PXD022601 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-11-18 01:41:05 | ID requested | |
⏵ 1 | 2021-09-09 13:49:24 | announced | |
Publication List
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] |
Keyword List
submitter keyword: human, LC-MSMS, cancer |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022601
- Label: PRIDE project
- Name: Evolution of Modularity, Interactome and Functions of GIV/Girdin (CCDC88A) from Invertebrates to Vertebrates