"Two novel human actin-like genes, ACTL7A and ACTL7B, were identified by cDNA selection and direct genomic sequencing from the familial dysautonomia candidate region on 9q31."

"ACTL7A is expressed in a wide variety of adult tissues, while the ACTL7B message was detected only in the testis and, to a lesser extent, in the prostate."

"The mRNA sizes and deduced molecular masses of t-actin 1/mACTl7b and t-actin 2/mACTl7a were 2.2 kilobases (kb) and 1.8 kb, and Mr 43.1 x 10(3) and Mr 47.2 x 10(3), respectively."

"In contrast, only T-ACTIN-2 was present in sperm heads and tails."

"Although the cellular locations of these two proteins are quite different (T-ACTIN-1 was found in the cytoplasm and T-ACTIN-2 was located in the nucleus), the expression of their proteins and mRNAs is controlled during development and limited during spermiogenesis."

"The two deduced amino acid sequences had 60% homology, and they had approximately 40% homology with other actins."

"the sequence of Arp7A has no major deletions or insertions within its predicted actin fold and has 43% sequence identity to β-actin, which is higher than that of Arp3"

"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)."

"Future studies will be required to establish the role of the Arp7A·Tes·Mena complex in the formation and function of the acroplaxome and whether it binds to and/or induces actin filament polymerization."

"sperm nuclei were obtained through CTAB treatment and isolated to over 99.9% purity without any tail fragments, acrosome or mitochondria as assessed by optical microscopy and transmission electron microscopy"

"This mutation is deleterious and causes sperm acrosomal ultrastructural defects."

"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."

"ACTL9 variations led to abnormal ultrastructure of the perinuclear theca (PT), and PLCζ was absent in the head and present in the neck of the mutant sperm, which contributed to failed normal calcium oscillations in oocytes and subsequent TFF."

"TEM showed that the ACTL7A variants caused ultrastructural defects in the acrosome and perinuclear theca."

"Protein expression of ACTL7A and phospholipase C zeta, a key sperm-borne oocyte activation factor, was significantly reduced in the affected sperm compared to healthy controls, suggesting that the ACLT7A variants lead to an oocyte activation deficiency and TFF."

"The mutant sperm failed to activate the oocyte, and sperm-borne oocyte activation factor phospholipase C zeta (PLCζ) discharge accompanied by ACTL7A was observed, leading to total fertilization failure (TFF)."

"Furthermore, mutant ACTL7A failed to attach to the acroplaxome and was discharged by cytoplasmic droplets, which led to the absence of ACTL7A in epididymal spermatozoa in mice."

"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."

"We identified a novel homozygous missense mutation c.224A > C (p.D75A) in ACTL7A gene in two infertile brothers with teratozoospermia by whole-exome sequencing (WES)."

"Significantly, we found a complete loss of subacrosomal filamentous actin (F-actin) structures in knock-out spermatids suggesting a regulatory role for subacrosomal F-actin."

"The KO spermatids did not lose F-actin in other cellular regions, indicating that ACTL7A is not globally required for F-actin formation within developing spermatids"

"As such, it is not yet clear whether ACTL7A may be the filament-forming actin in the acroplaxome, or whether its role is to nucleate, stabilize formation, and/or anchor F-actin formed by conventional ARPs to the nuclear surface."

"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."

"Loss of cylicin-1 in mice leads to a high incidence of malformed sperm heads with acrosome detachment from the nucleus."

"Cylicin-1 interacts with itself, several other PT proteins, the inner acrosomal membrane (IAM) protein SPACA1, and the nuclear envelope (NE) protein FAM209 to form an 'IAM-cylicins-NE' sandwich structure, anchoring the acrosome to the nucleus."

"ACTL7A, another essential PT protein, is required for acrosome biogenesis and mediates the tethering of the acrosomal outer membrane to the nucleus."

"PTHR11937 PTN008986528 GO:0005200 F IRD true PANTHER:PTN000940351"

"PTHR11937 PTN008986528 GO:0005198 F IBA false PANTHER:PTN000940351"

"* **Nucleotide cleft largely retained.** ACTL7A is 63.2% identical to actin across the 19 G-actin cleft positions (66.7% at the phosphate contacts), against 96.5% for conventional actins, 79.0% for Arp2/Arp3 and 36.9% for the divergent SWI/SNF Arps."

"* **The cleft is under disease-relevant constraint.** 2/5 ACTL7A variants reported in SPGF86 patients map into the nucleotide cleft, which covers only 4.6% of the protein (binomial p = 0.0193); 0/4 population polymorphisms do."