ASPM is a large calmodulin-associated microtubule protein concentrated at mitotic spindle poles and microtubule minus ends. It contributes to spindle organization and orientation through a conserved mechanism that limits minus-end growth and recruits katanin to microtubules, enhancing katanin-mediated severing. Human ASPM also occupies interphase nuclei and late-mitotic midbodies; its requirement for spindle-pole focusing varies with compensating factors such as CDK5RAP2. Biallelic pathogenic ASPM variants cause autosomal recessive primary microcephaly type 5 (MCPH5).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000922 spindle pole | IEA GO_REF:0000107 | ACCEPT | Summary: Conserved spindle-pole localization. Reason: The mouse orthology transfer agrees with direct antibody localization of endogenous human ASPM at mitotic spindle poles. |
| GO:0005516 calmodulin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Calmodulin association supports the conserved binding function. Reason: Mouse ASPM associates with calmodulin in oocytes and fibroblasts and co-purifies with calmodulin for functional reconstitution. In PMID:28436967, endogenous ASPM was tagged by CRISPR in cultured human cells; affinity isolation from mitotic cells followed by mass spectrometry also recovered calmodulin. This human co-association corroborates the existing orthology transfer. Neither cellular co-purification nor the mouse reconstitution is an isolated human binary-binding assay. |
| GO:0005634 nucleus | IDA PMID:21044324 Human ASPM participates in spindle organisation, spindle ori... | KEEP AS NON CORE | Summary: An interphase nuclear pool is directly observed. Reason: Endogenous human ASPM is predominantly nuclear during interphase and redistributes after nuclear-envelope breakdown. This is a cell-cycle-dependent pool, distinct from its best-characterized mitotic microtubule activity. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The nuclear vocabulary mapping agrees with human staining. Reason: The electronic location assignment is corroborated by endogenous interphase nuclear staining. A distinct nuclear molecular activity is not established by that localization. Supporting Evidence: |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Broad cytoplasmic occurrence is compatible with spindle association. Reason: ASPM occurs in cytoplasmic microtubule-associated structures; the broad location is consistent with the mouse donor and human mitotic staining. The more informative spindle-pole and minus-end locations define the central mechanism. |
| GO:0005813 centrosome | IEA GO_REF:0000107 | ACCEPT | Summary: Centrosomal association is cell-cycle dependent. Reason: The rat-donor source also demonstrates endogenous HeLa prophase centrosomal localization. Human mitotic ASPM surrounds the gamma-tubulin core in a pole-proximal ring, whereas the later study did not detect interphase centrosomal ASPM. These observations support the broad term without making ASPM a constitutive centriolar component. |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: The spindle location is directly corroborated. Reason: Endogenous human ASPM localizes to mitotic spindle poles and later spindle structures, supporting the existing subcellular-vocabulary mapping. |
| GO:0005874 microtubule | IEA GO_REF:0000120 | ACCEPT | Summary: ASPM associates with spindle microtubules and their minus ends. Reason: Human spindle staining depends on intact microtubules, and endogenous ASPM is recruited to newly exposed microtubule minus ends. This corroborates the component assertion from ARBA and mouse orthology. |
| GO:0007051 spindle organization | IEA GO_REF:0000117 | ACCEPT | Summary: Direct human experiments support the spindle-organization prediction. Reason: ASPM depletion and C-terminal dominant-negative fragments disrupt human spindle organization. The electronic assertion is consistent with this independently observed structural role. Supporting Evidence: |
| GO:0007051 spindle organization | IMP PMID:21044324 Human ASPM participates in spindle organisation, spindle ori... | ACCEPT | Summary: Human perturbations support spindle organization. Reason: Depletion and C-terminal-fragment experiments support participation in spindle organization. The later finding that CDK5RAP2 compensates for ASPM loss makes dependence context-sensitive without negating the role of ASPM. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: Apical occurrence is supported, but the membrane domain remains unresolved. Reason: The traced rat source reports ASPM at the ventricular apical surface and identifies aurora-B/CITK-positive midbody rings there. The inspected indexed legends and targeted passages establish apical occurrence but do not settle the plasma-membrane domain assignment; complete original Results, controls and figure pixels were not accessible. The positive donor evidence is retained. This incomplete assessment does not demonstrate that the curator over-annotated membrane residence. Supporting Evidence: |
| GO:0030496 midbody | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Midbody localization is supported in late mitosis. Reason: Human late-mitotic staining corroborates the rat and mouse midbody transfers. The specific late-cytokinesis mechanism remains less resolved than the spindle-pole/minus-end function. |
