HYKK Human
Description
Introduction to HYKK Human
HYKK Human, also known as Hydroxylysine Kinase (gene ID: 123688), is a protein-coding gene belonging to the aminoglycoside phosphotransferase family. It is located on chromosome 15q25.1 and encodes a 373-amino acid polypeptide (plus a 23-amino acid His-tag in recombinant forms) with a molecular mass of 44.3 kDa . The enzyme catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine, a critical step in lysine metabolism .
Key Synonyms and Identifiers
| Attribute | Detail |
|---|---|
| Gene Name | HYKK (AGPHD1) |
| Uniprot ID | A2RU49 |
| Entrez Gene ID | 123688 |
| Chromosomal Location | 15q25.1 |
Predicted Cellular Localization and Activity
| Aspect | Detail |
|---|---|
| Catalytic Activity | GTP-dependent phosphorylation of 5-hydroxy-L-lysine |
| Predicted Localization | Mitochondrial matrix (in silico) |
| Experimental Localization | Cytoplasmic (reported in some studies) |
Association with Lung Cancer
HYKK is implicated in genetic susceptibility to lung cancer through genome-wide association studies (GWAS). Variants near the HYKK locus (15q25.1) have been linked to increased risk, particularly in smoking-related contexts .
| Study | Key Finding |
|---|---|
| GWAS for Lung Cancer Susceptibility | HYKK locus identified as a major risk locus |
| COPD and Lung Cancer GWAS | HYKK variants correlate with airflow obstruction |
Potential Therapeutic Targets
While direct therapeutic applications are unexplored, HYKK’s role in lysine metabolism positions it as a candidate for studying metabolic disorders. For example, kinase inhibitors targeting related pathways (e.g., EGFR-related tyrosine kinases) are being repurposed for insulin resistance , suggesting broader metabolic implications.
Production and Application in Research
Recombinant HYKK Human is widely used in biochemical assays to study lysine metabolism and kinase activity. Key production parameters include:
| Parameter | Detail |
|---|---|
| Host Organism | E. coli |
| Storage Conditions | -20°C (long-term); 4°C (short-term) |
| Stability Enhancers | 0.1% HSA/BSA (recommended for freeze-thaw cycles) |
This protein serves as a critical tool for elucidating lysine-derived pathways and their dysregulation in disease .
Product Specs
Q&A
What is HYKK and what is its significance in human research?
HYKK Human is a single, non-glycosylated polypeptide chain containing 396 amino acids (1-373a.a) with a molecular mass of 44.3kDa . Its significance lies primarily in its association with nicotine metabolism and drug-related behavioral phenotypes . Understanding HYKK's function contributes to broader knowledge about genetic factors influencing substance use behaviors and potential therapeutic targets. When designing studies involving HYKK, researchers should consider both its molecular characteristics and its genetic expression patterns in relation to phenotypic outcomes.
How is recombinant HYKK Human typically prepared for research applications?
Recombinant HYKK Human is commonly produced in E. coli expression systems, where it is fused to a 23 amino acid His-tag at the N-terminus to facilitate purification . The protein is then isolated using proprietary chromatographic techniques to ensure purity and functional integrity . For experimental design purposes, researchers should verify the purity and activity of their HYKK preparations before conducting functional studies, as variations in preparation methods may influence experimental outcomes and reproducibility.
What are the optimal storage conditions for maintaining HYKK Human stability?
HYKK Human samples should be stored at 4°C if the entire vial will be used within 2-4 weeks . For longer-term storage, freezing at -20°C is recommended . To enhance stability during long-term storage, adding a carrier protein (0.1% HSA or BSA) is advised . Multiple freeze-thaw cycles should be avoided as they can compromise protein integrity and function . Researchers should document storage conditions in their methodologies and consider potential impacts of improper storage on experimental outcomes when analyzing unexpected results.
What single-subject research designs are most appropriate for studying HYKK-related phenotypes?
Single-subject research designs offer particular advantages when studying HYKK-related phenotypes due to the individuated nature of behavioral responses . These designs allow researchers to establish internal validity by using the same subject in both experimental and control conditions, controlling for individual genetic and physiological variations . For HYKK studies, multiple baseline designs or withdrawal designs can be particularly effective, especially when examining behavioral changes related to nicotine sensitivity or withdrawal . These approaches allow for the inductive process characteristic of early research phases and can decrease time and resource costs while providing valuable insights into individual variations in HYKK function .
How should researchers approach heterogeneity in HYKK expression and function across populations?
Heterogeneity in HYKK expression and function requires stratified randomization approaches in experimental design . Researchers should consider potential heterogeneous treatment effects based on observable characteristics such as genetic variants, sex, or environmental exposures . This involves including relevant subgroups as strata in the research design, which combines the benefits of covariate inclusion (increased precision) without associated drawbacks such as biased average treatment effect (ATE) . When analyzing HYKK-related phenotypes, covariate adjustment can be beneficial but should be carefully implemented to avoid biasing results, particularly with smaller sample sizes .
What evidence supports HYKK's role in nicotine-related phenotypes, and how should this guide experimental design?
The evidence supporting HYKK's role in nicotine-related phenotypes includes data on acute sensitivity, reward, consumption, and withdrawal . When designing experiments to investigate these relationships, researchers should consider a multi-level approach that integrates mouse model evidence with human genetic studies. Important experimental design considerations include controlling for variables such as prior nicotine exposure, genetic background, and environmental factors that may influence nicotine response. Quantitative trait locus (QTL) mapping approaches have proven valuable in identifying genomic regions associated with HYKK-related nicotine phenotypes , suggesting that integrating genetic mapping with functional studies can provide more comprehensive insights.
How should researchers address conflicting findings in HYKK studies?
When confronting contradictory findings in HYKK research, scientists should adopt a methodical approach that considers experimental design differences, population heterogeneity, and analytical methods . As noted by Lakatos (1978), "It would be wrong to assume that one must stay with a research programme until it has exhausted all its heuristic power" . This suggests that researchers should be open to exploring alternative experimental approaches when faced with conflicting evidence. Integrating both group-level and single-subject designs can provide complementary insights that address different aspects of internal validity . A systematic approach to reconciling contradictory findings includes:
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Examining methodological differences between studies
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Considering population-specific effects that might explain divergent results
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Evaluating measurement precision and statistical power across studies
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Designing targeted experiments to directly test competing hypotheses
What techniques are most effective for measuring HYKK expression and activity in different tissue types?
For measuring HYKK expression and activity, researchers should select methods based on their specific research questions and available tissue samples. RNA sequencing and quantitative PCR are effective for measuring transcript levels, while Western blotting and ELISA can quantify protein abundance. For functional characterization, enzyme activity assays specific to HYKK's kinase function should be optimized for the tissue of interest. Brain tissue analyses present particular challenges due to cell-type heterogeneity, making single-cell approaches increasingly valuable . When comparing human and mouse HYKK expression patterns, researchers should consider conservation of DNA/mRNA exon use and similarities in cell-type-specific expression , as these factors influence the translational relevance of animal model findings.
How can researchers effectively integrate HYKK mouse model findings with human genetic studies?
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Characterizing the degree of genetic and functional conservation between human and mouse HYKK
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Establishing parallel phenotypic measures across species
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Using conditional knockout or transgenic models to evaluate causality in mice
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Confirming findings through human genetic association studies
-
Validating functional effects in human cellular models
Product Science Overview
Hydroxylysine kinase (HYKK) is an enzyme that plays a crucial role in the metabolism of lysine, an essential amino acid. This enzyme is responsible for the phosphorylation of 5-hydroxy-L-lysine, a post-translationally modified form of lysine, using GTP as a phosphate donor . The human recombinant form of this enzyme is produced through recombinant DNA technology, allowing for its study and application in various research and therapeutic contexts.
The HYKK gene, also known as AGPHD1 (Aminoglycoside Phosphotransferase Domain-Containing Protein 1), is located on chromosome 15 in humans . The gene encodes a protein that is involved in the lysine degradation pathway, specifically in the saccharopine pathway . The enzyme is predicted to be located in the mitochondrial matrix, where it catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine .
Hydroxylysine kinase catalyzes the following chemical reaction: [ \text{GTP} + \text{5-hydroxy-L-lysine} \rightarrow \text{GDP} + \text{5-phosphonooxy-L-lysine} ] This reaction is essential for the metabolism of hydroxylysine, converting it into a phosphorylated form that can be further processed by other enzymes .
The phosphorylation of hydroxylysine by HYKK is a critical step in the lysine degradation pathway. This pathway is important for the catabolism of lysine, which is necessary for maintaining amino acid balance and producing energy in the form of ATP . Additionally, the products of lysine degradation are involved in various metabolic processes, including the synthesis of carnitine, a molecule essential for fatty acid metabolism .
The human recombinant form of hydroxylysine kinase is produced using recombinant DNA technology. This involves inserting the HYKK gene into a suitable expression vector, which is then introduced into a host organism, such as E. coli or yeast. The host organism expresses the HYKK protein, which can be purified and used for research or therapeutic purposes .
Recombinant hydroxylysine kinase is valuable for studying the enzyme’s structure, function, and role in lysine metabolism. It can also be used to investigate the molecular mechanisms underlying certain metabolic disorders, such as 5-hydroxylysinuria, which is characterized by the accumulation of hydroxylysine in the body . Furthermore, understanding the function of HYKK may provide insights into the development of new therapeutic strategies for treating metabolic diseases.
