Protein kinase C theta type

Details

Name
Protein kinase C theta type
Kind
protein
Synonyms
  • 2.7.11.13
  • nPKC-theta
  • PRKCT
Gene Name
PRKCQ
UniProtKB Entry
Q04759Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0002749|Protein kinase C theta type
MSPFLRIGLSNFDCGSCQSCQGEAVNPYCAVLVKEYVESENGQMYIQKKPTMYPPWDSTF
DAHINKGRVMQIIVKGKNVDLISETTVELYSLAERCRKNNGKTEIWLELKPQGRMLMNAR
YFLEMSDTKDMNEFETEGFFALHQRRGAIKQAKVHHVKCHEFTATFFPQPTFCSVCHEFV
WGLNKQGYQCRQCNAAIHKKCIDKVIAKCTGSAINSRETMFHKERFKIDMPHRFKVYNYK
SPTFCEHCGTLLWGLARQGLKCDACGMNVHHRCQTKVANLCGINQKLMAEALAMIESTQQ
ARCLRDTEQIFREGPVEIGLPCSIKNEARPPCLPTPGKREPQGISWESPLDEVDKMCHLP
EPELNKERPSLQIKLKIEDFILHKMLGKGSFGKVFLAEFKKTNQFFAIKALKKDVVLMDD
DVECTMVEKRVLSLAWEHPFLTHMFCTFQTKENLFFVMEYLNGGDLMYHIQSCHKFDLSR
ATFYAAEIILGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENMLGDAKTNTFC
GTPDYIAPEILLGQKYNHSVDWWSFGVLLYEMLIGQSPFHGQDEEELFHSIRMDNPFYPR
WLEKEAKDLLVKLFVREPEKRLGVRGDIRQHPLFREINWEELERKEIDPPFRPKVKSPFD
CSNFDKEFLNEKPRLSFADRALINSMDQNMFRNFSFMNPGMERLIS
Number of residues
706
Molecular Weight
81864.145
Theoretical pI
7.64
GO Classification
Functions
diacylglycerol-dependent serine/threonine kinase activity / protein kinase activity / protein serine kinase activity
Processes
CD4-positive, alpha-beta T cell proliferation / positive regulation of CD4-positive, alpha-beta T cell proliferation / positive regulation of interleukin-2 production / protein phosphorylation / regulation of DNA-templated transcription
Components
aggresome / centriolar satellite
General 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 in the calcium-dependent NFATC1 and NFATC2 transactivation (PubMed:21964608). 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. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity (PubMed:23509302). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231)
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0019109|Protein kinase C theta type (PRKCQ)
ATGTCGCCATTTCTTCGGATTGGCTTGTCCAACTTTGACTGCGGGTCCTGCCAGTCTTGT
CAGGGCGAGGCTGTTAACCCTTACTGTGCTGTGCTCGTCAAAGAGTATGTCGAATCAGAG
AACGGGCAGATGTATATCCAGAAAAAGCCTACCATGTACCCACCCTGGGACAGCACTTTT
GATGCCCATATCAACAAGGGAAGAGTCATGCAGATCATTGTGAAAGGCAAAAACGTGGAC
CTCATCTCTGAAACCACCGTGGAGCTCTACTCGCTGGCTGAGAGGTGCAGGAAGAACAAC
GGGAAGACAGAAATATGGTTAGAGCTGAAACCTCAAGGCCGAATGCTAATGAATGCAAGA
TACTTTCTGGAAATGAGTGACACAAAGGACATGAATGAATTTGAGACGGAAGGCTTCTTT
GCTTTGCATCAGCGCCGGGGTGCCATCAAGCAGGCAAAGGTCCACCACGTCAAGTGCCAC
GAGTTCACTGCCACCTTCTTCCCACAGCCCACATTTTGCTCTGTCTGCCACGAGTTTGTC
TGGGGCCTGAACAAACAGGGCTACCAGTGCCGACAATGCAATGCAGCAATTCACAAGAAG
TGTATTGATAAAGTTATAGCAAAGTGCACAGGATCAGCTATCAATAGCCGAGAAACCATG
TTCCACAAGGAGAGATTCAAAATTGACATGCCACACAGATTTAAAGTCTACAATTACAAG
AGCCCGACCTTCTGTGAACACTGTGGGACCCTGCTGTGGGGACTGGCACGGCAAGGACTC
AAGTGTGATGCATGTGGCATGAATGTGCATCATAGATGCCAGACAAAGGTGGCCAACCTT
TGTGGCATAAACCAGAAGCTAATGGCTGAAGCGCTGGCCATGATTGAGAGCACTCAACAG
GCTCGCTGCTTAAGAGATACTGAACAGATCTTCAGAGAAGGTCCGGTTGAAATTGGTCTC
CCATGCTCCATCAAAAATGAAGCAAGGCCGCCATGTTTACCGACACCGGGAAAAAGAGAG
CCTCAGGGCATTTCCTGGGAGTCTCCGTTGGATGAGGTGGATAAAATGTGCCATCTTCCA
GAACCTGAACTGAACAAAGAAAGACCATCTCTGCAGATTAAACTAAAAATTGAGGATTTT
ATCTTGCACAAAATGTTGGGGAAAGGAAGTTTTGGCAAGGTCTTCCTGGCAGAATTCAAG
AAAACCAATCAATTTTTCGCAATAAAGGCCTTAAAGAAAGATGTGGTCTTGATGGACGAT
GATGTTGAGTGCACGATGGTAGAGAAGAGAGTTCTTTCCTTGGCCTGGGAGCATCCGTTT
CTGACGCACATGTTTTGTACATTCCAGACCAAGGAAAACCTCTTTTTTGTGATGGAGTAC
CTCAACGGAGGGGACTTAATGTACCACATCCAAAGCTGCCACAAGTTCGACCTTTCCAGA
GCGACGTTTTATGCTGCTGAAATCATTCTTGGTCTGCAGTTCCTTCATTCCAAAGGAATA
GTCTACAGGGACCTGAAGCTAGATAACATCCTGTTAGACAAAGATGGACATATCAAGATC
GCGGATTTTGGAATGTGCAAGGAGAACATGTTAGGAGATGCCAAGACGAATACCTTCTGT
GGGACACCTGACTACATCGCCCCAGAGCTCTTCGTGCGAGAACCTGAGAAGAGGCTGGGC
GTGAGGGGAGACATCCGCCAGCACCCTTTGTTTCGGGAGATCAACTGGGAGGAACTTGAA
CGGAAGGAGATTGACCCACCGTTCCGGCCGAAAGTGAAATCACCATTTGACTGCAGCAAT
TTCGACAAAGAATTCTTAAACGAGAAGCCCCGGCTGTCATTTGCCGACAGAGCACTGATC
AACAGCATGGACCAGAATATGTTCAGGAACTTTTCCTTCATGAACCCCGGGATGGAGCGG
CTGATATCCTGA
Chromosome Location
10
Locus
10p15.1
External Identifiers
ResourceLink
UniProtKB IDQ04759
UniProtKB Entry NameKPCT_HUMAN
GenBank Protein ID558099
GenBank Gene IDL01087
GeneCard IDPRKCQ
GenAtlas IDPRKCQ
HGNC IDHGNC:9410
PDB ID(s)1XJD, 2ENJ, 2ENN, 2ENZ, 2JED, 4Q9Z, 4RA5, 5F9E
KEGG IDhsa:5588
IUPHAR/Guide To Pharmacology ID1488
NCBI Gene ID5588
General References
  1. Chang JD, Xu Y, Raychowdhury MK, Ware JA: 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. J Biol Chem. 1993 Jul 5;268(19):14208-14. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
StaurosporineexperimentalunknowntargetDetails
PhosphonothreonineexperimentalyestargetinhibitorDetails
DexfosfoserineexperimentalyestargetinhibitorDetails
Fostamatinibapproved, investigationalunknowntargetinhibitorDetails
SotrastaurininvestigationalyestargetinhibitorDetails