Actl7a

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001669 acrosomal vesicle	ISO GO_REF:0000121	MODIFY	Summary: Actl7a sits in the subacrosomal layer between the acrosome and the nucleus, not inside the acrosomal vesicle. Refine to perinuclear theca, which the gene already carries. Reason: GO:0001669 is the lysosome-related, hydrolase-containing vesicle itself. The study that resolved Actl7a's position at confocal resolution placed it, with TES and Mena, in the subacrosomal layer that links the acrosome to the nuclear envelope, and explicitly corrected earlier coarser readings. GO's perinuclear theca (GO:0033011) definition includes that subacrosomal layer, and GO:0033011 is already on this gene by ISS and ISO. Light-microscope acrosomal signal in the mouse donor is consistent with the acroplaxome immediately beneath the acrosome, so the essence of the row (acrosome-associated location) is sound and only the term is wrong. GO has no acroplaxome term, which is why curators fall back to the acrosome term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: MGI:MGI:1343051 SUPPORTS SOURCE BUT NOT TARGET Mouse Actl7a carries acrosomal vesicle from acrosomal-region signal; the same work places the protein in the subacrosomal layer of the perinuclear theca, so the term rather than the transfer is the problem. Proposed replacements: perinuclear theca Supporting Evidence: PMID:21278383 We have now extended these earlier studies and shown that Arp7A is actually localized in the subacrosomal layer, which is also known as the acroplaxome PMID:21278383 all three proteins are actually localized in the subacrosomal layer that links the acrosome to the nuclear envelope
GO:0001669 acrosomal vesicle	ISO GO_REF:0000121	MODIFY	Summary: Same acrosome-versus-acroplaxome correction as the mouse-sourced row; here the donor is human ACTL7A, whose acrosomal-vesicle rows rest on light-microscope signal in patient sperm. Reason: The human donor's acrosomal annotations come from immunofluorescence and electron microscopy of patient sperm that also report perinuclear-theca defects. At high resolution the protein is in the subacrosomal layer, part of the perinuclear theca, which this gene already carries. The transfer to rat is sound; the term is not. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:Q9Y615 SUPPORTS SOURCE BUT NOT TARGET Human ACTL7A acrosomal-vesicle rows (PMID:34727571, PMID:32923619) rest on acrosomal-region signal; the subacrosomal layer is the resolved location. Proposed replacements: perinuclear theca Supporting Evidence: PMID:21278383 We have now extended these earlier studies and shown that Arp7A is actually localized in the subacrosomal layer, which is also known as the acroplaxome
GO:0001669 acrosomal vesicle	ISS GO_REF:0000024	MODIFY	Summary: UniProt similarity transfer from mouse Actl7a of the acrosome location; refine to perinuclear theca, as for the ISO rows. Reason: Same reasoning as the ISO rows. The rat UniProt entry itself states the subacrosomal-layer location, which is part of the perinuclear theca, so the acrosomal-vesicle GO mapping does not match the curated location text. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:Q9QY84 SUPPORTS SOURCE BUT NOT TARGET Mouse Actl7a location is real but is the subacrosomal layer, not the acrosomal vesicle. Proposed replacements: perinuclear theca Supporting Evidence: file:rat/Actl7a/Actl7a-uniprot.txt Detected at the subacrosomal layer in round spermatids. PMID:21278383 all three proteins are actually localized in the subacrosomal layer that links the acrosome to the nuclear envelope
GO:0001669 acrosomal vesicle	ISS GO_REF:0000024	MODIFY	Summary: UniProt similarity transfer from human ACTL7A of the acrosome location; refine to perinuclear theca, as for the other acrosomal-vesicle rows. Reason: Same reasoning as the other acrosomal-vesicle rows: the resolved location is the subacrosomal layer of the perinuclear theca, which this gene already carries. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:Q9Y615 SUPPORTS SOURCE BUT NOT TARGET Human ACTL7A acrosomal signal is the acroplaxome immediately beneath the acrosome. Proposed replacements: perinuclear theca Supporting Evidence: PMID:21278383 We have now extended these earlier studies and shown that Arp7A is actually localized in the subacrosomal layer, which is also known as the acroplaxome
GO:0001673 male germ cell nucleus	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Nuclear pool of Actl7a in spermatocytes and early spermatids, transferred from the mouse ortholog; a real but secondary location with no known nuclear activity. Reason: Mouse Actl7a carries this term by IDA (PMID:12672658), and the 2023 knock-out study confirmed an intranuclear pool from spermatocytes to step 9 spermatids by 3D confocal imaging. The protein is testis-specific, so germ-cell nucleus is as precise as warranted. No nuclear function has been shown; the activity is exercised in the perinuclear theca, so the row is non-core. Supporting Evidence: PMID:12672658 T-ACTIN-1 was found in the cytoplasm and T-ACTIN-2 was located in the nucleus PMID:36734600 Our intracellular localization data show ACTL7A to be dynamically present within the nucleus and subacrosomal space and later associated with postacrosomal regions of developing spermatids.
GO:0001675 acrosome assembly	ISO GO_REF:0000121	ACCEPT	Summary: Core process. Transferred from mouse Actl7a, which carries two independent IMP annotations; the protein is a structural component of the acroplaxome that anchors the developing acrosome. Reason: Actl7a passes the participation test for this process: it is itself a component of the acroplaxome, the structure that anchors the forming acrosome to the nuclear envelope, and it is required for the subacrosomal F-actin of that structure. Knock-out mice show abnormal acrosomal granule migration and acrosomes peeling from the nucleus. The rat protein is a one-to-one ortholog with an identical TES-binding segment, so the transfer is sound. Supporting Evidence: PMID:36734600 Through the generation of an Actl7a knock-out mouse model, we consistently observed disruption of acrosomal biogenesis with abnormal migration of the acrosomal granule and peeling acrosomes during spermatid elongation. PMID:36734600 In addition to the acrosomal granule displacement defects, we also observed acrosomes peeling off in Actl7a KO spermatids, suggesting that ACTL7A-dependent F-actins also play a structural role for acrosomal anchoring and development PMID:41169243 ACTL7A, another essential PT protein, is required for acrosome biogenesis and mediates the tethering of the acrosomal outer membrane to the nucleus.
GO:0001675 acrosome assembly	ISS GO_REF:0000024	ACCEPT	Summary: Core process; UniProt curator transfer from mouse Actl7a, duplicating the RGD ISO row. Reason: Same claim and same mouse evidence as the ISO row; the curated UniProt function text for this entry states the acrosome attachment and granule-stability requirement. Supporting Evidence: file:rat/Actl7a/Actl7a-uniprot.txt Required for normal sperm head morphology, acroplaxome formation, acrosome attachment, and acrosome granule stability. PMID:36734600 Through the generation of an Actl7a knock-out mouse model, we consistently observed disruption of acrosomal biogenesis with abnormal migration of the acrosomal granule and peeling acrosomes during spermatid elongation.
GO:0005198 structural molecule activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function at the level the PAINT curator chose for the ACTL7 clade: a structural component of the perinuclear theca, not a filament-forming actin. Reason: The IBA comes from the PANTHER node that carries the ACTL7 proteins (PTN008986528), placed below the ancestral actin node (PTN000940351). The PAINT curator gave the clade the general structural term rather than the actin-specific structural constituent of cytoskeleton, which matches the biology: Actl7a is an architectural component of the acroplaxome and is needed for its subacrosomal F-actin, but it does not form filaments when expressed in somatic cells, and no nucleotide binding or ATPase activity has been measured. Rat Actl7a is inside the clade and has no evidence of divergence from its orthologs, so the inherited function stands. Supporting Evidence: PMID:36734600 we propose that ACTL7A forms a unique testis-specific protein complex to anchor and stabilize acrosomal adherence to the acroplaxome at least in part by facilitating the presence of F-actin in the subacrosomal space PMID:21278383 In contrast, when expressed in HeLa cells, GFP-Arp7A is cytoplasmic and does not assemble into filaments or co-localize with and/or affect the localization of Tes and Mena at focal adhesions (data not shown). file:rat/Actl7a/Actl7a-uniprot.txt Belongs to the actin family.
GO:0005634 nucleus	IBA GO_REF:0000033	MODIFY	Summary: Nuclear presence is real for the testis-specific Actl7a, but only in germ cells; refine to male germ cell nucleus, which the gene already carries. No nuclear activity is known. Reason: The PAINT node spans nuclear ARP9-like actin-related proteins (yeast ARP9 and its Candida and trypanosome relatives) and mouse Actl7a, and mouse Actl7a's own nuclear pool is documented by immunofluorescence (PMID:12672658, PMID:36734600). Rat Actl7a is a testis-specific protein, so its nucleus is a male germ cell nucleus (GO:0001673, a descendant of nucleus), already annotated to this gene by ISO. The is_active_in qualifier overstates the evidence, because no nuclear activity of Actl7a has been demonstrated; the location is non-core. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1343051 SUPPORTS TRANSFER Mouse Actl7a has nucleus by EXP/IDA and male germ cell nucleus by IDA (PMID:12672658). SGD:S000004636 SUPPORTS SOURCE BUT NOT TARGET Yeast ARP9 is a nuclear chromatin-remodelling subunit; that nuclear activity is not shown for Actl7a. PANTHER:PTN008986520 NOT RELEVANT Internal PANTHER node, not a protein. Proposed replacements: male germ cell nucleus Supporting Evidence: PMID:36734600 Our intracellular localization data show ACTL7A to be dynamically present within the nucleus and subacrosomal space and later associated with postacrosomal regions of developing spermatids.
GO:0005634 nucleus	IEA GO_REF:0000044	MODIFY	Summary: Mapping of the UniProt Nucleus location; correct but general for a germ-cell-specific protein. Refine to male germ cell nucleus. Reason: The UniProt Nucleus location is itself a similarity transfer from mouse Actl7a. Actl7a is only expressed in testis germ cells, so the specific term male germ cell nucleus (already on the gene) states the same claim more precisely. Proposed replacements: male germ cell nucleus Supporting Evidence: PMID:12672658 T-ACTIN-1 was found in the cytoplasm and T-ACTIN-2 was located in the nucleus
GO:0005634 nucleus	ISO GO_REF:0000121	MODIFY	Summary: Ortholog transfer of the mouse nuclear pool; refine to male germ cell nucleus, the term the same donor carries by IDA. Reason: The mouse donor carries both nucleus and the more specific male germ cell nucleus; the rat ISO already includes the specific term, which is the appropriate level for a testis-specific protein. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1343051 SUPPORTS TRANSFER Mouse nuclear pool documented by immunofluorescence (PMID:12672658, PMID:36734600). Proposed replacements: male germ cell nucleus Supporting Evidence: PMID:36734600 Three-dimensional (3D) rendered confocal z-stacks of spermatids at different developmental steps illustrating a clear intranuclear localization pattern of the protein in spermatocytes, round spermatids, elongating spermatids, and condensing spermatids.
GO:0005634 nucleus	ISS GO_REF:0000024	MODIFY	Summary: UniProt similarity transfer of the mouse nuclear location (GOA carries this row twice); refine to male germ cell nucleus. Reason: Same claim as the ISO row. The donor's own specific term, male germ cell nucleus, is the appropriate level for a protein expressed only in spermatogenic cells. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q9QY84 SUPPORTS TRANSFER Mouse nuclear pool in spermatocytes and spermatids. Proposed replacements: male germ cell nucleus Supporting Evidence: PMID:12672658 T-ACTIN-1 was found in the cytoplasm and T-ACTIN-2 was located in the nucleus
GO:0005737 cytoplasm	EXP PMID:21278383 Molecular recognition of the Tes LIM2-3 domains by the actin...	MODIFY	Summary: True but general; Actl7a's cytoplasmic locations are the perinuclear theca and, transiently, the Golgi apparatus. The evidence code is questionable because the paper has no rat cytoplasmic observation. Reason: PMID:21278383 (full text read) studied rat Actl7a only by co-immunoprecipitation from rat testis extracts. Its localization data come from mouse testis sections and from GFP-tagged human Arp7A in HeLa cells, where it is diffusely cytoplasmic; neither is an experiment on the rat protein, so EXP on the rat entry should be ISS. The claim itself holds: the perinuclear theca is a cytoskeletal structure that is part of the cytoplasm, and the Golgi association is also cytoplasmic. Both specific terms are supported and already on the gene, so the row is refined to them rather than kept at the root. Proposed replacements: perinuclear theca Golgi apparatus Supporting Evidence: PMID:21278383 In contrast, when expressed in HeLa cells, GFP-Arp7A is cytoplasmic PMID:21278383 all three proteins are actually localized in the subacrosomal layer that links the acrosome to the nuclear envelope
GO:0005737 cytoplasm	IBA GO_REF:0000033	MODIFY	Summary: Inherited cytoplasmic location for the ACTL7 clade; true but general. Refine to the perinuclear theca and Golgi apparatus. Reason: The PAINT node is seeded by the ACTL7 orthologs and the paralog Actl7b, each with experimental cytoplasmic evidence, and rat Actl7a itself is among the descendant evidences (its own EXP row), which is expected rather than circular. The cytoplasmic claim holds. For Actl7a the cytoplasmic site where it acts is the perinuclear theca (with a transient Golgi pool), both already annotated to this gene, so the row is refined to them. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1343051 SUPPORTS TRANSFER Mouse Actl7a cytoplasmic evidence (PMID:12672658, PMID:21278383, PMID:36734600). MGI:MGI:1343053 SUPPORTS TRANSFER Paralog Actl7b, cytoplasmic in haploid germ cells (PMID:12672658). RGD:1304697 SUPPORTS TRANSFER The target itself; its EXP row is one of the descendant evidences, as expected for IBA. UniProtKB:Q9Y615 SUPPORTS TRANSFER Human ACTL7A. PANTHER:PTN001377938 NOT RELEVANT Internal PANTHER node, not a protein. Proposed replacements: perinuclear theca Golgi apparatus Supporting Evidence: PMID:21278383 all three proteins are actually localized in the subacrosomal layer that links the acrosome to the nuclear envelope
GO:0005737 cytoplasm	IEA GO_REF:0000044	MODIFY	Summary: Mapping of the UniProt Cytoplasm location; true but general. Refine to the perinuclear theca and Golgi apparatus. Reason: Same claim as the other cytoplasm rows; the specific supported cytoplasmic compartments are already on the gene. Proposed replacements: perinuclear theca Golgi apparatus Supporting Evidence: file:rat/Actl7a/Actl7a-uniprot.txt Detected at the subacrosomal layer in round spermatids.
GO:0005737 cytoplasm	ISO GO_REF:0000121	MODIFY	Summary: Ortholog transfer of the mouse cytoplasmic location; true but general. Refine to the perinuclear theca and Golgi apparatus. Reason: Same claim as the other cytoplasm rows; the mouse donor's cytoplasmic pool is the perinuclear theca and the Golgi apparatus of spermatids, both already annotated to this gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: MGI:MGI:1343051 SUPPORTS TRANSFER Mouse Actl7a cytoplasmic evidence is real; the specific compartments are the acroplaxome and Golgi. Proposed replacements: perinuclear theca Golgi apparatus Supporting Evidence: PMID:21278383 Arp7A is associated with the Golgi apparatus prior to and throughout the biogenesis of the acrosome
GO:0005737 cytoplasm	ISS GO_REF:0000024	MODIFY	Summary: UniProt similarity transfer of the mouse cytoplasmic location; true but general. Refine to the perinuclear theca and Golgi apparatus. Reason: Same claim as the other cytoplasm rows; the specific supported compartments are already on the gene. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q9QY84 SUPPORTS TRANSFER Mouse cytoplasmic pool in spermatids. Proposed replacements: perinuclear theca Golgi apparatus Supporting Evidence: PMID:21278383 all three proteins are actually localized in the subacrosomal layer that links the acrosome to the nuclear envelope
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Real but transient association with the Golgi apparatus during acrosome biogenesis; kept as a non-core location. Reason: The UniProt Golgi location is a similarity transfer from mouse, whose Golgi association rests on co-staining with GM130 in round spermatids before and during acrosome biogenesis. The organelle claim holds. No sub-compartment was resolved (a single co-staining line), so the row stays at the organelle. TES and Mena are never on the Golgi, and the structural role is exercised in the acroplaxome, so the location is peripheral to the core function. Supporting Evidence: PMID:21278383 immunofluorescence analysis of testis sections reveals that Arp7A co-localizes with GM130 on the Golgi apparatus of round spermatids
GO:0005794 Golgi apparatus	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Ortholog transfer of the mouse Golgi association; real but transient, non-core. Reason: The mouse donor's Golgi evidence is GM130 co-staining in round spermatids (PMID:21278383), which cannot resolve a Golgi sub-compartment. The organelle claim holds for the ortholog and transfers; it is stage-specific and not where the structural function acts. Supporting Evidence: PMID:21278383 Arp7A is associated with the Golgi apparatus prior to and throughout the biogenesis of the acrosome
GO:0005794 Golgi apparatus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: The best-hedged Golgi row: colocalization with GM130 is exactly what was observed. Non-core. Reason: The mouse observation is co-staining of Arp7A with the Golgi marker GM130, for which the colocalizes_with qualifier is the precise statement. Real, stage-specific, peripheral to the core function. Supporting Evidence: PMID:21278383 immunofluorescence analysis of testis sections reveals that Arp7A co-localizes with GM130 on the Golgi apparatus of round spermatids
GO:0005794 Golgi apparatus	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: UniProt similarity transfer of the mouse Golgi association; real but transient, non-core. Reason: Same mouse GM130 co-staining evidence as the other Golgi rows. The organelle claim holds, no sub-compartment is resolved, and the location is peripheral to the acroplaxome function. Supporting Evidence: file:rat/Actl7a/Actl7a-uniprot.txt Detected at the Golgi apparatus during acrosome biogenesis.
GO:0005856 cytoskeleton	IEA GO_REF:0000044	MODIFY	Summary: True but general; the specific cytoskeletal structure is the perinuclear theca, which is a cytoskeleton descendant and is already on the gene. Reason: GO:0033011 perinuclear theca is_a GO:0005856 cytoskeleton (checked with OAK), and Actl7a's cytoskeletal location is the subacrosomal layer of the perinuclear theca. The row is refined to that term. Proposed replacements: perinuclear theca Supporting Evidence: PMID:21278383 We have now extended these earlier studies and shown that Arp7A is actually localized in the subacrosomal layer, which is also known as the acroplaxome
GO:0007286 spermatid development	ISO GO_REF:0000121	ACCEPT	Summary: Core process. Mouse Actl7a loss disrupts the acrosome-acroplaxome-manchette complex and sperm head shaping, which is spermatid development beyond acrosome assembly alone. Reason: Acrosome assembly is part_of spermatid development, but this row is not redundant with it: the mouse knock-out also produces small, malformed sperm heads through defects of the acrosome-acroplaxome-manchette complex, a head-shaping role that acrosome assembly does not cover. Actl7a contributes structurally to the acroplaxome, which is itself one of the spermatid structures being built, so it does part of the work of the process. Supporting Evidence: PMID:37667331 Immunofluorescence and TEM analyses revealed that the deletion of ACTL7A damaged the formation of acrosome-acroplaxome-manchette complex, leading to abnormalities in the shaping of sperm heads.
GO:0007286 spermatid development	ISS GO_REF:0000024	ACCEPT	Summary: Core process; UniProt curator transfer from mouse Actl7a, duplicating the ISO row. Reason: Same claim and evidence as the ISO row. Supporting Evidence: PMID:37667331 The new phenotype of small head sperm associated with loss of ACTL7A in patients was discovered, and further confirmed in Actl7a-KO mice.
GO:0008150 biological_process	ND GO_REF:0000015	REMOVE	Summary: Placeholder no-data annotation from 2018, superseded by the specific process annotations now on the gene. Reason: The ND code records that no process information was available when the row was made. Process annotations to acrosome assembly, spermatid development and fertilization now exist for rat Actl7a, backed by mouse knock-out studies, so the ND placeholder is obsolete. Supporting Evidence: PMID:36734600 Through the generation of an Actl7a knock-out mouse model, we consistently observed disruption of acrosomal biogenesis with abnormal migration of the acrosomal granule and peeling acrosomes during spermatid elongation.
GO:0009566 fertilization	ISO GO_REF:0000121	KEEP AS NON CORE	Summary: Mouse Actl7a knock-out sperm fail to fertilize in IVF and ICSI; true of the gene but a downstream consequence of its structural role in the sperm head, so kept as non-core. Reason: The mouse donor carries fertilization by IMP from two knock-out studies, and human patients with ACTL7A variants show total fertilization failure rescued by artificial oocyte activation. The sperm-borne defect is loss or mislocalization of PLC zeta and reduced zona binding, which follow from the disrupted acrosome and perinuclear theca. Actl7a is necessary for fertilization but no step of fertilization is shown to be performed by it; the term is as precise as the evidence allows and is retained as non-core. Supporting Evidence: PMID:35921706 Actl7a deficiency led to malformed formation of sperm acrosomes, male infertility, fertilization failure during in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and reduced sperm-zona pellucida (ZP) binding ability. PMID:32923619 Furthermore, the sperm from ACTL7A/Actl7a-mutated men and mice showed reduced expression and abnormal localization of PLCζ as a potential cause of embryonic arrest and failure of fertilization.
GO:0009566 fertilization	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: UniProt curator transfer of the mouse fertilization phenotype, duplicating the ISO row; non-core. Reason: Same claim and evidence as the ISO row: a necessity established by knock-out, downstream of the sperm-head structural role. Supporting Evidence: PMID:35921706 Actl7a deficiency led to malformed formation of sperm acrosomes, male infertility, fertilization failure during in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and reduced sperm-zona pellucida (ZP) binding ability.
GO:0031514 motile cilium	ISO GO_REF:0000121	UNDECIDED	Summary: Transfer of a 2003 mouse observation of T-actin 2 in sperm tails; the full text is not available and later higher-resolution work does not report a flagellar pool. Left undecided. Reason: The mouse donor row is an MGI IDA from PMID:12672658, whose cached record is abstract-only; the abstract states the protein was present in sperm heads and tails but the figures cannot be inspected. The 2023 mouse study mapped five localization patterns in detail (nuclear, acroplaxome, marginal ring, flagellar connecting piece region, postacrosomal) and none is along the flagellum proper; the connecting piece corresponds to GO:0120212 sperm head-tail coupling apparatus, which GO does not place inside the motile cilium. Whether the 2003 tail signal is a genuine flagellar pool, the connecting piece, or antibody background cannot be decided without the full text, so the row is neither accepted nor removed. Propagation Review Root cause: UNRESOLVED Sources checked: MGI:MGI:1343051 UNRESOLVED Mouse IDA from PMID:12672658 (abstract only); not confirmed by PMID:36734600, which reports a connecting-piece pool instead. Supporting Evidence: PMID:12672658 In contrast, only T-ACTIN-2 was present in sperm heads and tails. PMID:36734600 having flagellar connecting piece regional localization from Steps 7 to 14 spermatids
GO:0032991 protein-containing complex	IDA PMID:21278383 Molecular recognition of the Tes LIM2-3 domains by the actin...	ACCEPT	Summary: Direct rat evidence: Actl7a co-immunoprecipitates with TES and Mena from rat testis extracts, the complex whose core was solved crystallographically. Reason: This is the one experiment in the literature performed on rat Actl7a, and the full text was read. TES immunoprecipitates from rat testis extracts contain Arp7A and Mena but not actin, zyxin or profilin I, and the 1-65 Arp7A, LIM2-3 TES and EVH1 Mena ternary complex was solved by X-ray crystallography. GO has no specific term for this heterotrimer, so the root complex term is the most precise available; the binding activity itself is captured by a LIM domain binding row. Supporting Evidence: PMID:21278383 immunoblot analysis of Tes immunoprecipitations (IP) with the indicated antibodies reveals that Arp7A, Tes, and Mena are complexed to each other in rat testes extracts PMID:21278383 Here we show that Arp7A, which has 43% sequence identity with β-actin, forms a complex with the cytoskeletal proteins Tes and Mena in the subacrosomal layer of round spermatids.
GO:0032991 protein-containing complex	ISO GO_REF:0000121	ACCEPT	Summary: Ortholog transfer of the Arp7A-TES-Mena complex; consistent with the rat's own IDA row. Reason: The human donor's complex annotation rests on the same paper, whose immunoprecipitation was performed in rat testis extracts, so this row adds no independent evidence to the rat IDA row, but the claim is correct and core. Supporting Evidence: PMID:21278383 immunoblot analysis of Tes immunoprecipitations (IP) with the indicated antibodies reveals that Arp7A, Tes, and Mena are complexed to each other in rat testes extracts
GO:0033011 perinuclear theca	ISO GO_REF:0000121	ACCEPT	Summary: Core location. GO's perinuclear theca includes the subacrosomal layer (acroplaxome) where Actl7a acts, and the postacrosomal region it occupies later. Reason: Mouse Actl7a carries perinuclear theca by IDA (PMID:41169243), and the subacrosomal-layer localization of the Arp7A-TES-Mena complex is part of this structure. GO has no narrower acroplaxome term, so this is the most precise available location. Supporting Evidence: PMID:41169243 ACTL7A, another essential PT protein, is required for acrosome biogenesis and mediates the tethering of the acrosomal outer membrane to the nucleus. PMID:21278383 We have now extended these earlier studies and shown that Arp7A is actually localized in the subacrosomal layer, which is also known as the acroplaxome
GO:0033011 perinuclear theca	ISO GO_REF:0000121	ACCEPT	Summary: Core location, transferred from human ACTL7A; duplicates the mouse-sourced row. Reason: Same claim as the mouse-sourced row; the human ortholog's perinuclear-theca defects in patient sperm agree. Supporting Evidence: PMID:34727571 TEM showed that the ACTL7A variants caused ultrastructural defects in the acrosome and perinuclear theca.
GO:0033011 perinuclear theca	ISS GO_REF:0000024	ACCEPT	Summary: Core location; UniProt curator transfer from mouse Actl7a. Reason: Same claim as the ISO rows; the rat UniProt entry records the subacrosomal-layer location. Supporting Evidence: file:rat/Actl7a/Actl7a-uniprot.txt Detected at the subacrosomal layer in round spermatids.
GO:0030274 LIM domain binding	ISS PMID:21278383 Molecular recognition of the Tes LIM2-3 domains by the actin...	NEW	Summary: Proposed new molecular function. The N-terminal extension of Arp7A binds the tandem LIM2-3 domains of TES; the binding segment is identical in rat, and rat Actl7a is in complex with TES in rat testis. Reason: Direct binding, mapping, mutagenesis, isothermal titration calorimetry and the crystal structure used human Arp7A residues 1-65; the contact segment (human residues 28-45, LQTASLRDGPAKRAVWVR) is identical in rat Actl7a at residues 33-50 (reviewer comparison of the UniProt sequences), retaining both apolar-pocket alanines and the GPAK linker that the paper shows are critical. The rat protein co-immunoprecipitates with TES from rat testis. This is the gene's best-characterised molecular activity and is not an ancestor or descendant of any term on the gene; rat has no protein-binding row that it would replace. It is a molecular function, so the process-term bar does not apply. Supporting Evidence: PMID:21278383 The N-terminal 65-residue extension to the actin-like fold of Arp7A interacts directly with Tes. PMID:21278383 Two alanine residues from Arp7A that occupy equivalent apolar pockets in both LIM domains as well as an intervening GPAK linker that binds the LIM2-3 junction are critical for the Arp7A-Tes interaction. file:rat/Actl7a/Actl7a-uniprot.txt Interacts (via N-terminus) with TES (via LIM domain 2). file:rat/Actl7a/Actl7a-deep-research-manual.md human residues 28-45 (LQTASLRDGPAKRAVWVR) are identical in rat at residues 33-50

Gene Description

Existing Annotations Review

Core Functions

Tandem-LIM-domain ligand. The N-terminal extension, not the actin fold, binds the LIM2-3 domains of testin (TES), and the Actl7a-TES pair recruits Mena (ENAH) into a heterotrimer present in rat testis and located in the acroplaxome.

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