PXD019303-2

PXD019303 is an original dataset announced via ProteomeXchange.

Title	Hipk4 is a manchette-associated protein essential for spermiogenesis
Description	Nonobstructive azoospermia (NOA) is one of the most severe forms of male infertility, characterized by the absence of spermatozoa in the ejaculate. The etiology and genetic mechanism(s) of this disease remain largely unclear. Using Sanger sequence, we identified 12 heterozygous missense mutations and 2 heterozygous nonsense mutations in the HIPK4, encoding a serine/threonine kinase. Moreover, K490* mutant cause HIPK4 unstable in 293T cells. In accord with these findings, we observed that homozygous Hipk4-/- male mice were infertility owing to malformed and immotile spermatozoa, which are characterized by a deformed nucleus and a detached acrosome. Furthermore, we performed a phosphoproteomic analysis of testis from Hipk4 wild type and knockout mice, revealing multiple targets regulated by Hipk4 during spermiogenesis. Notably, manchette-associated protein Rimbp3 has multiple phosphorylation sites regulated by Hipk4. Moreover, Hipk4 and Rimbp3 deficiency mice display several common phenotypes, in particular with regard to the ectopic positioning of the manchette within spermatids, a presumed cause of sperm head deformities. Thus, Hipk4 might regulate manchette function through phosphorylation of Rimbp3, thereby playing essential role for sperm head formation and male fertility.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:38:34.569.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaofei Liu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-20 01:17:15	ID requested
1	2022-08-02 10:14:57	announced
⏵ 2	2024-10-22 05:38:35	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Hipk4, Spermiogenesis, Mouse

Guo Xuejiang
contact affiliation	State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
contact email	Guo_xuejiang@njmu.edu.cn
lab head
Xiaofei Liu
contact affiliation	Nanjing Medical University
contact email	1215224830@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019303
     1. Label: PRIDE project
     2. Name: Hipk4 is a manchette-associated protein essential for spermiogenesis