Reviewed, UniProtKB/Swiss-Prot Q64303 (PAK2_RAT)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase PAK 2
    EC=2.7.11.1
Alternative name(s):
    p21-activated kinase 2
      Short name=PAK-2
    Gamma-PAK
Cleaved into the following 2 chains:
    1- Recommended name:
            PAK-2p27
    2- Recommended name:
            PAK-2p34

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	The activated kinase acts on a variety of targets. Full length PAK 2 stimulates cell survival and cell growth. The process is, at least in part, mediated by phosphorylation and inhibition of pro-apoptotic BAD. Caspase-activated PAK-2p34 is involved in cell death response, probably involving the JNK signaling pathway 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. PAK-2p34 interacts with ARHGAP10. Interacts with SCRIB By similarity.
Subcellular location	Serine/threonine-protein kinase PAK 2: Cytoplasm 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. During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34 By similarity. Ubiquitinated, leading to its proteosomal 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 Direct protein sequencing
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-KW 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	14	CRIB
	Domain	249 – 500	252	Protein kinase
	Nucleotide binding	255 – 263	9	ATP By similarity
	Region	69 – 137	69	Autoregulatory region By similarity
	Region	69 – 112	44	GTPase-binding By similarity
	Region	88 – 248	161	Linker
	Motif	245 – 251	7	Nuclear localization signal By similarity
Sites
	Active site	368	1	Proton acceptor By similarity
	Binding site	278	1	ATP By similarity
	Site	212 – 213	2	Cleavage; by caspase-3 or caspase-3-like proteases By similarity
Amino acid modifications
	Modified residue	2	1	Phosphoserine By similarity
	Modified residue	38	1	N6-acetyllysine By similarity
	Modified residue	58	1	Phosphoserine By similarity
	Modified residue	60	1	Phosphothreonine By similarity
	Modified residue	128	1	N6-acetyllysine By similarity
	Modified residue	139	1	Phosphotyrosine Ref.5
	Modified residue	141	1	Phosphoserine Ref.5 Ref.4
	Modified residue	143	1	Phosphothreonine Ref.5
	Modified residue	169	1	Phosphothreonine By similarity
	Modified residue	402	1	Phosphothreonine; by autocatalysis By similarity
Experimental info
	Sequence conflict	82	1	H → Y in AAF06695. Ref.3
	Sequence conflict	418	1	K → E in AAF06695. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q64303-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A3F2FEE81C8D4294	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

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. 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: Kidney.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	S80221 mRNA. Translation: AAB35608.1. U35345 mRNA. Translation: AAA79064.1. U19967 mRNA. Translation: AAF06695.1.
IPI	IPI00211615.
RefSeq	NP_445758.2.
UniGene	Rn.3840
3D structure databases
HSSP	HSSP built from PDB template 1F3M based on UniProtKB Q13153.
SMR	Q64303. Positions 77-143, 228-519.
ModBase	Search...
Protein-protein interaction databases
STRING	Q64303.
PTM databases
PhosphoSite	Q64303.
Genome annotation databases
Ensembl	ENSRNOT00000049862; ENSRNOP00000040162; ENSRNOG00000001747; Rattus norvegicus. [Genome view]
GeneID	29432.
KEGG	rno:29432.
UCSC	NM_053306. rat.
Organism-specific databases
CTD	29432.
RGD	61953. Pak2.
Phylogenomic databases
HOVERGEN	Q64303.
OMA	NVDGGAK.
Enzyme and pathway databases
BRENDA	2.7.11.1. 248. 2.7.12.2. 248.
Gene expression databases
ArrayExpress	Q64303.
Genevestigator	Q64303.
GermOnline	ENSRNOG00000001747. Rattus norvegicus.
Family and domain databases
InterPro	IPR000095. PAK_box_Rho_bd. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR015750. Ser/Thr_Kinase_Pak-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
PANTHER	PTHR22986:SF84. Pak_like. 1 hit.
Pfam	PF00786. PBD. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00285. PBD. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
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 Resources
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 3, 2009
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)