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PAK1 (p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast))

Written2007-12Dina Stepanova, Jonathan Chernoff
Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA

(Note : for Links provided by Atlas : click)

Identity

Other namesPAKalpha
HGNC (Hugo) PAK1
LocusID (NCBI) 5058
Atlas_Id 41633
Location 11q13.5
Location_base_pair Starts at 77033060 and ends at 77185108 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order centromere - MYO7A   GDPD4   LOC387791   PAK1   DFFZp434E1119   FLJ38894   AQP11
Fusion genes
(updated 2016)
ARRB1 (11q13.4) / PAK1 (11q13.5)C16orf72 (16p13.2) / PAK1 (11q13.5)DDR1 (6p21.33) / PAK1 (11q13.5)
NARS2 (11q14.1) / PAK1 (11q13.5)PAK1 (11q13.5) / ARHGEF18 (19p13.2)PAK1 (11q13.5) / CNIH4 (1q42.11)
PAK1 (11q13.5) / ERG (21q22.2)PAK1 (11q13.5) / FANCA (16q24.3)PAK1 (11q13.5) / FAT3 (11q14.3)
PAK1 (11q13.5) / KCTD14 (11q14.1)PAK1 (11q13.5) / MYO7A (11q13.5)PAK1 (11q13.5) / NARS2 (11q14.1)
PAK1 (11q13.5) / PRSS23 (11q14.2)PAK1 (11q13.5) / TSTD2 (9q22.33)SPINT2 (19q13.2) / PAK1 (11q13.5)
UVRAG (11q13.5) / PAK1 (11q13.5)
Note PAK1 encodes a serine/threonine specific protein kinase that is a member of the PAK branch of the STE20 family. PAK1 plays a role in cell survival, polarity, and motility, and may have oncogenic function when overexpressed.

DNA/RNA

 
  The alignment of PAK1 mRNA to its genomic sequence.
Description The PAK1 gene contains 14 exons. The sizes of the exons 1-14 are 189, 100, 129, 147, 37, 119, 174, 63, 48, 112, 117, 99, 196, 137, and 86 bps. Exon 2 contains the translation initation ATG, and a few additional codons. Exon 13 contains the stop codon. Other features of the PAK1 gene, such as promoters or enhancer elements, have not been described.
Transcription PAK1 expression is particularly high in the brain. Other tissues which have reasonably high levels of PAK1 expression include spleen and skeletal muscle. The mRNA size is 1945 bps.

Protein

 
Description PAK1 is a highly conserved serine/threonine protein kinase of 545 amino acids and is a member of the PAK group of the STE20 family of serine/threonine protein kinases. Pak1 is active in a monomeric form; the non-active form is an autoinhibited homodimer. Pak1 contains a regulatory N-terminal regulatory domain and C-terminal catalytic domain The regulatory domain consists of a p21 GTPase-binding domain (PBD), an inhibitory domain (PID); five SH3-domains; and one non-classical SH3-binding site for the PIX family of proteins (PXP). Pak1 binds to activated forms of the GTPases Cdc42 and Rac. Pak1 homodimerizes through a motif adjacent to the p21-binding domain, and is autoinhibited. Upon binding to Cdc42 or Rac, Pak1 is activated and autophosphorylates. Pak1 has dozens of substrates, activating cytoskeletal and transcription pathways that enhance cell motility, proliferation, and survival.
Expression PAK1 is highly expressed in epithelium of tongue and larynx and in thyroid gland, expression also found in central nervous system (brain).
Localisation Under basal conditions, Pak1 localizes to the cytosol. Upon growth factor stimulation, Pak1 is recruited to the plasma membrane as well as the nucleus.
Function Cell survival and proliferation
Homology Similar to STE20 in budding yeast and PAK1 in fission yeast. Human PAK1 complements both these yeast genes.

