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UniProtKB - Q13177 (PAK2_HUMAN)

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Protein

Serine/threonine-protein kinase PAK 2

Gene

PAK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 motility, cell cycle progression, apoptosis or proliferation. 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. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

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-402 and allows the kinase domain to adopt an active structure (By similarity). Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei278ATPPROSITE-ProRule annotation1
Active sitei367Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi255 – 263ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cadherin binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein kinase activity Source: ProtInc
  • protein kinase binding Source: BHF-UCL
  • protein serine/threonine kinase activity Source: BHF-UCL
  • protein tyrosine kinase activator activity Source: BHF-UCL
  • Rac GTPase binding Source: CAFA
  • small GTPase binding Source: CAFA
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionAllosteric enzyme, Kinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Growth regulation, Host-virus interaction
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-164944 Nef and signal transduction
R-HSA-202433 Generation of second messenger molecules
R-HSA-211728 Regulation of PAK-2p34 activity by PS-GAP/RHG10
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-211736 Stimulation of the cell death response by PAK-2p34
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-389359 CD28 dependent Vav1 pathway
R-HSA-3928664 Ephrin signaling
R-HSA-399954 Sema3A PAK dependent Axon repulsion
R-HSA-428540 Activation of RAC1
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-445355 Smooth Muscle Contraction
R-HSA-5218920 VEGFR2 mediated vascular permeability
R-HSA-5621575 CD209 (DC-SIGN) signaling
R-HSA-5627123 RHO GTPases activate PAKs
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
SignaLinkiQ13177
SIGNORiQ13177

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 2 (EC:2.7.11.1)
Alternative name(s):
Gamma-PAK
PAK65
S6/H4 kinase
p21-activated kinase 2
Short name:
PAK-2
p58
Cleaved into the following 2 chains:
PAK-2p27
Short name:
p27
PAK-2p34
Short name:
p34
Alternative name(s):
C-t-PAK2
Gene namesi
Name:PAK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000180370.10
HGNCiHGNC:8591 PAK2
MIMi605022 gene
neXtProtiNX_Q13177

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, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi212D → N: Inhibits caspase-mediated cleavage. 1 Publication1
Mutagenesisi213G → A: Abolishes myristoylation of PAK-2p34 and membrane location. 1
Mutagenesisi239 – 243IVSIG → REGRS: Abolishes nuclear export. 1 Publication5
Mutagenesisi246 – 248KKK → MHE: Greatly inhibits nuclear localization. 1 Publication3
Mutagenesisi278K → R: Abolishes kinase activity and autophosphorylation. 1 Publication1
Mutagenesisi402T → A: Abolishes kinase activity and greatly inhibits autophosphorylation of PAK-2p27 and PAK-2p34. 1 Publication1

Organism-specific databases

DisGeNETi5062
OpenTargetsiENSG00000180370
PharmGKBiPA32918

Chemistry databases

ChEMBLiCHEMBL4487
GuidetoPHARMACOLOGYi2134

Polymorphism and mutation databases

BioMutaiPAK2
DMDMi143811432

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000864652 – 524Serine/threonine-protein kinase PAK 2Add BLAST523
ChainiPRO_00003049222 – 212PAK-2p27Add BLAST211
ChainiPRO_0000304923213 – 524PAK-2p34Add BLAST312

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei2PhosphoserineCombined sources1
Modified residuei20PhosphoserineCombined sources1
Modified residuei55PhosphoserineCombined sources1
Modified residuei58PhosphoserineCombined sources1
Modified residuei60PhosphothreonineCombined sources1
Modified residuei62N6-acetyllysineBy similarity1
Modified residuei64PhosphoserineCombined sources1
Modified residuei128N6-acetyllysineCombined sources1
Modified residuei134PhosphothreonineCombined sources1
Modified residuei139PhosphotyrosineCombined sources1
Modified residuei141PhosphoserineCombined sources1
Modified residuei143PhosphothreonineCombined sources1
Modified residuei152PhosphoserineBy similarity1
Modified residuei154PhosphothreonineCombined sources1
Modified residuei169PhosphothreonineCombined sources1
Modified residuei197PhosphoserineCombined sources1
Lipidationi213N-myristoyl glycine; in form PAK-2p341 Publication1
Modified residuei402Phosphothreonine; by autocatalysisCurated1

Post-translational modificationi

Full-length PAK2 is autophosphorylated when activated by CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-2p34, become highly autophosphorylated, with PAK-2p27 being phosphorylated on serine and PAK-2p34 on threonine residues, respectively. Autophosphorylation of PAK-2p27 can occur in the absence of any effectors and is dependent on phosphorylation of Thr-402, because PAK-2p27 is acting as an exogenous substrate.
During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34.
Ubiquitinated, leading to its proteasomal degradation.1 Publication
PAK-2p34 is myristoylated.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei212 – 213Cleavage; by caspase-3 or caspase-3-like proteases2 Publications2

Keywords - PTMi

Acetylation, Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ13177
MaxQBiQ13177
PaxDbiQ13177
PeptideAtlasiQ13177
PRIDEiQ13177
ProteomicsDBi59208

2D gel databases

OGPiQ13177

PTM databases

iPTMnetiQ13177
PhosphoSitePlusiQ13177
SwissPalmiQ13177

Miscellaneous databases

PMAP-CutDBiQ13177

Expressioni

Tissue specificityi

Ubiquitously expressed. Higher levels seen in skeletal muscle, ovary, thymus and spleen.

Gene expression databases

BgeeiENSG00000180370
CleanExiHS_PAK2
ExpressionAtlasiQ13177 baseline and differential
GenevisibleiQ13177 HS

Organism-specific databases

HPAiCAB007794

Interactioni

Subunit structurei

Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with SCRIB. Interacts with ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10 (PubMed:15471851, PubMed:16374509, PubMed:18716323, PubMed:19273597). Interacts with RAC1 (PubMed:20696164).5 Publications
(Microbial infection) Interacts with and activated by HIV-1 Nef.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein kinase binding Source: BHF-UCL
  • Rac GTPase binding Source: CAFA
  • small GTPase binding Source: CAFA
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi111098, 92 interactors
DIPiDIP-38249N
ELMiQ13177
IntActiQ13177, 87 interactors
MINTiQ13177
STRINGi9606.ENSP00000314067

Chemistry databases

BindingDBiQ13177

Structurei

Secondary structure

1524
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi123 – 126Combined sources4

3D structure databases

ProteinModelPortaliQ13177
SMRiQ13177
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13177

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini74 – 87CRIBPROSITE-ProRule annotationAdd BLAST14
Domaini249 – 499Protein kinasePROSITE-ProRule annotationAdd BLAST251

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni69 – 137Autoregulatory regionBy similarityAdd BLAST69
Regioni69 – 112GTPase-bindingBy similarityAdd BLAST44

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi245 – 251Nuclear localization signal7

Sequence similaritiesi

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.Curated

Phylogenomic databases

eggNOGiKOG0578 Eukaryota
ENOG410XP4K LUCA
GeneTreeiENSGT00920000148968
HOGENOMiHOG000234202
HOVERGENiHBG108518
InParanoidiQ13177
KOiK04410
OMAiVCEDKPP
OrthoDBiEOG091G04H8
PhylomeDBiQ13177
TreeFamiTF105351

Family and domain databases

CDDicd01093 CRIB_PAK_like, 1 hit
cd06655 STKc_PAK2, 1 hit
Gene3Di3.90.810.10, 1 hit
InterProiView protein in InterPro
IPR000095 CRIB_dom
IPR036936 CRIB_dom_sf
IPR011009 Kinase-like_dom_sf
IPR035065 PAK2/3
IPR033923 PAK_BD
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR035064 STK_PAK2
PANTHERiPTHR24361:SF250 PTHR24361:SF250, 1 hit
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.

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

Q13177-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR 
        60         70         80         90        100
HKIISIFSGT EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE 
       110        120        130        140        150
QWARLLQTSN ITKLEQKKNP QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF 
       160        170        180        190        200
PSGTPALNAK GTEAPAVVTE EEDDDEETAP PVIAPRPDHT KSIYTRSVID 
       210        220        230        240        250
PVPAPVGDSH VDGAAKSLDK QKKKTKMTDE EIMEKLRTIV SIGDPKKKYT 
       260        270        280        290        300
RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE 
       310        320        330        340        350
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR 
       360        370        380        390        400
ECLQALEFLH ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR 
       410        420        430        440        450
STMVGTPYWM APEVVTRKAY GPKVDIWSLG IMAIEMVEGE PPYLNENPLR 
       460        470        480        490        500
ALYLIATNGT PELQNPEKLS PIFRDFLNRC LEMDVEKRGS AKELLQHPFL 
       510        520 
KLAKPLSSLT PLIMAAKEAM KSNR
Length:524
Mass (Da):58,043
Last modified:April 3, 2007 - v3
Checksum:i00A7CD15F93D4180
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti90A → T in AAA75468 (PubMed:7744004).Curated1
Sequence conflicti150F → L in AAA65442 (Ref. 1) Curated1
Sequence conflicti225T → P in AAA65442 (Ref. 1) Curated1
Sequence conflicti258G → R in AAH69613 (PubMed:15489334).Curated1
Sequence conflicti329G → R in AAA75468 (PubMed:7744004).Curated1
Sequence conflicti338T → TA in AAA65442 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U24153 mRNA Translation: AAA65442.1
BC069613 mRNA Translation: AAH69613.1
U25975 mRNA Translation: AAA75468.1
CCDSiCCDS3321.1
PIRiS58682
RefSeqiNP_002568.2, NM_002577.4
XP_011511172.1, XM_011512870.2
XP_016861990.1, XM_017006501.1
UniGeneiHs.518530

Genome annotation databases

EnsembliENST00000327134; ENSP00000314067; ENSG00000180370
GeneIDi5062
KEGGihsa:5062
UCSCiuc003fwy.4 human

Similar proteinsi

Entry informationi

Entry nameiPAK2_HUMAN
AccessioniPrimary (citable) accession number: Q13177
Secondary accession number(s): Q13154, Q6ISC3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 3, 2007
Last modified: July 18, 2018
This is version 198 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. SIMILARITY comments
    Index of protein domains and families

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