Reviewed, UniProtKB/Swiss-Prot Q62829 (PAK3_RAT)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase PAK 3
    EC=2.7.11.1
Alternative name(s):
    p21-activated kinase 3
      Short name=PAK-3
    Beta-PAK
    p65-PAK

Gene names

Name:

Pak3

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	544 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Key regulator of synapse formation and plasticity in the hippocampus. Ref.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
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-421 and allows the kinase domain to adopt an active structure By similarity.
Subunit structure	Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Shows highly specific binding to the SH3 domains of phospholipase C-gamma and of adapter protein NCK By similarity. Interacts with the C-terminal of APP.
Tissue specificity	Detected at high levels in the brain and at low levels in the testis. Ref.2
Developmental stage	Found in the embryonic CNS with little expression elsewhere.
Post-translational modification	Autophosphorylated when activated by CDC42/p21. Ref.3
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
Domain	SH3-binding
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Allosteric enzyme Direct protein sequencing
Gene Ontology (GO)
Biological process	multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Traceable author statement. Source: RGD protein kinase cascade Traceable author statement. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion 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 – 544	544	Serine/threonine-protein kinase PAK 3		PRO_0000086473
Regions
	Domain	70 – 83	14	CRIB
	Domain	268 – 519	252	Protein kinase
	Nucleotide binding	274 – 282	9	ATP By similarity
	Region	65 – 135	71	Autoregulatory region By similarity
	Region	65 – 108	44	GTPase-binding By similarity
	Region	84 – 267	184	Linker
Sites
	Active site	387	1	Proton acceptor By similarity
	Binding site	297	1	ATP Probable
Amino acid modifications
	Modified residue	50	1	Phosphoserine; by autocatalysis Ref.3
	Modified residue	139	1	Phosphoserine; by autocatalysis Ref.3
	Modified residue	421	1	Phosphothreonine; by autocatalysis Ref.3
	Modified residue	520	1	N6-acetyllysine By similarity
Experimental info
	Mutagenesis	297	1	K → A: Loss of kinase activity. Ref.2
	Mutagenesis	421	1	T → E: Constitutively active. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q62829-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 7B940FC204A2B48B	FASTA	544	60,711
	10 20 30 40 50 60 MSDSLDNEEK PPAPPLRMNS NNRDSSALNH SSKPLPMAPE EKNKKARLRS IFPGGGDKTN 70 80 90 100 110 120 KKKEKERPEI SLPSDFEHTI HVGFDAVTGE FTGIPEQWAR LLQTSNITKL EQKKNPQAVL 130 140 150 160 170 180 DVLKFYDSKE TVNNQKYMSF TSGDKSAHGY IAAHQSNTKT ASEPPLAPPV SEEEDEEEEE 190 200 210 220 230 240 EEDDNEPPPV IAPRPEHTKS IYTRSVVESI ASPAAPNKEA TPPSAENANS STLYRNTDRQ 250 260 270 280 290 300 RKKSKMTDEE ILEKLRSIVS VGDPKKKYTR FEKIGQGASG TVYTALDIAT GQEVAIKQMN 310 320 330 340 350 360 LQQQPKKELI INEILVMREN KNPNIVNYLD SYLVGDELWV VMEYLAGGSL TDVVTETCMD 370 380 390 400 410 420 EGQIAAVCRE CLQALDFLHS NQVIHRDIKS DNILLGMDGS VKLTDFGFCA QITPEQSKRS 430 440 450 460 470 480 TMVGTPYWMA PEVVTRKAYG PKVDIWSLGI MAIEMVEGEP PYLNENPLRA LYLIATNGTP 490 500 510 520 530 540 ELQNPERLSA VFRDFLNRCL EMDVDRRGSA KELLQHPFLK LAKPLSSLTP LILAAKEAIK NSSR

References

[1]	"Molecular cloning of a new member of the p21-Cdc42/Rac-activated kinase (PAK) family." Manser E., Chong C., Zhao Z.-S., Leung T., Michael G., Hall C., Lim L. J. Biol. Chem. 270:25070-25078(1995) [PubMed: 7559638] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE OF 37-56. Tissue: Brain.
[2]	"DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3." McPhie D.L., Coopersmith R., Hines-Peralta A., Chen Y., Ivins K.J., Manly S.P., Kozlowski M.R., Neve K.A., Neve R.L. J. Neurosci. 23:6914-6927(2003) [PubMed: 12890786] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH APP, MUTAGENESIS OF LYS-297 AND THR-421.
[3]	"The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity." Chong C., Tan L., Lim L., Manser E. J. Biol. Chem. 276:17347-17353(2001) [PubMed: 11278486] [Abstract] Cited for: PHOSPHORYLATION AT SER-50; SER-139 AND THR-421.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U33314 mRNA. Translation: AAC52268.1.
IPI	IPI00327030.
PIR	A57597.
RefSeq	NP_062083.1.
UniGene	Rn.10128
3D structure databases
HSSP	HSSP built from PDB template 1EES based on UniProtKB Q61036.
SMR	Q62829. Positions 73-141, 247-538.
ModBase	Search...
Protein-protein interaction databases
STRING	Q62829.
PTM databases
PhosphoSite	Q62829.
Genome annotation databases
Ensembl	ENSRNOT00000006459; ENSRNOP00000006459; ENSRNOG00000004676; Rattus norvegicus. [Genome view] ENSRNOT00000033903; ENSRNOP00000029906; ENSRNOG00000004676; Rattus norvegicus. [Genome view]
GeneID	29433.
KEGG	rno:29433.
UCSC	NM_019210. rat.
Organism-specific databases
CTD	29433.
RGD	3251. Pak3.
Phylogenomic databases
HOVERGEN	Q62829.
Enzyme and pathway databases
BRENDA	2.7.11.1. 248.
Gene expression databases
ArrayExpress	Q62829.
Genevestigator	Q62829.
GermOnline	ENSRNOG00000004676. 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	609162.

Entry information

Entry name

PAK3_RAT

Accession

Primary (citable) accession number: Q62829

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	October 13, 2009
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)