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UniProtKB - Q8CIN4 (PAK2_MOUSE)

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Protein

Serine/threonine-protein kinase PAK 2

Gene

Pak2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. 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. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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-402 and allows the kinase domain to adopt an active structure. Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei278ATPPROSITE-ProRule annotation1
Active sitei367Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi255 – 263ATPPROSITE-ProRule annotation9

GO - Molecular functioni

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Growth regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-202433. Generation of second messenger molecules.
R-MMU-2871796. FCERI mediated MAPK activation.
R-MMU-389359. CD28 dependent Vav1 pathway.
R-MMU-399954. Sema3A PAK dependent Axon repulsion.
R-MMU-4420097. VEGFA-VEGFR2 Pathway.
R-MMU-5218920. VEGFR2 mediated vascular permeability.
R-MMU-5621575. CD209 (DC-SIGN) signaling.
R-MMU-5627123. RHO GTPases activate PAKs.
R-MMU-5687128. MAPK6/MAPK4 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 2 (EC:2.7.11.1)
Alternative name(s):
Gamma-PAK
p21-activated kinase 2
Short name:
PAK-2
Cleaved into the following 2 chains:
PAK-2p27
PAK-2p34
Gene namesi
Name:Pak2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1339984. Pak2.

Subcellular locationi

Serine/threonine-protein kinase PAK 2 :
  • Cytoplasm

    • Note: MYO18A mediates the cellular distribution of the PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell membrane.By similarity
PAK-2p34 :

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000864662 – 524Serine/threonine-protein kinase PAK 2Add BLAST523
ChainiPRO_00003049242 – 212PAK-2p27By similarityAdd BLAST211
ChainiPRO_0000304925213 – 524PAK-2p34By similarityAdd BLAST312

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei2PhosphoserineBy similarity1
Modified residuei20PhosphoserineBy similarity1
Modified residuei55PhosphoserineBy similarity1
Modified residuei58PhosphoserineBy similarity1
Modified residuei60PhosphothreonineBy similarity1
Modified residuei62N6-acetyllysineCombined sources1
Modified residuei64PhosphoserineBy similarity1
Modified residuei128N6-acetyllysineBy similarity1
Modified residuei134PhosphothreonineBy similarity1
Modified residuei139PhosphotyrosineCombined sources1
Modified residuei141PhosphoserineCombined sources1
Modified residuei143PhosphothreonineCombined sources1
Modified residuei152PhosphoserineCombined sources1
Modified residuei154PhosphothreonineBy similarity1
Modified residuei159PhosphothreonineCombined sources1
Modified residuei169PhosphothreonineBy similarity1
Modified residuei197PhosphoserineCombined sources1
Modified residuei402Phosphothreonine; by autocatalysisBy similarity1

Post-translational modificationi

Full length PAK2 is autophosphorylated when activated by CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-2p34, become highly autophosphorylated. Autophosphorylation of PAK-2p27 can occur in the absence of any effectors and is dependent on phosphorylation of Thr-402, because PAK-2p27 is acting as an exogenous substrate (By similarity).By similarity
During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34.By similarity
Ubiquitinated, leading to its proteasomal degradation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei212 – 213Cleavage; by caspase-3 or caspase-3-like proteasesBy similarity2

Keywords - PTMi

Acetylation, Lipoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8CIN4.
MaxQBiQ8CIN4.
PaxDbiQ8CIN4.
PeptideAtlasiQ8CIN4.
PRIDEiQ8CIN4.

PTM databases

iPTMnetiQ8CIN4.
PhosphoSitePlusiQ8CIN4.

Expressioni

Gene expression databases

BgeeiENSMUSG00000022781.
CleanExiMM_PAK2.
GenevisibleiQ8CIN4. MM.

Interactioni

Subunit structurei

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with SCRIB. Interacts with ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
HttP428592EBI-1559317,EBI-5327353

GO - Molecular functioni

Complete GO annotation...

Protein-protein interaction databases

BioGridi230244. 2 interactors.
DIPiDIP-39167N.
IntActiQ8CIN4. 4 interactors.
MINTiMINT-268891.
STRINGi10090.ENSMUSP00000023467.

Structurei

3D structure databases

ProteinModelPortaliQ8CIN4.
SMRiQ8CIN4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini74 – 87CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini249 – 499Protein kinasePROSITE-ProRule annotationAdd BLAST251

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni69 – 137Autoregulatory regionBy similarityAdd BLAST69
Regioni69 – 112GTPase-bindingBy similarityAdd BLAST44

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi245 – 251Nuclear localization signalBy similarity7

Sequence similaritiesi

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.Curated

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00860000133680.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ8CIN4.
KOiK04410.
OMAiDSGVCED.
OrthoDBiEOG091G04H8.
PhylomeDBiQ8CIN4.
TreeFamiTF105351.

Family and domain databases

CDDicd01093. CRIB_PAK_like. 1 hit.
cd06655. STKc_PAK2. 1 hit.
Gene3Di3.90.810.10. 1 hit.
InterProiView protein in InterPro
IPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR035065. PAK2.
IPR033923. PAK_BD.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR035064. STK_PAK2.
PANTHERiPTHR24361:SF592. PTHR24361:SF592. 1 hit.
PfamiView protein in Pfam
PF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8CIN4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR 
        60         70         80         90        100
NKIISIFSGT EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE 
       110        120        130        140        150
QWARLLQTSN ITKLEQKKNP QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF 
       160        170        180        190        200
PSGTPALNTK GSETSAVVTE EDDDDEDAAP PVIAPRPDHT KSIYTRSVID 
       210        220        230        240        250
PIPAPVGDSN VDSGAKSSDK QKKKAKMTDE EIMEKLRTIV SIGDPKKKYT 
       260        270        280        290        300
RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE 
       310        320        330        340        350
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR 
       360        370        380        390        400
ECLQALEFLH ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR 
       410        420        430        440        450
STMVGTPYWM APEVVTRKAY GPKVDIWSLG IMAIEMVEGE PPYLNENPLR 
       460        470        480        490        500
ALYLIATNGT PELQNPEKLS PIFRDFLNRC LEMDVEKRGS AKELLQHPFL 
       510        520 
KLAKPLSSLT PLILAAKEAM KSNR
Length:524
Mass (Da):57,930
Last modified:March 1, 2003 - v1
Checksum:iD8BDA7B193D41B1B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY167030 mRNA. Translation: AAN65624.1.
BC086650 mRNA. Translation: AAH86650.1.
CCDSiCCDS28112.1.
RefSeqiNP_796300.1. NM_177326.3.
XP_006522135.1. XM_006522072.3.
UniGeneiMm.234204.

Genome annotation databases

EnsembliENSMUST00000023467; ENSMUSP00000023467; ENSMUSG00000022781.
GeneIDi224105.
KEGGimmu:224105.
UCSCiuc007yyd.2. mouse.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiPAK2_MOUSE
AccessioniPrimary (citable) accession number: Q8CIN4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: March 1, 2003
Last modified: July 5, 2017
This is version 130 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families