PREX2 phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PREX2provided by HGNC
Official Full Name: phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2provided by HGNC
Primary source: HGNC:HGNC:22950
See related: Ensembl:ENSG00000046889 MIM:612139; AllianceGenome:HGNC:22950
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: DEP.2; DEPDC2; P-REX2; PPP1R129
Summary: 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]
Expression: Broad expression in fat (RPKM 6.7), brain (RPKM 5.0) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q13.2

Exon count:: 42

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (67952046..68237032)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (68378485..68663734)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (68864281..69149267)

Chromosome 8 - NC_000008.11 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: 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?

Structural analysis of the PTEN:P-Rex2 signaling complex reveals how cancer-associated mutations coordinate to hyperactivate Rac1.
Title: Structural analysis of the PTEN:P-Rex2 signaling complex reveals how cancer-associated mutations coordinate to hyperactivate Rac1.
Phosphatidylinositol 3,4,5-Trisphosphate-Dependent Rac Exchanger 2 Protein Facilitates Glioma Progression via Akt and Stat3 Signaling.
Title: Phosphatidylinositol 3,4,5-Trisphosphate-Dependent Rac Exchanger 2 Protein Facilitates Glioma Progression via Akt and Stat3 Signaling.
PREX2 gene's expression in gastric antral epithelial cells of patients with H. pylori infection.
Title: PREX2 gene's expression in gastric antral epithelial cells of patients with H. pylori infection.
Somatic mutations of PREX2 gene in patients with hepatocellular carcinoma.
Title: Somatic mutations of PREX2 gene in patients with hepatocellular carcinoma.
MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC.
Title: MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC.
CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction.
Title: CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction.
Study demonstrates that miR-637 inhibites melanoma cell proliferation by activation of AKT signaling pathway and induces apoptosis through regulation of Bcl-2/Bax expression via targeting P-REX2a.
Title: MiR-637 suppresses melanoma progression through directly targeting P-REX2a and inhibiting PTEN/AKT signaling pathway.
MiR-338-3p suppresses the TNF-alpha-induced lipogenesis in sebocytes by targeting PREX2a and down-regulating PI3K/AKT signaling.
Title: MiR-338-3p inhibits TNF-α-induced lipogenesis in human sebocytes.
Data suggest that PREX1 and PREX2 share similarities in amino acid sequence, domain structure, activation by PIP(3) [phosphatidylinositol 3,4,5-triphosphate] and G-protein-coupled receptors beta/gamma subunits; expression of PREX1 and PREX2 is altered in many cancers. [REVIEW]
Title: P-Rex1 and P-Rex2 RacGEFs and cancer.
complex signaling mechanisms that involve PREX2, PI3K/AKT/PTEN and downstream epigenetic machinery to deregulate expression of key cell cycle regulators
Title: Interplay between PREX2 mutations and the PI3K pathway and its effect on epigenetic regulation of gene expression in NRAS-mutant melanoma.

Submit: New GeneRIF Correction See all GeneRIFs (28)

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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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTPase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in adult locomotory behavior	IEA Inferred from Electronic Annotation more info
involved_in dendrite morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in cytosol	TAS Traceable Author Statement more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein

Names: DEP domain-containing protein 2; PtdIns(3,4,5)-dependent Rac exchanger 2; protein phosphatase 1, regulatory subunit 129

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.

Genomic

NG_047022.1 RefSeqGene

Range

5064..290050

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_024870.4 → NP_079146.2 phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein isoform a

See identical proteins and their annotated locations for NP_079146.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

AC103783, AC104416, AJ437636, BI457806, CR936666, R05648

Consensus CDS

CCDS6201.1

UniProtKB/Swiss-Prot

B4DFX0, Q32KL0, Q32KL1, Q6R7Q3, Q6R7Q4, Q70Z35, Q9H805, Q9H961

UniProtKB/TrEMBL

A0A2X0SZ31

Related

ENSP00000288368.4, ENST00000288368.5

Conserved Domains (6) summary

cd00992
Location:677 → 744

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd04439
Location:382 → 462

DEP_1_P-Rex; DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF ...

cd04440
Location:474 → 566

DEP_2_P-Rex; DEP (Dishevelled, Egl-10, and Pleckstrin) domain 2 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF ...

cd01224
Location:218 → 364

PH_Collybistin_ASEF; Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain

pfam00169
Location:248 → 356

PH; PH domain

pfam00621
Location:27 → 213

RhoGEF; RhoGEF domain
NM_025170.6 → NP_079446.3 phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein isoform b

See identical proteins and their annotated locations for NP_079446.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 3' UTR and coding region compared to variant 1, that causes a frameshift. The resulting isoform (b) is shorter and has a distinct C-terminus compared to isoform a.

Source sequence(s)

AC011853, AC104416, AJ437636, AK023049, BI457806

UniProtKB/Swiss-Prot

Q70Z35

Related

ENST00000529398.5

Conserved Domains (6) summary

cd00992
Location:677 → 744

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

cd04439
Location:382 → 462

DEP_1_P-Rex; DEP (Dishevelled, Egl-10, and Pleckstrin) domain 1 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF ...

cd04440
Location:474 → 566

DEP_2_P-Rex; DEP (Dishevelled, Egl-10, and Pleckstrin) domain 2 found in P-Rex-like proteins. The P-Rex family is the guanine-nucleotide exchange factor (GEF) for the small GTPase Rac that contains an N-terminal RhoGEF domain, two DEP and PDZ domains. Rac-GEF ...

cd01224
Location:218 → 364

PH_Collybistin_ASEF; Collybistin/APC-stimulated guanine nucleotide exchange factor pleckstrin homology (PH) domain

pfam00169
Location:248 → 356

PH; PH domain

pfam00621
Location:27 → 213

RhoGEF; RhoGEF 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

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

67952046..68237032

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047422268.1 → XP_047278224.1 phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein isoform X2
XM_047422267.1 → XP_047278223.1 phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

68378485..68663734

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054361290.1 → XP_054217265.1 phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein isoform X2
XM_054361289.1 → XP_054217264.1 phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein isoform X1