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Q02111

- KPCT_MOUSE

UniProt

Q02111 - KPCT_MOUSE

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Protein
Protein kinase C theta type
Gene
Prkcq, Pkcq
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - 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 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/AKT1.6 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei409 – 4091ATP By similarity
Active sitei504 – 5041Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri159 – 20951Phorbol-ester/DAG-type 1
Add
BLAST
Zinc fingeri231 – 28151Phorbol-ester/DAG-type 2
Add
BLAST
Nucleotide bindingi386 – 3949ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. protein binding Source: IntAct
  4. protein kinase C activity Source: MGI
Complete GO annotation...

GO - Biological processi

  1. immune system process Source: UniProtKB-KW
  2. inflammatory response Source: UniProtKB-KW
  3. intracellular signal transduction Source: MGI
  4. membrane protein ectodomain proteolysis Source: BHF-UCL
  5. negative regulation of T cell apoptotic process Source: UniProtKB
  6. negative regulation of insulin receptor signaling pathway Source: UniProtKB
  7. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  8. positive regulation of T cell activation Source: UniProtKB
  9. positive regulation of T cell proliferation Source: MGI
  10. positive regulation of T-helper 17 type immune response Source: UniProtKB
  11. positive regulation of T-helper 2 cell activation Source: UniProtKB
  12. positive regulation of interleukin-17 production Source: UniProtKB
  13. positive regulation of interleukin-2 biosynthetic process Source: MGI
  14. positive regulation of interleukin-4 production Source: UniProtKB
  15. protein phosphorylation Source: MGI
  16. regulation of platelet aggregation Source: UniProtKB
  17. regulation of transcription, DNA-templated Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Immunity, Inflammatory response

Keywords - Ligandi

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

Enzyme and pathway databases

ReactomeiREACT_188266. Inactivation, recovery and regulation of the phototransduction cascade.
REACT_205561. FCERI mediated NF-kB activation.
REACT_219232. Effects of PIP2 hydrolysis.
REACT_224460. Apoptotic cleavage of cellular proteins.
REACT_225145. Downstream TCR 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:97601. Prkcq.

Subcellular locationi

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.

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. immunological synapse Source: MGI
  3. plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 707707Protein kinase C theta type
PRO_0000055709Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei90 – 901Phosphotyrosine; by LCK By similarity
Modified residuei219 – 2191Phosphothreonine; by autocatalysis By similarity
Modified residuei348 – 3481Phosphoserine By similarity
Modified residuei538 – 5381Phosphothreonine; by PDPK1 By similarity
Modified residuei676 – 6761Phosphoserine; by autocatalysis Reviewed prediction
Modified residuei685 – 6851Phosphoserine By similarity
Modified residuei695 – 6951Phosphoserine; by autocatalysis Reviewed prediction

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.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ02111.
PaxDbiQ02111.
PRIDEiQ02111.

PTM databases

PhosphoSiteiQ02111.

Expressioni

Tissue specificityi

T-lymphocytes and skeletal muscle.2 Publications

Gene expression databases

ArrayExpressiQ02111.
BgeeiQ02111.
CleanExiMM_PRKCQ.
GenevestigatoriQ02111.

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.

Binary interactionsi

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

Protein-protein interaction databases

BioGridi202202. 3 interactions.
DIPiDIP-55947N.
IntActiQ02111. 4 interactions.
STRINGi10090.ENSMUSP00000028118.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi234 – 2374
Turni246 – 2483
Beta strandi254 – 2563
Beta strandi259 – 2624
Turni263 – 2653
Helixi271 – 2766

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4FKDX-ray1.63A232-281[»]
ProteinModelPortaliQ02111.
SMRiQ02111. Positions 3-126, 144-700.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini8 – 123116C2
Add
BLAST
Domaini380 – 634255Protein kinase
Add
BLAST
Domaini635 – 70672AGC-kinase C-terminal
Add
BLAST

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 C2 domain.

