AiPD: Autoinhibited Protein Database

Q8K045

Gene name	Pkn3 (Pknbeta)
Protein name	Serine/threonine-protein kinase N3
Names	EC 2.7.11.13 , Protein kinase PKN-beta , Protein-kinase C-related kinase 3
Species	Mus musculus (Mouse)
KEGG Pathway	mmu:263803
EC number	2.7.11.13: Protein-serine/threonine kinases
Protein Class

Descriptions

Serine/threonine-protein kinase N1 (PKN1) is a PKC-related serine/threonine protein kinase involved in specific signal transduction responses such as regulation of intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion, and transcription regulation in cells. Its kinase activity is enhanced by fatty acids such as arachidonic acid or the small GTP-binding protein Rho. Residues 455-511 of PKN selectively inhibit the kinase activity of the catalytic fragment of PKN1. Arachidonic acid relieves the catalytic activity of wild-type PKN from autoinhibition by residues 455-511 of PKN.

Autoinhibitory domains (AIDs)

387-443 (autoinhibitory domain) SS

Target domain	548-807 (Protein kinase domain)
Relief mechanism	Ligand binding, PTM
Assay

AID

387-443 (autoinhibitory domain)

Target domain

548-807 (Protein kinase domain)

Relief mechanism

Ligand binding (Arachidonic acid binding), PTM (Phosphorylation at Thr-774)

Assay

Accessory elements

690-713 (Activation loop from InterPro)

Target domain	548-807 (Protein kinase domain)
Relief mechanism
Assay

References

Yoshinaga C et al. (1999) "Mutational analysis of the regulatory mechanism of PKN: the regulatory region of PKN contains an arachidonic acid-sensitive autoinhibitory domain", Journal of biochemistry, 126, 475-84

Huang X et al. (2003) "Crystal structure of an inactive Akt2 kinase domain", Structure (London, England : 1993), 11, 21-30

Truebestein L et al. (2021) "Structure of autoinhibited Akt1 reveals mechanism of PIP(3)-mediated activation", Proceedings of the National Academy of Sciences of the United States of America, 118,

Lučić I et al. (2018) "Conformational sampling of membranes by Akt controls its activation and inactivation", Proceedings of the National Academy of Sciences of the United States of America, 115, E3940-E3949

Autoinhibited structure

Activated structure

1 structures for Q8K045

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q8K045-F1	Predicted				AlphaFoldDB

41 variants for Q8K045

Variant ID(s)	Position	Change	Diseaes Association	Provenance
rs251284148	14	K>E	No	EVA
rs3388544350	42	T>R	No	EVA
rs3388544322	44	R>Q	No	EVA
rs245130590	81	A>V	No	EVA
rs27179966	87	E>G	No	EVA
rs217426113	91	R>Q	No	EVA
rs240431821	92	A>V	No	EVA
rs3388534414	98	R>Q	No	EVA
rs3388539642	109	V>L	No	EVA
rs213896899	113	V>I	No	EVA
rs3388544298	129	P>T	No	EVA
rs253662551	184	A>T	No	EVA
rs3388543453	215	L>P	No	EVA
rs3388539408	254	M>L	No	EVA
rs3388542163	286	V>L	No	EVA
rs3388538107	295	A>T	No	EVA
rs3388543476	323	V>I	No	EVA
rs6306688	350	S>T	No	EVA
rs3388544348	360	E>*	No	EVA
rs864264004	369	D>N	No	EVA
rs3391399616	445	A>E	No	EVA
rs3388539419	454	L>W	No	EVA
rs237770524	464	A>V	No	EVA
rs3388544367	466	P>S	No	EVA
rs254736958	470	R>C	No	EVA
rs218106996	475	V>A	No	EVA
rs260326196	475	V>I	No	EVA
rs3388539779	477	G>E	No	EVA
rs3388539356	565	V>D	No	EVA
rs3388543466	587	R>P	No	EVA
rs3388539623	635	D>Y	No	EVA
rs3388541942	639	Q>R	No	EVA
rs3388542014	665	H>Y	No	EVA
rs3388534445	710	G>S	No	EVA
rs3388544347	755	E>*	No	EVA
rs3507669540	766	P>L	No	EVA
rs3388541757	823	P>T	No	EVA
rs3388543712	828	L>I	No	EVA
rs3388543403	841	F>S	No	EVA
rs3388542189	842	T>N	No	EVA
rs3540218408	856	S>A	No	EVA

No associated diseases with Q8K045

9 regional properties for Q8K045

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	548 - 807	IPR000719
domain	AGC-kinase, C-terminal	808 - 878	IPR000961
active_site	Serine/threonine-protein kinase, active site	669 - 681	IPR008271
domain	HR1 rho-binding domain	2 - 78	IPR011072-1
domain	HR1 rho-binding domain	86 - 166	IPR011072-2
domain	HR1 rho-binding domain	169 - 239	IPR011072-3
binding_site	Protein kinase, ATP binding site	554 - 577	IPR017441
domain	Protein kinase, C-terminal	830 - 870	IPR017892
domain	Serine/threonine-protein kinase N, first HR1 domain	10 - 75	IPR037313

Functions

		Description
EC Number	2.7.11.13	Protein-serine/threonine kinases
Subcellular Localization	Nucleus Cytoplasm, perinuclear region	Nuclear and perinuclear Golgi region
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

2 GO annotations of cellular component

Name	Definition
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
perinuclear region of cytoplasm	Cytoplasm situated near, or occurring around, the nucleus.

5 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
diacylglycerol-dependent serine/threonine kinase activity	Catalysis of the reaction
protein serine kinase activity	Catalysis of the reactions
protein serine/threonine kinase activity	Catalysis of the reactions
small GTPase binding	Binding to a small monomeric GTPase.

3 GO annotations of biological process

Name	Definition
epithelial cell migration	The orderly movement of an epithelial cell from one site to another, often during the development of a multicellular organism.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
phosphorylation	The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.

38 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P24583	PKC1	Protein kinase C-like 1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	SS
A1A4I4	PKN1	Serine/threonine-protein kinase N1	Bos taurus (Bovine)	SS
P83099	Pkcdelta	Putative protein kinase C delta type homolog	Drosophila melanogaster (Fruit fly)	PR
A1Z7T0	Pkn	Serine/threonine-protein kinase N	Drosophila melanogaster (Fruit fly)	SS
Q04759	PRKCQ	Protein kinase C theta type	Homo sapiens (Human)	PR
Q96LW2	RSKR	Ribosomal protein S6 kinase-related protein	Homo sapiens (Human)	PR
Q02156	PRKCE	Protein kinase C epsilon type	Homo sapiens (Human)	SS
P24723	PRKCH	Protein kinase C eta type	Homo sapiens (Human)	SS
Q05655	PRKCD	Protein kinase C delta type	Homo sapiens (Human)	SS
Q16512	PKN1	Serine/threonine-protein kinase N1	Homo sapiens (Human)	EV
Q16513	PKN2	Serine/threonine-protein kinase N2	Homo sapiens (Human)	EV
Q6P5Z2	PKN3	Serine/threonine-protein kinase N3	Homo sapiens (Human)	SS
P16054	Prkce	Protein kinase C epsilon type	Mus musculus (Mouse)	PR
P23298	Prkch	Protein kinase C eta type	Mus musculus (Mouse)	PR
Q02111	Prkcq	Protein kinase C theta type	Mus musculus (Mouse)	PR
Q9Z2A0	Pdpk1	3-phosphoinositide-dependent protein kinase 1	Mus musculus (Mouse)	SS
Q02956	Prkcz	Protein kinase C zeta type	Mus musculus (Mouse)	SS
Q62074	Prkci	Protein kinase C iota type	Mus musculus (Mouse)	SS
P70268	Pkn1	Serine/threonine-protein kinase N1	Mus musculus (Mouse)	SS
Q8BWW9	Pkn2	Serine/threonine-protein kinase N2	Mus musculus (Mouse)	SS
P28867	Prkcd	Protein kinase C delta type	Mus musculus (Mouse)	PR
P20444	Prkca	Protein kinase C alpha type	Mus musculus (Mouse)	SS
P63318	Prkcg	Protein kinase C gamma type	Mus musculus (Mouse)	SS
P68404	Prkcb	Protein kinase C beta type	Mus musculus (Mouse)	SS
Q60823	Akt2	RAC-beta serine/threonine-protein kinase	Mus musculus (Mouse)	PR
P31750	Akt1	RAC-alpha serine/threonine-protein kinase	Mus musculus (Mouse)	PR
Q9WUA6	Akt3	RAC-gamma serine/threonine-protein kinase	Mus musculus (Mouse)	PR
Q9ERE3	Sgk3	Serine/threonine-protein kinase Sgk3	Mus musculus (Mouse)	PR
Q8QZV4	Stk32c	Serine/threonine-protein kinase 32C	Mus musculus (Mouse)	PR
Q91VJ4	Stk38	Serine/threonine-protein kinase 38	Mus musculus (Mouse)	SS
Q7TSE6	Stk38l	Serine/threonine-protein kinase 38-like	Mus musculus (Mouse)	SS
Q63433	Pkn1	Serine/threonine-protein kinase N1	Rattus norvegicus (Rat)	SS
Q64617	Prkch	Protein kinase C eta type	Rattus norvegicus (Rat)	PR
P09216	Prkce	Protein kinase C epsilon type	Rattus norvegicus (Rat)	PR
P09215	Prkcd	Protein kinase C delta type	Rattus norvegicus (Rat)	PR
O08874	Pkn2	Serine/threonine-protein kinase N2	Rattus norvegicus (Rat)	SS
P34722	tpa-1	Protein kinase C-like 1	Caenorhabditis elegans	PR
A7MBL8	pkn2	Serine/threonine-protein kinase N2	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MEHRKPGTGQ	RAPKDEKEMV	RRAIQKELKI	KEGMENMRRV	ATDRRHLGHV	QQLLRASNRR
70	80	90	100	110	120
LEQLHGELRE	LHAQVLLPAS	AEPVTSEPQP	RAEQSRARLS	EALHRQLQVE	LKVKQGAENM
130	140	150	160	170	180
IHTCASGTPK	ERKLLAAAQQ	MLKDSQLKVA	LLRMKISSLE	SSGSPEPGPD	LLAEELQHRL
190	200	210	220	230	240
RVEAAVAAGA	KNVVKLLGGQ	RMQDRKALAE	AQAQLQESSQ	KLDLLRLALE	LLLERLPPTH
250	260	270	280	290	300
SLRSRVTQEL	WMAMLGNPQP	LGTLVKPIAL	TGTLQVRLLG	CKDLLVAVPG	RSPMAVLAGS
310	320	330	340	350	360
PSESWLRTRS	RQQRGGGELA	SEVLAVLKVD	NRVVGQTGWG	LVAEKSWDQS	FIISLDRARE
370	380	390	400	410	420
LEIGVHWRDW	RQLCGVAFLK	LEDFLDNACH	QLSLSLVPQG	RLFAQVTFCE	PVIERRPRLQ
430	440	450	460	470	480
RQRCIFSKRR	GRDFMRASQM	NLSMAAWGRL	VMSLLPPCSS	PNTASPPKGR	PSTAVCGTPS
490	500	510	520	530	540
AASPSNFLPM	KTLSKEDTKP	PPKPPRLYLQ	EPAPGTPCTK	RPHMDPRPAV	VPALAALSTR
550	560	570	580	590	600
KPPRLQDFRC	LAVLGRGHFG	KVLLVQYKGT	GKYYAIKALK	KQEVLGRDEI	DSLYCEKRIL
610	620	630	640	650	660
ETVGRTGHPF	LLSLLACLQT	SSHACFVTEF	LPGGDLMAQI	HEDVFPEPQA	CFYLACVVLG
670	680	690	700	710	720
LQFLHEKRII	YRDLKLDNLL	LDAQGFLKIA	DFGLCKEGIG	FGDRTSTFCG	TPEFLAPEVL
730	740	750	760	770	780
TQEAYTRAVD	WWGLGVLLYE	MLVGECPFPG	DTEEEVFECI	VSADVPCPHF	LSVQGLELIQ
790	800	810	820	830	840
KLLQKSPEKR	LGAGERDAEE	IKVQPFFRTT	NWQALLARTV	QPPFVPTLCG	PADLRYFEGE
850	860	870
FTSLPPTLTP	PVSQSSLTAR	QQAAFRDFDF	VSEQFLES