Global phosphoproteomics uncovers PANK2 phosphorylation sites and co-phosphoregulation networks
- 1Corresponding authors.
- 2Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, Karnataka, 575018, India
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.
Related
- Comparative Cell Cycle Phosphoproteomics Reveals Conserved Phosphorylation Events Across Cancer Cell Types
- Decoding the phosphorylation landscape of ITPR3 across calcium signaling and regulatory networks in cancer
- Co-Regulation Analysis of Domain-Specific Phosphosites Reveals Insights into the Phosphoregulation-Directed Functional Diversity of Nucleolin
- High-fidelity bispecific protease KRysin for deeper plasma proteomics and phosphoproteomics
- Tracking cellular biomolecular condensate dynamics under proteostatic stress with middle-down phosphoproteomics
BibTeX
@article{rajeev2026global,
title = {{Global phosphoproteomics uncovers PANK2 phosphorylation sites and co-phosphoregulation networks}},
author = {Athira C. Rajeev and Althaf Mahin and Athira Perunelly Gopalakrishnan and Prathik Basthikoppa Shivamurthy and Rajesh Raju},
journal = {Results in Chemistry},
year = {2026},
month = oct,
doi = {10.1016/j.rechem.2026.104004},
url = {https://doi.org/10.1016/j.rechem.2026.104004},
note = {CC BY},
}
RIS
TY - JOUR
TI - Global phosphoproteomics uncovers PANK2 phosphorylation sites and co-phosphoregulation networks
AU - Athira C. Rajeev
AU - Althaf Mahin
AU - Athira Perunelly Gopalakrishnan
AU - Prathik Basthikoppa Shivamurthy
AU - Rajesh Raju
PY - 2026
DA - 2026/10/30
JO - Results in Chemistry
DO - 10.1016/j.rechem.2026.104004
UR - https://doi.org/10.1016/j.rechem.2026.104004
AB - 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.
SN - 2211-7156
ER -