EKS-MUM-00176

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00176

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
AGC/PKC	460.4	4.6E-138	355	614	260

Status

Reviewed

Ensembl Protein

ENSMUSP00000021527

UniProt Accession

P23298; Q8K2K8;

Protein Name

Protein kinase C eta type

Protein Synonyms/Alias

PKC-L; nPKC-eta;

Gene Name

Prkch

Gene Synonyms/Alias

Prkch; Pkch;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000021108	ENSMUSP00000112499	ENSMUST00000119092
ENSMUSG00000021108	ENSMUSP00000021527	ENSMUST00000021527

Organism

Mus musculus

Functional Description

Calcium-independent, phospholipid- and diacylglycerol(DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1- dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis.

Protein Length

683

Protein Sequence
(FASTA)

MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD QVRVGQTSTK 60

QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN CTLQFQELLR TAGTSDTFEG 120

WVDLEPEGKV FVVITLTGSF TEATLQRDRI FKHFTRKRQR AMRRRVHQVN GHKFMATYLR 180

QPTYCSHCRE FIWGVFGKQG YQCQVCTCVV HKRCHHLIVT ACTCQNNINK VDAKIAEQRF 240

GINIPHKFNV HNYKVPTFCD HCGSLLWGIM RQGLQCKICK MNVHIRCQAN VAPNCGVNAV 300

ELAKTLAGMG LQPGNISPTS KLISRSTLRR QGKEGSKEGN GIGVNSSSRF GIDNFEFIRV 360

LGKGSFGKVM LARIKETGEL YAVKVLKKDV ILQDDDVECT MTEKRILSLA RNHPFLTQLF 420

CCFQTPDRLF FVMEFVNGGD LMFHIQKSRR FDEARARFYA AEIISALMFL HEKGIIYRDL 480

KLDNVLLDHE GHCKLADFGM CKEGICNGVT TATFCGTPDY IAPEILQEML YGPAVDWWAM 540

GVLLYEMLCG HAPFEAENED DLFEAILNDE VVYPTWLHED ATGILKSFMT KNPTMRLGSL 600

TQGGEHEILR HPFFKEIDWA QLNHRQLEPP FRPRIKSRED VSNFDPDFIK EEPVLTPIDE 660

GHLPMINQDE FRNFSYVSPE LQL 683

Nucleotide Sequence
(FASTA)

ATGTCGTCCG GCACGATGAA GTTCAATGGC TATCTGAGGG TCCGCATCGG AGAGGCTGTA 60

GGGCTGCAGC CCACCCGCTG GTCCCTGCGG CACTCGCTCT TCAAAAAGGG CCACCAGCTG 120

CTGGACCCCT ACCTGACGGT GAGCGTAGAC CAGGTACGCG TGGGCCAGAC CAGCACAAAG 180

CAGAAGACCA ACAAACCCAC CTACAACGAG GAGTTCTGCG CCAATGTCAC CGACGGCGGC 240

CACCTGGAGC TAGCCGTCTT CCACGAGACG CCCCTGGGTT ATGACCACTT TGTGGCCAAC 300

TGCACGCTGC AGTTCCAGGA GCTGTTGCGC ACGGCTGGTA CCTCGGACAC CTTCGAGGGC 360

TGGGTGGATC TGGAGCCTGA GGGGAAAGTG TTTGTGGTAA TAACCCTAAC AGGGAGTTTC 420

ACTGAAGCCA CTCTCCAGAG AGACCGCATC TTCAAGCATT TTACCAGGAA GCGCCAAAGG 480

GCTATGCGAA GACGAGTCCA TCAAGTGAAC GGACATAAGT TCATGGCCAC GTACCTGAGG 540

CAGCCCACCT ACTGCTCTCA TTGCCGAGAG TTCATCTGGG GAGTATTTGG GAAACAGGGT 600

TATCAATGCC AAGTGTGCAC CTGCGTCGTC CATAAACGCT GCCATCATCT AATTGTTACA 660

GCCTGCACTT GCCAAAACAA TATTAACAAA GTGGATGCCA AGATTGCAGA ACAGCGGTTT 720

GGCATCAACA TCCCACACAA GTTCAACGTT CACAATTACA AGGTGCCCAC GTTCTGTGAC 780

CACTGTGGCT CCCTGCTCTG GGGGATAATG CGACAAGGAC TTCAGTGTAA AATATGTAAG 840

ATGAATGTAC ATATTCGGTG TCAGGCGAAC GTGGCCCCAA ACTGCGGGGT GAATGCCGTG 900

GAGCTTGCCA AGACCCTGGC AGGGATGGGT CTCCAACCCG GAAATATTTC TCCAACCTCG 960

AAACTCATTT CCAGGTCGAC ACTAAGACGG CAGGGAAAGG AGGGCTCCAA AGAAGGAAAT 1020

GGGATCGGTG TTAACTCTTC CAGCAGATTC GGCATCGACA ACTTTGAGTT CATCCGGGTG 1080

TTGGGGAAGG GGAGCTTCGG GAAGGTGATG CTTGCCAGGA TAAAGGAGAC AGGAGAACTG 1140

TACGCCGTGA AGGTGCTGAA GAAGGACGTG ATTCTGCAGG ATGATGATGT AGAGTGCACC 1200

ATGACTGAGA AGAGGATCCT GTCCTTGGCC CGCAACCACC CCTTCCTCAC CCAGCTCTTC 1260

TGCTGCTTTC AGACTCCAGA CCGTCTGTTC TTTGTCATGG AGTTTGTGAA CGGAGGCGAC 1320

CTGATGTTCC ACATCCAAAA GTCCCGTCGT TTCGATGAAG CCCGTGCTCG TTTCTACGCC 1380

GCGGAGATCA TTTCTGCACT CATGTTCCTA CATGAGAAAG GTATCATCTA TAGAGACTTG 1440

AAACTGGACA ATGTGCTATT GGACCACGAA GGTCACTGTA AACTGGCCGA CTTTGGAATG 1500

TGCAAGGAGG GGATTTGTAA TGGGGTCACC ACAGCCACCT TCTGCGGTAC ACCCGACTAC 1560

ATTGCCCCGG AGATCCTTCA GGAGATGCTG TATGGACCTG CAGTAGACTG GTGGGCCATG 1620

GGTGTGTTGC TTTATGAGAT GCTGTGCGGA CATGCGCCCT TTGAGGCTGA AAATGAAGAT 1680

GACCTTTTTG AGGCCATACT GAATGATGAA GTCGTCTACC CCACCTGGCT CCACGAAGAT 1740

GCCACAGGGA TCCTCAAGTC TTTCATGACC AAGAACCCCA CCATGCGCTT GGGCAGCCTG 1800

ACTCAGGGAG GAGAGCATGA GATCCTGAGA CACCCTTTCT TTAAGGAAAT CGACTGGGCC 1860

CAGTTGAACC ATCGCCAGTT AGAGCCGCCT TTCCGACCTA GAATCAAATC CCGAGAAGAT 1920

GTCAGCAATT TTGACCCAGA CTTTATAAAA GAAGAGCCCG TCTTAACTCC GATTGATGAG 1980

GGACATCTTC CTATGATTAA CCAGGATGAG TTTAGAAACT TTTCCTATGT GTCACCGGAA 2040

TTGCAACTGT AG 2052

Domain Profile

S: 1     fellkvlGkGsfgkvllaelkktdelyaikvlkkdvvlqdddveltlvekrvlalaskkp  60

         fe+++vlGkGsfgkv+la+ k+t elya+kvlkkdv+lqdddve+t++ekr+l+la+++p

Q: 355   FEFIRVLGKGSFGKVMLARIKETGELYAVKVLKKDVILQDDDVECTMTEKRILSLARNHP  414

         89**********************************************************

S: 61    flvqlfscfqtedrlffvleyvnGGdlmfhiqkarklkeerarfyaaeiilalkflhekg  120

         fl+qlf+cfqt drlffv+e+vnGGdlmfhiqk+r+++e+rarfyaaeii+al+flhekg

Q: 415   FLTQLFCCFQTPDRLFFVMEFVNGGDLMFHIQKSRRFDEARARFYAAEIISALMFLHEKG  474

         ************************************************************

S: 121   iiyrdlkldnvlldaeGhikladfGlckeeilegkttstfcGtPdyiaPeilkeeeygks  180

         iiyrdlkldnvlld+eGh+kladfG+cke+i++g tt+tfcGtPdyiaPeil+e+ yg +

Q: 475   IIYRDLKLDNVLLDHEGHCKLADFGMCKEGICNGVTTATFCGTPDYIAPEILQEMLYGPA  534

         ************************************************************

S: 181   vdwwalGvllyemlagqsPfegededelfesilekevlyPkslskeaveilkglltkdpe  240

         vdwwa+Gvllyeml+g++Pfe+e+ed+lfe+il++ev+yP++l+++a+ ilk+++tk+p+

Q: 535   VDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLHEDATGILKSFMTKNPT  594

         ************************************************************

S: 241   krlGvk.eegeedikehaff  259

         +rlG+  + ge++i +h+ff

Q: 595   MRLGSLtQGGEHEILRHPFF  614

         *****65999*********9

Domain Sequence
(FASTA)

FEFIRVLGKG SFGKVMLARI KETGELYAVK VLKKDVILQD DDVECTMTEK RILSLARNHP 60

FLTQLFCCFQ TPDRLFFVME FVNGGDLMFH IQKSRRFDEA RARFYAAEII SALMFLHEKG 120

IIYRDLKLDN VLLDHEGHCK LADFGMCKEG ICNGVTTATF CGTPDYIAPE ILQEMLYGPA 180

VDWWAMGVLL YEMLCGHAPF EAENEDDLFE AILNDEVVYP TWLHEDATGI LKSFMTKNPT 240

MRLGSLTQGG EHEILRHPFF 260

Keyword

ATP-binding; Complete proteome; Cytoplasm; Differentiation; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005886	; C:plasma membrane
GO:0005524	; F:ATP binding
GO:0046872	; F:metal ion binding
GO:0004697	; F:protein kinase C activity
GO:0035556	; P:intracellular signal transduction
GO:0034351	; P:negative regulation of glial cell apoptotic process
GO:0050861	; P:positive regulation of B cell receptor signaling pathway
GO:0060252	; P:positive regulation of glial cell proliferation
GO:0045618	; P:positive regulation of keratinocyte differentiation
GO:0010744	; P:positive regulation of macrophage derived foam cell differentiation
GO:0051092	; P:positive regulation of NF-kappaB transcription factor activity
GO:2000810	; P:regulation of tight junction assembly

KEGG

mmu:18755

;

InterPros

IPR000961	; AGC-kinase_C.
IPR000008	; C2_Ca-dep.
IPR008973	; C2_Ca/lipid-bd_dom_CaLB.
IPR018029	; C2_membr_targeting.
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.
IPR002290	; Ser/Thr_dual-sp_kinase_dom.
IPR008271	; Ser/Thr_kinase_AS.

Pfam

PF00130	; C1_1; 2.
PF00168	; C2; 1.
PF00069	; Pkinase; 1.
PF00433	; Pkinase_C; 1.

SMARTs

SM00109	; C1; 2.
SM00239	; C2; 1.
SM00133	; S_TK_X; 1.
SM00220	; S_TKc; 1.

Prosites

PS51285	; AGC_KINASE_CTER; 1.
PS50004	; C2; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.
PS00479	; ZF_DAG_PE_1; 2.
PS50081	; ZF_DAG_PE_2; 2.

Prints

PR00008

; DAGPEDOMAIN.

Created Date

20-Feb-2013