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RAP1GAP (RAP1 GTPase activating protein)

Written2010-01Zixing Chen, Xuejun Shao
Jiangsu Institute of Hematology, 1st Affiliated Hospital, Soochow University, Suzhou 215006 JS, China

(Note : for Links provided by Atlas : click)

Identity

Alias (NCBI)RAPGAP
RAP1GA1
KIAA0474
RAP1GAP1
RAP1GAPII
HGNC (Hugo) RAP1GAP
HGNC Alias symbKIAA0474
RAP1GAP1
RAP1GAPII
HGNC Previous nameRAP1GA1
HGNC Previous nameRAP1, GTPase activating protein 1
LocusID (NCBI) 5909
Atlas_Id 42043
Location 1p36.12  [Link to chromosome band 1p36]
Location_base_pair Starts at 21596221 and ends at 21669357 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping RAP1GAP.png]
Local_order From centromere to telomere: NBPF3, ALPL, RAP1GAP, USP48, HSPG2.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
EIF4G3 (1p36.12)::RAP1GAP (1p36.12)RAP1GAP (1p36.12)::GLIS3 (9p24.2)RAP1GAP (1p36.12)::GOLGB1 (3q13.33)
RAP1GAP (1p36.12)::NIT2 (3q12.2)RAP1GAP (1p36.12)::USP48 (1p36.12)

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.

Protein

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

Note
  
Entity 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 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.
  

Bibliography

Activation of Rap1 promotes prostate cancer metastasis.
Bailey CL, Kelly P, Casey PJ.
Cancer Res. 2009 Jun 15;69(12):4962-8. Epub 2009 May 26.
PMID 19470770
 
Protein RAP1GAP in human myelodysplastic syndrome detected by flow cytometry and its clinical relevance.
Ika SA, Qi XF, Chen ZX.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Jun;17(3):612-7.
PMID 19549374
 
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, Goto M, Lee JS, Maldonado D, Taylor JM, Pan Q, Carey TE, Bradford CR, Prince ME, Cordell KG, Kirkwood KL, D'Silva NJ.
Cancer Res. 2008 May 15;68(10):3959-69.
PMID 18483282
 
Loss of Rap1GAP in papillary thyroid cancer.
Nellore A, Paziana K, Ma C, Tsygankova OM, Wang Y, Puttaswamy K, Iqbal AU, Franks SR, Lv Y, Troxel AB, Feldman MD, Meinkoth JL, Brose MS.
J Clin Endocrinol Metab. 2009 Mar;94(3):1026-32. Epub 2008 Dec 9.
PMID 19066305
 
Expression of Rap1GAP in human myeloid disease following microarray selection.
Qi X, Chen Z, Qian J, Cen J, Gu M.
Genet Mol Res. 2008 Apr 29;7(2):379-87.
PMID 18551404
 
Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier function.
Wittchen ES, Worthylake RA, Kelly P, Casey PJ, Quilliam LA, Burridge K.
J Biol Chem. 2005 Mar 25;280(12):11675-82. Epub 2005 Jan 20.
PMID 15661741
 
Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer.
Zhang L, Chenwei L, Mahmood R, van Golen K, Greenson J, Li G, D'Silva NJ, Li X, Burant CF, Logsdon CD, Simeone DM.
Cancer Res. 2006 Jan 15;66(2):898-906.
PMID 16424023
 
Rap1GAP inhibits tumor growth in oropharyngeal squamous cell carcinoma.
Zhang Z, Mitra RS, Henson BS, Datta NS, McCauley LK, Kumar P, Lee JS, Carey TE, D'Silva NJ.
Am J Pathol. 2006 Feb;168(2):585-96.
PMID 16436672
 
Down-regulation of Rap1GAP via promoter hypermethylation promotes melanoma cell proliferation, survival, and migration.
Zheng H, Gao L, Feng Y, Yuan L, Zhao H, Cornelius LA.
Cancer Res. 2009 Jan 15;69(2):449-57.
PMID 19147557
 

Citation

This paper should be referenced as such :
Chen, Z ; Shao, X
RAP1GAP (RAP1 GTPase activating protein)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(11):1034-1035.
Free journal version : [ pdf ]   [ DOI ]


External links

 

