6wlz

Structural highlights

Disease

VATA_HUMAN Non-specific early-onset epileptic encephalopathy;Autosomal recessive cutis laxa type 2, classic type. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

VATA_HUMAN Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:8463241). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). May play a role in neurite development and synaptic connectivity (PubMed:29668857).[UniProtKB:P50516]^{[1] [2] [3] [4]} (Microbial infection) Plays an important role in virion uncoating during Rabies virus replication after membrane fusion. Specifically, participates in the dissociation of incoming viral matrix M proteins uncoating through direct interaction.^[5]

See Also

• ATPase 3D structures

References

1. ↑ Miles AL, Burr SP, Grice GL, Nathan JA. The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, control HIF1α prolyl hydroxylation by regulating cellular iron levels. Elife. 2017 Mar 15;6:e22693. PMID:28296633 doi:10.7554/eLife.22693
2. ↑ Fassio A, Esposito A, Kato M, Saitsu H, Mei D, Marini C, Conti V, Nakashima M, Okamoto N, Olmez Turker A, Albuz B, Semerci Gündüz CN, Yanagihara K, Belmonte E, Maragliano L, Ramsey K, Balak C, Siniard A, Narayanan V, Ohba C, Shiina M, Ogata K, Matsumoto N, Benfenati F, Guerrini R. De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy. Brain. 2018 Jun 1;141(6):1703-1718. PMID:29668857 doi:10.1093/brain/awy092
3. ↑ van Hille B, Richener H, Evans DB, Green JR, Bilbe G. Identification of two subunit A isoforms of the vacuolar H(+)-ATPase in human osteoclastoma. J Biol Chem. 1993 Apr 5;268(10):7075-80 PMID:8463241
4. ↑ Vasanthakumar T, Rubinstein JL. Structure and Roles of V-type ATPases. Trends Biochem Sci. 2020 Apr;45(4):295-307. PMID:32001091 doi:10.1016/j.tibs.2019.12.007
5. ↑ Liu X, Li F, Zhang J, Wang L, Wang J, Wen Z, Wang Z, Shuai L, Wang X, Ge J, Zhao D, Bu Z. The ATPase ATP6V1A facilitates rabies virus replication by promoting virion uncoating and interacting with the viral matrix protein. J Biol Chem. 2021 Jan-Jun;296:100096. PMID:33208464 doi:10.1074/jbc.RA120.014190