CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012558
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Ribosomal protein S6 kinase alpha-1 
Protein Synonyms/Alias
 S6K-alpha-1; 90 kDa ribosomal protein S6 kinase 1; p90-RSK 1; p90RSK1; p90S6K; MAP kinase-activated protein kinase 1a; MAPK-activated protein kinase 1a; MAPKAP kinase 1a; MAPKAPK-1a; Ribosomal S6 kinase 1; RSK-1 
Gene Name
 RPS6KA1 
Gene Synonyms/Alias
 MAPKAPK1A; RSK1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
75LGQGSFGKVFLVRKVubiquitination[1]
278MTLILKAKLGMPQFLubiquitination[1]
316PDGAEEIKRHVFYSTubiquitination[2, 3]
500RGGELLDKILRQKFFubiquitination[1]
654TAKDLVSKMLHVDPHubiquitination[1]
Reference
 [1] 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]
 [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]
 [3] 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] 
Functional Description
 Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin- derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro- apoptotic proteins BAD and DAPK1 and suppressing their pro- apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression. 
Sequence Annotation
 DOMAIN 62 321 Protein kinase 1.
 DOMAIN 322 391 AGC-kinase C-terminal.
 DOMAIN 418 675 Protein kinase 2.
 NP_BIND 68 76 ATP (By similarity).
 NP_BIND 424 432 ATP (By similarity).
 ACT_SITE 187 187 Proton acceptor (By similarity).
 ACT_SITE 535 535 Proton acceptor (By similarity).
 BINDING 94 94 ATP (By similarity).
 BINDING 447 447 ATP (By similarity).
 MOD_RES 54 54 Phosphoserine.
 MOD_RES 221 221 Phosphoserine; by PDPK1 (Probable).
 MOD_RES 307 307 Phosphoserine.
 MOD_RES 348 348 Phosphothreonine.
 MOD_RES 359 359 Phosphothreonine.
 MOD_RES 363 363 Phosphoserine.
 MOD_RES 369 369 Phosphoserine.
 MOD_RES 380 380 Phosphoserine; by autocatalysis.
 MOD_RES 573 573 Phosphothreonine.
 MOD_RES 732 732 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Stress response; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 735 AA 
Protein Sequence
MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEGV LKEISITHHV KAGSEKADPS 60
HFELLKVLGQ GSFGKVFLVR KVTRPDSGHL YAMKVLKKAT LKVRDRVRTK MERDILADVN 120
HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF TRLSKEVMFT EEDVKFYLAE LALGLDHLHS 180
LGIIYRDLKP ENILLDEEGH IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA PEVVNRQGHS 240
HSADWWSYGV LMFEMLTGSL PFQGKDRKET MTLILKAKLG MPQFLSTEAQ SLLRALFKRN 300
PANRLGSGPD GAEEIKRHVF YSTIDWNKLY RREIKPPFKP AVAQPDDTFY FDTEFTSRTP 360
KDSPGIPPSA GAHQLFRGFS FVATGLMEDD GKPRAPQAPL HSVVQQLHGK NLVFSDGYVV 420
KETIGVGSYS ECKRCVHKAT NMEYAVKVID KSKRDPSEEI EILLRYGQHP NIITLKDVYD 480
DGKHVYLVTE LMRGGELLDK ILRQKFFSER EASFVLHTIG KTVEYLHSQG VVHRDLKPSN 540
ILYVDESGNP ECLRICDFGF AKQLRAENGL LMTPCYTANF VAPEVLKRQG YDEGCDIWSL 600
GILLYTMLAG YTPFANGPSD TPEEILTRIG SGKFTLSGGN WNTVSETAKD LVSKMLHVDP 660
HQRLTAKQVL QHPWVTQKDK LPQSQLSHQD LQLVKGAMAA TYSALNSSKP TPQLKPIESS 720
ILAQRRVRKL PSTTL 735 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005819; C:spindle; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB.
 GO:0000287; F:magnesium ion binding; IEA:InterPro.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0045597; P:positive regulation of cell differentiation; TAS:UniProtKB.
 GO:0030307; P:positive regulation of cell growth; TAS:UniProtKB.
 GO:2000491; P:positive regulation of hepatic stellate cell activation; IMP:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
 GO:0043620; P:regulation of DNA-dependent transcription in response to stress; TAS:UniProtKB.
 GO:0043555; P:regulation of translation in response to stress; TAS:UniProtKB.
 GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
 GO:0007268; P:synaptic transmission; TAS:Reactome.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR011009; Kinase-like_dom.
 IPR017892; Pkinase_C.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR016239; Ribosomal_S6_kinase_II.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00069; Pkinase
 PF00433; Pkinase_C 
SMART
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS