KIAA0513 Human

What is KIAA0513 and what are its basic structural features?

KIAA0513 is a 411 amino acid cytoplasmic protein with limited homology to proteins of known function. The gene exists as two alternatively spliced isoforms and is located on human chromosome 16, which contains over 900 genes and comprises approximately 3% of the human genome . The protein lacks well-characterized functional domains, making its molecular function challenging to predict through bioinformatic approaches alone . Structurally, research indicates that the N-terminal portion of KIAA0513 is particularly important for protein-protein interactions, as this region has been demonstrated to interact with several signaling proteins .

What is the expression pattern of KIAA0513 in human tissues?

KIAA0513 shows ubiquitous expression throughout the body but is particularly enriched in brain tissues . Within the brain, highest expression levels are observed in the cerebellum, followed by significant expression in the cerebral cortex, hippocampus, amygdala, pons, and putamen . At the cellular level, KIAA0513 expression is prominent in neurons but is also present in glial cells . Researchers investigating KIAA0513 should consider this differential expression pattern when designing tissue-specific experiments and selecting appropriate controls.

What protein interactions have been identified for KIAA0513?

Yeast two-hybrid screening has revealed that KIAA0513 interacts with several proteins including KIBRA, HAX-1, and INTS4 . These interaction partners are involved in neuroplasticity, apoptosis, and cytoskeletal regulation, suggesting that KIAA0513 may function in these cellular processes . Physical association between KIAA0513 and KIBRA has been confirmed by coimmunoprecipitation analysis . When designing experiments to study KIAA0513 function, researchers should consider these known interaction partners and the potential signaling pathways they implicate.

How is KIAA0513 expression altered in schizophrenia?

KIAA0513 was initially identified as being upregulated in the dorsolateral prefrontal cortex of subjects with schizophrenia through microarray analysis . This differential expression has been subsequently confirmed by quantitative RT-PCR methods . Researchers studying KIAA0513 in the context of schizophrenia should employ region-specific tissue sampling techniques focused on the dorsolateral prefrontal cortex and utilize both protein and mRNA quantification methods to comprehensively assess expression changes. Additionally, consideration of potential confounding factors such as medication history and disease duration is essential for accurate interpretation of results.

What is the significance of anti-KIAA0513 antibodies as biomarkers?

Serum antibodies against KIAA0513 (s-KIAA0513-Ab) have emerged as potential biomarkers for multiple conditions. These antibodies have shown significantly elevated levels in patients with various diseases compared to healthy donors, including:

• Atherosclerosis-related conditions: Acute ischemic stroke (AIS), transient ischemic attack (TIA), cardiovascular disease (CVD)

• Metabolic disorders: Diabetes mellitus (DM)

• Sleep disorders: Obstructive sleep apnea syndrome (OSAS)

• Kidney disease: Chronic kidney disease (CKD), especially nephrosclerosis-type CKD

• Solid cancers: Esophageal, gastric, colon, lung, and breast cancers

Receiver operating characteristic (ROC) analysis has demonstrated that the highest areas under the curve for anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD, and diabetes mellitus, suggesting particularly strong associations with these conditions .

How do anti-KIAA0513 antibody levels correlate with vascular parameters?

Spearman's correlation analysis has revealed significant associations between serum anti-KIAA0513 antibody levels and several markers of vascular health:

These correlations suggest that anti-KIAA0513 antibody levels may reflect underlying arterial alterations associated with atherosclerosis and stenosis . Interestingly, while KIAA0513 antibody levels were elevated in diabetes patients compared to healthy controls, they showed only weak correlation with blood sugar (p=0.023) and no significant correlation with HbA1c , suggesting that these antibodies may primarily reflect vascular complications rather than metabolic dysfunction.

What approaches are recommended for studying KIAA0513 protein expression?

When investigating KIAA0513 protein expression, researchers should employ multiple complementary techniques:

• Western blotting: Useful for quantification of total protein levels and detection of isoforms. Use well-validated antibodies with appropriate controls.

• Immunohistochemistry/immunocytochemistry: Essential for determining cellular and subcellular localization .

• In situ hybridization: Valuable for examining tissue-specific expression patterns, particularly in brain tissues where expression is enriched .

When studying brain tissues, region-specific analysis is crucial given the differential expression across brain areas. Additionally, researchers should differentiate between neuronal and glial expression through co-staining with cell-type specific markers, as KIAA0513 is expressed in both cell types .

How should researchers measure anti-KIAA0513 antibody levels in clinical samples?

For quantification of anti-KIAA0513 antibodies in serum samples, the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) has proven effective . When implementing this methodology:

• Use recombinant KIAA0513 protein (preferably the complete 301 amino acid sequence) as the antigen

• Verify antibody specificity through Western blot analysis before proceeding with quantitative measurements

• Include appropriate controls, particularly age and sex-matched healthy donors

• Consider potential confounding factors such as hypertension, which has shown significant association with anti-KIAA0513 antibody levels (p=0.0091)

The table below summarizes key variables that should be controlled for when measuring anti-KIAA0513 antibody levels:

What strategies are recommended for functional characterization of KIAA0513?

Given the limited homology to proteins of known function and absence of well-characterized domains, functional characterization of KIAA0513 requires multiple approaches:

• Protein-protein interaction studies: Yeast two-hybrid screening has been successful in identifying interaction partners . This should be validated by co-immunoprecipitation assays.

• Gene silencing: siRNA-mediated knockdown can provide insights into cellular functions. Commercial reagents such as KIAA0513 siRNA are available for this purpose .

