Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q04759 (KPCT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 166. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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:PRKCT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length706 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.8 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17 Ref.18 Ref.21

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.9 Ref.15 Ref.17

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.10 Ref.12 Ref.16 Ref.32 Ref.33

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
   Coding sequence diversityAlternative splicing
Polymorphism
   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_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Traceable author statement. Source: Reactome

axon guidance

Traceable author statement. Source: Reactome

blood coagulation

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

innate immune response

Traceable author statement. Source: Reactome

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.11Ref.18. Source: UniProtKB

negative regulation of insulin receptor signaling pathway

Inferred from mutant phenotype Ref.14. Source: UniProtKB

phototransduction, visible light

Traceable author statement. Source: Reactome

platelet activation

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.17. Source: UniProtKB

positive regulation of T cell activation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

positive regulation of interleukin-4 production

Inferred from sequence or structural similarity. Source: UniProtKB

protein ubiquitination

Traceable author statement. Source: GOC

regulation of cell growth

Non-traceable author statement Ref.3. Source: UniProtKB

regulation of platelet aggregation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of rhodopsin mediated signaling pathway

Traceable author statement. Source: Reactome

regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

rhodopsin mediated signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

immunological synapse

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   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 Ref.15. Source: UniProtKB

protein kinase C activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein serine/threonine kinase activity

Non-traceable author statement Ref.3. Source: UniProtKB

ubiquitin-protein transferase activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Alternative products

This entry describes 3 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.
Isoform 3 (identifier: Q04759-3)

The sequence of this isoform differs from the canonical sequence as follows:
     2-126: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 706706Protein kinase C theta type
PRO_0000055708

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

Amino acid modifications

Modified residue901Phosphotyrosine; by LCK Ref.10
Modified residue2191Phosphothreonine; by autocatalysis Ref.16
Modified residue3481Phosphoserine Ref.19
Modified residue5381Phosphothreonine; by PDPK1 Probable
Modified residue6761Phosphoserine Ref.12 Ref.16 Ref.20 Ref.33
Modified residue6851Phosphoserine Ref.19 Ref.28 Ref.31
Modified residue6951Phosphoserine Ref.12 Ref.16 Ref.19 Ref.20 Ref.31 Ref.32 Ref.33

Natural variations

Alternative sequence2 – 126125Missing in isoform 3.
VSP_054550
Alternative sequence550 – 61263Missing in isoform 2.
VSP_017294
Natural variant2401K → N in a colorectal adenocarcinoma sample; somatic mutation. Ref.34
VAR_042319
Natural variant3061D → V. Ref.34
Corresponds to variant rs45590231 [ dbSNP | Ensembl ].
VAR_042320
Natural variant3301P → L. Ref.1 Ref.4 Ref.34
Corresponds to variant rs2236379 [ dbSNP | Ensembl ].
VAR_020401
Natural variant3541D → N. Ref.34
Corresponds to variant rs34524148 [ dbSNP | Ensembl ].
VAR_042321

Experimental info

Mutagenesis901Y → F: Loss of function in T-cells proliferation. No effect on kinase activity. Ref.10
Mutagenesis1481A → E: Constitutively active form. Ref.10
Mutagenesis2191T → A: Loss of transactivation of the IL2 promoter and translocation to the plasma membrane. No effect on kinase activity. Ref.16
Mutagenesis4091K → A or E: Loss of kinase activity. Ref.10
Mutagenesis5381T → A: Loss of kinase activity. Ref.12 Ref.16
Mutagenesis6761S → A: Reduction in kinase activity. Ref.16
Mutagenesis6951S → A: Reduction in kinase activity. Ref.12 Ref.16
Sequence conflict7001G → R in AAA75571. Ref.1
Sequence conflict7001G → R in AAU29340. Ref.4

Secondary structure

.............................................................................................. 706
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 27, 2002. Version 3.
Checksum: B3C53AB892D5210A

FASTA70681,865
        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 

« Hide

Isoform 2 [UniParc].

Checksum: A3B688EBE8809B9E
Show »

FASTA64374,287
Isoform 3 [UniParc].

Checksum: ABB524BD5B3E2898
Show »

FASTA58167,560

References

« Hide '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]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Cerebellum.
[6]"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. expand/collapse author list , 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].
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]"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.
[18]"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.
[19]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"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.
[22]"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.
[23]"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.
[24]"Protein kinase C and beyond."
Spitaler M., Cantrell D.A.
Nat. Immunol. 5:785-790(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[25]"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.
[26]"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.
[27]"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.
[28]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[29]"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].
[30]"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.
[31]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[32]"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.
[33]"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.
[34]"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. expand/collapse author list , 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.
AK293935 mRNA. Translation: BAG57313.1.
AL158043 Genomic DNA. Translation: CAC12904.2.
AL137145 Genomic DNA. Translation: CAC10200.2.
BC101465 mRNA. Translation: AAI01466.1.
BC113359 mRNA. Translation: AAI13360.1.
CCDSCCDS55701.1. [Q04759-2]
CCDS7079.1. [Q04759-1]
PIRA45416.
RefSeqNP_001229342.1. NM_001242413.2. [Q04759-2]
NP_001269573.1. NM_001282644.1.
NP_001269574.1. NM_001282645.1. [Q04759-3]
NP_006248.1. NM_006257.4. [Q04759-1]
XP_006717528.1. XM_006717465.1. [Q04759-1]
UniGeneHs.498570.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1XJDX-ray2.00A362-706[»]
2ENJNMR-A1-125[»]
2ENNNMR-A144-213[»]
2ENZNMR-A227-284[»]
2JEDX-ray2.32A/B361-706[»]
ProteinModelPortalQ04759.
SMRQ04759. Positions 3-126, 144-281, 375-700.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111574. 27 interactions.
IntActQ04759. 17 interactions.
MINTMINT-4649766.
STRING9606.ENSP00000263125.

Chemistry

BindingDBQ04759.
ChEMBLCHEMBL2096620.
GuidetoPHARMACOLOGY1488.

PTM databases

PhosphoSiteQ04759.

Polymorphism databases

DMDM20141582.

Proteomic databases

MaxQBQ04759.
PaxDbQ04759.
PRIDEQ04759.

Protocols and materials databases

DNASU5588.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263125; ENSP00000263125; ENSG00000065675. [Q04759-1]
ENST00000397176; ENSP00000380361; ENSG00000065675. [Q04759-2]
ENST00000539722; ENSP00000441752; ENSG00000065675.
GeneID5588.
KEGGhsa:5588.
UCSCuc001iji.1. human. [Q04759-1]
uc009xim.2. human. [Q04759-2]

Organism-specific databases

CTD5588.
GeneCardsGC10M006509.
HGNCHGNC:9410. PRKCQ.
MIM600448. gene.
neXtProtNX_Q04759.
PharmGKBPA33773.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233022.
HOVERGENHBG108317.
InParanoidQ04759.
KOK18052.
OMAREPQGIS.
OrthoDBEOG77M8QM.
PhylomeDBQ04759.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.13. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_578. Apoptosis.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkQ04759.

Gene expression databases

ArrayExpressQ04759.
BgeeQ04759.
CleanExHS_PRKCQ.
GenevestigatorQ04759.

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

ChiTaRSPRKCQ. human.
EvolutionaryTraceQ04759.
GeneWikiPRKCQ.
GenomeRNAi5588.
NextBio21674.
PMAP-CutDBQ04759.
PROQ04759.
SOURCESearch...

Entry information

Entry nameKPCT_HUMAN
AccessionPrimary (citable) accession number: Q04759
Secondary accession number(s): B4DF52 expand/collapse secondary AC list , Q14DH6, Q3MJF1, Q64FY5, Q9H508, Q9H549
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: March 27, 2002
Last modified: July 9, 2014
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

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

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM