Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
TDP-43 is a transcriptional repressor: the testis-specific mouse acrv1 gene is a TDP-43 target in vivo.
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The paper's subject is TDP-43 as a repressor of the mouse acrv1 promoter; acrv1 is the transcriptional target, and no ACRV1 protein function is assayed.
"The present study tested the hypothesis that TDP-43 represses acrv1 gene transcription in spermatocytes."
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The conclusion drawn is about TDP-43 regulating acrv1 expression during spermatogenesis, not about ACRV1 participating in spermatogenesis.
"our study shows that TDP-43 is a transcriptional repressor and that it regulates spatiotemporal expression of the acrv1 gene during spermatogenesis"
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
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The network is a systematic yeast two-hybrid screen around neurodegeneration-related baits, and the authors themselves describe the edges as candidate interactions.
"connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins"
Biochemical and morphological characterization of the intra-acrosomal antigen SP-10 from human sperm.
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SP-10 lies throughout the human acrosome in a bilaminar array against the inner face of the outer acrosomal membrane and the outer face of the inner acrosomal membrane.
"Light and electron microscopic immunocytochemistry localized SP-10 throughout the acrosome, and electron microscopic evidence demonstrated a bilaminar array in association with the inner aspect of the outer acrosomal membrane and the outer aspect of the inner acrosomal membrane."
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It is not exposed on the surface of acrosome-intact ejaculated sperm, so it is inaccessible until the acrosome reaction.
"Immunofluorescence showed that SP-10 was not associated with the surface of acrosome-intact, ejaculated sperm."
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After the acrosome reaction it stays on the sperm head with the inner acrosomal membrane and equatorial segment.
"After induction of the acrosome reaction with the ionophore A23187, SP-10 remained displayed on the sperm head in association with the inner acrosomal membrane and equatorial segment."
Interactions of human sperm acrosomal protein SP-10 with the acrosomal membranes.
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Both the detergent-released and detergent-resistant SP-10 pools are hydrophilic, so SP-10 is peripheral to rather than integral in the acrosomal membranes.
"Phase partitioning of TX-114-released and TX-114-resistant SP-10 pools showed that both were hydrophilic, indicating that these pools consist of proteins that are peripherally associated with, rather than integral to, the acrosomal membranes."
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The detergent-resistant pool localises to the acrosomal matrix, inner acrosomal membrane and equatorial segment.
"TX-114-resistant SP-10 was associated with the equatorial segment and with TX-114-resistant portions of the acrosomal matrix and the inner acrosomal membrane."
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That pool is released by chaotropic salt or pH extremes but not by repeated detergent or 1.5 M NaCl, implying an uncharacterised matrix anchor.
"Together the results suggest that SP-10 is a hydrophilic peripheral acrosomal membrane protein that may be associated with a TX-114-resistant "anchor.""
Human SP-10: acrosomal distribution, processing, and fate after the acrosome reaction.
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Immunogold EM concentrates SP-10 in the principal segment and posterior bulb of the equatorial segment of the human sperm acrosome.
"Electron microscopic immunocytochemical observations of epididymal, ejaculated, and capacitated sperm revealed that colloidal gold labeling of SP-10 was most abundant within the principal segment and posterior bulb of the equatorial segment of the acrosome"
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After a follicular-fluid-induced acrosome reaction SP-10 is on the inner acrosomal membrane of the equatorial segment and on hybrid vesicles.
"After a follicular fluid-induced acrosome reaction, SP-10 was detected on the inner acrosomal membrane in the equatorial segment and was associated with hybrid vesicles."
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Processing is complete before ejaculation - no further cleavage occurs during epididymal transit, ejaculation or capacitation.
"no additional SP-10 bands were detected in extracts of cauda epididymal, ejaculated, or capacitated sperm, suggesting that no further processing of the 32-18-kDa SP-10 peptides occurred during epididymal transit, ejaculation, and capacitation."
A monoclonal antibody to human SP-10 inhibits in vitro the binding of human sperm to hamster oolemma but not to human Zona pellucida.
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A monoclonal antibody against SP-10 residues 135-149 blocked human sperm binding to zona-free hamster oolemma but not sperm-zona binding in the hemizona assay.
"Monoclonal Ab pep-SP10 inhibited sperm-oolemma binding in the zona-free hamster egg penetration test, but it did not inhibit sperm-zona binding in the hemizona assay."
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The authors conclude SP-10 on the equatorial region of acrosome-reacted sperm mediates sperm-oolemma binding independently of beta-1 integrins.
"human SP-10, expressed on the equatorial region of acrosome-reacted sperm, indeed mediates sperm-oolemma binding in a beta(1) integrin-independent manner, but not sperm-zona binding"
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Beta-1 integrins were positively excluded as the oolemmal ligand using F9 cells and beta-1-null derivatives, leaving the ligand unidentified.
"we demonstrated that the oolemmal ligands of human SP-10 did not include beta(1) integrins, the most promising candidates for oocyte ligands involved in sperm-oolemma binding"
Inhibition of bovine fertilization in vitro by antibodies to SP-10.
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Anti-human-SP-10 monoclonal and polyclonal antibodies reduced bovine in vitro fertilisation rates.
"Fertilization experiments in vitro demonstrated that monoclonal antibodies, as well as polyclonal antibodies, to human SP-10 significantly reduced fertilization rates of bovine oocytes by bovine spermatozoa."
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The effect was on sperm-zona secondary binding, i.e. the post-acrosome-reaction step, not primary binding.
"SP-10 antibodies exerted their anti-fertilization effect by reducing sperm-zona secondary binding."
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The antibodies also reduced completion of the acrosome reaction by capacitated sperm, a result not annotated here.
"Consistent with the accessibility of the SP-10 antigen following capacitation, SP-10 antibodies also reduced the ability of capacitated spermatozoa to complete the acrosome reaction."
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They also reduced the motility of capacitated but not noncapacitated sperm, which confounds the acrosome-reaction result.
"Furthermore, SP-10 antibodies affected the motility of capacitated spermatozoa, while not affecting the motility of noncapacitated spermatozoa."
Individual disruption of 12 testis-enriched genes via the CRISPR/Cas9 system does not affect the fertility of male mice.
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Acrv1 is one of twelve testis-enriched genes individually disrupted by CRISPR/Cas9 in mouse.
"In this study, 12 genes of interest were found to be dispensable for male mouse reproduction, at least individually, by generating KO mice with the CRIPR/Cas9 system."
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Testis appearance, testis histology and sperm motility were examined for every one of the twelve knockouts, Acrv1 included.
"we generated knockout mice for 12 genes (Acrv1, Adgrf3, Atp8b5, Cfap90, Cfap276, Fbxw5, Gm17266, Lrrd1, Mroh7, Nemp1, Spata45, and Trim36) that are expressed predominantly in the testis and examined the appearance and histological morphology of testes, sperm motility, and male fertility."
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Litter sizes sired by knockout males were indistinguishable from wild type.
"We found that the average number of pups sired by each KO male was 7 to 10 pups per litter during the mating period, comparable to the WT control (about 9 pups per litter), suggesting that there was no significant difference between the fecundity of KO and WT males."
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Immunising male rodents against SP-10 does not arrest spermiogenesis.
"Furthermore, the immunization with anti-human SP-10 antibody in male rodents did not induce the arrest of spermiogenesis (Sehgal et al., 1996)."
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SP-10 is described as abundant in the acrosomal matrix and inner acrosomal membrane across mammals.
"Acrv1 is an evolutionarily conserved gene encoding the sperm protein SP-10, which abundantly exists in the acrosomal matrix and the inner acrosomal membrane in mammals (Reddi, 2023)."
Cloning and sequencing of cDNAs coding for the human intra-acrosomal antigen SP-10.
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SP-10 is a 265-residue protein with a hydrophobic N-terminal signal peptide and three amino-acid repeat types occurring 16 times in the central third.
"Sequence data showed that three different amino acid repeats occurred a total of 16 times in the central third of the SP-10 protein."
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In 1990 no sequence homologue could be found, which is the claim later domain databases superseded.
"SP-10 cDNA sequences did not show any significant homology to other sequences found in the Genbank, National Biomedical Research Foundation, or Swiss sequence banks."
Characterization of alternatively spliced human SP-10 mRNAs.
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Eleven authentic alternatively spliced SP-10 mRNAs encode proteins of 81-265 residues, all from in-frame deletions in exons 2 and/or 3.
"The 11 alternatively spliced SP-10 mRNAs encoded proteins ranging from 81 to 265 amino acids."
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The four largest mRNAs make up over 99% of testis SP-10 message.
"Quantitative competitive RTPCR showed that the four largest SP-10 mRNAs represented the majority (> 99%) of the SP-10 message in testes from each of four men."
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The full-length 265-residue isoform is consistently the most abundant single form.
"the longest SP-10 mRNA, SP10-1, which encoded a 265 amino acid protein, was consistently the most abundant, comprising 53-72% of the total SP-10 message"
Purification and microsequencing of the intra-acrosomal protein SP-10. Evidence that SP-10 heterogeneity results from endoproteolytic processes.
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N-terminal sequencing of eight purified SP-10 peptides implies endoproteolysis at five distinct bonds, including a trypsin-like cut possibly by acrosin.
"endoproteases that act at five different peptide bonds are predicted to cleave SP-10"
Molecular and developmental studies of a sperm acrosome antigen recognized by HS-63 monoclonal antibody.
RNF17, a component of the mammalian germ cell nuage, is essential for spermiogenesis.
ZNF280A and ACRV1 enhance aerobic glycolysis and drive ovarian cancer progression via the PI3K/AKT signaling pathway.
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ZNF280A drives ACRV1 transcription in ovarian cancer cells by recruiting CUX2 to the ACRV1 promoter.
"Mechanistically, ZNF280A enhanced ACRV1 transcription by interacting with the transcription factor CUX2, thereby facilitating its recruitment to the ACRV1 promoter."
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Raised ACRV1 in these cells activates PI3K/AKT signalling and glycolysis.
"Elevated ZNF280A or ACRV1 expression activated PI3K/AKT signaling and increased glycolytic enzyme expression (PKM2 and LDHA), glucose uptake, lactate production, ATP generation, and extracellular acidification rate"
ACRV1 (SP-10): what the LU domain, the splice isoforms and the family do and do not license
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The C-terminal third of ACRV1 is a canonical Ly-6/uPAR three-finger domain with ten cysteines, the modal count across the human LU family, and every cysteine in the protein lies inside it.
"The domain carries **10 cysteines** at 190, 193, 202, 209, 217, 235, 239, 255, 256, 262"
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All splice isoforms with a measured abundance keep the LU domain complete; only the rare isoforms 8 and 11 truncate it, so splicing varies the disordered spacer rather than the folded module.
"All isoforms with a measured abundance retain the complete LU domain: **True**."
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ACRV1 is one of eleven of thirty reviewed human LU-domain proteins without a GPI anchor, matching its experimentally determined peripheral, chaotrope-releasable behaviour.
"ACRV1 is one of the few human LU-domain proteins with no GPI anchor"
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ACRV1 shares no subfamily-resolution signature with any other reviewed human LU-domain protein, so no paralogue-based inference is available to it.
"**No other reviewed human LU-domain protein shares either model**, so ACRV1 is a subfamily singleton in the human proteome."
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ACRV1's only experimental molecular-function annotation is bare protein binding, and the family's most widely shared function (acetylcholine receptor modulation, 7/30 members) sits in GPI-anchored or secreted surface members that ACRV1 does not resemble.
"ACRV1's own experimental molecular-function annotations are GO:0005515, of which informative: **none**."
UniProtKB P26436 (ASPX_HUMAN) flat-file record
Affinage mechanistic annotation for ACRV1 (human)