PXD067557

PXD067557 is an original dataset announced via ProteomeXchange.

Title	Functional dissection of SPOP in the amino acid level reveals comprehensive functional landscape of variants on tumorigenesis
Description	Numerous proteins display pleiotropic functions in different clinical contexts. However, molecular mechanism underlying such effects is rarely understood. The Speckle-type POZ protein (SPOP) is a typical example, showing tumor-suppressing or promoting effects due to different amino acid changes in different tumor types. Specifically, two distinct sets of variants in SPOP are commonly found in subsets of prostate cancer or endometrial cancer patients. To comprehensively characterize the functional landscape of SPOP alteration, we performed a deep mutational screening, elucidating functionality of 7,933 of 8,228 possible single amino acid changes (96.4% coverage). Utilizing the observation that overexpression of human SPOP leads to yeast growth arrest, we assessed the functionality of each variant using a yeast proliferation assay. In assessing these variants, we combined long-read and short-read sequencing reads. While long-read-based scores demonstrated improved concordance with functional classification, both platforms demonstrated a largely consistent classification pattern of external dataset with prediction score. Our DMS model enables a clear distinction between loss-of-function and putative gain-of-function, and reveals their differential characteristics in both protein structure and our functional validation. Our approach demonstrates the utility of our approach in high resolution mapping and amino acid-level interpretation of protein function.
HostingRepository	PRIDE
AnnounceDate	2026-04-20
AnnouncementXML	Submission_2026-04-19_21:53:44.222.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dohyun Han
SpeciesList	scientific name: Staphylococcus aureus; NCBI TaxID: NEWT:1280;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-21 05:32:07	ID requested
⏵ 1	2026-04-19 21:53:44	announced

Dataset with its publication pending

submitter keyword: Yeast, TMT, SPOP

Dohyun Han
contact affiliation	Proteomics and Metabolomics Core Facility, Biomedical Research Institute, Seoul National University Hospital
contact email	hdh03@snu.ac.kr
lab head
Dohyun Han
contact affiliation	Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital
contact email	hdh03@snu.ac.kr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067557
     1. Label: PRIDE project
     2. Name: Functional dissection of SPOP in the amino acid level reveals comprehensive functional landscape of variants on tumorigenesis