Q62829 (PAK3_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 100.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Serine/threonine-protein kinase PAK 3 EC=2.7.11.1 Alternative name(s): Beta-PAK p21-activated kinase 3 Short name=PAK-3 p65-PAK | ||
| Gene names |
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| 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. |
| 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 migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. 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. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. 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. Interacts with the C-terminal of APP. Interacts with ARHGEF6 and ARHGEF7 By similarity. Ref.2 |
| Subcellular location | Cytoplasm By similarity. |
| 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
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 | ||||||
| Compositional bias | 172 – 182 | 11 | Poly-Glu | ||||||
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
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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], 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 | |
|---|---|
| EMBL GenBank DDBJ | U33314 mRNA. Translation: AAC52268.1. |
| IPI | IPI00327030. |
| PIR | A57597. |
| RefSeq | NP_062083.1. NM_019210.1. |
| UniGene | Rn.10128. |
3D structure databases | |
| ProteinModelPortal | Q62829. |
| SMR | Q62829. Positions 73-141, 247-538. |
| ModBase | Search... |
Protein-protein interaction databases | |
| MINT | MINT-126419. |
| STRING | Q62829. |
PTM databases | |
| PhosphoSite | Q62829. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENSRNOT00000006459; ENSRNOP00000006459; ENSRNOG00000004676. |
| GeneID | 29433. |
| KEGG | rno:29433. |
| UCSC | NM_019210. rat. |
Organism-specific databases | |
| CTD | 5063. |
| RGD | 3251. Pak3. |
Phylogenomic databases | |
| eggNOG | roNOG10184. |
| GeneTree | ENSGT00580000081260. |
| HOVERGEN | HBG108518. |
| PhylomeDB | Q62829. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 5301. |
Gene expression databases | |
| ArrayExpress | Q62829. |
| Genevestigator | Q62829. |
| GermOnline | ENSRNOG00000004676. 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 | K05733. |
| 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 | 609162. |
Entry information
| Entry name | PAK3_RAT | ||||||||
| Accession | Primary (citable) accession number: Q62829 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| SIMILARITY comments Index of protein domains and families |

Clusters with