UniProtKB - A6H667 (A6H667_MOUSE)
Protein
Protein kinase C theta type
Gene
Prkcq
Organism
Mus musculus (Mouse)
Status
Functioni
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.UniRule annotation
Catalytic activityi
- EC:2.7.11.13ARBA annotation
- ATP + L-threonyl-[protein] = ADP + H+ + O-phospho-L-threonyl-[protein]UniRule annotationARBA annotationEC:2.7.11.13UniRule annotationARBA annotation
Cofactori
Mg2+UniRule annotation
Activity regulationi
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.UniRule annotation
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 409 | ATPUniRule annotation | 1 | |
Active sitei | 504 | Proton acceptorUniRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 386 – 394 | ATPUniRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calcium-dependent protein kinase C activity Source: UniProtKB-EC
GO - Biological processi
- cell chemotaxis Source: Ensembl
- inflammatory response Source: UniProtKB-KW
- intracellular signal transduction Source: InterPro
- negative regulation of insulin receptor signaling pathway Source: Ensembl
- negative regulation of T cell apoptotic process Source: Ensembl
- positive regulation of NF-kappaB transcription factor activity Source: Ensembl
- positive regulation of telomerase activity Source: Ensembl
- positive regulation of telomere capping Source: Ensembl
- positive regulation of telomere maintenance via telomerase Source: Ensembl
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinaseUniRule annotationARBA annotation, Transferase |
Biological process | Inflammatory responseUniRule annotation |
Ligand | ATP-bindingUniRule annotationARBA annotation, MagnesiumUniRule annotation, Metal-binding, Nucleotide-binding, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: Protein kinase C theta typeUniRule annotation (EC:2.7.11.13UniRule annotation)Alternative name(s): nPKC-thetaUniRule annotation |
Gene namesi | Name:PrkcqImported |
Organismi | Mus musculus (Mouse)Imported |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Organism-specific databases
MGIi | MGI:97601, Prkcq |
Subcellular locationi
Plasma membrane
- Cell membrane UniRule annotation; Peripheral membrane protein UniRule annotation
Other locations
- Cytoplasm UniRule annotation
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.UniRule annotation
Cytoskeleton
- centriolar satellite Source: Ensembl
Plasma Membrane
- plasma membrane Source: UniProtKB-SubCell
Other locations
Keywords - Cellular componenti
Cell membraneUniRule annotation, CytoplasmUniRule annotationARBA annotation, MembranePTM / Processingi
Keywords - PTMi
PhosphoproteinARBA annotationProteomic databases
EPDi | A6H667 |
PeptideAtlasi | A6H667 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000026778, Expressed in habenula and 197 other tissues |
ExpressionAtlasi | A6H667, baseline and differential |
Interactioni
Subunit structurei
Interacts with GLRX3 (via N-terminus).
Interacts with ECT2.
UniRule annotationChemistry databases
BindingDBi | A6H667 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 159 – 209 | Phorbol-ester/DAG-typeInterPro annotationAdd BLAST | 51 | |
Domaini | 231 – 281 | Phorbol-ester/DAG-typeInterPro annotationAdd BLAST | 51 | |
Domaini | 380 – 634 | Protein kinaseInterPro annotationAdd BLAST | 255 | |
Domaini | 635 – 706 | AGC-kinase C-terminalInterPro annotationAdd BLAST | 72 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 327 – 365 | DisorderedSequence analysisAdd BLAST | 39 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.UniRule annotationARBA annotation
Keywords - Domaini
Zinc-fingerARBA annotationPhylogenomic databases
HOGENOMi | CLU_000288_54_4_1 |
OrthoDBi | 222529at2759 |
Family and domain databases
CDDi | cd00029, C1, 2 hits cd05619, STKc_nPKC_theta, 1 hit |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR035892, C2_domain_sf IPR020454, DAG/PE-bd IPR011009, Kinase-like_dom_sf IPR034668, nPKC_theta IPR002219, PE/DAG-bd IPR027264, PKC_theta IPR017892, Pkinase_C IPR014376, Prot_kin_PKC_delta IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00130, C1_1, 2 hits PF00069, Pkinase, 1 hit PF00433, Pkinase_C, 1 hit |
PIRSFi | PIRSF000551, PKC_delta, 1 hit PIRSF501105, Protein_kin_C_theta, 1 hit |
PRINTSi | PR00008, DAGPEDOMAIN |
SMARTi | View protein in SMART SM00109, C1, 2 hits SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51285, 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, 1 hit PS50081, ZF_DAG_PE_2, 2 hits |
i Sequence
Sequence statusi: Complete.
A6H667-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSPFLRIGLS NFDCGTCQAC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP
60 70 80 90 100
TMYPPWDSTF DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN
110 120 130 140 150
GRTEIWLELK PQGRMLMNAR YFLEMSDTKD MSEFENEGFF ALHQRRGAIK
160 170 180 190 200
QAKVHHVKCH EFTATFFPQP TFCSVCHEFV WGLNKQGYQC RQCNAAIHKK
210 220 230 240 250
CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK SPTFCEHCGT
260 270 280 290 300
LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ
310 320 330 340 350
ARSLRDSEHI FREGPVEIGL PCSTKNETRP PCVPTPGKRE PQGISWDSPL
360 370 380 390 400
DGSNKSAGPP EPEVSMRRTS LQLKLKIDDF ILHKMLGKGS FGKVFLAEFK
410 420 430 440 450
RTNQFFAIKA LKKDVVLMDD DVECTMVEKR VLSLAWEHPF LTHMFCTFQT
460 470 480 490 500
KENLFFVMEY LNGGDLMYHI QSCHKFDLSR ATFYAAEVIL GLQFLHSKGI
510 520 530 540 550
VYRDLKLDNI LLDRDGHIKI ADFGMCKENM LGDAKTNTFC GTPDYIAPEI
560 570 580 590 600
LLGQKYNHSV DWWSFGVLVY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR
610 620 630 640 650
WLEREAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP
660 670 680 690 700
FRPKVKSPYD CSNFDKEFLS EKPRLSFADR ALINSMDQNM FSNFSFINPG
METLICS
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC138552 mRNA Translation: AAI38553.1 BC145769 mRNA Translation: AAI45770.1 |
RefSeqi | NP_032885.1, NM_008859.2 |
Genome annotation databases
GeneIDi | 18761 |
KEGGi | mmu:18761 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC138552 mRNA Translation: AAI38553.1 BC145769 mRNA Translation: AAI45770.1 |
RefSeqi | NP_032885.1, NM_008859.2 |
3D structure databases
SMRi | A6H667 |
ModBasei | Search... |
Chemistry databases
BindingDBi | A6H667 |
Proteomic databases
EPDi | A6H667 |
PeptideAtlasi | A6H667 |
Protocols and materials databases
Antibodypediai | 10940, 802 antibodies |
Genome annotation databases
GeneIDi | 18761 |
KEGGi | mmu:18761 |
Organism-specific databases
CTDi | 5588 |
MGIi | MGI:97601, Prkcq |
Phylogenomic databases
HOGENOMi | CLU_000288_54_4_1 |
OrthoDBi | 222529at2759 |
Miscellaneous databases
BioGRID-ORCSi | 18761, 3 hits in 19 CRISPR screens |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000026778, Expressed in habenula and 197 other tissues |
ExpressionAtlasi | A6H667, baseline and differential |
Family and domain databases
CDDi | cd00029, C1, 2 hits cd05619, STKc_nPKC_theta, 1 hit |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View protein in InterPro IPR000961, AGC-kinase_C IPR035892, C2_domain_sf IPR020454, DAG/PE-bd IPR011009, Kinase-like_dom_sf IPR034668, nPKC_theta IPR002219, PE/DAG-bd IPR027264, PKC_theta IPR017892, Pkinase_C IPR014376, Prot_kin_PKC_delta IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00130, C1_1, 2 hits PF00069, Pkinase, 1 hit PF00433, Pkinase_C, 1 hit |
PIRSFi | PIRSF000551, PKC_delta, 1 hit PIRSF501105, Protein_kin_C_theta, 1 hit |
PRINTSi | PR00008, DAGPEDOMAIN |
SMARTi | View protein in SMART SM00109, C1, 2 hits SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS51285, 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, 1 hit PS50081, ZF_DAG_PE_2, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | A6H667_MOUSE | |
Accessioni | A6H667Primary (citable) accession number: A6H667 | |
Entry historyi | Integrated into UniProtKB/TrEMBL: | February 5, 2008 |
Last sequence update: | February 5, 2008 | |
Last modified: | December 2, 2020 | |
This is version 122 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Unreviewed (UniProtKB/TrEMBL) |