PAK3

Protein identityUniProt · HPA

UniProt accession

O75914

Gene

PAK3

Ensembl

ENSG00000077264

Chromosome

X

Canonical length

559 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, RAS pathway related proteins

Subcellular location

Vesicles

OverviewNCBI Gene

The protein encoded by this gene is a serine-threonine kinase and forms an activated complex with GTP-bound RAS-like (P21), CDC2 and RAC1. This protein may be necessary for dendritic development and for the rapid cytoskeletal reorganization in dendritic spines associated with synaptic plasticity. Defects in this gene are the cause of a non-syndromic form of X-linked intellectual disability. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2017]

Canonical amino-acid sequenceUniProt

559 residues, UniProt reviewed canonical sequence.

>O75914|PAK3
     1  MSDGLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS IFPGGGDKTN
    61  KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTPDLYGSQM CPGKLPEGIP EQWARLLQTS
   121  NITKLEQKKN PQAVLDVLKF YDSKETVNNQ KYMSFTSGDK SAHGYIAAHP SSTKTASEPP
   181  LAPPVSEEED EEEEEEEDEN EPPPVIAPRP EHTKSIYTRS VVESIASPAV PNKEVTPPSA
   241  ENANSSTLYR NTDRQRKKSK MTDEEILEKL RSIVSVGDPK KKYTRFEKIG QGASGTVYTA
   301  LDIATGQEVA IKQMNLQQQP KKELIINEIL VMRENKNPNI VNYLDSYLVG DELWVVMEYL
   361  AGGSLTDVVT ETCMDEGQIA AVCRECLQAL DFLHSNQVIH RDIKSDNILL GMDGSVKLTD
   421  FGFCAQITPE QSKRSTMVGT PYWMAPEVVT RKAYGPKVDI WSLGIMAIEM VEGEPPYLNE
   481  NPLRALYLIA TNGTPELQNP ERLSAVFRDF LNRCLEMDVD RRGSAKELLQ HPFLKLAKPL
   541  SSLTPLIIAA KEAIKNSSR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PAK3 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

19 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PAK3.

Disease | AllUniProt

Conditions PAK3 is implicated in, by any mechanism.

• Intellectual developmental disorder, X-linked 30 (XLID30) MIM:300558

Disease | GeneticClinVar

31 pathogenic / likely-pathogenic of 300 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, X-linked 30
• Intellectual disability
• Inborn genetic diseases
• History of neurodevelopmental disorder
• Thyroid cancer, nonmedullary, 1

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)

0.29

gnomAD pLI

0.99

gnomAD missense Z

3.53

DepMap mean gene effect

0.03

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

• axonogenesis
• cell migration
• cellular response to starvation
• dendrite development
• dendritic spine morphogenesis
• ephrin receptor signaling pathway
• intracellular signal transduction
• regulation of actin cytoskeleton organization
• regulation of actin filament polymerization
• regulation of axonogenesis
• regulation of MAPK cascade
• regulation of postsynapse organization
• stimulatory C-type lectin receptor signaling pathway
• synapse organization

Molecular functions

• ATP binding
• MAP kinase kinase activity
• metal ion binding
• protein serine kinase activity
• protein serine/threonine kinase activity
• SH3 domain binding
• small GTPase binding

Cellular components

• cytoplasm
• cytosol
• glutamatergic synapse
• plasma membrane
• postsynaptic density

Protein domainsUniProt · Pfam · InterPro

• CRIB domain
• Protein kinase domain
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• Protein kinase, ATP binding site
• p21 activated kinase binding domain
• CRIB domain superfamily
• Serine/threonine-protein kinase PAK 3-like
• Protein kinase domain
• P21-Rho-binding domain
• p21-activated kinase 3, catalytic domain

KeywordsUniProt

• Allosteric enzyme
• ATP-binding
• Cytoplasm
• Developmental protein
• Intellectual disability
• Kinase
• Magnesium
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Serine/threonine-protein kinase
• SH3-binding
• Transferase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of PAK3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARHGEF6
• ARHGEF7
• GIT1
• GIT2
• RHOU
• RAC1