Affinage

MAP7D1

MAP7 domain-containing protein 1 · UniProt Q3KQU3

Round 2 corrected
Length
841 aa
Mass
92.8 kDa
Annotated
2026-04-28
42 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP7D1 is a microtubule-associated protein that functions as a microtubule-tethered activator of kinesin-1 and a regulator of microtubule stability, with roles spanning axon elongation, mitotic spindle integrity, DNA damage repair, and organelle positioning. MAP7D1 binds microtubules through its N-terminal domain and promotes kinesin-1 (KIF5B) landing and processivity both directly and allosterically through its C-terminal kinesin-binding domain, acting redundantly with MAP7 and MAP7D3 in HeLa cells (PMID:30770434). DCLK1 phosphorylates MAP7D1 at Ser315 to drive callosal axon elongation in cortical neurons (PMID:27503845), while MAP7D1 also interacts with Disheveled to mediate Wnt5a-dependent cortical microtubule plus-end targeting via a kinesin-1-dependent feedback loop (PMID:29880710). Beyond cytoskeletal functions, MAP7D1 participates in G1-phase DNA double-strand break repair by recruiting RAD50 and 53BP1 to damage sites (PMID:36852271), maintains acetylated stable microtubules in neuronal cells (PMID:35470240), and its loss of function causes multipolar spindles and lagging chromosomes during mitosis (PMID:40856631).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2016 High

    Establishing MAP7D1 as a phosphorylation-dependent effector of axon elongation resolved how DCLK1 kinase activity is transduced into cytoskeletal remodeling during cortical neuron development.

    Evidence Proteomic substrate identification, in vitro kinase assay, and in utero electroporation with phosphomimetic rescue in cortical neurons

    PMID:27503845

    Open questions at the time
    • Downstream mechanism by which Ser315 phosphorylation alters microtubule dynamics is unknown
    • Whether other kinases phosphorylate MAP7D1 at additional sites in neurons is untested
  2. 2018 High

    Demonstrating that MAP7D1 bridges Disheveled and kinesin-1 on microtubules established a Wnt5a-responsive feedback loop for cortical microtubule plus-end targeting, revealing a signaling-to-transport coupling mechanism.

    Evidence Reciprocal co-immunoprecipitation, live-cell imaging in HeLa cells, depletion/rescue, and cross-species validation in Drosophila

    PMID:29880710

    Open questions at the time
    • Structural basis of the MAP7D1–Disheveled interaction is unresolved
    • Physiological tissue context beyond cultured cells and Drosophila wings is unexplored
  3. 2019 High

    Reconstitution of MAP7D1–kinesin-1 interactions with purified proteins demonstrated that MAP7 family members promote kinesin-1 microtubule landing through both direct tethering and allosteric activation, defining the core molecular mechanism of MAP7D1 as a motor cofactor.

    Evidence Single-molecule TIRF assays with purified proteins, domain truncation mapping, siRNA knockdown in HeLa cells

    PMID:30770434

    Open questions at the time
    • Relative contributions of MAP7D1 versus MAP7 and MAP7D3 in specific tissues remain undefined
    • No high-resolution structure of the MAP7D1–kinesin-1 complex exists
  4. 2021 Medium

    Zebrafish map7d1b knockout revealed that MAP7D1 supports autophagic flux and protein homeostasis in cardiac muscle, extending its functional repertoire beyond cytoskeletal regulation to organelle quality control.

    Evidence Zebrafish knockout, doxorubicin-induced cardiomyopathy model, autophagic flux and protein aggregation assays

    PMID:34327238

    Open questions at the time
    • Whether autophagy impairment is a direct consequence of disrupted kinesin-1 transport or an independent mechanism is unclear
    • Mammalian cardiac phenotypes of MAP7D1 loss have not been reported
  5. 2022 Medium

    Distinguishing MAP7D1's microtubule-stabilizing mechanism (via acetylation) from MAP7D2's direct binding-based stabilization clarified how paralog-specific functions diversify the microtubule cytoskeleton in neuronal cells.

    Evidence siRNA/shRNA knockdown, nocodazole resistance assay, acetylated/detyrosinated tubulin immunofluorescence in N1-E115 neuronal cells

    PMID:35470240

    Open questions at the time
    • How MAP7D1 promotes tubulin acetylation (e.g., via αTAT1 recruitment) is unknown
    • In vivo neuronal consequences of selective MAP7D1 loss on stable microtubule pools are untested
  6. 2023 Medium

    Discovery that MAP7D1 recruits RAD50 and 53BP1 to DNA damage sites in G1 cells established an unexpected nuclear function for this microtubule-associated protein in the DNA double-strand break repair pathway.

    Evidence Quantitative AP-MS, γ-irradiation, chromatin fractionation, immunofluorescence, siRNA knockdown

    PMID:36852271

    Open questions at the time
    • Whether MAP7D1 translocates to the nucleus or acts via an indirect cytoskeletal-signaling mechanism is unresolved
    • The DNA repair function has not been independently replicated
  7. 2025 Medium

    Identification of a patient-derived MAP7D1 R201W mutation that disrupts microtubule binding and causes multipolar spindles and lagging chromosomes provided the first direct link between MAP7D1 dysfunction and mitotic fidelity defects in a disease context.

    Evidence Patient fibroblast analysis, mutant overexpression, siRNA knockdown, microtubule co-sedimentation, spindle morphology analysis in T98G and HEK293T cells

    PMID:40856631

    Open questions at the time
    • Whether MAP7D1 R201W is causative for the patient's Shwachman-Diamond syndrome phenotype or a modifier is not established
    • Mechanism linking MAP7D1 loss to RPS14 accumulation in dividing cells is unexplained
  8. 2025 Medium

    Showing that MAP7D1 preferentially partitions onto detyrosinated microtubules and that its density is nutrient-regulated to control lysosome positioning unified its kinesin-1 cofactor and tubulin-code reader activities into a nutrient-responsive transport mechanism.

    Evidence (preprint) Live-cell imaging, siRNA knockdown and overexpression, lysosome tracking, rigor kinesin localization assays

    PMID:bio_10.1101_2025.10.07.680844

    Open questions at the time
    • Findings are from a preprint not yet peer-reviewed
    • Signaling pathway linking nutrient status to MAP7D1 density changes is unidentified
    • Whether detyrosination preference applies in vivo in specific tissues is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of MAP7D1 bound to microtubules and/or kinesin-1, the molecular basis of its nuclear DNA repair role, and how nutrient signals regulate MAP7D1–microtubule partitioning remain major unresolved questions.
  • No structural data for MAP7D1 or its complexes exist
  • Nuclear versus cytoplasmic partitioning mechanism is unknown
  • Tissue-specific functional redundancy among MAP7 family paralogs is poorly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6
Localization
GO:0005856 cytoskeleton 6 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 1 R-HSA-1640170 Cell Cycle 1 R-HSA-73894 DNA Repair 1
Partners
BRCA1DCLK1DVL2KIF5BRAD50TP53BP1

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 DCLK1 phosphorylates MAP7D1 at serine 315 to promote axon elongation in cortical neurons. Knockdown of MAP7D1 in layer 2/3 cortical neurons impairs callosal axon elongation (but not radial migration), and a phosphomimetic MAP7D1 S315E mutant fully rescues axon elongation defects in Dclk1 knockdown neurons. Proteomic substrate identification, in vitro kinase assay, in utero electroporation knockdown, phosphomimetic rescue experiment Developmental neurobiology High 27503845
2018 MAP7D1 (together with MAP7) binds Disheveled, directs its cortical localization, and facilitates cortical targeting of microtubule plus-ends in response to Wnt5a signaling. Wnt5a signaling reciprocally promotes MAP7D1 movement toward microtubule plus-ends, and this dynamics requires Kinesin-1 member KIF5B. Disheveled also stabilizes MAP7D1. This MAP7/7D1–Disheveled feedback loop is evolutionarily conserved (Drosophila Ensconsin influences Disheveled localization in pupal wing cells). Co-immunoprecipitation, depletion/rescue experiments in HeLa cells, live-cell imaging, Drosophila genetic analysis EMBO reports High 29880710
2019 All four mammalian MAP7 family members (MAP7, MAP7D1, MAP7D3, MAP7D2) bind to kinesin-1. MAP7, MAP7D1, and MAP7D3 act redundantly in HeLa cells to enable kinesin-1-dependent transport and microtubule recruitment of KIF5B-560. MAP7 proteins promote kinesin-1 binding to microtubules both directly (via the N-terminal microtubule-binding domain and unstructured linker) and indirectly via an allosteric effect from the kinesin-binding C-terminal domain. In vitro reconstitution with purified proteins, single-molecule TIRF assays, siRNA knockdown in HeLa cells, domain mapping The Journal of cell biology High 30770434
2022 MAP7D1 is required for maintenance of acetylated stable microtubules in neuronal cells. In contrast to Map7D2 (which stabilizes microtubules via direct binding), Map7D1 stabilizes microtubules through a distinct mechanism involving acetylation. Loss of Map7D1 increases random cell migration rate and neurite outgrowth. Gene knockdown (siRNA/shRNA), nocodazole resistance assay, immunofluorescence for acetylated/detyrosinated tubulin, live-cell migration assay in N1-E115 neuronal cells Life science alliance Medium 35470240
2023 MAP7D1 interacts with DNA double-strand break repair proteins RAD50, BRCA1, and 53BP1. Downregulation of MAP7D1 causes strong G1 arrest and impairs DNA repair in G1-arrested cells, reducing RAD50 recruitment to chromatin and 53BP1 localization to damage sites, and increasing p53 phosphorylation after γ-irradiation. Quantitative proteomics (AP-MS), γ-irradiation, chromatin fractionation, immunofluorescence, siRNA knockdown iScience Medium 36852271
2021 MAP7D1 disruption in zebrafish (map7d1b) exacerbates doxorubicin-induced cardiomyopathy; mechanistically, loss of MAP7D1 function impairs autophagic degradation and elevates protein aggregation. MAP7D1/Map7d1b shows cardiac and skeletal muscle-specific expression with sarcomeric localization. Zebrafish knockout, doxorubicin treatment, autophagic flux assays, protein aggregation assays, immunofluorescence BioMed research international Medium 34327238
2021 MAP7D1 expression is regulated by TET1-mediated 5-hydroxymethylcytosine modification and promotes tumor growth and metastasis in breast cancer. Genome-wide 5hmC profiling, TET1 knockdown/overexpression, functional metastasis assays Genomics, proteomics & bioinformatics Medium 33716151
2025 A MAP7D1 R201W mutation in the microtubule-binding domain (found in a Shwachman-Diamond syndrome patient) acts as a loss-of-function mutation, disrupting MAP7D1 interaction with microtubules. This causes mitotic defects (multipolar/unstable spindles, lagging chromosomes, shortened inter-centrosomal distance) and accumulation of ribosomal protein RPS14 in dividing cells. Overexpression of mutant MAP7D1 or MAP7D1 depletion recapitulates these phenotypes in T98G and HEK293T cells. Patient fibroblast analysis, mutant overexpression, siRNA knockdown, immunofluorescence for spindle morphology and RPS14, microtubule co-sedimentation Disease models & mechanisms Medium 40856631
2025 MAP7D1 preferentially partitions onto detyrosinated microtubules (mediated by expanded microtubule lattice states), creating specialized tracks for kinesin-1 (KIF5B). MAP7D1 density on microtubules is dynamically modulated by nutrient availability — increasing during starvation (promoting perinuclear lysosome positioning) and decreasing upon nutrient stimulation (allowing peripheral lysosome migration). Altering MAP7D1 levels in either direction impairs lysosomal motility and nutrient-responsive positioning. Live-cell imaging, fluorescence microscopy, siRNA knockdown and overexpression, lysosome tracking, rigor kinesin localization assays bioRxivpreprint Medium bio_10.1101_2025.10.07.680844
2020 SARS-CoV-2 ORF10 protein physically associates with MAP7D1 in human cells, as identified by affinity-purification mass spectrometry. Affinity-purification mass spectrometry (AP-MS) in human cells expressing tagged viral proteins Nature Low 32353859

Source papers

Stage 0 corpus · 42 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
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
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
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
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
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
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
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2022 Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 256 35063084
2004 Proteome analysis of the human mitotic spindle. Molecular & cellular proteomics : MCP 224 15561729
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2015 FBXW7 modulates cellular stress response and metastatic potential through ​HSF1 post-translational modification. Nature cell biology 130 25720964
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
2019 MAP7 family proteins regulate kinesin-1 recruitment and activation. The Journal of cell biology 115 30770434
2016 A cascading activity-based probe sequentially targets E1-E2-E3 ubiquitin enzymes. Nature chemical biology 114 27182664
2000 The nuclear import of RCC1 requires a specific nuclear localization sequence receptor, karyopherin alpha3/Qip. The Journal of biological chemistry 56 10744690
2016 DCLK1 phosphorylates the microtubule-associated protein MAP7D1 to promote axon elongation in cortical neurons. Developmental neurobiology 37 27503845
2021 Emergence of unique SARS-CoV-2 ORF10 variants and their impact on protein structure and function. International journal of biological macromolecules 22 34863825
2023 Repair mechanism of Yishen Tongluo formula on mouse sperm DNA fragmentation caused by polystyrene microplastics. Pharmaceutical biology 17 36895195
2018 Map7/7D1 and Dvl form a feedback loop that facilitates microtubule remodeling and Wnt5a signaling. EMBO reports 17 29880710
2019 Characterization of whole blood transcriptome and early-life fecal microbiota in high and low responder pigs before, and after vaccination for Mycoplasma hyopneumoniae. Vaccine 16 30808565
2021 Genome-wide 5-Hydroxymethylcytosine Profiling Analysis Identifies MAP7D1 as A Novel Regulator of Lymph Node Metastasis in Breast Cancer. Genomics, proteomics & bioinformatics 13 33716151
2023 Microtubule-associated proteins MAP7 and MAP7D1 promote DNA double-strand break repair in the G1 cell cycle phase. iScience 9 36852271
2022 Map7D2 and Map7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells. Life science alliance 8 35470240
2023 Identification of Rare Variants Involved in High Myopia Unraveled by Whole Genome Sequencing. Ophthalmology science 6 37250922
2021 Disruption of MAP7D1 Gene Function Increases the Risk of Doxorubicin-Induced Cardiomyopathy and Heart Failure. BioMed research international 6 34327238
2025 A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells. Disease models & mechanisms 0 40856631