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PAK2 p21 (RAC1) activated kinase 2 [ Homo sapiens (human) ]

Gene ID: 5062, updated on 24-Nov-2020

Summary

Official Symbol
PAK2provided by HGNC
Official Full Name
p21 (RAC1) activated kinase 2provided by HGNC
Primary source
HGNC:HGNC:8591
See related
Ensembl:ENSG00000180370 MIM:605022
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
PAK65; PAKgamma
Summary
The p21 activated kinases (PAK) are critical effectors that link Rho GTPases to cytoskeleton reorganization and nuclear signaling. The PAK proteins are a family of serine/threonine kinases that serve as targets for the small GTP binding proteins, CDC42 and RAC1, and have been implicated in a wide range of biological activities. The protein encoded by this gene is activated by proteolytic cleavage during caspase-mediated apoptosis, and may play a role in regulating the apoptotic events in the dying cell. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in spleen (RPKM 22.2), appendix (RPKM 21.0) and 25 other tissues See more
Orthologs

Genomic context

See PAK2 in Genome Data Viewer
Location:
3q29
Exon count:
16
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (196739857..196832647)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (196466728..196559518)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene RNA, U6 small nuclear 646, pseudogene Neighboring gene centrosomal protein 19 Neighboring gene phosphatidylinositol glycan anchor biosynthesis class X Neighboring gene RNA, U4 small nuclear 89, pseudogene Neighboring gene RNA, U6 small nuclear 42, pseudogene Neighboring gene SUMO specific peptidase 5 Neighboring gene NCBP2 antisense RNA 1 Neighboring gene nuclear cap binding protein subunit 2

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease.
GeneReviews: Not available

Copy number response

Description
Copy number response
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated (2011-12-27)

ClinGen Genome Curation PagePubMed
Triplosensitivity

Little evidence for dosage pathogenicity (Last evaluated (2011-12-27)

ClinGen Genome Curation PagePubMed

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 activates LIMK1/2 by increased levels of LIMK1/2 phosphorylation. Gp120-mediated LIMK activation is dependent on the Rack-PAK-LIMK pathway through phosphorylation of PAK2 and Rac1 PubMed
Nef nef HIV-1 Nef requires the GTPase interaction site of PAK2 to facilitate interactions of Nef with EXOC PubMed
nef HIV-1 Nef requires PAK2 for the Nef-EXOC interaction PubMed
nef HIV-1 Nef-mediated PAK2 activation is found in multiple human cell lines of myeloid, lymphoid, and non-hematopoietic origin PubMed
nef The activation of PAK2 by HIV-1 Nef is critical for human intrathymic T-cell development PubMed
nef The association of HIV-1 Nef with PAK2 is important for enhancing activation of primary CD4/CD8+ T cells PubMed
nef Mutation of HIV-1 Nef amino acid residues at positions 85, 89, 187, 188, and 191 dramatically alters association with Pak2 without affecting Nef expression levels or CD4 and MHC-I downregulation PubMed
nef The Nef/hnRNPK/PKC-delta/Hck protein complex activates Pak2 activity but inhibits Pak1 activity, which induces paxillin phosphorylation on Ser272/274 and regulates paxillin/TACE association and secretion PubMed
nef HIV-1 Nef induces increased levels of Pak2 phosphorylation at positions serine 192/197 PubMed
nef HIV-1 Nef induces phosphorylation of MEK1 at position serine 298, which depends on Pak and Rac activity. The SH3 region mutation 72PXXP/AXXA75 in Nef results in loss of Pak association which decreases Nef-induced MEK1 phosphorylation PubMed
nef The association of HIV-1 Nef with Vav1, Pak2, and Nck1 is greatly reduced in SLP76-deficient T cells PubMed
nef The binding of HIV-1 Nef to the SH3 domain of Hck is required for Nef/activated PAK2 complex formation. A new locus GFP/F (G67, F68, P69 and F90) of Nef is involved in the Nef/activated PAK2 complex formation PubMed
nef The HIV-1 Nef highly conserved valine-glycine-phenylalanine amino acid triplet (VGF) motif is important for Nef-PAK2 association and cofilin hyper-phosphorylation PubMed
nef Nef-mediated microdomain recruitment of Vav1 is associated with the Nef-p21-activated kinase 2 (PAK2) signalosome. Nef residue F195 is identified as critical for Nef-mediated raft recruitment of Vav1 PubMed
nef HIV-1 Nef inactivates cofilin by inducing its hyperphosphorylation via association with PAK2 activity PubMed
nef HIV-1 Nef requires a PAK2 recruitment motif (F195/191I) for inhibition of actin remodeling and induction of cofilin hyperphosphorylation PubMed
nef Fusing GFP to the C-terminal end of Nef results in a reduction in the level of activated PAK-2 associated with Nef. The impaired PAK-2 activation with Nef-GFP is due to the large size of the GFP fusion protein PubMed
nef The mutation of all four glutamates (amino acids 62-65) to alanine in HIV-1 Nef impairs the ability of Nef to regulate p21-activated protein kinase 2 (PAK-2) and enhance viral particle infectivity PubMed
nef HIV-1 group N and group O nef alleles interact with PAK-2, albeit with different efficiencies PubMed
nef Hck-derived SH3 domains efficiently associate with HIV-1 Nef in cells and thereby potently inhibit SH3-dependent Nef functions, such as binding p21-activated kinase-2 (PAK2) PubMed
nef HIV-1 Nef binds to p21-activated kinase 2 (PAK2); this interaction is mediated through the N-terminal domain of Nef and the C-terminal part of the regulatory domain of PAK2 PubMed
nef HIV-1 Nef co-localizes with PAK-2 in lipid rafts; a palmitoylated Nef is highly enriched in lipid rafts and associates with higher levels of PAK-2 activity than wild type Nef PubMed
matrix gag hPAK65 has been demonstrated to phosphorylate HIV-1 Matrix on serine residues in vitro PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
cadherin binding HDA PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity TAS
Traceable Author Statement
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
 
protein serine/threonine kinase activity EXP
Inferred from Experiment
more info
PubMed 
protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
 
protein threonine kinase activity IEA
Inferred from Electronic Annotation
more info
 
protein tyrosine kinase activator activity IDA
Inferred from Direct Assay
more info
PubMed 
small GTPase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
T cell costimulation TAS
Traceable Author Statement
more info
 
T cell receptor signaling pathway TAS
Traceable Author Statement
more info
 
activation of protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
adherens junction assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
apoptotic process IEA
Inferred from Electronic Annotation
more info
 
bicellular tight junction assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to organic cyclic compound IEA
Inferred from Electronic Annotation
more info
 
dendritic spine development IEA
Inferred from Electronic Annotation
more info
 
interleukin-12-mediated signaling pathway TAS
Traceable Author Statement
more info
 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of protein kinase activity TAS
Traceable Author Statement
more info
PubMed 
negative regulation of stress fiber assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of extrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein localization to cell-cell junction IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of axonogenesis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of cytoskeleton organization IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of defense response to virus by virus TAS
Traceable Author Statement
more info
 
regulation of growth IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
signal transduction by protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
stimulatory C-type lectin receptor signaling pathway TAS
Traceable Author Statement
more info
 
stress-activated protein kinase signaling cascade IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
vascular endothelial growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cell-cell junction IMP
Inferred from Mutant Phenotype
more info
PubMed 
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
 
nucleus IEA
Inferred from Electronic Annotation
more info
 
perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 
postsynaptic density IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
serine/threonine-protein kinase PAK 2
Names
PAK-2
S6/H4 kinase
gamma-PAK
p21 (CDKN1A)-activated kinase 2
p21 protein (Cdc42/Rac)-activated kinase 2
p21-activated kinase 2
p58
NP_002568.2
XP_011511172.1
XP_016861990.1

NCBI Reference Sequences (RefSeq)

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

  1. NG_009227.1 RefSeqGene

    Range
    5001..97791
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_002577.4NP_002568.2  serine/threonine-protein kinase PAK 2

    See identical proteins and their annotated locations for NP_002568.2

    Status: REVIEWED

    Source sequence(s)
    AC127904, AK291339, BC069613, DB164364
    Consensus CDS
    CCDS3321.1
    UniProtKB/Swiss-Prot
    Q13177
    UniProtKB/TrEMBL
    A8K5M4
    Related
    ENSP00000314067.3, ENST00000327134.7
    Conserved Domains (2) summary
    cd06655
    Location:229524
    STKc_PAK2; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2
    pfam00786
    Location:73130
    PBD; P21-Rho-binding domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p13 Primary Assembly

    Range
    196739857..196832647
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017006501.1XP_016861990.1  serine/threonine-protein kinase PAK 2 isoform X1

    UniProtKB/Swiss-Prot
    Q13177
    Conserved Domains (2) summary
    cd06655
    Location:229524
    STKc_PAK2; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2
    pfam00786
    Location:73130
    PBD; P21-Rho-binding domain
  2. XM_011512870.2XP_011511172.1  serine/threonine-protein kinase PAK 2 isoform X1

    See identical proteins and their annotated locations for XP_011511172.1

    UniProtKB/Swiss-Prot
    Q13177
    Conserved Domains (2) summary
    cd06655
    Location:229524
    STKc_PAK2; Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2
    pfam00786
    Location:73130
    PBD; P21-Rho-binding domain
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