Affinage

ZMYM4

Zinc finger MYM-type protein 4 · UniProt Q5VZL5

Round 2 corrected
Length
1548 aa
Mass
172.8 kDa
Annotated
2026-04-28
39 papers in source corpus 4 papers cited in narrative 4 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ZMYM4 is a nuclear MYM-type zinc finger protein that is heavily SUMOylated and undergoes phosphorylation (PMID:15302935, PMID:32439918). It physically interacts with the B-MYB (MYBL2) transcription factor in a DNA-damage-stimulated manner, yet its depletion does not perturb the cell cycle, distinguishing it from B-MYB and pointing to a specific role in the DNA-damage response rather than in general cell-cycle control (PMID:32439918). ZMYM4 has also been biochemically classified as an mRNA-binding protein by UV-crosslinking interactome capture (PMID:22658674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2004 Low

    Establishing that ZMYM4 is a nuclear phosphoprotein provided the first post-translational-modification context, showing it resides in the nucleus and is subject to phosphorylation.

    Evidence Phosphopeptide enrichment from HeLa nuclear fractions followed by tandem mass spectrometry

    PMID:15302935

    Open questions at the time
    • Large-scale proteomics with no functional follow-up on ZMYM4 phosphorylation sites
    • Kinase(s) responsible for ZMYM4 phosphorylation unknown
    • Functional consequence of phosphorylation not tested
  2. 2012 Medium

    Classification of ZMYM4 as an mRNA-binding protein expanded its potential functions beyond transcription factor interaction, indicating it contacts poly(A)+ RNA in living cells.

    Evidence UV crosslinking followed by oligo(dT) capture and mass spectrometry in proliferating HeLa cells

    PMID:22658674

    Open questions at the time
    • Specific RNA targets of ZMYM4 not identified
    • Whether RNA binding is direct through MYM zinc-finger domains or mediated by a complex is unknown
  3. 2020 Medium

    Identification of ZMYM4 as a SUMOylated, DNA-damage-stimulated binding partner of B-MYB provided the first mechanistic link to the DNA-damage response and distinguished ZMYM4's function from cell-cycle regulation.

    Evidence Affinity purification–mass spectrometry and co-immunoprecipitation of B-MYB complexes, siRNA knockdown with cell-cycle analysis, and SUMOylation assay in HEK293 cells

    PMID:32439918

    Open questions at the time
    • Whether the ZMYM4–B-MYB interaction is direct or bridged by SUMO remains untested
    • Downstream effectors or targets of ZMYM4 in the DNA-damage response are unknown
    • No structural or domain-mapping data for the interaction

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise molecular activity of ZMYM4 — whether it functions as a transcriptional co-regulator, an RNA-processing factor, or a scaffold in DNA-damage signaling — remains unresolved.
  • No enzymatic activity demonstrated
  • No loss-of-function phenotype established beyond absence of cell-cycle defects
  • Relationship between RNA-binding capacity and B-MYB interaction not investigated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2
Partners
MYBL2

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 ZMYM4 was identified as a novel binding partner of B-MYB (MYBL2) transcription factor by affinity purification coupled to mass spectrometry. ZMYM4 is highly SUMOylated, and its interaction with B-MYB is stimulated upon induction of DNA damage. Knockdown of ZMYM4 in HEK293 cells had no obvious effect on the cell cycle, distinguishing its function from that of B-MYB (which causes G2/M arrest when depleted), suggesting a specific role for ZMYM4 in the DNA-damage response rather than general cell cycle control. Affinity purification–mass spectrometry (AP-MS), co-immunoprecipitation, siRNA knockdown with cell cycle analysis, SUMOylation assay Scientific reports Medium 32439918
2012 ZMYM4 was identified as a component of the mRNA interactome of proliferating human HeLa cells using UV crosslinking-based interactome capture, classifying it as an RNA-binding protein (RBP) by biochemical and statistical criteria. UV crosslinking followed by oligo(dT) capture and mass spectrometry (interactome capture) Cell Medium 22658674
2004 ZMYM4 was detected as a nuclear phosphoprotein in HeLa cells, with phosphorylation sites identified by mass spectrometry from the nuclear fraction, indicating it undergoes nuclear phosphorylation as a post-translational modification. Strong cation exchange chromatography enrichment of phosphopeptides from nuclear fraction followed by tandem MS Proceedings of the National Academy of Sciences of the United States of America Low 15302935
2011 A genome-wide RNAi morphology screen in Drosophila cells combined with human cell validation identified conserved regulators of cell morphology and migration; ZMYM4 (as a MYM-type zinc finger family member implicated in mental retardation) was among genes from this functional category examined in human cells for effects on cytoskeletal organization and cell shape. Genome-wide RNAi screen in Drosophila S2 cells for morphology phenotypes, followed by validation in human cells with siRNA knockdown and microscopy BMC biology Low 21834987

Source papers

Stage 0 corpus · 39 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2010 Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell 639 20850016
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2016 A High-Density Map for Navigating the Human Polycomb Complexome. Cell reports 216 27705803
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2019 Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets. Molecular cell 167 30686591
2011 Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration. BMC biology 164 21834987
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2009 Direct binding of CoREST1 to SUMO-2/3 contributes to gene-specific repression by the LSD1/CoREST1/HDAC complex. Molecular cell 140 19394292
2018 SHLD2/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice. The EMBO journal 124 30154076
2022 Human transcription factor protein interaction networks. Nature communications 123 35140242
2015 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. Molecular systems biology 120 25609649
2008 ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers. PloS one 72 18806873
2014 Characterization of the SUMO-binding activity of the myeloproliferative and mental retardation (MYM)-type zinc fingers in ZNF261 and ZNF198. PloS one 28 25133527
1999 Cloning and mapping of members of the MYM family. Genomics 24 10486218
2020 Characterization of the zinc finger proteins ZMYM2 and ZMYM4 as novel B-MYB binding proteins. Scientific reports 13 32439918
2000 Cloning of ZNF237, a novel member of the MYM gene family that maps to human chromosome 13q11-->q12. Cytogenetics and cell genetics 6 10894931
2021 Expression and Mutation Alterations of ZMYM4 Gene in Gastric and Colonic Cancers. Applied immunohistochemistry & molecular morphology : AIMM 3 33938481
2025 An exploration on the involvement of the methyltransferase like 3-m6A‑zinc finger MYM-type containing 1 axis in the progression of liver hepatocellular carcinoma. International journal of biological macromolecules 1 40187452
2026 A zinc finger MYM-type containing 3 (ZMYM3) allele is associated with autism spectrum disorder in Iranian people. Journal of neurogenetics 0 41958272
2014 Identification of Zinc Finger, MYM-type 2 (ZMYM2) as a regulator of sorafenib resistance in hepatocellular carcinoma cell lines. Journal of gastroenterology and hepatology 0 24716227