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FLASH GENE
Symbol PAK1 contributors: mct/npt/pgu - updated : 27-09-2016
HGNC name p21 protein (Cdc42/Rac)-activated kinase 1
HGNC id 8590
Corresponding disease
MCSZ2 microcephaly, seizures, and developmental delay 2
Location 11q14.1      Physical location : 77.033.060 - 77.185.108
Synonym name
  • p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related)
  • p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)
  • STE20 homolog, yeast
  • Synonym symbol(s) PAKalpha, MGC130000, MGC130001, Alpha-PAK
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 152.05 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    MAP6 6p12-p11 microtubule-associated protein 6 MGAT2 14q21 mannosyl (alpha-1,6-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase DGAT2 11q13.3 diacylglycerol O-acyltransferase homolog 2 (mouse) UVRAG 11q13 UV radiation resistance associated gene WNT11 11q13.5 wingless-type MMTV integration site family, member 11 PRKRIR 11q13.5 protein-kinase, interferon-inducible double stranded RNA dependent inhibitor, repressor of (P58 repressor) LOC387790 11 LOC387790 C11orf30 11q13.5 chromosome 11 open reading frame 30 GARP 11q13.5-q14 glycoprotein A repetitions predominant LOC390226 11 similar to Olfactory guanylyl cyclase GC-D precursor (Guanylate cyclase, olfactory) E2IG4 11q13.3 hypothetical protein, estradiol-induced PHCA 11q13.4 phytoceramidase, alkaline IMAGE:4907098 11q13.4 beta-1,3-N-acetylglucosaminyltransferase protein CAPN5 11q14 calpain 5 OMP 11q13 olfactory marker protein MYO7A 11q13.5 myosin VIIA (Usher syndrome 1B (autosomal recessive, severe)) LOC220032 11q13.4 GDPD domain containing protein LOC387791 11 similar to Mitochondrial import receptor subunit TOM20 homolog (Mitochondrial 20 kDa outer membrane protein) (Outer mitochondrial membrane receptor Tom20) PAK1 11q13.5-q14.1 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast) LOC387792 11 LOC387792 AQP11 11q13.4 aquaporin 11 CLNS1A 11q13.5-q14.1 chloride channel, nucleotide-sensitive, 1A HBXAP 11q13.4-q14.1 hepatitis B virus x associated protein PTD015 11q13.4 PTD015 protein MGC16733 11q13.4 hypothetical gene MGC16733 similar to CG12113 KCTD14 11q13.4 potassium channel tetramerisation domain containing 14 THRSP 11q13.5 thyroid hormone responsive (SPOT14 homolog, rat) NDUFC2 11q12.1-q13.14 NADH dehydrogenase (ubiquinone) 1, subcomplex unknown, 2, 14.5kDa ALG8 11pter-p15.5 asparagine-linked glycosylation 8 homolog (yeast, alpha-1,3-glucosyltransferase) LOC387793 11 hypothetical gene supported by BC062331 LOC387794 11 similar to ubiquitin specific protease 38; HP43.8KD protein USP35 11q13.4 ubiquitin specific protease 35 GAB2 11q13.4-q13.5 GRB2-associated binding protein 2 FLJ23441 11q13.4 hypothetical protein FLJ23441 ODZ4 11q13.4 odd Oz/ten-m homolog 4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - 3484 - 553 - 2007 18006851
    15 - 3435 - 545 - 2007 18006851
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Endocrinethyroid   highly
    Nervousbrain    
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a GBD domain
  • mono polymer homomer , dimer , trimer
    HOMOLOGY
    interspecies homolog to yeast S.cerevisiae Ste20 related
    homolog to murine Pak1
    homolog to C.elegans c09b8.7
    Homologene
    FAMILY
  • group I of the PAK family
  • STE Ser/Thr protein kinase family
  • STE20 subfamily
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text localized to centrosomes
    basic FUNCTION
  • p21/Cdc42/Rac1-activated kinase 1, serine/threonine kinase
  • downstream effector linking Rho GTPases to actin cytoskeleton
  • potentially involved in the regulation of a subset of cytoskeletal dynamics initiated by chemoattractant and phagocytic stimuli in human neutrophils
  • plays a crucial role in lamellipodia formation, and is at the interface between junction destabilization and increased motility during morphogenetic events
  • regulates the activation of Aurora A during mitosis
  • serine/threonine kinase implicated in regulation of cell motility and survival and in malignant transformation of mammary epithelial cells
  • cooperate with PAK2, PAK3 kinase, and CHL1, most likely in independent pathways, in regulating morphological development of the leading process/apical dendrite of embryonic cortical neurons
  • plays a fundamental role in controlling cell motility by linking a variety of extracellular signals to changes in actin cytoskeleton organization, cell shape, and adhesion dynamics
  • a novel and crucial role for PAK1 and CDH1 endocytosis in determining lumen size and shape, and also identify a mechanism for multiple lumen formation, a poorly understood process that occurs in salivary gland normal embryonic development and pathological conditions
  • having functions in novel signaling pathways in NF2
  • essential role of PAK1 and PAK3 in coordinating neuronal complexity and synaptic properties, suggesting the critical importance of dendrite/axon growth in dictating postnatal brain growth and attainment of normal brain size and function
