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Protein

Serine/threonine-protein kinase PAK 3

Gene

Pak3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

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-421 and allows the kinase domain to adopt an active structure (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei297ATPCurated1
Active sitei387Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi274 – 282ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • GTPase binding Source: RGD
  • MAP kinase kinase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activity Source: RGD
  • protein serine/threonine kinase activity Source: RGD
  • Rac GTPase binding Source: GO_Central
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

  • activation of protein kinase activity Source: GO_Central
  • axonogenesis Source: UniProtKB
  • cellular response to organic cyclic compound Source: Ensembl
  • dendrite development Source: UniProtKB
  • dendritic spine morphogenesis Source: UniProtKB
  • intracellular signal transduction Source: RGD
  • positive regulation of dendritic spine morphogenesis Source: RGD
  • positive regulation of DNA biosynthetic process Source: RGD
  • positive regulation of fibroblast migration Source: RGD
  • positive regulation of neuron apoptotic process Source: RGD
  • protein phosphorylation Source: RGD
  • regulation of actin cytoskeleton organization Source: RGD
  • regulation of actin filament polymerization Source: UniProtKB
  • regulation of axonogenesis Source: GO_Central
  • regulation of MAPK cascade Source: GO_Central
  • regulation of mitotic cell cycle Source: GO_Central
  • regulation of neuron projection development Source: RGD
  • Rho protein signal transduction Source: GO_Central
  • signal transduction by protein phosphorylation Source: GO_Central
  • stress-activated protein kinase signaling cascade Source: GO_Central

Keywordsi

Molecular functionDevelopmental protein, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 5301.
ReactomeiR-RNO-202433. Generation of second messenger molecules.
R-RNO-389359. CD28 dependent Vav1 pathway.
R-RNO-3928664. Ephrin signaling.
R-RNO-399954. Sema3A PAK dependent Axon repulsion.
R-RNO-5218920. VEGFR2 mediated vascular permeability.
R-RNO-5621575. CD209 (DC-SIGN) signaling.
R-RNO-5627123. RHO GTPases activate PAKs.
R-RNO-5687128. MAPK6/MAPK4 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 3 (EC:2.7.11.1)
Alternative name(s):
Beta-PAK
p21-activated kinase 3
Short name:
PAK-3
p65-PAK
Gene namesi
Name:Pak3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome X

Organism-specific databases

RGDi3251. Pak3.

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

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi297K → A: Loss of kinase activity. 1 Publication1
Mutagenesisi421T → E: Constitutively active. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864731 – 544Serine/threonine-protein kinase PAK 3Add BLAST544

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2PhosphoserineCombined sources1
Modified residuei4PhosphoserineCombined sources1
Modified residuei50Phosphoserine; by autocatalysis1 Publication1
Modified residuei139Phosphoserine; by autocatalysis1 Publication1
Modified residuei171PhosphoserineBy similarity1
Modified residuei421Phosphothreonine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated when activated by CDC42/p21.1 Publication
Neddylated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62829.
PRIDEiQ62829.

PTM databases

iPTMnetiQ62829.
PhosphoSitePlusiQ62829.

Expressioni

Tissue specificityi

Detected at high levels in the brain and at low levels in the testis.1 Publication

Developmental stagei

Found in the embryonic CNS with little expression elsewhere.

Gene expression databases

BgeeiENSRNOG00000004676.
GenevisibleiQ62829. RN.

Interactioni

Subunit structurei

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).By similarity

GO - Molecular functioni

  • GTPase binding Source: RGD
  • Rac GTPase binding Source: GO_Central
  • SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

BioGridi248080. 1 interactor.
IntActiQ62829. 1 interactor.
MINTiMINT-126419.
STRINGi10116.ENSRNOP00000006459.

Structurei

3D structure databases

ProteinModelPortaliQ62829.
SMRiQ62829.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini70 – 83CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini268 – 519Protein kinasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni65 – 135Autoregulatory regionBy similarityAdd BLAST71
Regioni65 – 108GTPase-bindingBy similarityAdd BLAST44
Regioni84 – 267LinkerAdd BLAST184

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi172 – 182Poly-GluAdd BLAST11

Sequence similaritiesi

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00860000133680.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ62829.
KOiK05733.
OMAiEFTPDLY.

Family and domain databases

CDDicd01093. CRIB_PAK_like. 1 hit.
cd06656. STKc_PAK3. 1 hit.
Gene3Di3.90.810.10. 1 hit.
InterProiView protein in InterPro
IPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR033923. PAK_BD.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR035063. STK_PAK3.
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.

Sequencei

Sequence statusi: Complete.

Q62829-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSDSLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS
60 70 80 90 100
IFPGGGDKTN KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTGIPEQWAR
110 120 130 140 150
LLQTSNITKL EQKKNPQAVL DVLKFYDSKE TVNNQKYMSF TSGDKSAHGY
160 170 180 190 200
IAAHQSNTKT ASEPPLAPPV SEEEDEEEEE EEDDNEPPPV IAPRPEHTKS
210 220 230 240 250
IYTRSVVESI ASPAAPNKEA TPPSAENANS STLYRNTDRQ RKKSKMTDEE
260 270 280 290 300
ILEKLRSIVS VGDPKKKYTR FEKIGQGASG TVYTALDIAT GQEVAIKQMN
310 320 330 340 350
LQQQPKKELI INEILVMREN KNPNIVNYLD SYLVGDELWV VMEYLAGGSL
360 370 380 390 400
TDVVTETCMD EGQIAAVCRE CLQALDFLHS NQVIHRDIKS DNILLGMDGS
410 420 430 440 450
VKLTDFGFCA QITPEQSKRS TMVGTPYWMA PEVVTRKAYG PKVDIWSLGI
460 470 480 490 500
MAIEMVEGEP PYLNENPLRA LYLIATNGTP ELQNPERLSA VFRDFLNRCL
510 520 530 540
EMDVDRRGSA KELLQHPFLK LAKPLSSLTP LILAAKEAIK NSSR
Length:544
Mass (Da):60,711
Last modified:November 1, 1996 - v1
Checksum:i7B940FC204A2B48B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U33314 mRNA. Translation: AAC52268.1.
PIRiA57597.
RefSeqiNP_062083.1. NM_019210.1.
XP_006257401.1. XM_006257339.3.
UniGeneiRn.10128.
Rn.45204.

Genome annotation databases

EnsembliENSRNOT00000006459; ENSRNOP00000006459; ENSRNOG00000004676.
ENSRNOT00000089141; ENSRNOP00000075221; ENSRNOG00000004676.
GeneIDi29433.
KEGGirno:29433.

Similar proteinsi

Entry informationi

Entry nameiPAK3_RAT
AccessioniPrimary (citable) accession number: Q62829
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: September 27, 2017
This is version 150 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

Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families