P23298 (KPCL_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein kinase C eta type
EC=2.7.11.13

Alternative name(s):
PKC-L
nPKC-eta

Gene names

Name:	Prkch
Synonyms:	Pkch

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	683 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.4 Ref.5 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-513 (activation loop of the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic region), need to be phosphorylated for its full activation.
Subunit structure	Interacts with DGKQ By similarity. Interacts with FYN and RALA. Ref.4 Ref.6
Subcellular location	Cytoplasm. Note: Associates with cell membrane during keratinocytes differentiation. Ref.4 Ref.6
Tissue specificity	Predominantly expressed in lunk and skin.
Domain	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 similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 C2 domain. Contains 2 phorbol-ester/DAG-type zinc fingers. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Cytoplasm
Domain	Repeat Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 683	683	Protein kinase C eta type		PRO_0000055706
Regions
	Domain	12 – 102	91	C2
	Domain	355 – 614	260	Protein kinase
	Domain	615 – 683	69	AGC-kinase C-terminal
	Zinc finger	171 – 222	52	Phorbol-ester/DAG-type 1
	Zinc finger	245 – 295	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	361 – 369	9	ATP By similarity
Sites
	Active site	479	1	Proton acceptor By similarity
	Binding site	384	1	ATP By similarity
Amino acid modifications
	Modified residue	57	1	Phosphothreonine By similarity
	Modified residue	317	1	Phosphoserine By similarity
	Modified residue	320	1	Phosphoserine By similarity
	Modified residue	513	1	Phosphothreonine; by PDPK1 By similarity
	Modified residue	656	1	Phosphothreonine Probable
	Modified residue	675	1	Phosphoserine Probable
Experimental info
	Sequence conflict	582	1	T → R in BAA14288. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P23298 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 50454A6AE1900AD3	FASTA	683	77,919
	10 20 30 40 50 60 MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD QVRVGQTSTK 70 80 90 100 110 120 QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN CTLQFQELLR TAGTSDTFEG 130 140 150 160 170 180 WVDLEPEGKV FVVITLTGSF TEATLQRDRI FKHFTRKRQR AMRRRVHQVN GHKFMATYLR 190 200 210 220 230 240 QPTYCSHCRE FIWGVFGKQG YQCQVCTCVV HKRCHHLIVT ACTCQNNINK VDAKIAEQRF 250 260 270 280 290 300 GINIPHKFNV HNYKVPTFCD HCGSLLWGIM RQGLQCKICK MNVHIRCQAN VAPNCGVNAV 310 320 330 340 350 360 ELAKTLAGMG LQPGNISPTS KLISRSTLRR QGKEGSKEGN GIGVNSSSRF GIDNFEFIRV 370 380 390 400 410 420 LGKGSFGKVM LARIKETGEL YAVKVLKKDV ILQDDDVECT MTEKRILSLA RNHPFLTQLF 430 440 450 460 470 480 CCFQTPDRLF FVMEFVNGGD LMFHIQKSRR FDEARARFYA AEIISALMFL HEKGIIYRDL 490 500 510 520 530 540 KLDNVLLDHE GHCKLADFGM CKEGICNGVT TATFCGTPDY IAPEILQEML YGPAVDWWAM 550 560 570 580 590 600 GVLLYEMLCG HAPFEAENED DLFEAILNDE VVYPTWLHED ATGILKSFMT KNPTMRLGSL 610 620 630 640 650 660 TQGGEHEILR HPFFKEIDWA QLNHRQLEPP FRPRIKSRED VSNFDPDFIK EEPVLTPIDE 670 680 GHLPMINQDE FRNFSYVSPE LQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A phorbol ester receptor/protein kinase, nPKC eta, a new member of the protein kinase C family predominantly expressed in lung and skin." Osada S., Mizuno K., Saido T.C., Akita Y., Suzuki K., Kuroki T., Ohno S. J. Biol. Chem. 265:22434-22440(1990) [PubMed: 2266135] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Epidermis.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Embryo.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N-3. Tissue: Mammary tumor.
[4]	"A PKC-eta/Fyn-dependent pathway leading to keratinocyte growth arrest and differentiation." Cabodi S., Calautti E., Talora C., Kuroki T., Stein P.L., Dotto G.P. Mol. Cell 6:1121-1129(2000) [PubMed: 11106751] [Abstract] Cited for: FUNCTION, INTERACTION WITH FYN, SUBCELLULAR LOCATION.
[5]	"PKC eta directs induction of IRF-4 expression and Ig kappa gene rearrangement in pre-BCR signaling pathway." Oda A., Ono T., Yamamoto M., Goitsuka R., Kitamura D. Int. Immunol. 20:1417-1426(2008) [PubMed: 18780722] [Abstract] Cited for: FUNCTION IN B-CELL SIGNALING.
[6]	"Direct binding of RalA to PKC? and its crucial role in morphological change during keratinocyte differentiation." Shirai Y., Morioka S., Sakuma M., Yoshino K., Otsuji C., Sakai N., Kashiwagi K., Chida K., Shirakawa R., Horiuchi H., Nishigori C., Ueyama T., Saito N. Mol. Biol. Cell 22:1340-1352(2011) [PubMed: 21346190] [Abstract] Cited for: FUNCTION, INTERACTION WITH RALA, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D90242 mRNA. Translation: BAA14288.1. AK164044 mRNA. Translation: BAE37603.1. BC031121 mRNA. Translation: AAH31121.1.
IPI	IPI00130491.
PIR	A23690.
RefSeq	NP_032882.2. NM_008856.3.
UniGene	Mm.341677.
3D structure databases
ProteinModelPortal	P23298.
SMR	P23298. Positions 3-137, 167-298, 352-681.
ModBase	Search...
Protein-protein interaction databases
STRING	P23298.
PTM databases
PhosphoSite	P23298.
Proteomic databases
PRIDE	P23298.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021527; ENSMUSP00000021527; ENSMUSG00000021108.
GeneID	18755.
KEGG	mmu:18755.
Organism-specific databases
CTD	5583.
MGI	MGI:97600. Prkch.
Phylogenomic databases
eggNOG	roNOG06998.
GeneTree	ENSGT00590000082973.
HOGENOM	HBG755340.
HOVERGEN	HBG108317.
InParanoid	P23298.
OrthoDB	EOG4P2Q1P.
PhylomeDB	P23298.
Enzyme and pathway databases
BRENDA	2.7.11.13. 3474.
Gene expression databases
ArrayExpress	P23298.
Bgee	P23298.
CleanEx	MM_PRKCH.
Genevestigator	P23298.
GermOnline	ENSMUSG00000021108. Mus musculus.
Family and domain databases
InterPro	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. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K06068.
Pfam	PF00130. C1_1. 2 hits. PF00168. C2. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000551. PKC_delta. 1 hit.
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 2 hits. SM00239. C2. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS50004. C2. 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. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

KPCL_MOUSE

Accession

Primary (citable) accession number: P23298
Secondary accession number(s): Q8K2K8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	July 27, 2011
Last modified:	January 25, 2012
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program