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Q16513 (PKN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase N2

EC=2.7.11.13
Alternative name(s):
PKN gamma
Protein kinase C-like 2
Protein-kinase C-related kinase 2
Gene names
Name:PKN2
Synonyms:PRK2, PRKCL2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length984 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. Ref.8 Ref.9 Ref.12 Ref.15 Ref.16 Ref.17 Ref.20 Ref.29 Ref.32 Ref.33

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Kinase activity is activated upon binding to GTP-bound Rhoa/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during apoptosis. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-816 (activation loop of the kinase domain) and Thr-958 (turn motif), need to be phosphorylated for its full activation. Ref.7 Ref.12 Ref.22

Subunit structure

Interacts (via the REM repeats) with RHOA (GTP-bound form preferentially). Interacts (via the REM repeats) with RAC1 (GTP-bound form preferentially). Interacts with NCK1 (via SH3 domains). Interacts with CD44 By similarity. Interacts with RHOA (GTP-bound form preferentially) and RAC1 (GTP-bound form preferentially); the interactions induce its autophosphorylation. Interacts (via C-terminal kinase domain) with PDPK1; the interaction stimulates PDPK1 kinase activity. Interacts with MAP3K2; the interaction activates PRK2 kinase activity in a MAP3K2-independent kinase activity. Interacts (via C-terminal domain) with AKT1; the interaction occurs with the C-terminal cleavage product of PRK2 in apoptotic cells. Interacts (via C-terminus) with PTPN13 (via PDZ 3 domain). Interacts with HCV NS5B (via N-terminal finger domain). Interacts with NCK1, NCK2 and RHOC. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.22 Ref.32

Subcellular location

Cytoplasm. Nucleus. Membrane By similarity. Cell projectionlamellipodium. Cytoplasmcytoskeleton. Cleavage furrow. Midbody. Cell junction. Note: Colocalizes with PTPN13 in lamellipodia-like structures, regions of large actin turnover. Accumulates during telophase at the cleavage furrow and concentrates finally around the midbody in cytokinesis. Recruited to nascent cell-cell contacts at the apical surface of cells. In the course of viral infection, colocalizes with HCV NS5B at perinuclear region in the cytoplasm. Ref.14 Ref.20

Tissue specificity

Ubiquitous. Expressed in numerous tumor cell lines, especially in bladder tumor cells. Ref.10 Ref.33

Induction

Up-regulated during keratinocyte differentiation. Ref.7 Ref.12 Ref.16 Ref.22

Domain

The N-terminal regioninterferes with the interaction between AKT1 and the C-terminal regionof PKN2.

The C1 domain does not bind the diacylglycerol (DAG).

The apoptotic C-terminal cleavage product inhibits EGF-induced kinase activity of AKT1 phosphorylation at 'Thr-308' and 'Ser-473' sites, PDPK1 autophosphorylation and kinases PRKCD and PRKCZ phosphorylations.

Post-translational modification

Autophosphorylated. Phosphorylated during mitosis. Ref.8 Ref.13 Ref.20

Activated by limited proteolysis with trypsin By similarity. Proteolytically cleaved by caspase-3 during the induction of apoptotic cell death. Ref.7

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=15.83 µM for HDAC5 Ref.29

Ontologies

Keywords
   Biological processApoptosis
Cell adhesion
Cell cycle
Cell division
Transcription
Transcription regulation
   Cellular componentCell junction
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapical junction assembly

Inferred from mutant phenotype Ref.32. Source: UniProtKB

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

epithelial cell migration

Inferred from direct assay Ref.33. Source: UniProtKB

positive regulation of cytokinesis

Inferred from mutant phenotype Ref.20. Source: UniProtKB

positive regulation of mitotic cell cycle

Inferred from mutant phenotype Ref.20. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.20. Source: UniProtKB

regulation of cell motility

Inferred from mutant phenotype Ref.33. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

signal transduction

Traceable author statement Ref.2. Source: ProtInc

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentapical junction complex

Inferred from direct assay Ref.32. Source: UniProtKB

centrosome

Inferred from direct assay. Source: HPA

cleavage furrow

Inferred from direct assay Ref.20. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.20. Source: UniProtKB

intermediate filament cytoskeleton

Inferred from direct assay. Source: HPA

lamellipodium

Inferred from direct assay Ref.14. Source: UniProtKB

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

midbody

Inferred from direct assay Ref.20. Source: UniProtKB

nucleus

Inferred from direct assay Ref.14. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

histone deacetylase binding

Inferred from direct assay Ref.29. Source: UniProtKB

poly(A) RNA binding

Inferred from direct assay PubMed 22658674. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10Ref.14Ref.32. Source: UniProtKB

protein kinase C activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein kinase activity

Traceable author statement Ref.2. Source: ProtInc

protein serine/threonine kinase activity

Inferred from direct assay Ref.29. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PDK1Q151186EBI-2511350,EBI-7016221

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16513-1)

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: Q16513-2)

The sequence of this isoform differs from the canonical sequence as follows:
     375-390: Missing.
Isoform 3 (identifier: Q16513-3)

The sequence of this isoform differs from the canonical sequence as follows:
     428-475: Missing.
Isoform 4 (identifier: Q16513-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-157: Missing.
Isoform 5 (identifier: Q16513-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-326: Missing.
     327-329: LTG → MNS

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 984984Serine/threonine-protein kinase N2
PRO_0000055722

Regions

Repeat44 – 11976REM 1
Repeat133 – 21381REM 2
Repeat214 – 29582REM 3
Domain330 – 463134C2
Domain657 – 916260Protein kinase
Domain917 – 98468AGC-kinase C-terminal
Nucleotide binding663 – 6719ATP By similarity
Region382 – 46382Necessary to rescue apical junction formation By similarity
Region917 – 97761Necessary for the catalytic activity
Region978 – 9847Negatively regulates the responsiveness of the catalytic activity by cardiolipin and is required for optimal activation by the GTP-bound RhoA

Sites

Active site7821Proton acceptor By similarity
Binding site6861ATP By similarity
Site117 – 1182Cleavage; by caspase-3
Site700 – 7012Cleavage; by caspase-3

Amino acid modifications

Modified residue771N6-acetyllysine By similarity
Modified residue1101Phosphoserine Ref.25
Modified residue1211Phosphothreonine Ref.25
Modified residue1241Phosphothreonine Ref.25
Modified residue3021Phosphoserine Ref.19 Ref.25 Ref.30
Modified residue3061Phosphoserine Ref.19 Ref.25 Ref.30
Modified residue3601Phosphoserine Ref.19 Ref.25 Ref.30
Modified residue3621Phosphoserine Ref.25
Modified residue5351Phosphoserine Ref.25
Modified residue5831Phosphoserine Ref.30
Modified residue6281Phosphothreonine Ref.25
Modified residue6311Phosphoserine Ref.25
Modified residue8161Phosphothreonine; by PDPK1 Ref.13
Modified residue9581Phosphothreonine Ref.18 Ref.24 Ref.25 Ref.30

Natural variations

Alternative sequence1 – 326326Missing in isoform 5.
VSP_042180
Alternative sequence1 – 157157Missing in isoform 4.
VSP_042181
Alternative sequence327 – 3293LTG → MNS in isoform 5.
VSP_042182
Alternative sequence375 – 39016Missing in isoform 2.
VSP_042183
Alternative sequence428 – 47548Missing in isoform 3.
VSP_042184
Natural variant941E → D.
Corresponds to variant rs12039846 [ dbSNP | Ensembl ].
VAR_050562
Natural variant1971A → E.
Corresponds to variant rs35207128 [ dbSNP | Ensembl ].
VAR_050563
Natural variant6551Q → R.
Corresponds to variant rs12085658 [ dbSNP | Ensembl ].
VAR_050564

Experimental info

Mutagenesis1171D → A: Prevents proteolytic processing by caspase-3 during apoptosis. Diminishes pro-apoptotic function; when associated with E-700. Ref.7 Ref.12
Mutagenesis6861K → R: Does not inhibit interaction with PTPN13. Ref.14
Mutagenesis7001D → E: Prevents proteolytic processing by caspase-3 during apoptosis. Diminishes pro-apoptotic function; when associated with A-117. Ref.7 Ref.12
Mutagenesis8161T → A: Reduces catalytic activity. Ref.22
Mutagenesis9581T → A: Abolishes catalytic activity. Ref.22
Mutagenesis9741F → A: Abolishes interaction with PDPK1 and prevents the phosphorylation of AKT1 at 'Ser-473'. Ref.9
Mutagenesis9771F → A or L: Abolishes interaction with PDPK1 and prevents the phosphorylation of AKT1 at 'Ser-473'. Reduces catalytic activity by 90%. Ref.9 Ref.22
Mutagenesis9771F → W or Y: Reduces catalytic activity by 50%. Ref.9 Ref.22
Mutagenesis9781D → A or S: Abolishes interaction with PDPK1 and prevents the phosphorylation of AKT1 at 'Ser-473'. Ref.9 Ref.22
Mutagenesis9781D → A: Does not inhibit catalytic activity. Ref.9 Ref.22
Mutagenesis9791Y → A: Abolishes interaction with PDPK1 and prevents the phosphorylation of AKT1 at 'Ser-473'. Ref.9 Ref.22
Mutagenesis9791Y → A: Reduces catalytic activity by 50%. Ref.9 Ref.22
Mutagenesis9791Y → F, L or W: Reduces catalytic activity by 25%. Ref.9 Ref.22
Mutagenesis9841C → S: Inhibits interaction with PTPN13. Ref.14
Sequence conflict4831I → V in BAG62673. Ref.3
Sequence conflict5651K → R in BAG60783. Ref.3
Sequence conflict6251K → R in BAG62673. Ref.3
Sequence conflict7951F → L in AAI25200. Ref.6

Secondary structure

...................................................... 984
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 687EC417A0F51C1D

FASTA984112,035
        10         20         30         40         50         60 
MASNPERGEI LLTELQGDSR SLPFSENVSA VQKLDFSDTM VQQKLDDIKD RIKREIRKEL 

        70         80         90        100        110        120 
KIKEGAENLR KVTTDKKSLA YVDNILKKSN KKLEELHHKL QELNAHIVVS DPEDITDCPR 

       130        140        150        160        170        180 
TPDTPNNDPR CSTSNNRLKA LQKQLDIELK VKQGAENMIQ MYSNGSSKDR KLHGTAQQLL 

       190        200        210        220        230        240 
QDSKTKIEVI RMQILQAVQT NELAFDNAKP VISPLELRME ELRHHFRIEF AVAEGAKNVM 

       250        260        270        280        290        300 
KLLGSGKVTD RKALSEAQAR FNESSQKLDL LKYSLEQRLN EVPKNHPKSR IIIEELSLVA 

       310        320        330        340        350        360 
ASPTLSPRQS MISTQNQYST LSKPAALTGT LEVRLMGCQD ILENVPGRSK ATSVALPGWS 

       370        380        390        400        410        420 
PSETRSSFMS RTSKSKSGSS RNLLKTDDLS NDVCAVLKLD NTVVGQTSWK PISNQSWDQK 

       430        440        450        460        470        480 
FTLELDRSRE LEISVYWRDW RSLCAVKFLR LEDFLDNQRH GMCLYLEPQG TLFAEVTFFN 

       490        500        510        520        530        540 
PVIERRPKLQ RQKKIFSKQQ GKTFLRAPQM NINIATWGRL VRRAIPTVNH SGTFSPQAPV 

       550        560        570        580        590        600 
PTTVPVVDVR IPQLAPPASD STVTKLDFDL EPEPPPAPPR ASSLGEIDES SELRVLDIPG 

       610        620        630        640        650        660 
QDSETVFDIQ NDRNSILPKS QSEYKPDTPQ SGLEYSGIQE LEDRRSQQRF QFNLQDFRCC 

       670        680        690        700        710        720 
AVLGRGHFGK VLLAEYKNTN EMFAIKALKK GDIVARDEVD SLMCEKRIFE TVNSVRHPFL 

       730        740        750        760        770        780 
VNLFACFQTK EHVCFVMEYA AGGDLMMHIH TDVFSEPRAV FYAACVVLGL QYLHEHKIVY 

       790        800        810        820        830        840 
RDLKLDNLLL DTEGFVKIAD FGLCKEGMGY GDRTSTFCGT PEFLAPEVLT ETSYTRAVDW 

       850        860        870        880        890        900 
WGLGVLIYEM LVGESPFPGD DEEEVFDSIV NDEVRYPRFL STEAISIMRR LLRRNPERRL 

       910        920        930        940        950        960 
GASEKDAEDV KKHPFFRLID WSALMDKKVK PPFIPTIRGR EDVSNFDDEF TSEAPILTPP 

       970        980 
REPRILSEEE QEMFRDFDYI ADWC 

« Hide

Isoform 2 [UniParc].

Checksum: BE8D7EDA728D78EE
Show »

FASTA968110,345
Isoform 3 [UniParc].

Checksum: 43128E92FEDC05B4
Show »

FASTA936106,217
Isoform 4 [UniParc].

Checksum: B08B24A67D1697CE
Show »

FASTA82794,136
Isoform 5 [UniParc].

Checksum: D0B6E1DEA98B3C0D
Show »

FASTA65875,171

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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: B-cell and Spleen.
[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. expand/collapse author list , 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 2; 4 AND 5).
Tissue: Placenta and Spleen.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 3).
[7]"Specific proteolysis of the kinase protein kinase C-related kinase 2 by caspase-3 during apoptosis. Identification by a novel, small pool expression cloning strategy."
Cryns V.L., Byun Y., Rana A., Mellor H., Lustig K.D., Ghanem L., Parker P.J., Kirschner M.W., Yuan J.
J. Biol. Chem. 272:29449-29453(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PROTEOLYTIC PROCESSING, MUTAGENESIS OF ASP-117 AND ASP-700.
[8]"The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization."
Vincent S., Settleman J.
Mol. Cell. Biol. 17:2247-2256(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAC1 AND RHOA, AUTOPHOSPHORYLATION.
[9]"PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2."
Balendran A., Casamayor A., Deak M., Paterson A., Gaffney P., Currie R., Downes C.P., Alessi D.R.
Curr. Biol. 9:393-404(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PDPK1, MUTAGENESIS OF PHE-974; PHE-977; ASP-978 AND TYR-979.
[10]"Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck."
Braverman L.E., Quilliam L.A.
J. Biol. Chem. 274:5542-5549(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCK1 AND NCK2, TISSUE SPECIFICITY.
[11]"MEK kinase 2 binds and activates protein kinase C-related kinase 2. Bifurcation of kinase regulatory pathways at the level of an MAPK kinase kinase."
Sun W., Vincent S., Settleman J., Johnson G.L.
J. Biol. Chem. 275:24421-24428(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K2.
[12]"Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage."
Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.
J. Biol. Chem. 275:34451-34458(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS, FUNCTION IN AKT1 ACTIVITY INHIBITION, ENZYME REGULATION, INTERACTION WITH AKT1, MUTAGENESIS OF ASP-117 AND ASP-700.
[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-816 BY PDPK1, INTERACTION WITH PDPK1.
[14]"The protein kinase C-related kinase PRK2 interacts with the protein tyrosine phosphatase PTP-BL via a novel PDZ domain binding motif."
Gross C., Heumann R., Erdmann K.S.
FEBS Lett. 496:101-104(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN13, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-686 AND CYS-984.
[15]"Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by a C-terminal PRK2 fragment."
Hodgkinson C.P., Sale G.J.
Biochemistry 41:561-569(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN KINASE ACTIVITY INHIBITION, INTERACTION WITH PDPK1.
[16]"Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in keratinocyte cell-cell adhesion."
Calautti E., Grossi M., Mammucari C., Aoyama Y., Pirro M., Ono Y., Li J., Dotto G.P.
J. Cell Biol. 156:137-148(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL ADHESION, INDUCTION.
[17]"Protein kinase C-related kinase 2 regulates hepatitis C virus RNA polymerase function by phosphorylation."
Kim S.J., Kim J.H., Kim Y.G., Lim H.S., Oh J.W.
J. Biol. Chem. 279:50031-50041(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HCV REPLICATION, FUNCTION IN PHOSPHORYLATION OF NS5B, INTERACTION WITH HCV NS5B.
[18]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-958, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"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-302; SER-306 AND SER-360, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"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.
[21]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"The C-terminus of PRK2/PKNgamma is required for optimal activation by RhoA in a GTP-dependent manner."
Lim W.G., Chen X., Liu J.P., Tan B.J., Zhou S., Smith A., Lees N., Hou L., Gu F., Yu X.Y., Du Y., Smith D., Verma C., Liu K., Duan W.
Arch. Biochem. Biophys. 479:170-178(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, INTERACTION WITH PDPK1, MUTAGENESIS OF THR-816; THR-958; PHE-977; ASP-978 AND TYR-979.
[23]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"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 THR-958, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[25]"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-110; THR-121; THR-124; SER-302; SER-306; SER-360; SER-362; SER-535; THR-628; SER-631 AND THR-958, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[26]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[29]"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 IN PHOSPHORYLATION OF HDAC5, BIOPHYSICOCHEMICAL PROPERTIES.
[30]"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-302; SER-306; SER-360; SER-583 AND THR-958, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[31]"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].
[32]"The Rho target PRK2 regulates apical junction formation in human bronchial epithelial cells."
Wallace S.W., Magalhaes A., Hall A.
Mol. Cell. Biol. 31:81-91(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAC1; RHOA AND RHOC.
[33]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U33052 mRNA. Translation: AAC50208.1.
S75548 mRNA. Translation: AAB33346.1.
AK298595 mRNA. Translation: BAG60783.1.
AK300304 mRNA. Translation: BAG62057.1.
AK301066 mRNA. Translation: BAG62673.1.
AL136381, AC119426 Genomic DNA. Translation: CAI23271.1.
CH471097 Genomic DNA. Translation: EAW73161.1.
CH471097 Genomic DNA. Translation: EAW73164.1.
BC125199 mRNA. Translation: AAI25200.1.
CCDSCCDS714.1. [Q16513-1]
PIRS67527.
RefSeqNP_006247.1. NM_006256.2. [Q16513-1]
XP_005271088.1. XM_005271031.1. [Q16513-2]
UniGeneHs.440833.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4CRSX-ray2.75A646-984[»]
ProteinModelPortalQ16513.
SMRQ16513. Positions 56-107, 136-199, 618-984.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111572. 27 interactions.
IntActQ16513. 14 interactions.
MINTMINT-198348.
STRING9606.ENSP00000359552.

Chemistry

BindingDBQ16513.
ChEMBLCHEMBL3032.
GuidetoPHARMACOLOGY1521.

PTM databases

PhosphoSiteQ16513.

Polymorphism databases

DMDM6225859.

Proteomic databases

MaxQBQ16513.
PaxDbQ16513.
PRIDEQ16513.

Protocols and materials databases

DNASU5586.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370505; ENSP00000359536; ENSG00000065243. [Q16513-4]
ENST00000370513; ENSP00000359544; ENSG00000065243. [Q16513-3]
ENST00000370521; ENSP00000359552; ENSG00000065243. [Q16513-1]
ENST00000544045; ENSP00000439643; ENSG00000065243. [Q16513-5]
GeneID5586.
KEGGhsa:5586.
UCSCuc001dmn.3. human. [Q16513-1]
uc009wcv.3. human. [Q16513-3]
uc010osp.2. human. [Q16513-2]

Organism-specific databases

CTD5586.
GeneCardsGC01P089149.
HGNCHGNC:9406. PKN2.
HPAHPA034861.
MIM602549. gene.
neXtProtNX_Q16513.
PharmGKBPA33770.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233032.
HOVERGENHBG108317.
InParanoidQ16513.
KOK06071.
OMARSQQMFQ.
PhylomeDBQ16513.
TreeFamTF102005.

Enzyme and pathway databases

BRENDA2.7.11.13. 2681.
SignaLinkQ16513.

Gene expression databases

ArrayExpressQ16513.
BgeeQ16513.
CleanExHS_PKN2.
GenevestigatorQ16513.

Family and domain databases

Gene3D1.10.287.160. 3 hits.
2.60.40.150. 2 hits.
InterProIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR011072. HR1_rho-bd.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF02185. HR1. 3 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTSM00239. C2. 1 hit.
SM00742. Hr1. 3 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF46585. SSF46585. 3 hits.
SSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

ChiTaRSPKN2. human.
GeneWikiPKN2.
GenomeRNAi5586.
NextBio21666.
PMAP-CutDBQ16513.
PROQ16513.
SOURCESearch...

Entry information

Entry namePKN2_HUMAN
AccessionPrimary (citable) accession number: Q16513
Secondary accession number(s): B4DQ21 expand/collapse secondary AC list , B4DTP5, B4DVG1, D3DT24, Q08AF4, Q9H1W4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM