Affinage

CNOT11

CCR4-NOT transcription complex subunit 11 · UniProt Q9UKZ1

Length
510 aa
Mass
55.2 kDa
Annotated
2026-06-09
25 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CNOT11 (C2ORF29) is a non-catalytic subunit of the human CCR4-NOT deadenylase complex that functions in post-transcriptional gene regulation (PMID:23232451). Together with CNOT10, it forms a distinct module that interacts with the N-terminal region of CNOT1, and CNOT11 is required for the association of CNOT10 with the complex (PMID:23232451). Structurally, two helical domains of CNOT1 sandwich CNOT10 and CNOT11, while the most conserved domain of CNOT11 protrudes as an 'antenna' domain that serves as a protein-protein interaction platform, binding the tumor suppressor and spermatogenic factor GGNBP2 (PMID:36586408). Functionally, CNOT11 acts as a central effector of tubulin mRNA autoregulation and basal tubulin mRNA stability, with its depletion impairing rapid tubulin mRNA degradation triggered by elevated soluble tubulin (PMID:41426964). In vivo, CNOT11 is required for timely establishment of mature hepatocyte gene expression programs, and its global loss is embryonic lethal, indicating an essential developmental role (PMID:42047232).

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2012 High

    Established that CNOT11 is a genuine subunit of the CCR4-NOT complex and defined its architectural role, resolving how the CNOT10/CNOT11 module attaches to the deadenylase machinery.

    Evidence Co-immunoprecipitation, affinity purification of CCR4-NOT, and knockdown/depletion in human cells

    PMID:23232451

    Open questions at the time
    • No structural detail on how the module docks onto CNOT1
    • Molecular function of the module within deadenylation left undefined
    • No mRNA targets identified
  2. 2022 High

    Defined the structural basis of the N-terminal module and revealed that CNOT11's conserved 'antenna' domain is a protein-protein interaction surface, providing a mechanistic role beyond mere scaffolding.

    Evidence High-resolution structural analysis of the CNOT1-CNOT10-CNOT11 module with biochemical validation of GGNBP2 binding

    PMID:36586408

    Open questions at the time
    • Functional consequence of GGNBP2 recruitment to the complex not established
    • Whether the antenna domain binds additional partners unknown
    • Link between antenna-mediated interactions and target mRNA selection not shown
  3. 2025 Medium

    Connected CNOT11 to a specific regulatory output by showing it is required for tubulin mRNA autoregulation and basal stability, demonstrating the module participates in target-specific mRNA decay.

    Evidence siRNA knockdown of CNOT11 with Roadblock-qPCR kinetic measurement of tubulin mRNA decay in human cells

    PMID:41426964

    Open questions at the time
    • Single lab, single method without orthogonal validation
    • Mechanism by which the module senses soluble tubulin to trigger decay not resolved
    • Whether CNOT11 directly contacts the target mRNA or recruits a sensing factor unknown
  4. 2026 Medium

    Demonstrated the physiological requirement for CNOT11 in mammalian development and organ maturation, showing the gene is essential and shapes hepatocyte gene expression programs.

    Evidence Hepatocyte-specific and global Cnot11 knockout mouse models with histology, Ki67 immunostaining, RNA-seq, and serum biochemistry

    PMID:42047232

    Open questions at the time
    • Direct mRNA targets driving the maturation phenotype not identified
    • Stage of embryonic lethality and underlying cause not defined
    • Connection between hepatocyte phenotype and deadenylase activity not mechanistically traced

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CNOT11 directs target-specific mRNA selection and how its antenna-domain interactions translate into the developmental and maturation programs remains unresolved.
  • No genome-wide map of CNOT11-dependent mRNA targets
  • Functional role of GGNBP2 recruitment in mRNA decay undefined
  • Mechanistic link between the antenna platform and physiological phenotypes missing

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2
Pathway
R-HSA-8953854 Metabolism of RNA 2
Partners
CNOT1CNOT10GGNBP2
Complex memberships
CCR4-NOTCNOT1-CNOT10-CNOT11 N-terminal module

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 C2ORF29 (CNOT11) is a bona fide subunit of the human CCR4-NOT complex; it interacts with the N-terminal region of CNOT1 and with CNOT10, and is required for the association of CNOT10 with the CCR4-NOT complex, forming a distinct CNOT10/CNOT11 module. Co-immunoprecipitation, affinity purification of CCR4-NOT complex, knockdown/depletion experiments RNA biology High 23232451
2022 High-resolution structural analysis of the human CNOT1-CNOT10-CNOT11 N-terminal module revealed that two helical domains of CNOT1 sandwich CNOT10 and CNOT11, with the most conserved domain of CNOT11 protruding into solvent as an 'antenna' domain. This antenna domain was identified as the binding site for GGNBP2 (a tumor suppressor and spermatogenic factor), establishing the N-terminal module as a protein-protein interaction platform. X-ray crystallography/cryo-EM structural approaches, biochemical interaction assays (pulldown/co-IP with GGNBP2) Cell reports High 36586408
2025 CNOT11 (together with CNOT1 and CNOT10) is a central effector of tubulin mRNA autoregulation and basal tubulin mRNA stability; siRNA knockdown of CNOT11 impairs rapid tubulin mRNA degradation triggered by elevated soluble tubulin levels. siRNA knockdown of CNOT11 coupled with Roadblock-qPCR kinetic measurements of tubulin mRNA levels microPublication biology Medium 41426964
2026 Hepatocyte-specific knockout of Cnot11 in mice causes delayed postnatal hepatocyte maturation (increased Ki67+ HNF4A+ cells, upregulated cell cycle genes, downregulated metabolic genes) and transient liver dysfunction, demonstrating that CNOT11 is required for timely establishment of mature hepatocyte gene expression programs. Global Cnot11 knockout is embryonic lethal, indicating an essential role in early development. Conditional (hepatocyte-specific) Cnot11 knockout mouse model, histology, Ki67 immunostaining, RNA-seq transcriptomics, serum biochemistry Genes to cells : devoted to molecular & cellular mechanisms Medium 42047232

Source papers

Stage 0 corpus · 25 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 AppppA binds to several proteins in Escherichia coli, including the heat shock and oxidative stress proteins DnaK, GroEL, E89, C45 and C40. The EMBO journal 75 1935909
2012 C2ORF29/CNOT11 and CNOT10 form a new module of the CCR4-NOT complex. RNA biology 61 23232451
2002 Evolution of the C30 carotenoid synthase CrtM for function in a C40 pathway. Journal of bacteriology 58 12426357
2010 Redesign, reconstruction, and directed extension of the Brevibacterium linens C40 carotenoid pathway in Escherichia coli. Applied and environmental microbiology 45 20525861
2006 Genes from a Dietzia sp. for synthesis of C40 and C50 beta-cyclic carotenoids. Gene 43 17008032
1997 NMR 15N relaxation and structural studies reveal slow conformational exchange in barstar C40/82A. Journal of molecular biology 39 9159486
2001 Functional properties of diapophytoene and related desaturases of C(30) and C(40) carotenoid biosynthetic pathways. Biochimica et biophysica acta 36 11566453
1976 Enzymatic synthesis of C40 carotenes by cell-free preparation from Halobacterium cutirubrum. Canadian journal of biochemistry 36 971465
2007 Use of transposon promoter-probe vectors in the metabolic engineering of the obligate methanotroph Methylomonas sp. strain 16a for enhanced C40 carotenoid synthesis. Applied and environmental microbiology 30 17261513
2006 Progress on molecular breeding and metabolic engineering of biosynthesis pathways of C(30), C(35), C(40), C(45), C(50) carotenoids. Biotechnology advances 29 17257797
2017 Enzyme-mediated biodegradation of long-chain n-alkanes (C32 and C40) by thermophilic bacteria. 3 Biotech 23 28567628
2007 Comparison of C40/82A and P27A C40/82A barstar mutants using 19F NMR. Biochemistry 22 17371049
2022 The human CNOT1-CNOT10-CNOT11 complex forms a structural platform for protein-protein interactions. Cell reports 21 36586408
2024 Enhancing astaxanthin biosynthesis and pathway expansion towards glycosylated C40 carotenoids by Corynebacterium glutamicum. Scientific reports 18 38582923
2021 Production of C20, C30 and C40 terpenes in the engineered phototrophic bacterium Rhodobacter capsulatus. Journal of biotechnology 10 34237394
2018 Unified Strategy for 1,5,9- and 1,5,7-Triols via Configuration-Encoded 1,5-Polyol Synthesis: Preparation and Coupling of C15-C25 and C26-C40 Fragments of Tetrafibricin. The Journal of organic chemistry 10 30372076
2017 Complete genome sequence of Flavobacterium kingsejongi WV39, a type species of the genus Flavobacterium and a microbial C40 carotenoid zeaxanthin producer. Journal of biotechnology 10 29199128
2023 Gas phase synthesis of the C40 nano bowl C40H10. Nature communications 9 36934084
1974 Interference in Carotenogenesis as a Mechanism of Action of the Pyridazinone Herbicide Sandoz 6706: Accumulation of C-40 Carotenoid Precursors Inhibition of beta-Carotene Synthesis and Enhancement of Phytoene Epoxidation. Plant physiology 6 16659000
2012 Down-regulation of replication factor C-40 (RFC40) causes chromosomal missegregation in neonatal and hypertrophic adult rat cardiac myocytes. PloS one 2 22720015
2022 The MreA Metal-Binding Sites C40, H65, and C69 Play a Critical Role in the Metal Tolerance of Pseudomonas putida KT2440. Current microbiology 1 35322302
2026 Liver-Specific Deletion of Cnot11 Delays Postnatal Hepatocyte Maturation and Transiently Impairs Liver Function in Mice. Genes to cells : devoted to molecular & cellular mechanisms 0 42047232
2025 The CCR4-NOT deadenylase complex mediates tubulin autoregulation via specific adapters CNOT10 and CNOT11. microPublication biology 0 41426964
1995 Electrolyte and total protein changes in nonheat acclimated horses performing treadmill exercise in cool (20 degrees C/40%RH), hot, dry (30 degrees C/40%RH) or hot, humid (30 degrees C/80%RH) conditions. Equine veterinary journal. Supplement 0 8933090
1989 [The role of the state of protein-lipid interactions in stimulated membranes in the conformation of C40-carotenoids]. Biofizika 0 2788461

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