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Q29502

- PAK2_RABIT

UniProt

Q29502 - PAK2_RABIT

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Protein

Serine/threonine-protein kinase PAK 2

Gene

PAK2

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript 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 (By similarity).By similarity

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. Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei212 – 2132Cleavage; by caspase-3 or caspase-3-like proteasesBy similarity
Binding sitei278 – 2781ATPPROSITE-ProRule annotation
Active sitei368 – 3681Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi255 – 2639ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein serine/threonine kinase activity Source: UniProtKB-KW
  3. protein tyrosine kinase activator activity Source: Ensembl

GO - Biological processi

  1. execution phase of apoptosis Source: UniProtKB
  2. negative regulation of apoptotic process Source: Ensembl
  3. negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis Source: Ensembl
  4. peptidyl-serine phosphorylation Source: Ensembl
  5. positive regulation of apoptotic process Source: UniProtKB
  6. positive regulation of extrinsic apoptotic signaling pathway Source: Ensembl
  7. protein autophosphorylation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.12. 1749.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PAK 2 (EC:2.7.11.1)
Alternative name(s):
Gamma-PAK
p21-activated kinase 2
Short name:
PAK-2
p21-activated protein kinase I
Short name:
PAKI
Cleaved into the following 2 chains:
Gene namesi
Name:PAK2
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
ProteomesiUP000001811: Chromosome 14

Subcellular locationi

Chain Serine/threonine-protein kinase PAK 2 : Cytoplasm By similarity
Note: MYO18A mediates the cellular distribution of the PAK2-ARHGEF7-GIT1 complex to the inner surface of the cell membrane.By similarity
Chain PAK-2p34 : Nucleus By similarity. Cytoplasmperinuclear region By similarity. Membrane By similarity; Lipid-anchor By similarity
Note: Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region.By similarity

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. membrane Source: UniProtKB-KW
  3. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 524523Serine/threonine-protein kinase PAK 2PRO_0000086467Add
BLAST
Chaini2 – 212211PAK-2p27By similarityPRO_0000304926Add
BLAST
Chaini213 – 524312PAK-2p34By similarityPRO_0000304927Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineBy similarity
Modified residuei2 – 21PhosphoserineBy similarity
Modified residuei58 – 581PhosphoserineBy similarity
Modified residuei62 – 621N6-acetyllysineBy similarity
Modified residuei128 – 1281N6-acetyllysineBy similarity
Modified residuei141 – 1411PhosphoserineBy similarity
Modified residuei169 – 1691PhosphothreonineBy similarity
Modified residuei197 – 1971PhosphoserineBy similarity
Modified residuei402 – 4021Phosphothreonine; by autocatalysisBy similarity

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. 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 (By similarity).By similarity
During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34.By similarity
Ubiquitinated, leading to its proteasomal degradation.By similarity

Keywords - PTMi

Acetylation, Lipoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ29502.

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 (By similarity).By similarity

Protein-protein interaction databases

IntActiQ29502. 1 interaction.
STRINGi9986.ENSOCUP00000007111.

Structurei

3D structure databases

ProteinModelPortaliQ29502.
SMRiQ29502. Positions 77-143, 228-519.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini74 – 8714CRIBPROSITE-ProRule annotationAdd
BLAST
Domaini249 – 500252Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni69 – 13769Autoregulatory regionBy similarityAdd
BLAST
Regioni69 – 11244GTPase-bindingBy similarityAdd
BLAST
Regioni88 – 248161LinkerAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi245 – 2517Nuclear localization signalBy similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119176.
HOGENOMiHOG000234202.
HOVERGENiHBG108518.
InParanoidiQ29502.
OMAiWLQYDMM.
OrthoDBiEOG7CK36J.
TreeFamiTF105351.

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.
IPR002290. Ser/Thr_dual-sp_kinase.
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.

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

Q29502-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR
60 70 80 90 100
NKIISIFSGT EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE
110 120 130 140 150
QWARLLQTSN ITKLEQKKNP QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF
160 170 180 190 200
PSGAPALNTK VSETSAVVTE EDDDDEEAAP PVIAPRPDHT KSIYTRSVID
210 220 230 240 250
PIPAPVGDSH VDSGAKSSDK 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):58,028
Last modified:November 1, 1996 - v1
Checksum:i397D71020EADFFCA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U46915 mRNA. Translation: AAC48537.1.
RefSeqiNP_001076225.1. NM_001082756.1.
UniGeneiOcu.2289.

Genome annotation databases

EnsembliENSOCUT00000008227; ENSOCUP00000007111; ENSOCUG00000008224.
GeneIDi100009535.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U46915 mRNA. Translation: AAC48537.1 .
RefSeqi NP_001076225.1. NM_001082756.1.
UniGenei Ocu.2289.

3D structure databases

ProteinModelPortali Q29502.
SMRi Q29502. Positions 77-143, 228-519.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q29502. 1 interaction.
STRINGi 9986.ENSOCUP00000007111.

Proteomic databases

PRIDEi Q29502.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSOCUT00000008227 ; ENSOCUP00000007111 ; ENSOCUG00000008224 .
GeneIDi 100009535.

Organism-specific databases

CTDi 5062.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000119176.
HOGENOMi HOG000234202.
HOVERGENi HBG108518.
InParanoidi Q29502.
OMAi WLQYDMM.
OrthoDBi EOG7CK36J.
TreeFami TF105351.

Enzyme and pathway databases

BRENDAi 2.7.1.12. 1749.

Family and domain databases

Gene3Di 3.90.810.10. 1 hit.
InterProi IPR000095. CRIB_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00786. PBD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00285. PBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS50108. CRIB. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Molecular cloning and sequencing of the cytostatic G protein-activated protein kinase PAK I."
    Jakobi R., Chen C., Tuazon P.T., Traugh J.A.
    J. Biol. Chem. 271:6206-6211(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiPAK2_RABIT
AccessioniPrimary (citable) accession number: Q29502
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 26, 2014
This is version 117 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3