Work

Global phosphoproteomics uncovers PANK2 phosphorylation sites and co-phosphoregulation networks

Year: 2026

Type: article

Abstract: Pantothenate kinase 2 (PANK2) is a mitochondrial enzyme that catalyzes the rate-limiting phosphorylation of pantothenic acid in coenzyme A (CoA) biosynthesis. Mutations in PANK2 cause pantothenate kinase-associated neurodegeneration (PKAN), a rare neurodegenerative disorder characterized by CoA deficiency, mitochondrial dysfunction, iron accumulation, and ferroptosis. This study provides a systematic, phosphoproteome-wide characterization of PANK2 regulation by integrating human phosphoproteomics data curated from 3825 studies, yielding 2359 datasets (2061 profile; 298 differential) reporting a Class-1 PANK2 phosphosite. We identify S168, S169, and S189 as the predominant phosphosites, located primarily in disordered regions outside the catalytic domain. Through high-confidence co-phosphoregulation analysis, we map extensive networks of positively and negatively co-phosphoregulated phosphosites on other proteins (PsOPs), along with potential upstream kinases including AKT1/2, ULK1, and MAPK pathway components, phosphatases e.g., PTPN1, CDC25B, and binary interactors like KSR1 and NFKB1. These correlative findings extend prior biochemical evidence of direct AKT phosphorylation of PANK2 and generate testable hypotheses regarding broader phospho-regulatory networks. Experimental validation will be required to establish causality and functional relevance for PKAN and CoA-deficiency disorders.

Source: Results in Chemistry

DOI: 10.1016/j.rechem.2026.104004

Authors: Athira C. Rajeev, Althaf Mahin, Athira Perunelly Gopalakrishnan, Prathik Basthikoppa Shivamurthy, Rajesh Raju

Institution: Yenepoya University

Language: English

Topic: Neurological diseases and metabolism

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,870