Q8BN21 (VRK2_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	503 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 histone H3. Phosphorylates 'Thr-18' of p53/TP53, and thereby increases its stability and activity. 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. May also phosphorylate MAPK8IP1. 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 By similarity. Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with MAP3K7, MAP2K7, MAP2K1, KSR1, RAN and MAPK8IP1 By similarity.
Subcellular location	Cytoplasm. Endoplasmic reticulum membrane; Single-pass type IV membrane protein Potential. Mitochondrion membrane; Single-pass type IV membrane protein Potential Ref.6.
Tissue specificity	Expressed in liver, kidney and muscle. Weakly expressed in thymus, bone marrow and spleen. Ref.5
Developmental stage	Weakly expressed in embryo compared to VRK1 and VRK3. Expressed from E10.5 to E14 in developing liver and then decreases. It increases again from E17.5 and remains thereafter. Highly expressed in hematopoietic embryonic tissues from E10.5 to E14.5. Weakly expressed in the yolk-sac. Ref.5
Post-translational modification	Autophosphorylated. Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to oxidative stress Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.6. Source: MGI regulation of MAPK cascade Inferred from sequence or structural similarity. Source: UniProtKB regulation of interleukin-1-mediated signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial membrane Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.6. Source: MGI
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8BN21-1)

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: Q8BN21-2)

The sequence of this isoform differs from the canonical sequence as follows:
     342-390: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q8BN21-3)

The sequence of this isoform differs from the canonical sequence as follows:
     151-163: LDVLEYIHENEYV → VSLRDLTGDLLDI
     164-503: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 503	503	Serine/threonine-protein kinase VRK2		PRO_0000086807
Regions
	Transmembrane	482 – 502	21	Helical; Anchor for type IV membrane protein; Potential
	Domain	29 – 313	285	Protein kinase
	Nucleotide binding	35 – 43	9	ATP By similarity
	Region	392 – 503	112	Interaction with MAP3K7 By similarity
Sites
	Active site	166	1	Proton acceptor By similarity
	Binding site	61	1	ATP By similarity
Amino acid modifications
	Modified residue	336	1	Phosphothreonine By similarity
Natural variations
	Alternative sequence	151 – 163	13	LDVLE…ENEYV → VSLRDLTGDLLDI in isoform 3.		VSP_008541
	Alternative sequence	164 – 503	340	Missing in isoform 3.		VSP_008542
	Alternative sequence	342 – 390	49	Missing in isoform 2.		VSP_008543
Experimental info
	Sequence conflict	33	1	K → R in AAN64922. Ref.1
	Sequence conflict	226	1	A → P in BAB28393. Ref.2
	Sequence conflict	319	1	P → L in BAE32620. Ref.2
	Sequence conflict	319	1	P → L in AAH13520. Ref.4
	Sequence conflict	333	1	H → R in BAE32620. Ref.2
	Sequence conflict	333	1	H → R in AAH13520. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 10, 2003. Version 2. Checksum: 6F29E3E412ECB221	FASTA	503	58,119
	10 20 30 40 50 60 MAPRRKEKYK LPVPLPEGKI LDDMEGNRWA LGKMIGSGGF GLIYLAFPTN KPNKDARHVI 70 80 90 100 110 120 KLEYQENGPL FSELKFYQRA AKRECIQKWI QQRKLDYLGI PVFYGFGLTD FKGRSYRFMV 130 140 150 160 170 180 MERLGIDLQK LLDQNGGFKK LTVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLDFTNPD 190 200 210 220 230 240 RVYLADYGLS YRYCPNGNHK QYQEDPRKGH NGTIEFTSLD AHKGVAPSRR SDVEILGYCM 250 260 270 280 290 300 LHWLFGKLPW EAKLDDPVAV QTAKTNLLDE LPESVLKWAP SGSSCSELVK YLMYVHNLAY 310 320 330 340 350 360 DDKPDYQKLK KILNPDGVPL GPLEFSTKVQ SVHVRTPAQQ KVDSPKATRK PANEFPAKFP 370 380 390 400 410 420 KKVHRETRAR QREEQEDSQP TMLQSRPAAP ENSRTRKIHE YSDIFSEMQS LQQTPSYMSF 430 440 450 460 470 480 QGSYCKPYLD CTRRDPIRKP RSLPRYRHTP TGNLGVTDLE SSPRFWPAIF QLTLSEETKA 490 500 DVYYYGITIF CLLIFVFLAL YFL
	Isoform 2 [UniParc]. Checksum: 4AAD5406E8214578	FASTA	454	52,493
	10 20 30 40 50 60 MAPRRKEKYK LPVPLPEGKI LDDMEGNRWA LGKMIGSGGF GLIYLAFPTN KPNKDARHVI 70 80 90 100 110 120 KLEYQENGPL FSELKFYQRA AKRECIQKWI QQRKLDYLGI PVFYGFGLTD FKGRSYRFMV 130 140 150 160 170 180 MERLGIDLQK LLDQNGGFKK LTVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLDFTNPD 190 200 210 220 230 240 RVYLADYGLS YRYCPNGNHK QYQEDPRKGH NGTIEFTSLD AHKGVAPSRR SDVEILGYCM 250 260 270 280 290 300 LHWLFGKLPW EAKLDDPVAV QTAKTNLLDE LPESVLKWAP SGSSCSELVK YLMYVHNLAY 310 320 330 340 350 360 DDKPDYQKLK KILNPDGVPL GPLEFSTKVQ SVHVRTPAQQ KENSRTRKIH EYSDIFSEMQ 370 380 390 400 410 420 SLQQTPSYMS FQGSYCKPYL DCTRRDPIRK PRSLPRYRHT PTGNLGVTDL ESSPRFWPAI 430 440 450 FQLTLSEETK ADVYYYGITI FCLLIFVFLA LYFL
	Isoform 3 [UniParc]. Checksum: 43B728DB7DC2FE52	FASTA	163	18,844
	10 20 30 40 50 60 MAPRRKEKYK LPVPLPEGKI LDDMEGNRWA LGKMIGSGGF GLIYLAFPTN KPNKDARHVI 70 80 90 100 110 120 KLEYQENGPL FSELKFYQRA AKRECIQKWI QQRKLDYLGI PVFYGFGLTD FKGRSYRFMV 130 140 150 160 MERLGIDLQK LLDQNGGFKK LTVLQLGIRM VSLRDLTGDL LDI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel gene, Pog, is necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd." Agoulnik A.I., Lu B., Zhu Q., Truong C., Ty M.T., Arango N., Chada K.K., Bishop C.E. Hum. Mol. Genet. 11:3047-3053(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: C57BL/6.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Strain: C57BL/6J and NOD. Tissue: Dendritic cell, Embryo, Eye and Spleen.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Kidney.
[5]	"Expression of the VRK (vaccinia-related kinase) gene family of p53 regulators in murine hematopoietic development." Vega F.M., Gonzalo P., Gaspar M.L., Lazo P.A. FEBS Lett. 544:176-180(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[6]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF513620 mRNA. Translation: AAN64922.1. AK012664 mRNA. Translation: BAB28393.1. AK053297 mRNA. Translation: BAC35335.1. AK154485 mRNA. Translation: BAE32620.1. AL929272, AC083815 Genomic DNA. Translation: CAI52021.1. BC013520 mRNA. Translation: AAH13520.1.
IPI	IPI00223614. IPI00319816. IPI00377449.
RefSeq	NP_001239376.1. NM_001252447.1. NP_081536.2. NM_027260.3.
UniGene	Mm.285351.
3D structure databases
ProteinModelPortal	Q8BN21.
SMR	Q8BN21. Positions 15-330.
ModBase	Search...
PTM databases
PhosphoSite	Q8BN21.
Proteomic databases
PRIDE	Q8BN21.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000078362; ENSMUSP00000077471; ENSMUSG00000064090. ENSMUST00000109504; ENSMUSP00000105130; ENSMUSG00000064090.
GeneID	69922.
KEGG	mmu:69922.
UCSC	uc007igf.2. mouse. uc007igg.2. mouse. uc011xsk.2. mouse.
Organism-specific databases
CTD	7444.
MGI	MGI:1917172. Vrk2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00690000101669.
HOVERGEN	HBG007532.
InParanoid	Q8BN21.
KO	K08816.
OMA	TRRRQKY.
OrthoDB	EOG4NZTT3.
Gene expression databases
ArrayExpress	Q8BN21.
Bgee	Q8BN21.
CleanEx	MM_VRK2.
Genevestigator	Q8BN21.
GermOnline	ENSMUSG00000064090. Mus musculus.
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
NextBio	330615.
SOURCE	Search...

Entry information

Entry name

VRK2_MOUSE

Accession

Primary (citable) accession number: Q8BN21
Secondary accession number(s): Q3U415 , Q5F1Z5, Q5SP88, Q8BPU8, Q8CJ46, Q91WS1, Q9CZF9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	October 10, 2003
Last modified:	May 29, 2013
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program