Recombinant Mouse Putative adenosylhomocysteinase 2 (Ahcyl1)
Description
Overview of Recombinant Mouse Putative Adenosylhomocysteinase 2 (Ahcyl1)
S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) is a member of the AHCY protein family, playing a role in S-adenosyl-L-homocysteine metabolism . AHCYL1, consisting of 540 amino acid residues, possesses a domain in the C-terminal region homologous to AHCY and multiple potential phosphorylation sites in the N-terminal region . Although AHCYL1 has an AHCY-like domain in the C-terminal domain, it lacks hydrolase activity for adenosylhomocysteine because of the substitution of important amino acids in the critical enzymatically active site .
Functional Characteristics
AHCYL1 has a different function from AHCY because AHCYL1 lacks several binding sites for S-adenosyl-L-homocysteine, irrespective of the conserved cysteines required for a tight globular structure of AHCY and NAD + binding motifs . Research indicates AHCYL1 functions as a sensor for S-adenosyl-l-homocysteine (SAH), which inhibits autophagy by interacting with PIK3C3 in an MTORC1-independent manner . The C terminus of AHCYL1 specifically interacts with SAH, promoting the binding of its N terminus to the catalytic domain of PIK3C3, thus inhibiting PIK3C3 .
Role in Lung Cancer
AHCYL1 has been identified as a regulator of cell differentiation status in non-small cell lung cancer (NSCLC) . Studies show that AHCYL1 inhibits lung cancer tumorigenesis by regulating cell plasticity .
AHCYL1 expression affects the metabolic status of lung cancer cells, but to a minor degree, and seems not to be associated with changes of histone methylation status . AHCYL1-depleted cells showed a slight increase of intracellular SAH, with no change in SAM levels, decreasing the SAM/SAH values, although to a small degree, and suggesting a lower methylation capacity in these cells .
Interaction with SAH
AHCYL1 interacts with SAH with a dissociation constant $$K_d = 12.5 \pm 1.6 \mu M$$, which is around the physiological concentration of SAH . The adenosine of SAH interacts with T155 and Q157, while N178 and D229 interact with the homocysteine tail . Mutation of T155A and Q157A, but not N178A and D229A, abolished the enhanced interaction by SAH .
Clinical Data on AHCYL1 Expression in Lung Cancer
The following table summarizes the relationship between AHCYL1 expression and clinicopathological features in lung cancer patients :
Table 1.
| AHCYL1 low no (%) | AHCYL1 high no (%) | p value | |
|---|---|---|---|
| Total no | 5 (25%) | 15 (75%) | |
| Age (years ± SD) | 64.9 (9.9) | 67.3 (8.2) | 0.539 |
| Gender (%) | 0.038 | ||
| Male | 5 (100%) | 6 (40%) | |
| Female | 0 (0%) | 9 (60%) | |
| Follow-up time (median-IQR) | 379(365–833) | 1694 (1246–2535) | 0.098 |
| Tumor size (mm ± SD) | 24.2 (9.9) | 31.3 (18.1) | 0.417 |
| Pleural infiltration (%) | 2 (40%) | 6 (40%) | 1.000 |
| Histologic grade (3 vs. 1–2) | 3 (60%) | 6 (40%) | 0.396 |
| UICC TNM Stage (II–III) | 1 (20%) | 6 (40%) | 0.406 |
| Ki67 (% median-IQR) | 60 (30–70) | 5 (5–17) | 0.004 |
Product Specs
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Target Background
- IRBIT forms signaling complexes with PIPKIalpha and NBCe1-B, whose activity is regulated by PI(4,5)P2. PMID: 26509711
- IRBIT suppresses CaMKIIalpha activity and contributes to catecholamine homeostasis through TH phosphorylation. PMID: 25922519
- Irbit was sequestered by InsP3 receptors (IP3Rs) in the endoplasmic reticulum PMID: 23542070
- IRBIT can directly interact with the IP3R, and that both the suppressor domain and the IP3-binding core of the IP3R are essential for a strong interaction. PMID: 16527252
- Phosphorylation of Ser71 and Ser74 enabled inhibition of IP3 binding to the IP3R by IRBIT PMID: 17635105
- Cloning, bacterial expression, and unique structure of adenosylhomocysteine hydrolase-like protein 1, or inositol 1,4,5-triphosphate receptor-binding protein. PMID: 18804558
- Data show that pNBC1 activation requires the IRBIT PEST domain, while CFTR activation requires multiple domains, suggesting that IRBIT is a key coordinator of epithelial fluid and HCO3- secretion. PMID: 19033647
- Results suggest that IRBIT modulates the polyadenylation state of specific mRNAs by controlling Fip1 cytoplasmic/nuclear partitioning and inhibiting PAP activity in response to phosphorylation changes. PMID: 19224921
