ID W5QJ13_SHEEP Unreviewed; 683 AA.
AC W5QJ13;
DT 16-APR-2014, integrated into UniProtKB/TrEMBL.
DT 16-APR-2014, sequence version 1.
DT 27-MAR-2024, entry version 65.
DE RecName: Full=Protein kinase C eta type {ECO:0000256|PIRNR:PIRNR000551};
DE EC=2.7.11.13 {ECO:0000256|PIRNR:PIRNR000551};
DE AltName: Full=PKC-L {ECO:0000256|PIRNR:PIRNR000551};
DE AltName: Full=nPKC-eta {ECO:0000256|PIRNR:PIRNR000551};
GN Name=PRKCH {ECO:0000313|Ensembl:ENSOARP00000022715.1};
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940 {ECO:0000313|Ensembl:ENSOARP00000022715.1, ECO:0000313|Proteomes:UP000002356};
RN [1] {ECO:0000313|Ensembl:ENSOARP00000022715.1, ECO:0000313|Proteomes:UP000002356}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Texel {ECO:0000313|Ensembl:ENSOARP00000022715.1,
RC ECO:0000313|Proteomes:UP000002356};
RX PubMed=20809919; DOI=10.1111/j.1365-2052.2010.02100.x;
RA Archibald A.L., Cockett N.E., Dalrymple B.P., Faraut T., Kijas J.W.,
RA Maddox J.F., McEwan J.C., Hutton Oddy V., Raadsma H.W., Wade C., Wang J.,
RA Wang W., Xun X.;
RT "The sheep genome reference sequence: a work in progress.";
RL Anim. Genet. 41:449-453(2010).
RN [2] {ECO:0000313|Ensembl:ENSOARP00000022715.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that is involved in the
CC regulation of cell differentiation in keratinocytes and pre-B cell
CC receptor, mediates regulation of epithelial tight junction integrity
CC and foam cell formation, and is required for glioblastoma proliferation
CC and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and
CC activates the tyrosine kinase FYN, which in turn blocks epidermal
CC growth factor receptor (EGFR) signaling and leads to keratinocyte
CC growth arrest and differentiation. Associates with the cyclin CCNE1-
CC CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1
CC dephosphorylation and thereby G1 arrest in keratinocytes. In
CC association with RALA activates actin depolymerization, which is
CC necessary for keratinocyte differentiation. In the pre-B cell receptor
CC signaling, functions downstream of BLNK by up-regulating IRF4, which in
CC turn activates L chain gene rearrangement. Regulates epithelial tight
CC junctions (TJs) by phosphorylating occludin (OCLN) on threonine
CC residues, which is necessary for the assembly and maintenance of TJs.
CC In association with PLD2 and via TLR4 signaling, is involved in
CC lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell
CC formation. Upon PMA stimulation, mediates glioblastoma cell
CC proliferation by activating the mTOR pathway, the PI3K/AKT pathway and
CC the ERK1-dependent phosphorylation of ELK1. Involved in the protection
CC of glioblastoma cells from irradiation-induced apoptosis by preventing
CC caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates
CC NF-kappa-B upstream signaling by activating IKBKB, and confers
CC protection against DNA damage-induced apoptosis.
CC {ECO:0000256|PIRNR:PIRNR000551}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC Evidence={ECO:0000256|ARBA:ARBA00000946};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13; Evidence={ECO:0000256|ARBA:ARBA00000569,
CC ECO:0000256|PIRNR:PIRNR000551};
CC -!- ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are
CC calcium-insensitive, but activated by diacylglycerol (DAG) and
CC phosphatidylserine. Three specific sites; Thr-513 (activation loop of
CC the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic
CC region), need to be phosphorylated for its full activation.
CC {ECO:0000256|PIRNR:PIRNR000551}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496,
CC ECO:0000256|PIRNR:PIRNR000551}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000256|ARBA:ARBA00005490,
CC ECO:0000256|PIRNR:PIRNR000551}.
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DR EMBL; AMGL01104088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AMGL01104089; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AMGL01104090; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_004010751.1; XM_004010702.3.
DR AlphaFoldDB; W5QJ13; -.
DR SMR; W5QJ13; -.
DR STRING; 9940.ENSOARP00000022715; -.
DR PaxDb; 9940-ENSOARP00000022715; -.
DR Ensembl; ENSOART00000023028.1; ENSOARP00000022715.1; ENSOARG00000021134.1.
DR eggNOG; KOG0694; Eukaryota.
DR HOGENOM; CLU_000288_54_4_1; -.
DR OMA; MTKNPNM; -.
DR OrthoDB; 841660at2759; -.
DR Proteomes; UP000002356; Chromosome 7.
DR Bgee; ENSOARG00000021134; Expressed in thymus and 51 other cell types or tissues.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0050861; P:positive regulation of B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IEA:Ensembl.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IEA:Ensembl.
DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IEA:Ensembl.
DR CDD; cd20835; C1_nPKC_epsilon-like_rpt1; 1.
DR CDD; cd20838; C1_nPKC_epsilon-like_rpt2; 1.
DR CDD; cd04014; C2_PKC_epsilon; 1.
DR CDD; cd05590; STKc_nPKC_eta; 1.
DR Gene3D; 3.30.60.20; -; 2.
DR Gene3D; 2.60.40.150; C2 domain; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR034665; nPKC_eta.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027431; PKC_eta.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR014376; Prot_kin_PKC_delta.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24351:SF198; PROTEIN KINASE C ETA TYPE; 1.
DR PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000551; PKC_delta; 2.
DR PIRSF; PIRSF501107; Protein_kin_C_eta; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR SUPFAM; SSF57889; Cysteine-rich domain; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 3: Inferred from homology;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRNR:PIRNR000551};
KW Cytoplasm {ECO:0000256|PIRNR:PIRNR000551};
KW Differentiation {ECO:0000256|PIRNR:PIRNR000551};
KW Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|PIRNR:PIRNR000551};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW ECO:0000256|PIRNR:PIRNR000551};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Reference proteome {ECO:0000313|Proteomes:UP000002356};
KW Serine/threonine-protein kinase {ECO:0000256|ARBA:ARBA00022527,
KW ECO:0000256|PIRNR:PIRNR000551};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000551};
KW Zinc {ECO:0000256|ARBA:ARBA00022833};
KW Zinc-finger {ECO:0000256|ARBA:ARBA00022771}.
FT DOMAIN 1..118
FT /note="C2"
FT /evidence="ECO:0000259|PROSITE:PS50004"
FT DOMAIN 171..222
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000259|PROSITE:PS50081"
FT DOMAIN 245..295
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000259|PROSITE:PS50081"
FT DOMAIN 355..614
FT /note="Protein kinase"
FT /evidence="ECO:0000259|PROSITE:PS50011"
FT DOMAIN 615..683
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51285"
FT ACT_SITE 479
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR000551-50"
FT BINDING 361..369
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000551-51"
FT BINDING 384
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000551-51,
FT ECO:0000256|PROSITE-ProRule:PRU10141"
SQ SEQUENCE 683 AA; 77835 MW; D7C4F930EAAA827E CRC64;
MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGYQL LDPYLTVSVD QVRVGQTSTK
QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN CTLQFQELLR TAGTSDTFEG
WVDLEPEGKV FVVITLTGSF TEATLQRDRI FKHFTRKRQR AMRRRVHQIN GHKFMATYLR
QPTYCSHCRE FIWGVFGKQG YQCQVCTCVV HKRCHHLIVT ACTCQNNINK VDSKTAEQRF
GINIPHKFSV HNYKVPTFCD HCGSLLWGIM RQGLQCKICK MNVHIRCQAN VAPNCGVNAV
ELAKTLAGMG LQPGNISPTS KLVSRSTLRR QGKESTKEGN GIGVNSSNRL GIDNFEFIRV
LGKGSFGKVM LARIKETGDL YAVKVLKKDV ILQDDDVECT MTEKRILSLA RNHPFLTQLF
CCFQTPDRLF FVMEFVNGGD LMFHIQKSRR FDEARARFYA AEIISALMFL HDKGIIYRDL
KLDNVLLDHE GHCKLADFGM CKEGICNGVT TATFCGTPDY IAPEILQEML YGPAVDWWAM
GVLLYEMLCG HAPFEAENED DLFEAILNDE VVYPTWLHED ATGILKSFMT KNPTMRLGSP
SQGGEHAILR HPFFKEIDWT QLNHRQVEPP FRPRIKSRED VSNFDPDFIK EEPVLTPIDE
GHLPMINQDE FRNFSFVSPE LHP
//
