MAP7D1 (MAP7 domain-containing protein 1) is a microtubule-associated protein of the MAP7 family that serves dual roles in cytoskeletal function. The protein contains an N-terminal MAP7 domain that binds the microtubule lattice and a C-terminal coiled-coil region that binds and activates kinesin-1 (KIF5). MAP7D1 functions as a microtubule-tethered adaptor and activator for kinesin-1, increasing kinesin-1 microtubule landing rate and processivity, thereby promoting plus-end-directed cargo transport. In neuronal cells, MAP7D1 specifically maintains acetylated, stable microtubules and regulates cell motility and neurite outgrowth. MAP7D1 also participates in Wnt5a signaling by binding Dishevelled (Dvl) and facilitating cortical microtubule remodeling. The protein localizes to the spindle during mitosis, to the centrosome, midbody, and generally to the microtubule cytoskeleton. MAP7 family members (MAP7, MAP7D1, MAP7D3) function redundantly in kinesin-1 recruitment, though MAP7D1 has distinct roles in microtubule stabilization through acetylation maintenance. Recent studies also implicate MAP7D1 in DNA double-strand break repair during G1 phase.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000226 microtubule cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: MAP7D1 is a microtubule-associated protein that plays key roles in microtubule organization. Studies show MAP7D1 maintains acetylated stable microtubules and regulates microtubule dynamics. Loss of MAP7D1 increases microtubule dynamics and alters cell motility (Kikuchi et al. 2022). The IBA annotation based on phylogenetic inference is well-supported by direct experimental evidence from the deep research review. Reason: This annotation accurately reflects the core function of MAP7D1. Multiple studies demonstrate that MAP7D1 is required for maintenance of acetylated/stable microtubules, and loss of MAP7D1 reduces MT stability and alters microtubule dynamics (Kikuchi et al. 2022). The MAP7 family proteins including MAP7D1 are essential for proper microtubule cytoskeleton function and kinesin-1-dependent transport. Supporting Evidence: file:human/MAP7D1/MAP7D1-deep-research-falcon.md MAP7D1 is required for maintenance of acetylated/stable microtubules; loss of Map7D1 reduces MT stability and alters cell migration and neurite outgrowth |
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: MAP7D1 is a member of the MAP7 family of microtubule-associated proteins. It contains an N-terminal MAP7 domain that binds the microtubule lattice. Multiple studies confirm its localization to the microtubule cytoskeleton. Reason: This cellular component annotation is well-supported. MAP7D1 binds microtubules via its N-terminal MAP7 domain and is consistently found associated with the microtubule cytoskeleton. Hooikaas et al. (2019) demonstrated that MAP7 family proteins engage microtubules and are required for kinesin-1 recruitment to microtubules. Supporting Evidence: file:human/MAP7D1/MAP7D1-deep-research-falcon.md MAP7-family proteins bind microtubules via an N-terminal MT-binding domain and bind kinesin-1 via a C-terminal domain |
| GO:0000226 microtubule cytoskeleton organization | IEA GO_REF:0000002 | ACCEPT | Summary: This IEA annotation based on InterPro mapping (IPR008604, MAP7 family) correctly identifies the biological process. The MAP7 family domain is specifically associated with microtubule organization functions. Reason: The InterPro-based inference is accurate. The MAP7 domain (IPR008604) is indeed associated with microtubule binding and organization. This is redundant with the IBA annotation but is an independent line of evidence supporting the same function. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location annotation indicates centrosome localization based on inference from mouse ortholog (UniProtKB:A2AJI0). This is consistent with MAP7D1's role in microtubule organization and its presence in the mitotic spindle. Reason: The centrosome localization is consistent with MAP7D1's function as a microtubule-associated protein. UniProt annotation states centrosome localization based on sequence similarity to mouse ortholog, which is well-supported given the conserved function of MAP7 family proteins. |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location annotation indicates spindle localization. This is strongly supported by the IDA annotation from PMID:15561729 which directly identified MAP7D1 (as KIAA1187) at the mitotic spindle. Reason: This annotation is consistent with and redundant with the IDA annotation from PMID:15561729. Spindle localization is well-established for MAP7D1. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: General cytoskeleton localization based on UniProt subcellular location vocabulary. While accurate, this is a very broad term when more specific terms apply. Reason: This annotation is too general. MAP7D1 is specifically associated with the microtubule cytoskeleton, not the general cytoskeleton. More specific terms (GO:0015630 microtubule cytoskeleton, GO:0005819 spindle) are more appropriate. Keep as non-core since it is technically true but not informative. |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation for microtubule cytoskeleton localization via MAP7 family domain. Redundant with IBA annotation but represents independent evidence. Reason: This IEA annotation correctly captures microtubule cytoskeleton localization based on the MAP7 domain. Redundant with the IBA but provides independent computational support. |
| GO:0030496 midbody | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location annotation indicates midbody localization, based on inference from mouse ortholog. The midbody is formed during cytokinesis and contains microtubules. Reason: Midbody localization is consistent with MAP7D1's role as a microtubule-associated protein and its presence in the spindle apparatus. UniProt annotation is based on sequence similarity to mouse ortholog. |
| GO:0005515 protein binding | IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by... | REMOVE | Summary: Large-scale protein-protein interaction mapping study using immunoprecipitation and mass spectrometry. This is an uninformative annotation that does not capture the specific binding partners or functional context. Reason: The term 'protein binding' (GO:0005515) is uninformative and does not provide insight into the molecular function of MAP7D1. The protein has well-characterized specific binding partners including kinesin-1 (KIF5) and Dishevelled (Dvl). A more informative annotation would be kinesin binding (GO:0019894) or microtubule binding (GO:0008017). Supporting Evidence: PMID:17353931 Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions |
| GO:0005515 protein binding | IPI PMID:21150319 Proteomic profiling of Myc-associated proteins | REMOVE | Summary: This annotation comes from a proteomics study of Myc-associated proteins. MAP7D1 was identified as a putative c-Myc interactor in a large-scale TAP-MS screen. The study found cytoskeletal proteins including microtubule-associated proteins among Myc interactors. However, this may represent an indirect or context-specific interaction rather than a core function. Reason: The term 'protein binding' is uninformative. This annotation is based on a high-throughput proteomics screen where MAP7D1 was found as a putative Myc interactor. The publication explicitly states these are "putative" interactors and the interaction may be indirect (possibly via cytoskeletal scaffolds). More specific MF terms like kinesin binding or microtubule binding should be used instead. Supporting Evidence: PMID:21150319 Combined data from multiple biological replicates provided a dataset of 418 non-redundant proteins, 389 of which are putative novel interactors |
| GO:0000226 microtubule cytoskeleton organization | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on manual transfer from mouse ortholog (UniProtKB:A2AJI0). This is consistent with the IBA annotation and direct evidence from multiple studies. Reason: This annotation is well-supported by sequence similarity to mouse ortholog and is consistent with direct experimental evidence for MAP7D1 function in microtubule organization. The mouse ortholog has experimentally verified function in microtubule stabilization. |
| GO:0005813 centrosome | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation for centrosome localization based on sequence similarity to mouse ortholog. Consistent with MAP7D1's role in microtubule organization from the centrosome. Reason: This annotation is consistent with the experimentally verified localization of the mouse ortholog and the general function of MAP7D1 as a microtubule-associated protein that organizes microtubules emanating from the centrosome. |
| GO:0005819 spindle | IDA PMID:15561729 Proteome analysis of the human mitotic spindle | ACCEPT | Summary: Direct experimental evidence from proteome analysis of the human mitotic spindle. Sauer et al. (2005) identified MAP7D1 (as KIAA1187) as a spindle component through mass spectrometry and confirmed its localization by tagging and imaging in transfected mitotic cells. Reason: This is strong experimental evidence. The publication describes purification of human mitotic spindles followed by MS/MS identification, where MAP7D1 (KIAA1187) was identified and then confirmed as a genuine spindle component through GFP-tagging and localization in mitotic cells. Supporting Evidence: PMID:15561729 Of these uncharacterized proteins, 17 were tagged and localized in transfected mitotic cells, resulting in the identification of six genuine spindle components (KIAA0008, CdcA8, KIAA1187, FLJ12649, FLJ90806, and C20Orf129) |
| GO:0008017 microtubule binding | IDA file:human/MAP7D1/MAP7D1-deep-research-falcon.md | NEW | Summary: MAP7D1 contains an N-terminal MAP7 domain that directly binds microtubules. This has been demonstrated through purified protein reconstitution experiments (Hooikaas et al. 2019). Reason: This molecular function annotation is missing from the current annotation set but is well-supported by experimental evidence. The MAP7 N-terminal domain directly binds the microtubule lattice. Supporting Evidence: file:human/MAP7D1/MAP7D1-deep-research-falcon.md MAP7 family proteins (including MAP7D1) bind microtubules via an N-terminal MT-binding domain and bind kinesin-1 via a C-terminal domain to increase kinesin-1 microtubule landing rate and processivity |
| GO:0019894 kinesin binding | IDA file:human/MAP7D1/MAP7D1-deep-research-falcon.md | NEW | Summary: MAP7D1 binds kinesin-1 (KIF5) through its C-terminal region. This interaction is critical for kinesin-1 recruitment to microtubules and activation of processive transport. Reason: Kinesin binding is a core molecular function of MAP7D1. The protein recruits and activates kinesin-1 through direct binding. This should replace the uninformative 'protein binding' annotation. Supporting Evidence: file:human/MAP7D1/MAP7D1-deep-research-falcon.md MAP7-family proteins bind the kinesin-1 stalk via a C-terminal domain; purified-protein reconstitution showed that MAP7 family proteins increase kinesin-1 microtubule landing rate and processivity |
| GO:1901610 positive regulation of vesicle transport along microtubule | IDA file:human/MAP7D1/MAP7D1-deep-research-falcon.md | NEW | Summary: MAP7D1 positively regulates kinesin-1-mediated transport along microtubules. At least one MAP7 family member is required for kinesin-1 transport, and MAP7D1 increases kinesin processivity and landing rate. Reason: This biological process annotation captures the functional consequence of MAP7D1's molecular activities (microtubule binding and kinesin binding). MAP7D1 is essential for enabling kinesin-1-driven transport. Supporting Evidence: file:human/MAP7D1/MAP7D1-deep-research-falcon.md In HeLa cells, at least one MAP7-family member (including MAP7D1) is necessary and sufficient to enable kinesin-1-driven transport. Family members elevate KIF5B landing frequency and processivity. |
| GO:0007026 negative regulation of microtubule depolymerization | ISS file:human/MAP7D1/MAP7D1-deep-research-falcon.md | NEW | Summary: MAP7D1 stabilizes microtubules through maintenance of acetylated stable microtubule population. Loss of MAP7D1 increases microtubule dynamics. Reason: MAP7D1 functions to stabilize microtubules and prevent their depolymerization. This is distinct from the general 'microtubule cytoskeleton organization' term and captures the specific stabilization function. Supporting Evidence: file:human/MAP7D1/MAP7D1-deep-research-falcon.md MAP7D1 is required for maintenance of acetylated/stable microtubules; loss of Map7D1 reduces MT stability and increases microtubule dynamics |
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Download this section (compressed HTML)Q: Does MAP7D1 have preference for specific microtubule subpopulations based on tubulin PTMs?
Q: What is the relationship between MAP7D1's kinesin-1 activation function and its role in maintaining acetylated microtubules?
Q: Is the DNA damage response function of MAP7D1 dependent on its microtubule binding activity?
Q: How do MAP7 family members partition their functions in different cell types and contexts?
Experiment: In vitro reconstitution experiments with purified MAP7D1 and acetylated vs detyrosinated microtubules to determine substrate preferences
Hypothesis: MAP7D1 preferentially binds acetylated microtubules
Type: biochemical assay
Experiment: Structure determination of MAP7D1 MAP7 domain bound to microtubule lattice
Hypothesis: MAP7D1 binds a specific site on the microtubule lattice
Type: structural biology
Experiment: Time-resolved proteomics to identify MAP7D1 interactome during DNA damage response
Hypothesis: MAP7D1 interacts with additional DDR proteins beyond RAD50, BRCA1, and 53BP1
Type: proteomics
Experiment: Comparison of MAP7D1 and MAP7D2 knockout phenotypes in neuronal differentiation assays
Hypothesis: MAP7D1 and MAP7D2 have distinct roles in neuronal development
Type: cell biology
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