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Protein

Serine/threonine-protein kinase PAK 2

Gene

Pak2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionAllosteric enzyme, Kinase, 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-3928664 Ephrin signaling
R-MMU-399954 Sema3A PAK dependent Axon repulsion
R-MMU-4420097 VEGFA-VEGFR2 Pathway
R-MMU-445355 Smooth Muscle Contraction
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:
Gene namesi
Name:Pak2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1339984 Pak2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230244, 3 interactors
DIPiDIP-39167N
IntActiQ8CIN4, 7 interactors
MINTiQ8CIN4
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

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
GeneTreeiENSGT00910000143994
HOGENOMiHOG000234202
HOVERGENiHBG108518
InParanoidiQ8CIN4
KOiK04410
OMAiVCEDKPP
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
IPR036936 CRIB_dom_sf
IPR011009 Kinase-like_dom_sf
IPR035065 PAK2/3
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR035064 STK_PAK2
PANTHERiPTHR24361:SF250 PTHR24361:SF250, 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

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: March 28, 2018
This is version 136 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

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health