Pak3 p21 (RAC1) activated kinase 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pak3provided by MGI
Official Full Name: p21 (RAC1) activated kinase 3provided by MGI
Primary source: MGI:MGI:1339656
See related: Ensembl:ENSMUSG00000031284 AllianceGenome:MGI:1339656
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Stk4; PAK-3; Pak65beta; Pak65alpha
Summary: Enables protein kinase activity and small GTPase binding activity. Involved in axonogenesis and dendritic spine morphogenesis. Acts upstream of or within cellular response to organic cyclic compound and dendritic spine development. Located in postsynaptic density. Is active in glutamatergic synapse. Is expressed in several structures, including central nervous system; gonad; liver; lung; and retina. Used to study non-syndromic X-linked intellectual disability 30. Human ortholog(s) of this gene implicated in non-syndromic X-linked intellectual disability 30. Orthologous to human PAK3 (p21 (RAC1) activated kinase 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in CNS E18 (RPKM 8.0), whole brain E14.5 (RPKM 6.4) and 8 other tissues See more
Orthologs: human all
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Genomic context

Location:: X F2; X 64.5 cM

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	X	NC_000086.8 (142301370..142580792)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	X	NC_000086.7 (143518366..143797796)

Chromosome X - NC_000086.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling.
Title: Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling.
PAK3 downregulation induces cognitive impairment following cranial irradiation.
Title: PAK3 downregulation induces cognitive impairment following cranial irradiation.
Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory.
Title: Disruption of PAK3 Signaling in Social Interaction Induced cFos Positive Cells Impairs Social Recognition Memory.
The intellectual disability PAK3 R67C mutation impacts cognitive functions and adult hippocampal neurogenesis.
Title: The intellectual disability PAK3 R67C mutation impacts cognitive functions and adult hippocampal neurogenesis.
Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation.
Title: Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation.
Furthermore, pharmacological inhibition of PAKs decreases ATXN1 levels in a mouse model of SCA1. To explore the potential of using PAK inhibitors in combination therapy, we combined the pharmacological inhibition of PAK with MSK1, a previously identified modulator of ATXN1, and examined their effects on ATXN1 levels. We found that inhibition of both pathways results in an additive decrease in ATXN1 levels.
Title: PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in spinocerebellar ataxia type 1.
Pak3 knockout (KO) mice had defects of oligodendrocyte differentiation in developing corpus callosum and to a lesser extent in anterior commissure, which were compensated at the adult stage. In vitro experiments in oligodendrocyte precursor (OPC) cultures, derived from Pak3 KO and wild type brains, support a developmental and cell-autonomous role for PAK3 in regulating OPC differentiation into mature oligodendrocytes.
Title: The intellectual disability protein PAK3 regulates oligodendrocyte precursor cell differentiation.
Our results indicate that Pak3 is a novel regulator of beta-cell differentiation and function. Pak3 acts downstream of Ngn3 to promote cell cycle exit and differentiation in the embryo by a mechanism that might involve repression of Ccnd1.
Title: Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice.
Pak proteins are key components of multiple engraftment-associated hematopoietic stem cells functions and play a direct role in activation of ERK in hematopoietic stem cells.
Title: The Rac GTPase effector p21-activated kinase is essential for hematopoietic stem/progenitor cell migration and engraftment.
PAK1 inhibits the activity of PAK3a but not of the splice variant PAK3b in a trans-regulatory manner. Altogether, these results show that PAK3 and PAK1 signaling may be coordinated by heterodimerization.
Title: The p21-activated kinase PAK3 forms heterodimers with PAK1 in brain implementing trans-regulation of PAK3 activity.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

DCX (e-PCR)
- UniSTS:506627

px-62a8 (e-PCR)
- UniSTS:258053

U39738 (e-PCR)
- UniSTS:125742

RH137889 (e-PCR)
- UniSTS:219976

AW061185 (e-PCR)
- UniSTS:209544

DXMit185 (e-PCR), detects polymorphism
- UniSTS:132077

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GTPase binding	ISO Inferred from Sequence Orthology more info
enables MAP kinase kinase activity	ISO Inferred from Sequence Orthology more info
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase activity	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables small GTPase binding	IPI Inferred from Physical Interaction more info	PubMed
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in axonogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to organic cyclic compound	IDA Inferred from Direct Assay more info	PubMed
involved_in dendrite development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within dendritic spine development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in dendritic spine morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of dendritic spine morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of fibroblast migration	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of actin cytoskeleton organization	ISO Inferred from Sequence Orthology more info
involved_in regulation of actin filament polymerization	ISO Inferred from Sequence Orthology more info
involved_in regulation of axonogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of neuron projection development	ISO Inferred from Sequence Orthology more info
involved_in regulation of postsynapse organization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynapse organization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endosome	ISO Inferred from Sequence Orthology more info
located_in glutamatergic synapse	IC Inferred by Curator more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IEP Inferred from Expression Pattern more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in postsynaptic density	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynaptic density	IEP Inferred from Expression Pattern more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein kinase PAK 3

Names: CDC42/RAC effector kinase PAK-B; beta-PAK; p21 protein (Cdc42/Rac)-activated kinase 3; p21-activated kinase 3

NP_001181975.1

EC 2.7.11.1

NP_001181976.1

EC 2.7.11.1

NP_001181977.1

EC 2.7.11.1

NP_001181978.1

EC 2.7.11.1

NP_032804.2

EC 2.7.11.1

XP_006528815.1

EC 2.7.11.1

XP_006528816.1

EC 2.7.11.1

XP_006528817.1

EC 2.7.11.1

XP_011246092.1

EC 2.7.11.1

XP_030107108.1

EC 2.7.11.1

XP_030107109.1

EC 2.7.11.1

XP_030107110.1

EC 2.7.11.1

XP_030107111.1

EC 2.7.11.1

XP_036017734.1

EC 2.7.11.1

XP_036017735.1

EC 2.7.11.1

XP_036017736.1

EC 2.7.11.1

XP_036017737.1

EC 2.7.11.1

XP_036017738.1

EC 2.7.11.1

XP_036017739.1

EC 2.7.11.1

XP_036017740.1

EC 2.7.11.1

XP_036017741.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_001195046.1 → NP_001181975.1 serine/threonine-protein kinase PAK 3 isoform A

See identical proteins and their annotated locations for NP_001181975.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longest isoform (A).

Source sequence(s)

AL691499, BX530055, BX813331

UniProtKB/TrEMBL

B1GX81

Conserved Domains (2) summary

cd06656
Location:284 → 580

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

cd01093
Location:68 → 149

CRIB_PAK_like; PAK (p21 activated kinase) Binding Domain (PBD), binds Cdc42p- and/or Rho-like small GTPases; also known as the Cdc42/Rac interactive binding (CRIB) motif; has been shown to inhibit transcriptional activation and cell transformation mediated by the ...
NM_001195047.1 → NP_001181976.1 serine/threonine-protein kinase PAK 3 isoform B

See identical proteins and their annotated locations for NP_001181976.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform B), compared to isoform A.

Source sequence(s)

AL691499, BX530055, BX813331

UniProtKB/TrEMBL

B1GX80

Conserved Domains (3) summary

cd06656
Location:269 → 565

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

smart00220
Location:289 → 540

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam00786
Location:69 → 145

PBD; P21-Rho-binding domain
NM_001195048.1 → NP_001181977.1 serine/threonine-protein kinase PAK 3 isoform C

See identical proteins and their annotated locations for NP_001181977.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and lacks an in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform C), compared to isoform A.

Source sequence(s)

AK158893, AL691499, BX530055, BX813331

Consensus CDS

CCDS57779.1

UniProtKB/Swiss-Prot

O88645, Q61036, Q8K1R5, Q8K1R6

Related

ENSMUSP00000033640.8, ENSMUST00000033640.14

Conserved Domains (2) summary

cd06656
Location:263 → 559

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 141

PBD; P21-Rho-binding domain
NM_001195049.1 → NP_001181978.1 serine/threonine-protein kinase PAK 3 isoform D

See identical proteins and their annotated locations for NP_001181978.1

Status: VALIDATED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and lacks two consecutive in-frame exons in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform D), compared to isoform A. Both variants 4 and 5 encode the same protein (isoform D).

Source sequence(s)

AL691499, BX530055, BX813331

Consensus CDS

CCDS30454.1

UniProtKB/Swiss-Prot

Q61036

Related

ENSMUSP00000108485.2, ENSMUST00000112864.8

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
NM_008778.3 → NP_032804.2 serine/threonine-protein kinase PAK 3 isoform D

See identical proteins and their annotated locations for NP_032804.2

Status: VALIDATED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and lacks two consecutive in-frame exons in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform D), compared to isoform A. Both variants 4 and 5 encode the same protein (isoform D).

Source sequence(s)

AL691499, BX322533, BX530055, BX813331

Consensus CDS

CCDS30454.1

UniProtKB/Swiss-Prot

Q61036

Related

ENSMUSP00000126562.3, ENSMUST00000172330.3

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000086.8 Reference GRCm39 C57BL/6J

Range

142301370..142580792

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036161842.1 → XP_036017735.1 serine/threonine-protein kinase PAK 3 isoform X1

UniProtKB/Swiss-Prot

O88645, Q61036, Q8K1R5, Q8K1R6

Conserved Domains (2) summary

cd06656
Location:263 → 559

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 141

PBD; P21-Rho-binding domain
XM_036161844.1 → XP_036017737.1 serine/threonine-protein kinase PAK 3 isoform X1

UniProtKB/Swiss-Prot

O88645, Q61036, Q8K1R5, Q8K1R6

Conserved Domains (2) summary

cd06656
Location:263 → 559

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 141

PBD; P21-Rho-binding domain
XM_036161841.1 → XP_036017734.1 serine/threonine-protein kinase PAK 3 isoform X1

UniProtKB/Swiss-Prot

O88645, Q61036, Q8K1R5, Q8K1R6

Conserved Domains (2) summary

cd06656
Location:263 → 559

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 141

PBD; P21-Rho-binding domain
XM_036161846.1 → XP_036017739.1 serine/threonine-protein kinase PAK 3 isoform X2

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
XM_036161847.1 → XP_036017740.1 serine/threonine-protein kinase PAK 3 isoform X2

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
XM_011247790.4 → XP_011246092.1 serine/threonine-protein kinase PAK 3 isoform X2

See identical proteins and their annotated locations for XP_011246092.1

UniProtKB/Swiss-Prot

Q61036

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
XM_030251249.2 → XP_030107109.1 serine/threonine-protein kinase PAK 3 isoform X2

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
XM_036161843.1 → XP_036017736.1 serine/threonine-protein kinase PAK 3 isoform X1

UniProtKB/Swiss-Prot

O88645, Q61036, Q8K1R5, Q8K1R6

Related

ENSMUSP00000108484.2, ENSMUST00000112863.8

Conserved Domains (2) summary

cd06656
Location:263 → 559

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 141

PBD; P21-Rho-binding domain
XM_030251248.2 → XP_030107108.1 serine/threonine-protein kinase PAK 3 isoform X1

UniProtKB/Swiss-Prot

O88645, Q61036, Q8K1R5, Q8K1R6

Conserved Domains (2) summary

cd06656
Location:263 → 559

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 141

PBD; P21-Rho-binding domain
XM_006528752.5 → XP_006528815.1 serine/threonine-protein kinase PAK 3 isoform X1

See identical proteins and their annotated locations for XP_006528815.1

UniProtKB/Swiss-Prot

O88645, Q61036, Q8K1R5, Q8K1R6

Conserved Domains (2) summary

cd06656
Location:263 → 559

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 141

PBD; P21-Rho-binding domain
XM_030251251.2 → XP_030107111.1 serine/threonine-protein kinase PAK 3 isoform X2

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
XM_006528753.4 → XP_006528816.1 serine/threonine-protein kinase PAK 3 isoform X2

See identical proteins and their annotated locations for XP_006528816.1

UniProtKB/Swiss-Prot

Q61036

Related

ENSMUSP00000108486.2, ENSMUST00000112865.8

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
XM_006528754.5 → XP_006528817.1 serine/threonine-protein kinase PAK 3 isoform X2

See identical proteins and their annotated locations for XP_006528817.1

UniProtKB/Swiss-Prot

Q61036

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
XM_036161845.1 → XP_036017738.1 serine/threonine-protein kinase PAK 3 isoform X1

UniProtKB/Swiss-Prot

O88645, Q61036, Q8K1R5, Q8K1R6

Conserved Domains (2) summary

cd06656
Location:263 → 559

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 141

PBD; P21-Rho-binding domain
XM_030251250.2 → XP_030107110.1 serine/threonine-protein kinase PAK 3 isoform X2

Conserved Domains (2) summary

cd06656
Location:248 → 544

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3

pfam00786
Location:69 → 126

PBD; P21-Rho-binding domain
XM_036161848.1 → XP_036017741.1 serine/threonine-protein kinase PAK 3 isoform X3

Conserved Domains (1) summary

cd06656
Location:230 → 526

STKc_PAK3; Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3