P51955 (NEK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	445 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. 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. Nucleus › nucleolus. Cytoplasm. Cytoplasm › cytoskeleton › centrosome. Cytoplasm › cytoskeleton › spindle pole. Chromosome › centromere › kinetochore. Chromosome › centromere By similarity. 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. 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. Cytoplasm › cytoskeleton › centrosome. 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.
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 process	Cell cycle Cell division Chromosome partition Meiosis Mitosis
Cellular component	Centromere Chromosome Cytoplasm Cytoskeleton Kinetochore Microtubule Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Ligand	ATP-binding Magnesium Metal-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	G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome cell division Inferred from electronic annotation. Source: UniProtKB-KW centrosome separation Inferred from direct assay Ref.18. Source: UniProtKB meiosis Inferred from electronic annotation. Source: UniProtKB-KW protein autophosphorylation Inferred from direct assay Ref.17. Source: UniProtKB regulation of attachment of spindle microtubules to kinetochore Inferred from mutant phenotype Ref.21. Source: UniProtKB regulation of mitotic centrosome separation Traceable author statement Ref.28. Source: UniProtKB spindle assembly Traceable author statement Ref.28. Source: UniProtKB
Cellular component	centrosome Inferred from direct assay PubMed 21399614. Source: UniProtKB condensed chromosome kinetochore Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome microtubule Inferred from electronic annotation. Source: UniProtKB-KW nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell spindle pole Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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
CDC27	P30260	2	EBI-633182,EBI-994813
cdc27	Q6GQ04	2	EBI-633182,EBI-995003	From a different organism.
NEK11	Q8NG66	2	EBI-687792,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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 445

445

Serine/threonine-protein kinase Nek2

PRO_0000086421

Regions

Domain

8 – 271

264

Protein kinase

Domain

306 – 334

29

Leucine-zipper

Nucleotide binding

14 – 22

9

ATP By similarity

Region

264 – 445

182

Interaction with PCNT

Region

329 – 445

117

Necessary for interaction with MAD1L1

Region

333 – 370

38

Required for microtubule binding and for localization to the centrosomes

Region

403 – 439

37

Interaction with SAV1 and STK3/MST2

Coiled coil

303 – 362

60

Potential

Coiled coil

406 – 430

25

Potential

Sites

Active site

141

1

Proton acceptor By similarity

Binding site

37

1

ATP

Amino acid modifications

Modified residue

170

1

Phosphothreonine; by autocatalysis Probable

Modified residue

171

1

Phosphoserine; by autocatalysis Probable

Modified residue

175

1

Phosphothreonine; by autocatalysis Ref.29

Modified residue

179

1

Phosphothreonine; by autocatalysis Ref.29

Modified residue

184

1

Phosphoserine Ref.20

Modified residue

241

1

Phosphoserine; by autocatalysis Ref.29

Modified residue

296

1

Phosphoserine Ref.20 Ref.23

Modified residue

299

1

Phosphoserine Ref.23

Modified residue

300

1

Phosphoserine Ref.20 Ref.23

Modified residue

356

1

Phosphoserine; by STK3/MST2 Ref.26 Ref.29

Modified residue

365

1

Phosphoserine; by STK3/MST2 Ref.26

Modified residue

387

1

Phosphoserine Ref.29

Modified residue

390

1

Phosphoserine Ref.29

Modified residue

397

1

Phosphoserine Ref.19 Ref.29

Modified residue

402

1

Phosphoserine Ref.29

Modified residue

406

1

Phosphoserine; by STK3/MST2 Ref.26

Modified residue

428

1

Phosphoserine Ref.29

Modified residue

438

1

Phosphoserine; by STK3/MST2 Ref.26

Natural variations

Alternative sequence

323 – 326

4

REER → KKKK in isoform 3.

VSP_015576

Alternative sequence

327 – 445

119

Missing in isoform 3.

VSP_015577

Alternative sequence

371 – 384

14

ELLNL…IKKKV → GMRINLVNRSWCYK in isoform 2.

VSP_015578

Alternative sequence

371 – 378

8

Missing in isoform 4.

VSP_041758

Alternative sequence

385 – 445

61

Missing in isoform 2.

VSP_015579

Natural variant

354

1

N → S. Ref.5 Ref.30
Corresponds to variant rs2230489 [ dbSNP | Ensembl ].

VAR_019990

Natural variant

410

1

C → Y. Ref.30
Corresponds to variant rs56102977 [ dbSNP | Ensembl ].

VAR_040907

Experimental info

Mutagenesis

37

1

K → R: Loss of kinase activity and of ability to activate NEK11. Ref.14 Ref.29

Mutagenesis

141

1

D → A: Loss of autophosphorylation. Ref.29

Mutagenesis

170

1

T → A: No effect on kinase activity. Ref.29

Mutagenesis

170

1

T → E: Kinase activity increased by two fold. Ref.29

Mutagenesis

171

1

S → A: No effect on kinase activity. Ref.29

Mutagenesis

171

1

S → D: Kinase activity increased by two fold. Ref.29

Mutagenesis

175

1

T → A: Kinase activity decreased by two fold. Ref.29

Mutagenesis

175

1

T → E: Kinase activity increased by two fold. Ref.29

Mutagenesis

179

1

T → A: Loss of kinase activity. Ref.29

Mutagenesis

179

1

T → E: Loss of kinase activity. Ref.29

Mutagenesis

241

1

S → A: Loss of kinase activity. Ref.29

Mutagenesis

241

1

S → D: Loss of kinase activity. Ref.29

Sequence conflict

84 – 85

2

IV → LY in CAA80912. Ref.8

Sequence conflict

325

1

E → K in BAD97073. Ref.5

Secondary structure

1

.

