Q29502 (PAK2_RABIT) Reviewed, UniProtKB/Swiss-Prot

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
p21-activated protein kinase I
Short name=PAKI

Cleaved into the following 2 chains:

1. PAK-2p27
2. PAK-2p34

Gene names

Name:

PAK2

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

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, autophosphorylated 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. 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	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 Reference proteome
Gene Ontology (GO)
Biological_process	execution phase of apoptosis Inferred from mutant phenotype PubMed 15471851. Source: UniProtKB negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis Inferred from electronic annotation. Source: Compara peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from mutant phenotype PubMed 15471851. Source: UniProtKB positive regulation of extrinsic apoptotic signaling pathway Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome 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 protein tyrosine kinase activator activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Arhgap10	Q6Y5D8	3	EBI-4406512,EBI-4396535	From a different organism.
Arhgap10	Q6Y5D8-1	4	EBI-4406512,EBI-4396677	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 524	523	Serine/threonine-protein kinase PAK 2		PRO_0000086467
	Chain	2 – 212	211	PAK-2p27 By similarity		PRO_0000304926
	Chain	213 – 524	312	PAK-2p34 By similarity		PRO_0000304927
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	N-acetylserine By similarity
	Modified residue	2	1	Phosphoserine By similarity
	Modified residue	58	1	Phosphoserine By similarity
	Modified residue	128	1	N6-acetyllysine By similarity
	Modified residue	139	1	Phosphotyrosine By similarity
	Modified residue	141	1	Phosphoserine By similarity
	Modified residue	143	1	Phosphothreonine By similarity
	Modified residue	169	1	Phosphothreonine By similarity
	Modified residue	197	1	Phosphoserine By similarity
	Modified residue	402	1	Phosphothreonine; by autocatalysis By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q29502 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 397D71020EADFFCA	FASTA	524	58,028
	10 20 30 40 50 60 MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR NKIISIFSGT 70 80 90 100 110 120 EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE QWARLLQTSN ITKLEQKKNP 130 140 150 160 170 180 QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF PSGAPALNTK VSETSAVVTE EDDDDEEAAP 190 200 210 220 230 240 PVIAPRPDHT KSIYTRSVID PIPAPVGDSH VDSGAKSSDK QKKKTKMTDE 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 PLIMAAKEAM KSNR

References

[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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U46915 mRNA. Translation: AAC48537.1.
RefSeq	NP_001076225.1. NM_001082756.1.
UniGene	Ocu.2289.
3D structure databases
ProteinModelPortal	Q29502.
SMR	Q29502. Positions 77-143, 228-519.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q29502. 1 interaction.
STRING	9986.ENSOCUP00000007111.
Proteomic databases
PRIDE	Q29502.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSOCUT00000008227; ENSOCUP00000007111; ENSOCUG00000008224.
GeneID	100009535.
Organism-specific databases
CTD	5062.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00680000099789.
HOGENOM	HOG000234202.
HOVERGEN	HBG108518.
OMA	APALNTK.
OrthoDB	EOG4M3988.
Enzyme and pathway databases
BRENDA	2.7.1.12. 1749.
Reactome	REACT_100962. Apoptosis. REACT_13505. Proteasome mediated degradation of PAK-2p34. REACT_13714. Regulation of PAK-2p34 activity by PS-GAP.
Family and domain databases
Gene3D	3.90.810.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR000095. PAK_box_Rho-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
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...

Entry information

Entry name

PAK2_RABIT

Accession

Primary (citable) accession number: Q29502

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 29, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program