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O88643 (PAK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Pak1
Synonyms:Paka
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length545 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.4 Ref.5 Ref.10 Ref.11

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

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.

Subunit structure

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 ofCDC2L1 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-terminus region); the interaction is direct, promotes PAK1 activity and occurs in a calcium-dependent manner By similarity. Ref.5 Ref.6 Ref.7 Ref.9 Ref.10

Subcellular location

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.

Post-translational modification

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. Ref.4 Ref.10 Ref.11

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Contains 1 CRIB domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Exocytosis
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Membrane
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termAllosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from Biological aspect of Ancestor. Source: RefGenome

actin cytoskeleton reorganization

Inferred from sequence or structural similarity. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

branching morphogenesis of an epithelial tube

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite development

Inferred from direct assay PubMed 12213441. Source: MGI

exocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of cell proliferation involved in contact inhibition

Inferred from sequence or structural similarity. Source: UniProtKB

neuromuscular junction development

Inferred from genetic interaction Ref.5. Source: MGI

positive regulation of JUN kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of intracellular estrogen receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of stress fiber assembly

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

receptor clustering

Inferred from genetic interaction Ref.5. Source: MGI

signal transduction by phosphorylation

Inferred from Biological aspect of Ancestor. Source: GOC

wound healing

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

axon

Inferred from direct assay PubMed 12950086. Source: MGI

cell-cell junction

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

focal adhesion

Traceable author statement PubMed 14580336. Source: MGI

growth cone

Inferred from direct assay PubMed 11604394. Source: MGI

nucleus

Inferred from direct assay PubMed 12950086. Source: MGI

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

collagen binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase activity

Inferred from direct assay PubMed 14580336PubMed 23528453. Source: MGI

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

receptor signaling protein serine/threonine kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 545544Serine/threonine-protein kinase PAK 1
PRO_0000086461

Regions

Domain75 – 8814CRIB
Domain270 – 521252Protein kinase
Nucleotide binding276 – 2849ATP By similarity
Region70 – 14071Autoregulatory region By similarity
Region70 – 10536GTPase-binding By similarity
Region132 – 270139Interaction with CRIPAK By similarity

Sites

Active site3891Proton acceptor By similarity
Binding site2991ATP By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue211Phosphoserine; by PKB and autocatalysis By similarity
Modified residue571Phosphoserine; by autocatalysis By similarity
Modified residue841Phosphothreonine; by OXSR1 By similarity
Modified residue1311Phosphotyrosine By similarity
Modified residue1421Phosphotyrosine By similarity
Modified residue1441Phosphoserine; by autocatalysis By similarity
Modified residue1491Phosphoserine; by autocatalysis By similarity
Modified residue1531Phosphotyrosine; by JAK2 By similarity
Modified residue1741Phosphoserine By similarity
Modified residue1851Phosphothreonine By similarity
Modified residue1991Phosphoserine; by autocatalysis By similarity
Modified residue2011Phosphotyrosine; by JAK2 By similarity
Modified residue2041Phosphoserine; by autocatalysis By similarity
Modified residue2121Phosphothreonine Ref.4
Modified residue2191Phosphothreonine By similarity
Modified residue2201Phosphoserine By similarity
Modified residue2231Phosphoserine By similarity
Modified residue2301Phosphothreonine By similarity
Modified residue2851Phosphotyrosine; by JAK2 By similarity
Modified residue4231Phosphothreonine; by autocatalysis, BRSK2 and PDPK1 Ref.10

Sequences

Sequence LengthMass (Da)Tools
O88643 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: A4861289534C3819

FASTA54560,737
        10         20         30         40         50         60 
MSNNGVDIQD KPPAPPMRNT STMIGAGSKD TGTLNHGSKP LPPNPEEKKK KDRFYRSILP 

        70         80         90        100        110        120 
GDKTNKKREK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP EQWARLLQTS NITKSEQKKN 

       130        140        150        160        170        180 
PQAVLDVLEF YNSKKTSNSK KYMSFTDKSA EDYNSSNTLN VKTVSETPAV PPVSEDDEDD 

       190        200        210        220        230        240 
DDDATPPPVI APRPEHTKSV YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE 

       250        260        270        280        290        300 
KQKKKPKMSD EEILEKLRSI VSVGDPKKKY TPFEKIGQGA SGTVYTAMDV ATGQEVAIKQ 

       310        320        330        340        350        360 
MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG SLTDVVTETC 

       370        380        390        400        410        420 
MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD GSVKLTDFGF CAQITPEQSK 

       430        440        450        460        470        480 
RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL GIMAIEMIEG EPPYLNENPL RALYLIATNG 

       490        500        510        520        530        540 
TPELQNPEKL SAIFRDFLQC CLEMDVEKRG SAKELLQHQF LKIAKPLSSL TPLMHAAKEA 


TKNNH 

« Hide

References

« Hide 'large scale' references
[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]"Phosphoproteomic analysis of the developing mouse brain."
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic brain.
[9]"Scrib regulates PAK activity during the cell migration process."
Nola S., Sebbagh M., Marchetto S., Osmani N., Nourry C., Audebert S., Navarro C., Rachel R., Montcouquiol M., Sans N., Etienne-Manneville S., Borg J.-P., Santoni M.-J.
Hum. Mol. Genet. 17:3552-3565(2008) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF082077 mRNA. Translation: AAC32375.1.
UniGeneMm.260227.

3D structure databases

ProteinModelPortalO88643.
SMRO88643. Positions 75-147, 249-541.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-32847N.
IntActO88643. 12 interactions.
MINTMINT-193245.
STRING10090.ENSMUSP00000033040.

PTM databases

PhosphoSiteO88643.

Proteomic databases

PaxDbO88643.
PRIDEO88643.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:1339975. Pak1.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000234202.
HOVERGENHBG108518.
InParanoidO88643.
PhylomeDBO88643.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.

Gene expression databases

CleanExMM_PAK1.
GenevestigatorO88643.

Family and domain databases

Gene3D3.90.810.10. 1 hit.
InterProIPR000095. 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]
PfamPF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROO88643.
SOURCESearch...

Entry information

Entry namePAK1_MOUSE
AccessionPrimary (citable) accession number: O88643
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot