Human Gene PREX2 (uc003xxv.1) Description and Page Index
  Description: Homo sapiens phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2 (PREX2), transcript variant 1, mRNA.
RefSeq Summary (NM_024870): The protein encoded by this gene belongs to the phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger (PREX) family, which are Dbl-type guanine-nucleotide exchange factors for Rac family small G proteins. Structural domains of this protein include the catalytic diffuse B-cell lymphoma homology and pleckstrin homology (DHPH) domain, two disheveled, EGL-10, and pleckstrin homology (DEP) domains, two PDZ domains, and a C-terminal inositol polyphosphate-4 phosphatase (IP4P) domain that is found in one of the isoforms. This protein facilitates the exchange of GDP for GTP on Rac1, allowing the GTP-bound Rac1 to activate downstream effectors. Studies also show that the pleckstrin homology domain of this protein interacts with the phosphatase and tensin homolog (PTEN) gene product to inhibit PTEN phosphatase activity, thus activating the phosphoinositide-3 kinase (PI3K) signaling pathway. Conversely, the PTEN gene product has also been shown to inhibit the GEF activity of this protein. This gene plays a role in insulin-signaling pathways, and either mutations or overexpression of this gene have been observed in some cancers. [provided by RefSeq, Apr 2016].
Transcript (Including UTRs)
   Position: hg19 chr8:68,864,603-69,143,897 Size: 279,295 Total Exon Count: 40 Strand: +
Coding Region
   Position: hg19 chr8:68,864,630-69,143,613 Size: 278,984 Coding Exon Count: 40 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:68,864,603-69,143,897)mRNA (may differ from genome)Protein (1606 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeTreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: PREX2_HUMAN
DESCRIPTION: RecName: Full=Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein; Short=P-Rex2; Short=PtdIns(3,4,5)-dependent Rac exchanger 2; AltName: Full=DEP domain-containing protein 2;
FUNCTION: Functions as a RAC1 guanine nucleotide exchange factor (GEF), activating Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. Mediates the activation of RAC1 in a PI3K-dependent manner. May be an important mediator of Rac signaling, acting directly downstream of both G protein- coupled receptors and phosphoinositide 3-kinase.
SUBUNIT: Interacts with RAC1.
TISSUE SPECIFICITY: Isoform 1 is highly expressed in skeletal muscle, heart and placenta, absent from peripheral blood leukocytes. Isoform 2 is expressed in skeletal muscle, kidney, small intestine, and placenta. Isoform 3 is expressed in the heart.
DOMAIN: PH domain confers substrate specificity and recognition. Able to discriminate between RAC1, RHOA, and CDC42.
DOMAIN: DH domain alone was unable to confer substrate specificity and recognition.
SIMILARITY: Contains 2 DEP domains.
SIMILARITY: Contains 1 DH (DBL-homology) domain.
SIMILARITY: Contains 2 PDZ (DHR) domains.
SIMILARITY: Contains 1 PH domain.
SEQUENCE CAUTION: Sequence=AK024079; Type=Frameshift; Positions=1134; Sequence=BAB14375.1; Type=Erroneous initiation;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PREX2
CDC HuGE Published Literature: PREX2
Positive Disease Associations: Creatinine , Exercise Test , Pancreatic Neoplasms , Tunica Media
Related Studies:
  1. Creatinine
    , , . [PubMed 0]
  2. Exercise Test
    Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics. [PubMed 17903301]
    In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
  3. Exercise Test
    Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics. [PubMed 17903301]
    In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PREX2
Diseases sorted by gene-association score: corneal dystrophy, endothelial, x-linked (11), corneal dystrophy, posterior polymorphous, 1 (8)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.84 RPKM in Brain - Caudate (basal ganglia)
Total median expression: 113.35 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 -6.4027-0.237 Picture PostScript Text
3' UTR -57.30284-0.202 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
IPR000591 - DEP_dom
IPR000219 - DH-domain
IPR001331 - GDS_CDC24_CS
IPR001478 - PDZ
IPR011993 - PH_like_dom
IPR001849 - Pleckstrin_homology
IPR011991 - WHTH_trsnscrt_rep_DNA-bd

Pfam Domains:
PF00169 - PH domain
PF00610 - Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)
PF00621 - RhoGEF domain

SCOP Domains:
46785 - "Winged helix" DNA-binding domain
48065 - DBL homology domain (DH-domain)
50156 - PDZ domain-like
50729 - PH domain-like

ModBase Predicted Comparative 3D Structure on Q70Z35
FrontTopSide
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
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005089 Rho guanyl-nucleotide exchange factor activity
GO:0005096 GTPase activator activity
GO:0030676 Rac guanyl-nucleotide exchange factor activity

Biological Process:
GO:0006469 negative regulation of protein kinase activity
GO:0007186 G-protein coupled receptor signaling pathway
GO:0008344 adult locomotory behavior
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0032007 negative regulation of TOR signaling
GO:0035023 regulation of Rho protein signal transduction
GO:0035556 intracellular signal transduction
GO:0043547 positive regulation of GTPase activity
GO:0048813 dendrite morphogenesis

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AJ437636 - Homo sapiens mRNA for P-Rex2 protein.
AY508997 - Homo sapiens P-Rex2B mRNA, complete cds, alternatively spliced.
AY508996 - Homo sapiens P-Rex2 mRNA, complete cds, alternatively spliced.
BC146369 - Synthetic construct Homo sapiens clone IMAGE:100015096, MGC:180201 phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2 (PREX2) mRNA, encodes complete protein.
BC148795 - Synthetic construct Homo sapiens clone IMAGE:100015912, MGC:183213 phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2 (PREX2) mRNA, encodes complete protein.
AK294299 - Homo sapiens cDNA FLJ56428 complete cds, highly similar to Homo sapiens DEP domain containing 2 (DEPDC2), transcript variant 1, mRNA.
AK023049 - Homo sapiens cDNA FLJ12987 fis, clone NT2RP3000068, weakly similar to SON OF SEVENLESS PROTEIN HOMOLOG 1.
AK024079 - Homo sapiens cDNA FLJ14017 fis, clone HEMBA1000505.
BC068571 - Homo sapiens cDNA clone IMAGE:5303271.
BC036055 - Homo sapiens cDNA clone IMAGE:5277616.
AY570973 - Homo sapiens PtdIns(3,4,5)-dependent rac exchanger-2 (PREX2) mRNA, partial cds.
JD449661 - Sequence 430685 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q70Z35 (Reactome details) participates in the following event(s):

R-HSA-8850961 PREX2 binds PTEN and inhibits it
R-HSA-8948751 Regulation of PTEN stability and activity
R-HSA-6807070 PTEN Regulation
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: DEPDC2, NM_024870, NP_079146, PREX2_HUMAN, Q32KL0, Q32KL1, Q6R7Q3, Q6R7Q4, Q70Z35, Q9H805, Q9H961
UCSC ID: uc003xxv.1
RefSeq Accession: NM_024870
Protein: Q70Z35 (aka PREX2_HUMAN)
CCDS: CCDS6201.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_024870.2
exon count: 40CDS single in 3' UTR: no RNA size: 5132
ORF size: 4821CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 9792.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

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