PXD019056

PXD019056 is an original dataset announced via ProteomeXchange.

Title	Wild-type and L317P mutant ARHGAP36 isoform 2 interactome
Description	ARHGAP36 is an atypical Rho GTPase-activating protein (GAP) family member that drives both spinal cord development and tumorigenesis, acting in part through an N-terminal motif that suppresses protein kinase A and activates Gli transcription factors. ARHGAP36 also contains isoform-specific N-terminal sequences, a central GAP-like module, and a unique C-terminal domain, and the functions of these regions remain unknown. Here we have mapped the ARHGAP36 structure-activity landscape using a deep sequencing-based mutagenesis screen and truncation mutant analyses. Using this approach, we have discovered several residues in the GAP homology domain that are essential for Gli activation and a role for the C-terminal domain in counteracting an N-terminal autoinhibitory motif that is present in certain ARHGAP36 isoforms. In addition, each of these sites modulates ARHGAP36 recruitment to the plasma membrane or primary cilium. Through comparative proteomics, we also have identified proteins that preferentially interact with active ARHGAP36, and we demonstrate that one binding partner, prolyl oligopeptidase-like protein, is a novel ARHGAP36 antagonist. Our work reveals multiple modes of ARHGAP36 regulation and establishes an experimental framework that can be applied towards other signaling proteins. This accession contains raw data from an interactome analysis of wild-type and L317P mutant ARHGAP36 isoform 2, represented in Fig. 5 and Dataset S2 of the associated publication.nactive GAP-like domain mutant, we have also identified prolyl oligopeptidase-like protein (PREPL) as a direct antagonist that decreases ARHGAP36 protein expression. In combination, our systems-level analyses uncover an ensemble of mechanisms that regulate ARHGAP36 expression, localization, and activity state, providing a potential means for context-specific ARHGAP36 functions. This accession contains raw data from an interactome analysis of wild-type and L317P mutant ARHGAP36 isoform 2, represented in Fig. 5 and Dataset S2 of the associated publication.
HostingRepository	PRIDE
AnnounceDate	2021-05-19
AnnouncementXML	Submission_2021-05-19_07:28:14.982.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD019056
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Patricia Nano
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Propionamide; Glu->pyro-Glu; Deamidated; Oxidation; Dioxidation; Acetyl; Gln->pyro-Glu
Instrument	Q Exactive HF-X; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-07 23:46:23	ID requested
⏵ 1	2021-05-19 07:28:15	announced

Nano PR, Johnson TK, Kudo T, Mooney NA, Ni J, Demeter J, Jackson PK, Chen JK, Structure-activity mapping of ARHGAP36 reveals regulatory roles for its GAP homology and C-terminal domains. PLoS One, 16(5):e0251684(2021) [pubmed]

submitter keyword: LC-MSMS,Mouse, NIH-3T3

James K. Chen
contact affiliation	Stanford University School of Medicine
contact email	jameschen@stanford.edu
lab head
Patricia Nano
contact affiliation	Stanford University School of Medicine
contact email	pnano@stanford.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019056
     1. Label: PRIDE project
     2. Name: Wild-type and L317P mutant ARHGAP36 isoform 2 interactome