CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011236
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein kinase C theta type 
Protein Synonyms/Alias
 nPKC-theta 
Gene Name
 PRKCQ 
Gene Synonyms/Alias
 PRKCT 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
49GQMYIQKKPTMYPPWubiquitination[1]
66TFDAHINKGRVMQIIubiquitination[1]
75RVMQIIVKGKNVDLIubiquitination[1, 2]
77MQIIVKGKNVDLISEubiquitination[1]
110TEIWLELKPQGRMLMubiquitination[2]
208CIDKVIAKCTGSAINubiquitination[1]
223SRETMFHKERFKIDMubiquitination[1]
227MFHKERFKIDMPHRFubiquitination[1]
235IDMPHRFKVYNYKSPubiquitination[1]
240RFKVYNYKSPTFCEHubiquitination[1]
276VHHRCQTKVANLCGIubiquitination[1]
286NLCGINQKLMAEALAubiquitination[1]
325IGLPCSIKNEARPPCubiquitination[1]
376PSLQIKLKIEDFILHubiquitination[1]
384IEDFILHKMLGKGSFacetylation[3]
384IEDFILHKMLGKGSFubiquitination[1]
388ILHKMLGKGSFGKVFubiquitination[1]
400KVFLAEFKKTNQFFAubiquitination[1]
429VECTMVEKRVLSLAWubiquitination[1]
506GIVYRDLKLDNILLDubiquitination[1]
527IADFGMCKENMLGDAubiquitination[1, 4]
535ENMLGDAKTNTFCGTubiquitination[1]
604FYPRWLEKEAKDLLVubiquitination[1]
620LFVREPEKRLGVRGDubiquitination[1]
672DKEFLNEKPRLSFADubiquitination[1]
Reference
 [1] 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]
 [2] 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]
 [3] 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]
 [4] 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
 Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non- redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates to the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non- canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. 
Sequence Annotation
 DOMAIN 8 123 C2.
 DOMAIN 380 634 Protein kinase.
 DOMAIN 635 706 AGC-kinase C-terminal.
 ZN_FING 159 209 Phorbol-ester/DAG-type 1.
 ZN_FING 231 281 Phorbol-ester/DAG-type 2.
 NP_BIND 386 394 ATP (By similarity).
 ACT_SITE 504 504 Proton acceptor (By similarity).
 BINDING 409 409 ATP.
 MOD_RES 90 90 Phosphotyrosine; by LCK.
 MOD_RES 219 219 Phosphothreonine; by autocatalysis.
 MOD_RES 348 348 Phosphoserine.
 MOD_RES 538 538 Phosphothreonine; by PDPK1 (Probable).
 MOD_RES 676 676 Phosphoserine.
 MOD_RES 685 685 Phosphoserine.
 MOD_RES 695 695 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; Immunity; Inflammatory response; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 706 AA 
Protein Sequence
MSPFLRIGLS NFDCGSCQSC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP TMYPPWDSTF 60
DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN GKTEIWLELK PQGRMLMNAR 120
YFLEMSDTKD MNEFETEGFF ALHQRRGAIK QAKVHHVKCH EFTATFFPQP TFCSVCHEFV 180
WGLNKQGYQC RQCNAAIHKK CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK 240
SPTFCEHCGT LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ 300
ARCLRDTEQI FREGPVEIGL PCSIKNEARP PCLPTPGKRE PQGISWESPL DEVDKMCHLP 360
EPELNKERPS LQIKLKIEDF ILHKMLGKGS FGKVFLAEFK KTNQFFAIKA LKKDVVLMDD 420
DVECTMVEKR VLSLAWEHPF LTHMFCTFQT KENLFFVMEY LNGGDLMYHI QSCHKFDLSR 480
ATFYAAEIIL GLQFLHSKGI VYRDLKLDNI LLDKDGHIKI ADFGMCKENM LGDAKTNTFC 540
GTPDYIAPEI LLGQKYNHSV DWWSFGVLLY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR 600
WLEKEAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP FRPKVKSPFD 660
CSNFDKEFLN EKPRLSFADR ALINSMDQNM FRNFSFMNPG MERLIS 706 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0001772; C:immunological synapse; IEA:Compara.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0005524; F:ATP binding; NAS:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004697; F:protein kinase C activity; IEA:EC.
 GO:0004674; F:protein serine/threonine kinase activity; NAS:UniProtKB.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
 GO:0006509; P:membrane protein ectodomain proteolysis; ISS:BHF-UCL.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
 GO:0070233; P:negative regulation of T cell apoptotic process; IMP:UniProtKB.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB.
 GO:0045086; P:positive regulation of interleukin-2 biosynthetic process; IEA:Compara.
 GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0042102; P:positive regulation of T cell proliferation; IEA:Compara.
 GO:2000318; P:positive regulation of T-helper 17 type immune response; ISS:UniProtKB.
 GO:2000570; P:positive regulation of T-helper 2 cell activation; ISS:UniProtKB.
 GO:0001558; P:regulation of cell growth; NAS:UniProtKB.
 GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR020454; DAG/PE-bd.
 IPR011009; Kinase-like_dom.
 IPR027264; PKC_theta.
 IPR017892; Pkinase_C.
 IPR014376; Prot_kin_PKC_delta.
 IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00130; C1_1
 PF00069; Pkinase
 PF00433; Pkinase_C 
SMART
 SM00109; C1
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS50004; C2
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS00479; ZF_DAG_PE_1
 PS50081; ZF_DAG_PE_2 
PRINTS
 PR00008; DAGPEDOMAIN.