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

    Gene ID: 22821, updated on 28-Oct-2024

    Summary

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    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

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    See RASA3 in Genome Data Viewer
    Location:
    13q34
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (113977783..114132623, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (113188423..113340668, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (114747194..114898098, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 452 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:114616152-114617351 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114622697-114623581 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8045 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114638965-114639466 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114639467-114639966 Neighboring gene chromosome 13 open reading frame 46 Neighboring gene SWI/SNF complex interacting GAS6 enhancer non-coding RNA Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114748299-114748799 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114789740-114790579 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114796667-114797608 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:114801666-114802865 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114804717-114805611 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8046 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8047 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114813561-114814350 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114812769-114813560 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114829337-114829856 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8048 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8049 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5554 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8050 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5555 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8051 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8052 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8053 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8054 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:114838566-114839765 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr13:114848666-114849865 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr13:114852049-114853248 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114875547-114876182 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:114876854-114877008 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr13:114878083-114878678 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:114878884-114880083 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114880307-114881171 Neighboring gene uncharacterized LOC124903221 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114882210-114883162 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114883163-114884114 Neighboring gene ReSE screen-validated silencer GRCh37_chr13:114884948-114885289 Neighboring gene RASA3 intronic transcript 1 Neighboring gene uncharacterized LOC107987192 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114892696-114893197 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114895306-114895935 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8055 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8056 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114897194-114897821 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5557 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114900119-114900619 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114906114-114907109 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8058 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8059 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114916272-114916772 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:114916773-114917273 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114927227-114928127 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114951001-114951592 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:114952186-114952777 Neighboring gene CFAP97 domain containing 2 Neighboring gene Sharpr-MPRA regulatory region 1096 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:114993807-114994308 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8061 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5558 Neighboring gene microRNA 548ar Neighboring gene cell division cycle 16

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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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    Related articles in PubMed

    1. GAP1IP4BP contains a novel group I pleckstrin homology domain that directs constitutive plasma membrane association. Cozier GE, et al. J Biol Chem, 2000 Sep 8. PMID 10869341
    2. Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of the GAP1 family. Cullen PJ, et al. Nature, 1995 Aug 10. PMID 7637787
    3. Tissue-specific expression and endogenous subcellular distribution of the inositol 1,3,4,5-tetrakisphosphate-binding proteins GAP1(IP4BP) and GAP1(m). Lockyer PJ, et al. Biochem Biophys Res Commun, 1999 Feb 16. PMID 10049724
    4. Inositol 1,3,4,5-tetrakisphosphate and Ca2+ homoeostasis: the role of GAP1IP4BP. Cullen PJ, et al. Biochem Soc Trans, 1997 Aug. PMID 9388588
    5. Isolation of InsP4 and InsP6 binding proteins from human platelets: InsP4 promotes Ca2+ efflux from inside-out plasma membrane vesicles containing 104 kDa GAP1IP4BP protein. O'Rourke F, et al. Biochem J, 1996 May 1. PMID 8645140, Free PMC Article

    See all (39) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. role in intracellular calcium homeostasis
      Title: Analyzing the role of the putative inositol 1,3,4,5-tetrakisphosphate receptor GAP1IP4BP in intracellular Ca2+ homeostasis.
    6. 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.
    Submit: New GeneRIF Correction

    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)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC46517, MGC47588

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium channel regulator 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 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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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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    NEW Try the new Transcript table

    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)

    1. 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

    2. 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

    3. 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_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      113977783..114132623 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047430157.1 → XP_047286113.1  ras GTPase-activating protein 3 isoform X4

    2. XM_047430155.1 → XP_047286111.1  ras GTPase-activating protein 3 isoform X2

    3. XM_047430156.1 → XP_047286112.1  ras GTPase-activating protein 3 isoform X3

    4. 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

    5. 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

    6. XM_047430158.1 → XP_047286114.1  ras GTPase-activating protein 3 isoform X4

    7. XM_047430161.1 → XP_047286117.1  ras GTPase-activating protein 3 isoform X4

    8. XM_047430163.1 → XP_047286119.1  ras GTPase-activating protein 3 isoform X4

    9. XM_047430162.1 → XP_047286118.1  ras GTPase-activating protein 3 isoform X4

    10. XM_047430160.1 → XP_047286116.1  ras GTPase-activating protein 3 isoform X4

    11. XM_047430154.1 → XP_047286110.1  ras GTPase-activating protein 3 isoform X1

    12. XM_047430159.1 → XP_047286115.1  ras GTPase-activating protein 3 isoform X5

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_011332698.1 Reference GRCh38.p14 PATCHES

      Range
      40809..191714 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054331721.1 → XP_054187696.1  ras GTPase-activating protein 3 isoform X4

    2. XM_054331718.1 → XP_054187693.1  ras GTPase-activating protein 3 isoform X2

    3. XM_054331719.1 → XP_054187694.1  ras GTPase-activating protein 3 isoform X3

    4. XM_054331717.1 → XP_054187692.1  ras GTPase-activating protein 3 isoform X2

    5. XM_054331720.1 → XP_054187695.1  ras GTPase-activating protein 3 isoform X2

    6. XM_054331722.1 → XP_054187697.1  ras GTPase-activating protein 3 isoform X4

    7. XM_054331726.1 → XP_054187701.1  ras GTPase-activating protein 3 isoform X4

    8. XM_054331725.1 → XP_054187700.1  ras GTPase-activating protein 3 isoform X4

    9. XM_054331724.1 → XP_054187699.1  ras GTPase-activating protein 3 isoform X4

    10. XM_054331716.1 → XP_054187691.1  ras GTPase-activating protein 3 isoform X1

    11. XM_054331723.1 → XP_054187698.1  ras GTPase-activating protein 3 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      113188423..113340668 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054374237.1 → XP_054230212.1  ras GTPase-activating protein 3 isoform X4

    2. XM_054374234.1 → XP_054230209.1  ras GTPase-activating protein 3 isoform X2

    3. XM_054374235.1 → XP_054230210.1  ras GTPase-activating protein 3 isoform X7

    4. XM_054374233.1 → XP_054230208.1  ras GTPase-activating protein 3 isoform X2

    5. XM_054374236.1 → XP_054230211.1  ras GTPase-activating protein 3 isoform X2

    6. XM_054374238.1 → XP_054230213.1  ras GTPase-activating protein 3 isoform X4

    7. XM_054374240.1 → XP_054230215.1  ras GTPase-activating protein 3 isoform X4

    8. XM_054374242.1 → XP_054230217.1  ras GTPase-activating protein 3 isoform X4

    9. XM_054374241.1 → XP_054230216.1  ras GTPase-activating protein 3 isoform X4

    10. XM_054374232.1 → XP_054230207.1  ras GTPase-activating protein 3 isoform X6

    11. XM_054374239.1 → XP_054230214.1  ras GTPase-activating protein 3 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14644.3 GenPept UniProtKB/Swiss-Prot:Q14644

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