CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005320
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein kinase C eta type 
Protein Synonyms/Alias
 PKC-L; nPKC-eta 
Gene Name
 PRKCH 
Gene Synonyms/Alias
 PKCL; PRKCL 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
36LRHSLFKKGHQLLDPubiquitination[1, 2, 3]
321GNISPTSKLVSRSTLubiquitination[2, 3]
337RQGKESSKEGNGIGVubiquitination[3]
363EFIRVLGKGSFGKVMubiquitination[3]
375KVMLARVKETGDLYAubiquitination[3]
404VECTMTEKRILSLARubiquitination[3]
481GIIYRDLKLDNVLLDubiquitination[3]
591ILKSFMTKNPTMRLGubiquitination[3]
615ILRHPFFKEIDWAQLubiquitination[2, 3]
Reference
 [1] 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]
 [2] 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]
 [3] 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] 
Functional Description
 Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1- dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. 
Sequence Annotation
 DOMAIN 12 113 C2.
 DOMAIN 355 614 Protein kinase.
 DOMAIN 615 683 AGC-kinase C-terminal.
 ZN_FING 171 222 Phorbol-ester/DAG-type 1.
 ZN_FING 245 295 Phorbol-ester/DAG-type 2.
 NP_BIND 361 369 ATP (By similarity).
 ACT_SITE 479 479 Proton acceptor (By similarity).
 BINDING 384 384 ATP (By similarity).
 MOD_RES 28 28 Phosphoserine; by autocatalysis
 MOD_RES 32 32 Phosphoserine; by autocatalysis
 MOD_RES 513 513 Phosphothreonine; by PDPK1 (Probable).
 MOD_RES 656 656 Phosphothreonine (Probable).  
Keyword
 3D-structure; ATP-binding; Complete proteome; Cytoplasm; Differentiation; Kinase; 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
 683 AA 
Protein Sequence
MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD QVRVGQTSTK 60
QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN CTLQFQELLR TTGASDTFEG 120
WVDLEPEGKV FVVITLTGSF TEATLQRDRI FKHFTRKRQR AMRRRVHQIN GHKFMATYLR 180
QPTYCSHCRE FIWGVFGKQG YQCQVCTCVV HKRCHHLIVT ACTCQNNINK VDSKIAEQRF 240
GINIPHKFSI HNYKVPTFCD HCGSLLWGIM RQGLQCKICK MNVHIRCQAN VAPNCGVNAV 300
ELAKTLAGMG LQPGNISPTS KLVSRSTLRR QGKESSKEGN GIGVNSSNRL GIDNFEFIRV 360
LGKGSFGKVM LARVKETGDL YAVKVLKKDV ILQDDDVECT MTEKRILSLA RNHPFLTQLF 420
CCFQTPDRLF FVMEFVNGGD LMFHIQKSRR FDEARARFYA AEIISALMFL HDKGIIYRDL 480
KLDNVLLDHE GHCKLADFGM CKEGICNGVT TATFCGTPDY IAPEILQEML YGPAVDWWAM 540
GVLLYEMLCG HAPFEAENED DLFEAILNDE VVYPTWLHED ATGILKSFMT KNPTMRLGSL 600
TQGGEHAILR HPFFKEIDWA QLNHRQIEPP FRPRIKSRED VSNFDPDFIK EEPVLTPIDE 660
GHLPMINQDE FRNFSYVSPE LQP 683 
Gene Ontology
 GO:0005829; C:cytosol; ISS:UniProtKB.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004699; F:calcium-independent protein kinase C activity; IEA:Compara.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004697; F:protein kinase C activity; TAS:ProtInc.
 GO:0034351; P:negative regulation of glial cell apoptotic process; IMP:UniProtKB.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0050861; P:positive regulation of B cell receptor signaling pathway; IMP:UniProtKB.
 GO:0060252; P:positive regulation of glial cell proliferation; IMP:UniProtKB.
 GO:0045618; P:positive regulation of keratinocyte differentiation; ISS:UniProtKB.
 GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISS:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
 GO:0070528; P:protein kinase C signaling cascade; IEA:Compara.
 GO:2000810; P:regulation of tight junction assembly; IMP:UniProtKB.
 GO:0007165; P:signal transduction; TAS:ProtInc. 
Interpro
 IPR000961; AGC-kinase_C.
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 IPR018029; C2_membr_targeting.
 IPR020454; DAG/PE-bd.
 IPR011009; Kinase-like_dom.
 IPR027431; PKC_eta.
 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
 PF00168; C2
 PF00069; Pkinase
 PF00433; Pkinase_C 
SMART
 SM00109; C1
 SM00239; C2
 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.