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O88643

- PAK1_MOUSE

UniProt

O88643 - PAK1_MOUSE

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Protein

Serine/threonine-protein kinase PAK 1

Gene
Pak1, Paka
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium By similarity.

Enzyme regulationi

Phosphorylation of Thr-84 by OXSR1 inhibits activation By similarity. Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-423 By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei299 – 2991ATP By similarity
Active sitei389 – 3891Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi276 – 2849ATP By similarity

GO - Molecular functioni

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

GO - Biological processi

  1. actin cytoskeleton organization Source: RefGenome
  2. actin cytoskeleton reorganization Source: UniProtKB
  3. apoptotic process Source: UniProtKB-KW
  4. axonogenesis Source: RefGenome
  5. branching morphogenesis of an epithelial tube Source: UniProtKB
  6. dendrite development Source: MGI
  7. exocytosis Source: UniProtKB-KW
  8. intracellular signal transduction Source: RefGenome
  9. negative regulation of cell proliferation involved in contact inhibition Source: UniProtKB
  10. neuromuscular junction development Source: MGI
  11. positive regulation of intracellular estrogen receptor signaling pathway Source: UniProtKB
  12. positive regulation of JUN kinase activity Source: UniProtKB
  13. positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
  14. positive regulation of protein phosphorylation Source: UniProtKB
  15. positive regulation of stress fiber assembly Source: UniProtKB
  16. protein autophosphorylation Source: UniProtKB
  17. protein phosphorylation Source: UniProtKB
  18. receptor clustering Source: MGI
  19. signal transduction by phosphorylation Source: GOC
  20. wound healing Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Exocytosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 1 (EC:2.7.11.1)
Alternative name(s):
Alpha-PAK
CDC42/RAC effector kinase PAK-A
p21-activated kinase 1
Short name:
PAK-1
p65-PAK
Gene namesi
Name:Pak1
Synonyms:Paka
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:1339975. Pak1.

Subcellular locationi

Cytoplasm By similarity. Cell junctionfocal adhesion By similarity. Cell membrane By similarity. Cell projectionruffle membrane By similarity
Note: Recruited to the cell membrane by interaction with CDC42 and RAC1. Recruited to focal adhesions upon activation. Colocalized with CIB1 within membrane ruffles during cell spreading upon readhesion to fibronectin By similarity.

GO - Cellular componenti

  1. axon Source: MGI
  2. cell-cell junction Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. focal adhesion Source: MGI
  5. Golgi apparatus Source: UniProtKB
  6. growth cone Source: MGI
  7. nucleus Source: MGI
  8. plasma membrane Source: UniProtKB
  9. ruffle Source: UniProtKB
  10. ruffle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 545544Serine/threonine-protein kinase PAK 1PRO_0000086461Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine By similarity
Modified residuei21 – 211Phosphoserine; by PKB and autocatalysis By similarity
Modified residuei57 – 571Phosphoserine; by autocatalysis By similarity
Modified residuei84 – 841Phosphothreonine; by OXSR1 By similarity
Modified residuei131 – 1311Phosphotyrosine By similarity
Modified residuei142 – 1421Phosphotyrosine By similarity
Modified residuei144 – 1441Phosphoserine; by autocatalysis By similarity
Modified residuei149 – 1491Phosphoserine; by autocatalysis By similarity
Modified residuei153 – 1531Phosphotyrosine; by JAK2 By similarity
Modified residuei174 – 1741Phosphoserine By similarity
Modified residuei185 – 1851Phosphothreonine By similarity
Modified residuei199 – 1991Phosphoserine; by autocatalysis By similarity
Modified residuei201 – 2011Phosphotyrosine; by JAK2 By similarity
Modified residuei204 – 2041Phosphoserine; by autocatalysis By similarity
Modified residuei212 – 2121Phosphothreonine1 Publication
Modified residuei219 – 2191Phosphothreonine By similarity
Modified residuei220 – 2201Phosphoserine By similarity
Modified residuei223 – 2231Phosphoserine By similarity
Modified residuei230 – 2301Phosphothreonine By similarity
Modified residuei285 – 2851Phosphotyrosine; by JAK2 By similarity
Modified residuei423 – 4231Phosphothreonine; by autocatalysis, BRSK2 and PDPK11 Publication

Post-translational modificationi

Autophosphorylated in trans, meaning that in a dimer, one kinase molecule phosphorylates the other one. Activated by autophosphorylation at Thr-423 in response to a conformation change, triggered by interaction with GTP-bound CDC42 or RAC1. Activated by phosphorylation at Thr-423 by BRSK2 and by PDPK1. Phosphorylated by JAK2 in response to PRL; this increases PAK1 kinase activity. Phosphorylated at Ser-21 by PKB/AKT; this reduces interaction with NCK1 and association with focal adhesion sites By similarity.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO88643.
PaxDbiO88643.
PRIDEiO88643.

PTM databases

PhosphoSiteiO88643.

Expressioni

Gene expression databases

CleanExiMM_PAK1.
GenevestigatoriO88643.

Interactioni

Subunit structurei

Homodimer in its autoinhibited state. Active as monomer. Component of cytoplasmic complexes, which also contains PXN, ARHGEF6 and GIT1. Interacts with NISCH By similarity. Interacts with DVL1; mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering By similarity. Binds to the caspase-cleaved p110 isoform of CDC2L1 and CDC2L2, p110C, but not the full-length proteins. Interacts with ARHGEF7. Interacts tightly with GTP-bound but not GDP-bound CDC42/P21 and RAC1. Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM (via cytoplasmic domain); the interaction is direct and enhanced in presence of RAC1. Interacts with SCRIB. Interacts with PDPK1. Interacts (via kinase domain) with RAF1. Interacts with NCK1 and NCK2. Interacts with TBCB. Interacts with CRIPAK. Interacts with BRSK2. Interacts with SNAI1. Interacts with CIB1 (via N-terminal region); the interaction is direct, promotes PAK1 activity and occurs in a calcium-dependent manner By similarity.5 Publications

Protein-protein interaction databases

DIPiDIP-32847N.
IntActiO88643. 12 interactions.
MINTiMINT-193245.
STRINGi10090.ENSMUSP00000033040.

Structurei

3D structure databases

ProteinModelPortaliO88643.
SMRiO88643. Positions 75-147, 249-541.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini75 – 8814CRIBAdd
BLAST
Domaini270 – 521252Protein kinaseAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni70 – 14071Autoregulatory region By similarityAdd
BLAST
Regioni70 – 10536GTPase-binding By similarityAdd
BLAST
Regioni132 – 270139Interaction with CRIPAK By similarityAdd
BLAST

Sequence similaritiesi

Contains 1 CRIB domain.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiO88643.
PhylomeDBiO88643.

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.

O88643-1 [UniParc]FASTAAdd to Basket

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MSNNGVDIQD KPPAPPMRNT STMIGAGSKD TGTLNHGSKP LPPNPEEKKK    50
KDRFYRSILP GDKTNKKREK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP 100
EQWARLLQTS NITKSEQKKN PQAVLDVLEF YNSKKTSNSK KYMSFTDKSA 150
EDYNSSNTLN VKTVSETPAV PPVSEDDEDD DDDATPPPVI APRPEHTKSV 200
YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE KQKKKPKMSD 250
EEILEKLRSI VSVGDPKKKY TPFEKIGQGA SGTVYTAMDV ATGQEVAIKQ 300
MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG 350
SLTDVVTETC MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD 400
GSVKLTDFGF CAQITPEQSK RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL 450
GIMAIEMIEG EPPYLNENPL RALYLIATNG TPELQNPEKL SAIFRDFLQC 500
CLEMDVEKRG SAKELLQHQF LKIAKPLSSL TPLMHAAKEA TKNNH 545
Length:545
Mass (Da):60,737
Last modified:November 1, 1998 - v1
Checksum:iA4861289534C3819
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF082077 mRNA. Translation: AAC32375.1.
UniGeneiMm.260227.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF082077 mRNA. Translation: AAC32375.1 .
UniGenei Mm.260227.

3D structure databases

ProteinModelPortali O88643.
SMRi O88643. Positions 75-147, 249-541.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-32847N.
IntActi O88643. 12 interactions.
MINTi MINT-193245.
STRINGi 10090.ENSMUSP00000033040.

PTM databases

PhosphoSitei O88643.

Proteomic databases

MaxQBi O88643.
PaxDbi O88643.
PRIDEi O88643.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Organism-specific databases

MGIi MGI:1339975. Pak1.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000234202.
HOVERGENi HBG108518.
InParanoidi O88643.
PhylomeDBi O88643.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 3474.

Miscellaneous databases

PROi O88643.
SOURCEi Search...

Gene expression databases

CleanExi MM_PAK1.
Genevestigatori O88643.

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. "Cloning, central nervous system expression and chromosomal mapping of the mouse PAK-1 and PAK-3 genes."
    Burbelo P.D., Kozak C.A., Finegold A.A., Hall A., Pirone D.M.
    Gene 232:209-215(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Lubec G., Sunyer B., Chen W.-Q.
    Submitted (JAN-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 204-215; 276-299; 309-320; 372-388 AND 472-489, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: OF1.
    Tissue: Hippocampus.
  3. "p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis."
    Schurmann A., Mooney A.F., Sanders L.C., Sells M.A., Wang H.G., Reed J.C., Bokoch G.M.
    Mol. Cell. Biol. 20:453-461(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "Pak1 phosphorylation on T212 affects microtubules in cells undergoing mitosis."
    Banerjee M., Worth D., Prowse D.M., Nikolic M.
    Curr. Biol. 12:1233-1239(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT THR-212.
  5. "Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1."
    Luo Z.G., Wang Q., Zhou J.Z., Wang J., Luo Z., Liu M., He X., Wynshaw-Boris A., Xiong W.C., Lu B., Mei L.
    Neuron 35:489-505(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN NEUROMUSCULAR JUNCTION DEVELOPMENT, INTERACTION WITH DVL1 AND MUSK.
  6. "The integrin-binding protein Nischarin regulates cell migration by inhibiting PAK."
    Alahari S.K., Reddig P.J., Juliano R.L.
    EMBO J. 23:2777-2788(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NISCH.
  7. "The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates Pak."
    Li W., Guan K.L.
    J. Biol. Chem. 279:32824-32831(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DSCAM.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic brain.
  9. Cited for: INTERACTION WITH SCRIB.
  10. "Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic beta-Cells."
    Nie J., Sun C., Faruque O., Ye G., Li J., Liang Q., Chang Z., Yang W., Han X., Shi Y.
    J. Biol. Chem. 287:26435-26444(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH BRSK2, PHOSPHORYLATION AT THR-423.
  11. "Beta-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6."
    Borroni E.M., Cancellieri C., Vacchini A., Benureau Y., Lagane B., Bachelerie F., Arenzana-Seisdedos F., Mizuno K., Mantovani A., Bonecchi R., Locati M.
    Sci. Signal. 6:RA30-RA30(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION.

Entry informationi

Entry nameiPAK1_MOUSE
AccessioniPrimary (citable) accession number: O88643
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1998
Last modified: June 11, 2014
This is version 132 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, Direct protein sequencing, 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

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