Human Gene RASA1 (ENST00000456692.6) from GENCODE V44
  Description: Homo sapiens RAS p21 protein activator 1 (RASA1), transcript variant 2, mRNA. (from RefSeq NM_022650)
RefSeq Summary (NM_022650): The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Mutations also have been associated with hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM) and Parkes Weber syndrome. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues. [provided by RefSeq, May 2012].
Gencode Transcript: ENST00000456692.6
Gencode Gene: ENSG00000145715.15
Transcript (Including UTRs)
   Position: hg38 chr5:87,268,933-87,391,931 Size: 122,999 Total Exon Count: 25 Strand: +
Coding Region
   Position: hg38 chr5:87,269,048-87,390,883 Size: 121,836 Coding Exon Count: 25 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:87,268,933-87,391,931)mRNA (may differ from genome)Protein (870 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: RASA1_HUMAN
DESCRIPTION: RecName: Full=Ras GTPase-activating protein 1; Short=GAP; Short=GTPase-activating protein; Short=RasGAP; AltName: Full=Ras p21 protein activator; AltName: Full=p120GAP;
FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1.
SUBUNIT: Interacts with SQTSM1. Interacts with SPSB1; the interaction does not promote degradation. Interacts with CAV2 (tyrosine phosphorylated form). Directly interacts with NCK1. Interacts with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1.
INTERACTION: P16333:NCK1; NbExp=6; IntAct=EBI-1026476, EBI-389883;
SUBCELLULAR LOCATION: Cytoplasm.
TISSUE SPECIFICITY: In placental villi, detected only in the trophoblast layer (cytotrophoblast and syncytiotrophoblast). Not detected in stromal, endothelial or Hofbauer cells (at protein level).
PTM: The N-terminus is blocked.
PTM: Phosphorylated by SRC and LCK. The phosphorylation SRC inhibits its ability to stimulate the Ras-GTPase activity, whereas phosphorylation by LCK does not display any effect on stimulation activity.
DISEASE: Note=Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas.
DISEASE: Defects in RASA1 are the cause of capillary malformation- arteriovenous malformation (CMAVM) [MIM:608354]. CMAVM is a disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome.
DISEASE: Defects in RASA1 are a cause of Parkes Weber syndrome (PKWS) [MIM:608355]. PKWS is a disorder characterized by a cutaneous flush with underlying multiple micro-arteriovenous fistulas, in association with soft tissue and skeletal hypertrophy of the affected limb.
SIMILARITY: Contains 1 C2 domain.
SIMILARITY: Contains 1 PH domain.
SIMILARITY: Contains 1 Ras-GAP domain.
SIMILARITY: Contains 2 SH2 domains.
SIMILARITY: Contains 1 SH3 domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RASA1";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: RASA1
Diseases sorted by gene-association score: capillary malformation-arteriovenous malformation* (1703), parkes weber syndrome* (1290), basal cell carcinoma 1* (520), rasa1-related disorders* (100), parkes weber syndrome, rasa1-related* (100), arteriovenous malformation (59), weber syndrome (39), stork bite (17), angiokeratoma circumscriptum (16), neurofibromatosis, type 1 (14), angioma serpiginosum (11), arteriovenous fistula (11), intracranial hemorrhage in brain cerebrovascular malformations (11), taylor's syndrome (9), nodular nonsuppurative panniculitis (9), skin hemangioma (8), capillary hemangioma (7), klippel-trenaunay-weber syndrome (6), immune hydrops fetalis (6), proteus syndrome, somatic (6), venous malformations, multiple cutaneous and mucosal (5), trophoblastic neoplasm (5), multiple enchondromatosis, maffucci type (5), noonan syndrome 1 (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D003993 Dibutyl Phthalate
  • C023514 2,6-dinitrotoluene
  • C093973 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • C049584 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • C553817 7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one
  • D000082 Acetaminophen
  • D016604 Aflatoxin B1
  • D000535 Aluminum
  • D001151 Arsenic
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 15.52 RPKM in Testis
Total median expression: 478.44 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -26.60115-0.231 Picture PostScript Text
3' UTR -199.701048-0.191 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000008 - C2_Ca-dep
IPR008973 - C2_Ca/lipid-bd_dom_CaLB
IPR018029 - C2_membr_targeting
IPR011993 - PH_like_dom
IPR001849 - Pleckstrin_homology
IPR001936 - RasGAP
IPR023152 - RasGAP_CS
IPR008936 - Rho_GTPase_activation_prot
IPR000980 - SH2
IPR001452 - SH3_domain

Pfam Domains:
PF00168 - C2 domain
PF00169 - PH domain
PF00616 - GTPase-activator protein for Ras-like GTPase
PF00017 - SH2 domain
PF00018 - SH3 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1WER - X-ray MuPIT 1WQ1 - X-ray MuPIT 2GQI - NMR MuPIT 2GSB - NMR MuPIT 2J05 - X-ray MuPIT 2J06 - X-ray MuPIT 4FSS - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P20936
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001784 phosphotyrosine binding
GO:0003924 GTPase activity
GO:0005096 GTPase activator activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0019870 potassium channel inhibitor activity
GO:0051020 GTPase binding

Biological Process:
GO:0000165 MAPK cascade
GO:0000281 mitotic cytokinesis
GO:0001570 vasculogenesis
GO:0001953 negative regulation of cell-matrix adhesion
GO:0007162 negative regulation of cell adhesion
GO:0007165 signal transduction
GO:0008360 regulation of cell shape
GO:0030833 regulation of actin filament polymerization
GO:0035556 intracellular signal transduction
GO:0043066 negative regulation of apoptotic process
GO:0043087 regulation of GTPase activity
GO:0043524 negative regulation of neuron apoptotic process
GO:0043547 positive regulation of GTPase activity
GO:0046580 negative regulation of Ras protein signal transduction
GO:0048013 ephrin receptor signaling pathway
GO:0048514 blood vessel morphogenesis
GO:0051252 regulation of RNA metabolic process

Cellular Component:
GO:0001726 ruffle
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0031235 intrinsic component of the cytoplasmic side of the plasma membrane


-  Descriptions from all associated GenBank mRNAs
  CR749722 - Homo sapiens mRNA; cDNA DKFZp434N071 (from clone DKFZp434N071).
AB209106 - Homo sapiens mRNA for RAS p21 protein activator 1 isoform 1 variant protein.
LF385533 - JP 2014500723-A/193036: Polycomb-Associated Non-Coding RNAs.
MA621110 - JP 2018138019-A/193036: Polycomb-Associated Non-Coding RNAs.
BC033015 - Homo sapiens RAS p21 protein activator (GTPase activating protein) 1, mRNA (cDNA clone MGC:26760 IMAGE:4829173), complete cds.
M23379 - Human GTPase-activating protein ras p21 (RASA) mRNA, complete cds.
CU689592 - Synthetic construct Homo sapiens gateway clone IMAGE:100017883 5' read RASA1 mRNA.
KJ891984 - Synthetic construct Homo sapiens clone ccsbBroadEn_01378 RASA1 gene, encodes complete protein.
KR709499 - Synthetic construct Homo sapiens clone CCSBHm_00002804 RASA1 (RASA1) mRNA, encodes complete protein.
KR709500 - Synthetic construct Homo sapiens clone CCSBHm_00002813 RASA1 (RASA1) mRNA, encodes complete protein.
AK300269 - Homo sapiens cDNA FLJ61389 complete cds, highly similar to Ras GTPase-activating protein 1.
BC070063 - Homo sapiens cDNA clone IMAGE:30335878, containing frame-shift errors.
BC020761 - Homo sapiens RAS p21 protein activator (GTPase activating protein) 1, mRNA (cDNA clone IMAGE:4733187), partial cds.
BC107870 - Homo sapiens cDNA clone IMAGE:4721787.
AK312739 - Homo sapiens cDNA, FLJ93145, Homo sapiens RAS p21 protein activator (GTPase activating protein)1 (RASA1), transcript variant 2, mRNA.
AK300263 - Homo sapiens cDNA FLJ53191 complete cds, highly similar to Ras GTPase-activating protein 1.
AK300406 - Homo sapiens cDNA FLJ59756 complete cds, highly similar to Ras GTPase-activating protein 1.
M23612 - Human GTPase-activating protein (GAP) mRNA, complete cds.
BC054891 - Homo sapiens RAS p21 protein activator (GTPase activating protein) 1, mRNA (cDNA clone IMAGE:6663865), partial cds.
LF209849 - JP 2014500723-A/17352: Polycomb-Associated Non-Coding RNAs.
MA445426 - JP 2018138019-A/17352: Polycomb-Associated Non-Coding RNAs.
LF332102 - JP 2014500723-A/139605: Polycomb-Associated Non-Coding RNAs.
MA567679 - JP 2018138019-A/139605: Polycomb-Associated Non-Coding RNAs.
JD355363 - Sequence 336387 from Patent EP1572962.
LF332100 - JP 2014500723-A/139603: Polycomb-Associated Non-Coding RNAs.
MA567677 - JP 2018138019-A/139603: Polycomb-Associated Non-Coding RNAs.
JD165729 - Sequence 146753 from Patent EP1572962.
JD287088 - Sequence 268112 from Patent EP1572962.
JD507060 - Sequence 488084 from Patent EP1572962.
JD349579 - Sequence 330603 from Patent EP1572962.
JD084647 - Sequence 65671 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04360 - Axon guidance

Reactome (by CSHL, EBI, and GO)

Protein P20936 (Reactome details) participates in the following event(s):

R-HSA-186798 GAP binds to PDGF-beta receptors only
R-HSA-4093330 EPHB binds p120-RasGAP
R-HSA-8849094 ARHGAP35 binds RASA1
R-HSA-8981355 RASA1 binds RAS:GTP
R-HSA-5218845 p-SPHK1 phosphorylates sphingosine to sphingosine 1-phosphate
R-HSA-8981353 RASA1 stimulates RAS GTPase activity
R-HSA-4093331 Ras:GTP binds p120-RasGAP
R-HSA-5658435 RAS GAPs bind RAS:GTP
R-HSA-5658231 RAS GAPs stimulate RAS GTPase activity
R-HSA-4093339 p120-RasGAP activates GTP hydrolysis on RAS, inactivating it
R-HSA-186763 Downstream signal transduction
R-HSA-3928662 EPHB-mediated forward signaling
R-HSA-8849471 PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-5218921 VEGFR2 mediated cell proliferation
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-6802949 Signaling by RAS mutants
R-HSA-186797 Signaling by PDGF
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-8848021 Signaling by PTK6
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-6802957 Oncogenic MAPK signaling
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-422475 Axon guidance
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-194138 Signaling by VEGF
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-5663202 Diseases of signal transduction
R-HSA-162582 Signal Transduction
R-HSA-1266738 Developmental Biology
R-HSA-5683057 MAPK family signaling cascades
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: B2R6W3, ENST00000456692.1, ENST00000456692.2, ENST00000456692.3, ENST00000456692.4, ENST00000456692.5, NM_022650, P20936, Q9UDI1, RASA, RASA1_HUMAN, uc003kix.1, uc003kix.2, uc003kix.3, uc003kix.4
UCSC ID: ENST00000456692.6
RefSeq Accession: NM_022650
Protein: P20936 (aka RASA1_HUMAN or RSG1_HUMAN)
CCDS: CCDS47243.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene RASA1:
rasa1-rel-dis (Capillary Malformation-Arteriovenous Malformation Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.