PXD052877

PXD052877 is an original dataset announced via ProteomeXchange.

Title	ER-phagy restrains inflammatory responses through receptor UBAC2
Description	ER-phagy, a selective degradation of endoplasmic reticulum (ER) fragment, plays a critical role in maintaining the ER homeostasis. Dysregulation of ER-phagy is involved in the unfolded protein response (UPR), which serves as a vital clue to evoke inflammatory disease. However, the molecular mechanism underpinning the connection between ER-phagy and disease remains poorly defined. Here, we identified ubiquitin-associated domain-containing protein 2 (UBAC2) as an ER-phagy receptor, but a negative regulator of inflammatory responses. UBAC2 harbors a canonical LC3-interacting region (LIR) in the cytoplasmic domain that bind to autophagosomal GABARAP. Upon ER-stress or autophagy activation condition, microtubule affinity-regulating kinase 2 (MARK2) catalyzes the phosphorylation of UBAC2 at serine (S) 223 to promote its dimerization. Dimerized UBAC2 exhibits a stronger ability to interact with GABARAP for selective degradation of ER. Moreover, UBAC2 restrains inflammatory responses and acute ulcerative colitis (UC) in mice through affecting the ER-phagy. Our findings reveal ER-phagy directed by MARK2-UBAC2 axis can provide therapy target for inflammatory disease.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_18:32:24.736.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xing he
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-05 17:49:44	ID requested
⏵ 1	2025-05-06 18:32:25	announced

He X, He H, Hou Z, Wang Z, Shi Q, Zhou T, Wu Y, Qin Y, Wang J, Cai Z, Cui J, Jin S, ER-phagy restrains inflammatory responses through its receptor UBAC2. EMBO J, 43(21):5057-5084(2024) [pubmed]

10.1038/s44318-024-00232-z;

submitter keyword: ER-phagy

UBAC2

MARK2

inflammatory responses

colitis

Xing He
contact affiliation	Sun Yat-sen University
contact email	hexing3@mail2.sysu.edu.cn
lab head
Xing he
contact affiliation	Sun Yat-sen University
contact email	hexing3@mail2.sysu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052877
     1. Label: PRIDE project
     2. Name: ER-phagy restrains inflammatory responses through receptor UBAC2