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Q8CIN4

- PAK2_MOUSE

UniProt

Q8CIN4 - PAK2_MOUSE

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Protein
Serine/threonine-protein kinase PAK 2
Gene
Pak2
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.1 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei212 – 2132Cleavage; by caspase-3 or caspase-3-like proteases By similarity
Binding sitei278 – 2781ATP By similarity
Active sitei367 – 3671Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi255 – 2639ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein binding Source: UniProtKB
  3. protein serine/threonine kinase activity Source: MGI
  4. protein tyrosine kinase activator activity Source: Ensembl
  5. receptor signaling protein serine/threonine kinase activity Source: RefGenome

GO - Biological processi

  1. actin cytoskeleton organization Source: RefGenome
  2. axonogenesis Source: RefGenome
  3. intracellular signal transduction Source: RefGenome
  4. negative regulation of apoptotic process Source: Ensembl
  5. negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: Ensembl
  6. peptidyl-serine phosphorylation Source: Ensembl
  7. positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
  8. protein autophosphorylation Source: MGI
  9. protein phosphorylation Source: MGI
  10. regulation of apoptotic process Source: RefGenome
  11. regulation of growth Source: UniProtKB-KW
  12. signal transduction by phosphorylation Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Growth regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_188530. FCERI mediated MAPK activation.
REACT_211941. Stimulation of the cell death response by PAK-2p34.
REACT_218318. Regulation of activated PAK-2p34 by proteasome mediated degradation.
REACT_225768. Generation of second messenger molecules.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 16

Organism-specific databases

MGIiMGI:1339984. Pak2.

Subcellular locationi

Chain 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.1 Publication
Chain 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.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: RefGenome
  2. membrane Source: UniProtKB-SubCell
  3. nucleus Source: UniProtKB-SubCell
  4. perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 524523Serine/threonine-protein kinase PAK 2
PRO_0000086466Add
BLAST
Chaini2 – 212211PAK-2p27 By similarity
PRO_0000304924Add
BLAST
Chaini213 – 524312PAK-2p34 By similarity
PRO_0000304925Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine By similarity
Modified residuei2 – 21Phosphoserine By similarity
Modified residuei58 – 581Phosphoserine By similarity
Modified residuei62 – 621N6-acetyllysine1 Publication
Modified residuei128 – 1281N6-acetyllysine By similarity
Modified residuei141 – 1411Phosphoserine2 Publications
Modified residuei169 – 1691Phosphothreonine By similarity
Modified residuei197 – 1971Phosphoserine1 Publication
Modified residuei402 – 4021Phosphothreonine; by autocatalysis By similarity

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.
During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34 By similarity.1 Publication
Ubiquitinated, leading to its proteasomal degradation By similarity.

Keywords - PTMi

Acetylation, Lipoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ8CIN4.
PaxDbiQ8CIN4.
PRIDEiQ8CIN4.

PTM databases

PhosphoSiteiQ8CIN4.

Expressioni

Gene expression databases

ArrayExpressiQ8CIN4.
BgeeiQ8CIN4.
CleanExiMM_PAK2.
GenevestigatoriQ8CIN4.

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.1 Publication

Binary interactionsi

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

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ8CIN4.
SMRiQ8CIN4. Positions 69-143, 228-519.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini74 – 8714CRIB
Add
BLAST
Domaini249 – 499251Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni69 – 13769Autoregulatory region By similarity
Add
BLAST
Regioni69 – 11244GTPase-binding By similarity
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi245 – 2517Nuclear localization signal By similarity

Sequence similaritiesi

Contains 1 CRIB domain.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00680000099789.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ8CIN4.
KOiK04410.
OMAiSIFYSNE.
OrthoDBiEOG7CK36J.
PhylomeDBiQ8CIN4.
TreeFamiTF105351.

Family and domain databases

Gene3Di3.90.810.10. 1 hit.
InterProiIPR000095. 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]
PfamiPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8CIN4-1 [UniParc]FASTAAdd to Basket

« Hide

MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR    50
NKIISIFSGT EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE 100
QWARLLQTSN ITKLEQKKNP QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF 150
PSGTPALNTK GSETSAVVTE EDDDDEDAAP PVIAPRPDHT KSIYTRSVID 200
PIPAPVGDSN VDSGAKSSDK QKKKAKMTDE EIMEKLRTIV SIGDPKKKYT 250
RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE 300
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR 350
ECLQALEFLH ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR 400
STMVGTPYWM APEVVTRKAY GPKVDIWSLG IMAIEMVEGE PPYLNENPLR 450
ALYLIATNGT PELQNPEKLS PIFRDFLNRC LEMDVEKRGS AKELLQHPFL 500
KLAKPLSSLT PLILAAKEAM KSNR 524
Length:524
Mass (Da):57,930
Last modified:March 1, 2003 - v1
Checksum:iD8BDA7B193D41B1B
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY167030 mRNA. Translation: AAN65624.1.
BC086650 mRNA. Translation: AAH86650.1.
CCDSiCCDS28112.1.
RefSeqiNP_796300.1. NM_177326.3.
XP_006522135.1. XM_006522072.1.
UniGeneiMm.234204.

Genome annotation databases

EnsembliENSMUST00000023467; ENSMUSP00000023467; ENSMUSG00000022781.
GeneIDi224105.
KEGGimmu:224105.
UCSCiuc007yyd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY167030 mRNA. Translation: AAN65624.1 .
BC086650 mRNA. Translation: AAH86650.1 .
CCDSi CCDS28112.1.
RefSeqi NP_796300.1. NM_177326.3.
XP_006522135.1. XM_006522072.1.
UniGenei Mm.234204.

3D structure databases

ProteinModelPortali Q8CIN4.
SMRi Q8CIN4. Positions 69-143, 228-519.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 230244. 2 interactions.
DIPi DIP-39167N.
IntActi Q8CIN4. 4 interactions.
MINTi MINT-268891.
STRINGi 10090.ENSMUSP00000023467.

PTM databases

PhosphoSitei Q8CIN4.

Proteomic databases

MaxQBi Q8CIN4.
PaxDbi Q8CIN4.
PRIDEi Q8CIN4.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000023467 ; ENSMUSP00000023467 ; ENSMUSG00000022781 .
GeneIDi 224105.
KEGGi mmu:224105.
UCSCi uc007yyd.1. mouse.

Organism-specific databases

CTDi 5062.
MGIi MGI:1339984. Pak2.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00680000099789.
HOGENOMi HOG000234202.
HOVERGENi HBG108518.
InParanoidi Q8CIN4.
KOi K04410.
OMAi SIFYSNE.
OrthoDBi EOG7CK36J.
PhylomeDBi Q8CIN4.
TreeFami TF105351.

Enzyme and pathway databases

Reactomei REACT_188530. FCERI mediated MAPK activation.
REACT_211941. Stimulation of the cell death response by PAK-2p34.
REACT_218318. Regulation of activated PAK-2p34 by proteasome mediated degradation.
REACT_225768. Generation of second messenger molecules.

Miscellaneous databases

NextBioi 377081.
PROi Q8CIN4.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8CIN4.
Bgeei Q8CIN4.
CleanExi MM_PAK2.
Genevestigatori Q8CIN4.

Family and domain databases

Gene3Di 3.90.810.10. 1 hit.
InterProi IPR000095. 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 ]
Pfami PF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141 AND SER-197, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. 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.

Entry informationi

Entry nameiPAK2_MOUSE
AccessioniPrimary (citable) accession number: Q8CIN4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: March 1, 2003
Last modified: September 3, 2014
This is version 101 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

Similar proteinsi