Rasa3 RAS p21 protein activator 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Rasa3provided by MGI
Official Full Name: RAS p21 protein activator 3provided by MGI
Primary source: MGI:MGI:1197013
See related: Ensembl:ENSMUSG00000031453 AllianceGenome:MGI:1197013
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: scat; GAPIII; hlb381; E130011G04
Summary: Predicted to enable intracellularly gated calcium channel activity. Predicted to be involved in intracellular signal transduction; negative regulation of Ras protein signal transduction; and platelet activation. Predicted to act upstream of or within cellular response to heat. Predicted to be located in cytoplasmic side of plasma membrane. Is expressed in several structures, including alimentary system; brain; genitourinary system; hemolymphoid system; and neural retina. Used to study aplastic anemia. Orthologous to human RASA3 (RAS p21 protein activator 3). [provided by Alliance of Genome Resources, Jan 2025]
Expression: Ubiquitous expression in spleen adult (RPKM 50.1), mammary gland adult (RPKM 30.6) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 A1.1; 8 6.29 cM

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (13617218..13727590, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (13567218..13677587, complement)

Chromosome 8 - NC_000074.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Rasa3 regulates stage-specific cell cycle progression in murine erythropoiesis.
Title: Rasa3 regulates stage-specific cell cycle progression in murine erythropoiesis.
Differential effects of RASA3 mutations on hematopoiesis are profoundly influenced by genetic background and molecular variant.
Title: Differential effects of RASA3 mutations on hematopoiesis are profoundly influenced by genetic background and molecular variant.
RASA3 promoted proteasome-mediated IRF4 protein degradation by facilitating interaction of IRF4 with E3-ubiquitin ligase Cbl-b. Therefore, a RASA3-IRF4-Cbl-b pathway specifically directs pTh17 cell generation by balancing reciprocal Th17-Th2 cell programs. These findings indicate that a distinct molecular program directs pTh17 cell generation and reveals targets for treating pTh17 cell-related pathology and diseases.
Title: RAS P21 Protein Activator 3 (RASA3) Specifically Promotes Pathogenic T Helper 17 Cell Generation by Repressing T-Helper-2-Cell-Biased Programs.
Rasa3 is a critical regulator of Rap1 in endothelial cells which controls adhesions properties and vascular lumen integrity; its specific endothelial cell inactivation results in occluded blood vessels, hemorrhages and early embryonic death in mouse, mimicking thus the Rasa3-/- mouse phenotype.
Title: Rasa3 controls turnover of endothelial cell adhesion and vascular lumen integrity by a Rap1-dependent mechanism.
these results support an important role for Rasa3 in PI3K-dependent integrin alphaIIbbeta3-mediated outside-in signaling and cell spreading.
Title: The Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) Binder Rasa3 Regulates Phosphoinositide 3-kinase (PI3K)-dependent Integrin αIIbβ3 Outside-in Signaling.
the function of RASA3 during megakaryopoiesis, megakaryocyte adhesion and migration as well as integrin signaling has been reported.
Title: The Ras/Rap GTPase activating protein RASA3: from gene structure to in vivo functions.
our results indicate that Rasa3 catalytic activity controls Rap1 activation and integrin signaling during megakaryocyte differentiation in mouse.
Title: Rasa3 controls megakaryocyte Rap1 activation, integrin signaling and differentiation into proplatelet.
Expression of RASA3 led to premature platelet activation and markedly reduced the life span of circulating platelets.
Title: RASA3 is a critical inhibitor of RAP1-dependent platelet activation.
Identified is in the scat (severe combined anemia and thrombocytopenia) mouse model a missense mutation (G125V) in the Rasa3 gene, encoding a Ras GTPase activating protein.
Title: The scat mouse model highlights RASA3, a GTPase activating protein, as a key regulator of vertebrate erythropoiesis and megakaryopoiesis.
RASA3 plays a critical, conserved, and nonredundant role for RASA3 in vertebrate hematopoiesis.
Title: Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis.

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Phenotypes

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Associated conditions

Description	Tests
severe combined anemia and thrombocytopenia GeneReviews: Not available

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1)
Endonuclease-mediated (2)
Spontaneous (1) 1 citation
Targeted (8) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8Mit60 (e-PCR), detects polymorphism
- UniSTS:131605

Rasa3 (e-PCR), detects polymorphism
- UniSTS:498483

C86362 (e-PCR)
- UniSTS:208241

D16Wox25 (e-PCR)
- UniSTS:518841

Rasa3 (e-PCR), detects polymorphism
- UniSTS:498401

AI326412 (e-PCR)
- UniSTS:179702

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables GTPase activator activity	IEA Inferred from Electronic Annotation more info
enables calcium channel regulator activity	IEA Inferred from Electronic Annotation more info
enables intracellularly gated calcium channel activity	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within cellular response to heat	ISO Inferred from Sequence Orthology more info	PubMed
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of Ras protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in platelet activation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasmic side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic side of plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: ras GTPase-activating protein 3

Names: GAP1(IP4BP); GAPIII activator 3; R-Ras gap; R-ras RTPase activating protein-3; Ras GTPase-activating protein III; ins P4-binding protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_009025.2 → NP_033051.2 ras GTPase-activating protein 3

Status: VALIDATED

Source sequence(s)

BC057300, CA749631

Consensus CDS

CCDS40234.1

UniProtKB/Swiss-Prot

Q60790, Q6PG24, Q925V1

UniProtKB/TrEMBL

Q3UGJ5

Related

ENSMUSP00000112998.3, ENSMUST00000117551.4

Conserved Domains (7) summary

smart00107
Location:679 → 714

BTK; Bruton's tyrosine kinase Cys-rich motif

cd04010
Location:146 → 288

C2B_RasA3; C2 domain second repeat present in RAS p21 protein activator 3 (RasA3)

cd08401
Location:13 → 133

C2A_RasA2_RasA3; C2 domain first repeat present in RasA2 and RasA3

cd05134
Location:297 → 565

RasGAP_RASA3; Ras-GTPase Activating Domain of RASA3

smart00323
Location:275 → 614

RasGAP; GTPase-activator protein for Ras-like GTPases

cd13371
Location:562 → 686

PH_GAP1_mammal-like; GAP1(IP4BP) pleckstrin homology (PH) domain

pfam00169
Location:577 → 676

PH; PH domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000074.7 Reference GRCm39 C57BL/6J

Range

13617218..13727590 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006508734.3 → XP_006508797.1 ras GTPase-activating protein 3 isoform X1

UniProtKB/TrEMBL

Q3UGJ5

Conserved Domains (5) summary

smart00107
Location:647 → 682

BTK; Bruton's tyrosine kinase Cys-rich motif

cd04010
Location:114 → 256

C2B_RasA3; C2 domain second repeat present in RAS p21 protein activator 3 (RasA3)

cd08401
Location:1 → 101

C2A_RasA2_RasA3; C2 domain first repeat present in RasA2 and RasA3

cd05134
Location:265 → 533

RasGAP_RASA3; Ras-GTPase Activating Domain of RASA3

cd13371
Location:530 → 654

PH_GAP1_mammal-like; GAP1(IP4BP) pleckstrin homology (PH) domain