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O35942 (NEK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length443 AA.
Sequence statusComplete.
Protein existenceEvidence 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 homodimers 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. Nucleusnucleolus By similarity. Cytoplasm By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasmcytoskeletonspindle pole By similarity. Chromosomecentromerekinetochore By similarity. Chromosomecentromere. Note: STK3/MST2 and SAV1 are required for its targeting to the centrosome. Colocalizes 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 1by 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 processCell cycle
Cell division
Chromosome partition
Meiosis
Mitosis
   Cellular componentCentromere
Chromosome
Cytoplasm
Cytoskeleton
Kinetochore
Microtubule
Nucleus
   DomainCoiled coil
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblastocyst development

Inferred from mutant phenotype PubMed 19117032. Source: MGI

centrosome separation

Inferred from electronic annotation. Source: Ensembl

chromosome segregation

Inferred from mutant phenotype PubMed 19117032. Source: MGI

meiotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic sister chromatid segregation

Inferred from mutant phenotype PubMed 15479717. 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

protein phosphorylation

Inferred from direct assay Ref.5. Source: MGI

regulation of attachment of spindle microtubules to kinetochore

Inferred from sequence or structural similarity. Source: UniProtKB

spindle assembly involved in mitosis

Inferred from mutant phenotype PubMed 19117032. Source: MGI

   Cellular_componentcentrosome

Inferred from electronic annotation. Source: Ensembl

condensed chromosome kinetochore

Inferred from electronic annotation. Source: UniProtKB-SubCell

condensed nuclear chromosome

Inferred from direct assay PubMed 15479717. Source: MGI

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

midbody

Inferred from direct assay PubMed 15479717. Source: MGI

nucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

spindle pole

Inferred from direct assay PubMed 15479717. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.6Ref.5. Source: MGI

protein kinase activity

Inferred from direct assay Ref.6Ref.5. Source: MGI

protein serine/threonine kinase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 443443Serine/threonine-protein kinase Nek2
PRO_0000086422

Regions

Domain8 – 271264Protein kinase
Nucleotide binding14 – 229ATP By similarity
Region264 – 443180Interaction with PCNT By similarity
Region306 – 33429Leucine-zipper
Region329 – 443115Necessary for interaction with MAD1L1 By similarity
Region333 – 37038Required for microtubule binding and for localization to the centrosomes By similarity
Region402 – 43736Interaction with SAV1 and STK3/MST2 By similarity
Coiled coil303 – 36159 Potential
Coiled coil403 – 42725 Potential

Sites

Active site1411Proton acceptor By similarity
Binding site371ATP By similarity

Amino acid modifications

Modified residue1701Phosphothreonine; by autocatalysis By similarity
Modified residue1711Phosphoserine; by autocatalysis By similarity
Modified residue1751Phosphothreonine; by autocatalysis By similarity
Modified residue1791Phosphothreonine; by autocatalysis By similarity
Modified residue2411Phosphoserine; by autocatalysis By similarity
Modified residue3561Phosphoserine; by STK3/MST2 By similarity
Modified residue3891Phosphoserine By similarity
Modified residue3961Phosphoserine By similarity
Modified residue4011Phosphoserine By similarity
Modified residue4361Phosphoserine; by STK3/MST2 By similarity

Experimental info

Sequence conflict691S → R in AAB67973. Ref.1
Sequence conflict691S → R in AAC35393. Ref.2
Sequence conflict691S → R in AAB70470. Ref.3
Sequence conflict2031G → A in AAB67973. Ref.1
Sequence conflict2531N → F in AAB67973. Ref.1
Sequence conflict2741L → M in AAB67973. Ref.1
Sequence conflict2741L → M in AAC35393. Ref.2
Sequence conflict2741L → M in AAB70470. Ref.3
Sequence conflict3111R → S in AAB67973. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O35942 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 1EF2CA320F60FB5C

FASTA44351,243
        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 

« Hide

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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].
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] [Europe PMC] [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] [Europe PMC] [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.
CCDSCCDS15623.1.
RefSeqNP_035022.2. NM_010892.3.
UniGeneMm.33773.
Mm.403999.

3D structure databases

ProteinModelPortalO35942.
SMRO35942. Positions 3-314.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201728. 4 interactions.
IntActO35942. 3 interactions.

PTM databases

PhosphoSiteO35942.

Proteomic databases

PaxDbO35942.
PRIDEO35942.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000027931; ENSMUSP00000027931; ENSMUSG00000026622.
GeneID18005.
KEGGmmu:18005.
UCSCuc007ecx.2. mouse.

Organism-specific databases

CTD4751.
MGIMGI:109359. Nek2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00720000108402.
HOGENOMHOG000233029.
HOVERGENHBG006461.
InParanoidQ3TPD7.
KOK08857.
OMASKCKDLK.
OrthoDBEOG715Q40.
TreeFamTF101184.

Gene expression databases

ArrayExpressO35942.
BgeeO35942.
GenevestigatorO35942.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio293015.
PROO35942.
SOURCESearch...

Entry information

Entry nameNEK2_MOUSE
AccessionPrimary (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: July 9, 2014
This is version 126 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot