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Protein

Serine/threonine-protein kinase Nek2

Gene

NEK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856).15 Publications
Isoform 1: Phosphorylates and activates NEK11 in G1/S-arrested cells.1 Publication
Isoform 2: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Activity 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)DescriptionActionsGraphical viewLength
Binding sitei37ATP1
Active sitei141Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi14 – 22ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activity Source: UniProtKB
  • protein phosphatase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, Chromosome partition, Meiosis, Mitosis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-179409 APC-Cdc20 mediated degradation of Nek2A
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259 Loss of Nlp from mitotic centrosomes
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912 Anchoring of the basal body to the plasma membrane
R-HSA-8854518 AURKA Activation by TPX2
SignaLinkiP51955
SIGNORiP51955

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
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000117650.12
HGNCiHGNC:7745 NEK2
MIMi604043 gene
neXtProtiNX_P51955

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Mutagenesisi37K → R: Loss of kinase activity and of ability to activate NEK11. 2 Publications1
Mutagenesisi141D → A: Loss of autophosphorylation. 1 Publication1
Mutagenesisi170T → A: No effect on kinase activity. 1 Publication1
Mutagenesisi170T → E: Kinase activity increased by two fold. 1 Publication1
Mutagenesisi171S → A: No effect on kinase activity. 1 Publication1
Mutagenesisi171S → D: Kinase activity increased by two fold. 1 Publication1
Mutagenesisi175T → A: Kinase activity decreased by two fold. 1 Publication1
Mutagenesisi175T → E: Kinase activity increased by two fold. 1 Publication1
Mutagenesisi179T → A: Loss of kinase activity. 1 Publication1
Mutagenesisi179T → E: Loss of kinase activity. 1 Publication1
Mutagenesisi241S → A: Loss of kinase activity. 1 Publication1
Mutagenesisi241S → D: Loss of kinase activity. 1 Publication1

Keywords - Diseasei

Retinitis pigmentosa

Organism-specific databases

DisGeNETi4751
MalaCardsiNEK2
MIMi615565 phenotype
OpenTargetsiENSG00000117650
Orphaneti791 Retinitis pigmentosa
PharmGKBiPA31546

Chemistry databases

ChEMBLiCHEMBL3835
GuidetoPHARMACOLOGYi2117

Polymorphism and mutation databases

BioMutaiNEK2
DMDMi1709252

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864211 – 445Serine/threonine-protein kinase Nek2Add BLAST445

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei170Phosphothreonine; by autocatalysis1 Publication1
Modified residuei171Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei175Phosphothreonine; by autocatalysis1 Publication1
Modified residuei179Phosphothreonine; by autocatalysis1 Publication1
Modified residuei184PhosphoserineCombined sources1
Modified residuei241Phosphoserine; by autocatalysis1 Publication1
Modified residuei296PhosphoserineCombined sources1
Modified residuei300PhosphoserineCombined sources1
Modified residuei356Phosphoserine; by STK3/MST22 Publications1
Modified residuei365Phosphoserine; by STK3/MST21 Publication1
Modified residuei387Phosphoserine1 Publication1
Modified residuei390Phosphoserine1 Publication1
Modified residuei397PhosphoserineCombined sources1 Publication1
Modified residuei402Phosphoserine1 Publication1
Modified residuei406Phosphoserine; by STK3/MST21 Publication1
Modified residuei428Phosphoserine1 Publication1
Modified residuei438Phosphoserine; by STK3/MST21 Publication1

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

EPDiP51955
MaxQBiP51955
PaxDbiP51955
PeptideAtlasiP51955
PRIDEiP51955
ProteomicsDBi56453
56454 [P51955-2]
56455 [P51955-3]
56456 [P51955-4]

PTM databases

iPTMnetiP51955
PhosphoSitePlusiP51955

Miscellaneous databases

PMAP-CutDBiP51955

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.2 Publications

Gene expression databases

BgeeiENSG00000117650 Expressed in 153 organ(s), highest expression level in testis
CleanExiHS_NEK2
ExpressionAtlasiP51955 baseline and differential
GenevisibleiP51955 HS

Organism-specific databases

HPAiCAB017530
HPA064967

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 SGO1 (PubMed:14978040, PubMed:15358203, PubMed:15388344, PubMed:15161910, PubMed:17621308, PubMed:18086858, PubMed:18297113, PubMed:20599736, PubMed:20034488). Isoform 1 interacts with STK3/MST2 (via SARAH domain) and SAV1 (via SARAH domain) (PubMed:21076410). Isoform 1 and isoform 2 interact with MAD2L1 (PubMed:20034488). Isoform 1 and isoform 4 interact with PPP1CA and PPP1CC (PubMed:15659832, PubMed:17283141). Interacts with CEP68; the interaction leads to phosphorylation of CEP68. Interacts with CNTLN; the interaction leads to phosphorylation of CNTLN (PubMed:24554434). Isoform 1 interacts with CEP85 (PubMed:26220856).By similarity16 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110826, 54 interactors
CORUMiP51955
IntActiP51955, 40 interactors
MINTiP51955
STRINGi9606.ENSP00000355966

Chemistry databases

BindingDBiP51955

Structurei

Secondary structure

1445
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP51955
SMRiP51955
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51955

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 271Protein kinasePROSITE-ProRule annotationAdd BLAST264

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni264 – 445Interaction with PCNT1 PublicationAdd BLAST182
Regioni301 – 445Interaction with CEP851 PublicationAdd BLAST145
Regioni306 – 334Leucine-zipperAdd BLAST29
Regioni329 – 445Necessary for interaction with MAD1L11 PublicationAdd BLAST117
Regioni333 – 370Required for microtubule binding and for localization to the centrosomesAdd BLAST38
Regioni403 – 439Interaction with SAV1 and STK3/MST21 PublicationAdd BLAST37

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili303 – 362Sequence analysisAdd BLAST60
Coiled coili406 – 430Sequence analysisAdd BLAST25

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0591 Eukaryota
ENOG410XNQP LUCA
GeneTreeiENSGT00760000118997
HOVERGENiHBG006461
InParanoidiP51955
KOiK20872
OMAiAYNQKEL
OrthoDBiEOG091G07PD
PhylomeDBiP51955
TreeFamiTF101184

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6U4U2F6U4U2_HUMAN
Serine/threonine-protein kinase Nek...
NEK2
388Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti84 – 85IV → LY in CAA80912 (PubMed:8274451).Curated2
Sequence conflicti325E → K in BAD97073 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019990354N → S2 PublicationsCorresponds to variant dbSNP:rs2230489Ensembl.1
Natural variantiVAR_040907410C → Y1 PublicationCorresponds to variant dbSNP:rs56102977Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015576323 – 326REER → KKKK in isoform 3. 1 Publication4
Alternative sequenceiVSP_015577327 – 445Missing in isoform 3. 1 PublicationAdd BLAST119
Alternative sequenceiVSP_015578371 – 384ELLNL…IKKKV → GMRINLVNRSWCYK in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_041758371 – 378Missing in isoform 4. 1 Publication8
Alternative sequenceiVSP_015579385 – 445Missing in isoform 2. 1 PublicationAdd BLAST61

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
AC096637 Genomic DNA No translation available.
AL356310 Genomic DNA No translation available.
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.3 human [P51955-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNEK2_HUMAN
AccessioniPrimary (citable) accession number: P51955
Secondary accession number(s): Q53FD6
, Q5I1Z9, Q5VXZ1, Q6NZX8, Q7Z634, Q86XH2, Q96QN9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 12, 2018
This is version 199 of the entry and version 1 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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