MAP7D2 is a microtubule-associated protein of the MAP7/ensconsin family that localizes to the proximal axon and serves as a critical cofactor for kinesin-1-mediated cargo transport. The protein directly binds microtubules via its N-terminal region and interacts with kinesin-1 family members (KIF5A/B/C) through its C-terminus. MAP7D2 functions to recruit and activate kinesin-1 on microtubules at the proximal axon/axon initial segment, thereby gating anterograde transport of organelles (mitochondria, lysosomes, ER-derived vesicles) into the axon. It stabilizes microtubules through direct binding and plays roles in controlling cell motility and neurite outgrowth. The protein also localizes to centrosomes, midbody during cytokinesis, and neuron projections. Recent GWAS studies have implicated MAP7D2 in age-related hearing loss, consistent with its expression in inner ear hair cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000226 microtubule cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation based on phylogenetic inference from MAP7 family members. MAP7D2 belongs to the MAP7 family which includes MAP7, MAP7D1, MAP7D2, and MAP7D3, all of which regulate microtubule organization. Pan et al. 2019 demonstrated that MAP7D2 localizes to microtubules and regulates their organization at the proximal axon. Kikuchi et al. 2022 showed MAP7D2 stabilizes microtubules through direct binding [file:human/MAP7D2/MAP7D2-deep-research-falcon.md]. Reason: This annotation is well-supported by both phylogenetic evidence and direct experimental studies. MAP7D2 clearly functions in microtubule cytoskeleton organization as a core function, recruiting kinesin-1 to microtubules and stabilizing them. Supporting Evidence: PMID:30784582 MAP7D2 Localizes to the Proximal Axon and Locally Promotes Kinesin-1-Mediated Cargo Transport into the Axon file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 and MAP7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells |
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for cellular component. MAP7D2 is active in the microtubule cytoskeleton, binding directly to microtubules and recruiting kinesin-1 motor proteins. This is the primary site of MAP7D2 function. Reason: This cellular component annotation accurately reflects where MAP7D2 functions. The protein binds microtubules via its N-terminal domain and this is its primary site of activity. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2's N-terminus binds microtubules; its C-terminus underlies kinesin-1 interaction |
| GO:0000226 microtubule cytoskeleton organization | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation from combined automated methods, consistent with ortholog annotations and InterPro domain predictions. This duplicates the IBA annotation with different evidence. Reason: While this duplicates the IBA annotation, the IEA annotation correctly captures the same function from automated pipelines. The annotation is accurate. Supporting Evidence: PMID:30784582 MAP7D2 Localizes to the Proximal Axon and Locally Promotes Kinesin-1-Mediated Cargo Transport into the Axon |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation based on ortholog data. Kikuchi et al. 2022 showed that MAP7D2 is prominent at centrosomes in neuronal cell lines. UniProt also notes centrosomal localization based on similarity evidence. Reason: Centrosome localization is supported by experimental data from mouse orthologs and is consistent with MAP7D2's role as a microtubule-associated protein. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 is prominent at centrosomes and partially along microtubules |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProtKB subcellular location mapping. This is a broader term than GO:0015630 (microtubule cytoskeleton). Reason: While this is a more general term than the microtubule cytoskeleton annotation, it is not incorrect. MAP7D2 is indeed a cytoskeleton-associated protein. The more specific microtubule cytoskeleton annotation provides better granularity. Supporting Evidence: UniProt:Q96T17 Cytoplasm, cytoskeleton |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation from combined automated methods, duplicating the IBA annotation. Well-supported by ortholog data. Reason: Accurate annotation consistent with the IBA evidence. MAP7D2 functions at the microtubule cytoskeleton. Supporting Evidence: PMID:30784582 MAP7D2 Localizes to the Proximal Axon and Locally Promotes Kinesin-1-Mediated Cargo Transport into the Axon |
| GO:0030424 axon | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation based on ortholog data. This is strongly supported by experimental evidence. Pan et al. 2019 demonstrated that MAP7D2 accumulates at the proximal axon in hippocampal neurons, and this localization is critical for its function in gating kinesin-1-mediated transport. Reason: Axon localization is a core aspect of MAP7D2 function and is directly supported by published experimental evidence from PMID:30784582 (Pan et al. 2019). Supporting Evidence: PMID:30784582 MAP7D2-N) accumulates at the proximal axon file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 localizes to the proximal axon and locally promotes kinesin-1-mediated cargo transport into the axon |
| GO:0030496 midbody | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IEA annotation based on ortholog data. Kikuchi et al. 2022 showed MAP7D2 accumulates at the midbody during cytokinesis. UniProt confirms this localization by similarity. Reason: Midbody localization during cytokinesis is a secondary aspect of MAP7D2 function, not its core role in axonal transport. The annotation is accurate but represents a non-core function. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md accumulates at the midbody during cytokinesis |
| GO:0043005 neuron projection | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation based on ortholog data. MAP7D2 localizes to neuron projections, particularly the axon. This is consistent with its primary role in neurons. Reason: Neuron projection localization is accurate and represents a core aspect of MAP7D2 function in neuronal cells. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 concentrates at the proximal axon (overlapping the AIS region) in developing hippocampal neurons |
| GO:0005874 microtubule | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation from Ensembl Compara ortholog transfer. MAP7D2 directly binds microtubules via its N-terminal domain. Kikuchi et al. 2022 determined binding affinity (KD ~6x10^-7 M). Reason: Microtubule localization is fundamental to MAP7D2 function. The protein directly binds microtubules as demonstrated biochemically. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md Microtubule co-sedimentation determined an apparent KD on the order of ~6x10^-7 M |
| GO:0008017 microtubule binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation from combined automated methods. Microtubule binding is a core molecular function of MAP7D2, mediated by the N-terminal region. Reason: This is a core molecular function of MAP7D2. The protein binds microtubules directly and this binding is essential for its function in kinesin-1 recruitment. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 directly binds microtubules via its N-terminal half |
| GO:0019894 kinesin binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation from combined automated methods. MAP7D2 interacts with kinesin-1 family members (KIF5A, KIF5B, KIF5C) through its C-terminal domain. This interaction is critical for promoting kinesin-1-mediated axonal transport. Reason: Kinesin binding is a core molecular function of MAP7D2. The protein serves as a cofactor that recruits and activates kinesin-1 on microtubules. Supporting Evidence: PMID:30784582 Kinesin-1-Mediated Cargo Transport into the Axon file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7 family proteins regulate kinesin-1 recruitment and activation |
| GO:0061564 axon development | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation from Ensembl Compara. MAP7D2 contributes to axon development by facilitating polarized entry of cargoes into axons, supporting axon formation and branching. Reason: Axon development is a core biological process for MAP7D2. The protein's role in kinesin-1-mediated cargo transport at the proximal axon directly contributes to axon development and neuronal polarity. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 facilitates polarized entry of cargoes (mitochondria, lysosomes, ER-derived organelles) into axons, thereby contributing to axon formation, branching, and neuronal migration |
| GO:0140778 microtubule stabilizing activity | IEA GO_REF:0000107 | ACCEPT | Summary: IEA annotation from Ensembl Compara. MAP7D2 stabilizes microtubules through direct binding. Kikuchi et al. 2022 showed that MAP7D2 loss reduces nocodazole resistance (indicating reduced MT stability). Reason: Microtubule stabilizing activity is a core molecular function of MAP7D2. This has been directly demonstrated experimentally. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 directly binds microtubules via its N-terminal half and stabilizes microtubules |
| GO:0000226 microtubule cytoskeleton organization | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to rat ortholog (D4A4L4). This duplicates the IBA annotation with different evidence type. Reason: The annotation accurately captures MAP7D2's role in microtubule cytoskeleton organization. ISS evidence from well-characterized orthologs is reliable. Supporting Evidence: PMID:30784582 MAP7D2 Localizes to the Proximal Axon and Locally Promotes Kinesin-1-Mediated Cargo Transport into the Axon |
| GO:0008017 microtubule binding | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity. Duplicates the IEA annotation. Microtubule binding is well-established for MAP7D2. Reason: Core molecular function accurately captured. The ISS evidence provides additional confidence from ortholog studies. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2's N-terminus binds microtubules |
| GO:0019894 kinesin binding | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity. Duplicates the IEA annotation. Kinesin binding is a core function of MAP7D2. Reason: Core molecular function. MAP7D2 binding to kinesin-1 family members is essential for its biological role. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 interacts with kinesin-1 family members (KIF5A/B/C) |
| GO:0061564 axon development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity. Duplicates the IEA annotation. Axon development is a core process for MAP7D2. Reason: Core biological process. MAP7D2's role in axon development through kinesin-1 recruitment is well-documented. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md contributing to axon formation, branching, and neuronal migration |
| GO:0005813 centrosome | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to mouse ortholog (A2AG50). Duplicates the IEA annotation. Centrosome localization is documented. Reason: Accurate cellular localization supported by ortholog studies. Centrosome localization is consistent with MAP7D2's role in microtubule organization. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 is prominent at centrosomes |
| GO:0005874 microtubule | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity. Duplicates the IEA annotation. MAP7D2 localizes to microtubules via direct binding. Reason: Core cellular localization. MAP7D2 directly binds and localizes to microtubules. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 directly binds microtubules via its N-terminal half |
| GO:0030496 midbody | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation based on sequence similarity. Duplicates the IEA annotation. Midbody localization during cytokinesis is documented. Reason: Accurate localization but represents a non-core function. Midbody accumulation during cytokinesis is secondary to MAP7D2's primary role in axonal transport. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md accumulates at the midbody during cytokinesis |
| GO:0043005 neuron projection | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity. Duplicates the IEA annotation. MAP7D2 localizes to neuron projections, especially axons. Reason: Core cellular localization for MAP7D2's function in neurons. Supporting Evidence: file:human/MAP7D2/MAP7D2-deep-research-falcon.md MAP7D2 concentrates at the proximal axon (overlapping the AIS region) in developing hippocampal neurons |
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Download this section (compressed HTML)Q: Does MAP7D2 have specific roles in inner ear hair cells beyond general kinesin-1 recruitment, given the GWAS association with hearing loss?
Q: What is the relationship between MAP7D2 and other MAP7 family members in regulating axonal transport - are they redundant or do they have distinct cargo specificities?
Q: Does MAP7D2 play a role in non-neuronal cell types, given its expression in brain and epididymis?
Experiment: Conditional knockout of MAP7D2 in mouse inner ear to validate hearing loss phenotype
Hypothesis: Loss of MAP7D2 in inner ear cells leads to hearing impairment due to disrupted intracellular transport
Experiment: Live imaging of cargo transport in neurons with MAP7D2 depletion to determine cargo specificity
Hypothesis: MAP7D2 has cargo-specific roles in axonal transport distinct from other MAP7 family members
Experiment: Structure determination of MAP7D2-microtubule and MAP7D2-kinesin-1 complexes to understand molecular mechanism
Hypothesis: MAP7D2 binds simultaneously to microtubules and kinesin-1 to facilitate motor protein recruitment
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