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Protein

Serine/threonine-protein kinase PAK 1

Gene

Pak1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

Mg2+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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei299 – 2991ATPPROSITE-ProRule annotation
Active sitei389 – 3891Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi276 – 2849ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

  1. actin cytoskeleton organization Source: GO_Central
  2. actin cytoskeleton reorganization Source: UniProtKB
  3. apoptotic process Source: UniProtKB-KW
  4. axonogenesis Source: GO_Central
  5. branching morphogenesis of an epithelial tube Source: UniProtKB
  6. dendrite development Source: MGI
  7. exocytosis Source: UniProtKB-KW
  8. intracellular signal transduction Source: GO_Central
  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 Componenti: 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).By similarity

GO - Cellular componenti

  1. axon Source: MGI
  2. cell-cell junction Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. dendrite Source: MGI
  5. focal adhesion Source: MGI
  6. Golgi apparatus Source: UniProtKB
  7. growth cone Source: MGI
  8. neuronal postsynaptic density Source: MGI
  9. nucleus Source: MGI
  10. plasma membrane Source: UniProtKB
  11. protein complex Source: MGI
  12. ruffle Source: UniProtKB
  13. 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 – 11RemovedBy similarity
Chaini2 – 545544Serine/threonine-protein kinase PAK 1PRO_0000086461Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei21 – 211Phosphoserine; by PKB and autocatalysisBy similarity
Modified residuei57 – 571Phosphoserine; by autocatalysisBy similarity
Modified residuei84 – 841Phosphothreonine; by OXSR1By similarity
Modified residuei115 – 1151PhosphoserineBy similarity
Modified residuei131 – 1311PhosphotyrosineBy similarity
Modified residuei142 – 1421PhosphotyrosineBy similarity
Modified residuei144 – 1441Phosphoserine; by autocatalysisBy similarity
Modified residuei149 – 1491Phosphoserine; by autocatalysisBy similarity
Modified residuei153 – 1531Phosphotyrosine; by JAK2By similarity
Modified residuei174 – 1741PhosphoserineBy similarity
Modified residuei185 – 1851PhosphothreonineBy similarity
Modified residuei199 – 1991Phosphoserine; by autocatalysisBy similarity
Modified residuei201 – 2011Phosphotyrosine; by JAK2By similarity
Modified residuei204 – 2041Phosphoserine; by autocatalysisBy similarity
Modified residuei212 – 2121Phosphothreonine1 Publication
Modified residuei219 – 2191PhosphothreonineBy similarity
Modified residuei220 – 2201PhosphoserineBy similarity
Modified residuei223 – 2231PhosphoserineBy similarity
Modified residuei230 – 2301PhosphothreonineBy similarity
Modified residuei285 – 2851Phosphotyrosine; by JAK2By 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).By similarity

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).By similarity

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliO88643.
SMRiO88643. Positions 75-147, 188-541.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini75 – 8814CRIBPROSITE-ProRule annotationAdd
BLAST
Domaini270 – 521252Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni70 – 14071Autoregulatory regionBy similarityAdd
BLAST
Regioni70 – 10536GTPase-bindingBy similarityAdd
BLAST
Regioni132 – 270139Interaction with CRIPAKBy similarityAdd
BLAST

Sequence similaritiesi

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

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.
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

« Hide

        10         20         30         40         50
MSNNGVDIQD KPPAPPMRNT STMIGAGSKD TGTLNHGSKP LPPNPEEKKK
60 70 80 90 100
KDRFYRSILP GDKTNKKREK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP
110 120 130 140 150
EQWARLLQTS NITKSEQKKN PQAVLDVLEF YNSKKTSNSK KYMSFTDKSA
160 170 180 190 200
EDYNSSNTLN VKTVSETPAV PPVSEDDEDD DDDATPPPVI APRPEHTKSV
210 220 230 240 250
YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE KQKKKPKMSD
260 270 280 290 300
EEILEKLRSI VSVGDPKKKY TPFEKIGQGA SGTVYTAMDV ATGQEVAIKQ
310 320 330 340 350
MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG
360 370 380 390 400
SLTDVVTETC MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD
410 420 430 440 450
GSVKLTDFGF CAQITPEQSK RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL
460 470 480 490 500
GIMAIEMIEG EPPYLNENPL RALYLIATNG TPELQNPEKL SAIFRDFLQC
510 520 530 540
CLEMDVEKRG SAKELLQHQF LKIAKPLSSL TPLMHAAKEA TKNNH
Length:545
Mass (Da):60,737
Last modified:October 31, 1998 - v1
Checksum:iA4861289534C3819
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF082077 mRNA. Translation: AAC32375.1.
UniGeneiMm.260227.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF082077 mRNA. Translation: AAC32375.1.
UniGeneiMm.260227.

3D structure databases

ProteinModelPortaliO88643.
SMRiO88643. Positions 75-147, 188-541.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiO88643.

Proteomic databases

MaxQBiO88643.
PaxDbiO88643.
PRIDEiO88643.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1339975. Pak1.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiO88643.
PhylomeDBiO88643.

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.

Miscellaneous databases

PROiO88643.
SOURCEiSearch...

Gene expression databases

CleanExiMM_PAK1.
GenevestigatoriO88643.

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.
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]
ProtoNetiSearch...

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(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Lubec G., Sunyer B., Chen W.-Q.
    Submitted (DEC-2008) 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(1999) [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(2001) [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(2001) [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(2003) [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(2003) [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(2011) [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(2012) [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 14, 1998
Last sequence update: October 31, 1998
Last modified: March 3, 2015
This is version 138 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.