GO:0007346), regulation of cellular senescence (GO:2000772), regulation of fibroblast proliferation (GO:0048145), negative regulation of programmed cell death (GO:0043069), regulation of programmed cell death (GO:0043067), negative regulation of cellular catabolic process (GO:0031330), gastrulation (GO:0007369), nuclear transport (GO:0051169), signal transduction by p53 class mediator (GO:0072331), lymphocyte differentiation (GO:0030098), brain development (GO:0007420), negative regulation of neurogenesis (GO:0050768), embryonic organ development (GO:0048568), negative regulation of DNA metabolic process (GO:0051053), nervous system development (GO:0007399), heart morphogenesis (GO:0003007), nucleic acid metabolic process (GO:0090304), protein transport (GO:0015031), heterocycle biosynthetic process (GO:0018130), DNA metabolic process (GO:0006259), central nervous system development (GO:0007417), negative regulation of glial cell proliferation (GO:0060253), negative regulation of cellular biosynthetic process (GO:0031327), regulation of RNA metabolic process (GO:0051252), response to ionizing radiation (GO:0010212), release of cytochrome c from mitochondria (GO:0001836), gene expression (GO:0010467), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), negative regulation of stem cell proliferation (GO:2000647), programmed necrotic cell death (GO:0097300), membrane organization (GO:0061024), neuroblast proliferation (GO:0007405), hemopoiesis (GO:0030097), response to cytokine (GO:0034097), segmentation (GO:0035282), regulation of carbohydrate catabolic process (GO:0043470), cell cycle checkpoint signaling (GO:0000075), positive regulation of phosphorus metabolic process (GO:0010562), negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090101), positive regulation of programmed cell death (GO:0043068), positive regulation of membrane permeability (GO:1905710), autophagy of mitochondrion (GO:0000422), lactate metabolic process (GO:0006089), positive regulation of gene expression (GO:0010628), regulation of carbohydrate metabolic process (GO:0006109), regulation of nervous system development (GO:0051960), regulation of apoptotic signaling pathway (GO:2001233), somite development (GO:0061053), mononuclear cell proliferation (GO:0032943), regulation of necrotic cell death (GO:0010939), nucleobase-containing compound biosynthetic process (GO:0034654), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), regulation of mitochondrial membrane permeability (GO:0046902), negative regulation of miRNA-mediated gene silencing (GO:0060965), regulation of cell cycle phase transition (GO:1901987), positive regulation of protein metabolic process (GO:0051247), T cell activation (GO:0042110), negative regulation of macromolecule biosynthetic process (GO:0010558), protein stabilization (GO:0050821), response to type II interferon (GO:0034341), regulation of cellular catabolic process (GO:0031329), organelle organization (GO:0006996), negative regulation of RNA metabolic process (GO:0051253), regulation of intracellular signal transduction (GO:1902531), regulation of phosphorus metabolic process (GO:0051174), anterior/posterior pattern specification (GO:0009952), glucose metabolic process (GO:0006006), photoperiodism (GO:0009648), mitochondrion organization (GO:0007005), selective autophagy (GO:0061912), RNA metabolic process (GO:0016070), regulation of apoptotic process (GO:0042981), negative regulation of gliogenesis (GO:0014014), positive regulation of phosphate metabolic process (GO:0045937), regulation of RNA biosynthetic process (GO:2001141), regulation of neuron apoptotic process (GO:0043523), DNA repair (GO:0006281), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), cellular response to cytokine stimulus (GO:0071345), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), mitotic DNA integrity checkpoint signaling (GO:0044774), regulation of DNA replication (GO:0006275), positive regulation of RNA biosynthetic process (GO:1902680), regulation of transcription from RNA polymerase II promoter in response to stress (GO:0043618), positive regulation of protein modification process (GO:0031401), regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902108), nucleocytoplasmic transport (GO:0006913), cellular response to transforming growth factor beta stimulus (GO:0071560), positive regulation of apoptotic process (GO:0043065), regulation of intrinsic apoptotic signaling pathway (GO:2001242), regulation of gene silencing by RNA (GO:0060966), hexose catabolic process (GO:0019320), regulation of signal transduction by p53 class mediator (GO:1901796), necroptotic process (GO:0070266), cellular response to ionizing radiation (GO:0071479), response to gamma radiation (GO:0010332), fermentation (GO:0006113), cellular response to light stimulus (GO:0071482), gliogenesis (GO:0042063), regulation of programmed necrotic cell death (GO:0062098), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), negative regulation of cell cycle G1/S phase transition (GO:1902807), negative regulation of proteolysis (GO:0045861), response to X-ray (GO:0010165), RNA biosynthetic process (GO:0032774), nucleic acid-templated transcription (GO:0097659), negative regulation of mitochondrion organization (GO:0010823), protein import into nucleus (GO:0006606), T cell activation involved in immune response (GO:0002286), mitochondrial DNA metabolic process (GO:0032042), regulation of proteolysis (GO:0030162), regulation of production of small RNA involved in gene silencing by RNA (GO:0070920), regulation of mitochondrion organization (GO:0010821), muscle cell apoptotic process (GO:0010657), apoptotic mitochondrial changes (GO:0008637), carboxylic acid metabolic process (GO:0019752), T cell proliferation (GO:0042098), transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0007178), mitochondrial membrane organization (GO:0007006), negative regulation of macroautophagy (GO:0016242), interferon-mediated signaling pathway (GO:0140888), mitophagy (GO:0000423), mononuclear cell differentiation (GO:1903131), response to UV (GO:0009411), regulation of neuroblast proliferation (GO:1902692), regulation of neurogenesis (GO:0050767), generation of neurons (GO:0048699), regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043516), negative regulation of RNA biosynthetic process (GO:1902679), DNA damage checkpoint signaling (GO:0000077), regulation of post-transcriptional gene silencing (GO:0060147), negative regulation of DNA replication (GO:0008156), positive regulation of neuron apoptotic process (GO:0043525), DNA integrity checkpoint signaling (GO:0031570), chordate embryonic development (GO:0043009), protein localization to organelle (GO:0033365), DNA damage response, signal transduction by p53 class mediator (GO:0030330), regulation of protein modification process (GO:0031399), T cell differentiation (GO:0030217), negative regulation of mitotic cell cycle phase transition (GO:1901991), regulation of macroautophagy (GO:0016241), negative regulation of neuroblast proliferation (GO:0007406), negative regulation of apoptotic process (GO:0043066), regulation of DNA-templated transcription (GO:0006355), chromosome organization (GO:0051276), organelle disassembly (GO:1903008), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), regulation of phosphate metabolic process (GO:0019220), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), positive regulation of mitochondrial membrane permeability (GO:0035794), cellular response to decreased oxygen levels (GO:0036294), positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress (GO:1990440), regulation of mitotic cell cycle phase transition (GO:1901990), mitotic G1/S transition checkpoint signaling (GO:0044819), regulation of autophagy of mitochondrion (GO:1903146), B cell differentiation (GO:0030183), leukocyte apoptotic process (GO:0071887), regulation of cell cycle G1/S phase transition (GO:1902806), cellular response to type II interferon (GO:0071346), in utero embryonic development (GO:0001701), positive regulation of transcription from RNA polymerase II promoter in response to stress (GO:0036003), regulation of leukocyte apoptotic process (GO:2000106), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), mitotic G1 DNA damage checkpoint signaling (GO:0031571), regulation of muscle cell apoptotic process (GO:0010660), regulation of fibroblast apoptotic process (GO:2000269), positive regulation of leukocyte apoptotic process (GO:2000108), positive regulation of nucleic acid-templated transcription (GO:1903508), regulation of post-transcriptional gene silencing by RNA (GO:1900368), positive regulation of phosphorylation (GO:0042327), glucose catabolic process (GO:0006007), positive regulation of protein phosphorylation (GO:0001934), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), double-strand break repair (GO:0006302), regulation of transcription by RNA polymerase II (GO:0006357), mitotic DNA damage checkpoint signaling (GO:0044773), regulation of miRNA maturation (GO:1903798), positive regulation of DNA-templated transcription (GO:0045893), regulation of histone modification (GO:0031056), regulation of intrinsic apoptotic signaling pathway by p53 class mediator (GO:1902253), T cell differentiation in thymus (GO:0033077), type II interferon-mediated signaling pathway (GO:0060333), response to UV-C (GO:0010225), cellular response to UV (GO:0034644), mitochondrial genome maintenance (GO:0000002), protein localization to nucleus (GO:0034504), positive regulation of histone modification (GO:0031058), import into nucleus (GO:0051170), regulation of protein phosphorylation (GO:0001932), negative regulation of DNA-templated transcription (GO:0045892), lymphocyte apoptotic process (GO:0070227), monocarboxylic acid metabolic process (GO:0032787), regulation of nucleic acid-templated transcription (GO:1903506), regulation of protein deacetylation (GO:0090311), DNA-templated transcription (GO:0006351), regulation of mitophagy (GO:1901524), ncRNA metabolic process (GO:0034660), regulation of phosphorylation (GO:0042325), mitochondrion disassembly (GO:0061726), positive regulation of protein deacetylation (GO:0090312), DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest (GO:0006977), regulation of gliogenesis (GO:0014013), positive regulation of muscle cell apoptotic process (GO:0010661), negative regulation of nucleic acid-templated transcription (GO:1903507), regulation of G1/S transition of mitotic cell cycle (GO:2000045), transforming growth factor beta receptor signaling pathway (GO:0007179), cellular response to gamma radiation (GO:0071480), glycolytic fermentation (GO:0019660), ncRNA transcription (GO:0098781), regulation of lymphocyte apoptotic process (GO:0070228), negative regulation of transcription by RNA polymerase II (GO:0000122), rRNA metabolic process (GO:0016072), regulation of striated muscle cell apoptotic process (GO:0010662), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), regulation of miRNA-mediated gene silencing (GO:0060964), positive regulation of transcription by RNA polymerase II (GO:0045944)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), cytosol (GO:0005829), site of DNA damage (GO:0090734), cytoplasm (GO:0005737), membrane-enclosed lumen (GO:0031974), replication fork (GO:0005657), mitochondrion (GO:0005739), organelle lumen (GO:0043233), site of double-strand break (GO:0035861), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), non-membrane-bounded organelle (GO:0043228), intracellular membrane-bounded organelle (GO:0043231), mitochondrial matrix (GO:0005759), intracellular organelle lumen (GO:0070013), intracellular non-membrane-bounded organelle (GO:0043232), chromosome (GO:0005694), nucleus (GO:0005634), germ cell nucleus (GO:0043073)

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BioReason Chat Export

Exported on March 22, 2026 at 01:33 AM

Organism: Mus musculus

Sequence:

MTAMEESQSDISLELPLSQETFSGLWKLLPPEDILPSPHCMDDLLLPQDVEEFFEGPSEALRVSGAPAAQDPVTETPGPVAPAPATPWPLSSFVPSQKTYQGNYGFHLGFLQSGTAKSVMCTYSPPLNKLFCQLAKTCPVQLWVSATPPAGSRVRAMAIYKKSQHMTEVVRRCPHHERCSDGDGLAPPQHLIRVEGNLYPEYLEDRQTFRHSVVVPYEPPEAGSEYTTIHYKYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRDSFEVRVCACPGRDRRTEEENFRKKEVLCPELPPGSAKRALPTCTSASPPQKKKPLDGEYFTLKIRGRKRFEMFRELNEALELKDAHATEESGDSRAHSSYLKTKKGQSTSRHKKTMVKKVGPDSD

Thinking Trace

I begin by dissecting the InterPro architecture. The protein is classified broadly by IPR002117 (p53 tumour suppressor family, residues 6–362), immediately suggesting a transcriptional regulator that orchestrates stress and checkpoint pathways. Near the N-terminus sits IPR013872 (p53, transactivation domain, residues 9–32), a low-complexity activation module that recruits coactivators and corepressors. The central core comprises IPR011615 (p53, DNA-binding domain, residues 97–286), reinforced by two overlapping superfamily signatures—IPR012346 (p53/RUNT-type transcription factor, DNA-binding domain superfamily, residues 92–292) and IPR008967 (p53-like transcription factor, DNA-binding domain superfamily, residues 94–284)—which together define a structured site-recognition fold that binds specific DNA elements and couples sequence-specific contacts to regulatory responses. Embedded within this core is IPR057064 (p53, central conserved site, residues 234–246), a hallmark motif that stabilizes the DNA-binding architecture and coordinates allosteric communication. At the C-terminus, IPR010991 (p53, tetramerisation domain, residues 316–353) and its higher-order envelope IPR036674 (p53-like tetramerisation domain superfamily, residues 316–357) enforce assembly into a homotetramer. This ordered layout—an N-terminal activation region, a central site-specific DNA-binding core with a conserved stabilization motif, and a C-terminal oligomerization hub—causally dictates a sequence-specific DNA-binding transcription factor that operates as a tetrameric switch.

From these domains, the molecular function follows directly. The presence of a dedicated transactivation domain (IPR013872) coupled to the structured DNA-binding core (IPR011615 and its superfamilies) establishes RNA polymerase II-dependent transcriptional regulation. The tetramerisation module (IPR010991/IPR036674) amplifies affinity and specificity by cooperative assembly, a common strategy for high-fidelity transcriptional control. This architecture yields DNA-binding transcription factor activity with sequence specificity and supports both activation and repression depending on cofactor recruitment. Therefore, the molecular function is best captured by GO:0003700 DNA-binding transcription factor activity, sequence-specific DNA binding.

Biological process emerges as a consequence of this regulatory capacity. A p53-family transcriptional hub that binds and modulates promoter/enhancer activity is poised to govern checkpoints and stress responses. The conserved central site and tetrameric assembly ensure robust control over gene networks that halt cell cycle progression and promote repair or apoptosis when genomic integrity is compromised. This causal chain aligns with control of the cell cycle and apoptosis and situates the protein at the heart of stress-responsive transcriptional programs. Accordingly, the most defensible process annotations are GO:0051726 regulation of cell cycle and GO:0006915 apoptotic process.

Cellular location follows from function and architecture. A DNA-binding transcriptional regulator must access chromatin; the presence of a transactivation domain and a canonical DNA-binding core necessitate nuclear residence, consistent with a soluble nuclear regulator. Thus, the cellular component is the nucleus (GO:0005634).

Mechanistically, I hypothesize a tetrameric transcriptional switch that senses intracellular stress and enforces checkpoints. The N-terminal activation domain recruits chromatin-modifying coactivators (e.g., acetyltransferases) or corepressors, while the central domain binds specific promoter elements and transmits signals through the conserved site to tune transcriptional output. The tetramerisation domain concentrates binding interfaces to stabilize higher-order assemblies on DNA. Likely partners include E3 ubiquitin ligases that set protein turnover thresholds, chromatin remodelers that gate promoter accessibility, and checkpoint kinases that phosphorylate and modulate its activity. Together, these interactions allow dynamic repression or activation of genes governing cell cycle arrest and apoptosis within the nucleus.

Functional Summary

A nuclear, tetramer-forming transcriptional regulator that uses an N‑terminal activation module and a central site-recognition core to control RNA polymerase II–dependent gene programs. By assembling into a cooperative homotetramer, it binds specific promoter elements, recruits chromatin-modifying cofactors, and toggles between activation and repression to enforce checkpoint pathways that govern cell cycle control and trigger apoptosis under stress.

UniProt Summary

Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activating protein that acts downstream of a signal mediated by a DNA damage-stress pathway. Appears to regulate at least two distinct pathways: the mediation of apoptotic pathways by p53/TP53, and repression of cell cycle progression by impeding the G2/M transition (By similarity).

InterPro Domains

• p53 tumour suppressor family (IPR002117, family) — residues 6-362
• p53, transactivation domain (IPR013872, domain) — residues 9-32
• p53/RUNT-type transcription factor, DNA-binding domain superfamily (IPR012346, homologous_superfamily) — residues 92-292
• p53-like transcription factor, DNA-binding domain superfamily (IPR008967, homologous_superfamily) — residues 94-284
• p53, DNA-binding domain (IPR011615, domain) — residues 97-286
• p53, central conserved site (IPR057064, conserved_site) — residues 234-246
• p53, tetramerisation domain (IPR010991, domain) — residues 316-353
• p53-like tetramerisation domain superfamily (IPR036674, homologous_superfamily) — residues 316-357

GO Terms

Molecular Function: molecular_function (GO:0003674), molecular function regulator activity (GO:0098772), binding (GO:0005488), transcription regulator activity (GO:0140110), enzyme regulator activity (GO:0030234), DNA-binding transcription factor activity, sequence-specific DNA binding (GO:0003700), organic cyclic compound binding (GO:0097159), heterocyclic compound binding (GO:1901363), chromatin binding (GO:0003682), protein binding (GO:0005515), nucleic acid binding (GO:0003676), DNA-binding transcription activator activity (GO:0001216), enzyme binding (GO:0019899), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), ubiquitin-like protein ligase binding (GO:0044389), transcription regulatory region nucleic acid binding (GO:0001067), DNA binding (GO:0003677), ubiquitin protein ligase binding (GO:0031625), sequence-specific DNA binding (GO:0043565), transcription cis-regulatory region binding (GO:0000976), double-stranded DNA binding (GO:0003690), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978)

Biological Process: biological_process (GO:0008150), localization (GO:0051179), signaling (GO:0023052), biological regulation (GO:0065007), response to stimulus (GO:0050896), biological process involved in interspecies interaction between organisms (GO:0044419), growth (GO:0040007), negative regulation of biological process (GO:0048519), positive regulation of biological process (GO:0048518), regulation of biological process (GO:0050789), multicellular organismal process (GO:0032501), rhythmic process (GO:0048511), developmental process (GO:0032502), cellular process (GO:0009987), metabolic process (GO:0008152), immune system process (GO:0002376), cellular localization (GO:0051641), anatomical structure development (GO:0048856), negative regulation of signaling (GO:0023057), immune response (GO:0006955), cell cycle process (GO:0022402), pattern specification process (GO:0007389), cellular component organization or biogenesis (GO:0071840), regulation of multicellular organismal process (GO:0051239), anatomical structure formation involved in morphogenesis (GO:0048646), negative regulation of metabolic process (GO:0009892), regulation of biological quality (GO:0065008), regulation of cellular process (GO:0050794), regulation of response to stimulus (GO:0048583), cellular response to stimulus (GO:0051716), multicellular organism growth (GO:0035264), process utilizing autophagic mechanism (GO:0061919), negative regulation of cellular process (GO:0048523), cellular developmental process (GO:0048869), response to abiotic stimulus (GO:0009628), biosynthetic process (GO:0009058), regulation of metabolic process (GO:0019222), establishment of localization (GO:0051234), catabolic process (GO:0009056), macromolecule localization (GO:0033036), negative regulation of gene silencing by RNA (GO:0060967), immune effector process (GO:0002252), negative regulation of post-transcriptional gene silencing (GO:0060149), cell communication (GO:0007154), positive regulation of cellular process (GO:0048522), response to external stimulus (GO:0009605), developmental growth (GO:0048589), anatomical structure morphogenesis (GO:0009653), response to chemical (GO:0042221), leukocyte activation (GO:0045321), cell population proliferation (GO:0008283), nitrogen compound metabolic process (GO:0006807), negative regulation of multicellular organismal process (GO:0051241), regulation of developmental process (GO:0050793), response to biotic stimulus (GO:0009607), cell death (GO:0008219), response to endogenous stimulus (GO:0009719), regulation of signaling (GO:0023051), negative regulation of developmental process (GO:0051093), response to other organism (GO:0051707), signal transduction (GO:0007165), multicellular organism development (GO:0007275), cell activation (GO:0001775), determination of adult lifespan (GO:0008340), regulation of circadian rhythm (GO:0042752), circadian rhythm (GO:0007623), cell cycle (GO:0007049), organic substance metabolic process (GO:0071704), cellular metabolic process (GO:0044237), small molecule metabolic process (GO:0044281), positive regulation of metabolic process (GO:0009893), response to stress (GO:0006950), negative regulation of response to stimulus (GO:0048585), primary metabolic process (GO:0044238), behavior (GO:0007610), negative regulation of post-transcriptional gene silencing by RNA (GO:1900369), neural precursor cell proliferation (GO:0061351), negative regulation of cellular component organization (GO:0051129), response to external biotic stimulus (GO:0043207), reactive oxygen species metabolic process (GO:0072593), response to radiation (GO:0009314), regulation of response to stress (GO:0080134), stem cell proliferation (GO:0072089), regulation of tissue remodeling (GO:0034103), animal organ development (GO:0048513), regulation of signal transduction (GO:0009966), regulation of macromolecule metabolic process (GO:0060255), cellular aromatic compound metabolic process (GO:0006725), carbohydrate metabolic process (GO:0005975), negative regulation of cell cycle process (GO:0010948), establishment of protein localization (GO:0045184), autophagy (GO:0006914), response to inorganic substance (GO:0010035), intracellular transport (GO:0046907), cardiac septum morphogenesis (GO:0060411), negative regulation of macromolecule metabolic process (GO:0010605), organic acid metabolic process (GO:0006082), embryo development (GO:0009790), negative regulation of cell cycle (GO:0045786), cellular macromolecule metabolic process (GO:0044260), regulation of cell cycle process (GO:0010564), positive regulation of nitrogen compound metabolic process (GO:0051173), regulation of membrane permeability (GO:0090559), negative regulation of nitrogen compound metabolic process (GO:0051172), organic substance biosynthetic process (GO:1901576), small molecule catabolic process (GO:0044282), positive regulation of macromolecule metabolic process (GO:0010604), heterocycle metabolic process (GO:0046483), negative regulation of cell population proliferation (GO:0008285), regulation of cellular response to stress (GO:0080135), glial cell proliferation (GO:0014009), hindbrain development (GO:0030902), establishment of localization in cell (GO:0051649), cellular biosynthetic process (GO:0044249), monosaccharide metabolic process (GO:0005996), cellular nitrogen compound metabolic process (GO:0034641), regulation of protein stability (GO:0031647), macromolecule metabolic process (GO:0043170), positive regulation of biosynthetic process (GO:0009891), negative regulation of carbohydrate metabolic process (GO:0045912), innate immune response (GO:0045087), defense response to other organism (GO:0098542), regulation of multicellular organismal development (GO:2000026), cellular response to environmental stimulus (GO:0104004), regulation of cell population proliferation (GO:0042127), regulation of cell death (GO:0010941), somitogenesis (GO:0001756), regionalization (GO:0003002), positive regulation of cellular metabolic process (GO:0031325), cellular response to stress (GO:0033554), negative regulation of cell differentiation (GO:0045596), transport (GO:0006810), cellular macromolecule localization (GO:0070727), regulation of cellular metabolic process (GO:0031323), negative regulation of catabolic process (GO:0009895), negative regulation of biosynthetic process (GO:0009890), regulation of primary metabolic process (GO:0080090), generation of precursor metabolites and energy (GO:0006091), rhythmic behavior (GO:0007622), regulation of cellular response to growth factor stimulus (GO:0090287), negative regulation of signal transduction (GO:0009968), positive regulation of cell death (GO:0010942), response to hypoxia (GO:0001666), programmed cell death (GO:0012501), negative regulation of cell death (GO:0060548), cell development (GO:0048468), leukocyte activation involved in immune response (GO:0002366), response to xenobiotic stimulus (GO:0009410), cell differentiation (GO:0030154), negative regulation of nervous system development (GO:0051961), cellular catabolic process (GO:0044248), system development (GO:0048731), response to oxygen levels (GO:0070482), cardiac septum development (GO:0003279), response to growth factor (GO:0070848), cellular response to endogenous stimulus (GO:0071495), lymphocyte activation (GO:0046649), neuron death (GO:0070997), regulation of cell cycle (GO:0051726), regulation of catabolic process (GO:0009894), cerebellum development (GO:0021549), animal organ morphogenesis (GO:0009887), organic cyclic compound metabolic process (GO:1901360), leukocyte proliferation (GO:0070661), cellular response to abiotic stimulus (GO:0071214), apoptotic signaling pathway (GO:0097190), regulation of nitrogen compound metabolic process (GO:0051171), negative regulation of small molecule metabolic process (GO:0062014), regulation of cell differentiation (GO:0045595), cellular component organization (GO:0016043), cell surface receptor signaling pathway (GO:0007166), organic substance catabolic process (GO:1901575), regulation of cellular component organization (GO:0051128), organic hydroxy compound metabolic process (GO:1901615), negative regulation of cell communication (GO:0010648), mitotic cell cycle process (GO:1903047), intracellular signal transduction (GO:0035556), response to oxidative stress (GO:0006979), defense response (GO:0006952), response to osmotic stress (GO:0006970), circadian behavior (GO:0048512), cardiac chamber development (GO:0003205), negative regulation of cellular metabolic process (GO:0031324), metencephalon development (GO:0022037), response to organic substance (GO:0010033), necrotic cell death (GO:0070265), fibroblast proliferation (GO:0048144), cell fate commitment (GO:0045165), embryonic morphogenesis (GO:0048598), nucleobase-containing compound metabolic process (GO:0006139), head development (GO:0060322), regulation of cell communication (GO:0010646), tissue development (GO:0009888), cellular response to chemical stimulus (GO:0070887), cell activation involved in immune response (GO:0002263), regulation of biosynthetic process (GO:0009889), regulation of small molecule metabolic process (GO:0062012), entrainment of circadian clock (GO:0009649), cardiac chamber morphogenesis (GO:0003206), response to ischemia (GO:0002931), mitotic cell cycle (GO:0000278), nitrogen compound transport (GO:0071705), monosaccharide catabolic process (GO:0046365), T cell lineage commitment (GO:0002360), regulation of macromolecule biosynthetic process (GO:0010556), cellular response to oxygen levels (GO:0071453), regulation of protein metabolic process (GO:0051246), oxoacid metabolic process (GO:0043436), negative regulation of neural precursor cell proliferation (GO:2000178), negative regulation of reactive oxygen species metabolic process (GO:2000378), regulation of cellular carbohydrate metabolic process (GO:0010675), positive regulation of necrotic cell death (GO:0010940), regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090092), regulation of glial cell proliferation (GO:0060251), organic substance transport (GO:0071702), mitotic cell cycle checkpoint signaling (GO:0007093), regulation of gene expression (GO:0010468), entrainment of circadian clock by photoperiod (GO:0043153), regulation of neural precursor cell proliferation (GO:2000177), positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus (GO:1901522), intracellular protein transport (GO:0006886), negative regulation of autophagy (GO:0010507), circulatory system development (GO:0072359), response to decreased oxygen levels (GO:0036293), regulation of DNA-templated transcription in response to stress (GO:0043620), negative regulation of mitotic cell cycle (GO:0045930), intrinsic apoptotic signaling pathway (GO:0097193), negative regulation of fibroblast proliferation (GO:0048147), energy derivation by oxidation of organic compounds (GO:0015980), carbohydrate catabolic process (GO:0016052), cytokine-mediated signaling pathway (GO:0019221), cellular component disassembly (GO:0022411), negative regulation of gene expression (GO:0010629), B cell activation (GO:0042113), heart development (GO:0007507), mitochondrial transport (GO:0006839), positive regulation of neuron death (GO:1901216), cellular response to radiation (GO:0071478), cellular response to hypoxia (GO:0071456), response to transforming growth factor beta (GO:0071559), response to light stimulus (GO:0009416), hexose metabolic process (GO:0019318), lymphocyte proliferation (GO:0046651), leukocyte differentiation (GO:0002521), enzyme-linked receptor protein signaling pathway (GO:0007167), regulation of reactive oxygen species metabolic process (GO:2000377), regulation of DNA metabolic process (GO:0051052), cellular response to DNA damage stimulus (GO:0006974), cellular response to organic substance (GO:0071310), signal transduction in response to DNA damage (GO:0042770), aromatic compound biosynthetic process (GO:0019438), establishment of protein localization to organelle (GO:0072594), regulation of cell development (GO:0060284), negative regulation of protein metabolic process (GO:0051248), regulation of glucose metabolic process (GO:0010906), regulation of autophagy (GO:0010506), regulation of neuron death (GO:1901214), response to salt stress (GO:0009651), regulation of response to DNA damage stimulus (GO:2001020), macroautophagy (GO:0016236), response to endoplasmic reticulum stress (GO:0034976), positive regulation of macromolecule biosynthetic process (GO:0010557), neurogenesis (GO:0022008), negative regulation of organelle organization (GO:0010639), regulation of generation of precursor metabolites and energy (GO:0043467), positive regulation of RNA metabolic process (GO:0051254), neuron apoptotic process (GO:0051402), apoptotic process (GO:0006915), regulation of cellular biosynthetic process (GO:0031326), regulation of stem cell proliferation (GO:0072091), regulation of nucleobase-containing compound metabolic process (GO:0019219), regulation of organelle organization (GO:0033043), cellular nitrogen compound biosynthetic process (GO:0044271), protein localization (GO:0008104), regulation of cellular response to transforming growth factor beta stimulus (GO:1903844), epithelium development (GO:0060429), negative regulation of cell development (GO:0010721), positive regulation of cellular biosynthetic process (GO:0031328), lymphocyte activation involved in immune response (GO:0002285), cellular response to growth factor stimulus (GO:0071363), embryo development ending in birth or egg hatching (GO:0009792), negative regulation of cell cycle phase transition (GO:1901988), macromolecule biosynthetic process (GO:0009059), organic cyclic compound biosynthetic process (GO:1901362), regulation of mitotic cell cycle (GO:0007346), regulation of cellular senescence (GO:2000772), regulation of fibroblast proliferation (GO:0048145), negative regulation of programmed cell death (GO:0043069), regulation of programmed cell death (GO:0043067), negative regulation of cellular catabolic process (GO:0031330), gastrulation (GO:0007369), nuclear transport (GO:0051169), signal transduction by p53 class mediator (GO:0072331), lymphocyte differentiation (GO:0030098), brain development (GO:0007420), negative regulation of neurogenesis (GO:0050768), embryonic organ development (GO:0048568), negative regulation of DNA metabolic process (GO:0051053), nervous system development (GO:0007399), heart morphogenesis (GO:0003007), nucleic acid metabolic process (GO:0090304), protein transport (GO:0015031), heterocycle biosynthetic process (GO:0018130), DNA metabolic process (GO:0006259), central nervous system development (GO:0007417), negative regulation of glial cell proliferation (GO:0060253), negative regulation of cellular biosynthetic process (GO:0031327), regulation of RNA metabolic process (GO:0051252), response to ionizing radiation (GO:0010212), release of cytochrome c from mitochondria (GO:0001836), gene expression (GO:0010467), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), negative regulation of stem cell proliferation (GO:2000647), programmed necrotic cell death (GO:0097300), membrane organization (GO:0061024), neuroblast proliferation (GO:0007405), hemopoiesis (GO:0030097), response to cytokine (GO:0034097), segmentation (GO:0035282), regulation of carbohydrate catabolic process (GO:0043470), cell cycle checkpoint signaling (GO:0000075), positive regulation of phosphorus metabolic process (GO:0010562), negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090101), positive regulation of programmed cell death (GO:0043068), positive regulation of membrane permeability (GO:1905710), autophagy of mitochondrion (GO:0000422), lactate metabolic process (GO:0006089), positive regulation of gene expression (GO:0010628), regulation of carbohydrate metabolic process (GO:0006109), regulation of nervous system development (GO:0051960), regulation of apoptotic signaling pathway (GO:2001233), somite development (GO:0061053), mononuclear cell proliferation (GO:0032943), regulation of necrotic cell death (GO:0010939), nucleobase-containing compound biosynthetic process (GO:0034654), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), regulation of mitochondrial membrane permeability (GO:0046902), negative regulation of miRNA-mediated gene silencing (GO:0060965), regulation of cell cycle phase transition (GO:1901987), positive regulation of protein metabolic process (GO:0051247), T cell activation (GO:0042110), negative regulation of macromolecule biosynthetic process (GO:0010558), protein stabilization (GO:0050821), response to type II interferon (GO:0034341), regulation of cellular catabolic process (GO:0031329), organelle organization (GO:0006996), negative regulation of RNA metabolic process (GO:0051253), regulation of intracellular signal transduction (GO:1902531), regulation of phosphorus metabolic process (GO:0051174), anterior/posterior pattern specification (GO:0009952), glucose metabolic process (GO:0006006), photoperiodism (GO:0009648), mitochondrion organization (GO:0007005), selective autophagy (GO:0061912), RNA metabolic process (GO:0016070), regulation of apoptotic process (GO:0042981), negative regulation of gliogenesis (GO:0014014), positive regulation of phosphate metabolic process (GO:0045937), regulation of RNA biosynthetic process (GO:2001141), regulation of neuron apoptotic process (GO:0043523), DNA repair (GO:0006281), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), cellular response to cytokine stimulus (GO:0071345), intrinsic apoptotic signaling pathway in response to DNA damage (GO:0008630), mitotic DNA integrity checkpoint signaling (GO:0044774), regulation of DNA replication (GO:0006275), positive regulation of RNA biosynthetic process (GO:1902680), regulation of transcription from RNA polymerase II promoter in response to stress (GO:0043618), positive regulation of protein modification process (GO:0031401), regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902108), nucleocytoplasmic transport (GO:0006913), cellular response to transforming growth factor beta stimulus (GO:0071560), positive regulation of apoptotic process (GO:0043065), regulation of intrinsic apoptotic signaling pathway (GO:2001242), regulation of gene silencing by RNA (GO:0060966), hexose catabolic process (GO:0019320), regulation of signal transduction by p53 class mediator (GO:1901796), necroptotic process (GO:0070266), cellular response to ionizing radiation (GO:0071479), response to gamma radiation (GO:0010332), fermentation (GO:0006113), cellular response to light stimulus (GO:0071482), gliogenesis (GO:0042063), regulation of programmed necrotic cell death (GO:0062098), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), negative regulation of cell cycle G1/S phase transition (GO:1902807), negative regulation of proteolysis (GO:0045861), response to X-ray (GO:0010165), RNA biosynthetic process (GO:0032774), nucleic acid-templated transcription (GO:0097659), negative regulation of mitochondrion organization (GO:0010823), protein import into nucleus (GO:0006606), T cell activation involved in immune response (GO:0002286), mitochondrial DNA metabolic process (GO:0032042), regulation of proteolysis (GO:0030162), regulation of production of small RNA involved in gene silencing by RNA (GO:0070920), regulation of mitochondrion organization (GO:0010821), muscle cell apoptotic process (GO:0010657), apoptotic mitochondrial changes (GO:0008637), carboxylic acid metabolic process (GO:0019752), T cell proliferation (GO:0042098), transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0007178), mitochondrial membrane organization (GO:0007006), negative regulation of macroautophagy (GO:0016242), interferon-mediated signaling pathway (GO:0140888), mitophagy (GO:0000423), mononuclear cell differentiation (GO:1903131), response to UV (GO:0009411), regulation of neuroblast proliferation (GO:1902692), regulation of neurogenesis (GO:0050767), generation of neurons (GO:0048699), regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043516), negative regulation of RNA biosynthetic process (GO:1902679), DNA damage checkpoint signaling (GO:0000077), regulation of post-transcriptional gene silencing (GO:0060147), negative regulation of DNA replication (GO:0008156), positive regulation of neuron apoptotic process (GO:0043525), DNA integrity checkpoint signaling (GO:0031570), chordate embryonic development (GO:0043009), protein localization to organelle (GO:0033365), DNA damage response, signal transduction by p53 class mediator (GO:0030330), regulation of protein modification process (GO:0031399), T cell differentiation (GO:0030217), negative regulation of mitotic cell cycle phase transition (GO:1901991), regulation of macroautophagy (GO:0016241), negative regulation of neuroblast proliferation (GO:0007406), negative regulation of apoptotic process (GO:0043066), regulation of DNA-templated transcription (GO:0006355), chromosome organization (GO:0051276), organelle disassembly (GO:1903008), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), regulation of phosphate metabolic process (GO:0019220), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), positive regulation of mitochondrial membrane permeability (GO:0035794), cellular response to decreased oxygen levels (GO:0036294), positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress (GO:1990440), regulation of mitotic cell cycle phase transition (GO:1901990), mitotic G1/S transition checkpoint signaling (GO:0044819), regulation of autophagy of mitochondrion (GO:1903146), B cell differentiation (GO:0030183), leukocyte apoptotic process (GO:0071887), regulation of cell cycle G1/S phase transition (GO:1902806), cellular response to type II interferon (GO:0071346), in utero embryonic development (GO:0001701), positive regulation of transcription from RNA polymerase II promoter in response to stress (GO:0036003), regulation of leukocyte apoptotic process (GO:2000106), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), mitotic G1 DNA damage checkpoint signaling (GO:0031571), regulation of muscle cell apoptotic process (GO:0010660), regulation of fibroblast apoptotic process (GO:2000269), positive regulation of leukocyte apoptotic process (GO:2000108), positive regulation of nucleic acid-templated transcription (GO:1903508), regulation of post-transcriptional gene silencing by RNA (GO:1900368), positive regulation of phosphorylation (GO:0042327), glucose catabolic process (GO:0006007), positive regulation of protein phosphorylation (GO:0001934), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), double-strand break repair (GO:0006302), regulation of transcription by RNA polymerase II (GO:0006357), mitotic DNA damage checkpoint signaling (GO:0044773), regulation of miRNA maturation (GO:1903798), positive regulation of DNA-templated transcription (GO:0045893), regulation of histone modification (GO:0031056), regulation of intrinsic apoptotic signaling pathway by p53 class mediator (GO:1902253), T cell differentiation in thymus (GO:0033077), type II interferon-mediated signaling pathway (GO:0060333), response to UV-C (GO:0010225), cellular response to UV (GO:0034644), mitochondrial genome maintenance (GO:0000002), protein localization to nucleus (GO:0034504), positive regulation of histone modification (GO:0031058), import into nucleus (GO:0051170), regulation of protein phosphorylation (GO:0001932), negative regulation of DNA-templated transcription (GO:0045892), lymphocyte apoptotic process (GO:0070227), monocarboxylic acid metabolic process (GO:0032787), regulation of nucleic acid-templated transcription (GO:1903506), regulation of protein deacetylation (GO:0090311), DNA-templated transcription (GO:0006351), regulation of mitophagy (GO:1901524), ncRNA metabolic process (GO:0034660), regulation of phosphorylation (GO:0042325), mitochondrion disassembly (GO:0061726), positive regulation of protein deacetylation (GO:0090312), DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest (GO:0006977), regulation of gliogenesis (GO:0014013), positive regulation of muscle cell apoptotic process (GO:0010661), negative regulation of nucleic acid-templated transcription (GO:1903507), regulation of G1/S transition of mitotic cell cycle (GO:2000045), transforming growth factor beta receptor signaling pathway (GO:0007179), cellular response to gamma radiation (GO:0071480), glycolytic fermentation (GO:0019660), ncRNA transcription (GO:0098781), regulation of lymphocyte apoptotic process (GO:0070228), negative regulation of transcription by RNA polymerase II (GO:0000122), rRNA metabolic process (GO:0016072), regulation of striated muscle cell apoptotic process (GO:0010662), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), regulation of miRNA-mediated gene silencing (GO:0060964), positive regulation of transcription by RNA polymerase II (GO:0045944)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), cytosol (GO:0005829), site of DNA damage (GO:0090734), cytoplasm (GO:0005737), membrane-enclosed lumen (GO:0031974), replication fork (GO:0005657), mitochondrion (GO:0005739), organelle lumen (GO:0043233), site of double-strand break (GO:0035861), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), non-membrane-bounded organelle (GO:0043228), intracellular membrane-bounded organelle (GO:0043231), mitochondrial matrix (GO:0005759), intracellular organelle lumen (GO:0070013), intracellular non-membrane-bounded organelle (GO:0043232), chromosome (GO:0005694), nucleus (GO:0005634), germ cell nucleus (GO:0043073)

Generated by BioReason

BioReason-Pro RL Review: Trp53 (mouse)

Source: Trp53-deep-research-bioreason-rl.md

• Correctness: 5/5
• Completeness: 4/5

Functional Summary Review

The BioReason functional summary is accurate and well-articulated:

A nuclear, tetramer-forming transcriptional regulator that uses an N-terminal activation module and a central site-recognition core to control RNA polymerase II-dependent gene programs. By assembling into a cooperative homotetramer, it binds specific promoter elements, recruits chromatin-modifying cofactors, and toggles between activation and repression to enforce checkpoint pathways that govern cell cycle control and trigger apoptosis under stress.

This correctly identifies: (1) the nuclear localization (GO:0005634), (2) the tetramerization domain and cooperative DNA binding, (3) the N-terminal transactivation domain, (4) the central DNA-binding domain, (5) RNA polymerase II transcriptional regulation (GO:0000981), (6) the dual activator/repressor function, (7) cell cycle control (GO:0051726), and (8) apoptosis induction (GO:0006915). The curated review's IBA annotations include GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0042771 (intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator), and GO:0042981 (regulation of apoptotic process).

The UniProt summary for mouse Trp53 describes it as a "tumor suppressor" that "induces growth arrest or apoptosis" and acts as "a trans-activating protein that acts downstream of a signal mediated by a DNA damage-stress pathway" -- all consistent with the BioReason summary.

The mention of "toggling between activation and repression" is a good nuance that captures the dual transcriptional function. The description of "checkpoint pathways" accurately reflects the DNA damage checkpoint role.

Minor gaps: The summary does not mention the specific DNA damage response context, the MDM2-mediated regulation of p53 stability, post-translational modifications that activate p53, or its roles in senescence and autophagy. The metabolic reprogramming functions (glycolysis regulation, ferroptosis) established for p53 are also absent.

Comparison with interpro2go:

The curated review has two GO_REF:0000002 annotations: GO:0006915 (apoptotic process) and GO:0051262 (protein tetramerization). BioReason's summary correctly captures both -- the apoptotic role and the tetramer formation. BioReason adds substantial value by explaining the mechanistic link between tetramerization and cooperative DNA binding, and by describing the dual activator/repressor function. The interpro2go annotations are basic; BioReason weaves them into a coherent functional narrative.

Notes on thinking trace

The trace provides careful analysis of the p53-family domain architecture: transactivation domain, DNA-binding domain (with the conserved central site), and tetramerization domain. The mechanistic model of a tetrameric transcriptional switch that senses stress and enforces checkpoints is accurate. The hypothesis about E3 ubiquitin ligase partners (MDM2) and checkpoint kinases (ATM/ATR/CHK1/CHK2) is well-supported.