PXD008333

PXD008333 is an original dataset announced via ProteomeXchange.

Title	Identification of a damaging variant rs35033974 associated with idiopathic male infertility through degradation of TEX101 protein and its transient interactome
Description	Human TEX101 is a testis-specific cell membrane protein expressed exclusively in male germ cells and a validated biomarker of male infertility. TEX101 was suggested to function as a cell surface chaperone of numerous proteins involved in sperm migration and sperm-egg interaction. However, the precise functional roles of human TEX101 in spermatogenesis and fertilization are unknown. Here, we show that a common homozygous variant rs35033974 of TEX101 (G99V) with ~1% frequency in the general population may be associated with idiopathic male infertility. Spermatozoa from patients with homozygous rs35033974 exhibited near-complete degradation of variant G99V TEX101 protein and concomitant degradation of its interactome, as revealed by proteomic measurements. Substantially reduced levels of numerous testis-specific membrane proteins involved in sperm migration and sperm-oocyte fusion (including LY6K, IZUMO3 and ADAM29) were confirmed in spermatozoa of men with homozygous G99V variant. These men were previously diagnosed with idiopathic male infertility or oligospermia and failed the treatment by intrauterine insemination. Collectively, these data may facilitate diagnostics of idiopathic male infertility, provides a rational for selection of male infertility treatments and validate TEX101 and its interactome as targets to develop non-hormonal male contraceptives.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:42:07.473.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Schiza
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-30 01:17:48	ID requested
1	2018-11-21 07:58:56	announced
⏵ 2	2024-10-22 04:42:07	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: A disintegrin and metalloproteinase domain-containing protein 29

interactome

testis-specific proteins

spermatozoa

single nucleotide polymorphism (SNP)

deleterious variant

unexplained infertility,TEX101

testis-expressed sequence 101 protein

LY6K

Lymphocyte antigen 6 complex, locus K

ADAM29

Dr. Eleftherios P. Diamandis
contact affiliation	Head of Clinical Biochemistry Mount Sinai Hospital and University Health Network, Professor & Head, Division of Clinical Biochemistry Department of Laboratory Medicine & Pathobiology, University of Toronto
contact email	eleftherios.diamandis@sinaihealthsystem.ca
lab head
Christina Schiza
contact affiliation	University of Toronto
contact email	sxristina2011@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/11/PXD008333

PRIDE project URI

• PRIDE
  1. PXD008333
     1. Label: PRIDE project
     2. Name: Identification of a damaging variant rs35033974 associated with idiopathic male infertility through degradation of TEX101 protein and its transient interactome