PXD002103

PXD002103 is an original dataset announced via ProteomeXchange.

Title	FIH regulates cellular metabolism through hydroxylation of the deubiquitinase OTUB1.
Description	The asparagine hydroxylase, factor inhibiting HIF (FIH) confers oxygen-dependence upon the hypoxia-inducible factor (HIF), a master regulator of the cellular adaptive response to hypoxia. Studies investigating whether asparagine hydroxylation is a general regulatory oxygen-dependent modification have identified multiple non-HIF targets for FIH. However the functional consequences of this outside of the HIF pathway remain unclear. Here, we demonstrate that the deubiquitinase ovarian tumor domain containing, ubiquitin aldehyde binding protein 1 (OTUB1) is a substrate for hydroxylation by endogenous FIH on N22. Mutation of N22 leads to a profound change in the interaction of OTUB1 with proteins important in cellular metabolism. Furthermore, mutant OTUB1 (lacking the hydroxylation site) impairs cellular metabolic processes when compared to wild type. Based on these data, we hypothesize that OTUB1 is a target for functional hydroxylation by FIH, and propose that this provides new insight into the regulation of cellular energy metabolism during hypoxia.
HostingRepository	PRIDE
AnnounceDate	2016-01-11
AnnouncementXML	Submission_2016-01-26_06:44:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Javier Rodriguez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-27 01:31:29	ID requested
1	2016-01-11 06:18:54	announced
⏵ 2	2016-01-26 06:44:03	announced	Updated publication reference for PubMed record(s): 26752685.

Scholz CC, Rodriguez J, Pickel C, Burr S, Fabrizio JA, Nolan KA, Spielmann P, Cavadas MA, Crifo B, Halligan DN, Nathan JA, Peet DJ, Wenger RH, Von Kriegsheim A, Cummins EP, Taylor CT, FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1. PLoS Biol, 14(1):e1002347(2016) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: Hydroxylase, hypoxia, metabolism, ubiquitin, deubiquitinating enzyme.

Cormac Taylar
contact affiliation	Principal Investigator. SBI (System Biology Ireland), Conway Institute, UCD
contact email	cormac.taylor@ucd.ie
lab head
Javier Rodriguez
contact affiliation	SBI (SYSTEM BIOLOGY IRELAND)
contact email	javier.rodriguez@ucd.ie
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/2016/01/PXD002103

PRIDE project URI

• PRIDE
  1. PXD002103
     1. Label: PRIDE project
     2. Name: FIH regulates cellular metabolism through hydroxylation of the deubiquitinase OTUB1.