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Protein

Protein kinase C eta type

Gene

Prkch

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity

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

  • ATP binding Source: UniProtKB-KW
  • calcium-independent protein kinase C activity Source: RGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Differentiation

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13. 5301.
ReactomeiR-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi621888. Prkch.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: Ensembl
  • cytosol Source: RGD
  • extracellular exosome Source: Ensembl
  • membrane Source: RGD
  • plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2094266.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557071 – 683Protein kinase C eta typeAdd BLAST683

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei28PhosphoserineBy similarity1
Modified residuei317PhosphoserineBy similarity1
Modified residuei513Phosphothreonine; by PDPK1Curated1
Modified residuei656PhosphothreonineCombined sources1
Modified residuei675PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ64617.
PRIDEiQ64617.

PTM databases

iPTMnetiQ64617.
PhosphoSitePlusiQ64617.

Expressioni

Gene expression databases

BgeeiENSRNOG00000004873.
ExpressionAtlasiQ64617. baseline and differential.
GenevisibleiQ64617. RN.

Interactioni

Subunit structurei

Interacts with DGKQ, FYN and RALA.By similarity

Protein-protein interaction databases

BioGridi249621. 2 interactors.
STRINGi10116.ENSRNOP00000006729.

Structurei

3D structure databases

ProteinModelPortaliQ64617.
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

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 2 phorbol-ester/DAG-type zinc fingers.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

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.
InParanoidiQ64617.
KOiK18051.
OMAiYLKVRIG.
OrthoDBiEOG091G0QRS.
PhylomeDBiQ64617.
TreeFamiTF351133.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000551. PKC_delta. 1 hit.
PIRSF501107. Protein_kin_C_eta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q64617-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD
60 70 80 90 100
QVRVGQTSTK QKTNKPTYNE EFCTNVSDGG 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 HPFFKEIDWV QLNHRQLEPP FRPRIKSRED VSNFDPDFIK
660 670 680
EEPVLTPIDE GHLPMINQDE FRNFSYVSPE LQP
Length:683
Mass (Da):77,947
Last modified:November 1, 1997 - v1
Checksum:i2F5B7078D1206510
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X68400 mRNA. Translation: CAA48466.1.
BC081782 mRNA. Translation: AAH81782.1.
PIRiI60246. S29478.
RefSeqiNP_112347.1. NM_031085.2.
UniGeneiRn.10398.

Genome annotation databases

EnsembliENSRNOT00000006729; ENSRNOP00000006729; ENSRNOG00000004873.
GeneIDi81749.
KEGGirno:81749.
UCSCiRGD:621888. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X68400 mRNA. Translation: CAA48466.1.
BC081782 mRNA. Translation: AAH81782.1.
PIRiI60246. S29478.
RefSeqiNP_112347.1. NM_031085.2.
UniGeneiRn.10398.

3D structure databases

ProteinModelPortaliQ64617.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249621. 2 interactors.
STRINGi10116.ENSRNOP00000006729.

Chemistry databases

ChEMBLiCHEMBL2094266.

PTM databases

iPTMnetiQ64617.
PhosphoSitePlusiQ64617.

Proteomic databases

PaxDbiQ64617.
PRIDEiQ64617.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000006729; ENSRNOP00000006729; ENSRNOG00000004873.
GeneIDi81749.
KEGGirno:81749.
UCSCiRGD:621888. rat.

Organism-specific databases

CTDi5583.
RGDi621888. Prkch.

Phylogenomic databases

eggNOGiKOG0694. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiQ64617.
KOiK18051.
OMAiYLKVRIG.
OrthoDBiEOG091G0QRS.
PhylomeDBiQ64617.
TreeFamiTF351133.

Enzyme and pathway databases

BRENDAi2.7.11.13. 5301.
ReactomeiR-RNO-114508. Effects of PIP2 hydrolysis.

Miscellaneous databases

PROiQ64617.

Gene expression databases

BgeeiENSRNOG00000004873.
ExpressionAtlasiQ64617. baseline and differential.
GenevisibleiQ64617. RN.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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.
[Graphical view]
PfamiPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000551. PKC_delta. 1 hit.
PIRSF501107. Protein_kin_C_eta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKPCL_RAT
AccessioniPrimary (citable) accession number: Q64617
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 30, 2016
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.