PREX2

Protein identityUniProt · HPA

UniProt accession

Q70Z35

Gene

PREX2

Ensembl

ENSG00000046889

Chromosome

8

Canonical length

1606 aa

Protein class

Cancer-related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Endoplasmic reticulum

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1606 residues, UniProt reviewed canonical sequence.

>Q70Z35|PREX2
     1  MSEDSRGDSR AESAKDLEKQ LRLRVCVLSE LQKTERDYVG TLEFLVSAFL HRMNQCAASK
    61  VDKNVTEETV KMLFSNIEDI LAVHKEFLKV VEECLHPEPN AQQEVGTCFL HFKDKFRIYD
   121  EYCSNHEKAQ KLLLELNKIR TIRTFLLNCM LLGGRKNTDV PLEGYLVTPI QRICKYPLIL
   181  KELLKRTPRK HSDYAAVMEA LQAMKAVCSN INEAKRQMEK LEVLEEWQSH IEGWEGSNIT
   241  DTCTEMLMCG VLLKISSGNI QERVFFLFDN LLVYCKRKHR RLKNSKASTD GHRYLFRGRI
   301  NTEVMEVENV DDGTADFHSS GHIVVNGWKI HNTAKNKWFV CMAKTPEEKH EWFEAILKER
   361  ERRKGLKLGM EQDTWVMISE QGEKLYKMMC RQGNLIKDRK RKLTTFPKCF LGSEFVSWLL
   421  EIGEIHRPEE GVHLGQALLE NGIIHHVTDK HQFKPEQMLY RFRYDDGTFY PRNEMQDVIS
   481  KGVRLYCRLH SLFTPVIRDK DYHLRTYKSV VMANKLIDWL IAQGDCRTRE EAMIFGVGLC
   541  DNGFMHHVLE KSEFKDEPLL FRFFSDEEME GSNMKHRLMK HDLKVVENVI AKSLLIKSNE
   601  GSYGFGLEDK NKVPIIKLVE KGSNAEMAGM EVGKKIFAIN GDLVFMRPFN EVDCFLKSCL
   661  NSRKPLRVLV STKPRETVKI PDSADGLGFQ IRGFGPSVVH AVGRGTVAAA AGLHPGQCII
   721  KVNGINVSKE THASVIAHVT ACRKYRRPTK QDSIQWVYNS IESAQEDLQK SHSKPPGDEA
   781  GDAFDCKVEE VIDKFNTMAI IDGKKEHVSL TVDNVHLEYG VVYEYDSTAG IKCNVVEKMI
   841  EPKGFFSLTA KILEALAKSD EHFVQNCTSL NSLNEVIPTD LQSKFSALCS ERIEHLCQRI
   901  SSYKKFSRVL KNRAWPTFKQ AKSKISPLHS SDFCPTNCHV NVMEVSYPKT STSLGSAFGV
   961  QLDSRKHNSH DKENKSSEQG KLSPMVYIQH TITTMAAPSG LSLGQQDGHG LRYLLKEEDL
  1021  ETQDIYQKLL GKLQTALKEV EMCVCQIDDL LSSITYSPKL ERKTSEGIIP TDSDNEKGER
  1081  NSKRVCFNVA GDEQEDSGHD TISNRDSYSD CNSNRNSIAS FTSICSSQCS SYFHSDEMDS
  1141  GDELPLSVRI SHDKQDKIHS CLEHLFSQVD SITNLLKGQA VVRAFDQTKY LTPGRGLQEF
  1201  QQEMEPKLSC PKRLRLHIKQ DPWNLPSSVR TLAQNIRKFV EEVKCRLLLA LLEYSDSETQ
  1261  LRRDMVFCQT LVATVCAFSE QLMAALNQMF DNSKENEMET WEASRRWLDQ IANAGVLFHF
  1321  QSLLSPNLTD EQAMLEDTLV ALFDLEKVSF YFKPSEEEPL VANVPLTYQA EGSRQALKVY
  1381  FYIDSYHFEQ LPQRLKNGGG FKIHPVLFAQ ALESMEGYYY RDNVSVEEFQ AQINAASLEK
  1441  VKQYNQKLRA FYLDKSNSPP NSTSKAAYVD KLMRPLNALD ELYRLVASFI RSKRTAACAN
  1501  TACSASGVGL LSVSSELCNR LGACHIIMCS SGVHRCTLSV TLEQAIILAR SHGLPPRYIM
  1561  QATDVMRKQG ARVQNTAKNL GVRDRTPQSA PRLYKLCEPP PPAGEE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PREX2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

11 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PREX2.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 232 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cerebral arteriovenous malformation

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.61

gnomAD pLI

0

gnomAD missense Z

1.73

DepMap mean gene effect

0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult locomotory behavior
• dendrite morphogenesis
• G protein-coupled receptor signaling pathway
• negative regulation of TOR signaling
• phosphatidylinositol 3-kinase/protein kinase B signal transduction
• regulation of small GTPase mediated signal transduction

Molecular functions

• GTPase activator activity
• guanyl-nucleotide exchange factor activity
• protein serine/threonine kinase inhibitor activity

Cellular components

• cytosol
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Dbl homology domain
• DEP domain
• Guanine-nucleotide dissociation stimulator, CDC24, conserved site
• PDZ domain
• Pleckstrin homology domain
• PH-like domain superfamily
• Dbl homology (DH) domain superfamily
• PDZ superfamily
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Regulators of mTOR signaling and Rac activation
• SOS1/NGEF-like, PH domain
• PDZ domain
• Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP)
• RhoGEF domain
• SOS1/NGEF-like PH domain
• PREX2, DEP domain 1

KeywordsUniProt

• Guanine-nucleotide releasing factor
• Repeat

InteractionsUniProt · HPA

Protein binding partners of PREX2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RAC1