ATP13A1
- Known as:
- ATP13A1
- Catalog number:
- 002272A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ATP13A1
Related genes to: ATP13A1
- Gene:
- ATP13A1 NIH gene
- Name:
- ATPase 13A1
- Previous symbol:
- ATP13A
- Synonyms:
- KIAA1825, FLJ31858, CGI-152
- Chromosome:
- 19p13.11
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-12
- Date modifiied:
- 2016-02-11
Related products to: ATP13A1
Related articles to: ATP13A1
- P5A-ATPases constitute a distinct branch of the P-type ATPase superfamily implicated in endoplasmic reticulum (ER) quality control through the removal or reorientation of transmembrane segments. Although genetic and structural studies have suggested a role for these enzymes in transmembrane-helix handling, biochemical evidence linking substrate interaction to catalytic activity has remained limited. Here, we show that purified Saccharomyces cerevisiae Spf1p, a prototypical P5A-ATPase, is stimulated by C-terminal domains of tail-anchored (TA) proteins. Fusion constructs containing the transmembrane and C-terminal regions of either Fis1p (FIS) or the bacterial TA protein YgiM (YGIM) increased ATP hydrolysis approximately twofold in a lipid-dependent and vanadate-sensitive manner. Disruption of membrane-proximal basic residues, either by deletion of the FIS C-terminal KKR motif or by alanine substitution in the YGIM C-terminal tail, markedly reduced stimulation, indicating that C-terminal positive charges contribute to activation. YGIM stimulated Spf1p ATPase activity in a concentration-dependent and saturable manner (Km ≈ 0.12 μM) and increased the relative contribution of a high-affinity component in vanadate inhibition. In pulldown assays, binding of YGIM to Spf1p was enhanced when the enzyme was stabilized in an EP-like conformation using beryllium fluoride. Structural inspection of the EP state revealed a conserved acidic patch at the luminal entrance of the central cavity, forming a vestibular ring positioned to interact electrostatically with basic C-terminal tails of TA proteins. Altogether, these results support the role of TA proteins as transported substrates of P5A-ATPases and highlight charge-based interactions at the luminal cavity entrance as a key determinant of substrate-dependent activation. - Source: PubMed
Publication date: 2026/05/27
Cianci Elio OMazzitelli Luciana RAdamo Hugo P - The accurate targeting of proteins to their designated cellular compartments is essential for maintaining proper cellular architecture and function. However, interpreting and sorting the highly variable targeting sequences in secreted and membrane proteins present a substantial challenge for achieving precise localization within the secretory pathway. In this study, we demonstrate that atypical signal sequences, characterized by high hydrophobicity and/or the absence of characteristic charges, are recognized by the signal recognition particle and targeted to the endoplasmic reticulum in a reverse orientation. These misoriented signal sequences are subsequently dislocated by the P5A-ATPase ATP13A1 and delivered to SEC61 for further translocation. Using cryo-electron microscopy, we determined the structures of human ATP13A1 in multiple conformations (3.40- to 3.87-angstrom resolution), revealing key residues within its substrate-binding pocket that engage signal sequences through polar interactions. Collectively, our findings elucidate a comprehensive, substrate-specific translocation pathway that ensures both high efficiency and fidelity in protein subcellular localization. - Source: PubMed
Publication date: 2025/06/11
Yang XiaoyanLi YiYang ChengxiLi TingtingFang ZhiyuFeng ZhigangLiao JunZou Yan - In this issue, Ji et al. show how a multipass membrane protein that initially inserts into the endoplasmic reticulum in a mostly inverted topology is post-translationally dislocated, re-inserted, and folded with the help of ATP13A1, a P-type ATPase. - Source: PubMed
Hegde Ramanujan S - Many multi-spanning membrane proteins contain poorly hydrophobic transmembrane domains (pTMDs) protected from phospholipid in mature structure. Nascent pTMDs are difficult for translocon to recognize and insert. How pTMDs are discerned and packed into mature, muti-spanning configuration remains unclear. Here, we report that pTMD elicits a post-translational topogenesis pathway for its recognition and integration. Using six-spanning protein adenosine triphosphate-binding cassette transporter G2 (ABCG2) and cultured human cells as models, we show that ABCG2's pTMD2 can pass through translocon into the endoplasmic reticulum (ER) lumen, yielding an intermediate with inserted yet mis-oriented downstream TMDs. After translation, the intermediate recruits P5A-ATPase ATP13A1, which facilitates TMD re-orientation, allowing further folding and the integration of the remaining lumen-exposed pTMD2. Depleting ATP13A1 or disrupting pTMD-characteristic residues arrests intermediates with mis-oriented and exposed TMDs. Our results explain how a "difficult" pTMD is co-translationally skipped for insertion and post-translationally buried into the final correct structure at the late folding stage to avoid excessive lipid exposure. - Source: PubMed
Publication date: 2024/05/08
Ji JiaCui Meng-KeZou RongWu Ming-ZhiGe Man-XiLi JiqiangZhang Zai-Rong - DNA replication, transcription, and translation in eukaryotic cells occur with decreasing but still high fidelity. In contrast, for the estimated 33% of the human proteome that is inserted as transmembrane (TM) proteins, insertion with a non-functional inverted topology is frequent. Correct topology is essential for function and trafficking to appropriate cellular compartments and is controlled principally by responses to charged residues within 15 residues of the inserted TM domain (TMD); the flank with the higher positive charge remains in the cytosol (inside), following the positive inside rule (PIR). Yeast () mutants that increase insertion contrary to the PIR were selected. Mutants with strong phenotypes were found only in and (human cell orthologs are and ) with, at the time, no known relevant functions. Spf1/Atp13A1 is now known to dislocate to the cytosol TM proteins inserted contrary to the PIR, allowing energy-conserving reinsertion. We hypothesize that Spf1 and Ste24 both recognize the short, positively charged ER luminal peptides of TM proteins inserted contrary to the PIR, accepting these peptides into their large membrane-spanning, water-filled cavities through interaction with their many interior surface negative charges. While entry was demonstrated for Spf1, no published evidence directly demonstrates substrate entry to the Ste24 cavity, internal access to its zinc metalloprotease (ZMP) site, or active withdrawal of fragments, which may be essential for function. Spf1 and Ste24 comprise a PIR quality control system that is conserved in all eukaryotes and presumably evolved in prokaryotic progenitors as they gained differentiated membrane functions. About 75% of the PIR is imposed by this quality control system, which joins the UPR, ERAD, and autophagy (ER-phagy) in coordinated, overlapping quality control of ER protein function. - Source: PubMed
Publication date: 2023/08/03
Tipper Donald JHarley Carol A