• Subcellular localization studies: Determine the precise intracellular distribution through confocal microscopy with fluorescently tagged KIAA0513 or specific antibodies.

• Pathway analysis: Based on known interactions with KIBRA, HAX-1, and INTS4, researchers should examine effects on neuroplasticity, apoptotic signaling, and cytoskeletal organization .

When designing functional studies, researchers should consider the cell type context, as KIAA0513 function may differ between neurons and glial cells based on its differential expression .

How might researchers investigate the mechanistic link between KIAA0513 and vascular pathologies?

The discovery that anti-KIAA0513 antibodies correlate with markers of atherosclerosis suggests that KIAA0513 may play a role in vascular health . To investigate this mechanistic link:

• Develop vascular cell models: Study KIAA0513 expression and function in endothelial cells, vascular smooth muscle cells, and macrophages involved in atherosclerotic plaque formation.

• Assess KIAA0513 regulation under atherogenic conditions: Examine how KIAA0513 expression changes in response to inflammatory cytokines, oxidized LDL, and hyperglycemic conditions.

• Evaluate KIAA0513's impact on endothelial function: Determine whether KIAA0513 affects endothelial permeability, nitric oxide production, or inflammatory adhesion molecule expression.

• Investigate KIAA0513 in animal models of atherosclerosis: Consider transgenic approaches to modulate KIAA0513 expression in atherogenic mouse models.

These approaches may help clarify whether KIAA0513 plays a causative role in vascular disease or is merely a biomarker of disease processes.

What challenges exist in interpreting KIAA0513 expression data across disease states?

Several methodological challenges warrant consideration when analyzing KIAA0513 expression:

• Isoform-specific analysis: KIAA0513 exists as two alternatively spliced isoforms , which may have distinct functions. Researchers should employ techniques that can distinguish between these isoforms.

• Cell-type heterogeneity: Given differential expression between neurons and glial cells , bulk tissue analysis may mask cell-type specific changes. Single-cell approaches or cell sorting may be necessary for precise characterization.

• Causality versus correlation: Elevated KIAA0513 expression in conditions like schizophrenia or increased anti-KIAA0513 antibodies in vascular diseases may represent compensatory responses rather than causative factors. Mechanistic studies are essential to differentiate between these possibilities.

• Confounding factors: Consider medication effects, disease duration, and comorbidities when interpreting expression changes, particularly in complex disorders like schizophrenia.

How can researchers address the potential role of KIAA0513 in neurodevelopmental processes?

Given KIAA0513's enrichment in brain tissues and association with schizophrenia , investigating its neurodevelopmental functions is warranted:

• Temporal expression analysis: Characterize KIAA0513 expression throughout brain development using developmental tissue series.

• Neuronal differentiation models: Study KIAA0513's role in neuronal differentiation using stem cell-derived neuronal cultures or neuroblastoma differentiation models.

• Cytoskeletal regulation: Given KIAA0513's interaction with cytoskeletal regulatory proteins , examine its effects on neurite outgrowth, axon guidance, and synapse formation.

• Circuit-specific analysis: Investigate whether KIAA0513 expression is enriched in specific neural circuits relevant to schizophrenia, such as cortico-striatal-thalamic pathways.

This developmental perspective may provide insights into how KIAA0513 dysregulation contributes to neurodevelopmental disorders.

What genomic and transcriptomic approaches might advance KIAA0513 research?

To better understand KIAA0513 regulation and function:

• Promoter analysis: Characterize the KIAA0513 promoter region to identify regulatory elements and transcription factor binding sites.

• Epigenetic profiling: Investigate DNA methylation and histone modifications at the KIAA0513 locus in different tissues and disease states.

• RNA-seq after KIAA0513 modulation: Perform transcriptomic analysis following KIAA0513 knockdown or overexpression to identify downstream pathways.

• Alternative splicing: Characterize the functional differences between KIAA0513 isoforms and the regulation of their alternative splicing.

These approaches may clarify how KIAA0513 expression is regulated in different contexts and provide insights into its biological functions.

How might researchers leverage KIAA0513 antibody biomarkers for clinical applications?

The potential of anti-KIAA0513 antibodies as biomarkers for multiple diseases suggests several research directions:

• Longitudinal studies: Determine whether anti-KIAA0513 antibody levels predict disease progression or treatment response.

• Combinatorial biomarker panels: Evaluate whether combining anti-KIAA0513 antibodies with other biomarkers improves diagnostic accuracy.

• Point-of-care testing: Develop simplified assays for anti-KIAA0513 antibody detection suitable for clinical implementation.

• Therapeutic targeting: Investigate whether modulating KIAA0513 function or reducing anti-KIAA0513 antibody levels affects disease outcomes.

Research in these areas could translate the basic science of KIAA0513 into clinically relevant applications.

What is the potential significance of KIAA0513 as a common link between neuropsychiatric and vascular pathologies?

The association of KIAA0513 with both schizophrenia and vascular diseases presents an intriguing research avenue:

• Cerebrovascular function in schizophrenia: Investigate whether KIAA0513-related vascular abnormalities contribute to the neurobiology of schizophrenia.

• Inflammatory signaling: Examine KIAA0513's role in inflammatory processes common to both neuropsychiatric and vascular diseases.

• Blood-brain barrier function: Study whether KIAA0513 affects blood-brain barrier integrity, which has implications for both cerebrovascular health and neuropsychiatric disorders.

• Shared genetic risk: Explore whether genetic variants affecting KIAA0513 expression or function confer risk for both schizophrenia and vascular diseases.

This integrative approach may reveal unexpected connections between these seemingly disparate disease categories and potentially identify novel therapeutic targets.