CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012020
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase PAK 1 
Protein Synonyms/Alias
 Alpha-PAK; p21-activated kinase 1; PAK-1; p65-PAK 
Gene Name
 PAK1 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
29TMIGAGSKDAGTLNHacetylation[1]
256SDEEILEKLRSIVSVacetylation[1]
299TGQEVAIKQMNLQQQubiquitination[2]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 
Functional Description
 Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. 
Sequence Annotation
 DOMAIN 75 88 CRIB.
 DOMAIN 270 521 Protein kinase.
 NP_BIND 276 284 ATP.
 NP_BIND 345 347 ATP.
 REGION 70 140 Autoregulatory region.
 REGION 75 105 GTPase-binding.
 REGION 132 270 Interaction with CRIPAK.
 ACT_SITE 389 389 Proton acceptor.
 BINDING 299 299 ATP.
 MOD_RES 21 21 Phosphoserine; by PKB and autocatalysis.
 MOD_RES 57 57 Phosphoserine; by autocatalysis.
 MOD_RES 84 84 Phosphothreonine; by OXSR1 (By
 MOD_RES 131 131 Phosphotyrosine.
 MOD_RES 142 142 Phosphotyrosine.
 MOD_RES 144 144 Phosphoserine.
 MOD_RES 149 149 Phosphoserine.
 MOD_RES 153 153 Phosphotyrosine; by JAK2.
 MOD_RES 174 174 Phosphoserine.
 MOD_RES 185 185 Phosphothreonine.
 MOD_RES 199 199 Phosphoserine; by autocatalysis (By
 MOD_RES 201 201 Phosphotyrosine; by JAK2.
 MOD_RES 204 204 Phosphoserine.
 MOD_RES 212 212 Phosphothreonine.
 MOD_RES 219 219 Phosphothreonine.
 MOD_RES 220 220 Phosphoserine.
 MOD_RES 223 223 Phosphoserine.
 MOD_RES 225 225 Phosphothreonine (By similarity).
 MOD_RES 230 230 Phosphothreonine.
 MOD_RES 285 285 Phosphotyrosine; by JAK2.
 MOD_RES 423 423 Phosphothreonine; by autocatalysis, BRSK2  
Keyword
 3D-structure; Allosteric enzyme; Alternative splicing; Apoptosis; ATP-binding; Cell junction; Cell membrane; Complete proteome; Cytoplasm; Exocytosis; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 545 AA 
Protein Sequence
MSNNGLDIQD KPPAPPMRNT STMIGAGSKD AGTLNHGSKP LPPNPEEKKK KDRFYRSILP 60
GDKTNKKKEK ERPEISLPSD FEHTIHVGFD AVTGEFTGMP EQWARLLQTS NITKSEQKKN 120
PQAVLDVLEF YNSKKTSNSQ KYMSFTDKSA EDYNSSNALN VKAVSETPAV PPVSEDEDDD 180
DDDATPPPVI APRPEHTKSV YTRSVIEPLP VTPTRDVATS PISPTENNTT PPDALTRNTE 240
KQKKKPKMSD EEILEKLRSI VSVGDPKKKY TRFEKIGQGA SGTVYTAMDV ATGQEVAIKQ 300
MNLQQQPKKE LIINEILVMR ENKNPNIVNY LDSYLVGDEL WVVMEYLAGG SLTDVVTETC 360
MDEGQIAAVC RECLQALEFL HSNQVIHRDI KSDNILLGMD GSVKLTDFGF CAQITPEQSK 420
RSTMVGTPYW MAPEVVTRKA YGPKVDIWSL GIMAIEMIEG EPPYLNENPL RALYLIATNG 480
TPELQNPEKL SAIFRDFLNR CLEMDVEKRG SAKELLQHQF LKIAKPLSSL TPLIAAAKEA 540
TKNNH 545 
Gene Ontology
 GO:0030424; C:axon; ISS:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030425; C:dendrite; ISS:UniProtKB.
 GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
 GO:0005794; C:Golgi apparatus; IDA:HPA.
 GO:0030426; C:growth cone; IEA:Compara.
 GO:0014704; C:intercalated disc; ISS:UniProtKB.
 GO:0031965; C:nuclear membrane; ISS:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:HGNC.
 GO:0043234; C:protein complex; IDA:UniProtKB.
 GO:0001726; C:ruffle; IDA:UniProtKB.
 GO:0030018; C:Z disc; ISS:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0031532; P:actin cytoskeleton reorganization; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:UniProtKB.
 GO:0032869; P:cellular response to insulin stimulus; IEA:Compara.
 GO:0033554; P:cellular response to stress; IEA:Compara.
 GO:0016358; P:dendrite development; IEA:Compara.
 GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0060244; P:negative regulation of cell proliferation involved in contact inhibition; IMP:UniProtKB.
 GO:0007528; P:neuromuscular junction development; IEA:Compara.
 GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB.
 GO:0043507; P:positive regulation of JUN kinase activity; IMP:UniProtKB.
 GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
 GO:0051496; P:positive regulation of stress fiber assembly; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0043113; P:receptor clustering; IEA:Compara.
 GO:0001666; P:response to hypoxia; IEA:Compara.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
 GO:0042060; P:wound healing; IMP:UniProtKB. 
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. 
Pfam
 PF00786; PBD
 PF00069; Pkinase 
SMART
 SM00285; PBD
 SM00220; S_TKc 
PROSITE
 PS50108; CRIB
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS