Q04759 (KPCT_HUMAN) 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:	PRKCT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	706 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.7 Ref.10 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.20
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.
Subunit structure	Interacts with GLRX3 (via N-terminus). Interacts with ECT2. Part of a lipid raft complex composed at least of BCL10, CARD11, MALT1 and IKBKB. Ref.8 Ref.14 Ref.16
Subcellular location	Cytoplasm. Cell membrane; 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.
Tissue specificity	Expressed in skeletal muscle, T-cells, megakaryoblastic cells and platelets. Ref.1
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. Ref.9 Ref.11 Ref.15 Ref.31 Ref.32
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
Coding sequence diversity	Alternative splicing Polymorphism
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	T cell receptor signaling pathway Traceable author statement. Source: Reactome axon guidance Traceable author statement. Source: Reactome cellular component disassembly involved in execution phase of apoptosis Traceable author statement. Source: Reactome inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Non-traceable author statement Ref.1. Source: UniProtKB membrane protein ectodomain proteolysis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of T cell apoptotic process Inferred from mutant phenotype Ref.10Ref.17. Source: UniProtKB negative regulation of insulin receptor signaling pathway Inferred from mutant phenotype Ref.13. Source: UniProtKB platelet activation Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.16. Source: UniProtKB positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of T-helper 17 type immune response Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of T-helper 2 cell activation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-17 production Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-2 biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of interleukin-4 production Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell growth Non-traceable author statement Ref.3. Source: UniProtKB regulation of platelet aggregation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome immunological synapse Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	ATP binding Non-traceable author statement. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Non-traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-374762,EBI-374762
BTK	Q06187	2	EBI-374762,EBI-624835
FYN	P06241	7	EBI-374762,EBI-515315
GLRX3	O76003	5	EBI-374762,EBI-374781
HSF1	Q00613	2	EBI-374762,EBI-719620
Irs1	P35570	2	EBI-374762,EBI-520230	From a different organism.
LCK	P06239	2	EBI-374762,EBI-1348
MAP4K3	Q8IVH8	4	EBI-374762,EBI-1758170
PRKCZ	Q05513	3	EBI-374762,EBI-295351

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q04759-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q04759-2)

The sequence of this isoform differs from the canonical sequence as follows:
     550-612: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 706

706

Protein kinase C theta type

PRO_0000055708

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

Amino acid modifications

Modified residue

90

1

Phosphotyrosine; by LCK Ref.9

Modified residue

219

1

Phosphothreonine; by autocatalysis Ref.15

Modified residue

348

1

Phosphoserine Ref.18

Modified residue

538

1

Phosphothreonine; by PDPK1 Probable

Modified residue

676

1

Phosphoserine Ref.11 Ref.15 Ref.19 Ref.32

Modified residue

685

1

Phosphoserine Ref.18 Ref.27 Ref.30

Modified residue

695

1

Phosphoserine Ref.11 Ref.15 Ref.18 Ref.19 Ref.30 Ref.31 Ref.32

Natural variations

Alternative sequence

550 – 612

63

Missing in isoform 2.

VSP_017294

Natural variant

240

1

K → N in a colorectal adenocarcinoma sample; somatic mutation. Ref.33

VAR_042319

Natural variant

306

1

D → V. Ref.33
Corresponds to variant rs45590231 [ dbSNP | Ensembl ].

VAR_042320

Natural variant

330

1

P → L. Ref.1 Ref.4 Ref.33
Corresponds to variant rs2236379 [ dbSNP | Ensembl ].

VAR_020401

Natural variant

354

1

D → N. Ref.33
Corresponds to variant rs34524148 [ dbSNP | Ensembl ].

VAR_042321

Experimental info

Mutagenesis

90

1

Y → F: Loss of function in T-cells proliferation. No effect on kinase activity. Ref.9

Mutagenesis

148

1

A → E: Constitutively active form. Ref.9

Mutagenesis

219

1

T → A: Loss of transactivation of the IL2 promoter and translocation to the plasma membrane. No effect on kinase activity. Ref.15

Mutagenesis

409

1

K → A or E: Loss of kinase activity. Ref.9

Mutagenesis

538

1

T → A: Loss of kinase activity. Ref.11 Ref.15

Mutagenesis

676

1

S → A: Reduction in kinase activity. Ref.15

Mutagenesis

695

1

S → A: Reduction in kinase activity. Ref.11 Ref.15

Sequence conflict

700

1

G → R in AAA75571. Ref.1

Sequence conflict

700

1

G → R in AAU29340. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

706

Helix Strand Turn

Details...

Beta strand

5 – 13

9

Beta strand

28 – 39

12

Beta strand

42 – 52

11

Beta strand

56 – 62

7

Beta strand

69 – 75

7

Beta strand

83 – 89

7

Helix

90 – 98

9

Turn

99 – 101

3

Beta strand

103 – 108

6

Beta strand

110 – 112

3

Beta strand

114 – 121

8

Beta strand

155 – 159

5

Beta strand

161 – 165

5

Beta strand

174 – 176

3

Beta strand

187 – 189

3

Beta strand

191 – 193

3

Beta strand

196 – 199

4

Helix

200 – 202

3

Beta strand

234 – 236

3

Beta strand

246 – 248

3

Beta strand

255 – 257

3

Beta strand

259 – 265

7

Turn

271 – 276

6

Turn

281 – 283

3

Helix

377 – 379

3

Beta strand

380 – 388

9

Beta strand

390 – 399

10

Turn

400 – 402

3

Beta strand

405 – 412

8

Helix

413 – 418

6

Helix

422 – 435

14

Beta strand

444 – 449

6

Beta strand

451 – 459

9

Helix

466 – 473

8

Helix

478 – 497

20

Helix

507 – 509

3

Beta strand

510 – 512

3

Beta strand

518 – 520

3

Helix

543 – 545

3

Helix

548 – 551

4

Helix

559 – 574

16

Helix

584 – 593

10

Helix

604 – 613

10

Helix

618 – 620

3

Helix

628 – 630

3

Helix

632 – 634

3

Helix

639 – 643

5

Turn

667 – 670

4

Helix

680 – 685

6

Turn

690 – 693

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 27, 2002. Version 3. Checksum: B3C53AB892D5210A	FASTA	706	81,865
	10 20 30 40 50 60 MSPFLRIGLS NFDCGSCQSC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP TMYPPWDSTF 70 80 90 100 110 120 DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN GKTEIWLELK PQGRMLMNAR 130 140 150 160 170 180 YFLEMSDTKD MNEFETEGFF 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 ARCLRDTEQI FREGPVEIGL PCSIKNEARP PCLPTPGKRE PQGISWESPL DEVDKMCHLP 370 380 390 400 410 420 EPELNKERPS LQIKLKIEDF ILHKMLGKGS FGKVFLAEFK KTNQFFAIKA LKKDVVLMDD 430 440 450 460 470 480 DVECTMVEKR VLSLAWEHPF LTHMFCTFQT KENLFFVMEY LNGGDLMYHI QSCHKFDLSR 490 500 510 520 530 540 ATFYAAEIIL GLQFLHSKGI VYRDLKLDNI LLDKDGHIKI ADFGMCKENM LGDAKTNTFC 550 560 570 580 590 600 GTPDYIAPEI LLGQKYNHSV DWWSFGVLLY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR 610 620 630 640 650 660 WLEKEAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP FRPKVKSPFD 670 680 690 700 CSNFDKEFLN EKPRLSFADR ALINSMDQNM FRNFSFMNPG MERLIS
	Isoform 2 [UniParc]. Checksum: A3B688EBE8809B9E	FASTA	643	74,287
	10 20 30 40 50 60 MSPFLRIGLS NFDCGSCQSC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP TMYPPWDSTF 70 80 90 100 110 120 DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN GKTEIWLELK PQGRMLMNAR 130 140 150 160 170 180 YFLEMSDTKD MNEFETEGFF 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 ARCLRDTEQI FREGPVEIGL PCSIKNEARP PCLPTPGKRE PQGISWESPL DEVDKMCHLP 370 380 390 400 410 420 EPELNKERPS LQIKLKIEDF ILHKMLGKGS FGKVFLAEFK KTNQFFAIKA LKKDVVLMDD 430 440 450 460 470 480 DVECTMVEKR VLSLAWEHPF LTHMFCTFQT KENLFFVMEY LNGGDLMYHI QSCHKFDLSR 490 500 510 520 530 540 ATFYAAEIIL GLQFLHSKGI VYRDLKLDNI LLDKDGHIKI ADFGMCKENM LGDAKTNTFC 550 560 570 580 590 600 GTPDYIAPEL FVREPEKRLG VRGDIRQHPL FREINWEELE RKEIDPPFRP KVKSPFDCSN 610 620 630 640 FDKEFLNEKP RLSFADRALI NSMDQNMFRN FSFMNPGMER LIS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). A new member of the nPKC family expressed in skeletal muscle, megakaryoblastic cells, and platelets." Chang J.D., Xu Y., Raychowdhury M.K., Ware J.A. J. Biol. Chem. 268:14208-14214(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT LEU-330.
[2]	Erratum Chang J.D., Xu Y., Raychowdhury M.K., Ware J.A. J. Biol. Chem. 269:31322-31322(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"Molecular cloning and characterization of PKC theta, a novel member of the protein kinase C (PKC) gene family expressed predominantly in hematopoietic cells." Baier G., Telford D., Giampa L., Coggeshall K.M., Baier-Bitterlich G., Isakov N., Altman A. J. Biol. Chem. 268:4997-5004(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Blood.
[4]	Li H., Ke R., Zhou G., Shen C., Zhong G., Lin L., Yang S. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-330.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[7]	"Protein kinase C-theta isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes." Baier-Bitterlich G., Uberall F., Bauer B., Fresser F., Wachter H., Grunicke H., Utermann G., Altman A., Baier G. Mol. Cell. Biol. 16:1842-1850(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF JUN.
[8]	"Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain." Witte S., Villalba M., Bi K., Liu Y., Isakov N., Altman A. J. Biol. Chem. 275:1902-1909(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GLRX3.
[9]	"Regulation of protein kinase Ctheta function during T cell activation by Lck-mediated tyrosine phosphorylation." Liu Y., Witte S., Liu Y.C., Doyle M., Elly C., Altman A. J. Biol. Chem. 275:3603-3609(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-90, MUTAGENESIS OF TYR-90; ALA-148 AND LYS-409.
[10]	"Protein kinase C-theta mediates a selective T cell survival signal via phosphorylation of BAD." Villalba M., Bushway P., Altman A. J. Immunol. 166:5955-5963(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF BAD.
[11]	"Phosphorylation of the protein kinase C-theta activation loop and hydrophobic motif regulates its kinase activity, but only activation loop phosphorylation is critical to in vivo nuclear-factor-kappaB induction." Liu Y., Graham C., Li A., Fisher R.J., Shaw S. Biochem. J. 361:255-265(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-538; SER-676 AND SER-695, MUTAGENESIS OF THR-538 AND SER-695.
[12]	"SPAK kinase is a substrate and target of PKCtheta in T-cell receptor-induced AP-1 activation pathway." Li Y., Hu J., Vita R., Sun B., Tabata H., Altman A. EMBO J. 23:1112-1122(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF STK39/SPAK.
[13]	"Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1 at Ser(1101)." Li Y., Soos T.J., Li X., Wu J., Degennaro M., Sun X., Littman D.R., Birnbaum M.J., Polakiewicz R.D. J. Biol. Chem. 279:45304-45307(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF IRS1.
[14]	"Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity." Liu X.F., Ishida H., Raziuddin R., Miki T. Mol. Cell. Biol. 24:6665-6675(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ECT2.
[15]	"Critical role of novel Thr-219 autophosphorylation for the cellular function of PKCtheta in T lymphocytes." Thuille N., Heit I., Fresser F., Krumbock N., Bauer B., Leuthaeusser S., Dammeier S., Graham C., Copeland T.D., Shaw S., Baier G. EMBO J. 24:3869-3880(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT THR-219; THR-538; SER-676 AND SER-695, MUTAGENESIS OF THR-219; THR-538; SER-676 AND SER-695.
[16]	"Phosphorylation of the CARMA1 linker controls NF-kappaB activation." Sommer K., Guo B., Pomerantz J.L., Bandaranayake A.D., Moreno-Garcia M.E., Ovechkina Y.L., Rawlings D.J. Immunity 23:561-574(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CARD11, SUBUNIT.
[17]	"Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by up-regulating Bcl-xL." Manicassamy S., Gupta S., Huang Z., Sun Z. J. Immunol. 176:6709-6716(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF BCL-X(L)/BCL2L1.
[18]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-348; SER-685 AND SER-695, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-676 AND SER-695, MASS SPECTROMETRY.
[20]	"PKC-theta modulates the strength of T cell responses by targeting Cbl-b for ubiquitination and degradation." Gruber T., Hermann-Kleiter N., Hinterleitner R., Fresser F., Schneider R., Gastl G., Penninger J.M., Baier G. Sci. Signal. 2:RA30-RA30(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CBLB.
[21]	"Protein kinase C(theta) in T cell activation." Isakov N., Altman A. Annu. Rev. Immunol. 20:761-794(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[22]	"Protein kinase C-theta (PKC theta): a key enzyme in T cell life and death." Altman A., Villalba M. J. Biochem. 132:841-846(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[23]	"Protein kinase C and beyond." Spitaler M., Cantrell D.A. Nat. Immunol. 5:785-790(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[24]	"Selective function of PKC-theta in T cells." Manicassamy S., Gupta S., Sun Z. Cell. Mol. Immunol. 3:263-270(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[25]	"Protein kinase C theta (PKCtheta): a key player in T cell life and death." Hayashi K., Altman A. Pharmacol. Res. 55:537-544(2007) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[26]	"T-cell fate and function: PKC-theta and beyond." Marsland B.J., Kopf M. Trends Immunol. 29:179-185(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[27]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-685, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[28]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"Protein kinase C-theta in platelet activation." Cohen S., Braiman A., Shubinsky G., Isakov N. FEBS Lett. 585:3208-3215(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN PLATELET ACTIVATION.
[30]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-685 AND SER-695, MASS SPECTROMETRY.
[31]	"Catalytic domain crystal structure of protein kinase C-theta (PKCtheta)." Xu Z.B., Chaudhary D., Olland S., Wolfrom S., Czerwinski R., Malakian K., Lin L., Stahl M.L., Joseph-McCarthy D., Benander C., Fitz L., Greco R., Somers W.S., Mosyak L. J. Biol. Chem. 279:50401-50409(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 362-706, PHOSPHORYLATION AT THR-538 AND SER-695.
[32]	"The crystal structure of the kinase domain of the protein kinase C theta in complex with Nvp-Xaa228." Stark W., Bitsch F., Berner A., Buelens F., Graff P., Depersin H., Fendrich G., Geiser M., Knecht R., Rahuel J., Rummel G., Schlaeppi J.M., Schmitz R., Strauss A., Wagner J. Submitted (JAN-2007) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS) OF 361-706, PHOSPHORYLATION AT SER-676 AND SER-695.
[33]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-240; VAL-306; LEU-330 AND ASN-354.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L01087 mRNA. Translation: AAA75571.1.
L07032 mRNA. Translation: AAA60101.1.
AY702977 mRNA. Translation: AAU29340.1.
AL158043 Genomic DNA. Translation: CAC12904.2.
AL137145 Genomic DNA. Translation: CAC10200.2.
BC101465 mRNA. Translation: AAI01466.1.
BC113359 mRNA. Translation: AAI13360.1.

IPI

IPI00029196.
IPI00470691.

PIR

A45416.

RefSeq

NP_001229342.1. NM_001242413.1.
NP_006248.1. NM_006257.3.

UniGene

Hs.498570.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XJD	X-ray	2.00	A	362-706	[»]
2ENJ	NMR	-	A	1-126	[»]
2ENN	NMR	-	A	144-213	[»]
2ENZ	NMR	-	A	227-284	[»]
2JED	X-ray	2.32	A/B	361-706	[»]

ProteinModelPortal

Q04759.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q04759. 14 interactions.

MINT

MINT-4649766.

STRING

9606.ENSP00000263125.

PTM databases

PhosphoSite

Q04759.

Polymorphism databases

DMDM

20141582.

Proteomic databases

PaxDb

Q04759.

PRIDE

Q04759.

Protocols and materials databases

DNASU

5588.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263125; ENSP00000263125; ENSG00000065675.
ENST00000397176; ENSP00000380361; ENSG00000065675.

GeneID

5588.

KEGG

hsa:5588.

UCSC

uc001iji.1. human.
uc009xim.2. human.

Organism-specific databases

CTD

5588.

GeneCards

GC10M006509.

HGNC

HGNC:9410. PRKCQ.

MIM

600448. gene.

neXtProt

NX_Q04759.

PharmGKB

PA33773.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233022.

HOVERGEN

HBG108317.

InParanoid

Q04759.

KO

K06068.

OMA

REPQGIS.

OrthoDB

EOG4J9MZ9.

PhylomeDB

Q04759.

Enzyme and pathway databases

BRENDA

2.7.11.13. 2681.

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
endothelinpathway. Endothelins.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_578. Apoptosis.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q04759.

Bgee

Q04759.

CleanEx

HS_PRKCQ.

Genevestigator

Q04759.

GermOnline

ENSG00000065675. Homo sapiens.

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

BindingDB

Q04759.

ChEMBL

CHEMBL3920.

ChiTaRS

PRKCQ. human.

EvolutionaryTrace

Q04759.

GenomeRNAi

5588.

NextBio

21674.

PMAP-CutDB

Q04759.

SOURCE

Search...

Entry information

Entry name

KPCT_HUMAN

Accession

Primary (citable) accession number: Q04759
Secondary accession number(s): Q14DH6 , Q3MJF1, Q64FY5, Q9H508, Q9H549

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	March 27, 2002
Last modified:	May 1, 2013
This is version 153 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.