Affinage

MAP7D3

MAP7 domain-containing protein 3 · UniProt Q8IWC1

Length
876 aa
Mass
98.4 kDa
Annotated
2026-06-10
9 papers in source corpus 7 papers cited in narrative 7 extracted findings
Cross-family judge faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP7D3 is a microtubule-associated protein that binds and stabilizes microtubules and contributes to mitotic spindle integrity and accurate chromosome segregation (PMID:15561729, PMID:27284004). It engages microtubules through its MAP7 domain together with a C-terminal tail that contacts the tubulin C-terminal tail and competes with tau for the same binding site, promoting microtubule polymerization in vitro (PMID:24927501). On the spindle, MAP7D3 forms a complex with DDA3 (PSRC1) and restrains DDA3-dependent recruitment of the kinesin-13 depolymerase Kif2a to spindle minus ends; loss of MAP7D3 produces aberrant Kif2a activity, reduced spindle stability, and segregation defects spanning unaligned, lagging, and bridged chromosomes (PMID:27284004). Beyond mitosis, MAP7D3 supports spermatogonial stem cell self-renewal (PMID:32376790). The available corpus does not establish the molecular detail of MAP7D3-dependent kinesin-1 activation beyond a structural-modeling inference that its binding to the KHC coiled-coil disrupts the autoinhibited motor conformation (PMID:40791459).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2004 Medium

    Established MAP7D3 as a bona fide spindle-associated protein, placing an uncharacterized FLJ12649 product within the mitotic apparatus.

    Evidence MS/MS proteomics of purified human mitotic spindles plus localization of tagged protein in mitotic cells

    PMID:15561729

    Open questions at the time
    • No molecular function or microtubule-binding mechanism defined
    • Spindle role not yet linked to a phenotype
  2. 2014 High

    Defined the biochemical basis of microtubule association, showing MAP7D3 binds microtubules via its MAP7 domain and C-terminal tail and promotes polymerization, competing with tau.

    Evidence In vitro reconstitution with quantified binding (Kd ~3 µM), sedimentation and tau-competition assays, tubulin C-tail binding

    PMID:24927501

    Open questions at the time
    • Cellular consequence of tau competition not tested
    • Contribution of N-terminal regions to binding not resolved here
  3. 2016 High

    Connected MAP7D3's spindle localization to a mechanism for accurate segregation, showing it acts through a DDA3 complex to limit Kif2a-mediated minus-end depolymerization.

    Evidence Co-IP complex identification, siRNA knockdown with defined mitotic phenotypes, immunofluorescence of Kif2a recruitment

    PMID:27284004

    Open questions at the time
    • Direct vs indirect inhibition of Kif2a recruitment not fully separated
    • Structural basis of MAP7D3–DDA3 interaction unknown
  4. 2020 Medium

    Extended MAP7D3 function beyond mitosis to tissue-specific stem cell biology by implicating it in spermatogonial stem cell self-renewal.

    Evidence siRNA knockdown in mouse spermatogonial stem cells with self-renewal assay readout

    PMID:32376790

    Open questions at the time
    • Molecular pathway linking MAP7D3 to self-renewal not defined
    • Single method, single lab
  5. 2023 Low

    Linked MAP7D3 loss-of-function to human phenotypes, associating truncating variants with intellectual disability/autistic traits and with impaired sperm capacitation.

    Evidence NGS/exome sequencing, segregation analysis, patient sperm RT-PCR/western blot, in vitro capacitation assays, 3D modeling

    PMID:37520705 PMID:37817054

    Open questions at the time
    • Mechanistic claims rest on structural prediction without experimental validation
    • Sperm phenotype confounded by co-occurring IQCH variant
    • Causality for neurodevelopmental phenotype not functionally proven
  6. 2025 Medium

    Proposed a kinesin-1 regulatory role, modeling MAP7D3 binding to the KHC coiled-coil as a means to relieve motor autoinhibition.

    Evidence 8.0-Å cryo-EM of autoinhibited kinesin-1 heterotetramer, structural modeling of the MAP7D3 site, motility assays (preprint)

    PMID:40791459

    Open questions at the time
    • MAP7D3 interaction inferred from modeling rather than directly resolved
    • Preprint, single study
    • Activation not shown for endogenous MAP7D3 in cells

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MAP7D3's microtubule-stabilizing activity, spindle regulation, kinesin-1 activation, and tissue-specific roles are integrated into a single mechanistic program remains unresolved.
  • No structure of MAP7D3 bound to microtubules or kinesin
  • Direct demonstration of kinesin-1 activation by MAP7D3 lacking
  • Mechanism connecting microtubule function to stem cell self-renewal unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 2
Pathway
R-HSA-1640170 Cell Cycle 1
Partners
KIF2APSRC1

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 MAP7D3 (FLJ12649) was identified as a component of the human mitotic spindle by mass spectrometry analysis of purified spindles, and tagged MAP7D3 localized to the mitotic spindle in transfected cells. MS/MS proteomics of purified human mitotic spindles; fluorescence localization of tagged protein in transfected mitotic cells Molecular & cellular proteomics : MCP Medium 15561729
2014 The MAP7 domain (MD) of MAP7D3, together with its C-terminal tail (CT), binds to microtubules and promotes microtubule polymerization in vitro; MDCT binds reconstituted microtubules with an apparent Kd of ~3 µM, localizes along preassembled microtubules, competes with tau for the same binding site, and binds the C-terminal tail of tubulin. In vitro microtubule polymerization assays, sedimentation binding assays, competition experiments with tau, immunostaining of tagged protein on microtubules, binding to tubulin in HeLa cell extracts PloS one High 24927501
2016 MAP7D3 (Mdp3) forms a complex with DDA3 (PSRC1) and controls spindle microtubule dynamics at the minus end by inhibiting DDA3-mediated recruitment of the kinesin-13 depolymerase Kif2a to the spindle; depletion of MAP7D3 results in aberrant Kif2a activity, decreased spindle stability, unaligned chromosomes in metaphase, lagging chromosomes in anaphase, and chromosome bridges in telophase/cytokinesis. Co-immunoprecipitation (complex identification), siRNA knockdown with defined mitotic phenotypes, immunofluorescence of spindle localization and Kif2a recruitment Journal of cell science High 27284004
2020 Knockdown of Mtap7d3 in mouse spermatogonial stem cells (SSCs) inhibits SSC self-renewal in vitro, establishing a role for MAP7D3 in spermatogonial stem cell maintenance. siRNA knockdown in mouse SSCs with self-renewal assay readout Journal of medical genetics Medium 32376790
2025 Structural modeling and functional studies suggest that MAP7D3 binding to the kinesin-1 KHC coiled-coil region competes with intramolecular coiled-coil interactions that stabilize the autoinhibited kinesin-1 conformation, thereby activating kinesin-1 motor activity. 8.0-Å cryo-EM structure of autoinhibited kinesin-1 heterotetramer; structural modeling of MAP7D3 interaction site; functional motility assays bioRxivpreprint Medium 40791459
2023 A frameshift mutation c.2174_2177del (p.Thr725MetfsTer2) in MAP7D3, causing loss of the C-terminal tail, was identified in two siblings with severe intellectual disability and autistic traits; 3D modeling predicts this truncation destabilizes the protein and may impair kinesin-1 binding to microtubules via an allosteric effect. Next-generation sequencing, segregation analysis, 3D protein modeling Journal of molecular neuroscience : MN Low 37817054
2023 Truncating variants in MAP7D3 in an infertile asthenozoospermic patient reduced MAP7D3 transcripts and protein in spermatozoa, and patient spermatozoa were unable to induce phosphorylation cascades associated with capacitation. Exome sequencing; RT-PCR and western blot of patient sperm; in vitro capacitation phosphorylation assays iScience Low 37520705

Source papers

Stage 0 corpus · 9 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Proteome analysis of the human mitotic spindle. Molecular & cellular proteomics : MCP 224 15561729
2014 C-terminal region of MAP7 domain containing protein 3 (MAP7D3) promotes microtubule polymerization by binding at the C-terminal tail of tubulin. PloS one 25 24927501
2020 Human X chromosome exome sequencing identifies BCORL1 as contributor to spermatogenesis. Journal of medical genetics 21 32376790
2016 DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics. Journal of cell science 16 27284004
2016 Muscle hypertrophy as the presenting sign in a patient with a complete FHL1 deletion. Clinical genetics 8 27409453
2023 Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing. Asian journal of andrology 6 36259570
2023 Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans. iScience 4 37520705
2023 A Novel Mutation in the MAP7D3 Gene in Two Siblings with Severe Intellectual Disability and Autistic Traits: Concurrent Assessment of BDNF Functional Polymorphism, X-Inactivation and Oxidative Stress to Explain Disease Severity. Journal of molecular neuroscience : MN 4 37817054
2025 Structural Basis of Kinesin-1 Autoinhibition and Its Control of Microtubule-Based Motility. bioRxiv : the preprint server for biology 3 40791459

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