Mutations

Note No mutations in the PAK1 gene have been reported

Implicated in

Note
Entity Cancers
Disease There is emerging evidence that the Pak family may play a key role in several human malignancies, including breast, ovarian, head and neck, colon, thyroid, and renal cancer. In human breast cancer, the expression level of Pak1 correlates with the tumor grade, with higher expression in less differentiated ductal carcinomas of the breast (grade III tumors) than in grade II and grade I tumors. Pak1 overexpression is also associated with tamoxifen resistance in breast cancer. In human tumors, Pak1 is not itself activated by mutation: rather, Pak1 is overexpressed by unknown mechanisms. Pak1 may also play a role in transformation by Kaposi's sarcoma-associated herpes virus, which induces Kaposi's sarcoma and primary effusion lymphomas.
Prognosis Recently, it has been shown that the level of phosphorylated (activated) Pak1 Level in the cytoplasm correlates with shorter survival time in patients with glioblastoma. As noted above, Pak1 expression may also correlate with tamoxifen resistance in breast cancer.
  

Bibliography

A brain serine/threonine protein kinase activated by Cdc42 and Rac1.
Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L
Nature. 1994 ; 367 (6458) : 40-46.
PMID 8107774
 
Emerging from the Pak: the p21-activated protein kinase family.
Sells MA, Chernoff J
Trends in cell biology. 1997 ; 7 (4) : 162-167.
PMID 17708935
 
Pak to the future.
Bagrodia S, Cerione RA
Trends in cell biology. 1999 ; 9 (9) : 350-355.
PMID 10461188
 
The Ste20 group kinases as regulators of MAP kinase cascades.
Dan I, Watanabe NM, Kusumi A
Trends in cell biology. 2001 ; 11 (5) : 220-230.
PMID 11316611
 
p21-activated kinases: three more join the Pak.
Jaffer ZM, Chernoff J
The international journal of biochemistry & cell biology. 2002 ; 34 (7) : 713-717.
PMID 11950587
 
Biology of the p21-activated kinases.
Bokoch GM
Annual review of biochemistry. 2003 ; 72 : 743-781.
PMID 12676796
 
The genetics of Pak.
Hofmann C, Shepelev M, Chernoff J
Journal of cell science. 2004 ; 117 (Pt 19) : 4343-4354.
PMID 15331659
 
p21-activated kinases in cancer.
Kumar R, Gururaj AE, Barnes CJ
Nature reviews. Cancer. 2006 ; 6 (6) : 459-471.
PMID 16723992
 

Citation

This paper should be referenced as such :
Stepanova, D ; Chernoff, J
PAK1 (p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast))
Atlas Genet Cytogenet Oncol Haematol. 2008;12(4):318-319.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PAK1ID41633ch11q13.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  Mycosis fungoides/Sezary's syndrome
t(4;11)(q35;q23) KMT2A/SORBS2

