Affinage

Showing MCRIP1 — FAM195B is a alias.

MCRIP1

Mapk-regulated corepressor-interacting protein 1 · UniProt C9JLW8

Length
97 aa
Mass
10.9 kDa
Annotated
2026-06-10
9 papers in source corpus 4 papers cited in narrative 5 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCRIP1 is an ERK-responsive regulator of the CtBP transcriptional co-repressor that gates whether CtBP-dependent gene silencing occurs (PMID:25728771). In its unphosphorylated state, MCRIP1 binds CtBP and competitively blocks CtBP's interaction with DNA-binding repressors, preventing assembly of the CtBP co-repressor complex on target promoters (PMID:25728771). ERK directly phosphorylates MCRIP1, causing it to dissociate from CtBP; freed CtBP then binds the DNA-binding repressor ZEB1 and is recruited to the E-cadherin promoter, driving chromatin modifications that silence E-cadherin during epithelial-mesenchymal transition (PMID:25728771). This switch is conserved in vivo: in Drosophila, depletion of the MCRIP ortholog phenocopies MAPK activation by reducing DE-cadherin, placing MCRIP downstream of MAPK in cadherin silencing (PMID:33012036). The same CtBP-inhibitory activity operates in a developmental context, where MCRIP1 interferes with CtBP interactions with the lung-enriched repressors Foxp1 and Foxp2 to keep the surfactant protein B and C promoters active; Mcrip1-null mice die of neonatal respiratory distress from aberrant surfactant gene repression (PMID:31240265). Independently of its CtBP role, MCRIP1 (FAM195B/GRAN2) binds the RNA helicase DDX6 in an RNA-independent manner and relocalizes to stress granules upon cellular stress (PMID:26184334).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2015 High

    Established the core mechanism by which MCRIP1 couples ERK signaling to transcriptional repression: it answered how a kinase signal is converted into CtBP-dependent gene silencing.

    Evidence ERK substrate identification, reciprocal Co-IP, competitive binding and phosphorylation assays, ChIP and promoter-reporter assays in mammalian cells

    PMID:25728771

    Open questions at the time
    • The phosphorylation site(s) and the structural basis of the MCRIP1-CtBP interaction are not defined
    • Whether MCRIP1 regulates CtBP at promoters beyond E-cadherin in EMT is not established here
  2. 2015 High

    Defined the unphosphorylated-state function as a competitive inhibitor, showing MCRIP1 acts by occluding CtBP's binding to DNA-bound repressors rather than by altering CtBP levels.

    Evidence Co-immunoprecipitation and competitive pulldown assays

    PMID:25728771

    Open questions at the time
    • The binding interface that overlaps between MCRIP1 and ZEB1 on CtBP is not mapped
  3. 2015 Medium

    Identified a CtBP-independent activity by showing MCRIP1 binds the RNA helicase DDX6 and partitions into stress granules, raising a possible role in translational control during stress.

    Evidence IP-mass spectrometry with DDX6 bait, RNase treatment for RNA-independence, fluorescence microscopy of stress granule localization

    PMID:26184334

    Open questions at the time
    • Functional consequence of the DDX6 interaction is not characterized
    • Whether stress granule recruitment intersects with the CtBP/ERK axis is unknown
  4. 2019 High

    Extended the CtBP-inhibitory model to a physiological, essential context, demonstrating that MCRIP1 keeps surfactant genes active by blocking CtBP-Foxp1/Foxp2 interactions, and that its loss is neonatally lethal.

    Evidence Homozygous Mcrip1 knockout mouse model, Co-IP of CtBP-Foxp1/Foxp2, ChIP and chromatin state analysis at SP-B/SP-C promoters

    PMID:31240265

    Open questions at the time
    • Whether surfactant gene repression in vivo is ERK-regulated is not tested
    • Tissue contexts beyond lung where MCRIP1 is required are not addressed
  5. 2020 Medium

    Provided in vivo genetic confirmation that MCRIP function lies downstream of MAPK in cadherin silencing, validating the mammalian biochemical model in a whole-organism epistasis setting.

    Evidence RNAi depletion of Drosophila MCRIP ortholog in mxc mutant hemocytes with DE-cadherin and lymph gland phenotype readouts

    PMID:33012036

    Open questions at the time
    • Single-lab ortholog study; direct CtBP involvement in the fly phenotype not biochemically confirmed
    • Phosphorylation-dependence of the fly phenotype not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the two activities of MCRIP1 — CtBP regulation and DDX6/stress-granule association — are mechanistically related, and whether they are coordinated by ERK signaling, remains unresolved.
  • No structural model of MCRIP1 or its binding interfaces
  • Functional role of DDX6 binding undefined
  • Phosphosite mapping on MCRIP1 absent from the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2 R-HSA-4839726 Chromatin organization 2
Partners
CTBP1DDX6

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 MCRIP1 is a direct substrate of ERK kinase; when phosphorylated by ERK, MCRIP1 dissociates from the transcriptional co-repressor CtBP, allowing CtBP to interact with the DNA-binding repressor ZEB1 and be recruited to the E-cadherin promoter, resulting in chromatin modifications that silence E-cadherin expression during epithelial-mesenchymal transition. ERK substrate identification, co-immunoprecipitation, competitive binding assays, phosphorylation assays, chromatin immunoprecipitation, promoter-reporter assays Molecular cell High 25728771
2015 In the absence of ERK signaling, MCRIP1 binds to CtBP and competitively inhibits the CtBP–ZEB1 interaction, thereby preventing assembly of the CtBP co-repressor complex on target gene promoters. Co-immunoprecipitation, competitive binding/pulldown assays Molecular cell High 25728771
2019 MCRIP1 promotes lung surfactant protein B (SP-B) and SP-C expression in alveolar epithelial cells by interfering with interactions between CtBP and the lung-enriched transcriptional repressors Foxp1 and Foxp2, thereby preventing recruitment of the CtBP co-repressor complex to SP-B and SP-C promoters and maintaining them in an active chromatin state. Homozygous Mcrip1 knockout mice die from respiratory distress due to abnormal repression of these surfactant proteins. Mcrip1 knockout mouse model (homozygous), co-immunoprecipitation (CtBP–Foxp1/Foxp2 interaction), chromatin immunoprecipitation (promoter occupancy), chromatin state analysis Communications biology High 31240265
2015 FAM195B (GRAN2/MCRIP1) interacts with the RNA helicase DDX6 in an RNA-independent manner and re-localizes from the cytoplasm to stress granules upon cellular stress exposure, suggesting a role in translation repression during the stress response. Immunoprecipitation–mass spectrometry (DDX6 as bait), RNase treatment to confirm RNA-independence, fluorescence microscopy for stress granule localization Biomolecules Medium 26184334
2020 In Drosophila, depletion of the MCRIP ortholog (dMCRIP) in mxc mutant hemocytes phenocopies MAPK cascade activation by reducing DE-cadherin levels and enhancing lymph gland hyperplasia, placing dMCRIP downstream of MAPK signaling in cadherin gene silencing in vivo. Genetic epistasis — RNAi-mediated depletion of Drosophila MCRIP in mxcmbn1 mutant background, quantification of DE-cadherin levels and lymph gland phenotype Genes to cells Medium 33012036

Source papers

Stage 0 corpus · 9 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during epithelial-mesenchymal transition by regulating the co-repressor CtBP. Molecular cell 68 25728771
2015 Comprehensive Protein Interactome Analysis of a Key RNA Helicase: Detection of Novel Stress Granule Proteins. Biomolecules 28 26184334
1989 Measurement of antibody affinity for cell surface antigens using an enzyme-linked immunosorbent assay. Journal of immunological methods 28 2607151
2023 Shear Stress Markedly Alters the Proteomic Response to Hypoxia in Human Pulmonary Endothelial Cells. American journal of respiratory cell and molecular biology 19 36730645
2023 Fecal microbiota transplantation alleviates experimental colitis through the Toll-like receptor 4 signaling pathway. World journal of gastroenterology 16 37662857
1969 EXPERIMENTAL OBSERVATIONS ON THE INFLUENCE OF TEMPERATURE, LIGHT, AND SALINITY ON CELL DIVISION OF THE MARINE DIATOM, DETONULA CONFERVACEA (CLEVE) GRAN(2). Journal of phycology 10 27096246
2019 MCRIP1 promotes the expression of lung-surfactant proteins in mice by disrupting CtBP-mediated epigenetic gene silencing. Communications biology 5 31240265
2020 Enhancement of leukemia-like phenotypes in Drosophila mxc mutant larvae due to activation of the RAS-MAP kinase cascade possibly via down-regulation of DE-cadherin. Genes to cells : devoted to molecular & cellular mechanisms 4 33012036
2026 Culture-dependent baseline states and drug response programs in myxofibrosarcoma models across 2D and 3D systems. Human cell 0 42012768

Missed literature

Know a paper Affinage missed for MCRIP1? Flag it for the maintainers and the community.

No submissions yet.