Q6P5Z2 (PKN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase N3
EC=2.7.11.13

Alternative name(s):
Protein kinase PKN-beta
Protein-kinase C-related kinase 3

Gene names

Name:	PKN3
Synonyms:	PKNBETA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	889 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Contributes to invasiveness in malignant prostate cancer. Ref.4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Two specific sites, Thr-718 (activation loop of the kinase domain) and Thr-860 (turn motif), need to be phosphorylated for its full activation By similarity.
Subcellular location	Nucleus. Cytoplasm › perinuclear region. Note: Nuclear and perinuclear Golgi region. Ref.1
Tissue specificity	Expressed in prostate tumors and various cancer cell lines. Not expressed in adult tissues. Ref.1
Domain	The C1 domain does not bind the diacylglycerol (DAG).
Post-translational modification	Autophosphorylated. Ref.1 Ref.4
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 protein kinase domain. Contains 3 REM (Hr1) repeats.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	epithelial cell migration Inferred from direct assay PubMed 21754995. Source: UniProtKB signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	Golgi apparatus Traceable author statement Ref.1. Source: ProtInc nucleus Traceable author statement Ref.1. Source: ProtInc perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from electronic annotation. Source: EC protein kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARHGAP10	A1A4S6	4	EBI-1384335,EBI-1390944
ARHGAP26	Q9UNA1	4	EBI-1384335,EBI-1390913

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 889	889	Serine/threonine-protein kinase N3		PRO_0000055725
Regions
	Repeat	18 – 90	73	REM 1
	Repeat	105 – 181	77	REM 2
	Repeat	182 – 255	74	REM 3
	Domain	559 – 818	260	Protein kinase
	Domain	819 – 889	71	AGC-kinase C-terminal
	Nucleotide binding	565 – 573	9	ATP By similarity
	Compositional bias	463 – 554	92	Pro-rich
Sites
	Active site	684	1	Proton acceptor By similarity
	Binding site	588	1	ATP By similarity
Amino acid modifications
	Modified residue	544	1	Phosphoserine Ref.5 Ref.6 Ref.7
	Modified residue	548	1	Phosphoserine Ref.6
	Modified residue	718	1	Phosphothreonine Ref.4
	Modified residue	722	1	Phosphothreonine Ref.5
	Modified residue	860	1	Phosphothreonine Ref.5 Ref.7
Natural variations
	Natural variant	180	1	A → E. Ref.8 Corresponds to variant rs56251280 [ dbSNP | Ensembl ].		VAR_042346
	Natural variant	404	1	V → L. Corresponds to variant rs12932 [ dbSNP | Ensembl ].		VAR_050565
Experimental info
	Mutagenesis	588	1	K → E: Abolishes autophosphorylation and catalytic activity. Ref.1 Ref.4
	Mutagenesis	588	1	K → R: Abolishes catalytic activity. Ref.1 Ref.4
	Mutagenesis	718	1	T → A: Abolishes phosphorylation. Ref.4
	Sequence conflict	444	1	A → R in BAA85625. Ref.1
	Sequence conflict	627	1	A → V in BAA85625. Ref.1
	Sequence conflict	636	1	C → R in BAA85625. Ref.1
	Sequence conflict	738	1	R → Q in BAA85625. Ref.1
	Sequence conflict	744	1	G → A in BAA85625. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q6P5Z2 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: F3891DA1420DF54E	FASTA	889	99,421
	10 20 30 40 50 60 MEEGAPRQPG PSQWPPEDEK EVIRRAIQKE LKIKEGVENL RRVATDRRHL GHVQQLLRSS 70 80 90 100 110 120 NRRLEQLHGE LRELHARILL PGPGPGPAEP VASGPRPWAE QLRARHLEAL RRQLHVELKV 130 140 150 160 170 180 KQGAENMTHT CASGTPKERK LLAAAQQMLR DSQLKVALLR MKISSLEASG SPEPGPELLA 190 200 210 220 230 240 EELQHRLHVE AAVAEGAKNV VKLLSSRRTQ DRKALAEAQA QLQESSQKLD LLRLALEQLL 250 260 270 280 290 300 EQLPPAHPLR SRVTRELRAA VPGYPQPSGT PVKPTALTGT LQVRLLGCEQ LLTAVPGRSP 310 320 330 340 350 360 AAALASSPSE GWLRTKAKHQ RGRGELASEV LAVLKVDNRV VGQTGWGQVA EQSWDQTFVI 370 380 390 400 410 420 PLERARELEI GVHWRDWRQL CGVAFLRLED FLDNACHQLS LSLVPQGLLF AQVTFCDPVI 430 440 450 460 470 480 ERRPRLQRQE RIFSKRRGQD FLRASQMNLG MAAWGRLVMN LLPPCSSPST ISPPKGCPRT 490 500 510 520 530 540 PTTLREASDP ATPSNFLPKK TPLGEEMTPP PKPPRLYLPQ EPTSEETPRT KRPHMEPRTR 550 560 570 580 590 600 RGPSPPASPT RKPPRLQDFR CLAVLGRGHF GKVLLVQFKG TGKYYAIKAL KKQEVLSRDE 610 620 630 640 650 660 IESLYCEKRI LEAVGCTGHP FLLSLLACFQ TSSHACFVTE FVPGGDLMMQ IHEDVFPEPQ 670 680 690 700 710 720 ARFYVACVVL GLQFLHEKKI IYRDLKLDNL LLDAQGFLKI ADFGLCKEGI GFGDRTSTFC 730 740 750 760 770 780 GTPEFLAPEV LTQEAYTRAV DWWGLGVLLY EMLVGECPFP GDTEEEVFDC IVNMDAPYPG 790 800 810 820 830 840 FLSVQGLEFI QKLLQKCPEK RLGAGEQDAE EIKVQPFFRT TNWQALLART IQPPFVPTLC 850 860 870 880 GPADLRYFEG EFTGLPPALT PPAPHSLLTA RQQAAFRDFD FVSERFLEP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of PKNbeta, a novel isoform of protein kinase PKN: expression and arachidonic acid dependency are different from those of PKNalpha." Oishi K., Mukai H., Shibata H., Takahashi M., Ono Y. Biochem. Biophys. Res. Commun. 261:808-814(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-588, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Cervix carcinoma.
[2]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[4]	"PKN3 is required for malignant prostate cell growth downstream of activated PI 3-kinase." Leenders F., Moepert K., Schmiedeknecht A., Santel A., Czauderna F., Aleku M., Penschuck S., Dames S., Sternberger M., Roehl T., Wellmann A., Arnold W., Giese K., Kaufmann J., Klippel A. EMBO J. 23:3303-3313(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MALIGNANT CELL GROWTH, PHOSPHORYLATION AT THR-718, MUTAGENESIS OF LYS-588 AND THR-718.
[5]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544; THR-722 AND THR-860, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544 AND SER-548, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544 AND THR-860, MASS SPECTROMETRY.
[8]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-180.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB019692 mRNA. Translation: BAA85625.1. AL441992 Genomic DNA. Translation: CAI15401.1. BC062558 mRNA. Translation: AAH62558.1.
IPI	IPI00413780.
PIR	JC7083.
RefSeq	NP_037487.2. NM_013355.3.
UniGene	Hs.300485.
3D structure databases
ProteinModelPortal	Q6P5Z2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6P5Z2. 2 interactions.
MINT	MINT-192027.
STRING	9606.ENSP00000291906.
PTM databases
PhosphoSite	Q6P5Z2.
Polymorphism databases
DMDM	74749130.
Proteomic databases
PaxDb	Q6P5Z2.
PRIDE	Q6P5Z2.
Protocols and materials databases
DNASU	29941.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000291906; ENSP00000291906; ENSG00000160447.
GeneID	29941.
KEGG	hsa:29941.
UCSC	uc004bvw.3. human.
Organism-specific databases
CTD	29941.
GeneCards	GC09P131464.
HGNC	HGNC:17999. PKN3.
MIM	610714. gene.
neXtProt	NX_Q6P5Z2.
PharmGKB	PA134919098.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233032.
HOVERGEN	HBG108317.
InParanoid	Q6P5Z2.
KO	K06071.
OMA	IFSKRRG.
OrthoDB	EOG40ZQWW.
PhylomeDB	Q6P5Z2.
Gene expression databases
ArrayExpress	Q6P5Z2.
Bgee	Q6P5Z2.
CleanEx	HS_PKN3.
Genevestigator	Q6P5Z2.
GermOnline	ENSG00000160447. Homo sapiens.
Family and domain databases
Gene3D	1.10.287.160. 3 hits.
InterPro	IPR000961. AGC-kinase_C. IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR011072. HR1_rho-bd. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF02185. HR1. 3 hits. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
SMART	SM00239. C2. 1 hit. SM00742. Hr1. 3 hits. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF56112. Kinase_like. 1 hit. SSF46585. PKN_effector. 3 hits.
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. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	29941.
NextBio	52593.
SOURCE	Search...

Entry information

Entry name

PKN3_HUMAN

Accession

Primary (citable) accession number: Q6P5Z2
Secondary accession number(s): Q9UM03

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.