Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q8CIN4

- PAK2_MOUSE

UniProt

Q8CIN4 - PAK2_MOUSE

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 102 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 similarity

    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)LengthDescriptionGraphical viewFeature identifierActions
    Sitei212 – 2132Cleavage; by caspase-3 or caspase-3-like proteasesBy similarity
    Binding sitei278 – 2781ATPPROSITE-ProRule annotation
    Active sitei367 – 3671Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi255 – 2639ATPPROSITE-ProRule annotation

    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

    GO - Biological processi

    1. negative regulation of apoptotic process Source: Ensembl
    2. negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: Ensembl
    3. peptidyl-serine phosphorylation Source: Ensembl
    4. positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
    5. protein autophosphorylation Source: MGI
    6. protein phosphorylation Source: MGI
    7. regulation of growth Source: UniProtKB-KW

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

    GO - Cellular componenti

    1. membrane Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell
    3. perinuclear region of cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 524523Serine/threonine-protein kinase PAK 2PRO_0000086466Add
    BLAST
    Chaini2 – 212211PAK-2p27By similarityPRO_0000304924Add
    BLAST
    Chaini213 – 524312PAK-2p34By similarityPRO_0000304925Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei2 – 21PhosphoserineBy similarity
    Modified residuei58 – 581PhosphoserineBy similarity
    Modified residuei62 – 621N6-acetyllysine1 Publication
    Modified residuei128 – 1281N6-acetyllysineBy similarity
    Modified residuei141 – 1411Phosphoserine2 Publications
    Modified residuei169 – 1691PhosphothreonineBy similarity
    Modified residuei197 – 1971Phosphoserine1 Publication
    Modified residuei402 – 4021Phosphothreonine; by autocatalysisBy 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.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

    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.By similarity

    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.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini74 – 8714CRIBPROSITE-ProRule annotationAdd
    BLAST
    Domaini249 – 499251Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni69 – 13769Autoregulatory regionBy similarityAdd
    BLAST
    Regioni69 – 11244GTPase-bindingBy similarityAdd
    BLAST

    Motif

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

    Sequence similaritiesi

    Contains 1 CRIB domain.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    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

    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: October 1, 2014
    This is version 102 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