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Protein

Serine/threonine-protein kinase PAK 1

Gene

Pak1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mg2+By similarity

Activity 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)DescriptionActionsGraphical viewLength
Binding sitei299ATPPROSITE-ProRule annotation1
Active sitei389Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi276 – 284ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • collagen binding Source: UniProtKB
  • identical protein binding Source: MGI
  • protein kinase activity Source: MGI
  • protein kinase binding Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB
  • Rac GTPase binding Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionAllosteric enzyme, Kinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Exocytosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 3474

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 1Curated (EC:2.7.11.1By similarity)
Alternative name(s):
Alpha-PAKBy similarity
CDC42/RAC effector kinase PAK-A
p21-activated kinase 1By similarity
Short name:
PAK-1
p65-PAKBy similarity
Gene namesi
Name:Pak1Imported
Synonyms:Paka
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1339975 Pak1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000864612 – 545Serine/threonine-protein kinase PAK 1Add BLAST544

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei21Phosphoserine; by PKB and autocatalysisBy similarity1
Modified residuei57Phosphoserine; by autocatalysisBy similarity1
Modified residuei84Phosphothreonine; by OXSR1By similarity1
Modified residuei115PhosphoserineBy similarity1
Modified residuei131PhosphotyrosineBy similarity1
Modified residuei142PhosphotyrosineBy similarity1
Modified residuei144Phosphoserine; by autocatalysisBy similarity1
Modified residuei149Phosphoserine; by autocatalysisBy similarity1
Modified residuei153Phosphotyrosine; by JAK2By similarity1
Modified residuei174PhosphoserineBy similarity1
Modified residuei185PhosphothreonineBy similarity1
Modified residuei199Phosphoserine; by autocatalysisBy similarity1
Modified residuei201Phosphotyrosine; by JAK2By similarity1
Modified residuei204Phosphoserine; by autocatalysisBy similarity1
Modified residuei212PhosphothreonineCombined sources1 Publication1
Modified residuei219PhosphothreonineBy similarity1
Modified residuei220PhosphoserineCombined sources1
Modified residuei223PhosphoserineCombined sources1
Modified residuei225PhosphothreonineCombined sources1
Modified residuei229PhosphothreonineCombined sources1
Modified residuei230PhosphothreonineCombined sources1
Modified residuei285Phosphotyrosine; by JAK2By similarity1
Modified residuei423Phosphothreonine; by autocatalysis, BRSK2 and PDPK11 Publication1

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
PeptideAtlasiO88643
PRIDEiO88643

PTM databases

iPTMnetiO88643
PhosphoSitePlusiO88643

Expressioni

Gene expression databases

CleanExiMM_PAK1

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 (PubMed:15229651). 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 (By similarity). Interacts with ARHGEF7 (By similarity). 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 (PubMed:15169762). Interacts with SCRIB (PubMed:18716323). Interacts with PDPK1 (By similarity). Interacts (via kinase domain) with RAF1 (By similarity). Interacts with NCK1 and NCK2 (By similarity). Interacts with TBCB (By similarity). Interacts with CRIPAK (By similarity). Interacts with BRSK2 (PubMed:22669945). Interacts with SNAI1 (By similarity). Interacts with CIB1 (via N-terminal region); the interaction is direct, promotes PAK1 activity and occurs in a calcium-dependent manner (By similarity). Interacts with INPP5K (PubMed:22751929).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cdc42P607662EBI-457240,EBI-81763

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-32847N
IntActiO88643, 17 interactors
MINTiO88643
STRINGi10090.ENSMUSP00000033040

Structurei

3D structure databases

ProteinModelPortaliO88643
SMRiO88643
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini75 – 88CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini270 – 521Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni70 – 140Autoregulatory regionBy similarityAdd BLAST71
Regioni70 – 105GTPase-bindingBy similarityAdd BLAST36
Regioni132 – 270Interaction with CRIPAKBy similarityAdd BLAST139

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
HOGENOMiHOG000234202
HOVERGENiHBG108518
InParanoidiO88643
PhylomeDBiO88643

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
Gene3Di3.90.810.10, 1 hit
InterProiView protein in InterPro
IPR000095 CRIB_dom
IPR036936 CRIB_dom_sf
IPR011009 Kinase-like_dom_sf
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50108 CRIB, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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:November 1, 1998 - v1
Checksum:iA4861289534C3819
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G5E884G5E884_MOUSE
Non-specific serine/threonine prote...
Pak1 mCG_7049
544Annotation score:
S4R2K7S4R2K7_MOUSE
Serine/threonine-protein kinase PAK...
Pak1
178Annotation score:
A0A0U1RQ87A0A0U1RQ87_MOUSE
Serine/threonine-protein kinase PAK...
Pak1
118Annotation score:

Sequence databases

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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-32847N
IntActiO88643, 17 interactors
MINTiO88643
STRINGi10090.ENSMUSP00000033040

PTM databases

iPTMnetiO88643
PhosphoSitePlusiO88643

Proteomic databases

MaxQBiO88643
PaxDbiO88643
PeptideAtlasiO88643
PRIDEiO88643

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1339975 Pak1

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
HOGENOMiHOG000234202
HOVERGENiHBG108518
InParanoidiO88643
PhylomeDBiO88643

Enzyme and pathway databases

BRENDAi2.7.11.1 3474

Miscellaneous databases

PROiPR:O88643
SOURCEiSearch...

Gene expression databases

CleanExiMM_PAK1

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
Gene3Di3.90.810.10, 1 hit
InterProiView protein in InterPro
IPR000095 CRIB_dom
IPR036936 CRIB_dom_sf
IPR011009 Kinase-like_dom_sf
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50108 CRIB, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPAK1_MOUSE
AccessioniPrimary (citable) accession number: O88643
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1998
Last modified: November 7, 2018
This is version 169 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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