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Q29502

- PAK2_RABIT

UniProt

Q29502 - PAK2_RABIT

Protein

Serine/threonine-protein kinase PAK 2

Gene

PAK2

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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 sitei368 – 3681Proton 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: IntAct
    3. protein serine/threonine kinase activity Source: UniProtKB-KW
    4. protein tyrosine kinase activator activity Source: Ensembl

    GO - Biological processi

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

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.1.12. 1749.
    ReactomeiREACT_223446. Regulation of PAK-2p34 activity by PS-GAP/RHG10.

    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
    p21-activated protein kinase I
    Short name:
    PAKI
    Cleaved into the following 2 chains:
    Gene namesi
    Name:PAK2
    OrganismiOryctolagus cuniculus (Rabbit)
    Taxonomic identifieri9986 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
    ProteomesiUP000001811: Chromosome 14

    Subcellular locationi

    Chain Serine/threonine-protein kinase PAK 2 : Cytoplasm By similarity
    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. cytosol Source: Reactome
    2. membrane Source: UniProtKB-SubCell
    3. nucleoplasm Source: Reactome
    4. 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_0000086467Add
    BLAST
    Chaini2 – 212211PAK-2p27By similarityPRO_0000304926Add
    BLAST
    Chaini213 – 524312PAK-2p34By similarityPRO_0000304927Add
    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-acetyllysineBy similarity
    Modified residuei128 – 1281N6-acetyllysineBy similarity
    Modified residuei141 – 1411PhosphoserineBy similarity
    Modified residuei169 – 1691PhosphothreonineBy similarity
    Modified residuei197 – 1971PhosphoserineBy similarity
    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

    PRIDEiQ29502.

    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

    Protein-protein interaction databases

    IntActiQ29502. 1 interaction.
    STRINGi9986.ENSOCUP00000007111.

    Structurei

    3D structure databases

    ProteinModelPortaliQ29502.
    SMRiQ29502. Positions 77-143, 228-519.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini74 – 8714CRIBPROSITE-ProRule annotationAdd
    BLAST
    Domaini249 – 500252Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni69 – 13769Autoregulatory regionBy similarityAdd
    BLAST
    Regioni69 – 11244GTPase-bindingBy similarityAdd
    BLAST
    Regioni88 – 248161LinkerAdd
    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.
    OMAiWLQYDMM.
    OrthoDBiEOG7CK36J.
    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.

    Q29502-1 [UniParc]FASTAAdd to Basket

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    MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR    50
    NKIISIFSGT EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE 100
    QWARLLQTSN ITKLEQKKNP QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF 150
    PSGAPALNTK VSETSAVVTE EDDDDEEAAP PVIAPRPDHT KSIYTRSVID 200
    PIPAPVGDSH VDSGAKSSDK QKKKTKMTDE 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 PLIMAAKEAM KSNR 524
    Length:524
    Mass (Da):58,028
    Last modified:November 1, 1996 - v1
    Checksum:i397D71020EADFFCA
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U46915 mRNA. Translation: AAC48537.1.
    RefSeqiNP_001076225.1. NM_001082756.1.
    UniGeneiOcu.2289.

    Genome annotation databases

    EnsembliENSOCUT00000008227; ENSOCUP00000007111; ENSOCUG00000008224.
    GeneIDi100009535.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U46915 mRNA. Translation: AAC48537.1 .
    RefSeqi NP_001076225.1. NM_001082756.1.
    UniGenei Ocu.2289.

    3D structure databases

    ProteinModelPortali Q29502.
    SMRi Q29502. Positions 77-143, 228-519.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q29502. 1 interaction.
    STRINGi 9986.ENSOCUP00000007111.

    Proteomic databases

    PRIDEi Q29502.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSOCUT00000008227 ; ENSOCUP00000007111 ; ENSOCUG00000008224 .
    GeneIDi 100009535.

    Organism-specific databases

    CTDi 5062.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00680000099789.
    HOGENOMi HOG000234202.
    HOVERGENi HBG108518.
    OMAi WLQYDMM.
    OrthoDBi EOG7CK36J.
    TreeFami TF105351.

    Enzyme and pathway databases

    BRENDAi 2.7.1.12. 1749.
    Reactomei REACT_223446. Regulation of PAK-2p34 activity by PS-GAP/RHG10.

    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. "Molecular cloning and sequencing of the cytostatic G protein-activated protein kinase PAK I."
      Jakobi R., Chen C., Tuazon P.T., Traugh J.A.
      J. Biol. Chem. 271:6206-6211(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].

    Entry informationi

    Entry nameiPAK2_RABIT
    AccessioniPrimary (citable) accession number: Q29502
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 115 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3