Q9WTQ0 (KPCT_RAT) 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

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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 By similarity. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1 By similarity. Ref.3
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. Ref.4
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.
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.3
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	aging Inferred from expression pattern. Source: RGD intracellular signal transduction Inferred from direct assay. Source: RGD neuron differentiation Inferred from expression pattern. Source: RGD positive regulation of NF-kappaB import into nucleus Inferred from mutant phenotype. Source: RGD positive regulation of filopodium assembly Inferred from mutant phenotype. Source: RGD positive regulation of protein secretion Inferred from direct assay. Source: RGD positive regulation of stress fiber assembly Inferred from mutant phenotype. Source: RGD regulation of G2/M transition of mitotic cell cycle Inferred from mutant phenotype. Source: RGD regulation of vasoconstriction Inferred from expression pattern. Source: RGD respiratory burst Inferred from expression pattern. Source: RGD response to glucose stimulus Inferred from expression pattern. Source: RGD response to heat Inferred from expression pattern. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD response to insulin stimulus Inferred from expression pattern. Source: RGD response to organic cyclic compound Inferred from expression pattern. Source: RGD tissue regeneration Inferred from expression pattern. Source: RGD
Cellular component	cytoplasm Inferred from direct assay. Source: RGD membrane fraction Inferred from direct assay. Source: RGD neuromuscular junction Inferred from direct assay. Source: RGD nucleus Inferred from direct assay. Source: RGD sarcolemma Inferred from direct assay. Source: RGD soluble fraction Inferred from direct assay. Source: RGD
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: RGD protein kinase C activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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_0000270836
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	384	1	N6-acetyllysine By similarity
	Modified residue	536	1	Phosphothreonine By similarity
	Modified residue	538	1	Phosphothreonine; by PDPK1 By similarity
	Modified residue	657	1	Phosphoserine 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

Sequences

	Sequence		Length	Mass (Da)
	Q9WTQ0 [UniParc]. Last modified January 9, 2007. Version 2. Checksum: 7F82E35DE0C09DB9	FASTA	707	81,750
	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 ALHHRRGAIK QAKVHHVKCH EFTATFFPQP TFCSVCHEFV 190 200 210 220 230 240 WGLNKQGYQC RRCNAAIHKK CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK 250 260 270 280 290 300 SPTFCEHCGT LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ 310 320 330 340 350 360 ARTLRDSEHI FREGPIEISF PRSIKSETRP PCVPTPGKSE PQGICWESPL DGADKTAQPP 370 380 390 400 410 420 EPEVNLQRAS LQLKLKIDDF ILHKMLGKGS FGKVFLAEFK RTKQFFAIKA 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 DWWSFGVLLY 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

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed: 15057822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[2]	"Localization of mRNAs for novel, atypical as well as conventional protein kinase C (PKC) isoforms in the brain of developing and mature rats." Minami H., Owada Y., Suzuki R., Handa Y., Kondo H. J. Mol. Neurosci. 15:121-135(2000) [PubMed: 11220785] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 524-667. Strain: Wistar. Tissue: Brain.
[3]	"Protein kinase C-theta phosphorylation of moesin in the actin-binding sequence." Pietromonaco S.F., Simons P.C., Altman A., Elias L. J. Biol. Chem. 273:7594-7603(1998) [PubMed: 9516463] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MSN.
[4]	"PICOT, protein kinase C theta-interacting protein, is a novel regulator of FcepsilonRI-mediated mast cell activation." Kato N., Motohashi S., Okada T., Ozawa T., Mashima K. Cell. Immunol. 251:62-67(2008) [PubMed: 18479680] [Abstract] Cited for: INTERACTION WITH GLRX3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AABR03106275 Genomic DNA. No translation available. AABR03107517 Genomic DNA. No translation available. AABR03106934 Genomic DNA. No translation available. AABR03106283 Genomic DNA. No translation available. AABR03107733 Genomic DNA. No translation available. AABR03106804 Genomic DNA. No translation available. AABR03108584 Genomic DNA. No translation available. AABR03106764 Genomic DNA. No translation available. AB020614 mRNA. Translation: BAA78371.1.
IPI	IPI00364921.
UniGene	Rn.225125.
3D structure databases
HSSP	HSSP built from PDB template 1XJD based on UniProtKB Q04759.
ProteinModelPortal	Q9WTQ0.
SMR	Q9WTQ0. Positions 3-126, 144-213, 227-284, 375-700.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9WTQ0.
PTM databases
PhosphoSite	Q9WTQ0.
Proteomic databases
PRIDE	Q9WTQ0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
RGD	620968. Prkcq.
Phylogenomic databases
eggNOG	roNOG07577.
GeneTree	ENSGT00590000082973.
HOVERGEN	HBG108317.
InParanoid	Q9WTQ0.
OrthoDB	EOG4J9MZ9.
PhylomeDB	Q9WTQ0.
Gene expression databases
ArrayExpress	Q9WTQ0.
Genevestigator	Q9WTQ0.
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]
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...

Entry information

Entry name

KPCT_RAT

Accession

Primary (citable) accession number: Q9WTQ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 9, 2007
Last sequence update:	January 9, 2007
Last modified:	January 25, 2012
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program