Q02111 (KPCT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › 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
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	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 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 regulation of platelet aggregation Inferred from mutant phenotype PubMed 19433059. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay PubMed 12618484PubMed 12867038. Source: MGI immunological synapse Inferred from direct assay PubMed 11728336PubMed 12867038PubMed 15117976PubMed 15128768. Source: MGI
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from direct assay PubMed 12618484. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAP4K3	Q8IVH8	4	EBI-2639157,EBI-1758170	From a different organism.
Map4k3	Q99JP0	2	EBI-2639157,EBI-5324222
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

C2

Domain

380 – 634

255

Protein kinase

Domain

635 – 706

72

AGC-kinase C-terminal

Zinc finger

159 – 209

51

Phorbol-ester/DAG-type 1

Zinc finger

231 – 281

51

Phorbol-ester/DAG-type 2

Nucleotide binding

386 – 394

9

ATP By similarity

Sites

Active site

504

1

Proton acceptor By similarity

Binding site

409

1

ATP By similarity

Amino acid modifications

Modified residue

90

1

Phosphotyrosine; by LCK By similarity

Modified residue

219

1

Phosphothreonine; by autocatalysis By similarity

Modified residue

348

1

Phosphoserine By similarity

Modified residue

538

1

Phosphothreonine; by PDPK1 By similarity

Modified residue

676

1

Phosphoserine; by autocatalysis Potential

Modified residue

685

1

Phosphoserine By similarity

Modified residue

695

1

Phosphoserine; by autocatalysis Potential

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

707

Helix Strand Turn

Details...

Beta strand

234 – 237

4

Turn

246 – 248

3

Beta strand

254 – 256

3

Beta strand

259 – 262

4

Turn

263 – 265

3

Helix

271 – 276

6

Sequences

	Sequence		Length	Mass (Da)
	Q02111 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: 7A16492116CD2880	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

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.

IPI

IPI00124496.

PIR

A44500.

RefSeq

NP_032885.1. NM_008859.2.

UniGene

Mm.329993.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4FKD	X-ray	1.63	A	232-281	[»]

ProteinModelPortal

Q02111.

SMR

Q02111. Positions 3-126, 144-700.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q02111. 4 interactions.

STRING

10090.ENSMUSP00000028118.

PTM databases

PhosphoSite

Q02111.

Proteomic databases

PaxDb

Q02111.

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

COG0515.

GeneTree

ENSGT00700000104479.

HOGENOM

HOG000233022.

HOVERGEN

HBG108317.

InParanoid

Q02111.

KO

K06068.

OMA

REPQGIS.

OrthoDB

EOG4J9MZ9.

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.
IPR027264. PKC_theta.
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.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

PIRSF

PIRSF000551. PKC_delta. 1 hit.
PIRSF501105. Protein_kin_C_theta. 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

ChEMBL

CHEMBL1075295.

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:	May 1, 2013
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program