RASA3 RAS p21 protein activator 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RASA3provided by HGNC
Official Full Name: RAS p21 protein activator 3provided by HGNC
Primary source: HGNC:HGNC:20331
See related: Ensembl:ENSG00000185989 MIM:605182; AllianceGenome:HGNC:20331
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GAPIII; GAP1IP4BP
Summary: This gene encodes a protein that binds inositol 1,3,4,5-tetrakisphosphate and stimulates the GTPase activity of Ras p21. This protein functions as a negative regulator of the Ras signalling pathway. It is localized to the cell membrane via a pleckstrin homology (PH) domain in the C-terminal region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
Expression: Ubiquitous expression in fat (RPKM 14.2), lymph node (RPKM 12.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 13q34

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (113977783..114132623, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (113188423..113340668, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (114747194..114898098, complement)

Chromosome 13 - NC_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
model in which the Ras GAP-related domain of GAP1(IP4BP) functions to stabilize the switch II region of Rap1, allowing stabilization of the transition state during GTP hydrolysis initiated by the arginine finger
Title: The ability of GAP1IP4BP to function as a Rap1 GTPase-activating protein (GAP) requires its Ras GAP-related domain and an arginine finger rather than an asparagine thumb.
role in intracellular calcium homeostasis
Title: Analyzing the role of the putative inositol 1,3,4,5-tetrakisphosphate receptor GAP1IP4BP in intracellular Ca2+ homeostasis.
GAP1IP4BP is an inositol 1,3,4,5-tetrakisphosphate regulated plasma membrane associated Ras and Rap GAP. Membrane association results from its PH domain binding phosphatidylinositol 4,5-bisphosphate.
Title: Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-30142 (e-PCR)
- UniSTS:59916

SHGC-145617 (e-PCR)
- UniSTS:174683

SHGC-153448 (e-PCR)
- UniSTS:177756

STS-A09781 (e-PCR)
- UniSTS:70076

SHGC-156053 (e-PCR)
- UniSTS:182740

STS-W90753 (e-PCR)
- UniSTS:2536

RH104222 (e-PCR)
- UniSTS:98547

SHGC-145856 (e-PCR)
- UniSTS:174839

G20512 (e-PCR)
- UniSTS:58621

A005U29 (e-PCR)
- UniSTS:58622

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase activator activity	IEA Inferred from Electronic Annotation more info
enables intracellularly gated calcium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in calcium-mediated signaling	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 signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: ras GTPase-activating protein 3

Names: GTPase activating protein III; GTPase-activating protein 1 family, inositol 1,3,4,5-tetrakisphosphate-binding protein; Ins(1,3,4,5)P4-binding protein; 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_001320821.2 → NP_001307750.1 ras GTPase-activating protein 3 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains two alternate exons in the 5' region and initiates translation at a downstream start codon compared to variant 1. The encoded isoform (2) has a much shorter N-terminus than isoform 1.

Source sequence(s)

AK128094, AL161774, BC047242, DA328760

UniProtKB/Swiss-Prot

Q14644

Conserved Domains (3) summary

smart00107
Location:296 → 331

BTK; Bruton's tyrosine kinase Cys-rich motif

cd13371
Location:179 → 303

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

cl02569
Location:1 → 182

RasGAP; Ras GTPase Activating Domain
NM_001320822.2 → NP_001307751.1 ras GTPase-activating protein 3 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon compared to variant 1. The encoded isoform (3) has a shorter N-terminus than isoform 1.

Source sequence(s)

AK294913, AL161774, BC047242

UniProtKB/Swiss-Prot

Q14644

Conserved Domains (7) 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

smart00323
Location:243 → 582

RasGAP; GTPase-activator protein for Ras-like GTPases

cd13371
Location:530 → 654

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

pfam00169
Location:545 → 644

PH; PH domain
NM_007368.4 → NP_031394.2 ras GTPase-activating protein 3 isoform 1

See identical proteins and their annotated locations for NP_031394.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AK128094, BC038456, BC047242, DA328760

Consensus CDS

CCDS32016.1

UniProtKB/Swiss-Prot

A6NL15, F8W6X8, Q14644, Q8IUY2

Related

ENSP00000335029.7, ENST00000334062.8

Conserved Domains (5) 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

cd13371
Location:562 → 686

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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000013.11 Reference GRCh38.p14 Primary Assembly

Range

113977783..114132623 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047430157.1 → XP_047286113.1 ras GTPase-activating protein 3 isoform X4
XM_047430155.1 → XP_047286111.1 ras GTPase-activating protein 3 isoform X2
XM_047430156.1 → XP_047286112.1 ras GTPase-activating protein 3 isoform X3
XM_011534841.4 → XP_011533143.1 ras GTPase-activating protein 3 isoform X2

See identical proteins and their annotated locations for XP_011533143.1

UniProtKB/Swiss-Prot

Q14644

Conserved Domains (7) 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

smart00323
Location:243 → 582

RasGAP; GTPase-activator protein for Ras-like GTPases

cd13371
Location:530 → 654

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

pfam00169
Location:545 → 644

PH; PH domain
XM_011534842.3 → XP_011533144.1 ras GTPase-activating protein 3 isoform X2

See identical proteins and their annotated locations for XP_011533144.1

UniProtKB/Swiss-Prot

Q14644

Conserved Domains (7) 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

smart00323
Location:243 → 582

RasGAP; GTPase-activator protein for Ras-like GTPases

cd13371
Location:530 → 654

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

pfam00169
Location:545 → 644

PH; PH domain
XM_047430158.1 → XP_047286114.1 ras GTPase-activating protein 3 isoform X4
XM_047430161.1 → XP_047286117.1 ras GTPase-activating protein 3 isoform X4
XM_047430163.1 → XP_047286119.1 ras GTPase-activating protein 3 isoform X4
XM_047430162.1 → XP_047286118.1 ras GTPase-activating protein 3 isoform X4
XM_047430160.1 → XP_047286116.1 ras GTPase-activating protein 3 isoform X4
XM_047430154.1 → XP_047286110.1 ras GTPase-activating protein 3 isoform X1
XM_047430159.1 → XP_047286115.1 ras GTPase-activating protein 3 isoform X5