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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei297 – 2971ATPCurated
Active sitei387 – 3871Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi274 – 2829ATPPROSITE-ProRule annotation

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

GO - Biological processi

  • axonogenesis Source: UniProtKB
  • cellular response to organic cyclic compound Source: Ensembl
  • dendrite development Source: UniProtKB
  • dendritic spine development Source: Ensembl
  • 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 neuron projection development Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome X

Organism-specific databases

RGDi3251. Pak3.

Subcellular locationi

GO - Cellular componenti

  • endosome Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi297 – 2971K → A: Loss of kinase activity. 1 Publication
Mutagenesisi421 – 4211T → E: Constitutively active. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 544544Serine/threonine-protein kinase PAK 3PRO_0000086473Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21PhosphoserineCombined sources
Modified residuei4 – 41PhosphoserineCombined sources
Modified residuei50 – 501Phosphoserine; by autocatalysis1 Publication
Modified residuei139 – 1391Phosphoserine; by autocatalysis1 Publication
Modified residuei171 – 1711PhosphoserineBy similarity
Modified residuei421 – 4211Phosphothreonine; by autocatalysis1 Publication

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.
PhosphoSiteiQ62829.

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

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

Protein-protein interaction databases

BioGridi248080. 1 interaction.
MINTiMINT-126419.
STRINGi10116.ENSRNOP00000006459.

Structurei

3D structure databases

ProteinModelPortaliQ62829.
SMRiQ62829. Positions 73-141, 247-538.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini70 – 8314CRIBPROSITE-ProRule annotationAdd
BLAST
Domaini268 – 519252Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni65 – 13571Autoregulatory regionBy similarityAdd
BLAST
Regioni65 – 10844GTPase-bindingBy similarityAdd
BLAST
Regioni84 – 267184LinkerAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi172 – 18211Poly-GluAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00840000129718.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ62829.
KOiK05733.
OMAiXCLQALD.
OrthoDBiEOG7CK36J.

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.
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.

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_006257339.2.
UniGeneiRn.10128.
Rn.45204.

Genome annotation databases

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

Cross-referencesi

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_006257339.2.
UniGeneiRn.10128.
Rn.45204.

3D structure databases

ProteinModelPortaliQ62829.
SMRiQ62829. Positions 73-141, 247-538.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248080. 1 interaction.
MINTiMINT-126419.
STRINGi10116.ENSRNOP00000006459.

PTM databases

iPTMnetiQ62829.
PhosphoSiteiQ62829.

Proteomic databases

PaxDbiQ62829.
PRIDEiQ62829.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5063.
RGDi3251. Pak3.

Phylogenomic databases

eggNOGiKOG0578. Eukaryota.
ENOG410XP4K. LUCA.
GeneTreeiENSGT00840000129718.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ62829.
KOiK05733.
OMAiXCLQALD.
OrthoDBiEOG7CK36J.

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.

Miscellaneous databases

NextBioi609162.
PROiQ62829.

Gene expression databases

GenevisibleiQ62829. RN.

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.
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. "Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family."
    Manser E., Chong C., Zhao Z.-S., Leung T., Michael G., Hall C., Lim L.
    J. Biol. Chem. 270:25070-25078(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 37-56.
    Tissue: Brain.
  2. "DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3."
    McPhie D.L., Coopersmith R., Hines-Peralta A., Chen Y., Ivins K.J., Manly S.P., Kozlowski M.R., Neve K.A., Neve R.L.
    J. Neurosci. 23:6914-6927(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH APP, MUTAGENESIS OF LYS-297 AND THR-421.
  3. "The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity."
    Chong C., Tan L., Lim L., Manser E.
    J. Biol. Chem. 276:17347-17353(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-50; SER-139 AND THR-421.
  4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND SER-4, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiPAK3_RAT
AccessioniPrimary (citable) accession number: Q62829
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: May 11, 2016
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. SIMILARITY comments
    Index of protein domains and families

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 one 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.