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445

Helix Strand Turn

Details...

Helix

5 – 7

3

Beta strand

8 – 16

9

Beta strand

18 – 27

10

Turn

28 – 30

3

Beta strand

33 – 39

7

Helix

46 – 58

13

Beta strand

70 – 75

6

Beta strand

82 – 87

6

Helix

94 – 104

11

Helix

110 – 130

21

Helix

144 – 146

3

Beta strand

147 – 149

3

Beta strand

155 – 157

3

Helix

160 – 165

6

Helix

185 – 188

4

Helix

195 – 211

17

Helix

221 – 230

10

Helix

242 – 251

10

Helix

256 – 258

3

Helix

262 – 266

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Nek2A) [UniParc]. Last modified October 1, 1996. Version 1. Checksum: D33A37778ABB6D9E	FASTA	445	51,763
	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
	Isoform 2 (Nek2B) [UniParc]. Checksum: EBFA8B6BB07480FB	FASTA	384	44,906
	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 RKFLSLASNP GMRINLVNRS WCYK
	Isoform 3 [UniParc]. Checksum: 3F3FDD8262E77964	FASTA	326	37,956
	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 PVLSELKLKE IQLQERERAL KAKKKK
	Isoform 4 (Nek2C) (Nek2A-T) [UniParc]. Checksum: BF89938C50FAD817	FASTA	437	50,909
	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 VIKKKVHFSG ESKENIMRSE NSESQLTSKS KCKDLKKRLH AAQLRAQALS 430 DIEKNYQLKS RQILGMR

References

	« Hide 'large scale' referencesShow '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: 7522034] [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: 11742531] [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. , 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: 16710414] [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: 15489334] [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: 8274451] [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: 15659832] [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: 14978040] [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: 12857871] [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: 15358203] [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: 15388344] [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: 15161910] [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: 17283141] [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: 17621308] [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: 17626005] [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: 18086858] [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: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397, MASS SPECTROMETRY. 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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184; SER-296 AND SER-300, MASS SPECTROMETRY. 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: 18297113] [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: 19941817] [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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296; SER-299 AND SER-300, MASS SPECTROMETRY.
[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: 20599736] [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: 20034488] [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: 21076410] [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: 21669869] [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: 16280549] [Abstract] Cited for: REVIEW.
[29]	"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: 17197699] [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, MASS SPECTROMETRY.
[30]	"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: 17344846] [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.

IPI

IPI00021331.
IPI00641713.
IPI00647904.
IPI01025730.

PIR

G01452.
I38215.

RefSeq

NP_001191111.1. NM_001204182.1.
NP_001191112.1. NM_001204183.1.
NP_002488.1. NM_002497.3.

UniGene

Hs.153704.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JAV	X-ray	2.20	A	1-271	[»]
2W5A	X-ray	1.55	A	1-271	[»]
2W5B	X-ray	2.40	A	1-271	[»]
2W5H	X-ray	2.33	A	1-271	[»]
2WQO	X-ray	2.17	A	1-271	[»]
2XK3	X-ray	2.20	A	1-271	[»]
2XK4	X-ray	2.10	A	1-271	[»]
2XK6	X-ray	2.20	A	1-271	[»]
2XK7	X-ray	1.99	A	1-271	[»]
2XK8	X-ray	2.00	A	1-271	[»]
2XKC	X-ray	2.50	A	1-271	[»]
2XKD	X-ray	1.96	A	1-271	[»]
2XKE	X-ray	2.20	A	1-271	[»]
2XKF	X-ray	2.35	A	1-271	[»]
2XNM	X-ray	1.85	A	1-271	[»]
2XNN	X-ray	2.50	A	1-271	[»]
2XNO	X-ray	1.98	A	1-271	[»]
2XNP	X-ray	1.98	A	1-271	[»]

ProteinModelPortal

P51955.

SMR

P51955. Positions 3-273.

ModBase

Search...

Protein-protein interaction databases

IntAct

P51955. 11 interactions.

STRING

P51955.

PTM databases

PhosphoSite

P51955.

Polymorphism databases

DMDM

1709252.

Proteomic databases

PRIDE

P51955.

Protocols and materials databases

DNASU

4751.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366999; ENSP00000355966; ENSG00000117650.

GeneID

4751.

KEGG

hsa:4751.

UCSC

uc001hir.2. human.
uc001his.4. human.

Organism-specific databases

CTD

4751.

GeneCards

GC01M211836.

H-InvDB

HIX0023615.

HGNC

HGNC:7745. NEK2.

HPA

CAB017530.

MIM

604043. gene.

neXtProt

NX_P51955.

PharmGKB

PA31546.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00640000091094.

HOVERGEN

HBG006461.

InParanoid

P51955.

KO

K08857.

OMA

QELCVRE.

OrthoDB

EOG4XKV70.

PhylomeDB

P51955.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

foxm1pathway. FOXM1 transcription factor network.

Reactome

REACT_115566. Cell Cycle.
REACT_8017. APC-Cdc20 mediated degradation of Nek2A.

Gene expression databases

ArrayExpress

P51955.

Bgee

Q5I1Z9.

CleanEx

HS_NEK2.

Genevestigator

P51955.

GermOnline

ENSG00000117650. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

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

EvolutionaryTrace

P51955.

NextBio

18310.

PMAP-CutDB

P51955.

SOURCE

Search...

Entry information

Entry name

NEK2_HUMAN

Accession

Primary (citable) accession number: P51955
Secondary accession number(s): Q53FD6 , Q5I1Z9, Q5VXZ1, Q6NZX8, Q7Z634, Q86XH2, Q96QN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 16, 2012
This is version 137 of the entry and version 1 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.