External links

Nomenclature
HGNC (Hugo)PAK1   8590
Cards
AtlasPAK1ID41633ch11q13
Entrez_Gene (NCBI)PAK1  5058  p21 protein (Cdc42/Rac)-activated kinase 1
GeneCards (Weizmann)PAK1
Ensembl hg19 (Hinxton)ENSG00000149269 [Gene_View]  chr11:77033060-77185108 [Contig_View]  PAK1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000149269 [Gene_View]  chr11:77033060-77185108 [Contig_View]  PAK1 [Vega]
ICGC DataPortalENSG00000149269
TCGA cBioPortalPAK1
AceView (NCBI)PAK1
Genatlas (Paris)PAK1
WikiGenes5058
SOURCE (Princeton)PAK1
Genomic and cartography
GoldenPath hg19 (UCSC)PAK1  -     chr11:77033060-77185108 -  11q13.5-q14.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PAK1  -     11q13.5-q14.1   [Description]    (hg38-Dec_2013)
EnsemblPAK1 - 11q13.5-q14.1 [CytoView hg19]  PAK1 - 11q13.5-q14.1 [CytoView hg38]
Mapping of homologs : NCBIPAK1 [Mapview hg19]  PAK1 [Mapview hg38]
OMIM602590   
Gene and transcription
Genbank (Entrez)AF071884 AK055228 AK293098 AK295344 AK296006
RefSeq transcript (Entrez)NM_001128620 NM_002576
RefSeq genomic (Entrez)NC_000011 NC_018922 NG_029900 NT_167190 NW_004929380
Consensus coding sequences : CCDS (NCBI)PAK1
Cluster EST : UnigeneHs.435714 [ NCBI ]
CGAP (NCI)Hs.435714
Alternative Splicing GalleryENSG00000149269
Gene ExpressionPAK1 [ NCBI-GEO ]   PAK1 [ EBI - ARRAY_EXPRESS ]   PAK1 [ SEEK ]   PAK1 [ MEM ]
Gene Expression Viewer (FireBrowse)PAK1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5058
GTEX Portal (Tissue expression)PAK1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13153 (Uniprot)
NextProtQ13153  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13153
Splice isoforms : SwissVarQ13153 (Swissvar)
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusQ13153
Domaine pattern : Prosite (Expaxy)CRIB (PS50108)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)CRIB_dom    Kinase-like_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser/Thr_dual-sp_kinase    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)PBD (PF00786)    Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam00786    pfam00069   
Domain families : Smart (EMBL)PBD (SM00285)  S_TKc (SM00220)  
DMDM Disease mutations5058
Blocks (Seattle)PAK1
PDB (SRS)1F3M    1YHV    1YHW    1ZSG    2HY8    2QME    3DVP    3FXZ    3FY0    3Q4Z    3Q52    3Q53    4DAW    4EQC    4O0R    4O0T    4P90    4ZJI    4ZJJ    4ZLO    4ZY4    4ZY5    4ZY6    5DEY    5DFP   
PDB (PDBSum)1F3M    1YHV    1YHW    1ZSG    2HY8    2QME    3DVP    3FXZ    3FY0    3Q4Z    3Q52    3Q53    4DAW    4EQC    4O0R    4O0T    4P90    4ZJI    4ZJJ    4ZLO    4ZY4    4ZY5    4ZY6    5DEY    5DFP   
PDB (IMB)1F3M    1YHV    1YHW    1ZSG    2HY8    2QME    3DVP    3FXZ    3FY0    3Q4Z    3Q52    3Q53    4DAW    4EQC    4O0R    4O0T    4P90    4ZJI    4ZJJ    4ZLO    4ZY4    4ZY5    4ZY6    5DEY    5DFP   
PDB (RSDB)1F3M    1YHV    1YHW    1ZSG    2HY8    2QME    3DVP    3FXZ    3FY0    3Q4Z    3Q52    3Q53    4DAW    4EQC    4O0R    4O0T    4P90    4ZJI    4ZJJ    4ZLO    4ZY4    4ZY5    4ZY6    5DEY    5DFP   
Structural Biology KnowledgeBase1F3M    1YHV    1YHW    1ZSG    2HY8    2QME    3DVP    3FXZ    3FY0    3Q4Z    3Q52    3Q53    4DAW    4EQC    4O0R    4O0T    4P90    4ZJI    4ZJJ    4ZLO    4ZY4    4ZY5    4ZY6    5DEY    5DFP   
SCOP (Structural Classification of Proteins)1F3M    1YHV    1YHW    1ZSG    2HY8    2QME    3DVP    3FXZ    3FY0    3Q4Z    3Q52    3Q53    4DAW    4EQC    4O0R    4O0T    4P90    4ZJI    4ZJJ    4ZLO    4ZY4    4ZY5    4ZY6    5DEY    5DFP   
CATH (Classification of proteins structures)1F3M    1YHV    1YHW    1ZSG    2HY8    2QME    3DVP    3FXZ    3FY0    3Q4Z    3Q52    3Q53    4DAW    4EQC    4O0R    4O0T    4P90    4ZJI    4ZJJ    4ZLO    4ZY4    4ZY5    4ZY6    5DEY    5DFP   
SuperfamilyQ13153
Human Protein AtlasENSG00000149269
Peptide AtlasQ13153
HPRD03995
IPIIPI00656138   IPI00289746   IPI00980126   IPI00977723   IPI00983370   IPI00985496   IPI00983507   IPI00975628   IPI00984051   IPI00977128   IPI00981750   IPI00984815   
Protein Interaction databases
DIP (DOE-UCLA)Q13153
IntAct (EBI)Q13153
FunCoupENSG00000149269
BioGRIDPAK1
STRING (EMBL)PAK1
ZODIACPAK1
Ontologies - Pathways
QuickGOQ13153
Ontology : AmiGOMAPK cascade  mitotic cell cycle  response to hypoxia  ruffle  positive regulation of protein phosphorylation  stimulatory C-type lectin receptor signaling pathway  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  receptor signaling protein serine/threonine kinase activity  protein binding  protein binding  collagen binding  ATP binding  cytoplasm  Golgi apparatus  cytosol  plasma membrane  plasma membrane  cell-cell junction  focal adhesion  protein phosphorylation  exocytosis  apoptotic process  axonogenesis  intercalated disc  protein kinase binding  signal transduction by protein phosphorylation  Z disc  positive regulation of cell migration  axon  dendrite  T cell costimulation  actin cytoskeleton reorganization  actin cytoskeleton reorganization  filamentous actin  nuclear membrane  ruffle membrane  cellular response to insulin stimulus  positive regulation of peptidyl-serine phosphorylation  positive regulation of intracellular estrogen receptor signaling pathway  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  wound healing  protein complex  positive regulation of JUN kinase activity  protein autophosphorylation  ephrin receptor signaling pathway  branching morphogenesis of an epithelial tube  neuron projection morphogenesis  T cell receptor signaling pathway  positive regulation of stress fiber assembly  negative regulation of cell proliferation involved in contact inhibition  invadopodium  
Ontology : EGO-EBIMAPK cascade  mitotic cell cycle  response to hypoxia  ruffle  positive regulation of protein phosphorylation  stimulatory C-type lectin receptor signaling pathway  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  receptor signaling protein serine/threonine kinase activity  protein binding  protein binding  collagen binding  ATP binding  cytoplasm  Golgi apparatus  cytosol  plasma membrane  plasma membrane  cell-cell junction  focal adhesion  protein phosphorylation  exocytosis  apoptotic process  axonogenesis  intercalated disc  protein kinase binding  signal transduction by protein phosphorylation  Z disc  positive regulation of cell migration  axon  dendrite  T cell costimulation  actin cytoskeleton reorganization  actin cytoskeleton reorganization  filamentous actin  nuclear membrane  ruffle membrane  cellular response to insulin stimulus  positive regulation of peptidyl-serine phosphorylation  positive regulation of intracellular estrogen receptor signaling pathway  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  wound healing  protein complex  positive regulation of JUN kinase activity  protein autophosphorylation  ephrin receptor signaling pathway  branching morphogenesis of an epithelial tube  neuron projection morphogenesis  T cell receptor signaling pathway  positive regulation of stress fiber assembly  negative regulation of cell proliferation involved in contact inhibition  invadopodium  
Pathways : BIOCARTAAngiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling [Genes]    fMLP induced chemokine gene expression in HMC-1 cells [Genes]    MAPKinase Signaling Pathway [Genes]    Influence of Ras and Rho proteins on G1 to S Transition [Genes]    Role of PI3K subunit p85 in regulation of Actin Organization and Cell Migration [Genes]    Rac 1 cell motility signaling pathway [Genes]    Links between Pyk2 and Map Kinases [Genes]    TNFR1 Signaling Pathway [Genes]    Signaling of Hepatocyte Growth Factor Receptor [Genes]    Ras-Independent pathway in NK cell-mediated cytotoxicity [Genes]    FAS signaling pathway ( CD95 ) [Genes]    Agrin in Postsynaptic Differentiation [Genes]   
Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Ras signaling pathway    Chemokine signaling pathway    Axon guidance    Focal adhesion    Natural killer cell mediated cytotoxicity    T cell receptor signaling pathway    Fc gamma R-mediated phagocytosis    Regulation of actin cytoskeleton    Epithelial cell signaling in Helicobacter pylori infection    Proteoglycans in cancer    Renal cell carcinoma   
REACTOMEQ13153 [protein]
REACTOME PathwaysR-HSA-3928662 EPHB-mediated forward signaling [pathway]
REACTOME PathwaysR-HSA-3928664 Ephrin signaling [pathway]
REACTOME PathwaysR-HSA-5687128 MAPK6/MAPK4 signaling [pathway]
REACTOME PathwaysR-HSA-202433 Generation of second messenger molecules [pathway]
REACTOME PathwaysR-HSA-445144 Signal transduction by L1 [pathway]
REACTOME PathwaysR-HSA-376172 DSCAM interactions [pathway]
REACTOME PathwaysR-HSA-428540 Activation of Rac [pathway]
REACTOME PathwaysR-HSA-5218920 VEGFR2 mediated vascular permeability [pathway]
REACTOME PathwaysR-HSA-5627123 RHO GTPases activate PAKs [pathway]
REACTOME PathwaysR-HSA-399954 Sema3A PAK dependent Axon repulsion [pathway]
REACTOME PathwaysR-HSA-2871796 FCERI mediated MAPK activation [pathway]
REACTOME PathwaysR-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation [pathway]
REACTOME PathwaysR-HSA-5621575 CD209 (DC-SIGN) signaling [pathway]
REACTOME PathwaysR-HSA-389359 CD28 dependent Vav1 pathway [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkPAK1
Wikipedia pathwaysPAK1
Orthology - Evolution
OrthoDB5058
GeneTree (enSembl)ENSG00000149269
Phylogenetic Trees/Animal Genes : TreeFamPAK1
Homologs : HomoloGenePAK1
Homology/Alignments : Family Browser (UCSC)PAK1
Gene fusions - Rearrangements
Fusion : MitelmanARRB1/PAK1 [11q13.4/11q13.5]  [t(11;11)(q13;q14)]  
Fusion : MitelmanDDR1/PAK1 [6p21.33/11q13.5]  [t(6;11)(p21;q14)]  
Fusion : MitelmanPAK1/ARHGEF18 [11q13.5/19p13.2]  [t(11;19)(q14;p13)]  
Fusion : MitelmanPAK1/CNIH4 [11q13.5/1q42.11]  [t(1;11)(q42;q14)]  
Fusion : MitelmanPAK1/ERG [11q13.5/21q22.2]  [t(11;21)(q14;q22)]  
Fusion : MitelmanPAK1/KCTD14 [11q13.5/11q14.1]  [t(11;11)(q14;q14)]  
Fusion : MitelmanPAK1/MYO7A [11q13.5/11q13.5]  [t(11;11)(q13;q14)]  
Fusion : MitelmanPAK1/NARS2 [11q13.5/11q14.1]  [t(11;11)(q14;q14)]  
Fusion : MitelmanPAK1/PRSS23 [11q13.5/11q14.2]  [t(11;11)(q14;q14)]  
Fusion : MitelmanUVRAG/PAK1 [11q13.5/11q13.5]  [t(11;11)(q13;q14)]  
Fusion: TCGAARRB1 11q13.4 PAK1 11q13.5 BRCA
Fusion: TCGADDR1 6p21.33 PAK1 11q13.5 OV
Fusion: TCGAPAK1 11q13.5 ARHGEF18 19p13.2 BRCA
Fusion: TCGAPAK1 11q13.5 CNIH4 1q42.11 LUAD
Fusion: TCGAPAK1 11q13.5 ERG 21q22.2 BRCA
Fusion: TCGAPAK1 11q13.5 KCTD14 11q14.1 BRCA
Fusion: TCGAPAK1 11q13.5 MYO7A 11q13.5 BRCA
Fusion: TCGAPAK1 11q13.5 NARS2 11q14.1 PRAD
Fusion: TCGAPAK1 11q13.5 PRSS23 11q14.2 BRCA
Fusion: TCGAUVRAG 11q13.5 PAK1 11q13.5 BRCA
Polymorphisms : SNP, variants
NCBI Variation ViewerPAK1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PAK1
dbVarPAK1
ClinVarPAK1
1000_GenomesPAK1 
Exome Variant ServerPAK1
ExAC (Exome Aggregation Consortium)PAK1 (select the gene name)
Genetic variants : HAPMAP5058
Genomic Variants (DGV)PAK1 [DGVbeta]
Mutations
ICGC Data PortalPAK1 
TCGA Data PortalPAK1 
Broad Tumor PortalPAK1
OASIS PortalPAK1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPAK1 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PAK1
DgiDB (Drug Gene Interaction Database)PAK1
DoCM (Curated mutations)PAK1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PAK1 (select a term)
intoGenPAK1
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)11:77033060-77185108  ENSG00000149269
CONAN: Copy Number AnalysisPAK1 
Mutations and Diseases : HGMDPAK1
OMIM602590   
MedgenPAK1
Genetic Testing Registry PAK1
NextProtQ13153 [Medical]
TSGene5058
GENETestsPAK1
Huge Navigator PAK1 [HugePedia]
snp3D : Map Gene to Disease5058
BioCentury BCIQPAK1
ClinGenPAK1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5058
Chemical/Pharm GKB GenePA32917
Clinical trialPAK1
Miscellaneous
canSAR (ICR)PAK1 (select the gene name)
Probes
Litterature
PubMed382 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePAK1
EVEXPAK1
GoPubMedPAK1
iHOPPAK1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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