The ARL4A gene is located on chromosome 7 at the cytogenetic location 7p21.3 . The gene encodes a protein that consists of 200 amino acids and has a molecular weight of approximately 25 kDa . The protein contains a nuclear localization signal, which allows it to be present in both nuclear and extranuclear cell compartments .
ARL4A is expressed in various tissues, with the highest expression levels observed in the testis . It is also expressed in other tissues, including the spleen, intestine, brain, heart, liver, lung, and thymus, albeit at lower levels . In situ hybridization studies have shown that ARL4A is expressed in germ cells of pubertal and adult testis but not in prepubertal testis .
ARL4A functions as a small GTP-binding protein that cycles between an inactive GDP-bound form and an active GTP-bound form . The rate of cycling is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) . Unlike some other GTP-binding proteins, ARL4A does not act as an allosteric activator of the cholera toxin catalytic subunit . Instead, it recruits proteins such as CYTH1, CYTH2, CYTH3, and CYTH4 to the plasma membrane in its GDP-bound form .
Research has indicated that ARL4A may play a role in sperm production, as its expression is highest in the testis and is involved in the differentiation of germ cells . Additionally, ARL4A has been implicated in various cellular processes, including vesicle trafficking and endocytosis, which are crucial for maintaining cellular homeostasis .