MAP7D3 (MAP7 domain-containing protein 3, also known as MDP3) is a microtubule-associated protein belonging to the MAP7 family. It promotes microtubule assembly and stability through direct binding to tubulin and microtubules via two distinct regions: N-terminal coiled-coil domains and a C-terminal MAP7 domain with C-terminal tail. The C-terminal region (MDCT) binds microtubules with Kd ~3.0 uM by engaging the tubulin C-terminal tails and competes with tau for overlapping binding sites. MAP7D3 also recruits and activates kinesin-1 motor protein through its MAP7 domain, enhancing kinesin-1 landing rate and processivity on microtubules. Unlike other MAP7 family members, MAP7D3 can be co-transported with kinesin-1 due to its higher kinesin affinity and lower microtubule affinity. Additionally, MAP7D3 modulates HDAC6 activity to maintain tubulin acetylation. The protein localizes to the mitotic spindle and microtubule cytoskeleton throughout mitosis, with expression varying during the cell cycle.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000226 microtubule cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation based on phylogenetic inference. MAP7D3 is a well-established member of the MAP7 family that regulates microtubule organization through promoting assembly and stability (PMID:22142902, PMID:24927501). This annotation is supported by experimental evidence from other annotations and is phylogenetically consistent with MAP7 family function. Reason: The IBA annotation accurately captures MAP7D3's role in microtubule cytoskeleton organization. Direct experimental evidence demonstrates that MAP7D3 regulates cellular microtubule assembly in cold recovery and nocodazole washout assays (PMID:22142902) and promotes microtubule polymerization in vitro (PMID:24927501). This function is conserved across MAP7 family members. Supporting Evidence: PMID:22142902 Cold recovery and nocodazole washout assays further demonstrated an important role for Mdp3 in regulating cellular microtubule assembly. PMID:24927501 It was shown to promote the assembly and stability of microtubules in vitro as well as in cells file:human/MAP7D3/MAP7D3-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for cellular component localization. MAP7D3 localizes to microtubules throughout mitosis and associates with the microtubule cytoskeleton as demonstrated by immunofluorescence microscopy and cosedimentation assays (PMID:22142902). Reason: The cellular component annotation is well-supported. Experimental evidence shows MAP7D3 associates with microtubules and localizes to the microtubule cytoskeleton throughout mitosis. UniProt confirms subcellular location at microtubules throughout mitosis. Supporting Evidence: PMID:22142902 Immunofluorescence microscopy and microtubule cosedimentation assays revealed that Mdp3 also associated with microtubules. |
| GO:0000226 microtubule cytoskeleton organization | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation based on InterPro domain mapping (IPR008604 - MAP7 family). This is a broader automated annotation that is consistent with the IBA and IDA annotations for the same term. Reason: While this is an automated annotation based on domain presence, it is consistent with experimental evidence and the IBA annotation. The MAP7 domain (IPR008604) is characteristic of proteins involved in microtubule cytoskeleton organization. |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProt subcellular location mapping. MAP7D3 was identified in proteome analysis of the mitotic spindle and localizes to the spindle upon overexpression (PMID:15561729, PMID:24927501). Reason: UniProt explicitly states MAP7D3 localizes to the spindle (Cytoplasm, cytoskeleton, spindle) based on experimental evidence from PMID:15561729. This annotation is appropriately derived from the UniProt subcellular location vocabulary. Supporting Evidence: PMID:24927501 MAP7D3 was identified during the proteome analysis of mitotic spindle of HeLa cells and shown to localize at the mitotic spindle upon overexpression [25]. |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation based on InterPro domain mapping. This is consistent with the IBA annotation for the same cellular component term. Reason: The automated annotation based on MAP7 family domain presence is consistent with experimental evidence showing MAP7D3 localizes to microtubules. This annotation is appropriately redundant with the IBA annotation. |
| GO:0046785 microtubule polymerization | IDA PMID:24927501 C-terminal region of MAP7 domain containing protein 3 (MAP7D... | ACCEPT | Summary: Direct experimental evidence showing MAP7D3's C-terminal region promotes microtubule polymerization. Yadav et al. (2014) demonstrated that the MDCT fragment containing the MAP7 domain and C-terminal tail promotes tubulin polymerization in vitro through light scattering assays and sedimentation assays. Reason: This is a core function of MAP7D3. The paper provides compelling in vitro evidence using purified proteins that MAP7D3 promotes microtubule polymerization. The MDCT fragment was shown to promote polymerization more effectively than the individual MD or CT domains, and this activity was dependent on the tubulin C-terminal tail. This represents a more specific annotation than the broader "microtubule cytoskeleton organization" term. Supporting Evidence: PMID:24927501 a longer fragment MDCT that contained the MAP7 domain (MD) with the C-terminal tail (CT) of the protein promoted microtubule polymerization to a greater extent than MD and CT individually. PMID:24927501 Tubulin (10 µM) was incubated without and with 1, 2 and 4 µM MDCT in PEM buffer for 5 min on ice. Subsequently, 1 mM GTP was added to the sample and the assembly kinetics was monitored at 37°C by 90° light scattering |
| GO:0000226 microtubule cytoskeleton organization | IDA PMID:22142902 Mdp3 is a novel microtubule-binding protein that regulates m... | ACCEPT | Summary: Direct experimental evidence from Sun et al. (2011) demonstrating MAP7D3 (Mdp3) regulates microtubule assembly and stability in cells. Cold recovery and nocodazole washout assays showed its role in cellular microtubule assembly, and the protein enhanced microtubule stability. Reason: This IDA annotation is well-supported by experimental data. The paper established MAP7D3 as a novel microtubule-binding protein through multiple complementary approaches including GST-pulldown, immunofluorescence, cosedimentation, cold recovery, and nocodazole washout assays. This is a core function of the protein. Supporting Evidence: PMID:22142902 Cold recovery and nocodazole washout assays further demonstrated an important role for Mdp3 in regulating cellular microtubule assembly. Our data also showed that Mdp3 significantly enhanced the stability of cellular microtubules. |
| GO:0008017 microtubule binding | IDA PMID:22142902 Mdp3 is a novel microtubule-binding protein that regulates m... | ACCEPT | Summary: Core molecular function annotation. Sun et al. (2011) demonstrated direct binding of MAP7D3 to microtubules through multiple experimental approaches including microtubule cosedimentation assays, GST-pulldown, and immunofluorescence microscopy. Reason: This is the primary molecular function of MAP7D3 as a microtubule-associated protein. The evidence from PMID:22142902 is direct and compelling, showing that MAP7D3 associates with microtubules through its N-terminal coiled-coil domains. Additional support comes from PMID:24927501 showing the C-terminal region also binds microtubules with Kd ~3.0 uM. Supporting Evidence: PMID:22142902 Immunofluorescence microscopy and microtubule cosedimentation assays revealed that Mdp3 also associated with microtubules. Serial deletion experiments showed that the two coiled coil motifs of Mdp3 were critical for its interaction with tubulin and microtubules. PMID:24927501 MDCT bound to reconstituted microtubules with an apparent dissociation constant of 3.0 ± 0.5 µM. |
| GO:0015631 tubulin binding | IDA PMID:22142902 Mdp3 is a novel microtubule-binding protein that regulates m... | ACCEPT | Summary: Molecular function annotation for direct tubulin binding. GST-pulldown assays demonstrated that MAP7D3 interacts with tubulin both in cells and in vitro (PMID:22142902). Additional evidence from PMID:24927501 shows binding to tubulin C-terminal tails and competition with tau. Reason: This annotation captures the direct binding of MAP7D3 to tubulin subunits. While microtubule binding (GO:0008017) is also annotated, tubulin binding is distinct as it can refer to binding of soluble tubulin dimers. The evidence shows MAP7D3 binds both soluble tubulin and polymerized microtubules through its coiled-coil domains. Supporting Evidence: PMID:22142902 by GST-pulldown assays, we found that Mdp3 interacted with tubulin both in cells and in vitro. PMID:24927501 Competition experiments with tau indicated that MDCT shares its binding site on microtubules with tau. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: HDA annotation from high-throughput mass spectrometry proteomics study of NK cell membranes. MAP7D3 was identified among 1843 proteins in membrane fractions, though it is predicted to be transiently associated with membranes rather than being an integral membrane protein. Reason: This annotation is not incorrect - MAP7D3 was detected in membrane proteomics experiments. However, MAP7D3 is primarily a cytoskeletal protein that localizes to microtubules and the spindle. The membrane association is likely transient or reflects association with membrane-associated microtubules rather than direct membrane localization. This is not a core localization for the protein. UniProt also lists membrane (HDA) but the primary localization is cytoplasm/cytoskeleton/spindle. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. |
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