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00750000117339.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiQ02111.
KOiK18052.
OMAiREPQGIS.
PhylomeDBiQ02111.
TreeFamiTF102004.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. 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]
PfamiPF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000551. PKC_delta. 1 hit.
PIRSF501105. Protein_kin_C_theta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
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.
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.

Q02111-1 [UniParc]FASTAAdd to Basket

« Hide

MSPFLRIGLS NFDCGTCQAC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP    50
TMYPPWDSTF DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN 100
GRTEIWLELK PQGRMLMNAR YFLEMSDTKD MSEFENEGFF ALHQRRGAIK 150
QAKVHHVKCH EFTATFFPQP TFCSVCHEFV WGLNKQGYQC RQCNAAIHKK 200
CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK SPTFCEHCGT 250
LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ 300
ARSLRDSEHI FREGPVEIGL PCSTKNETRP PCVPTPGKRE PQGISWDSPL 350
DGSNKSAGPP EPEVSMRRTS LQLKLKIDDF ILHKMLGKGS FGKVFLAEFK 400
RTNQFFAIKA LKKDVVLMDD DVECTMVEKR VLSLAWEHPF LTHMFCTFQT 450
KENLFFVMEY LNGGDLMYHI QSCHKFDLSR ATFYAAEVIL GLQFLHSKGI 500
VYRDLKLDNI LLDRDGHIKI ADFGMCKENM LGDAKTNTFC GTPDYIAPEI 550
LLGQKYNHSV DWWSFGVLVY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR 600
WLEREAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP 650
FRPKVKSPYD CSNFDKEFLS EKPRLSFADR ALINSMDQNM FSNFSFINPG 700
METLICS 707
Length:707
Mass (Da):81,573
Last modified:July 1, 1993 - v1
Checksum:i7A16492116CD2880
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D11091 mRNA. Translation: BAA01864.1 .
CCDSi CCDS15682.1.
PIRi A44500.
RefSeqi NP_032885.1. NM_008859.2.
UniGenei Mm.329993.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4FKD X-ray 1.63 A 232-281 [» ]
ProteinModelPortali Q02111.
SMRi Q02111. Positions 3-126, 144-700.
ModBasei Search...

Protein-protein interaction databases

BioGridi 202202. 3 interactions.
DIPi DIP-55947N.
IntActi Q02111. 4 interactions.
STRINGi 10090.ENSMUSP00000028118.

Chemistry

ChEMBLi CHEMBL1075295.

PTM databases

PhosphoSitei Q02111.

Proteomic databases

MaxQBi Q02111.
PaxDbi Q02111.
PRIDEi Q02111.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000028118 ; ENSMUSP00000028118 ; ENSMUSG00000026778 .
GeneIDi 18761.
KEGGi mmu:18761.
UCSCi uc008iic.1. mouse.

Organism-specific databases

CTDi 5588.
MGIi MGI:97601. Prkcq.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00750000117339.
HOGENOMi HOG000233022.
HOVERGENi HBG108317.
InParanoidi Q02111.
KOi K18052.
OMAi REPQGIS.
PhylomeDBi Q02111.
TreeFami TF102004.

Enzyme and pathway databases

Reactomei REACT_188266. Inactivation, recovery and regulation of the phototransduction cascade.
REACT_205561. FCERI mediated NF-kB activation.
REACT_219232. Effects of PIP2 hydrolysis.
REACT_224460. Apoptotic cleavage of cellular proteins.
REACT_225145. Downstream TCR signaling.

Miscellaneous databases

NextBioi 294949.
PROi Q02111.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q02111.
Bgeei Q02111.
CleanExi MM_PRKCQ.
Genevestigatori Q02111.

Family and domain databases

Gene3Di 2.60.40.150. 1 hit.
InterProi IPR000961. 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 ]
Pfami PF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view ]
PIRSFi PIRSF000551. PKC_delta. 1 hit.
PIRSF501105. Protein_kin_C_theta. 1 hit.
PRINTSi PR00008. DAGPEDOMAIN.
SMARTi SM00109. C1. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiKPCT_MOUSE
AccessioniPrimary (citable) accession number: Q02111
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: September 3, 2014
This is version 140 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

3D-structure, Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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