Q86Y07 (VRK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase VRK2
EC=2.7.11.1

Alternative name(s):
Vaccinia-related kinase 2

Gene names

Name:

VRK2

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

General annotation (Comments)

Function	Serine/threonine kinase that regulates several signal transduction pathways. Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes. Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins. Downregulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to ERBB2 and HRAS. Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant. Ref.2 Ref.9 Ref.11 Ref.12 Ref.14 Ref.15 Ref.17 Isoform 2 phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity. Ref.2 Ref.9 Ref.11 Ref.12 Ref.14 Ref.15 Ref.17
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3. Ref.14
Subunit structure	Isoform 1 interacts with MAP3K7, MAP2K7, MAP2K1 and KSR1. Isoform 1 and isoform 2 interact with RAN and MAPK8IP1. Isoform 1 interacts with Epstein-Barr virus BHRF1; this interaction is involved in protecting cells from apoptosis. Ref.10 Ref.12 Ref.14 Ref.15 Ref.17
Subcellular location	Isoform 1: Cytoplasm. Endoplasmic reticulum membrane; Single-pass type IV membrane protein Potential. Mitochondrion membrane; Single-pass type IV membrane protein Potential Ref.2 Ref.9 Ref.14 Ref.15 Ref.17. Isoform 2: Cytoplasm. Nucleus Ref.2 Ref.9 Ref.14 Ref.15 Ref.17.
Tissue specificity	Isoform 1 and isoform 2 are expressed in various tumor cell lines. Expression of isoform 1 inversely correlates with ERBB2 in breast carcinomas (at protein level). Widely expressed. Highly expressed in fetal liver, skeletal muscle, pancreas, heart, peripheral blood leukocytes and testis. Ref.1 Ref.2 Ref.17
Post-translational modification	Isoform 1 and isoform 2 are autophosphorylated. Ref.2 Ref.9
Sequence similarities	Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence CAD54446.2 differs from that shown. Reason: Aberrant splicing.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to oxidative stress Inferred from mutant phenotype Ref.12. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.9Ref.2. Source: UniProtKB regulation of MAPK cascade Inferred from mutant phenotype Ref.17. Source: UniProtKB regulation of interleukin-1-mediated signaling pathway Inferred from mutant phenotype Ref.15. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum membrane Inferred from direct assay Ref.15. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial membrane Inferred from direct assay Ref.15. Source: UniProtKB nucleus Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.9Ref.11Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BHRF1	P03182	7	EBI-1207615,EBI-1207659	From a different organism.
KSR1	Q8IVT5	4	EBI-1207615,EBI-486984
Ksr1	Q61097	8	EBI-1207633,EBI-1536336	From a different organism.
MAP2K1	Q02750	2	EBI-1207615,EBI-492564
Map3k7	Q62073	3	EBI-1207633,EBI-1775345	From a different organism.
Mapk8ip1	Q9WVI9-2	2	EBI-1207636,EBI-288464	From a different organism.
NFATC2	Q13469	4	EBI-1207636,EBI-716258
Nfatc2	Q60591	2	EBI-1207633,EBI-643104	From a different organism.
RAN	P62826	2	EBI-1207633,EBI-286642
Tab1	Q8CF89	2	EBI-1207633,EBI-1778503	From a different organism.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q86Y07-1)

Also known as: VRK2A;

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: Q86Y07-2)

Also known as: VRK2B;

The sequence of this isoform differs from the canonical sequence as follows:
     395-397: EST → VEA
     398-508: Missing.

Isoform 3 (identifier: Q86Y07-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q86Y07-4)

Also known as: 5;

The sequence of this isoform differs from the canonical sequence as follows:
     1-118: Missing.

Isoform 5 (identifier: Q86Y07-5)

Also known as: 6;

The sequence of this isoform differs from the canonical sequence as follows:
     395-396: ES → FR
     397-508: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 508

508

Serine/threonine-protein kinase VRK2

PRO_0000086806

Regions

Transmembrane

487 – 507

21

Helical; Anchor for type IV membrane protein; Potential

Domain

29 – 319

291

Protein kinase

Nucleotide binding

35 – 43

9

ATP By similarity

Region

397 – 508

112

Interaction with MAP3K7

Sites

Active site

166

1

Proton acceptor By similarity

Binding site

61

1

ATP By similarity

Amino acid modifications

Modified residue

336

1

Phosphothreonine Ref.13

Natural variations

Alternative sequence

1 – 118

118

Missing in isoform 4.

VSP_008534

Alternative sequence

1 – 23

23

Missing in isoform 3.

VSP_008533

Alternative sequence

395 – 397

3

EST → VEA in isoform 2.

VSP_008537

Alternative sequence

395 – 396

2

ES → FR in isoform 5.

VSP_008535

Alternative sequence

397 – 508

112

Missing in isoform 5.

VSP_008536

Alternative sequence

398 – 508

111

Missing in isoform 2.

VSP_008538

Natural variant

50

1

N → D. Ref.20
Corresponds to variant rs34130684 [ dbSNP | Ensembl ].

VAR_041293

Natural variant

157

1

I → M. Ref.20
Corresponds to variant rs35966666 [ dbSNP | Ensembl ].

VAR_041294

Natural variant

167

1

I → V. Ref.1 Ref.2 Ref.8 Ref.20
Corresponds to variant rs1051061 [ dbSNP | Ensembl ].

VAR_017095

Natural variant

211

1

N → S.
Corresponds to variant rs36081172 [ dbSNP | Ensembl ].

VAR_051681

Experimental info

Sequence conflict

419

1

K → E in AAO73048. Ref.3

Sequence conflict

419

1

K → E in AAO73049. Ref.3

Sequence conflict

419

1

K → E in AAO73051. Ref.3

Secondary structure

1

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508

Helix Strand Turn

Details...

Beta strand

20 – 22

3

Beta strand

28 – 34

7

Beta strand

43 – 51

9

Helix

53 – 55

3

Beta strand

58 – 64

7

Helix

69 – 80

12

Helix

83 – 93

11

Beta strand

103 – 113

11

Beta strand

115 – 122

8

Beta strand

124 – 127

4

Helix

128 – 131

4

Helix

134 – 136

3

Helix

140 – 159

20

Helix

169 – 171

3

Beta strand

172 – 178

7

Beta strand

181 – 184

4

Beta strand

191 – 194

4

Helix

195 – 197

3

Helix

206 – 208

3

Turn

214 – 216

3

Helix

219 – 223

5

Helix

229 – 245

17

Helix

251 – 253

3

Helix

257 – 269

13

Turn

270 – 272

3

Helix

273 – 278

6

Helix

286 – 296

11

Helix

306 – 313

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (VRK2A) [UniParc]. Last modified March 7, 2006. Version 3. Checksum: 9F3F6FCC9280568F	FASTA	508	58,141
	10 20 30 40 50 60 MPPKRNEKYK LPIPFPEGKV LDDMEGNQWV LGKKIGSGGF GLIYLAFPTN KPEKDARHVV 70 80 90 100 110 120 KVEYQENGPL FSELKFYQRV AKKDCIKKWI ERKQLDYLGI PLFYGSGLTE FKGRSYRFMV 130 140 150 160 170 180 MERLGIDLQK ISGQNGTFKK STVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLGYKNPD 190 200 210 220 230 240 QVYLADYGLS YRYCPNGNHK QYQENPRKGH NGTIEFTSLD AHKGVALSRR SDVEILGYCM 250 260 270 280 290 300 LRWLCGKLPW EQNLKDPVAV QTAKTNLLDE LPQSVLKWAP SGSSCCEIAQ FLVCAHSLAY 310 320 330 340 350 360 DEKPNYQALK KILNPHGIPL GPLDFSTKGQ SINVHTPNSQ KVDSQKAATK QVNKAHNRLI 370 380 390 400 410 420 EKKVHSERSA ESCATWKVQK EEKLIGLMNN EAAQESTRRR QKYQESQEPL NEVNSFPQKI 430 440 450 460 470 480 SYTQFPNSFY EPHQDFTSPD IFKKSRSPSW YKYTSTVSTG ITDLESSTGL WPTISQFTLS 490 500 EETNADVYYY RIIIPVLLML VFLALFFL
	Isoform 2 (VRK2B) [UniParc]. Checksum: 0308378DD02D85EC	FASTA	397	45,030
	10 20 30 40 50 60 MPPKRNEKYK LPIPFPEGKV LDDMEGNQWV LGKKIGSGGF GLIYLAFPTN KPEKDARHVV 70 80 90 100 110 120 KVEYQENGPL FSELKFYQRV AKKDCIKKWI ERKQLDYLGI PLFYGSGLTE FKGRSYRFMV 130 140 150 160 170 180 MERLGIDLQK ISGQNGTFKK STVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLGYKNPD 190 200 210 220 230 240 QVYLADYGLS YRYCPNGNHK QYQENPRKGH NGTIEFTSLD AHKGVALSRR SDVEILGYCM 250 260 270 280 290 300 LRWLCGKLPW EQNLKDPVAV QTAKTNLLDE LPQSVLKWAP SGSSCCEIAQ FLVCAHSLAY 310 320 330 340 350 360 DEKPNYQALK KILNPHGIPL GPLDFSTKGQ SINVHTPNSQ KVDSQKAATK QVNKAHNRLI 370 380 390 EKKVHSERSA ESCATWKVQK EEKLIGLMNN EAAQVEA
	Isoform 3 [UniParc]. Checksum: 425363D6092A57FC	FASTA	485	55,446
	10 20 30 40 50 60 MEGNQWVLGK KIGSGGFGLI YLAFPTNKPE KDARHVVKVE YQENGPLFSE LKFYQRVAKK 70 80 90 100 110 120 DCIKKWIERK QLDYLGIPLF YGSGLTEFKG RSYRFMVMER LGIDLQKISG QNGTFKKSTV 130 140 150 160 170 180 LQLGIRMLDV LEYIHENEYV HGDIKAANLL LGYKNPDQVY LADYGLSYRY CPNGNHKQYQ 190 200 210 220 230 240 ENPRKGHNGT IEFTSLDAHK GVALSRRSDV EILGYCMLRW LCGKLPWEQN LKDPVAVQTA 250 260 270 280 290 300 KTNLLDELPQ SVLKWAPSGS SCCEIAQFLV CAHSLAYDEK PNYQALKKIL NPHGIPLGPL 310 320 330 340 350 360 DFSTKGQSIN VHTPNSQKVD SQKAATKQVN KAHNRLIEKK VHSERSAESC ATWKVQKEEK 370 380 390 400 410 420 LIGLMNNEAA QESTRRRQKY QESQEPLNEV NSFPQKISYT QFPNSFYEPH QDFTSPDIFK 430 440 450 460 470 480 KSRSPSWYKY TSTVSTGITD LESSTGLWPT ISQFTLSEET NADVYYYRII IPVLLMLVFL ALFFL
	Isoform 4 (5) [UniParc]. Checksum: 9F320B446A872E5D	FASTA	390	44,411
	10 20 30 40 50 60 MVMERLGIDL QKISGQNGTF KKSTVLQLGI RMLDVLEYIH ENEYVHGDIK AANLLLGYKN 70 80 90 100 110 120 PDQVYLADYG LSYRYCPNGN HKQYQENPRK GHNGTIEFTS LDAHKGVALS RRSDVEILGY 130 140 150 160 170 180 CMLRWLCGKL PWEQNLKDPV AVQTAKTNLL DELPQSVLKW APSGSSCCEI AQFLVCAHSL 190 200 210 220 230 240 AYDEKPNYQA LKKILNPHGI PLGPLDFSTK GQSINVHTPN SQKVDSQKAA TKQVNKAHNR 250 260 270 280 290 300 LIEKKVHSER SAESCATWKV QKEEKLIGLM NNEAAQESTR RRQKYQESQE PLNEVNSFPQ 310 320 330 340 350 360 KISYTQFPNS FYEPHQDFTS PDIFKKSRSP SWYKYTSTVS TGITDLESST GLWPTISQFT 370 380 390 LSEETNADVY YYRIIIPVLL MLVFLALFFL
	Isoform 5 (6) [UniParc]. Checksum: 773C8DD02D85EC43	FASTA	396	45,034
	10 20 30 40 50 60 MPPKRNEKYK LPIPFPEGKV LDDMEGNQWV LGKKIGSGGF GLIYLAFPTN KPEKDARHVV 70 80 90 100 110 120 KVEYQENGPL FSELKFYQRV AKKDCIKKWI ERKQLDYLGI PLFYGSGLTE FKGRSYRFMV 130 140 150 160 170 180 MERLGIDLQK ISGQNGTFKK STVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLGYKNPD 190 200 210 220 230 240 QVYLADYGLS YRYCPNGNHK QYQENPRKGH NGTIEFTSLD AHKGVALSRR SDVEILGYCM 250 260 270 280 290 300 LRWLCGKLPW EQNLKDPVAV QTAKTNLLDE LPQSVLKWAP SGSSCCEIAQ FLVCAHSLAY 310 320 330 340 350 360 DEKPNYQALK KILNPHGIPL GPLDFSTKGQ SINVHTPNSQ KVDSQKAATK QVNKAHNRLI 370 380 390 EKKVHSERSA ESCATWKVQK EEKLIGLMNN EAAQFR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to Vaccinia virus B1R kinase." Nezu J., Oku A., Jones M.H., Shimane M. Genomics 45:327-331(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT VAL-167. Tissue: Liver.
[2]	"The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines." Blanco S., Klimcakova L., Vega F.M., Lazo P.A. FEBS J. 273:2487-2504(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), IDENTIFICATION (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, VARIANT VAL-167.
[3]	"Identification of 6 different isoforms for Vaccinia-related kinase 2 (VRK2) gene." Suriyapperuma S.P., Sarfarazi M. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4 AND 5).
[4]	"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] (ISOFORM 4). Tissue: Colon.
[5]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Testis.
[6]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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. , 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].
[8]	"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 1), VARIANT VAL-167.
[9]	"Characterization of three paralogous members of the Mammalian vaccinia related kinase family." Nichols R.J., Traktman P. J. Biol. Chem. 279:7934-7946(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION.
[10]	"Human cellular protein VRK2 interacts specifically with Epstein-Barr virus BHRF1, a homologue of Bcl-2, and enhances cell survival." Li L.Y., Liu M.Y., Shih H.M., Tsai C.H., Chen J.Y. J. Gen. Virol. 87:2869-2878(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EPSTEIN-BARR VIRUS BHRF1.
[11]	"The vaccinia-related kinases phosphorylate the N' terminus of BAF, regulating its interaction with DNA and its retention in the nucleus." Nichols R.J., Wiebe M.S., Traktman P. Mol. Biol. Cell 17:2451-2464(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Vaccinia-related kinase 2 modulates the stress response to hypoxia mediated by TAK1." Blanco S., Santos C., Lazo P.A. Mol. Cell. Biol. 27:7273-7283(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAP3K7.
[13]	"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-336, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Proteomics identification of nuclear Ran GTPase as an inhibitor of human VRK1 and VRK2 (vaccinia-related kinase) activities." Sanz-Garcia M., Lopez-Sanchez I., Lazo P.A. Mol. Cell. Proteomics 7:2199-2214(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAN, ENZYME REGULATION.
[15]	"Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein." Blanco S., Sanz-Garcia M., Santos C.R., Lazo P.A. PLoS ONE 3:E1660-E1660(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAPK8IP1; MAPK3K7 AND MAP2K7.
[16]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[17]	"VRK2 inhibits mitogen-activated protein kinase signaling and inversely correlates with ErbB2 in human breast cancer." Fernandez I.F., Blanco S., Lozano J., Lazo P.A. Mol. Cell. Biol. 30:4687-4697(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAP2K1 AND KSR1, TISSUE SPECIFICITY.
[18]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[19]	"Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site." Scheeff E.D., Eswaran J., Bunkoczi G., Knapp S., Manning G. Structure 17:128-138(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 14-335.
[20]	"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] ASP-50; MET-157 AND VAL-167.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB000450 mRNA. Translation: BAA19109.1.
AJ512204 mRNA. Translation: CAD54446.2. Sequence problems.
AY228367 mRNA. Translation: AAO73047.1.
AY228368 mRNA. Translation: AAO73048.1.
AY228369 mRNA. Translation: AAO73049.1.
AY228370 mRNA. Translation: AAO73050.1.
AY228371 mRNA. Translation: AAO73051.1.
AY228372 mRNA. Translation: AAO73052.1.
AK296611 mRNA. Translation: BAG59222.1.
AK223540 mRNA. Translation: BAD97260.1.
AC007250 Genomic DNA. Translation: AAY15019.1.
AC068193 Genomic DNA. Translation: AAX93262.1.
AC073215 Genomic DNA. Translation: AAY14648.1.
CH471053 Genomic DNA. Translation: EAX00062.1.
CH471053 Genomic DNA. Translation: EAX00064.1.
CH471053 Genomic DNA. Translation: EAX00066.1.
CH471053 Genomic DNA. Translation: EAX00067.1.
CH471053 Genomic DNA. Translation: EAX00068.1.
BC027854 mRNA. Translation: AAH27854.1.

IPI

IPI00329275.
IPI00375427.
IPI00375428.
IPI00375429.
IPI00893010.

RefSeq

NP_001123952.1. NM_001130480.2.
NP_001123953.1. NM_001130481.2.
NP_001123954.1. NM_001130482.2.
NP_001123955.1. NM_001130483.2.
NP_006287.2. NM_006296.6.

UniGene

Hs.631890.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V62	X-ray	1.70	A/B	14-335	[»]

ProteinModelPortal

Q86Y07.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q86Y07. 17 interactions.

PTM databases

PhosphoSite

Q86Y07.

Polymorphism databases

DMDM

90116515.

Proteomic databases

PaxDb

Q86Y07.

PRIDE

Q86Y07.

Protocols and materials databases

DNASU

7444.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340157; ENSP00000342381; ENSG00000028116.
ENST00000412104; ENSP00000404156; ENSG00000028116.
ENST00000417641; ENSP00000402375; ENSG00000028116.
ENST00000435505; ENSP00000408002; ENSG00000028116.
ENST00000440705; ENSP00000398323; ENSG00000028116.

GeneID

7444.

KEGG

hsa:7444.

UCSC

uc002rzo.2. human.
uc002rzs.3. human.

Organism-specific databases

CTD

7444.

GeneCards

GC02P058185.

H-InvDB

HIX0002070.

HGNC

HGNC:12719. VRK2.

HPA

CAB046459.
HPA047503.

MIM

602169. gene.

neXtProt

NX_Q86Y07.

PharmGKB

PA37331.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG007532.

InParanoid

Q86Y07.

KO

K08816.

OMA

TRRRQKY.

PhylomeDB

Q86Y07.

Gene expression databases

ArrayExpress

Q86Y07.

Bgee

Q86Y07.

Genevestigator

Q86Y07.

GermOnline

ENSG00000028116. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

BindingDB

Q86Y07.

ChEMBL

CHEMBL1649059.

ChiTaRS

VRK2. human.

EvolutionaryTrace

Q86Y07.

GenomeRNAi

7444.

NextBio

29154.

SOURCE

Search...

Entry information

Entry name

VRK2_HUMAN

Accession

Primary (citable) accession number: Q86Y07
Secondary accession number(s): B4DKL0 , D6W5D4, D6W5D6, Q49AK9, Q53EU9, Q53S39, Q53S77, Q53TU1, Q86Y08, Q86Y09, Q86Y10, Q86Y11, Q86Y12, Q8IXI5, Q99987

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	March 7, 2006
Last modified:	May 1, 2013
This is version 115 of the entry and version 3 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.