PXD030823-1

PXD030823 is an original dataset announced via ProteomeXchange.

Title	The Okur-Chung Neurodevelopmental Syndrome (OCNDS) mutation CK2K198R leads to a rewiring of kinase specificity
Description	Okur-Chung Neurodevelopmental Syndrome (OCNDS) is caused by heterozygous mutations to the CSNK2A1 gene, which encodes the alpha subunit of casein kinase II (CK2). The most frequently occurring mutation is lysine 198 to arginine (K198R). To investigate the impact of this mutation, we first generated a high-resolution phosphorylation motif of CK2WT, including the first characterization of specificity for tyrosine phosphorylation activity. A second high resolution motif representing CK2K198R substrate specificity was also generated. Here we report the impact of the OCNDS associated CK2K198R mutation. Contrary to prior speculation, the mutation does not result in a loss of function, but rather shifts the substrate specificity of the kinase. Broadly speaking the mutation leads to 1) a decreased preference for acidic residues in the +1 position, 2) a decreased preference for threonine phosphorylation, 3) an increased preference for tyrosine phosphorylation, and 4) an alteration of the tyrosine phosphorylation specificity motif. To further investigate the result of this mutation we have developed a probability-based scoring method, allowing us to predict shifts in phosphorylation in the K198R mutant relative to the wild type kinase. As an initial step we have applied the methodology to the set of axonally localized ion channels in an effort to uncover potential alterations of the phosphoproteome associated with the OCNDS disease condition.
HostingRepository	PRIDE
AnnounceDate	2022-05-31
AnnouncementXML	Submission_2022-05-31_02:30:37.049.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeremy Balsbaugh
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-07 12:57:42	ID requested
⏵ 1	2022-05-31 02:30:37	announced

Caefer DM, Phan NQ, Liddle JC, Balsbaugh JL, O'Shea JP, Tzingounis AV, Schwartz D, Leads to a Rewiring of Kinase Specificity. Front Mol Biosci, 9():850661(2022) [pubmed]

submitter keyword: Okur-Chung, phosphoproteomics, CKII, CK2, kinase, mutation, phosphorylation, ProPeL

Jeremy Balsbaugh
contact affiliation	Proteomics & Metabolomics Facility, University of Connecticut
contact email	jeremy.balsbaugh@uconn.edu
lab head
Jeremy Balsbaugh
contact affiliation	University of Connecticut
contact email	jeremy.balsbaugh@uconn.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030823
     1. Label: PRIDE project
     2. Name: The Okur-Chung Neurodevelopmental Syndrome (OCNDS) mutation CK2K198R leads to a rewiring of kinase specificity