Q61036 (PAK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	559 AA.
Sequence status	Complete.
Protein existence	Evidence 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. 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. Ref.7 Ref.11
Disruption phenotype	Mice show significant abnormalities in synaptic plasticity as well as deficiencies in learning and memory. Pak1-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 component	Cytoplasm
Coding sequence diversity	Alternative splicing
Domain	SH3-binding
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	axonogenesis Inferred from mutant phenotype Ref.12. Source: UniProtKB dendrite development Inferred from mutant phenotype Ref.12. Source: UniProtKB regulation of actin filament polymerization Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP 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. Source: BHF-UCL SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 559

559

Serine/threonine-protein kinase PAK 3

PRO_0000086470

Regions

Domain

70 – 83

14

CRIB

Domain

283 – 534

252

Protein kinase

Nucleotide binding

289 – 297

9

ATP By similarity

Region

65 – 150

86

Autoregulatory region By similarity

Region

65 – 123

59

GTPase-binding By similarity

Region

84 – 282

199

Linker

Compositional bias

187 – 197

11

Poly-Glu

Sites

Active site

402

1

Proton acceptor By similarity

Binding site

312

1

ATP Probable

Amino acid modifications

Modified residue

50

1

Phosphoserine; by autocatalysis By similarity

Modified residue

154

1

Phosphoserine; by autocatalysis By similarity

Modified residue

436

1

Phosphothreonine; by autocatalysis By similarity

Modified residue

535

1

N6-acetyllysine By similarity

Natural variations

Alternative sequence

93 – 107

15

Missing in isoform 2.

VSP_010243

Experimental info

Mutagenesis

67

1

R → C: Decreases interaction of PAK3 with CDC42 but increases interaction with RAC1. Ref.10

Mutagenesis

312

1

K → A: Loss of kinase activity. Ref.8

Sequence conflict

176

1

A → G in AAC52354. Ref.1

Sequence conflict

286

1

F → L Ref.1

Sequence conflict

286

1

F → L Ref.3

Sequence conflict

376

1

E → V in AAC52354. Ref.1

Sequence conflict

508

1

R → H in AAC52354. Ref.1

Sequence conflict

540

1

L → M in AAC31969. Ref.3

Secondary structure

1

.

.

.

559

Helix Strand Turn

Details...

Turn

88 – 89

2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2004. Version 2. Checksum: 9AD07B0328F0B08C	FASTA	559	62,398
	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
	Isoform 2 [UniParc]. Checksum: 72E323575DC18E0F	FASTA	544	60,781
	10 20 30 40 50 60 MSDSLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS IFPGGGDKTN 70 80 90 100 110 120 KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTGIPEQWAR LLQTSNITKL EQKKNPQAVL 130 140 150 160 170 180 DVLKFYDSKE TVNNQKYMSF TSGDKSAHGY IAAHQSNTKT ASEPPLAPPV SEEEDEEEEE 190 200 210 220 230 240 EEDDNEPPPV IAPRPEHTKS IYTRSVVESI ASPAAPNKED IPPSAENANS TTLYRNTDRQ 250 260 270 280 290 300 RKKSKMTDEE ILEKLRSIVS VGDPKKKYTR FEKIGQGASG TVYTALDIAT GQEVAIKQMN 310 320 330 340 350 360 LQQQPKKELI INEILVMREN KNPNIVNYLD SYLVGDELWV VMEYLAGGSL TDVVTETCMD 370 380 390 400 410 420 EGQIAAVCRE CLQALDFLHS NQVIHRDIKS DNILLGMDGS VKLTDFGFCA QITPEQSKRS 430 440 450 460 470 480 TMVGTPYWMA PEVVTRKAYG PKVDIWSLGI MAIEMVEGEP PYLNENPLRA LYLIATNGTP 490 500 510 520 530 540 ELQNPERLSA VFRDFLNRCL EMDVDRRGSA KELLQHPFLK LAKPLSSLTP LIIAAKEAIK NSSR

References

	« Hide 'large scale' referencesShow '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: 7559398] [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: 10352232] [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: 12464619] [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. , 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: 16141072] [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: 15489334] [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: 12242269] [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: 15574732] [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: 16014725] [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: 17537723] [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: 20540949] [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: 21115725] [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: 10747784] [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.

IPI

IPI00262114.
IPI00411094.

PIR

I49376.

RefSeq

NP_001181977.1. NM_001195048.1.
NP_001181978.1. NM_001195049.1.
NP_032804.2. NM_008778.3.

UniGene

Mm.40035.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EES	NMR	-	B	65-123	[»]

ProteinModelPortal

Q61036.

SMR

Q61036. Positions 65-156, 262-553.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-447N.

IntAct

Q61036. 4 interactions.

STRING

Q61036.

PTM databases

PhosphoSite

Q61036.

Proteomic databases

PRIDE

Q61036.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000033640; ENSMUSP00000033640; ENSMUSG00000031284.
ENSMUST00000070348; ENSMUSP00000064224; ENSMUSG00000031284.
ENSMUST00000112863; ENSMUSP00000108484; ENSMUSG00000031284.
ENSMUST00000112864; ENSMUSP00000108485; ENSMUSG00000031284.
ENSMUST00000112865; ENSMUSP00000108486; ENSMUSG00000031284.
ENSMUST00000112868; ENSMUSP00000108489; ENSMUSG00000031284.
ENSMUST00000171626; ENSMUSP00000127211; ENSMUSG00000031284.
ENSMUST00000172330; ENSMUSP00000126562; ENSMUSG00000031284.

GeneID

18481.

KEGG

mmu:18481.

Organism-specific databases

CTD

5063.

MGI

MGI:1339656. Pak3.

Phylogenomic databases

GeneTree

ENSGT00580000081260.

HOVERGEN

HBG108518.

InParanoid

Q61036.

OMA

SANENDM.

OrthoDB

EOG45DWP5.

PhylomeDB

Q61036.

Enzyme and pathway databases

BRENDA

2.7.1.12. 3474.

Gene expression databases

ArrayExpress

Q61036.

Bgee

Q61036.

CleanEx

MM_PAK3.
MM_STK4.

Genevestigator

Q61036.

GermOnline

ENSMUSG00000031284. Mus musculus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000095. PAK_box_Rho-bd.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

KO

K05733.

Pfam

PF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

294190.

SOURCE

Search...

Entry information

Entry name

PAK3_MOUSE

Accession

Primary (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:	December 14, 2011
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program