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Q8BTW9

- PAK4_MOUSE

UniProt

Q8BTW9 - PAK4_MOUSE

Protein

Serine/threonine-protein kinase PAK 4

Gene

Pak4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      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 migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei352 – 3521ATPPROSITE-ProRule annotation
    Active sitei442 – 4421Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi329 – 3379ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. cell cycle Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Cell cycle

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase PAK 4 (EC:2.7.11.1)
    Alternative name(s):
    p21-activated kinase 4
    Short name:
    PAK-4
    Gene namesi
    Name:Pak4
    Synonyms:Kiaa1142
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 7

    Organism-specific databases

    MGIiMGI:1917834. Pak4.

    Subcellular locationi

    Cytoplasm
    Note: Seems to shuttle between cytoplasmic compartments depending on the activating effector. For example, can be found on the cell periphery after activation of growth-factor or integrin-mediated signaling pathways By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Mice die at embryonic day 11.5 probably due to a defect in the fetal heart. They show strong defects in neuronal development and axonal outgrowth. Spinal cord motor neurons and interneurons failed to differentiate and migrate to their proper position. Nervous system-specific conditional PAK4 deletion mice display growth retardation and die prematurely.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 593593Serine/threonine-protein kinase PAK 4PRO_0000086475Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei41 – 411PhosphoserineBy similarity
    Modified residuei104 – 1041PhosphoserineBy similarity
    Modified residuei148 – 1481PhosphoserineBy similarity
    Modified residuei181 – 1811Phosphoserine2 Publications
    Modified residuei187 – 1871PhosphothreonineBy similarity
    Modified residuei195 – 1951PhosphoserineBy similarity
    Modified residuei257 – 2571PhosphoserineBy similarity
    Modified residuei266 – 2661PhosphoserineBy similarity
    Modified residuei293 – 2931PhosphoserineBy similarity
    Modified residuei476 – 4761Phosphoserine; by autocatalysis3 Publications

    Post-translational modificationi

    Autophosphorylated on serine residues when activated by CDC42/p21.By similarity
    Phosphorylated on tyrosine residues upon stimulation of FGFR2.4 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ8BTW9.
    PaxDbiQ8BTW9.
    PRIDEiQ8BTW9.

    PTM databases

    PhosphoSiteiQ8BTW9.

    Expressioni

    Gene expression databases

    BgeeiQ8BTW9.
    CleanExiMM_PAK4.
    GenevestigatoriQ8BTW9.

    Interactioni

    Subunit structurei

    Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1 By similarity. Interacts with FGFR2 and GRB2.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi214149. 1 interaction.
    IntActiQ8BTW9. 1 interaction.
    MINTiMINT-4106515.
    STRINGi10090.ENSMUSP00000103918.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8BTW9.
    SMRiQ8BTW9. Positions 10-44, 300-593.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini11 – 2414CRIBPROSITE-ProRule annotationAdd
    BLAST
    Domaini323 – 574252Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni25 – 322298LinkerAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi4 – 74Poly-Lys
    Compositional biasi105 – 1084Poly-Pro
    Compositional biasi216 – 29883Pro-richAdd
    BLAST
    Compositional biasi242 – 2465Poly-Ser

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00670000097939.
    HOGENOMiHOG000234205.
    HOVERGENiHBG108518.
    InParanoidiQ8BTW9.
    KOiK05734.
    OMAiIDPACIT.
    OrthoDBiEOG73804D.
    PhylomeDBiQ8BTW9.
    TreeFamiTF105352.

    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.
    [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.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q8BTW9-1 [UniParc]FASTAAdd to Basket

    « Hide

    MFGKKKKRVE ISAPSNFEHR VHTGFDQHEQ KFTGLPRQWQ SLIEESARRP    50
    KPLIDPACIT SIQPGAPKTI VRGSKGAKDG ALTLLLDEFE NMSVTRSNSL 100
    RRESPPPPAR AHQENGMLEE RAAPARMAPD KAGSRARATG HSEAGSGSGD 150
    RRRVGPEKRP KSSRDGPGGP QEASRDKRPL SGPDVSTPQP GSLTSGTKLA 200
    AGRPFNTYPR ADTDHPPRGA QGEPHTMAPN GPSATGLAAP QSSSSSRPPT 250
    RARGAPSPGV LGPHASEPQL APPARALAAP AVPPAPGPPG PRSPQREPQR 300
    VSHEQFRAAL QLVVDPGDPR SYLDNFIKIG EGSTGIVCIA TVRSSGKLVA 350
    VKKMDLRKQQ RRELLFNEVV IMRDYRHENV VEMYNSYLVG DELWVVMEFL 400
    EGGALTDIVT HTRMNEEQIA AVCLAVLQAL AVLHAQGVIH RDIKSDSILL 450
    THDGRVKLSD FGFCAQVSKE VPRRKSLVGT PYWMAPELIS RLPYGPEVDI 500
    WSLGVMVIEM VDGEPPYFNE PPLKAMKMIR DNLPPRLKNL HKASPSLKGF 550
    LDRLLVRDPA QRATAAELLK HPFLTKAGPP ASIVPLMRQH RTR 593
    Length:593
    Mass (Da):64,623
    Last modified:March 1, 2003 - v1
    Checksum:i4AFA91DD73D4C6D5
    GO

    Sequence cautioni

    The sequence BAC98108.2 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti5 – 51K → R in AAO61496. (PubMed:12529371)Curated
    Sequence conflicti248 – 2481P → L in AAO61496. (PubMed:12529371)Curated
    Sequence conflicti564 – 5641T → P in BAB30889. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY217016 mRNA. Translation: AAO61496.1.
    AK129298 mRNA. Translation: BAC98108.2. Different initiation.
    AK017713 mRNA. Translation: BAB30889.1.
    AK088512 mRNA. Translation: BAC40396.1.
    BC048238 mRNA. Translation: AAH48238.1.
    CCDSiCCDS21049.1.
    RefSeqiNP_081746.1. NM_027470.3.
    XP_006540419.1. XM_006540356.1.
    UniGeneiMm.21876.

    Genome annotation databases

    EnsembliENSMUST00000032823; ENSMUSP00000032823; ENSMUSG00000030602.
    ENSMUST00000108283; ENSMUSP00000103918; ENSMUSG00000030602.
    GeneIDi70584.
    KEGGimmu:70584.
    UCSCiuc009fzh.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY217016 mRNA. Translation: AAO61496.1 .
    AK129298 mRNA. Translation: BAC98108.2 . Different initiation.
    AK017713 mRNA. Translation: BAB30889.1 .
    AK088512 mRNA. Translation: BAC40396.1 .
    BC048238 mRNA. Translation: AAH48238.1 .
    CCDSi CCDS21049.1.
    RefSeqi NP_081746.1. NM_027470.3.
    XP_006540419.1. XM_006540356.1.
    UniGenei Mm.21876.

    3D structure databases

    ProteinModelPortali Q8BTW9.
    SMRi Q8BTW9. Positions 10-44, 300-593.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 214149. 1 interaction.
    IntActi Q8BTW9. 1 interaction.
    MINTi MINT-4106515.
    STRINGi 10090.ENSMUSP00000103918.

    PTM databases

    PhosphoSitei Q8BTW9.

    Proteomic databases

    MaxQBi Q8BTW9.
    PaxDbi Q8BTW9.
    PRIDEi Q8BTW9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000032823 ; ENSMUSP00000032823 ; ENSMUSG00000030602 .
    ENSMUST00000108283 ; ENSMUSP00000103918 ; ENSMUSG00000030602 .
    GeneIDi 70584.
    KEGGi mmu:70584.
    UCSCi uc009fzh.1. mouse.

    Organism-specific databases

    CTDi 10298.
    MGIi MGI:1917834. Pak4.
    Rougei Search...

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00670000097939.
    HOGENOMi HOG000234205.
    HOVERGENi HBG108518.
    InParanoidi Q8BTW9.
    KOi K05734.
    OMAi IDPACIT.
    OrthoDBi EOG73804D.
    PhylomeDBi Q8BTW9.
    TreeFami TF105352.

    Miscellaneous databases

    ChiTaRSi PAK4. mouse.
    NextBioi 331922.
    PROi Q8BTW9.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8BTW9.
    CleanExi MM_PAK4.
    Genevestigatori Q8BTW9.

    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.
    [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.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "p21-activated protein kinase 4 (PAK4) interacts with the keratinocyte growth factor receptor and participates in keratinocyte growth factor-mediated inhibition of oxidant-induced cell death."
      Lu Y., Pan Z.-Z., Devaux Y., Ray P.
      J. Biol. Chem. 278:10374-10380(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH FGFR2 AND GRB2, PHOSPHORYLATION AT TYROSINE RESIDUES.
      Strain: BALB/c.
    2. "Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
      Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
      DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Embryonic tail.
    3. Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.
      Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    4. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: NOD.
      Tissue: Embryo and Thymus.
    5. "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: FVB/N.
      Tissue: Colon.
    6. "Cytoskeletal changes regulated by the PAK4 serine/threonine kinase are mediated by LIM kinase 1 and cofilin."
      Dan C., Kelly A., Bernard O., Minden A.
      J. Biol. Chem. 276:32115-32121(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF LIMK1.
    7. "PAK4 kinase is essential for embryonic viability and for proper neuronal development."
      Qu J., Li X., Novitch B.G., Zheng Y., Kohn M., Xie J.M., Kozinn S., Bronson R., Beg A.A., Minden A.
      Mol. Cell. Biol. 23:7122-7133(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    8. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-476, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic brain.
    9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-476, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    10. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. "PAK4 is required for regulation of the cell-cycle regulatory protein p21, and for control of cell-cycle progression."
      Nekrasova T., Minden A.
      J. Cell. Biochem. 112:1795-1806(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "A key role for Pak4 in proliferation and differentiation of neural progenitor cells."
      Tian Y., Lei L., Minden A.
      Dev. Biol. 353:206-216(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiPAK4_MOUSE
    AccessioniPrimary (citable) accession number: Q8BTW9
    Secondary accession number(s): Q6ZPX0, Q80Z97, Q9CS71
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 10, 2004
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 105 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

    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