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Protein

Protein kinase C theta type

Gene

Prkcq

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

Functioni

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 in 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/AKT1.6 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-538 (activation loop of the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic region), need to be phosphorylated for its full activation (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei409ATPPROSITE-ProRule annotation1
Active sitei504Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri159 – 209Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri231 – 281Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi386 – 394ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • cell chemotaxis Source: MGI
  • immune system process Source: UniProtKB-KW
  • inflammatory response Source: UniProtKB-KW
  • intracellular signal transduction Source: MGI
  • membrane protein ectodomain proteolysis Source: BHF-UCL
  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
  • negative regulation of T cell apoptotic process Source: UniProtKB
  • peptidyl-serine phosphorylation Source: GO_Central
  • positive regulation of interleukin-17 production Source: UniProtKB
  • positive regulation of interleukin-2 biosynthetic process Source: MGI
  • positive regulation of interleukin-4 production Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of T cell activation Source: UniProtKB
  • positive regulation of T cell proliferation Source: MGI
  • positive regulation of telomerase activity Source: MGI
  • positive regulation of telomere capping Source: MGI
  • positive regulation of telomere maintenance via telomerase Source: MGI
  • positive regulation of T-helper 17 type immune response Source: UniProtKB
  • positive regulation of T-helper 2 cell activation Source: UniProtKB
  • protein phosphorylation Source: MGI
  • regulation of platelet aggregation Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processImmunity, Inflammatory response
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-111465 Apoptotic cleavage of cellular proteins
R-MMU-114508 Effects of PIP2 hydrolysis
R-MMU-202424 Downstream TCR signaling
R-MMU-2871837 FCERI mediated NF-kB activation
R-MMU-373752 Netrin-1 signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C theta type (EC:2.7.11.13)
Alternative name(s):
nPKC-theta
Gene namesi
Name:Prkcq
Synonyms:Pkcq
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:97601 Prkcq

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

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1075295

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557091 – 707Protein kinase C theta typeAdd BLAST707

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei90Phosphotyrosine; by LCKBy similarity1
Modified residuei219Phosphothreonine; by autocatalysisBy similarity1
Modified residuei348PhosphoserineBy similarity1
Modified residuei538Phosphothreonine; by PDPK1By similarity1
Modified residuei676Phosphoserine; by autocatalysisSequence analysisBy similarity1
Modified residuei685PhosphoserineBy similarity1
Modified residuei695Phosphoserine; by autocatalysisSequence analysisBy similarity1

Post-translational modificationi

Autophosphorylation at Thr-219 is required for targeting to the TCR and cellular function of PRKCQ upon antigen receptor ligation. Following TCR stimulation, phosphorylated at Tyr-90 and Ser-685 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ02111
MaxQBiQ02111
PaxDbiQ02111
PRIDEiQ02111

PTM databases

iPTMnetiQ02111
PhosphoSitePlusiQ02111

Expressioni

Tissue specificityi

T-lymphocytes and skeletal muscle.2 Publications

Gene expression databases

BgeeiENSMUSG00000026778
CleanExiMM_PRKCQ
ExpressionAtlasiQ02111 baseline and differential
GenevisibleiQ02111 MM

Interactioni

Subunit structurei

Interacts with GLRX3 (via N-terminus). Interacts with ECT2. Part of a membrane raft complex composed at least of BCL10, CARD11, MALT1 and IKBKB (By similarity).By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi202202, 5 interactors
DIPiDIP-55947N
IntActiQ02111, 6 interactors
STRINGi10090.ENSMUSP00000028118

Chemistry databases

BindingDBiQ02111

Structurei

Secondary structure

1707
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi234 – 237Combined sources4
Turni246 – 248Combined sources3
Beta strandi254 – 256Combined sources3
Beta strandi259 – 262Combined sources4
Turni263 – 265Combined sources3
Helixi271 – 276Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4FKDX-ray1.63A232-281[»]
ProteinModelPortaliQ02111
SMRiQ02111
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 123C2Add BLAST116
Domaini380 – 634Protein kinasePROSITE-ProRule annotationAdd BLAST255
Domaini635 – 706AGC-kinase C-terminalAdd BLAST72

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 fingeri159 – 209Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri231 – 281Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0694 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00820000126964
HOGENOMiHOG000233022
HOVERGENiHBG108317
InParanoidiQ02111
KOiK18052
OMAiEPQGISW
OrthoDBiEOG091G0QRS
PhylomeDBiQ02111
TreeFamiTF102004

Family and domain databases

CDDicd00029 C1, 2 hits
cd05619 STKc_nPKC_theta, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR035892 C2_domain_sf
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR034668 nPKC_theta
IPR002219 PE/DAG-bd
IPR027264 PKC_theta
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
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000551 PKC_delta, 1 hit
PIRSF501105 Protein_kin_C_theta, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 2 hits
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 AGC_KINASE_CTER, 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.

Q02111-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSPFLRIGLS NFDCGTCQAC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP
60 70 80 90 100
TMYPPWDSTF DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN
110 120 130 140 150
GRTEIWLELK PQGRMLMNAR YFLEMSDTKD MSEFENEGFF ALHQRRGAIK
160 170 180 190 200
QAKVHHVKCH EFTATFFPQP TFCSVCHEFV WGLNKQGYQC RQCNAAIHKK
210 220 230 240 250
CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK SPTFCEHCGT
260 270 280 290 300
LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ
310 320 330 340 350
ARSLRDSEHI FREGPVEIGL PCSTKNETRP PCVPTPGKRE PQGISWDSPL
360 370 380 390 400
DGSNKSAGPP EPEVSMRRTS LQLKLKIDDF ILHKMLGKGS FGKVFLAEFK
410 420 430 440 450
RTNQFFAIKA LKKDVVLMDD DVECTMVEKR VLSLAWEHPF LTHMFCTFQT
460 470 480 490 500
KENLFFVMEY LNGGDLMYHI QSCHKFDLSR ATFYAAEVIL GLQFLHSKGI
510 520 530 540 550
VYRDLKLDNI LLDRDGHIKI ADFGMCKENM LGDAKTNTFC GTPDYIAPEI
560 570 580 590 600
LLGQKYNHSV DWWSFGVLVY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR
610 620 630 640 650
WLEREAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP
660 670 680 690 700
FRPKVKSPYD CSNFDKEFLS EKPRLSFADR ALINSMDQNM FSNFSFINPG

METLICS
Length:707
Mass (Da):81,573
Last modified:July 1, 1993 - v1
Checksum:i7A16492116CD2880
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D11091 mRNA Translation: BAA01864.1
CCDSiCCDS15682.1
PIRiA44500
RefSeqiNP_032885.1, NM_008859.2
UniGeneiMm.329993

Genome annotation databases

EnsembliENSMUST00000028118; ENSMUSP00000028118; ENSMUSG00000026778
GeneIDi18761
KEGGimmu:18761
UCSCiuc008iic.1 mouse

Similar proteinsi

Entry informationi

Entry nameiKPCT_MOUSE
AccessioniPrimary (citable) accession number: Q02111
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: March 28, 2018
This is version 173 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health