Q16512 (PKN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase N1
EC=2.7.11.13

Alternative name(s):
Protease-activated kinase 1
Short name=PAK-1
Protein kinase C-like 1
Protein kinase C-like PKN
Protein kinase PKN-alpha
Protein-kinase C-related kinase 1
Serine-threonine protein kinase N

Gene names

Name:	PKN1
Synonyms:	PAK1, PKN, PRK1, PRKCL1

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	942 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. Ref.7 Ref.8 Ref.10 Ref.14 Ref.15 Ref.18 Ref.21 Ref.25 Ref.29
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.21
Enzyme regulation	Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-774 (activation loop of the kinase domain) and Ser-916 (turn motif), need to be phosphorylated for its full activation. Ref.9 Ref.12
Subunit structure	Interacts with ZA20D3 By similarity. Interacts with ANDR. Interacts with PRKCB. Interacts (via REM 1 and REM 2 repeats) with RAC1. Interacts (via REM 1 repeat) with RHOA. Interacts with RHOB. In case of infection, interacts with S.typhimurium protein sspH1. Interacts (via C-terminus) with PDPK1. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.25 Ref.26
Subcellular location	Cytoplasm. Nucleus. Endosome. Cell membrane; Peripheral membrane protein. Cleavage furrow. Midbody. Note: Associates with chromatin in a ligand-dependent manner. Localization to endosomes is mediated via its interaction with RHOB. Association to the cell membrane is dependent on Ser-374 phosphorylation. Accumulates during telophase at the cleavage furrow and finally concentrates around the midbody in cytokinesis. Ref.11 Ref.15 Ref.18
Tissue specificity	Found ubiquitously. Expressed in heart, brain, placenta, lung, skeletal muscle, kidney and pancreas. Expressed in numerous tumor cell lines, especially in breast tumor cells. Ref.29
Domain	The C1 domain does not bind the diacylglycerol (DAG).
Post-translational modification	Autophosphorylated; preferably on serine. Phosphorylated during mitosis. Ref.13 Ref.18 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.
Biophysicochemical properties	Kinetic parameters: KM=20.6 µM for HDAC5 Ref.25

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cell membrane Cytoplasm Endosome Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chromatin regulator Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of JUN kinase activity Traceable author statement PubMed 8805275. Source: ProtInc epithelial cell migration Inferred from mutant phenotype Ref.29. Source: UniProtKB hyperosmotic response Inferred from electronic annotation. Source: Compara regulation of cell motility Inferred from mutant phenotype Ref.29. Source: UniProtKB regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.15. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cleavage furrow Inferred from direct assay Ref.18. Source: UniProtKB cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: Compara endosome Inferred from direct assay Ref.11. Source: UniProtKB midbody Inferred from direct assay Ref.18. Source: UniProtKB nucleus Inferred from direct assay Ref.15. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW GTP-Rho binding Inferred from direct assay Ref.31Ref.11. Source: UniProtKB Rac GTPase binding Inferred from direct assay Ref.34. Source: UniProtKB androgen receptor binding Inferred from direct assay Ref.15Ref.21. Source: UniProtKB chromatin binding Inferred from direct assay Ref.21. Source: UniProtKB histone binding Inferred from direct assay Ref.21. Source: UniProtKB histone deacetylase binding Inferred from direct assay Ref.25. Source: UniProtKB histone kinase activity (H3-T11 specific) Inferred from direct assay Ref.21. Source: UniProtKB ligand-dependent nuclear receptor transcription coactivator activity Inferred from direct assay Ref.15. Source: UniProtKB protein kinase C activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CCDC85B	Q15834	2	EBI-602382,EBI-739674
MAPK12	P53778	2	EBI-602382,EBI-602406
MLTK	Q9NYL2-1	2	EBI-602382,EBI-687346

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q16512-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q16512-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: MASDAVQ → MAEANNPSEQELE

Note: No experimental confirmation available.

Isoform 3 (identifier: Q16512-3)

The sequence of this isoform differs from the canonical sequence as follows:
     603-603: S → R
     604-942: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 942

942

Serine/threonine-protein kinase N1

PRO_0000055719

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

Site

108 – 109

2

Cleavage; by caspase-3

Site

454 – 455

2

Cleavage; by caspase-3

Site

558 – 559

2

Cleavage; by caspase-3

Amino acid modifications

Modified residue

205

1

Phosphoserine Ref.20 Ref.23

Modified residue

374

1

Phosphoserine By similarity

Modified residue

448

1

N6-acetyllysine Ref.24

Modified residue

533

1

Phosphoserine Ref.17 Ref.22 Ref.23 Ref.27

Modified residue

537

1

Phosphoserine Ref.20 Ref.22 Ref.23 Ref.27

Modified residue

559

1

Phosphoserine Ref.22 Ref.23

Modified residue

562

1

Phosphoserine Ref.17 Ref.22 Ref.23 Ref.27 Ref.30

Modified residue

774

1

Phosphothreonine; by PDPK1 Ref.13

Modified residue

778

1

Phosphothreonine Ref.19

Modified residue

914

1

Phosphothreonine Ref.23

Modified residue

916

1

Phosphoserine Ref.22 Ref.23

Natural variations

Alternative sequence

1 – 7

7

MASDAVQ → MAEANNPSEQELE in isoform 2.

VSP_038143

Alternative sequence

603

1

S → R in isoform 3.

VSP_039213

Alternative sequence

604 – 942

339

Missing in isoform 3.

VSP_039214

Natural variant

185

1

R → C in a metastatic melanoma sample; somatic mutation. Ref.35

VAR_042337

Natural variant

197

1

A → E. Ref.35

VAR_042338

Natural variant

436

1

R → W. Ref.35
Corresponds to variant rs35132656 [ dbSNP | Ensembl ].

VAR_042339

Natural variant

520

1

R → Q. Ref.35
Corresponds to variant rs56273055 [ dbSNP | Ensembl ].

VAR_042340

Natural variant

555

1

L → I. Ref.3 Ref.35
Corresponds to variant rs34309238 [ dbSNP | Ensembl ].

VAR_042341

Natural variant

635

1

R → Q. Ref.35
Corresponds to variant rs35416389 [ dbSNP | Ensembl ].

VAR_042342

Natural variant

718

1

I → V. Ref.6 Ref.35
Corresponds to variant rs2230539 [ dbSNP | Ensembl ].

VAR_042343

Natural variant

873

1

F → L in a breast infiltrating ductal carcinoma sample; somatic mutation. Ref.35

VAR_042344

Natural variant

901

1

V → I. Ref.3 Ref.5 Ref.35
Corresponds to variant rs10846 [ dbSNP | Ensembl ].

VAR_014937

Natural variant

921

1

A → V in a colorectal adenocarcinoma sample; somatic mutation. Ref.35

VAR_042345

Experimental info

Mutagenesis

108

1

D → A: Abolishes cleavage by caspase-3 and formation of AF1 fragment. Ref.12

Mutagenesis

451

1

D → A: Abolishes cleavage by caspase-3 and formation of 70 kDa fragment. Ref.12

Mutagenesis

454

1

D → A: Abolishes cleavage by caspase-3 and formation of 70 kDa fragment. Ref.12

Mutagenesis

558

1

D → A: Abolishes cleavage by caspase-3 and formation of AF3 fragment. Ref.12

Mutagenesis

560

1

D → A: Abolishes cleavage by caspase-3 and formation of AF3 fragment. Ref.12

Mutagenesis

644

1

K → E: Abolishes Serine/threonine-protein kinase activity. Ref.1 Ref.21

Mutagenesis

644

1

K → R: Substantial reduction of autophosphorylation. Ref.1 Ref.21

Sequence conflict

191

1

G → D in AAB33345. Ref.2

Sequence conflict

191

1

G → D in AAC50209. Ref.2

Sequence conflict

562

1

S → P in BAG36611. Ref.3

Sequence conflict

736

1

I → T no nucleotide entry Ref.6

Sequence conflict

750

1

T → A no nucleotide entry Ref.6

Sequence conflict

800

1

G → A no nucleotide entry Ref.6

Sequence conflict

812

1

E → G in BAG36611. Ref.3

Sequence conflict

887

1

L → P in BAG53845. Ref.3

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

Beta strand

194 – 196

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 22, 2009. Version 2. Checksum: 61360295EC70BB8E	FASTA	942	103,932
	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 GQLENQAAPD 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
	Isoform 2 [UniParc]. Checksum: 882D58AABCFDCEE1	FASTA	948	104,673
	10 20 30 40 50 60 MAEANNPSEQ ELESEPRSWS LLEQLGLAGA DLAAPGVQQQ LELERERLRR EIRKELKLKE 70 80 90 100 110 120 GAENLRRATT DLGRSLGPVE LLLRGSSRRL DLLHQQLQEL HAHVVLPDPA ATHDGPQSPG 130 140 150 160 170 180 AGGPTCSATN LSRVAGLEKQ LAIELKVKQG AENMIQTYSN GSTKDRKLLL TAQQMLQDSK 190 200 210 220 230 240 TKIDIIRMQL RRALQAGQLE NQAAPDDTQG SPDLGAVELR IEELRHHFRV EHAVAEGAKN 250 260 270 280 290 300 VLRLLSAAKA PDRKAVSEAQ EKLTESNQKL GLLREALERR LGELPADHPK GRLLREELAA 310 320 330 340 350 360 ASSAAFSTRL AGPFPATHYS TLCKPAPLTG TLEVRVVGCR DLPETIPWNP TPSMGGPGTP 370 380 390 400 410 420 DSRPPFLSRP ARGLYSRSGS LSGRSSLKAE AENTSEVSTV LKLDNTVVGQ TSWKPCGPNA 430 440 450 460 470 480 WDQSFTLELE RARELELAVF WRDQRGLCAL KFLKLEDFLD NERHEVQLDM EPQGCLVAEV 490 500 510 520 530 540 TFRNPVIERI PRLRRQKKIF SKQQGKAFQR ARQMNIDVAT WVRLLRRLIP NATGTGTFSP 550 560 570 580 590 600 GASPGSEART TGDISVEKLN LGTDSDSSPQ KSSRDPPSSP SSLSSPIQES TAPELPSETQ 610 620 630 640 650 660 ETPGPALCSP LRKSPLTLED FKFLAVLGRG HFGKVLLSEF RPSGELFAIK ALKKGDIVAR 670 680 690 700 710 720 DEVESLMCEK RILAAVTSAG HPFLVNLFGC FQTPEHVCFV MEYSAGGDLM LHIHSDVFSE 730 740 750 760 770 780 PRAIFYSACV VLGLQFLHEH KIVYRDLKLD NLLLDTEGYV KIADFGLCKE GMGYGDRTST 790 800 810 820 830 840 FCGTPEFLAP EVLTDTSYTR AVDWWGLGVL LYEMLVGESP FPGDDEEEVF DSIVNDEVRY 850 860 870 880 890 900 PRFLSAEAIG IMRRLLRRNP ERRLGSSERD AEDVKKQPFF RTLGWEALLA RRLPPPFVPT 910 920 930 940 LSGRTDVSNF DEEFTGEAPT LSPPRDARPL TAAEQAAFLD FDFVAGGC
	Isoform 3 [UniParc]. Checksum: 9CC7C140CE6C5547	FASTA	603	66,060
	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 GQLENQAAPD 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 LCR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-644. Tissue: Hippocampus.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANTS ILE-555 AND ILE-901. Tissue: Kidney, Synovium and Thymus.
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORMS 1 AND 3), VARIANT ILE-901. Tissue: Brain and Placenta.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 700-800 (ISOFORMS 1/2), VARIANT VAL-718.
[7]	"PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163." Palmer R.H., Schonwasser D.C., Rahman D., Pappin D.J., Herget T., Parker P.J. FEBS Lett. 378:281-285(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MARCKS.
[8]	"PKN associates and phosphorylates the head-rod domain of neurofilament protein." Mukai H., Toshimori M., Shibata H., Kitagawa M., Shimakawa M., Miyahara M., Sunakawa H., Ono Y. J. Biol. Chem. 271:9816-9822(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NEFH; NEFL AND NEFM.
[9]	"Protein kinase N (PKN) and PKN-related protein rhophilin as targets of small GTPase Rho." Watanabe G., Saito Y., Madaule P., Ishizaki T., Fujisawa K., Morii N., Mukai H., Ono Y., Kakizuka A., Narumiya S. Science 271:645-648(1996) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH RHOA.
[10]	"Domain-specific phosphorylation of vimentin and glial fibrillary acidic protein by PKN." Matsuzawa K., Kosako H., Inagaki N., Shibata H., Mukai H., Ono Y., Amano M., Kaibuchi K., Matsuura Y., Azuma I., Inagaki M. Biochem. Biophys. Res. Commun. 234:621-625(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GFAP AND VIM.
[11]	"PRK1 is targeted to endosomes by the small GTPase, RhoB." Mellor H., Flynn P., Nobes C.D., Hall A., Parker P.J. J. Biol. Chem. 273:4811-4814(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH RHOB.
[12]	"Proteolytic activation of PKN by caspase-3 or related protease during apoptosis." Takahashi M., Mukai H., Toshimori M., Miyamoto M., Ono Y. Proc. Natl. Acad. Sci. U.S.A. 95:11566-11571(1998) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, PROTEOLYTIC PROCESSING, MUTAGENESIS OF ASP-108; ASP-451; ASP-454; ASP-558 AND ASP-560.
[13]	"Phosphorylation of protein kinase N by phosphoinositide-dependent protein kinase-1 mediates insulin signals to the actin cytoskeleton." Dong L.Q., Landa L.R., Wick M.J., Zhu L., Mukai H., Ono Y., Liu F. Proc. Natl. Acad. Sci. U.S.A. 97:5089-5094(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-774 BY PDPK1, INTERACTION WITH PDPK1.
[14]	"Phosphorylation of tau is regulated by PKN." Taniguchi T., Kawamata T., Mukai H., Hasegawa H., Isagawa T., Yasuda M., Hashimoto T., Terashima A., Nakai M., Mori H., Ono Y., Tanaka C. J. Biol. Chem. 276:10025-10031(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAPT.
[15]	"A novel inducible transactivation domain in the androgen receptor: implications for PRK in prostate cancer." Metzger E., Muller J.M., Ferrari S., Buettner R., Schule R. EMBO J. 22:270-280(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ANDR.
[16]	"A Salmonella type III secretion effector interacts with the mammalian serine/threonine protein kinase PKN1." Haraga A., Miller S.I. Cell. Microbiol. 8:837-846(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH S.TYPHIMURIUM SSPH1.
[17]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-533 AND SER-562, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from cytokinesis." Schmidt A., Durgan J., Magalhaes A., Hall A. EMBO J. 26:1624-1636(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[19]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-778, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"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-205 AND SER-537, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[21]	"Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation." Metzger E., Yin N., Wissmann M., Kunowska N., Fischer K., Friedrichs N., Patnaik D., Higgins J.M., Potier N., Scheidtmann K.H., Buettner R., Schule R. Nat. Cell Biol. 10:53-60(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF LYS-644.
[22]	"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-533; SER-537; SER-559; SER-562 AND SER-916, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[23]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205; SER-533; SER-537; SER-559; SER-562; THR-914 AND SER-916, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[24]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-448, MASS SPECTROMETRY.
[25]	"Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases." Harrison B.C., Huynh K., Lundgaard G.L., Helmke S.M., Perryman M.B., McKinsey T.A. FEBS Lett. 584:1103-1110(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH HDAC5; HDAC7 AND HDAC9.
[26]	"Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4." Metzger E., Imhof A., Patel D., Kahl P., Hoffmeyer K., Friedrichs N., Muller J.M., Greschik H., Kirfel J., Ji S., Kunowska N., Beisenherz-Huss C., Gunther T., Buettner R., Schule R. Nature 464:792-796(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRKCB.
[27]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-533; SER-537 AND SER-562, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[28]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration." Lachmann S., Jevons A., De Rycker M., Casamassima A., Radtke S., Collazos A., Parker P.J. PLoS ONE 6:E21732-E21732(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL MIGRATION, TISSUE SPECIFICITY.
[30]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562, MASS SPECTROMETRY.
[31]	"The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1." Maesaki R., Ihara K., Shimizu T., Kuroda S., Kaibuchi K., Hakoshima T. Mol. Cell 4:793-803(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 13-98 IN COMPLEX WITH RHOA.
[32]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 13-98.
[33]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 116-199 IN COMPLEX WITH RAC1.
[34]	"The Rac1 polybasic region is required for interaction with its effector PRK1." Modha R., Campbell L.J., Nietlispach D., Buhecha H.R., Owen D., Mott H.R. J. Biol. Chem. 283:1492-1500(2008) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 122-199 IN COMPLEX WITH RAC1.
[35]	"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: 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D26181 mRNA. Translation: BAA05169.1.
S75546 mRNA. Translation: AAB33345.1.
U33053 mRNA. Translation: AAC50209.1.
AK123007 mRNA. Translation: BAG53845.1.
AK292130 mRNA. Translation: BAF84819.1.
AK313886 mRNA. Translation: BAG36611.1.
AC008569 Genomic DNA. No translation available.
BC040061 mRNA. Translation: AAH40061.1.
BC094766 mRNA. Translation: AAH94766.1.

IPI

IPI00002803.
IPI00412672.
IPI00965991.

PIR

JC2129.
S51162.

RefSeq

NP_002732.3. NM_002741.3.
NP_998725.1. NM_213560.1.

UniGene

Hs.466044.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q16512.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-34240N.

IntAct

Q16512. 11 interactions.

MINT

MINT-118694.

STRING

9606.ENSP00000343325.

PTM databases

PhosphoSite

Q16512.

Polymorphism databases

DMDM

259016304.

Proteomic databases

PaxDb

Q16512.

PRIDE

Q16512.

Protocols and materials databases

DNASU

5585.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000242783; ENSP00000242783; ENSG00000123143.
ENST00000342216; ENSP00000343325; ENSG00000123143.

GeneID

5585.

KEGG

hsa:5585.

UCSC

uc002myp.3. human.
uc002myq.3. human.

Organism-specific databases

CTD

5585.

GeneCards

GC19P014544.

H-InvDB

HIX0027472.

HGNC

HGNC:9405. PKN1.

HPA

CAB010278.
HPA003982.

MIM

601032. gene.

neXtProt

NX_Q16512.

PharmGKB

PA33769.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG108317.

KO

K06071.

OMA

EFRSSGE.

OrthoDB

EOG4VDPXV.

Enzyme and pathway databases

BRENDA

2.7.11.13. 2681.

Pathway_Interaction_DB

ar_tf_pathway. Regulation of Androgen receptor activity.
p38gammadeltapathway. Signaling mediated by p38-gamma and p38-delta.

SignaLink

Q16512.

Gene expression databases

Bgee

Q16512.

CleanEx

HS_PKN1.

Genevestigator

Q16512.

GermOnline

ENSG00000123143. 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.
PS50004. C2. False negative.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16512.

ChEMBL

CHEMBL3384.

ChiTaRS

PKN1. human.

EvolutionaryTrace

Q16512.

GenomeRNAi

5585.

NextBio

21660.

PMAP-CutDB

Q16512.

SOURCE

Search...

Entry information

Entry name

PKN1_HUMAN

Accession

Primary (citable) accession number: Q16512
Secondary accession number(s): A8K7W5 , B2R9R4, B3KVN3, Q15143, Q504U4, Q8IUV5, Q9UD44

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	September 22, 2009
Last modified:	May 29, 2013
This is version 155 of the entry and version 2 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.