| GO:0036449 microtubule minus-end | IDA PMID:21044324 Human ASPM participates in spindle organisation, spindle ori... | ACCEPT | Summary: Direct human evidence supports microtubule minus-end localization. Reason: Pole-proximal and central-spindle staining, redistribution after microtubule perturbation, and subsequent recruitment to newly exposed ends support minus-end association in human cells. |
| GO:0051445 regulation of meiotic cell cycle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse oocyte experiments support the meiotic context. Reason: Mouse ASPM morpholino treatment disrupts meiotic spindle organization and progression. Retain the human orthology transfer as a germ-cell context; this evidence does not establish direct human oocyte activity or a specific checkpoint mechanism. Supporting Evidence: |
| GO:0051653 spindle localization | IMP PMID:21044324 Human ASPM participates in spindle organisation, spindle ori... | MODIFY | Summary: Refine spindle localization to establishment of mitotic spindle orientation. Reason: Live imaging of ASPM-depleted human U2OS cells in the original PMID:21044324 measures division-axis alignment relative to the culture dish. Human knockout and ASPM-katanin interface experiments in PMID:28436967 independently show spindle misorientation. Targeted HeLa experiments in PMID:27562601 connect ASPM-dependent CITK recruitment and astral microtubules to the same orientation phenotype. GO:0000132 names this mitotic alignment process more precisely than the broader source term. The original asymmetric-division category describes geometry, not a measured change in daughter-cell fate. Proposed replacements: establishment of mitotic spindle orientation |
| GO:0072687 meiotic spindle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse donor localizes to the meiotic spindle. Reason: Mouse oocyte staining places ASPM along meiotic spindle microtubules. The existing human orthology transfer is retained as context-specific localization. Supporting Evidence: |
| GO:0097431 mitotic spindle pole | IDA PMID:15972725 The microcephaly ASPM gene is expressed in proliferating tis... | ACCEPT | Summary: The original source reports human mitotic-pole staining. Reason: The original study explicitly reports antibody localization at mitotic spindle poles in cultured human cells; the later human study independently corroborates this location. |
| GO:0097431 mitotic spindle pole | IDA PMID:21044324 Human ASPM participates in spindle organisation, spindle ori... | ACCEPT | Summary: Endogenous human ASPM localizes to mitotic spindle poles. Reason: Human-cell antibody staining places ASPM at pole-proximal spindle microtubules. The distribution surrounds rather than exactly overlaps the gamma-tubulin core. Supporting Evidence: |
| GO:0097431 mitotic spindle pole | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic mitotic-pole assertion is corroborated. Reason: Direct human localization agrees with the combined ARBA, rat and mouse evidence for mitotic spindle poles. |
| GO:0051011 microtubule minus-end binding | ISS PMID:28436967 Microtubule minus-end regulation at spindle poles by an ASPM... | NEW | Summary: Infer a conserved minus-end-binding activity from the mouse ortholog and human cellular recruitment. Reason: Purified short mouse ASPM with calmodulin binds and tracks microtubule minus ends, with ASPM domain mapping supporting its contribution. The same preparation slows minus-end growth and blocks outgrowth at higher concentrations; ASPM recruits katanin and enhances its severing activity. These are active outputs of ASPM association, while the ATP-dependent severing chemistry belongs to katanin. Endogenous human ASPM is recruited to newly generated minus ends in cells. Together these support a conserved molecular-function inference from the established mouse ortholog, not a purified human IDA or an isoform-specific human claim. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which human ASPM isoforms bind and track microtubule minus ends, and how do their calmodulin and katanin interactions differ?
Q: Does rat apical ASPM occupy the plasma-membrane domain or adjacent cytokinetic midbody structures?
Q: Which compensating spindle-pole factors determine the consequences of human ASPM loss in neural progenitors?
Q: Which direct late-cytokinesis activity, if any, does human ASPM perform beyond organizing spindle and midbody microtubules? The observed cytokinesis failures are not fully explained by spindle misorientation, but the executing mechanism remains unresolved.
Experiment: Reconstitute separately purified human ASPM isoforms with defined calmodulin and microtubules to measure minus-end binding and growth inhibition, then add katanin separately to quantify recruitment-dependent enhancement of severing.
Hypothesis: Human ASPM has conserved minus-end binding and growth-regulatory outputs, but the existing purified mouse preparation does not resolve the activities or concentration dependence of individual human isoforms.
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