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Q61036 (PAK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase PAK 3

EC=2.7.11.1
Alternative name(s):
Beta-PAK
CDC42/RAC effector kinase PAK-B
p21-activated kinase 3
Short name=PAK-3
Gene names
Name:Pak3
Synonyms:Pak-3, Pakb, Stk4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length559 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. Ref.7 Ref.8 Ref.10 Ref.11

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-436 and allows the kinase domain to adopt an active structure By similarity.

Subunit structure

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Shows highly specific binding to the SH3 domains of phospholipase C-gamma and of adapter protein NCK. Interacts with the C-terminal of APP. Interacts with ARHGEF6 and ARHGEF7 By similarity.

Subcellular location

Cytoplasm By similarity.

Post-translational modification

Autophosphorylated when activated by CDC42/p21.

Neddylated By similarity.

Disruption phenotype

Mice show significant abnormalities in synaptic plasticity as well as deficiencies in learning and memory. Pak1 and Pak3 double knockout mice display reduced brains characterized by simplified neuronal dendrites/axons and reduced synapse density. Ref.9 Ref.12

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
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainSH3-binding
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Allosteric enzyme
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from Biological aspect of Ancestor. Source: RefGenome

axonogenesis

Inferred from mutant phenotype Ref.12. Source: UniProtKB

dendrite development

Inferred from mutant phenotype Ref.12. Source: UniProtKB

intracellular signal transduction

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of actin filament polymerization

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MAP kinase kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Rho GTPase binding

Inferred from physical interaction PubMed 10445846. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 23022564PubMed 7493928. Source: IntAct

receptor signaling protein serine/threonine kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDC42P609533EBI-457317,EBI-81752From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q61036-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q61036-2)

The sequence of this isoform differs from the canonical sequence as follows:
     93-107: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 559559Serine/threonine-protein kinase PAK 3
PRO_0000086470

Regions

Domain70 – 8314CRIB
Domain283 – 534252Protein kinase
Nucleotide binding289 – 2979ATP By similarity
Region65 – 15086Autoregulatory region By similarity
Region65 – 12359GTPase-binding By similarity
Region84 – 282199Linker
Compositional bias187 – 19711Poly-Glu

Sites

Active site4021Proton acceptor By similarity
Binding site3121ATP Probable

Amino acid modifications

Modified residue501Phosphoserine; by autocatalysis By similarity
Modified residue1541Phosphoserine; by autocatalysis By similarity
Modified residue4361Phosphothreonine; by autocatalysis By similarity

Natural variations

Alternative sequence93 – 10715Missing in isoform 2.
VSP_010243

Experimental info

Mutagenesis671R → C: Decreases interaction of PAK3 with CDC42 but increases interaction with RAC1. Ref.10
Mutagenesis3121K → A: Loss of kinase activity. Ref.8
Sequence conflict1761A → G in AAC52354. Ref.1
Sequence conflict2861F → L Ref.1
Sequence conflict2861F → L Ref.3
Sequence conflict3761E → V in AAC52354. Ref.1
Sequence conflict5081R → H in AAC52354. Ref.1
Sequence conflict5401L → M in AAC31969. Ref.3

Secondary structure

... 559
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 10, 2004. Version 2.
Checksum: 9AD07B0328F0B08C

FASTA55962,398
        10         20         30         40         50         60 
MSDSLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS IFPGGGDKTN 

        70         80         90        100        110        120 
KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTPDLYGSQM CPGKLPEGIP EQWARLLQTS 

       130        140        150        160        170        180 
NITKLEQKKN PQAVLDVLKF YDSKETVNNQ KYMSFTSGDK SAHGYIAAHQ SNTKTASEPP 

       190        200        210        220        230        240 
LAPPVSEEED EEEEEEEDDN EPPPVIAPRP EHTKSIYTRS VVESIASPAA PNKEDIPPSA 

       250        260        270        280        290        300 
ENANSTTLYR NTDRQRKKSK MTDEEILEKL RSIVSVGDPK KKYTRFEKIG QGASGTVYTA 

       310        320        330        340        350        360 
LDIATGQEVA IKQMNLQQQP KKELIINEIL VMRENKNPNI VNYLDSYLVG DELWVVMEYL 

       370        380        390        400        410        420 
AGGSLTDVVT ETCMDEGQIA AVCRECLQAL DFLHSNQVIH RDIKSDNILL GMDGSVKLTD 

       430        440        450        460        470        480 
FGFCAQITPE QSKRSTMVGT PYWMAPEVVT RKAYGPKVDI WSLGIMAIEM VEGEPPYLNE 

       490        500        510        520        530        540 
NPLRALYLIA TNGTPELQNP ERLSAVFRDF LNRCLEMDVD RRGSAKELLQ HPFLKLAKPL 

       550 
SSLTPLIIAA KEAIKNSSR 

« Hide

Isoform 2 [UniParc].

Checksum: 72E323575DC18E0F
Show »

FASTA54460,781

References

« Hide 'large scale' references
[1]"Identification of a mouse p21Cdc42/Rac activated kinase."
Bagrodia S., Taylor S.J., Creasy C.L., Chernoff J., Cerione R.A.
J. Biol. Chem. 270:22731-22737(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Fibroblast.
[2]Erratum
Bagrodia S., Taylor S.J., Creasy C.L., Chernoff J., Cerione R.A.
J. Biol. Chem. 271:1250-1250(1996)
[3]"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] (ISOFORM 2).
[4]"A new constitutively active brain Pak3 isoform displays modified specificities towards Rac and Cdc42 GTPases."
Rousseau V., Goupille O., Morin N., Barnier J.V.
J. Biol. Chem. 278:3912-3920(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain.
[5]"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. expand/collapse author list , 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] (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Medulla oblongata.
[6]"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] (ISOFORM 2).
Strain: C3H/He.
Tissue: Mesenchymal stem cell.
[7]"p21-activated kinase increases the calcium sensitivity of rat triton-skinned cardiac muscle fiber bundles via a mechanism potentially involving novel phosphorylation of troponin I."
Buscemi N., Foster D.B., Neverova I., Van Eyk J.E.
Circ. Res. 91:509-516(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TNNI3.
[8]"The mental retardation protein PAK3 contributes to synapse formation and plasticity in hippocampus."
Boda B., Alberi S., Nikonenko I., Node-Langlois R., Jourdain P., Moosmayer M., Parisi-Jourdain L., Muller D.
J. Neurosci. 24:10816-10825(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-312.
[9]"Abnormal long-lasting synaptic plasticity and cognition in mice lacking the mental retardation gene Pak3."
Meng J., Meng Y., Hanna A., Janus C., Jia Z.
J. Neurosci. 25:6641-6650(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[10]"The p21-activated kinase 3 implicated in mental retardation regulates spine morphogenesis through a Cdc42-dependent pathway."
Kreis P., Thevenot E., Rousseau V., Boda B., Muller D., Barnier J.V.
J. Biol. Chem. 282:21497-21506(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ARG-67.
[11]"Structural and kinetic effects of PAK3 phosphorylation mimic of cTnI(S151E) on the cTnC-cTnI interaction in the cardiac thin filament."
Ouyang Y., Mamidi R., Jayasundar J.J., Chandra M., Dong W.J.
J. Mol. Biol. 400:1036-1045(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TNNI3.
[12]"p21-Activated kinases 1 and 3 control brain size through coordinating neuronal complexity and synaptic properties."
Huang W., Zhou Z., Asrar S., Henkelman M., Xie W., Jia Z.
Mol. Cell. Biol. 31:388-403(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[13]"Structure of the complex of Cdc42Hs with a peptide derived from P-21 activated kinase."
Gizachew D., Guo W., Chohan K.K., Sutcliffe M.J., Oswald R.E.
Biochemistry 39:3963-3971(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 65-92 AND 108-123 IN COMPLEX WITH CDC42.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U39738 mRNA. Translation: AAC52354.1.
AF082297 mRNA. Translation: AAC31969.1.
AJ496262 mRNA. Translation: CAD42790.1.
AJ496263 mRNA. Translation: CAD42791.1.
AK031853 mRNA. Translation: BAC27580.1.
BC053403 mRNA. Translation: AAH53403.1.
CCDSCCDS30454.1. [Q61036-2]
CCDS57779.1. [Q61036-1]
PIRI49376.
RefSeqNP_001181977.1. NM_001195048.1. [Q61036-1]
NP_001181978.1. NM_001195049.1. [Q61036-2]
NP_032804.2. NM_008778.3. [Q61036-2]
XP_006528814.1. XM_006528751.1. [Q61036-1]
XP_006528815.1. XM_006528752.1. [Q61036-1]
XP_006528816.1. XM_006528753.1. [Q61036-2]
XP_006528817.1. XM_006528754.1. [Q61036-2]
UniGeneMm.40035.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EESNMR-B63-123[»]
ProteinModelPortalQ61036.
SMRQ61036. Positions 65-156, 262-553.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202021. 3 interactions.
DIPDIP-447N.
IntActQ61036. 5 interactions.
MINTMINT-151864.

PTM databases

PhosphoSiteQ61036.

Proteomic databases

MaxQBQ61036.
PaxDbQ61036.
PRIDEQ61036.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033640; ENSMUSP00000033640; ENSMUSG00000031284. [Q61036-1]
ENSMUST00000112863; ENSMUSP00000108484; ENSMUSG00000031284. [Q61036-1]
ENSMUST00000112864; ENSMUSP00000108485; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000112865; ENSMUSP00000108486; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000112868; ENSMUSP00000108489; ENSMUSG00000031284. [Q61036-2]
ENSMUST00000172330; ENSMUSP00000126562; ENSMUSG00000031284. [Q61036-2]
GeneID18481.
KEGGmmu:18481.
UCSCuc009umg.2. mouse. [Q61036-1]

Organism-specific databases

CTD5063.
MGIMGI:1339656. Pak3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00680000099789.
HOGENOMHOG000234202.
HOVERGENHBG108518.
InParanoidQ61036.
KOK05733.
OMASANENDM.
OrthoDBEOG7CK36J.
TreeFamTF105351.

Enzyme and pathway databases

BRENDA2.7.1.12. 3474.

Gene expression databases

ArrayExpressQ61036.
BgeeQ61036.
CleanExMM_PAK3.
MM_STK4.
GenevestigatorQ61036.

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

EvolutionaryTraceQ61036.
NextBio294190.
PROQ61036.
SOURCESearch...

Entry information

Entry namePAK3_MOUSE
AccessionPrimary (citable) accession number: Q61036
Secondary accession number(s): O88645, Q8K1R5, Q8K1R6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 10, 2004
Last modified: July 9, 2014
This is version 146 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

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