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Protein

Serine/threonine-protein kinase Nek2

Gene

NEK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.13 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

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.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei37 – 371ATP
Active sitei141 – 1411Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi14 – 229ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. protein kinase activity Source: UniProtKB
  4. protein phosphatase binding Source: UniProtKB
  5. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Source: Reactome
  2. blastocyst development Source: Ensembl
  3. cell division Source: UniProtKB-KW
  4. centrosome separation Source: UniProtKB
  5. chromosome segregation Source: UniProtKB
  6. G2/M transition of mitotic cell cycle Source: Reactome
  7. meiotic cell cycle Source: UniProtKB-KW
  8. mitotic cell cycle Source: Reactome
  9. mitotic nuclear division Source: ProtInc
  10. mitotic sister chromatid segregation Source: Ensembl
  11. mitotic spindle assembly Source: Ensembl
  12. negative regulation of centriole-centriole cohesion Source: UniProtKB
  13. negative regulation of DNA binding Source: Ensembl
  14. organelle organization Source: Reactome
  15. protein autophosphorylation Source: UniProtKB
  16. protein phosphorylation Source: UniProtKB
  17. regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
  18. regulation of mitotic centrosome separation Source: UniProtKB
  19. regulation of mitotic nuclear division Source: ProtInc
  20. spindle assembly Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Chromosome partition, Meiosis, Mitosis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_15296. Recruitment of mitotic centrosome proteins and complexes.
REACT_15364. Loss of Nlp from mitotic centrosomes.
REACT_15451. Loss of proteins required for interphase microtubule organization from the centrosome.
REACT_160315. Regulation of PLK1 Activity at G2/M Transition.
REACT_267965. Anchoring of the basal body to the plasma membrane.
REACT_8017. APC-Cdc20 mediated degradation of Nek2A.
SignaLinkiP51955.

Names & Taxonomyi

Protein namesi
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 namesi
Name:NEK2
Synonyms:NEK2A, NLK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:7745. NEK2.

Subcellular locationi

Isoform 1 :
  1. Nucleus
  2. Nucleusnucleolus
  3. Cytoplasm
  4. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome
  5. Cytoplasmcytoskeletonspindle pole
  6. Chromosomecentromerekinetochore
  7. Chromosomecentromere By similarity

  8. 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.
Isoform 2 :
  1. Cytoplasm

  2. Note: Predominantly cytoplasmic.

GO - Cellular componenti

  1. centrosome Source: UniProtKB
  2. condensed chromosome kinetochore Source: UniProtKB-SubCell
  3. condensed nuclear chromosome Source: Ensembl
  4. cytoplasm Source: HPA
  5. cytosol Source: Reactome
  6. intercellular bridge Source: HPA
  7. kinetochore Source: UniProtKB
  8. microtubule Source: UniProtKB-KW
  9. midbody Source: Ensembl
  10. nucleolus Source: UniProtKB-SubCell
  11. nucleus Source: HPA
  12. protein complex Source: UniProtKB
  13. spindle pole Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Microtubule, Nucleus

Pathology & Biotechi

Involvement in diseasei

Retinitis pigmentosa 67 (RP67)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:615565

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi37 – 371K → R: Loss of kinase activity and of ability to activate NEK11. 2 Publications
Mutagenesisi141 – 1411D → A: Loss of autophosphorylation. 1 Publication
Mutagenesisi170 – 1701T → A: No effect on kinase activity. 1 Publication
Mutagenesisi170 – 1701T → E: Kinase activity increased by two fold. 1 Publication
Mutagenesisi171 – 1711S → A: No effect on kinase activity. 1 Publication
Mutagenesisi171 – 1711S → D: Kinase activity increased by two fold. 1 Publication
Mutagenesisi175 – 1751T → A: Kinase activity decreased by two fold. 1 Publication
Mutagenesisi175 – 1751T → E: Kinase activity increased by two fold. 1 Publication
Mutagenesisi179 – 1791T → A: Loss of kinase activity. 1 Publication
Mutagenesisi179 – 1791T → E: Loss of kinase activity. 1 Publication
Mutagenesisi241 – 2411S → A: Loss of kinase activity. 1 Publication
Mutagenesisi241 – 2411S → D: Loss of kinase activity. 1 Publication

Keywords - Diseasei

Retinitis pigmentosa

Organism-specific databases

MIMi615565. phenotype.
Orphaneti791. Retinitis pigmentosa.
PharmGKBiPA31546.

Polymorphism and mutation databases

BioMutaiNEK2.
DMDMi1709252.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 445445Serine/threonine-protein kinase Nek2PRO_0000086421Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei170 – 1701Phosphothreonine; by autocatalysis1 Publication
Modified residuei171 – 1711Phosphoserine; by autocatalysis1 Publication
Modified residuei175 – 1751Phosphothreonine; by autocatalysis1 Publication
Modified residuei179 – 1791Phosphothreonine; by autocatalysis1 Publication
Modified residuei241 – 2411Phosphoserine; by autocatalysis1 Publication
Modified residuei296 – 2961Phosphoserine2 Publications
Modified residuei356 – 3561Phosphoserine; by STK3/MST22 Publications
Modified residuei365 – 3651Phosphoserine; by STK3/MST21 Publication
Modified residuei387 – 3871Phosphoserine1 Publication
Modified residuei390 – 3901Phosphoserine1 Publication
Modified residuei397 – 3971Phosphoserine2 Publications
Modified residuei402 – 4021Phosphoserine1 Publication
Modified residuei406 – 4061Phosphoserine; by STK3/MST21 Publication
Modified residuei428 – 4281Phosphoserine1 Publication
Modified residuei438 – 4381Phosphoserine; by STK3/MST21 Publication

Post-translational modificationi

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.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP51955.
PaxDbiP51955.
PRIDEiP51955.

PTM databases

PhosphoSiteiP51955.

Miscellaneous databases

PMAP-CutDBP51955.

Expressioni

Tissue specificityi

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.2 Publications

Inductioni

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.

Gene expression databases

BgeeiP51955.
CleanExiHS_NEK2.
ExpressionAtlasiP51955. baseline and differential.
GenevestigatoriP51955.

Organism-specific databases

HPAiCAB017530.
HPA047522.

Interactioni

Subunit structurei

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.By similarity14 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi110826. 38 interactions.
IntActiP51955. 31 interactions.
MINTiMINT-3019433.
STRINGi9606.ENSP00000355966.

Structurei

Secondary structure

1
445
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi5 – 73Combined sources
Beta strandi8 – 169Combined sources
Beta strandi18 – 2710Combined sources
Turni28 – 303Combined sources
Beta strandi33 – 408Combined sources
Helixi41 – 433Combined sources
Helixi46 – 6116Combined sources
Beta strandi70 – 767Combined sources
Helixi77 – 793Combined sources
Beta strandi81 – 877Combined sources
Helixi94 – 10310Combined sources
Helixi110 – 13021Combined sources
Helixi144 – 1463Combined sources
Beta strandi147 – 1493Combined sources
Beta strandi151 – 1533Combined sources
Beta strandi155 – 1573Combined sources
Helixi162 – 1654Combined sources
Helixi171 – 1777Combined sources
Helixi185 – 1895Combined sources
Helixi195 – 21117Combined sources
Helixi221 – 23010Combined sources
Helixi242 – 25110Combined sources
Helixi256 – 2583Combined sources
Helixi262 – 2665Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP51955.
SMRiP51955. Positions 3-363.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51955.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini8 – 271264Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni264 – 445182Interaction with PCNTAdd
BLAST
Regioni306 – 33429Leucine-zipperAdd
BLAST
Regioni329 – 445117Necessary for interaction with MAD1L1Add
BLAST
Regioni333 – 37038Required for microtubule binding and for localization to the centrosomesAdd
BLAST
Regioni403 – 43937Interaction with SAV1 and STK3/MST2Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili303 – 36260Sequence AnalysisAdd
BLAST
Coiled coili406 – 43025Sequence AnalysisAdd
BLAST

Domaini

The leucine-zipper domain is required for its dimerization and activation.1 Publication

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118997.
HOVERGENiHBG006461.
InParanoidiP51955.
KOiK08857.
OMAiSKCKDLK.
OrthoDBiEOG715Q40.
PhylomeDBiP51955.
TreeFamiTF101184.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P51955-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPSRAEDYEV LYTIGTGSYG RCQKIRRKSD GKILVWKELD YGSMTEAEKQ
60 70 80 90 100
MLVSEVNLLR ELKHPNIVRY YDRIIDRTNT TLYIVMEYCE GGDLASVITK
110 120 130 140 150
GTKERQYLDE EFVLRVMTQL TLALKECHRR SDGGHTVLHR DLKPANVFLD
160 170 180 190 200
GKQNVKLGDF GLARILNHDT SFAKTFVGTP YYMSPEQMNR MSYNEKSDIW
210 220 230 240 250
SLGCLLYELC ALMPPFTAFS QKELAGKIRE GKFRRIPYRY SDELNEIITR
260 270 280 290 300
MLNLKDYHRP SVEEILENPL IADLVADEQR RNLERRGRQL GEPEKSQDSS
310 320 330 340 350
PVLSELKLKE IQLQERERAL KAREERLEQK EQELCVRERL AEDKLARAEN
360 370 380 390 400
LLKNYSLLKE RKFLSLASNP ELLNLPSSVI KKKVHFSGES KENIMRSENS
410 420 430 440
ESQLTSKSKC KDLKKRLHAA QLRAQALSDI EKNYQLKSRQ ILGMR
Length:445
Mass (Da):51,763
Last modified:October 1, 1996 - v1
Checksum:iD33A37778ABB6D9E
GO
Isoform 2 (identifier: P51955-2) [UniParc]FASTAAdd to basket

Also known as: Nek2B

The sequence of this isoform differs from the canonical sequence as follows:
     371-384: ELLNLPSSVIKKKV → GMRINLVNRSWCYK
     385-445: Missing.

Show »
Length:384
Mass (Da):44,906
Checksum:iEBFA8B6BB07480FB
GO
Isoform 3 (identifier: P51955-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     323-326: REER → KKKK
     327-445: Missing.

Show »
Length:326
Mass (Da):37,956
Checksum:i3F3FDD8262E77964
GO
Isoform 4 (identifier: P51955-4) [UniParc]FASTAAdd to basket

Also known as: Nek2C, Nek2A-T

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

Show »
Length:437
Mass (Da):50,909
Checksum:iBF89938C50FAD817
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti84 – 852IV → LY in CAA80912 (PubMed:8274451).Curated
Sequence conflicti325 – 3251E → K in BAD97073 (Ref. 5) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti354 – 3541N → S.2 Publications
Corresponds to variant rs2230489 [ dbSNP | Ensembl ].
VAR_019990
Natural varianti410 – 4101C → Y.1 Publication
Corresponds to variant rs56102977 [ dbSNP | Ensembl ].
VAR_040907

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei323 – 3264REER → KKKK in isoform 3. 1 PublicationVSP_015576
Alternative sequencei327 – 445119Missing in isoform 3. 1 PublicationVSP_015577Add
BLAST
Alternative sequencei371 – 38414ELLNL…IKKKV → GMRINLVNRSWCYK in isoform 2. 1 PublicationVSP_015578Add
BLAST
Alternative sequencei371 – 3788Missing in isoform 4. 1 PublicationVSP_041758
Alternative sequencei385 – 44561Missing in isoform 2. 1 PublicationVSP_015579Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1500.1. [P51955-1]
CCDS55682.1. [P51955-2]
PIRiG01452.
I38215.
RefSeqiNP_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]
UniGeneiHs.153704.

Genome annotation databases

EnsembliENST00000366998; ENSP00000355965; ENSG00000117650. [P51955-2]
ENST00000366999; ENSP00000355966; ENSG00000117650. [P51955-1]
GeneIDi4751.
KEGGihsa:4751.
UCSCiuc001hir.2. human. [P51955-1]
uc001his.4. human. [P51955-2]

Polymorphism and mutation databases

BioMutaiNEK2.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1500.1. [P51955-1]
CCDS55682.1. [P51955-2]
PIRiG01452.
I38215.
RefSeqiNP_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]
UniGeneiHs.153704.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP51955.
SMRiP51955. Positions 3-363.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110826. 38 interactions.
IntActiP51955. 31 interactions.
MINTiMINT-3019433.
STRINGi9606.ENSP00000355966.

Chemistry

BindingDBiP51955.
ChEMBLiCHEMBL3835.
GuidetoPHARMACOLOGYi2117.

PTM databases

PhosphoSiteiP51955.

Polymorphism and mutation databases

BioMutaiNEK2.
DMDMi1709252.

Proteomic databases

MaxQBiP51955.
PaxDbiP51955.
PRIDEiP51955.

Protocols and materials databases

DNASUi4751.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366998; ENSP00000355965; ENSG00000117650. [P51955-2]
ENST00000366999; ENSP00000355966; ENSG00000117650. [P51955-1]
GeneIDi4751.
KEGGihsa:4751.
UCSCiuc001hir.2. human. [P51955-1]
uc001his.4. human. [P51955-2]

Organism-specific databases

CTDi4751.
GeneCardsiGC01M211836.
HGNCiHGNC:7745. NEK2.
HPAiCAB017530.
HPA047522.
MIMi604043. gene.
615565. phenotype.
neXtProtiNX_P51955.
Orphaneti791. Retinitis pigmentosa.
PharmGKBiPA31546.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118997.
HOVERGENiHBG006461.
InParanoidiP51955.
KOiK08857.
OMAiSKCKDLK.
OrthoDBiEOG715Q40.
PhylomeDBiP51955.
TreeFamiTF101184.

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_15296. Recruitment of mitotic centrosome proteins and complexes.
REACT_15364. Loss of Nlp from mitotic centrosomes.
REACT_15451. Loss of proteins required for interphase microtubule organization from the centrosome.
REACT_160315. Regulation of PLK1 Activity at G2/M Transition.
REACT_267965. Anchoring of the basal body to the plasma membrane.
REACT_8017. APC-Cdc20 mediated degradation of Nek2A.
SignaLinkiP51955.

Miscellaneous databases

EvolutionaryTraceiP51955.
GeneWikiiNEK2.
GenomeRNAii4751.
NextBioi18310.
PMAP-CutDBP51955.
PROiP51955.
SOURCEiSearch...

Gene expression databases

BgeeiP51955.
CleanExiHS_NEK2.
ExpressionAtlasiP51955. baseline and differential.
GenevestigatoriP51955.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: FUNCTION, INTERACTION WITH CTNB1.
  19. 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. 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. Cited for: REVIEW.
  29. Cited for: INVOLVEMENT IN RP67.
  30. 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.
    , 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.

Entry informationi

Entry nameiNEK2_HUMAN
AccessioniPrimary (citable) accession number: P51955
Secondary accession number(s): Q53FD6
, Q5I1Z9, Q5VXZ1, Q6NZX8, Q7Z634, Q86XH2, Q96QN9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 29, 2015
This is version 169 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.