Nomenclature
HGNC (Hugo)RAP1GAP   9858
Cards
AtlasRAP1GAPID42043ch1p36
Entrez_Gene (NCBI)RAP1GAP    RAP1 GTPase activating protein
AliasesRAP1GA1; RAP1GAP1; RAP1GAPII; RAPGAP
GeneCards (Weizmann)RAP1GAP
Ensembl hg19 (Hinxton)ENSG00000076864 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000076864 [Gene_View]  ENSG00000076864 [Sequence]  chr1:21596221-21669357 [Contig_View]  RAP1GAP [Vega]
ICGC DataPortalENSG00000076864
TCGA cBioPortalRAP1GAP
AceView (NCBI)RAP1GAP
Genatlas (Paris)RAP1GAP
SOURCE (Princeton)RAP1GAP
Genetics Home Reference (NIH)RAP1GAP
Genomic and cartography
GoldenPath hg38 (UCSC)RAP1GAP  -     chr1:21596221-21669357 -  1p36.12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RAP1GAP  -     1p36.12   [Description]    (hg19-Feb_2009)
GoldenPathRAP1GAP - 1p36.12 [CytoView hg19]  RAP1GAP - 1p36.12 [CytoView hg38]
ImmunoBaseENSG00000076864
Genome Data Viewer NCBIRAP1GAP [Mapview hg19]  
OMIM600278   
Gene and transcription
Genbank (Entrez)AB003930 AB007943 AF114047 AI301600 AI827348
RefSeq transcript (Entrez)NM_001145657 NM_001145658 NM_001330383 NM_001350524 NM_001350525 NM_001350526 NM_001350527 NM_001350528 NM_001388200 NM_001388201 NM_001388202 NM_001388203 NM_001388204 NM_001388205 NM_001388206 NM_001388207 NM_001388208 NM_001388209 NM_001388210 NM_001388211 NM_001388212 NM_001388213 NM_001388214 NM_001388215 NM_001388216 NM_001388217 NM_001388218 NM_001388219 NM_001388220 NM_001388221 NM_001388222 NM_001388223 NM_001388224 NM_001388225 NM_001388226 NM_001388227 NM_001388228 NM_001388229 NM_001388230 NM_001388231 NM_001388233 NM_001388234 NM_001388235 NM_001388236 NM_001388237 NM_001388238 NM_001388239 NM_001388240 NM_001388241 NM_001388242 NM_001388243 NM_001388244 NM_001388245 NM_001388246 NM_001388247 NM_001388248 NM_001388249 NM_001388250 NM_001388251 NM_001388252 NM_001388253 NM_001388254 NM_001388255 NM_001388256 NM_001388258 NM_001388259 NM_001388261 NM_001388263 NM_001388264 NM_001388266 NM_001388267 NM_001388269 NM_001388270 NM_001388273 NM_001388276 NM_001388279 NM_001388280 NM_001388281 NM_001388282 NM_001388283 NM_001388284 NM_001388285 NM_001388286 NM_001388287 NM_001388288 NM_001388289 NM_001388290 NM_001388291 NM_001388292 NM_001388293 NM_001388294 NM_001388295 NM_001388296 NM_002885
Consensus coding sequences : CCDS (NCBI)RAP1GAP
Gene ExpressionRAP1GAP [ NCBI-GEO ]   RAP1GAP [ EBI - ARRAY_EXPRESS ]   RAP1GAP [ SEEK ]   RAP1GAP [ MEM ]
Gene Expression Viewer (FireBrowse)RAP1GAP [ Firebrowse - Broad ]
GenevisibleExpression of RAP1GAP in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5909
GTEX Portal (Tissue expression)RAP1GAP
Human Protein AtlasENSG00000076864-RAP1GAP [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP47736   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP47736  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP47736
PhosPhoSitePlusP47736
Domaine pattern : Prosite (Expaxy)GOLOCO (PS50877)    RAPGAP (PS50085)   
Domains : Interpro (EBI)GoLoco_motif    Rap/Ran-GAP_sf    Rap_GAP_dom   
Domain families : Pfam (Sanger)GoLoco (PF02188)    Rap_GAP (PF02145)   
Domain families : Pfam (NCBI)pfam02188    pfam02145   
Domain families : Smart (EMBL)GoLoco (SM00390)  
Conserved Domain (NCBI)RAP1GAP
PDB (RSDB)1SRQ    3BRW   
PDB Europe1SRQ    3BRW   
PDB (PDBSum)1SRQ    3BRW   
PDB (IMB)1SRQ    3BRW   
Structural Biology KnowledgeBase1SRQ    3BRW   
SCOP (Structural Classification of Proteins)1SRQ    3BRW   
CATH (Classification of proteins structures)1SRQ    3BRW   
SuperfamilyP47736
AlphaFold pdb e-kbP47736   
Human Protein Atlas [tissue]ENSG00000076864-RAP1GAP [tissue]
HPRD02609
Protein Interaction databases
DIP (DOE-UCLA)P47736
IntAct (EBI)P47736
BioGRIDRAP1GAP
STRING (EMBL)RAP1GAP
ZODIACRAP1GAP
Ontologies - Pathways
QuickGOP47736
Ontology : AmiGOGolgi membrane  adaptive immune response  GTPase activity  GTPase activator activity  GTPase activator activity  protein binding  cytoplasm  early endosome  cytosol  cytosol  signal transduction  axon guidance  membrane  membrane  axon  dendrite  small GTPase binding  protein homodimerization activity  neuronal cell body  regulation of GTPase activity  positive regulation of GTPase activity  negative regulation of neuron differentiation  regulation of small GTPase mediated signal transduction  activation of GTPase activity  negative regulation of microvillus assembly  negative regulation of GTP binding  negative regulation of thyroid gland epithelial cell proliferation  cellular response to glial cell derived neurotrophic factor  
Ontology : EGO-EBIGolgi membrane  adaptive immune response  GTPase activity  GTPase activator activity  GTPase activator activity  protein binding  cytoplasm  early endosome  cytosol  cytosol  signal transduction  axon guidance  membrane  membrane  axon  dendrite  small GTPase binding  protein homodimerization activity  neuronal cell body  regulation of GTPase activity  positive regulation of GTPase activity  negative regulation of neuron differentiation  regulation of small GTPase mediated signal transduction  activation of GTPase activity  negative regulation of microvillus assembly  negative regulation of GTP binding  negative regulation of thyroid gland epithelial cell proliferation  cellular response to glial cell derived neurotrophic factor  
Pathways : KEGGRap1 signaling pathway   
REACTOMEP47736 [protein]
REACTOME PathwaysR-HSA-8853659 [pathway]   
NDEx NetworkRAP1GAP
Atlas of Cancer Signalling NetworkRAP1GAP
Wikipedia pathwaysRAP1GAP
Orthology - Evolution
OrthoDB5909
GeneTree (enSembl)ENSG00000076864
Phylogenetic Trees/Animal Genes : TreeFamRAP1GAP
Homologs : HomoloGeneRAP1GAP
Homology/Alignments : Family Browser (UCSC)RAP1GAP
Gene fusions - Rearrangements
Fusion : MitelmanEIF4G3::RAP1GAP [1p36.12/1p36.12]  
Fusion : MitelmanRAP1GAP::GOLGB1 [1p36.12/3q13.33]  
Fusion : MitelmanRAP1GAP::NIT2 [1p36.12/3q12.2]  
Fusion : MitelmanRAP1GAP::USP48 [1p36.12/1p36.12]  
Fusion : QuiverRAP1GAP
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRAP1GAP [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RAP1GAP
dbVarRAP1GAP
ClinVarRAP1GAP
MonarchRAP1GAP
1000_GenomesRAP1GAP 
Exome Variant ServerRAP1GAP
GNOMAD BrowserENSG00000076864
Varsome BrowserRAP1GAP
ACMGRAP1GAP variants
VarityP47736
Genomic Variants (DGV)RAP1GAP [DGVbeta]
DECIPHERRAP1GAP [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRAP1GAP 
Mutations
ICGC Data PortalRAP1GAP 
TCGA Data PortalRAP1GAP 
Broad Tumor PortalRAP1GAP
OASIS PortalRAP1GAP [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRAP1GAP  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DRAP1GAP
Mutations and Diseases : HGMDRAP1GAP
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
BioMutaRAP1GAP
DgiDB (Drug Gene Interaction Database)RAP1GAP
DoCM (Curated mutations)RAP1GAP
CIViC (Clinical Interpretations of Variants in Cancer)RAP1GAP
NCG (London)RAP1GAP
Cancer3DRAP1GAP
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600278   
Orphanet
DisGeNETRAP1GAP
MedgenRAP1GAP
Genetic Testing Registry RAP1GAP
NextProtP47736 [Medical]
GENETestsRAP1GAP
Target ValidationRAP1GAP
Huge Navigator RAP1GAP [HugePedia]
ClinGenRAP1GAP
Clinical trials, drugs, therapy
MyCancerGenomeRAP1GAP
Protein Interactions : CTDRAP1GAP
Pharm GKB GenePA34220
PharosP47736
Clinical trialRAP1GAP
Miscellaneous
canSAR (ICR)RAP1GAP
HarmonizomeRAP1GAP
DataMed IndexRAP1GAP
Probes
Litterature
PubMed74 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
EVEXRAP1GAP
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:26:32 CEST 2021

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