Serine/threonine-protein kinase PAK 2 - Rattus norvegicus (Rat)

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Q64303 (PAK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified November 16, 2011. Version 107. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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

Gene names

Name:

Pak2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	524 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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 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.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
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-402 and allows the kinase domain to adopt an active structure. Following caspase cleavage, autophosphorylted PAK-2p34 is constitutively active By similarity.
Subunit structure	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.
Subcellular location	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. PAK-2p34: Nucleus By similarity. Cytoplasm › perinuclear region By similarity. Membrane; Lipid-anchor By similarity. Note: Interaction with ARHGAP10 probably changes PAK-2p34 location to cytoplasmic perinuclear region By similarity.
Post-translational modification	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. Ref.4 Ref.5 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.
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 Membrane Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Lipoprotein Phosphoprotein Ubl conjugation
Technical term	Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 524

524

Serine/threonine-protein kinase PAK 2

PRO_0000086468

Chain

1 – 212

212

PAK-2p27 By similarity

PRO_0000304928

Chain

213 – 524

312

PAK-2p34 By similarity

PRO_0000304929

Regions

Domain

74 – 87

CRIB

Domain

249 – 500

252

Protein kinase

Nucleotide binding

255 – 263

ATP By similarity

Region

69 – 137

Autoregulatory region By similarity

Region

69 – 112

GTPase-binding By similarity

Region

88 – 248

161

Linker

Motif

245 – 251

Nuclear localization signal By similarity

Sites

Active site

368

Proton acceptor By similarity

Binding site

278

ATP By similarity

Site

212 – 213

Cleavage; by caspase-3 or caspase-3-like proteases By similarity

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

N6-acetyllysine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphothreonine By similarity

Modified residue

128

N6-acetyllysine By similarity

Modified residue

139

Phosphotyrosine Ref.5

Modified residue

141

Phosphoserine Ref.4 Ref.5

Modified residue

143

Phosphothreonine Ref.5

Modified residue

169

Phosphothreonine By similarity

Modified residue

197

Phosphoserine By similarity

Modified residue

402

Phosphothreonine; by autocatalysis By similarity

Experimental info

Sequence conflict

H → Y in AAF06695. Ref.3

Sequence conflict

418

K → E in AAF06695. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

Q64303 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: A3F2FEE81C8D4294
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FASTA

524

57,960

        10         20         30         40         50         60 
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR NKIISIFSST 

        70         80         90        100        110        120 
EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE QWARLLQTSN ITKLEQKKNP 

       130        140        150        160        170        180 
QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF PSGTPALNTK GSETSAVVTE EDDDDEDAAP 

       190        200        210        220        230        240 
PVIAPRPDHT KSIYTRSVID PIPAPVGDSN VDSGAKSSDK QKKKAKMTDE EIMEKLRTIV 

       250        260        270        280        290        300 
SIGDPKKKYT RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE 

       310        320        330        340        350        360 
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR ECLQALEFLH 

       370        380        390        400        410        420 
ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR STMVGTPYWM APEVVTRKAY 

       430        440        450        460        470        480 
GPKVDIWSLG IMAIEMVEGE PPYLNENPLR ALYLIATNGT PELQNPEKLS PIFRDFLNRC 

       490        500        510        520 
LEMDVEKRGS AKELLQHPFL KLAKPLSSLT PLILAAKEAM KSNR

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and molecular cloning of a p21cdc42/rac1-activated serine/threonine kinase that is rapidly activated by thrombin in platelets." Teo M., Manser E., Lim L. J. Biol. Chem. 270:26690-26697(1995) [PubMed: 7592896] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Brain and Testis.
[2]	Mabel T. Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Conservation of STE20-responsive MAP kinase activation in eukaryotic organisms." Marcus S., Polverino A., Robbins D., Hutchison M., Xu H., Asouline G., Cobb M., Wigler M. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Forebrain.
[4]	"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS." Moser K., White F.M. J. Proteome Res. 5:98-104(2006) [PubMed: 16396499] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-141, MASS SPECTROMETRY. Strain: Fischer. Tissue: Liver.
[5]	"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites." Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A. Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed: 16641100] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-139; SER-141 AND THR-143, MASS SPECTROMETRY. Tissue: Renal collecting duct.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S80221 mRNA. Translation: AAB35608.1. U35345 mRNA. Translation: AAA79064.1. U19967 mRNA. Translation: AAF06695.1.
IPI	IPI00211615.
RefSeq	NP_445758.2. NM_053306.2.
UniGene	Rn.3840.
3D structure databases
ProteinModelPortal	Q64303.
SMR	Q64303. Positions 77-143, 228-519.
ModBase	Search...
Protein-protein interaction databases
STRING	Q64303.
PTM databases
PhosphoSite	Q64303.
Proteomic databases
PRIDE	Q64303.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000049862; ENSRNOP00000040162; ENSRNOG00000001747.
GeneID	29432.
KEGG	rno:29432.
UCSC	NM_053306. rat.
Organism-specific databases
CTD	5062.
RGD	61953. Pak2.
Phylogenomic databases
eggNOG	roNOG12509.
GeneTree	ENSGT00580000081260.
HOVERGEN	HBG108518.
InParanoid	Q64303.
OMA	PDLSKGQ.
OrthoDB	EOG4M3988.
PhylomeDB	Q64303.
Enzyme and pathway databases
BRENDA	2.7.12.2. 5301.
Gene expression databases
ArrayExpress	Q64303.
Genevestigator	Q64303.
GermOnline	ENSRNOG00000001747. Rattus norvegicus.
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	K04410.
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	609158.

Entry information

Entry name

PAK2_RAT

Accession

Primary (citable) accession number: Q64303
Secondary accession number(s): Q9QYU0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	November 16, 2011
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Cleaved into the following 2 chains:

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents