Human Gene PAK3 (ENST00000372007.10_9) from GENCODE V47lift37
  Description: p21 (RAC1) activated kinase 3, transcript variant 7 (from RefSeq NR_136748.1)
Gencode Transcript: ENST00000372007.10_9
Gencode Gene: ENSG00000077264.17_13
Transcript (Including UTRs)
   Position: hg19 chrX:110,339,419-110,470,589 Size: 131,171 Total Exon Count: 18 Strand: +
Coding Region
   Position: hg19 chrX:110,366,332-110,463,675 Size: 97,344 Coding Exon Count: 14 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:110,339,419-110,470,589)mRNA (may differ from genome)Protein (544 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PAK3_HUMAN
DESCRIPTION: RecName: Full=Serine/threonine-protein kinase PAK 3; EC=2.7.11.1; AltName: Full=Beta-PAK; AltName: Full=Oligophrenin-3; AltName: Full=p21-activated kinase 3; Short=PAK-3;
FUNCTION: Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
COFACTOR: Magnesium (By similarity).
ENZYME REGULATION: Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-436 and allows the kinase domain to adopt an active structure (By similarity).
SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Shows highly specific binding to the SH3 domains of phospholipase C-gamma and of adapter protein NCK. Interacts with the C-terminal of APP (By similarity). Interacts with ARHGEF6 and ARHGEF7.
INTERACTION: P60953-2:CDC42; NbExp=2; IntAct=EBI-3389553, EBI-287394; P63000:RAC1; NbExp=2; IntAct=EBI-3389553, EBI-413628;
SUBCELLULAR LOCATION: Cytoplasm (By similarity).
TISSUE SPECIFICITY: Restricted to the nervous system. Highly expressed in postmitotic neurons of the developing and postnatal cerebral cortex and hippocampus.
PTM: Autophosphorylated when activated by CDC42/p21.
DISEASE: Defects in PAK3 are the cause of mental retardation X- linked type 30 (MRX30) [MIM:300558]; also called X-linked mental retardation type 47 (MRX47). Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non- syndromic mental retardation patients do not manifest other clinical signs.
SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
SIMILARITY: Contains 1 CRIB domain.
SIMILARITY: Contains 1 protein kinase domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PAK3";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PAK3
Diseases sorted by gene-association score: mental retardation, x-linked 30/47* (1200), x-linked non-specific intellectual disability* (175)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl
  • C063002 2,3-dimethoxy-1,4-naphthoquinone
  • C548651 2-(1'H-indolo-3'-carbonyl)thiazole-4-carboxylic acid methyl ester
  • C030370 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone
  • C477187 5-(4-methylpiperazin-1-yl)-2-(2'-(3,4-dimethoxyphenyl)-5'-benzimidazolyl)benzimidazole
  • D034341 Aristolochic Acids
  • D001194 Asbestos
  • D001564 Benzo(a)pyrene
  • D002104 Cadmium
  • D004390 Chlorpyrifos
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 12.12 RPKM in Pituitary
Total median expression: 110.41 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -256.60577-0.445 Picture PostScript Text
3' UTR -1818.306914-0.263 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000095 - PAK_box_Rho-bd
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF00786 - P21-Rho-binding domain
PF07714 - Protein tyrosine and serine/threonine kinase

SCOP Domains:
56112 - Protein kinase-like (PK-like)

ModBase Predicted Comparative 3D Structure on O75914
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003824 catalytic activity
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004708 MAP kinase kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0017048 Rho GTPase binding
GO:0017124 SH3 domain binding
GO:0046872 metal ion binding
GO:0048365 Rac GTPase binding
GO:0051020 GTPase binding

Biological Process:
GO:0000165 MAPK cascade
GO:0000187 activation of MAPK activity
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0006468 protein phosphorylation
GO:0007266 Rho protein signal transduction
GO:0007275 multicellular organism development
GO:0007346 regulation of mitotic cell cycle
GO:0007409 axonogenesis
GO:0008152 metabolic process
GO:0010763 positive regulation of fibroblast migration
GO:0010975 regulation of neuron projection development
GO:0016310 phosphorylation
GO:0016358 dendrite development
GO:0016477 cell migration
GO:0030833 regulation of actin filament polymerization
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031295 T cell costimulation
GO:0032956 regulation of actin cytoskeleton organization
GO:0042981 regulation of apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0048013 ephrin receptor signaling pathway
GO:0050770 regulation of axonogenesis
GO:0050808 synapse organization
GO:0050852 T cell receptor signaling pathway
GO:0060996 dendritic spine development
GO:0060997 dendritic spine morphogenesis
GO:0061003 positive regulation of dendritic spine morphogenesis
GO:0071407 cellular response to organic cyclic compound
GO:2000573 positive regulation of DNA biosynthetic process

Cellular Component:
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005829 cytosol
GO:0005886 plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AK290504 - Homo sapiens cDNA FLJ78276 complete cds, highly similar to Homo sapiens p21 (CDKN1A)-activated kinase 3 (PAK3), mRNA.
AK315284 - Homo sapiens cDNA, FLJ96299, highly similar to Homo sapiens p21 (CDKN1A)-activated kinase 3 (PAK3), mRNA.
AK128022 - Homo sapiens cDNA FLJ46141 fis, clone TESTI2052985, highly similar to Serine/threonine-protein kinase PAK 3 (EC 2.7.1.-).
AF155651 - Human P21 activated kinase-3 mRNA.
BC117353 - Homo sapiens p21 (CDKN1A)-activated kinase 3, mRNA (cDNA clone IMAGE:40125904).
BC117355 - Homo sapiens p21 (CDKN1A)-activated kinase 3, mRNA (cDNA clone IMAGE:40125906).
BC143544 - Homo sapiens cDNA clone IMAGE:9052055.
BC152761 - Synthetic construct Homo sapiens clone IMAGE:100016002, MGC:184157 p21 protein (Cdc42/Rac)-activated kinase 3 (PAK3) mRNA, encodes complete protein.
AB102659 - Homo sapiens PAK3 mRNA for p21-activated kinase 3, complete cds.
AF068864 - Homo sapiens p21-activated kinase 3 (PAK3) mRNA, complete cds.
AM943850 - Homo sapiens mRNA for PAK3b protein (PAK3 gene), variant b.
AM943851 - Homo sapiens mRNA for PAK3c protein (PAK3 gene), variant c.
AM943852 - Homo sapiens mRNA for PAK3cb protein (PAK3 gene), variant cb.
EF491800 - Homo sapiens clone PAK3 mRNA, partial sequence; alternatively spliced.
EF491818 - Homo sapiens clone PAK3 mRNA, partial sequence; alternatively spliced.
JD027577 - Sequence 8601 from Patent EP1572962.
JD035575 - Sequence 16599 from Patent EP1572962.
JD033258 - Sequence 14282 from Patent EP1572962.
AK124702 - Homo sapiens cDNA FLJ42712 fis, clone BRAMY3008044.
JD564324 - Sequence 545348 from Patent EP1572962.
JD329066 - Sequence 310090 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O75914 (Reactome details) participates in the following event(s):

R-HSA-8981926 RAC1 and CDC42 activate PAK3
R-HSA-430183 NCK binds PAK
R-HSA-389788 Activation of PAKs by RAC1 and CDC42
R-HSA-399930 Activation of PAK by Rac1
R-HSA-3928641 PAK binds RAC and bPIX
R-HSA-428531 Recruitment of PAK to NCK
R-HSA-5357472 PAK1-3 autophosphorylates
R-HSA-5627775 Autophosphorylation of PAK1,2,3
R-HSA-5357483 RAC1 binds PAK1-3
R-HSA-399939 Autophosphorylation of PAK
R-HSA-5357445 PAK1-3 dimer disassociates
R-HSA-5624492 PAK phosphorylates p21 RAF1 on S338
R-HSA-3928625 PAKs autophosphorylate
R-HSA-442832 PAK phosphorylates cortactin
R-HSA-5687086 PAK1,2,3 phosphorylates MAPK6,4
R-HSA-5357477 PAK1-3 phosphorylates VE-cadherin
R-HSA-3928640 PAKs phosphorylate MLC
R-HSA-399952 Phosphorylation of LIMK-1 by PAK
R-HSA-5627123 RHO GTPases activate PAKs
R-HSA-202433 Generation of second messenger molecules
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-399954 Sema3A PAK dependent Axon repulsion
R-HSA-3928664 Ephrin signaling
R-HSA-428540 Activation of RAC1
R-HSA-195258 RHO GTPase Effectors
R-HSA-5218920 VEGFR2 mediated vascular permeability
R-HSA-202403 TCR signaling
R-HSA-389356 CD28 co-stimulation
R-HSA-5683057 MAPK family signaling cascades
R-HSA-373755 Semaphorin interactions
R-HSA-5621575 CD209 (DC-SIGN) signaling
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-376176 Signaling by ROBO receptors
R-HSA-194315 Signaling by Rho GTPases
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-1280218 Adaptive Immune System
R-HSA-388841 Costimulation by the CD28 family
R-HSA-162582 Signal Transduction
R-HSA-422475 Axon guidance
R-HSA-5621481 C-type lectin receptors (CLRs)
R-HSA-194138 Signaling by VEGF
R-HSA-168256 Immune System
R-HSA-1266738 Developmental Biology
R-HSA-168249 Innate Immune System
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases

-  Other Names for This Gene
  Alternate Gene Symbols: A8K389, B1GX77, B1GX78, B1GX79, ENST00000372007.1, ENST00000372007.2, ENST00000372007.3, ENST00000372007.4, ENST00000372007.5, ENST00000372007.6, ENST00000372007.7, ENST00000372007.8, ENST00000372007.9, NR_136748, O75914, OPHN3, PAK3_HUMAN, Q5JWX1, Q5JWX2, Q7Z2D6, Q7Z2E4, Q7Z3Z8, Q8WWK5, Q8WX23, Q9P0J8, uc318jop.1, uc318jop.2
UCSC ID: ENST00000372007.10_9
RefSeq Accession: NM_002578.5
Protein: O75914 (aka PAK3_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.