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UniProtKB - Q04759 (KPCT_HUMAN)

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Protein

Protein kinase C theta type

Gene

PRKCQ

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 in 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/AKT1.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+

Enzyme 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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei409ATP1
Active sitei504Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri159 – 209Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri231 – 281Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi386 – 394ATPPROSITE-ProRule annotation9

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processImmunity, Inflammatory response
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13 2681
ReactomeiR-HSA-111465 Apoptotic cleavage of cellular proteins
R-HSA-114508 Effects of PIP2 hydrolysis
R-HSA-202424 Downstream TCR signaling
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-373752 Netrin-1 signaling
R-HSA-418597 G alpha (z) signalling events
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
SABIO-RKiQ04759
SignaLinkiQ04759
SIGNORiQ04759

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C theta type (EC:2.7.11.13)
Alternative name(s):
nPKC-theta
Gene namesi
Name:PRKCQ
Synonyms:PRKCT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000065675.14
HGNCiHGNC:9410 PRKCQ
MIMi600448 gene
neXtProtiNX_Q04759

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi90Y → F: Loss of function in T-cells proliferation. No effect on kinase activity. 1 Publication1
Mutagenesisi148A → E: Constitutively active form. 1 Publication1
Mutagenesisi219T → A: Loss of transactivation of the IL2 promoter and translocation to the plasma membrane. No effect on kinase activity. 1 Publication1
Mutagenesisi409K → A or E: Loss of kinase activity. 1 Publication1
Mutagenesisi538T → A: Loss of kinase activity. 2 Publications1
Mutagenesisi676S → A: Reduction in kinase activity. 1 Publication1
Mutagenesisi695S → A: Reduction in kinase activity. 2 Publications1

Organism-specific databases

DisGeNETi5588
OpenTargetsiENSG00000065675
PharmGKBiPA33773

Chemistry databases

ChEMBLiCHEMBL3920
DrugBankiDB04522 Phosphonoserine
DB02482 Phosphonothreonine
DB02010 Staurosporine
DB00675 Tamoxifen
GuidetoPHARMACOLOGYi1488

Polymorphism and mutation databases

BioMutaiPRKCQ
DMDMi20141582

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557081 – 706Protein kinase C theta typeAdd BLAST706

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei90Phosphotyrosine; by LCK1 Publication1
Modified residuei219Phosphothreonine; by autocatalysis1 Publication1
Modified residuei348PhosphoserineCombined sources1
Modified residuei538Phosphothreonine; by PDPK13 Publications1
Modified residuei676PhosphoserineCombined sources3 Publications1
Modified residuei685PhosphoserineCombined sources1
Modified residuei695PhosphoserineCombined sources4 Publications1

Post-translational modificationi

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-685.5 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ04759
MaxQBiQ04759
PaxDbiQ04759
PeptideAtlasiQ04759
PRIDEiQ04759
ProteomicsDBi58279
58280 [Q04759-2]

PTM databases

CarbonylDBiQ04759
iPTMnetiQ04759
PhosphoSitePlusiQ04759

Miscellaneous databases

PMAP-CutDBiQ04759

Expressioni

Tissue specificityi

Expressed in skeletal muscle, T-cells, megakaryoblastic cells and platelets.1 Publication

Gene expression databases

BgeeiENSG00000065675
CleanExiHS_PRKCQ
ExpressionAtlasiQ04759 baseline and differential
GenevisibleiQ04759 HS

Organism-specific databases

HPAiHPA065279
HPA073098

Interactioni

Subunit structurei

Interacts with GLRX3 (via N-terminus). Interacts with ECT2. Part of a lipid raft complex composed at least of BCL10, CARD11, MALT1 and IKBKB.3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111574, 31 interactors
IntActiQ04759, 19 interactors
MINTiQ04759
STRINGi9606.ENSP00000263125

Chemistry databases

BindingDBiQ04759

Structurei

Secondary structure

1706
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 13Combined sources9
Beta strandi28 – 39Combined sources12
Beta strandi42 – 52Combined sources11
Beta strandi56 – 62Combined sources7
Beta strandi69 – 75Combined sources7
Beta strandi83 – 89Combined sources7
Helixi90 – 98Combined sources9
Turni99 – 101Combined sources3
Beta strandi103 – 108Combined sources6
Beta strandi110 – 112Combined sources3
Beta strandi114 – 121Combined sources8
Beta strandi155 – 159Combined sources5
Beta strandi161 – 165Combined sources5
Beta strandi174 – 176Combined sources3
Beta strandi187 – 189Combined sources3
Beta strandi191 – 193Combined sources3
Beta strandi196 – 199Combined sources4
Helixi200 – 202Combined sources3
Beta strandi234 – 236Combined sources3
Beta strandi246 – 248Combined sources3
Beta strandi255 – 257Combined sources3
Beta strandi259 – 265Combined sources7
Turni271 – 276Combined sources6
Turni281 – 283Combined sources3
Helixi377 – 379Combined sources3
Beta strandi380 – 388Combined sources9
Beta strandi390 – 399Combined sources10
Turni400 – 402Combined sources3
Beta strandi405 – 412Combined sources8
Helixi413 – 418Combined sources6
Helixi422 – 435Combined sources14
Beta strandi444 – 449Combined sources6
Beta strandi451 – 459Combined sources9
Beta strandi463 – 465Combined sources3
Helixi466 – 473Combined sources8
Helixi478 – 497Combined sources20
Helixi507 – 509Combined sources3
Beta strandi510 – 512Combined sources3
Beta strandi518 – 520Combined sources3
Helixi543 – 545Combined sources3
Helixi548 – 551Combined sources4
Helixi559 – 574Combined sources16
Helixi584 – 593Combined sources10
Helixi604 – 613Combined sources10
Helixi618 – 620Combined sources3
Helixi628 – 630Combined sources3
Helixi632 – 634Combined sources3
Helixi639 – 643Combined sources5
Helixi666 – 669Combined sources4
Helixi680 – 685Combined sources6
Turni690 – 693Combined sources4
Helixi699 – 706Combined sources8

3D structure databases

ProteinModelPortaliQ04759
SMRiQ04759
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04759

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 123C2Add BLAST116
Domaini380 – 634Protein kinasePROSITE-ProRule annotationAdd BLAST255
Domaini635 – 706AGC-kinase C-terminalAdd BLAST72

Domaini

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.

Sequence similaritiesi

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri159 – 209Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri231 – 281Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0694 Eukaryota
ENOG410XNPH LUCA
GeneTreeiENSGT00920000148938
HOGENOMiHOG000233022
HOVERGENiHBG108317
InParanoidiQ04759
KOiK18052
OMAiEPQGISW
OrthoDBiEOG091G0QRS
PhylomeDBiQ04759
TreeFamiTF102004

Family and domain databases

CDDicd00029 C1, 2 hits
cd05619 STKc_nPKC_theta, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00130 C1_1, 2 hits
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000551 PKC_delta, 1 hit
PIRSF501105 Protein_kin_C_theta, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 2 hits
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView 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, 2 hits
PS50081 ZF_DAG_PE_2, 2 hits

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q04759-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSPFLRIGLS NFDCGSCQSC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP 
        60         70         80         90        100
TMYPPWDSTF DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN 
       110        120        130        140        150
GKTEIWLELK PQGRMLMNAR YFLEMSDTKD MNEFETEGFF 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
ARCLRDTEQI FREGPVEIGL PCSIKNEARP PCLPTPGKRE PQGISWESPL 
       360        370        380        390        400
DEVDKMCHLP EPELNKERPS LQIKLKIEDF ILHKMLGKGS FGKVFLAEFK 
       410        420        430        440        450
KTNQFFAIKA LKKDVVLMDD DVECTMVEKR VLSLAWEHPF LTHMFCTFQT 
       460        470        480        490        500
KENLFFVMEY LNGGDLMYHI QSCHKFDLSR ATFYAAEIIL GLQFLHSKGI 
       510        520        530        540        550
VYRDLKLDNI LLDKDGHIKI ADFGMCKENM LGDAKTNTFC GTPDYIAPEI 
       560        570        580        590        600
LLGQKYNHSV DWWSFGVLLY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR 
       610        620        630        640        650
WLEKEAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP 
       660        670        680        690        700
FRPKVKSPFD CSNFDKEFLN EKPRLSFADR ALINSMDQNM FRNFSFMNPG 

MERLIS
Length:706
Mass (Da):81,865
Last modified:March 27, 2002 - v3
Checksum:iB3C53AB892D5210A
GO
Isoform 2 (identifier: Q04759-2) [UniParc]FASTAAdd to basket

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

Show »
Length:643
Mass (Da):74,287
Checksum:iA3B688EBE8809B9E
GO
Isoform 3 (identifier: Q04759-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     2-126: Missing.

Note: No experimental confirmation available.
Show »
Length:581
Mass (Da):67,560
Checksum:iABB524BD5B3E2898
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti700G → R in AAA75571 (PubMed:7686153).Curated1
Sequence conflicti700G → R in AAU29340 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042319240K → N in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042320306D → V1 PublicationCorresponds to variant dbSNP:rs45590231Ensembl.1
Natural variantiVAR_020401330P → L3 PublicationsCorresponds to variant dbSNP:rs2236379Ensembl.1
Natural variantiVAR_042321354D → N1 PublicationCorresponds to variant dbSNP:rs34524148Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0545502 – 126Missing in isoform 3. 1 PublicationAdd BLAST125
Alternative sequenceiVSP_017294550 – 612Missing in isoform 2. 1 PublicationAdd BLAST63

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L01087 mRNA Translation: AAA75571.1
L07032 mRNA Translation: AAA60101.1
AY702977 mRNA Translation: AAU29340.1
AK293935 mRNA Translation: BAG57313.1
AL158043 Genomic DNA No translation available.
AL137145 Genomic DNA No translation available.
BC101465 mRNA Translation: AAI01466.1
BC113359 mRNA Translation: AAI13360.1
CCDSiCCDS55701.1 [Q04759-2]
CCDS60482.1 [Q04759-3]
CCDS7079.1 [Q04759-1]
PIRiA45416
RefSeqiNP_001229342.1, NM_001242413.2 [Q04759-2]
NP_001269573.1, NM_001282644.1
NP_001269574.1, NM_001282645.1 [Q04759-3]
NP_001310194.1, NM_001323265.1 [Q04759-1]
NP_001310195.1, NM_001323266.1 [Q04759-3]
NP_006248.1, NM_006257.4 [Q04759-1]
XP_006717528.1, XM_006717465.3 [Q04759-1]
XP_016871899.1, XM_017016410.1 [Q04759-1]
XP_016871900.1, XM_017016411.1 [Q04759-3]
UniGeneiHs.498570

Genome annotation databases

EnsembliENST00000263125; ENSP00000263125; ENSG00000065675 [Q04759-1]
ENST00000397176; ENSP00000380361; ENSG00000065675 [Q04759-2]
ENST00000539722; ENSP00000441752; ENSG00000065675 [Q04759-3]
GeneIDi5588
KEGGihsa:5588
UCSCiuc001ijj.3 human [Q04759-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKPCT_HUMAN
AccessioniPrimary (citable) accession number: Q04759
Secondary accession number(s): B4DF52
, Q14DH6, Q3MJF1, Q64FY5, Q9H508, Q9H549
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: March 27, 2002
Last modified: June 20, 2018
This is version 205 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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