O35942 (NEK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase Nek2
EC=2.7.11.1

Alternative name(s):
Never in mitosis A-related kinase 2
Short name=NimA-related protein kinase 2

Gene names

Name:

Nek2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	443 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates and activates NEK11 in G1/S-arrested cells. Ref.5 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Its catalytic activity is inhibited by the inhibitor CCT241950. In the presence of this inhibitor, displays an autoinhibited conformation: Tyr-70 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix By similarity.
Subunit structure	Forms homo- and heterodimers. Interacts with CDC20, CTNB1, MAD1L1, MAD2L1, MAPK, NEK11, NPM1, NDC80, PCNT, PPP1CA, PPP1CC and SGOL1. Interacts with STK3/MST2 (via SARAH domain) and SAV1 (via SARAH domain) By similarity. Interacts with NECAB3 and HMGA2. Ref.5 Ref.6
Subcellular location	Nucleus. Nucleus › nucleolus By similarity. Cytoplasm By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Cytoplasm › cytoskeleton › spindle pole By similarity. Chromosome › centromere › kinetochore By similarity. Chromosome › centromere. Note: STK3/MST2 and SAV1 are required for its targeting to the centrosome. Co-localizes with SGOL1 and MAD1L1 at the kinetochore. Not associated with kinetochore in the interphase but becomes associated with it upon the breakdown of the nuclear envelope. Has a nucleolar targeting/ retention activity via a coiled-coil domain at the C-terminal end By similarity. Ref.1
Tissue specificity	Most abundantly expressed in testis. Low levels found in mid-gestation embryo, ovary, placenta, intestine, thymus and skin. Within the testis, expression restricted to germ cells with highest levels detected in spermatocytes at pachytene and diplotene stages. Also expressed in meiotic pachytene oocytes. Ref.1 Ref.3
Domain	The leucine-zipper domain is required for its dimerization and activation By similarity.
Post-translational modification	Activated by autophosphorylation. Protein phosphatase 1 represses autophosphorylation and activation of isoform 1 by dephosphorylation. Phosphorylation by STK3/MST2 is necessary for its localization to the centrosome By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Chromosome partition Meiosis Mitosis
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Kinetochore Microtubule Nucleus
Domain	Coiled coil
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW meiosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic sister chromatid segregation Inferred from mutant phenotype. Source: MGI negative regulation of DNA binding Inferred from direct assay Ref.6. Source: MGI protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of attachment of spindle microtubules to kinetochore Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell condensed nuclear chromosome Inferred from direct assay. Source: MGI microtubule Inferred from electronic annotation. Source: UniProtKB-KW midbody Inferred from direct assay. Source: MGI nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell spindle pole Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 443	443	Serine/threonine-protein kinase Nek2		PRO_0000086422
Regions
	Domain	8 – 271	264	Protein kinase
	Domain	306 – 334	29	Leucine-zipper
	Nucleotide binding	14 – 22	9	ATP By similarity
	Region	264 – 443	180	Interaction with PCNT By similarity
	Region	329 – 443	115	Necessary for interaction with MAD1L1 By similarity
	Region	333 – 370	38	Required for microtubule binding and for localization to the centrosomes By similarity
	Region	402 – 437	36	Interaction with SAV1 and STK3/MST2 By similarity
	Coiled coil	303 – 361	59	Potential
	Coiled coil	403 – 427	25	Potential
Sites
	Active site	141	1	Proton acceptor By similarity
	Binding site	37	1	ATP By similarity
Amino acid modifications
	Modified residue	170	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	171	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	175	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	179	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	184	1	Phosphoserine By similarity
	Modified residue	241	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	299	1	Phosphoserine By similarity
	Modified residue	300	1	Phosphoserine By similarity
	Modified residue	356	1	Phosphoserine; by STK3/MST2 By similarity
	Modified residue	389	1	Phosphoserine By similarity
	Modified residue	396	1	Phosphoserine By similarity
	Modified residue	401	1	Phosphoserine By similarity
	Modified residue	436	1	Phosphoserine; by STK3/MST2 By similarity
Experimental info
	Sequence conflict	69	1	S → R in AAB67973. Ref.1
	Sequence conflict	69	1	S → R in AAC35393. Ref.2
	Sequence conflict	69	1	S → R in AAB70470. Ref.3
	Sequence conflict	203	1	G → A in AAB67973. Ref.1
	Sequence conflict	253	1	N → F in AAB67973. Ref.1
	Sequence conflict	274	1	L → M in AAB67973. Ref.1
	Sequence conflict	274	1	L → M in AAC35393. Ref.2
	Sequence conflict	274	1	L → M in AAB70470. Ref.3
	Sequence conflict	311	1	R → S in AAB67973. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O35942 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 1EF2CA320F60FB5C	FASTA	443	51,243
	10 20 30 40 50 60 MPSRVEDYEV LHSIGTGSYG RCQKIRRKSD GKILVWKELD YGSMTEVEKQ MLVSEVNLLR 70 80 90 100 110 120 ELKHPNIVSY YDRIIDRTNT TLYIVMEYCE GGDLASVISK GTKDRQYLEE EFVLRVMTQL 130 140 150 160 170 180 TLALKECHRR SDGGHTVLHR DLKPANVFLD SKHNVKLGDF GLARILNHDT SFAKTFVGTP 190 200 210 220 230 240 YYMSPEQMSC LSYNEKSDIW SLGCLLYELC ALMPPFTAFN QKELAGKIRE GRFRRIPYRY 250 260 270 280 290 300 SDGLNDLITR MLNLKDYHRP SVEEILESPL IADLVAEEQR RNLERRGRRS GEPSKLPDSS 310 320 330 340 350 360 PVLSELKLKE RQLQDREQAL RAREDILEQK ERELCIRERL AEDKLARAES LMKNYSLLKE 370 380 390 400 410 420 HRLLCLAGGP ELDLPSSAMK KKVHFHGESK ENTARSENSE SYLAKSKCRD LKKRLHAAQL 430 440 RAQALADIEK NYQLKSRQIL GMR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The NIMA-related kinase 2, Nek2, is expressed in specific stages of the meiotic cell cycle and associates with meiotic chromosomes." Rhee K., Wolgemuth D.J. Development 124:2167-2177(1997) [PubMed: 9187143] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: Swiss Webster. Tissue: Testis.
[2]	"Murine NIMA-related kinases are expressed in patterns suggesting distinct functions in gametogenesis and a role in the nervous system." Arama E., Yanai A., Kilfin G., Motro B. Oncogene 16:1813-1823(1998) [PubMed: 9583679] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The in vivo expression pattern of mouse Nek2, a NIMA-related kinase, indicates a role in both mitosis and meiosis." Tanaka K., Parvinen M., Nigg E.A. Exp. Cell Res. 237:264-274(1997) [PubMed: 9434622] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Brain.
[4]	"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: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Eye and Heart.
[5]	"NIP1/XB51/NECAB3 is a potential substrate of Nek2, suggesting specific roles of Nek2 in Golgi." Yoo J.C., Chang J.R., Kim S.H., Jang S.K., Wolgemuth D.J., Kim K., Rhee K. Exp. Cell Res. 292:393-402(2004) [PubMed: 14697346] [Abstract] Cited for: FUNCTION, INTERACTION WITH NECAB3.
[6]	"Phosphorylation of high-mobility group protein A2 by Nek2 kinase during the first meiotic division in mouse spermatocytes." Di Agostino S., Fedele M., Chieffi P., Fusco A., Rossi P., Geremia R., Sette C. Mol. Biol. Cell 15:1224-1232(2004) [PubMed: 14668482] [Abstract] Cited for: FUNCTION, INTERACTION WITH HMGA2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U95610 mRNA. Translation: AAB67973.1. AF013166 mRNA. Translation: AAC35393.1. AF007247 mRNA. Translation: AAB70470.1. AK147072 mRNA. Translation: BAE27653.1. AK164467 mRNA. Translation: BAE37799.1.
IPI	IPI00136199.
RefSeq	NP_035022.2. NM_010892.3.
UniGene	Mm.33773. Mm.403999.
3D structure databases
ProteinModelPortal	O35942.
SMR	O35942. Positions 3-273.
ModBase	Search...
Protein-protein interaction databases
IntAct	O35942. 3 interactions.
STRING	O35942.
PTM databases
PhosphoSite	O35942.
Proteomic databases
PRIDE	O35942.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000027931; ENSMUSP00000027931; ENSMUSG00000026622.
GeneID	18005.
KEGG	mmu:18005.
NMPDR	fig|10090.3.peg.1739.
Organism-specific databases
CTD	4751.
MGI	MGI:109359. Nek2.
Phylogenomic databases
eggNOG	roNOG06758.
HOGENOM	HBG755340.
HOVERGEN	HBG006461.
InParanoid	O35942.
OrthoDB	EOG4XKV70.
PhylomeDB	O35942.
Gene expression databases
ArrayExpress	O35942.
Bgee	O35942.
Genevestigator	O35942.
GermOnline	ENSMUSG00000026622. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K08857.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 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
SOURCE	Search...

Entry information

Entry name

NEK2_MOUSE

Accession

Primary (citable) accession number: O35942
Secondary accession number(s): O35959, Q3TPD7

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	July 27, 2011
Last modified:	December 14, 2011
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program