  • implicated in signaling by growth factor receptors and morphogenetic processes that control cell polarity, invasion, and actin cytoskeleton organization
  • essential role of PAK1 and PAK3 in coordinating neuronal complexity and synaptic properties
  • critical molecule coordinating cytoskeletal systems for efficient cell migration
  • kinase activity of PAK1 is necessary for PAK1-induced transformation
  • PAK1 and PAK3 belong to group I of the PAK family and control cell movement and division
  • PAK3 and PAK1 signaling may be coordinated by heterodimerization
  • physiological role of PAK1-INPP5K binding in the regulation of insulin signaling in skeletal muscle
  • GIT1/ARHGEF7 signaling proteins with PAK1 kinase represent a novel regulatory mechanism of microtubule nucleation in interphase cells
  • key regulator of actin dynamics, cell proliferation and cell survival
  • has an anti-arrhythmic and anti-hypertrophic, protective function
  • important role of PAK1 in controlling postnatal brain development and attaining a normal brain volume
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    text regulating cell mobility and morphology
    PATHWAY
    metabolism
    signaling signal transduction
  • JNK1 cascade (Jun N -terminal kinase MAP kinase pathway
  • PAK1-MORC2 axis is likely critical for orchestrating the interplay between chromatin dynamics and the maintenance of genomic integrity through sequentially integrating multiple essential enzymatic processes
  • synapse formation mediated by EPHB1/DLG3/PAK1 signaling in the early postnatal brain may be crucial for cognitive development
  • a component
  • could form an heterotrimeric complex with PPM1E and PPM1F
  • KIF3A-PAK1 signaling coordinates planar polarization of the hair bundle and the basal body in hair cells
  • AKT1-PAK1-AJUBA feedback loop integrates spatiotemporal signaling with actin remodeling at cell-cell contacts and stabilizes preassembled cadherin complexes
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GTP bound cdc 42/p21
  • Rac1
  • PAK1IP1 binding
  • strong direct interaction of PGM1 with PAK1, and PAK1-mediated phosphorylation of PGM1 selectively on threonine 466 significantly increased PGM enzymatic activity
  • GIT2 has been implicated in regulating cell spreading and motility through its transient recruitment of the p21-activated kinase (PAK1) to focal adhesions
  • binding to Scrib-ARHGEF7-GIT1 complex
  • interacting with CDC2L2 (PAK1 may serve as a downstream effector of CDC2L2 during mitosis progression)
  • cooperate with DYNLL1 in malignant transformation of breast cancer cells (DYNLL1 facilitates nuclear import of PAK1, function indispensable during vertebrate development)
  • Rac effector PAK1 transiently activated upon cell-cell adhesion and directly phosphorylated AJUBA (Thr172)
  • simultaneously activates MAPK and MET signaling; the latter via inhibition of merlin
  • STRADA regulates PAK1 in STK11-null cells to oversee cancer cell polarity and invasion
  • inhibits the activity of PAK3a but not of the splice variant PAK3b in a trans-regulatory manner
  • interacts with WNT signaling to regulate tissue polarity and gene expression
  • PAK1 interacts with phospholipid membrane domains via E-Syt2, where it may cooperate in the SYT2-dependent endocytosis of activated FGFR1 by modulating cortical actin stability
  • NCAM1 interacts with PAK1 in growth cones of neurons
  • DLG3 has unique roles in cortical synapse development by mediating EPHB1 and its downstream PAK1 signaling pathway
  • PAK1 can stimulate MAP2K1/MAP2K2 activity in a kinase-independent manner, probably by serving as a scaffold to facilitate interaction of RAF1
  • CSNK2A1 is an upstream activating kinase of PAK1, providing a novel mechanism for PAK1 activation
  • ARHGEF7 and GIT1 are required for synaptic GABA(A)R surface stability through the activity of the GTPase RAC1 and downstream effector PAK1
  • INPP5K interacts with PAK1 and glucose-regulated protein 78 (HSPA5), both of which are necessary for the regulation of insulin signaling
  • cell & other
    REGULATION
    activated by cdc42/p21
    rac1
    autophosphorylation
    DSCAM
    CSNK2A1, that is an upstream activating kinase of PAK1, providing a novel mechanism for PAK1 activation
    inhibited by binding to PAK1IP1
    PPM1F and PPM1E
    ASSOCIATED DISORDERS
    corresponding disease(s) MCSZ2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in breast cancer
    tumoral     --over  
    in ovarian, breast, and bladder cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurology  
    may serve as a useful therapeutic target in NF2
    cancerreproductivebreast
    PAK1-directed therapy in breast cancer
    cancerlung 
    evidence for potential antitumor efficacy of PAK1 inhibition in squamous nonsmall cell lung carcinomas
    ANIMAL & CELL MODELS