Details for: HYKK

Gene ID: 123688

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: HYKK

Ensembl ID: ENSG00000188266

Description: hydroxylysine kinase

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ependymal cell CL0000065
    CSI 3.5
    rCSI 7.11%
    PRS 90.11
  • neural progenitor cell CL0011020
    CSI 2.74
    rCSI 12.04%
    PRS 92.24
  • respiratory suprabasal cell CL4033048
    CSI 2.61
    rCSI 3.35%
    PRS 98.56

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [HYKK](/details-gene/123688), or hydroxylysine kinase, is a protein-coding gene located on chromosome 15q25.1. Functionally, it is an enzyme with amino acid kinase activity, localized to the mitochondrial matrix, that plays a specific role in the catabolism of lysine through phosphorylation. Expression data suggests a specialized function, with significant expression observed in distinct cell populations including [ependymal cells](/details-cell/CL0000065), [neural progenitor cells](/details-cell/CL0011020), and [respiratory suprabasal cells](/details-cell/CL4033048), indicating a potential role in the metabolic processes of these specific cell types. ## Cellular Roles and Expression Landscape The expression profile of [HYKK](/details-gene/123688) points towards a specialized role in discrete cell populations rather than broad, ubiquitous function. **Overall**, the gene shows its highest significance in [ependymal cells](/details-cell/CL0000065) (CSI: 3.50), which form the epithelial lining of the brain's ventricular system. This is followed by high significance in [neural progenitor cells](/details-cell/CL0011020) (CSI: 2.74), suggesting a potential involvement in neurodevelopment or the maintenance of neural stem cell pools. Interestingly, [HYKK](/details-gene/123688) also demonstrates significant expression in [respiratory suprabasal cells](/details-cell/CL4033048) (CSI: 2.61). The pattern of high expression in these diverse, specialized cell types from both the central nervous system and respiratory epithelium suggests that its metabolic function may be particularly important for cells with high metabolic demand, specific structural roles, or active proliferation. ## Pathways and Molecular Function Functionally, [HYKK](/details-gene/123688) is an enzyme with hydroxylysine kinase activity ([GO:0047992](https://www.ebi.ac.uk/QuickGO/term/GO:0047992)), contributing to the broader biological process of phosphorylation ([GO:0016310](https://www.ebi.ac.uk/QuickGO/term/GO:0016310)). Its molecular function was specifically identified as a hydroxylysine kinase involved in the degradation pathway of hydroxylysine ([Link](https://doi.org/10.1074/jbc.m111.323485)). This role places it within the lysine catabolic process ([GO:0006554](https://www.ebi.ac.uk/QuickGO/term/GO:0006554)), a key pathway in the metabolism of amino acids ([R-HSA-71291](https://reactome.org/content/detail/R-HSA-71291)). The Reactome database further annotates its involvement in lysine catabolism ([R-HSA-71064](https://reactome.org/content/detail/R-HSA-71064)). Consistent with its role in core energy metabolism, the [HYKK](/details-gene/123688) protein is localized to the mitochondrial matrix ([GO:0005759](https://www.ebi.ac.uk/QuickGO/term/GO:0005759)). This localization and function are consistent with its high expression in metabolically active progenitor and epithelial cells. ## Research Directions The specific expression pattern of [HYKK](/details-gene/123688) in distinct cell populations, coupled with its defined metabolic role, prompts several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in [ependymal cells](/details-cell/CL0000065), [HYKK](/details-gene/123688)-mediated lysine catabolism may be essential for maintaining the metabolic homeostasis and barrier function of the ependymal lining, potentially influencing cerebrospinal fluid composition. 2. The high expression of [HYKK](/details-gene/123688) in [neural progenitor cells](/details-cell/CL0011020) suggests that this metabolic pathway is crucial for providing energy or biosynthetic precursors required for self-renewal and differentiation during neurodevelopment. Dysregulation of [HYKK](/details-gene/123688) could therefore impair the proper formation of neural tissues. **Experimental Approach:** To test the hypothesis regarding its role in neural progenitors, a robust experimental plan could be implemented. Using a human induced pluripotent stem cell (iPSC) model, [HYKK](/details-gene/123688) could be knocked out using CRISPR-Cas9. These knockout and wild-type iPSCs would then be differentiated into [neural progenitor cells](/details-cell/CL0011020). Subsequent analysis using single-cell RNA sequencing could reveal defects in the differentiation trajectory towards neurons or glia. Furthermore, metabolic flux analysis could be performed to directly measure changes in lysine catabolism and its impact on central carbon metabolism in the absence of [HYKK](/details-gene/123688) function. **Therapeutic Potential:** As an enzyme in a core metabolic pathway, [HYKK](/details-gene/123688) could represent a potential therapeutic target, particularly in diseases characterized by metabolic reprogramming. For instance, in certain types of brain tumors that may arise from or share characteristics with [neural progenitor cells](/details-cell/CL0011020), there could be a dependency on the lysine catabolism pathway. In such a context, specific inhibition of [HYKK](/details-gene/123688) might selectively target cancer cells. However, its expression in other specialized cells, such as those in the respiratory epithelium, suggests that systemic inhibition could lead to off-target effects, necessitating the development of highly targeted delivery systems or inhibitors.

Genular Protein ID: 3842892374

Symbol: HYKK_HUMAN

Name: Hydroxylysine kinase

UniProtKB Accession Codes:

A2RU49 B7ZMA5 F8W6X5 Q6ZTN0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChEBI 5 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 2 EMBL 5 Ensembl 5 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 1 RefSeq 2 Rhea 1 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 22241472

Title: Molecular identification of hydroxylysine kinase and of ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and phosphoethanolamine.

PubMed ID: 22241472

DOI: 10.1074/jbc.m111.323485

Sequence Information:

  • Length: 373
  • Mass: 41933
  • Checksum: C8BF3521D8D980A2
  • Sequence:
    • MSSGNYQQSE ALSKPTFSEE QASALVESVF GLKVSKVRPL PSYDDQNFHV YVSKTKDGPT 
EYVLKISNTK ASKNPDLIEV QNHIIMFLKA AGFPTASVCH TKGDNTASLV SVDSGSEIKS 
YLVRLLTYLP GRPIAELPVS PQLLYEIGKL AAKLDKTLQR FHHPKLSSLH RENFIWNLKN 
VPLLEKYLYA LGQNRNREIV EHVIHLFKEE VMTKLSHFRE CINHGDLNDH NILIESSKSA 
SGNAEYQVSG ILDFGDMSYG YYVFEVAITI MYMMIESKSP IQVGGHVLAG FESITPLTAV 
EKGALFLLVC SRFCQSLVMA AYSCQLYPEN KDYLMVTAKT GWKHLQQMFD MGQKAVEEIW 
FETAKSYESG ISM