CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012025
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase PAK 2 
Protein Synonyms/Alias
 Gamma-PAK; PAK65; S6/H4 kinase; p21-activated kinase 2; PAK-2; p58; PAK-2p27; p27; PAK-2p34; p34; C-t-PAK2 
Gene Name
 PAK2 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
28TIFSTGGKDPLSANHacetylation[1]
38LSANHSLKPLPSVPEacetylation[2, 3, 4]
52EEKKPRHKIISIFSGubiquitination[5]
62SIFSGTEKGSKKKEKacetylation[1, 4]
62SIFSGTEKGSKKKEKubiquitination[5]
65SGTEKGSKKKEKERPubiquitination[5]
113LQTSNITKLEQKKNPubiquitination[5, 6]
117NITKLEQKKNPQAVLubiquitination[5]
118ITKLEQKKNPQAVLDubiquitination[5]
128QAVLDVLKFYDSNTVacetylation[2]
128QAVLDVLKFYDSNTVubiquitination[5]
136FYDSNTVKQKYLSFTubiquitination[1, 5, 7]
138DSNTVKQKYLSFTPPubiquitination[5]
147LSFTPPEKDGFPSGTubiquitination[5]
226DKQKKKTKMTDEEIMubiquitination[5]
235TDEEIMEKLRTIVSIubiquitination[5]
254KKYTRYEKIGQGASGubiquitination[5]
278LGQEVAIKQINLQKQubiquitination[1, 5]
284IKQINLQKQPKKELIubiquitination[5]
370QVIHRDIKSDNVLLGubiquitination[5, 8]
399QITPEQSKRSTMVGTubiquitination[5, 7, 8]
468PELQNPEKLSPIFRDubiquitination[5, 8]
487CLEMDVEKRGSAKELubiquitination[5]
492VEKRGSAKELLQHPFubiquitination[5]
504HPFLKLAKPLSSLTPubiquitination[5]
517TPLIMAAKEAMKSNRubiquitination[6]
Reference
 [1] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [2] 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]
 [3] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [4] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [8] 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
 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. 
Sequence Annotation
 DOMAIN 74 87 CRIB.
 DOMAIN 249 499 Protein kinase.
 NP_BIND 255 263 ATP (By similarity).
 REGION 69 137 Autoregulatory region (By similarity).
 REGION 69 112 GTPase-binding (By similarity).
 MOTIF 245 251 Nuclear localization signal.
 ACT_SITE 367 367 Proton acceptor (By similarity).
 BINDING 278 278 ATP (By similarity).
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 2 2 Phosphoserine.
 MOD_RES 58 58 Phosphoserine.
 MOD_RES 128 128 N6-acetyllysine.
 MOD_RES 141 141 Phosphoserine.
 MOD_RES 143 143 Phosphothreonine (By similarity).
 MOD_RES 169 169 Phosphothreonine.
 MOD_RES 197 197 Phosphoserine.
 MOD_RES 402 402 Phosphothreonine; by autocatalysis
 LIPID 213 213 N-myristoyl glycine; in form PAK-2p34.  
Keyword
 3D-structure; Acetylation; Allosteric enzyme; Apoptosis; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Growth regulation; Host-virus interaction; Kinase; Lipoprotein; Membrane; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 524 AA 
Protein Sequence
MSDNGELEDK PPAPPVRMSS TIFSTGGKDP LSANHSLKPL PSVPEEKKPR HKIISIFSGT 60
EKGSKKKEKE RPEISPPSDF EHTIHVGFDA VTGEFTGMPE QWARLLQTSN ITKLEQKKNP 120
QAVLDVLKFY DSNTVKQKYL SFTPPEKDGF PSGTPALNAK GTEAPAVVTE EEDDDEETAP 180
PVIAPRPDHT KSIYTRSVID PVPAPVGDSH VDGAAKSLDK QKKKTKMTDE EIMEKLRTIV 240
SIGDPKKKYT RYEKIGQGAS GTVFTATDVA LGQEVAIKQI NLQKQPKKEL IINEILVMKE 300
LKNPNIVNFL DSYLVGDELF VVMEYLAGGS LTDVVTETCM DEAQIAAVCR ECLQALEFLH 360
ANQVIHRDIK SDNVLLGMEG SVKLTDFGFC AQITPEQSKR STMVGTPYWM APEVVTRKAY 420
GPKVDIWSLG IMAIEMVEGE PPYLNENPLR ALYLIATNGT PELQNPEKLS PIFRDFLNRC 480
LEMDVEKRGS AKELLQHPFL KLAKPLSSLT PLIMAAKEAM KSNR 524 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0030296; F:protein tyrosine kinase activator activity; IDA:BHF-UCL.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:2001271; P:negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; IDA:UniProtKB.
 GO:0006469; P:negative regulation of protein kinase activity; TAS:ProtInc.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:MGI.
 GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
 GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
 GO:0016032; P:viral reproduction; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
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