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P51955 (NEK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 160. 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 Nek2

EC=2.7.11.1
Alternative name(s):
HSPK 21
Never in mitosis A-related kinase 2
Short name=NimA-related protein kinase 2
NimA-like protein kinase 1
Gene names
Name:NEK2
Synonyms:NEK2A, NLK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length445 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. Isoform 1 phosphorylates and activates NEK11 in G1/S-arrested cells. Isoform 2, which is not present in the nucleolus, does not. Ref.2 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.21 Ref.25 Ref.26

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Isoform 1 is inhibited by ionizing radiation in the presence of PPP1CA. 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. Ref.14 Ref.15 Ref.22

Subunit structure

Isoform 1, isoform 2 and isoform 4 form homo- and heterodimers. Interacts with NECAB3 and HMGA2 By similarity. Isoform 1 interacts with CDC20, CTNB1, MAD1L1, MAPK, NEK11, NPM1, NDC80, PCNT and SGOL1. Isoform 1 interacts with STK3/MST2 (via SARAH domain) and SAV1 (via SARAH domain). Isoform 1 and isoform 2 interact with MAD2L1. Isoform 1 and isoform 4 interact with PPP1CA and PPP1CC. Ref.2 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.21 Ref.24 Ref.25 Ref.26

Subcellular location

Isoform 1: Nucleus. Nucleusnucleolus. Cytoplasm. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmcytoskeletonspindle pole. Chromosomecentromerekinetochore. Chromosomecentromere By similarity. 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. Ref.2 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.25 Ref.26

Isoform 2: Cytoplasm. Note: Predominantly cytoplasmic. Ref.2 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.25 Ref.26

Isoform 4: Nucleus. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Note: Predominantly nuclear. Ref.2 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.16 Ref.17 Ref.25 Ref.26

Tissue specificity

Isoform 1 and isoform 2 are expressed in peripheral blood T-cells and a wide variety of transformed cell types. Isoform 1 and isoform 4 are expressed in the testis. Up-regulated in various cancer cell lines, as well as primary breast tumors. Ref.2 Ref.9

Induction

Expression and activity peak in the G2 phase of the mitotic cycle and decrease once the cells have entered mitosis due to degradation by the anaphase promoting complex APC/C-CDC20. In G1 phase, both isoform 1 and isoform 2 are almost undetectable. However, at the G1/S transition, there is an increase in expression of both isoforms which then remain at this increased level throughout S and G2. At the onset of mitosis, isoform 1 undergoes a rapid disappearance whereas isoform 2 continues to be present at about the same level as in G2. During the rest of mitosis, isoform 1 remains absent, while isoform 2 only begins to decline upon re-entry into the next G1 phase. Ref.14 Ref.15 Ref.22

Domain

The leucine-zipper domain is required for its dimerization and activation. Ref.27

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.

Involvement in disease

Retinitis pigmentosa 67 (RP67) [MIM:615565]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.29

Sequence similarities

Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAH65932.1 differs from that shown. Reason: Frameshift at position 213.

Ontologies

Keywords
   Biological processCell cycle
Cell division
Chromosome partition
Meiosis
Mitosis
   Cellular componentCentromere
Chromosome
Cytoplasm
Cytoskeleton
Kinetochore
Microtubule
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseRetinitis pigmentosa
   DomainCoiled coil
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG2/M transition of mitotic cell cycle

Traceable author statement. Source: Reactome

blastocyst development

Inferred from electronic annotation. Source: Ensembl

centrosome separation

Inferred from direct assay Ref.18. Source: UniProtKB

chromosome segregation

Inferred from direct assay Ref.10. Source: UniProtKB

meiotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic nuclear division

Traceable author statement PubMed 9430639. Source: ProtInc

mitotic sister chromatid segregation

Inferred from electronic annotation. Source: Ensembl

negative regulation of DNA binding

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from direct assay Ref.17. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.26. Source: UniProtKB

regulation of attachment of spindle microtubules to kinetochore

Inferred from mutant phenotype Ref.21. Source: UniProtKB

regulation of mitosis

Traceable author statement PubMed 9430639. Source: ProtInc

regulation of mitotic centrosome separation

Traceable author statement Ref.28. Source: UniProtKB

spindle assembly

Traceable author statement Ref.28. Source: UniProtKB

spindle assembly involved in mitosis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcentrosome

Inferred from direct assay PubMed 21399614. Source: UniProtKB

condensed chromosome kinetochore

Inferred from electronic annotation. Source: UniProtKB-SubCell

condensed nuclear chromosome

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

intercellular bridge

Inferred from direct assay. Source: HPA

kinetochore

Inferred from direct assay Ref.10. Source: UniProtKB

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

midbody

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay. Source: HPA

protein complex

Inferred from mutant phenotype PubMed 10880350. Source: UniProtKB

spindle pole

Inferred from electronic annotation. Source: UniProtKB-SubCell

   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 PubMed 10880350Ref.10Ref.16Ref.18PubMed 9647649. Source: UniProtKB

protein kinase activity

Inferred from direct assay PubMed 10880350Ref.18. Source: UniProtKB

protein phosphatase binding

Inferred from physical interaction PubMed 10880350. Source: UniProtKB

protein serine/threonine kinase activity

Traceable author statement Ref.28. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ANAPC4Q9UJX56EBI-633182,EBI-2554854
CDC27P302602EBI-633182,EBI-994813
cdc27Q6GQ042EBI-633182,EBI-995003From a different organism.
NEK11Q8NG665EBI-633182,EBI-633195

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P51955-1)

Also known as: Nek2A;

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: P51955-2)

Also known as: Nek2B;

The sequence of this isoform differs from the canonical sequence as follows:
     371-384: ELLNLPSSVIKKKV → GMRINLVNRSWCYK
     385-445: Missing.
Isoform 3 (identifier: P51955-3)

The sequence of this isoform differs from the canonical sequence as follows:
     323-326: REER → KKKK
     327-445: Missing.
Isoform 4 (identifier: P51955-4)

Also known as: Nek2C; Nek2A-T;

The sequence of this isoform differs from the canonical sequence as follows:
     371-378: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 445445Serine/threonine-protein kinase Nek2
PRO_0000086421

Regions

Domain8 – 271264Protein kinase
Nucleotide binding14 – 229ATP By similarity
Region264 – 445182Interaction with PCNT
Region306 – 33429Leucine-zipper
Region329 – 445117Necessary for interaction with MAD1L1
Region333 – 37038Required for microtubule binding and for localization to the centrosomes
Region403 – 43937Interaction with SAV1 and STK3/MST2
Coiled coil303 – 36260 Potential
Coiled coil406 – 43025 Potential

Sites

Active site1411Proton acceptor By similarity
Binding site371ATP

Amino acid modifications

Modified residue1701Phosphothreonine; by autocatalysis Probable
Modified residue1711Phosphoserine; by autocatalysis Probable
Modified residue1751Phosphothreonine; by autocatalysis Ref.30
Modified residue1791Phosphothreonine; by autocatalysis Ref.30
Modified residue2411Phosphoserine; by autocatalysis Ref.30
Modified residue2961Phosphoserine Ref.20 Ref.23
Modified residue3561Phosphoserine; by STK3/MST2 Ref.26 Ref.30
Modified residue3651Phosphoserine; by STK3/MST2 Ref.26
Modified residue3871Phosphoserine Ref.30
Modified residue3901Phosphoserine Ref.30
Modified residue3971Phosphoserine Ref.19 Ref.30
Modified residue4021Phosphoserine Ref.30
Modified residue4061Phosphoserine; by STK3/MST2 Ref.26
Modified residue4281Phosphoserine Ref.30
Modified residue4381Phosphoserine; by STK3/MST2 Ref.26

Natural variations

Alternative sequence323 – 3264REER → KKKK in isoform 3.
VSP_015576
Alternative sequence327 – 445119Missing in isoform 3.
VSP_015577
Alternative sequence371 – 38414ELLNL…IKKKV → GMRINLVNRSWCYK in isoform 2.
VSP_015578
Alternative sequence371 – 3788Missing in isoform 4.
VSP_041758
Alternative sequence385 – 44561Missing in isoform 2.
VSP_015579
Natural variant3541N → S. Ref.5 Ref.31
Corresponds to variant rs2230489 [ dbSNP | Ensembl ].
VAR_019990
Natural variant4101C → Y. Ref.31
Corresponds to variant rs56102977 [ dbSNP | Ensembl ].
VAR_040907

Experimental info

Mutagenesis371K → R: Loss of kinase activity and of ability to activate NEK11. Ref.14 Ref.30
Mutagenesis1411D → A: Loss of autophosphorylation. Ref.30
Mutagenesis1701T → A: No effect on kinase activity. Ref.30
Mutagenesis1701T → E: Kinase activity increased by two fold. Ref.30
Mutagenesis1711S → A: No effect on kinase activity. Ref.30
Mutagenesis1711S → D: Kinase activity increased by two fold. Ref.30
Mutagenesis1751T → A: Kinase activity decreased by two fold. Ref.30
Mutagenesis1751T → E: Kinase activity increased by two fold. Ref.30
Mutagenesis1791T → A: Loss of kinase activity. Ref.30
Mutagenesis1791T → E: Loss of kinase activity. Ref.30
Mutagenesis2411S → A: Loss of kinase activity. Ref.30
Mutagenesis2411S → D: Loss of kinase activity. Ref.30
Sequence conflict84 – 852IV → LY in CAA80912. Ref.8
Sequence conflict3251E → K in BAD97073. Ref.5

Secondary structure

............................................ 445
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Nek2A) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: D33A37778ABB6D9E

FASTA44551,763
        10         20         30         40         50         60 
MPSRAEDYEV LYTIGTGSYG RCQKIRRKSD GKILVWKELD YGSMTEAEKQ MLVSEVNLLR 

        70         80         90        100        110        120 
ELKHPNIVRY YDRIIDRTNT TLYIVMEYCE GGDLASVITK GTKERQYLDE EFVLRVMTQL 

       130        140        150        160        170        180 
TLALKECHRR SDGGHTVLHR DLKPANVFLD GKQNVKLGDF GLARILNHDT SFAKTFVGTP 

       190        200        210        220        230        240 
YYMSPEQMNR MSYNEKSDIW SLGCLLYELC ALMPPFTAFS QKELAGKIRE GKFRRIPYRY 

       250        260        270        280        290        300 
SDELNEIITR MLNLKDYHRP SVEEILENPL IADLVADEQR RNLERRGRQL GEPEKSQDSS 

       310        320        330        340        350        360 
PVLSELKLKE IQLQERERAL KAREERLEQK EQELCVRERL AEDKLARAEN LLKNYSLLKE 

       370        380        390        400        410        420 
RKFLSLASNP ELLNLPSSVI KKKVHFSGES KENIMRSENS ESQLTSKSKC KDLKKRLHAA 

       430        440 
QLRAQALSDI EKNYQLKSRQ ILGMR 

« Hide

Isoform 2 (Nek2B) [UniParc].

Checksum: EBFA8B6BB07480FB
Show »

FASTA38444,906
Isoform 3 [UniParc].

Checksum: 3F3FDD8262E77964
Show »

FASTA32637,956
Isoform 4 (Nek2C) (Nek2A-T) [UniParc].

Checksum: BF89938C50FAD817
Show »

FASTA43750,909

References

« Hide 'large scale' references
[1]"Cell cycle-dependent expression of Nek2, a novel human protein kinase related to the NIMA mitotic regulator of Aspergillus nidulans."
Schultz S.J., Fry A.M., Suetterlin C., Ried T., Nigg E.A.
Cell Growth Differ. 5:625-635(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Nasopharynx, Placenta and T-cell.
[2]"Alternative splice variants of the human centrosome kinase Nek2 exhibit distinct patterns of expression in mitosis."
Hames R.S., Fry A.M.
Biochem. J. 361:77-85(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DIMERIZATION.
[3]"Molecular cloning and expression of NLK1, a human NIMA-like kinase."
Lu K.P., Hunter T.
Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]Suzuki Y., Sugano S., 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), VARIANT SER-354.
Tissue: Testis.
[6]"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].
[7]"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] (ISOFORMS 1 AND 3).
Tissue: Mammary gland, Skin and Uterus.
[8]"Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans."
Schultz S.J., Nigg E.A.
Cell Growth Differ. 4:821-830(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 83-203.
[9]"Alternatively spliced protein variants as potential therapeutic targets for male infertility and contraception."
Fardilha M., Wu W., Sa R., Fidalgo S., Sousa C., Mota C., da Cruz e Silva O.A., da Cruz e Silva E.F.
Ann. N. Y. Acad. Sci. 1030:468-478(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 216-445 (ISOFORM 4), INTERACTION WITH PPP1CC, TISSUE SPECIFICITY.
Tissue: Testis.
[10]"NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling."
Lou Y., Yao J., Zereshki A., Dou Z., Ahmed K., Wang H., Hu J., Wang Y., Yao X.
J. Biol. Chem. 279:20049-20057(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 305-445, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAD1L1.
[11]"Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles."
Faragher A.J., Fry A.M.
Mol. Biol. Cell 14:2876-2889(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]"Nek2A specifies the centrosomal localization of Erk2."
Lou Y., Xie W., Zhang D.F., Yao J.H., Luo Z.F., Wang Y.Z., Shi Y.Y., Yao X.B.
Biochem. Biophys. Res. Commun. 321:495-501(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAPK1.
[13]"Nek2A kinase regulates the localization of numatrin to centrosome in mitosis."
Yao J., Fu C., Ding X., Guo Z., Zenreski A., Chen Y., Ahmed K., Liao J., Dou Z., Yao X.
FEBS Lett. 575:112-118(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NPM1.
[14]"Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells."
Noguchi K., Fukazawa H., Murakami Y., Uehara Y.
J. Biol. Chem. 279:32716-32727(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, INTERACTION WITH NEK11, MUTAGENESIS OF LYS-37.
[15]"Protein phosphatase-1alpha regulates centrosome splitting through Nek2."
Mi J., Guo C., Brautigan D.L., Larner J.M.
Cancer Res. 67:1082-1089(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, INTERACTION WITH PPP1CA AND PPP1CC.
[16]"Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis."
Fu G., Ding X., Yuan K., Aikhionbare F., Yao J., Cai X., Jiang K., Yao X.
Cell Res. 17:608-618(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SGOL1.
[17]"Alternative splicing controls nuclear translocation of the cell cycle-regulated Nek2 kinase."
Wu W., Baxter J.E., Wattam S.L., Hayward D.G., Fardilha M., Knebel A., Ford E.M., da Cruz e Silva E.F., Fry A.M.
J. Biol. Chem. 282:26431-26440(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, INTERACTION WITH PPP1A.
[18]"beta-Catenin is a Nek2 substrate involved in centrosome separation."
Bahmanyar S., Kaplan D.D., Deluca J.G., Giddings T.H. Jr., O'Toole E.T., Winey M., Salmon E.D., Casey P.J., Nelson W.J., Barth A.I.
Genes Dev. 22:91-105(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CTNB1.
[19]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[20]"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 SER-296, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability."
Du J., Cai X., Yao J., Ding X., Wu Q., Pei S., Jiang K., Zhang Y., Wang W., Shi Y., Lai Y., Shen J., Teng M., Huang H., Fei Q., Reddy E.S., Zhu J., Jin C., Yao X.
Oncogene 27:4107-4114(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NDC80.
[22]"An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9."
Richards M.W., O'Regan L., Mas-Droux C., Blot J.M., Cheung J., Hoelder S., Fry A.M., Bayliss R.
Mol. Cell 36:560-570(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[23]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"Involvement of a centrosomal protein kendrin in the maintenance of centrosome cohesion by modulating Nek2A kinase activity."
Matsuo K., Nishimura T., Hayakawa A., Ono Y., Takahashi M.
Biochem. Biophys. Res. Commun. 398:217-223(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PCNT.
[25]"Nek2 targets the mitotic checkpoint proteins Mad2 and Cdc20: a mechanism for aneuploidy in cancer."
Liu Q., Hirohashi Y., Du X., Greene M.I., Wang Q.
Exp. Mol. Pathol. 88:225-233(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAD2L1 AND CDC20.
[26]"Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction."
Mardin B.R., Lange C., Baxter J.E., Hardy T., Scholz S.R., Fry A.M., Schiebel E.
Nat. Cell Biol. 12:1166-1176(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STK3/MST2 AND SAV1, PHOSPHORYLATION AT SER-356; SER-365; SER-406 AND SER-438.
[27]"An undecided coiled-coil: the leucine zipper of NEK2 kinase exhibits atypical conformational exchange dynamics."
Croasdale R., Ivins F.J., Muskett F., Daviter T., Scott D.J., Hardy T., Smerdon S.J., Fry A.M., Pfuhl M.
J. Biol. Chem. 286:27537-27547(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN LEUCINE-ZIPPER.
[28]"Caught Nek-ing: cilia and centrioles."
Quarmby L.M., Mahjoub M.R.
J. Cell Sci. 118:5161-5169(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[29]"Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene."
Nishiguchi K.M., Tearle R.G., Liu Y.P., Oh E.C., Miyake N., Benaglio P., Harper S., Koskiniemi-Kuendig H., Venturini G., Sharon D., Koenekoop R.K., Nakamura M., Kondo M., Ueno S., Yasuma T.R., Beckmann J.S., Ikegawa S., Matsumoto N. expand/collapse author list , Terasaki H., Berson E.L., Katsanis N., Rivolta C.
Proc. Natl. Acad. Sci. U.S.A. 110:16139-16144(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN RP67.
[30]"Structure and regulation of the human Nek2 centrosomal kinase."
Rellos P., Ivins F.J., Baxter J.E., Pike A., Nott T.J., Parkinson D.M., Das S., Howell S., Fedorov O., Shen Q.Y., Fry A.M., Knapp S., Smerdon S.J.
J. Biol. Chem. 282:6833-6842(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-271 IN COMPLEX WITH INHIBITOR SU11652, PHOSPHORYLATION AT THR-170; SER-171; THR-175; THR-179; SER-241; SER-356; SER-387; SER-390; SER-397; SER-402 AND SER-428, MUTAGENESIS OF LYS-37; ASP-141; THR-170; SER-171; THR-175; THR-179 AND SER-241, IDENTIFICATION BY MASS SPECTROMETRY.
[31]"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. expand/collapse author list , 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] SER-354 AND TYR-410.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z29066 mRNA. Translation: CAA82309.1.
AY045701 mRNA. Translation: AAK92212.1.
U11050 mRNA. Translation: AAA19558.1.
BT019729 mRNA. Translation: AAV38534.1.
AK223353 mRNA. Translation: BAD97073.1.
AL356310, AC096637 Genomic DNA. Translation: CAH72901.1.
BC043502 mRNA. Translation: AAH43502.2.
BC052807 mRNA. Translation: AAH52807.1.
BC065932 mRNA. Translation: AAH65932.1. Frameshift.
Z25425 mRNA. Translation: CAA80912.1.
AY863109 mRNA. Translation: AAW56418.1.
CCDSCCDS1500.1. [P51955-1]
CCDS55682.1. [P51955-2]
PIRG01452.
I38215.
RefSeqNP_001191111.1. NM_001204182.1.
NP_001191112.1. NM_001204183.1. [P51955-2]
NP_002488.1. NM_002497.3. [P51955-1]
XP_005273204.1. XM_005273147.1. [P51955-4]
UniGeneHs.153704.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JAVX-ray2.20A1-271[»]
2W5AX-ray1.55A1-271[»]
2W5BX-ray2.40A1-271[»]
2W5HX-ray2.33A1-271[»]
2WQOX-ray2.17A1-271[»]
2XK3X-ray2.20A1-271[»]
2XK4X-ray2.10A1-271[»]
2XK6X-ray2.20A1-271[»]
2XK7X-ray1.99A1-271[»]
2XK8X-ray2.00A1-271[»]
2XKCX-ray2.50A1-271[»]
2XKDX-ray1.96A1-271[»]
2XKEX-ray2.20A1-271[»]
2XKFX-ray2.35A1-271[»]
2XNMX-ray1.85A1-271[»]
2XNNX-ray2.50A1-271[»]
2XNOX-ray1.98A1-271[»]
2XNPX-ray1.98A1-271[»]
4A4XX-ray2.40A1-271[»]
4AFEX-ray2.60A1-271[»]
ProteinModelPortalP51955.
SMRP51955. Positions 3-363.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110826. 36 interactions.
IntActP51955. 31 interactions.
MINTMINT-3019433.
STRING9606.ENSP00000355966.

Chemistry

BindingDBP51955.
ChEMBLCHEMBL3835.
GuidetoPHARMACOLOGY2117.

PTM databases

PhosphoSiteP51955.

Polymorphism databases

DMDM1709252.

Proteomic databases

MaxQBP51955.
PaxDbP51955.
PRIDEP51955.

Protocols and materials databases

DNASU4751.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366998; ENSP00000355965; ENSG00000117650. [P51955-2]
ENST00000366999; ENSP00000355966; ENSG00000117650. [P51955-1]
GeneID4751.
KEGGhsa:4751.
UCSCuc001hir.2. human. [P51955-1]
uc001his.4. human. [P51955-2]

Organism-specific databases

CTD4751.
GeneCardsGC01M211836.
HGNCHGNC:7745. NEK2.
HPACAB017530.
HPA047522.
MIM604043. gene.
615565. phenotype.
neXtProtNX_P51955.
Orphanet791. Retinitis pigmentosa.
PharmGKBPA31546.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG006461.
InParanoidP51955.
KOK08857.
OMASKCKDLK.
OrthoDBEOG715Q40.
PhylomeDBP51955.
TreeFamTF101184.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_115566. Cell Cycle.
REACT_8017. APC-Cdc20 mediated degradation of Nek2A.
SignaLinkP51955.

Gene expression databases

ArrayExpressP51955.
BgeeP51955.
CleanExHS_NEK2.
GenevestigatorP51955.

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

EvolutionaryTraceP51955.
GeneWikiNEK2.
GenomeRNAi4751.
NextBio18310.
PMAP-CutDBP51955.
PROP51955.
SOURCESearch...

Entry information

Entry nameNEK2_HUMAN
AccessionPrimary (citable) accession number: P51955
Secondary accession number(s): Q53FD6 expand/collapse secondary AC list , Q5I1Z9, Q5VXZ1, Q6NZX8, Q7Z634, Q86XH2, Q96QN9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 160 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