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Q02111 (KPCT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein kinase C theta type

EC=2.7.11.13
Alternative name(s):
nPKC-theta
Gene names
Name:Prkcq
Synonyms:Pkcq
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length707 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

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.

Subunit structure

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.

Subcellular location

Cytoplasm By similarity. Cell membrane By similarity; Peripheral membrane protein. Note: In resting T-cells, mostly localized in cytoplasm. In response to TCR stimulation, associates with lipid rafts and then localizes in the immunological synapse By similarity.

Tissue specificity

T-lymphocytes and skeletal muscle. Ref.1 Ref.2

Domain

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.

Post-translational modification

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. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 C2 domain.

Contains 2 phorbol-ester/DAG-type zinc fingers.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
   Cellular componentCell membrane
Cytoplasm
Membrane
   DomainRepeat
Zinc-finger
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processimmune system process

Inferred from electronic annotation. Source: UniProtKB-KW

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Inferred from mutant phenotype PubMed 12867038. Source: MGI

membrane protein ectodomain proteolysis

Inferred from direct assay PubMed 9857183. Source: BHF-UCL

negative regulation of T cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.3. Source: UniProtKB

positive regulation of T cell activation

Inferred from mutant phenotype Ref.3. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from mutant phenotype PubMed 12867038. Source: MGI

positive regulation of T-helper 17 type immune response

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of T-helper 2 cell activation

Inferred from mutant phenotype Ref.4. Source: UniProtKB

positive regulation of interleukin-17 production

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of interleukin-2 biosynthetic process

Inferred from mutant phenotype PubMed 12867038. Source: MGI

positive regulation of interleukin-4 production

Inferred from mutant phenotype Ref.4. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 12618484. Source: MGI

regulation of platelet aggregation

Inferred from mutant phenotype PubMed 19433059. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from mutant phenotype Ref.3. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 12618484PubMed 12867038. Source: MGI

immunological synapse

Inferred from direct assay PubMed 11728336PubMed 12867038PubMed 15117976PubMed 15128768PubMed 23793062. Source: MGI

plasma membrane

Inferred from direct assay PubMed 12618484PubMed 12867038. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 20178747PubMed 21983831. Source: IntAct

protein kinase C activity

Inferred from direct assay PubMed 12618484. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAP4K3Q8IVH84EBI-2639157,EBI-1758170From a different organism.
Map4k3Q99JP02EBI-2639157,EBI-5324222
NfixP70257-23EBI-2639157,EBI-2639084

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 707707Protein kinase C theta type
PRO_0000055709

Regions

Domain8 – 123116C2
Domain380 – 634255Protein kinase
Domain635 – 70672AGC-kinase C-terminal
Zinc finger159 – 20951Phorbol-ester/DAG-type 1
Zinc finger231 – 28151Phorbol-ester/DAG-type 2
Nucleotide binding386 – 3949ATP By similarity

Sites

Active site5041Proton acceptor By similarity
Binding site4091ATP By similarity

Amino acid modifications

Modified residue901Phosphotyrosine; by LCK By similarity
Modified residue2191Phosphothreonine; by autocatalysis By similarity
Modified residue3481Phosphoserine By similarity
Modified residue5381Phosphothreonine; by PDPK1 By similarity
Modified residue6761Phosphoserine; by autocatalysis Potential
Modified residue6851Phosphoserine By similarity
Modified residue6951Phosphoserine; by autocatalysis Potential

Secondary structure

............ 707
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q02111 [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: 7A16492116CD2880

FASTA70781,573
        10         20         30         40         50         60 
MSPFLRIGLS NFDCGTCQAC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP TMYPPWDSTF 

        70         80         90        100        110        120 
DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN GRTEIWLELK PQGRMLMNAR 

       130        140        150        160        170        180 
YFLEMSDTKD MSEFENEGFF ALHQRRGAIK QAKVHHVKCH EFTATFFPQP TFCSVCHEFV 

       190        200        210        220        230        240 
WGLNKQGYQC RQCNAAIHKK CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK 

       250        260        270        280        290        300 
SPTFCEHCGT LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ 

       310        320        330        340        350        360 
ARSLRDSEHI FREGPVEIGL PCSTKNETRP PCVPTPGKRE PQGISWDSPL DGSNKSAGPP 

       370        380        390        400        410        420 
EPEVSMRRTS LQLKLKIDDF ILHKMLGKGS FGKVFLAEFK RTNQFFAIKA LKKDVVLMDD 

       430        440        450        460        470        480 
DVECTMVEKR VLSLAWEHPF LTHMFCTFQT KENLFFVMEY LNGGDLMYHI QSCHKFDLSR 

       490        500        510        520        530        540 
ATFYAAEVIL GLQFLHSKGI VYRDLKLDNI LLDRDGHIKI ADFGMCKENM LGDAKTNTFC 

       550        560        570        580        590        600 
GTPDYIAPEI LLGQKYNHSV DWWSFGVLVY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR 

       610        620        630        640        650        660 
WLEREAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP FRPKVKSPYD 

       670        680        690        700 
CSNFDKEFLS EKPRLSFADR ALINSMDQNM FSNFSFINPG METLICS 

« Hide

References

[1]"A new member of the protein kinase C family, nPKC theta, predominantly expressed in skeletal muscle."
Osada S., Mizuno K., Saido T.C., Suzuki K., Kuroki T., Ohno S.
Mol. Cell. Biol. 12:3930-3938(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AUTOPHOSPHORYLATION, TISSUE SPECIFICITY.
[2]"PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes."
Sun Z., Arendt C.W., Ellmeier W., Schaeffer E.M., Sunshine M.J., Gandhi L., Annes J., Petrzilka D., Kupfer A., Schwartzberg P.L., Littman D.R.
Nature 404:402-407(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF NF-KAPPA-B, TISSUE SPECIFICITY.
[3]"Protein kinase C theta affects Ca2+ mobilization and NFAT cell activation in primary mouse T cells."
Pfeifhofer C., Kofler K., Gruber T., Tabrizi N.G., Lutz C., Maly K., Leitges M., Baier G.
J. Exp. Med. 197:1525-1535(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIVATION OF NFATC1 AND NFATC2.
[4]"Protein kinase C theta is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses."
Marsland B.J., Soos T.J., Spaeth G., Littman D.R., Kopf M.
J. Exp. Med. 200:181-189(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN T-HELPER 2 ACTIVATION.
[5]"Resistance to experimental autoimmune encephalomyelitis and impaired IL-17 production in protein kinase C theta-deficient mice."
Tan S.L., Zhao J., Bi C., Chen X.C., Hepburn D.L., Wang J., Sedgwick J.D., Chintalacharuvu S.R., Na S.
J. Immunol. 176:2872-2879(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN T-HELPER 17 ACTIVATION.
[6]"Protein kinase C theta (PKCtheta)-dependent phosphorylation of PDK1 at Ser504 and Ser532 contributes to palmitate-induced insulin resistance."
Wang C., Liu M., Riojas R.A., Xin X., Gao Z., Zeng R., Wu J., Dong L.Q., Liu F.
J. Biol. Chem. 284:2038-2044(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PDPK1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D11091 mRNA. Translation: BAA01864.1.
CCDSCCDS15682.1.
PIRA44500.
RefSeqNP_032885.1. NM_008859.2.
UniGeneMm.329993.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4FKDX-ray1.63A232-281[»]
ProteinModelPortalQ02111.
SMRQ02111. Positions 3-126, 144-700.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202202. 3 interactions.
DIPDIP-55947N.
IntActQ02111. 4 interactions.
STRING10090.ENSMUSP00000028118.

Chemistry

ChEMBLCHEMBL1075295.

PTM databases

PhosphoSiteQ02111.

Proteomic databases

MaxQBQ02111.
PaxDbQ02111.
PRIDEQ02111.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000028118; ENSMUSP00000028118; ENSMUSG00000026778.
GeneID18761.
KEGGmmu:18761.
UCSCuc008iic.1. mouse.

Organism-specific databases

CTD5588.
MGIMGI:97601. Prkcq.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117339.
HOGENOMHOG000233022.
HOVERGENHBG108317.
InParanoidQ02111.
KOK18052.
OMAREPQGIS.
PhylomeDBQ02111.
TreeFamTF102004.

Gene expression databases

ArrayExpressQ02111.
BgeeQ02111.
CleanExMM_PRKCQ.
GenevestigatorQ02111.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
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_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000551. PKC_delta. 1 hit.
PIRSF501105. Protein_kin_C_theta. 1 hit.
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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.
[Graphical view]
ProtoNetSearch...

Other

NextBio294949.
PROQ02111.
SOURCESearch...

Entry information

Entry nameKPCT_MOUSE
AccessionPrimary (citable) accession number: Q02111
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: July 9, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot