Protein kinase C theta type - Mus musculus (Mouse)

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Q02111 (KPCT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 114. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Protein kinase C theta type
EC=2.7.11.13

Alternative name(s):
nPKC-theta

Gene names

Name:	Prkcq
Synonyms:	Pkcq

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	707 AA.
Sequence status	Complete.
Protein existence	Evidence 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 Ref.6
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 process	Immunity Inflammatory response
Cellular component	Cell membrane Cytoplasm Membrane
Domain	Repeat Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from mutant phenotype. Source: MGI membrane protein ectodomain proteolysis Inferred from direct assay. Source: BHF-UCL positive regulation of T cell proliferation Inferred from mutant phenotype. Source: MGI positive regulation of interleukin-2 biosynthetic process Inferred from mutant phenotype. Source: MGI
Cellular component	cytoplasm Inferred from direct assay. Source: MGI immunological synapse Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein kinase C activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Nfix	P70257-2	3	EBI-2639157,EBI-2639084

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 707

707

Protein kinase C theta type

PRO_0000055709

Regions

Domain

8 – 123

116

Domain

380 – 634

255

Protein kinase

Domain

635 – 706

AGC-kinase C-terminal

Zinc finger

159 – 209

Phorbol-ester/DAG-type 1

Zinc finger

231 – 281

Phorbol-ester/DAG-type 2

Nucleotide binding

386 – 394

ATP By similarity

Sites

Active site

504

Proton acceptor By similarity

Binding site

409

ATP By similarity

Amino acid modifications

Modified residue

Phosphotyrosine; by LCK By similarity

Modified residue

219

Phosphothreonine; by autocatalysis By similarity

Modified residue

348

Phosphoserine By similarity

Modified residue

384

N6-acetyllysine By similarity

Modified residue

536

Phosphothreonine By similarity

Modified residue

538

Phosphothreonine; by PDPK1 By similarity

Modified residue

657

Phosphoserine By similarity

Modified residue

676

Phosphoserine; by autocatalysis Potential

Modified residue

685

Phosphoserine By similarity

Modified residue

695

Phosphoserine; by autocatalysis Potential

Sequences

Sequence

Length

Mass (Da)

Tools

Q02111 [UniParc].

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

FASTA

707

81,573

        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

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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: 1508194] [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: 10746729] [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: 12782715] [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: 15263025] [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: 16493044] [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: 19047061] [Abstract] Cited for: FUNCTION IN THE PHOSPHORYLATION OF PDPK1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D11091 mRNA. Translation: BAA01864.1.
IPI	IPI00124496.
PIR	A44500.
RefSeq	NP_032885.1. NM_008859.2.
UniGene	Mm.329993.
3D structure databases
ProteinModelPortal	Q02111.
SMR	Q02111. Positions 3-126, 144-213, 227-703.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q02111. 2 interactions.
STRING	Q02111.
PTM databases
PhosphoSite	Q02111.
Proteomic databases
PRIDE	Q02111.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000028118; ENSMUSP00000028118; ENSMUSG00000026778.
GeneID	18761.
KEGG	mmu:18761.
Organism-specific databases
CTD	5588.
MGI	MGI:97601. Prkcq.
Phylogenomic databases
eggNOG	roNOG07577.
HOGENOM	HBG755340.
HOVERGEN	HBG108317.
InParanoid	Q02111.
OMA	QRRGAIK.
OrthoDB	EOG4J9MZ9.
PhylomeDB	Q02111.
Gene expression databases
ArrayExpress	Q02111.
Bgee	Q02111.
CleanEx	MM_PRKCQ.
Genevestigator	Q02111.
GermOnline	ENSMUSG00000026778. Mus musculus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR020454. DAG/PE-bd. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR014376. Prot_kin_PKC_delta. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K06068.
Pfam	PF00130. C1_1. 2 hits. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000551. PKC_delta. 1 hit.
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 2 hits. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS50004. C2. False negative. 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]
ProtoNet	Search...
Other
NextBio	294949.
SOURCE	Search...

Entry information

Entry name

KPCT_MOUSE

Accession

Primary (citable) accession number: Q02111

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	January 25, 2012
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents