This entry represents the transmembrane domain from ER/Golgi membrane proteins including V-type proton ATPase subunit S1 V0 complex accessory subunit Ac45 (VAS1, also known as V0 complex accessory subunit Ac45, ATP6AP1) from animals and the yeast homologue V0 assembly protein 1 (VOA1) which are essential for V0 ATPase assembly, stability and function [, ]. In humans, mutations of ATP6AP1 cause immunodeficiency with hypogammaglobulinemia, hepatopathy and neurocognitive abnormalities []. This entry also includes ER membrane BIG1 proteins from yeast, involved in cell wall biogenesis.
This entry represents the luminal domain (LD) found in eukaryotic V-type proton ATPase subunit S1 (VAS1), involved in V-ATPase V0 assembly, also known as Ac45 subunit (ATP6AP1) [, ]. This domain folds as a globular β-prism structure which is structurally similar to LAMP1-3, thus, the LD domain of Ac45 is an evolutionarily conserved member of the LAMP family []. Ac45 is an ER membrane protein that guides the V-type ATPase into specialised subcellular compartments []and is critical for Vo complex assembly as it connects to multiple Vo subunitsand phospholipids in the c-ring []. Missense mutations in the X-linked ATP6AP1 gene cause immunodeficiency in males that leads to recurrent bacterial infection, hepatopathy, cognitive impairment, and abnormal protein glycosylation [].
V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra- and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release []. V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins [].This entry represents the V0 complex Ac45 accessory subunit (ATP6AP1, also known as V-type proton ATPase subunit S1), an ER/Golgi membrane protein. This subunit is synthesized as an N-glycosylated 60kDa precursor that is intracellularly cleaved to a protein of about 45kDa. This subunit plays a crucial role on V0 assembly, stability and function as it connects to multiple V0 subunits and phospholipids in the c-ring []. This subunit assists the V-ATPase in the acidification of neuroendocrine granules []and guides the V-ATPase into specialized subcellular compartments such as neuroendocrine regulated secretory vesicles or the ruffled border of the osteoclast []. In humans, mutations of ATP6AP1 cause immunodeficiency with hypogammaglobulinemia, hepatopathy and neurocognitive abnormalities [].
