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Protein

Protein kinase C eta type

Gene

Prkch

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-513 (activation loop of the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic region), need to be phosphorylated for its full activation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei384ATPPROSITE-ProRule annotation1
Active sitei479Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri171 – 222Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST52
Zinc fingeri245 – 295Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi361 – 369ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processDifferentiation
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13. 3474.
ReactomeiR-MMU-114508. Effects of PIP2 hydrolysis.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C eta type (EC:2.7.11.13)
Alternative name(s):
PKC-L
nPKC-eta
Gene namesi
Name:Prkch
Synonyms:Pkch
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:97600. Prkch.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4992.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557061 – 683Protein kinase C eta typeAdd BLAST683

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28PhosphoserineBy similarity1
Modified residuei317PhosphoserineCombined sources1
Modified residuei513Phosphothreonine; by PDPK1By similarity1
Modified residuei656PhosphothreonineBy similarityCurated1
Modified residuei675PhosphoserineBy similarityCurated1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP23298.
MaxQBiP23298.
PaxDbiP23298.
PRIDEiP23298.

PTM databases

iPTMnetiP23298.
PhosphoSitePlusiP23298.

Expressioni

Tissue specificityi

Predominantly expressed in lung and skin.

Gene expression databases

BgeeiENSMUSG00000021108.
CleanExiMM_PRKCH.
ExpressionAtlasiP23298. baseline and differential.
GenevisibleiP23298. MM.

Interactioni

Subunit structurei

Interacts with DGKQ (By similarity). Interacts with FYN and RALA.By similarity2 Publications

GO - Molecular functioni

  • enzyme binding Source: MGI
  • Ral GTPase binding Source: UniProtKB

Protein-protein interaction databases

IntActiP23298. 2 interactors.
MINTiMINT-4100035.
STRINGi10090.ENSMUSP00000021527.

Chemistry databases

BindingDBiP23298.

Structurei

3D structure databases

ProteinModelPortaliP23298.
SMRiP23298.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 102C2PROSITE-ProRule annotationAdd BLAST91
Domaini355 – 614Protein kinasePROSITE-ProRule annotationAdd BLAST260
Domaini615 – 683AGC-kinase C-terminalAdd BLAST69

Domaini

The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri171 – 222Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST52
Zinc fingeri245 – 295Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0694. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiP23298.
KOiK18051.
OMAiNHRQLEP.
OrthoDBiEOG091G0QRS.
TreeFamiTF351133.

Family and domain databases

CDDicd00029. C1. 2 hits.
cd05590. STKc_nPKC_eta. 1 hit.
Gene3Di2.60.40.150. 1 hit.
InterProiView protein in InterPro
IPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR034665. nPKC_eta.
IPR002219. PE/DAG-bd.
IPR027431. PKC_eta.
IPR017892. Pkinase_C.
IPR014376. Prot_kin_PKC_delta.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
PIRSFiPIRSF000551. PKC_delta. 1 hit.
PIRSF501107. Protein_kin_C_eta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiView protein in SMART
SM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS51285. AGC_KINASE_CTER. 1 hit.
PS50004. C2. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.

Sequencei

Sequence statusi: Complete.

P23298-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD
60 70 80 90 100
QVRVGQTSTK QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN
110 120 130 140 150
CTLQFQELLR TAGTSDTFEG WVDLEPEGKV FVVITLTGSF TEATLQRDRI
160 170 180 190 200
FKHFTRKRQR AMRRRVHQVN GHKFMATYLR QPTYCSHCRE FIWGVFGKQG
210 220 230 240 250
YQCQVCTCVV HKRCHHLIVT ACTCQNNINK VDAKIAEQRF GINIPHKFNV
260 270 280 290 300
HNYKVPTFCD HCGSLLWGIM RQGLQCKICK MNVHIRCQAN VAPNCGVNAV
310 320 330 340 350
ELAKTLAGMG LQPGNISPTS KLISRSTLRR QGKEGSKEGN GIGVNSSSRF
360 370 380 390 400
GIDNFEFIRV LGKGSFGKVM LARIKETGEL YAVKVLKKDV ILQDDDVECT
410 420 430 440 450
MTEKRILSLA RNHPFLTQLF CCFQTPDRLF FVMEFVNGGD LMFHIQKSRR
460 470 480 490 500
FDEARARFYA AEIISALMFL HEKGIIYRDL KLDNVLLDHE GHCKLADFGM
510 520 530 540 550
CKEGICNGVT TATFCGTPDY IAPEILQEML YGPAVDWWAM GVLLYEMLCG
560 570 580 590 600
HAPFEAENED DLFEAILNDE VVYPTWLHED ATGILKSFMT KNPTMRLGSL
610 620 630 640 650
TQGGEHEILR HPFFKEIDWA QLNHRQLEPP FRPRIKSRED VSNFDPDFIK
660 670 680
EEPVLTPIDE GHLPMINQDE FRNFSYVSPE LQL
Length:683
Mass (Da):77,919
Last modified:July 27, 2011 - v2
Checksum:i50454A6AE1900AD3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti582T → R in BAA14288 (PubMed:2266135).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D90242 mRNA. Translation: BAA14288.1.
AK164044 mRNA. Translation: BAE37603.1.
BC031121 mRNA. Translation: AAH31121.1.
CCDSiCCDS25976.1.
PIRiA23690.
RefSeqiNP_001300906.1. NM_001313977.1.
NP_032882.2. NM_008856.4.
UniGeneiMm.341677.

Genome annotation databases

EnsembliENSMUST00000021527; ENSMUSP00000021527; ENSMUSG00000021108.
GeneIDi18755.
KEGGimmu:18755.
UCSCiuc007nwn.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiKPCL_MOUSE
AccessioniPrimary (citable) accession number: P23298
Secondary accession number(s): Q8K2K8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: July 27, 2011
Last modified: August 30, 2017
This is version 171 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families