Reviewed, UniProtKB/Swiss-Prot Q16512 (PKN1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase N1
    EC=2.7.11.13
Alternative name(s):
    Protein kinase C-like 1
    Protein-kinase C-related kinase 1
    Protein kinase C-like PKN
    Serine-threonine protein kinase N
    Protein kinase PKN-alpha

Gene names

Name:	PKN1
Synonyms:	PKN, PRK1, PRKCL1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	942 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Can phosphorylate ribosomal protein S6. Mediates GTPase Rho dependent intracellular signaling By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Two specific sites, Thr-774 (activation loop of the kinase domain) and Ser-916 (turn motif), need to be phosphorylated for its full activation By similarity.
Subunit structure	Interacts with ZA20D3 By similarity. Interacts with RhoA and Rac1.
Subcellular location	CytoplasmBy similarity.
Tissue specificity	Found ubiquitously. Expressed in heart, brain, placenta, lung, skeletal muscle, kidney and pancreas.
Domain	The C1 domain does not bind the diacylglycerol (DAG).
Post-translational modification	Autophosphorylated; preferably on serine. Activated by limited proteolysis with trypsin By similarity.
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 1 protein kinase domain. Contains 3 REM (Hr1) repeats.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	activation of JNK activity Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct protein kinase activity Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MAP2K3	P46734	1	EBI-602382,EBI-602462
MAP2K6	P52564	1	EBI-602382,EBI-448135
MAPK12	P53778	1	EBI-602382,EBI-602406
MAPK14	Q16539	1	EBI-602382,EBI-73946
MLTK	Q9NYL2-1	1	EBI-602382,EBI-687346
RHOA	P61586	1	EBI-602382,EBI-446668

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 942

942

Serine/threonine-protein kinase N1

Regions

Repeat

34 – 110

77

REM 1

Repeat

123 – 209

87

REM 2

Repeat

210 – 291

82

REM 3

Domain

325 – 461

137

C2

Domain

615 – 874

260

Protein kinase

Domain

875 – 942

68

AGC-kinase C-terminal

Nucleotide binding

621 – 629

9

ATP By similarity

Sites

Active site

740

1

Proton acceptor By similarity

Binding site

644

1

ATP By similarity

Amino acid modifications

Modified residue

376

1

Phosphoserine

Modified residue

562

1

Phosphoserine

Modified residue

774

1

Phosphothreonine Probable

Modified residue

778

1

Phosphothreonine

Modified residue

916

1

Phosphoserine

Natural variations

Natural variant

185

1

R → C in a metastatic melanoma sample; somatic mutation.

Natural variant

197

1

A → E

Natural variant

436

1

R → W

Natural variant

520

1

R → Q

Natural variant

555

1

L → I

Natural variant

635

1

R → Q

Natural variant

718

1

I → V

Natural variant

873

1

F → L in a breast infiltrating ductal carcinoma sample; somatic mutation.

Natural variant

901

1

V → I: dbSNP rs10846.

Natural variant

921

1

A → V in a colorectal adenocarcinoma sample; somatic mutation.

Experimental info

Mutagenesis

644

1

K → R: Substantial reduction of autophosphorylation

Sequence conflict

191

1

D → G in BAA05169. Ref.3

Sequence conflict

191

1

D → G in AAH40061. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

942

Helix Strand Turn

Details...

Helix

15 – 18

4

Helix

29 – 66

38

Helix

71 – 95

25

Turn

122 – 124

3

Helix

126 – 154

29

Beta strand

155 – 157

3

Helix

160 – 192

33

Sequences

	Sequence		Length	Mass (Da)
	Q16512-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A89E40DCAEF560E3	FASTA	942	103,990
	10 20 30 40 50 60 MASDAVQSEP RSWSLLEQLG LAGADLAAPG VQQQLELERE RLRREIRKEL KLKEGAENLR 70 80 90 100 110 120 RATTDLGRSL GPVELLLRGS SRRLDLLHQQ LQELHAHVVL PDPAATHDGP QSPGAGGPTC 130 140 150 160 170 180 SATNLSRVAG LEKQLAIELK VKQGAENMIQ TYSNGSTKDR KLLLTAQQML QDSKTKIDII 190 200 210 220 230 240 RMQLRRALQA DQLENQAAPD DTQGSPDLGA VELRIEELRH HFRVEHAVAE GAKNVLRLLS 250 260 270 280 290 300 AAKAPDRKAV SEAQEKLTES NQKLGLLREA LERRLGELPA DHPKGRLLRE ELAAASSAAF 310 320 330 340 350 360 STRLAGPFPA THYSTLCKPA PLTGTLEVRV VGCRDLPETI PWNPTPSMGG PGTPDSRPPF 370 380 390 400 410 420 LSRPARGLYS RSGSLSGRSS LKAEAENTSE VSTVLKLDNT VVGQTSWKPC GPNAWDQSFT 430 440 450 460 470 480 LELERARELE LAVFWRDQRG LCALKFLKLE DFLDNERHEV QLDMEPQGCL VAEVTFRNPV 490 500 510 520 530 540 IERIPRLRRQ KKIFSKQQGK AFQRARQMNI DVATWVRLLR RLIPNATGTG TFSPGASPGS 550 560 570 580 590 600 EARTTGDISV EKLNLGTDSD SSPQKSSRDP PSSPSSLSSP IQESTAPELP SETQETPGPA 610 620 630 640 650 660 LCSPLRKSPL TLEDFKFLAV LGRGHFGKVL LSEFRPSGEL FAIKALKKGD IVARDEVESL 670 680 690 700 710 720 MCEKRILAAV TSAGHPFLVN LFGCFQTPEH VCFVMEYSAG GDLMLHIHSD VFSEPRAIFY 730 740 750 760 770 780 SACVVLGLQF LHEHKIVYRD LKLDNLLLDT EGYVKIADFG LCKEGMGYGD RTSTFCGTPE 790 800 810 820 830 840 FLAPEVLTDT SYTRAVDWWG LGVLLYEMLV GESPFPGDDE EEVFDSIVND EVRYPRFLSA 850 860 870 880 890 900 EAIGIMRRLL RRNPERRLGS SERDAEDVKK QPFFRTLGWE ALLARRLPPP FVPTLSGRTD 910 920 930 940 VSNFDEEFTG EAPTLSPPRD ARPLTAAEQA AFLDFDFVAG GC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of multiple, novel, protein kinase C-related gene products." Palmer R.H., Ridden J., Parker P.J. FEBS Lett. 356:5-8(1994) [PubMed: 7988719] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning and expression patterns of two members of a novel protein-kinase-C-related kinase family." Palmer R.H., Ridden J., Parker P.J. Eur. J. Biochem. 227:344-351(1995) [PubMed: 7851406] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[3]	"A novel protein kinase with leucine zipper-like sequences: its catalytic domain is highly homologous to that of protein kinase C." Mukai H., Ono Y. Biochem. Biophys. Res. Commun. 199:897-904(1994) [PubMed: 8135837] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-644. Tissue: Hippocampus.
[4]	"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], VARIANT ILE-901. Tissue: Brain.
[5]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-916, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562 AND SER-916, MASS SPECTROMETRY.
[9]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-778, MASS SPECTROMETRY.
[10]	"Biochemical and crystallographic characterization of a Rho effector domain of the protein serine/threonine kinase N in a complex with RhoA." Maesaki R., Shimizu T., Ihara K., Kuroda S., Kaibuchi K., Hakoshima T. J. Struct. Biol. 126:166-170(1999) [PubMed: 10388627] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 13-98.
[11]	"Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1)." Owen D., Lowe P.N., Nietlispach D., Brosnan C.E., Chirgadze D.Y., Parker P.J., Blundell T.L., Mott H.R. J. Biol. Chem. 278:50578-50587(2003) [PubMed: 14514689] [Abstract] Cited for: STRUCTURE BY NMR OF 116-199.
[12]	"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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-185; GLU-197; TRP-436; GLN-520; ILE-555; GLN-635; VAL-718; LEU-873; ILE-901 AND VAL-921.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U33053 mRNA. Translation: AAC50209.1.
S75546 mRNA. Translation: AAB33345.1.
D26181 mRNA. Translation: BAA05169.1.
BC040061 mRNA. Translation: AAH40061.1.

PIR

JC2129.

RefSeq

NP_002732.3.
NP_998725.1.

UniGene

Hs.466044

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CXZ	X-ray	2.20	B	13-98	[»]
1URF	NMR	-	A	122-199	[»]
2RMK	NMR	-	B	122-199	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16512.

PTM databases

PhosphoSite

Q16512.

Genome annotation databases

Ensembl

ENSG00000123143. Homo sapiens. [Contig view]

GeneID

5585.

KEGG

hsa:5585.

Organism-specific databases

H-InvDB

HIX0027472.

HGNC

HGNC:9405. PKN1.

HPA

CAB010278.
HPA003982.

MIM

601032. gene.

PharmGKB

PA33769.

GenAtlas

Search...

GeneCards

Search...

GeneLynx

Search...

Phylogenomic databases

HOVERGEN

Q16512.

Gene expression databases

CleanEx

HS_PKN1.

GermOnline

ENSG00000123143. Homo sapiens.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR000861. HR1-like_rho-bd.
IPR011072. HR1_rho-bd.
IPR000961. Pkinase_C.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

Gene3D

G3DSA:1.10.287.160. HR1_rho-bd. 3 hits.

Pfam

PF02185. HR1. 3 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00239. C2. 1 hit.
SM00742. Hr1. 3 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS51285. AGC_KINASE_CTER. 1 hit.
PS50004. C2. False negative.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

BLOCKS

Search...

Other Resources

LinkHub

Q16512.

SOURCE

Search...

ProtoNet

Search...

Entry information

Entry name

PKN1_HUMAN

Accession

Primary (citable) accession number: Q16512
Secondary accession number(s): Q15143, Q8IUV5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1996
Last modified:	July 22, 2008
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)