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Q8CIN4 (PAK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. PAK-2p27
  2. PAK-2p34
Gene names
Name:Pak2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

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

Subunit structure

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. Ref.6

Subcellular location

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. Ref.4

PAK-2p34: Nucleus By similarity. Cytoplasmperinuclear region By similarity. Membrane; Lipid-anchor By similarity. Note: Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region By similarity. Ref.4

Post-translational modification

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.

During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34 By similarity. Ref.4

Ubiquitinated, leading to its proteasomal degradation By similarity.

Sequence similarities

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

Contains 1 CRIB domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Growth regulation
   Cellular componentCytoplasm
Membrane
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Lipoprotein
Phosphoprotein
Ubl conjugation
   Technical termAllosteric enzyme
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from Biological aspect of Ancestor. Source: RefGenome

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

intracellular signal transduction

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from sequence orthology PubMed 11805089. Source: MGI

protein phosphorylation

Inferred from sequence orthology PubMed 11805089. Source: MGI

regulation of apoptotic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of growth

Inferred from electronic annotation. Source: UniProtKB-KW

signal transduction by phosphorylation

Inferred from Biological aspect of Ancestor. Source: GOC

   Cellular_componentcytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence orthology PubMed 11805089. Source: MGI

protein tyrosine kinase activator activity

Inferred from electronic annotation. Source: Ensembl

receptor signaling protein serine/threonine kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HttP428592EBI-1559317,EBI-5327353

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 524523Serine/threonine-protein kinase PAK 2
PRO_0000086466
Chain2 – 212211PAK-2p27 By similarity
PRO_0000304924
Chain213 – 524312PAK-2p34 By similarity
PRO_0000304925

Regions

Domain74 – 8714CRIB
Domain249 – 499251Protein kinase
Nucleotide binding255 – 2639ATP By similarity
Region69 – 13769Autoregulatory region By similarity
Region69 – 11244GTPase-binding By similarity
Motif245 – 2517Nuclear localization signal By similarity

Sites

Active site3671Proton acceptor By similarity
Binding site2781ATP By similarity
Site212 – 2132Cleavage; by caspase-3 or caspase-3-like proteases By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue21Phosphoserine By similarity
Modified residue581Phosphoserine By similarity
Modified residue621N6-acetyllysine Ref.8
Modified residue1281N6-acetyllysine By similarity
Modified residue1411Phosphoserine Ref.5 Ref.7
Modified residue1691Phosphothreonine By similarity
Modified residue1971Phosphoserine Ref.5
Modified residue4021Phosphothreonine; by autocatalysis By similarity

Sequences

Sequence LengthMass (Da)Tools
Q8CIN4 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: D8BDA7B193D41B1B

FASTA52457,930
        10         20         30         40         50         60 
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR NKIISIFSGT 

        70         80         90        100        110        120 
EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE QWARLLQTSN ITKLEQKKNP 

       130        140        150        160        170        180 
QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF PSGTPALNTK GSETSAVVTE EDDDDEDAAP 

       190        200        210        220        230        240 
PVIAPRPDHT KSIYTRSVID PIPAPVGDSN VDSGAKSSDK QKKKAKMTDE EIMEKLRTIV 

       250        260        270        280        290        300 
SIGDPKKKYT RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE 

       310        320        330        340        350        360 
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR ECLQALEFLH 

       370        380        390        400        410        420 
ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR STMVGTPYWM APEVVTRKAY 

       430        440        450        460        470        480 
GPKVDIWSLG IMAIEMVEGE PPYLNENPLR ALYLIATNGT PELQNPEKLS PIFRDFLNRC 

       490        500        510        520 
LEMDVEKRGS AKELLQHPFL KLAKPLSSLT PLILAAKEAM KSNR 

« Hide

References

« Hide 'large scale' references
[1]"Negative control of the Myc protein by the stress-responsive kinase Pak2."
Huang Z., Traugh J.A., Bishop J.M.
Mol. Cell. Biol. 24:1582-1594(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6J.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[3]"p21-activated protein kinase gamma-PAK suppresses programmed cell death of BALB3T3 fibroblasts."
Jakobi R., Moertl E., Koeppel M.A.
J. Biol. Chem. 276:16624-16634(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BAD.
[4]"Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation."
Jakobi R., McCarthy C.C., Koeppel M.A., Stringer D.K.
J. Biol. Chem. 278:38675-38685(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, CLEAVAGE.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141 AND SER-197, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[6]"Scrib regulates PAK activity during the cell migration process."
Nola S., Sebbagh M., Marchetto S., Osmani N., Nourry C., Audebert S., Navarro C., Rachel R., Montcouquiol M., Sans N., Etienne-Manneville S., Borg J.-P., Santoni M.-J.
Hum. Mol. Genet. 17:3552-3565(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SCRIB.
[7]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[8]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-62, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY167030 mRNA. Translation: AAN65624.1.
BC086650 mRNA. Translation: AAH86650.1.
CCDSCCDS28112.1.
RefSeqNP_796300.1. NM_177326.3.
XP_006522135.1. XM_006522072.1.
UniGeneMm.234204.

3D structure databases

ProteinModelPortalQ8CIN4.
SMRQ8CIN4. Positions 69-143, 228-519.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid230244. 2 interactions.
DIPDIP-39167N.
IntActQ8CIN4. 4 interactions.
MINTMINT-268891.
STRING10090.ENSMUSP00000023467.

PTM databases

PhosphoSiteQ8CIN4.

Proteomic databases

MaxQBQ8CIN4.
PaxDbQ8CIN4.
PRIDEQ8CIN4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000023467; ENSMUSP00000023467; ENSMUSG00000022781.
GeneID224105.
KEGGmmu:224105.
UCSCuc007yyd.1. mouse.

Organism-specific databases

CTD5062.
MGIMGI:1339984. Pak2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00680000099789.
HOGENOMHOG000234202.
HOVERGENHBG108518.
InParanoidQ8CIN4.
KOK04410.
OMASIFYSNE.
OrthoDBEOG7CK36J.
PhylomeDBQ8CIN4.
TreeFamTF105351.

Gene expression databases

ArrayExpressQ8CIN4.
BgeeQ8CIN4.
CleanExMM_PAK2.
GenevestigatorQ8CIN4.

Family and domain databases

Gene3D3.90.810.10. 1 hit.
InterProIPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio377081.
PROQ8CIN4.
SOURCESearch...

Entry information

Entry namePAK2_MOUSE
AccessionPrimary (citable) accession number: Q8CIN4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot