PXD022601

PXD022601 is an original dataset announced via ProteomeXchange.

Title	Evolution of Modularity, Interactome and Functions of GIV/Girdin (CCDC88A) from Invertebrates to Vertebrates
Description	PDZ domains are one of the most abundant protein domains in eukaryotes and frequently found on junction-localized scaffold proteins. Various signaling molecules bind to PDZ proteins via PDZ-binding motifs (PBM) and finetune cellular signaling. Here we describe the presence of a PBM on GIV/Girdin (CCDC88A) that is conserved throughout evolution, from invertebrates to vertebrates, and is generated as a long isoform-variant in humans, which we named GIV-L. Unlike GIV, which lacks PBM and is cytosolic, GIV-L localizes to the cell junctions, and has a unique PDZ-interactome, which impacts GIV-L’s ability to bind and activate trimeric G-protein, Gi through its guanine-nucleotide exchange modulator (GEM) module; the GEM module is found exclusively in vertebrates. Thus, the two functional modules in GIV evolved sequentially: the ability to bind PDZ proteins via the PBM evolved earlier in invertebrates, whereas G-protein binding and activation may have evolved later only among vertebrates. Phenotypic studies in Caco-2 cells revealed that GIV and GIV-L may have antagonistic effects on cell growth, proliferation (cell cycle), and survival. Immunohistochemical analyses in human colon tissues showed that GIV expression increases with a concomitant decrease in GIV-L during cancer initiation. Taken together, these findings reveal how GIV/CCDC88A in humans displays evolutionary flexibility in modularity, which allows the resultant isoforms to play opposing roles either as a tumor suppressor (GIV-L) or as an oncogene (GIV).
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_13:49:23.420.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Majid Ghassemian
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-18 01:41:05	ID requested
⏵ 1	2021-09-09 13:49:24	announced

Ear J, Abd El-Hafeez AA, Roy S, Ngo T, Rajapakse N, Choi J, Khandelwal S, Ghassemian M, McCaffrey L, Kufareva I, Sahoo D, Ghosh P, A long isoform of GIV/Girdin contains a PDZ-binding module that regulates localization and G-protein binding. J Biol Chem, 296():100493(2021) [pubmed]

submitter keyword: human, LC-MSMS, cancer

Pradipta Ghosh
contact affiliation	Department of Medicine, University of California San Diego, La Jolla, California 92093
contact email	prghosh@ucsd.edu
lab head
Majid Ghassemian
contact affiliation	Scientist
contact email	mghassem@ucsd.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022601
     1. Label: PRIDE project
     2. Name: Evolution of Modularity, Interactome and Functions of GIV/Girdin (CCDC88A) from Invertebrates to Vertebrates