RAP1GAP (RAP1 GTPase activating protein)
2010-01-01 Zixing Chen , Xuejun Shao AffiliationJiangsu Institute of Hematology, 1st Affiliated Hospital, Soochow University, Suzhou 215006 JS, China
Identity
HGNC
LOCATION
1p36.12
LOCUSID
ALIAS
RAP1GA1,RAP1GAP1,RAP1GAPII,RAPGAP
FUSION GENES
DNA/RNA
Description
25 exons encompassing about 73 kb of genomic DNA.
Transcription
About 3.334 kb mRNA, and has three transcript variant, RAP1 GTPase activating protein isoform a, b, c.
Proteins
Description
663 amino acids; homodimer and heterodimer with RAP1B.
Expression
Significant expression seen in the brain, kidney and pancreas. Abundant in the cerebral cortex and expressed at much lower levels in the spinal cord. Not detected in the lymphoid tissues. (according to Swiss-Prot).
Localisation
Golgi apparatus membrane; Peripheral membrane protein (according to Swiss-Prot).
Function
GTPase activator for the nuclear Ras-related regulatory protein Rap1, converting it to the putatively inactive GDP-bound state (according to Swiss-Prot); Regulation of small GTPase-mediated signal transduction.
Homology
The RAP1GAP gene is conserved in cow, mouse, rat, zebrafish, fruit fly, mosquito, and C. elegans.
Implicated in
Entity name
Solid tumors
Disease
Papillary thyroid cancer, pancreatic cancer, prostate cancer, melanoma tumors
Oncogenesis
Rap1GAP, which acts as a GTPase activator for the nuclear Ras-related regulatory protein Rap1, was a specific negative regulator of Rap1, and the monomeric G protein Rap1 has been implicated in cancer tumorigenesis. It signals to pathways involved in cell adhesion, migration, and survival. Loss of Rap1GAP was discovered in papillary thyroid cancer, pancreatic cancer, prostate cancer, melanoma tumors, and their cell lines, all of them exhibited increased Rap1 activity, that activation of Rap1 promotes cell proliferation and migration potentiality through the mitogen-activated protein kinase pathway and integrin activation. As a putative tumor suppressor gene, Rap1GAP inhibits tumor growth but induces MMP2- and MMP9-mediated squamous cell carcinoma invasion and tumor progression, suggesting a role for this protein as a biomarker for early N-stage, aggressive squamous cell carcinomas.
Entity name
Myelodysplastic syndrome (MDS)
Disease
The expression level of Rap1GAP in MDS patients significantly increased as compared with patients with non-malignant blood diseases or acute myeloid leukemia (AML). Among MDS patients, the expression level of Rap1GAP in MDS-refractory anemia (RA) was significantly higher than that in MDS-refractory anemia with excess of blasts (RAEB).
On the other hand, inhibiting Rap1 activity by expression of Rap1GAP increased leukocyte transendothelial migration, providing physiological relevance to the hypothesis that Rap1 augments barrier function of inter-endothelial cell junctions, implying the relevance of Rap1GAP in the regulation of haematogenesis.
On the other hand, inhibiting Rap1 activity by expression of Rap1GAP increased leukocyte transendothelial migration, providing physiological relevance to the hypothesis that Rap1 augments barrier function of inter-endothelial cell junctions, implying the relevance of Rap1GAP in the regulation of haematogenesis.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 19470770 | 2009 | Activation of Rap1 promotes prostate cancer metastasis. | Bailey CL et al |
| 19549374 | 2009 | Protein RAP1GAP in human myelodysplastic syndrome detected by flow cytometry and its clinical relevance. | Ika SA et al |
| 18483282 | 2008 | Rap1GAP promotes invasion via induction of matrix metalloproteinase 9 secretion, which is associated with poor survival in low N-stage squamous cell carcinoma. | Mitra RS et al |
| 19066305 | 2009 | Loss of Rap1GAP in papillary thyroid cancer. | Nellore A et al |
| 18551404 | 2008 | Expression of Rap1GAP in human myeloid disease following microarray selection. | Qi X et al |
| 15661741 | 2005 | Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier function. | Wittchen ES et al |
| 16424023 | 2006 | Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer. | Zhang L et al |
| 16436672 | 2006 | Rap1GAP inhibits tumor growth in oropharyngeal squamous cell carcinoma. | Zhang Z et al |
| 19147557 | 2009 | Down-regulation of Rap1GAP via promoter hypermethylation promotes melanoma cell proliferation, survival, and migration. | Zheng H et al |
Other Information
Locus ID:
NCBI: 5909
MIM: 600278
HGNC: 9858
Ensembl: ENSG00000076864
Variants:
dbSNP: 5909
ClinVar: 5909
TCGA: ENSG00000076864
COSMIC: RAP1GAP
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38154105 | 2023 | Downregulating miR-184 relieves calcium oxalate crystal-mediated renal cell damage via activating the Rap1 signaling pathway. | 0 |
| 38154105 | 2023 | Downregulating miR-184 relieves calcium oxalate crystal-mediated renal cell damage via activating the Rap1 signaling pathway. | 0 |
| 35054818 | 2022 | Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation. | 1 |
| 35429959 | 2022 | CpG Island Methylation of the Rap1Gap Gene in Medullary Thyroid Cancer. | 1 |
| 35054818 | 2022 | Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation. | 1 |
| 35429959 | 2022 | CpG Island Methylation of the Rap1Gap Gene in Medullary Thyroid Cancer. | 1 |
| 34311462 | 2021 | RAP1GAP Functions as a Tumor Suppressor Gene and Is Regulated by DNA Methylation in Differentiated Thyroid Cancer. | 4 |
| 34840979 | 2021 | Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells. | 1 |
| 34311462 | 2021 | RAP1GAP Functions as a Tumor Suppressor Gene and Is Regulated by DNA Methylation in Differentiated Thyroid Cancer. | 4 |
| 34840979 | 2021 | Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells. | 1 |
| 31879129 | 2020 | Shank3 Binds to and Stabilizes the Active Form of Rap1 and HRas GTPases via Its NTD-ANK Tandem with Distinct Mechanisms. | 9 |
| 31879129 | 2020 | Shank3 Binds to and Stabilizes the Active Form of Rap1 and HRas GTPases via Its NTD-ANK Tandem with Distinct Mechanisms. | 9 |
| 29758923 | 2018 | Reduced expression of Rap1GAP as a prognostic biomarker for primary gastric cancer patients. | 4 |
| 30144784 | 2018 | Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK/MAPK Activation. | 10 |
| 29758923 | 2018 | Reduced expression of Rap1GAP as a prognostic biomarker for primary gastric cancer patients. | 4 |
Citation
Zixing Chen ; Xuejun Shao
RAP1GAP (RAP1 GTPase activating protein)
Atlas Genet Cytogenet Oncol Haematol. 2010-01-01
Online version: http://atlasgeneticsoncology.org/gene/42043/rap1gap-(rap1-gtpase-activating-protein)
