UniProtKB - O35942 (NEK2_MOUSE)
Protein
Serine/threonine-protein kinase Nek2
Gene
Nek2
Organism
Mus musculus (Mouse)
Status
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 (By similarity). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (By similarity). Phosphorylates and activates NEK11 in G1/S-arrested cells. Involved in the regulation of centrosome disjunction (By similarity).By similarity2 Publications
Catalytic activityi
Cofactori
Activity regulationi
Its catalytic activity is inhibited by the inhibitor CCT241950. In the presence of this inhibitor, displays an autoinhibited conformation: Tyr-70 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 37 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 141 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 14 – 22 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- protein kinase activity Source: MGI
- protein phosphatase binding Source: MGI
- protein serine/threonine kinase activity Source: GO_Central
GO - Biological processi
- blastocyst development Source: MGI
- cell division Source: UniProtKB-KW
- centrosome separation Source: MGI
- chromosome segregation Source: MGI
- meiotic cell cycle Source: UniProtKB-KW
- mitotic sister chromatid segregation Source: MGI
- mitotic spindle assembly Source: MGI
- negative regulation of centriole-centriole cohesion Source: MGI
- negative regulation of DNA binding Source: MGI
- positive regulation of telomerase activity Source: MGI
- positive regulation of telomere capping Source: MGI
- positive regulation of telomere maintenance via telomerase Source: MGI
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: MGI
- regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
- regulation of mitotic centrosome separation Source: UniProtKB
- regulation of mitotic nuclear division Source: GO_Central
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle, Cell division, Chromosome partition, Meiosis, Mitosis |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-179409 APC-Cdc20 mediated degradation of Nek2A R-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition R-MMU-380259 Loss of Nlp from mitotic centrosomes R-MMU-380270 Recruitment of mitotic centrosome proteins and complexes R-MMU-380284 Loss of proteins required for interphase microtubule organization from the centrosome R-MMU-380320 Recruitment of NuMA to mitotic centrosomes R-MMU-5620912 Anchoring of the basal body to the plasma membrane R-MMU-8854518 AURKA Activation by TPX2 |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein kinase Nek2 (EC:2.7.11.1)Alternative name(s): Never in mitosis A-related kinase 2 Short name: NimA-related protein kinase 2 |
Gene namesi | Name:Nek2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:109359 Nek2 |
Subcellular locationi
Cytoskeleton
- centrosome By similarity
- spindle pole By similarity
Nucleus
Other locations
- Cytoplasm By similarity
- kinetochore By similarity
- centromere 1 Publication
Note: STK3/MST2 and SAV1 are required for its targeting to the centrosome. Colocalizes with SGO1 and MAD1L1 at the kinetochore. Not associated with kinetochore in the interphase but becomes associated with it upon the breakdown of the nuclear envelope. Has a nucleolar targeting/ retention activity via a coiled-coil domain at the C-terminal end (By similarity).By similarity
Cytoskeleton
- centrosome Source: UniProtKB
- microtubule Source: UniProtKB-KW
- spindle pole Source: MGI
Nucleus
- condensed nuclear chromosome Source: MGI
- nucleolus Source: UniProtKB-SubCell
- nucleoplasm Source: MGI
- nucleus Source: GO_Central
Other locations
- condensed chromosome kinetochore Source: UniProtKB-SubCell
- cytoplasm Source: UniProtKB-SubCell
- kinetochore Source: MGI
- midbody Source: MGI
- protein-containing complex Source: MGI
Keywords - Cellular componenti
Centromere, Chromosome, Cytoplasm, Cytoskeleton, Kinetochore, Microtubule, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086422 | 1 – 443 | Serine/threonine-protein kinase Nek2Add BLAST | 443 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 170 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 171 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 175 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 179 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 184 | PhosphoserineBy similarity | 1 | |
Modified residuei | 241 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 300 | PhosphoserineBy similarity | 1 | |
Modified residuei | 356 | Phosphoserine; by STK3/MST2By similarity | 1 | |
Modified residuei | 389 | PhosphoserineBy similarity | 1 | |
Modified residuei | 396 | PhosphoserineBy similarity | 1 | |
Modified residuei | 401 | PhosphoserineBy similarity | 1 | |
Modified residuei | 436 | Phosphoserine; by STK3/MST2By similarity | 1 |
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.By similarity
Keywords - PTMi
PhosphoproteinProteomic databases
MaxQBi | O35942 |
PaxDbi | O35942 |
PRIDEi | O35942 |
PTM databases
iPTMneti | O35942 |
PhosphoSitePlusi | O35942 |
Expressioni
Tissue specificityi
Most abundantly expressed in testis. Low levels found in mid-gestation embryo, ovary, placenta, intestine, thymus and skin. Within the testis, expression restricted to germ cells with highest levels detected in spermatocytes at pachytene and diplotene stages. Also expressed in meiotic pachytene oocytes.2 Publications
Gene expression databases
Bgeei | ENSMUSG00000026622 Expressed in 195 organ(s), highest expression level in testis |
Genevisiblei | O35942 MM |
Interactioni
Subunit structurei
Forms homodimers and heterodimers. Interacts with CDC20, CTNB1, MAD1L1, MAD2L1, MAPK, NEK11, NPM1, NDC80, PCNT, PPP1CA, PPP1CC and SGO1. Interacts with STK3/MST2 (via SARAH domain) and SAV1 (via SARAH domain) (By similarity). Interacts with NECAB3 and HMGA2 (PubMed:14697346, PubMed:14668482). Interacts with CEP68; the interaction leads to phosphorylation of CEP68. Interacts with CNTLN; the interaction leads to phosphorylation of CNTLN. Interacts with CEP85 (By similarity).By similarity2 Publications
GO - Molecular functioni
- protein phosphatase binding Source: MGI
Protein-protein interaction databases
BioGridi | 201728, 38 interactors |
IntActi | O35942, 37 interactors |
STRINGi | 10090.ENSMUSP00000027931 |
Structurei
3D structure databases
ProteinModelPortali | O35942 |
SMRi | O35942 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 8 – 271 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 264 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 264 – 443 | Interaction with PCNTBy similarityAdd BLAST | 180 | |
Regioni | 301 – 443 | Interaction with CEP85By similarityAdd BLAST | 143 | |
Regioni | 306 – 334 | Leucine-zipperAdd BLAST | 29 | |
Regioni | 329 – 443 | Necessary for interaction with MAD1L1By similarityAdd BLAST | 115 | |
Regioni | 333 – 370 | Required for microtubule binding and for localization to the centrosomesBy similarityAdd BLAST | 38 | |
Regioni | 402 – 437 | Interaction with SAV1 and STK3/MST2By similarityAdd BLAST | 36 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 303 – 361 | Sequence analysisAdd BLAST | 59 | |
Coiled coili | 403 – 427 | Sequence analysisAdd BLAST | 25 |
Domaini
The leucine-zipper domain is required for its dimerization and activation.By similarity
Sequence similaritiesi
Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.Curated
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG0591 Eukaryota ENOG410XNQP LUCA |
GeneTreei | ENSGT00940000156989 |
HOGENOMi | HOG000233029 |
HOVERGENi | HBG006461 |
InParanoidi | O35942 |
KOi | K20872 |
OMAi | AYNQKEL |
OrthoDBi | 1290401at2759 |
TreeFami | TF101184 |
Family and domain databases
InterProi | View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR008271 Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069 Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220 S_TKc, 1 hit |
SUPFAMi | SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit |
i Sequence
Sequence statusi: Complete.
O35942-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPSRVEDYEV LHSIGTGSYG RCQKIRRKSD GKILVWKELD YGSMTEVEKQ
60 70 80 90 100
MLVSEVNLLR ELKHPNIVSY YDRIIDRTNT TLYIVMEYCE GGDLASVISK
110 120 130 140 150
GTKDRQYLEE EFVLRVMTQL TLALKECHRR SDGGHTVLHR DLKPANVFLD
160 170 180 190 200
SKHNVKLGDF GLARILNHDT SFAKTFVGTP YYMSPEQMSC LSYNEKSDIW
210 220 230 240 250
SLGCLLYELC ALMPPFTAFN QKELAGKIRE GRFRRIPYRY SDGLNDLITR
260 270 280 290 300
MLNLKDYHRP SVEEILESPL IADLVAEEQR RNLERRGRRS GEPSKLPDSS
310 320 330 340 350
PVLSELKLKE RQLQDREQAL RAREDILEQK ERELCIRERL AEDKLARAES
360 370 380 390 400
LMKNYSLLKE HRLLCLAGGP ELDLPSSAMK KKVHFHGESK ENTARSENSE
410 420 430 440
SYLAKSKCRD LKKRLHAAQL RAQALADIEK NYQLKSRQIL GMR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 69 | S → R in AAB67973 (PubMed:9187143).Curated | 1 | |
Sequence conflicti | 69 | S → R in AAC35393 (PubMed:9583679).Curated | 1 | |
Sequence conflicti | 69 | S → R in AAB70470 (PubMed:9434622).Curated | 1 | |
Sequence conflicti | 203 | G → A in AAB67973 (PubMed:9187143).Curated | 1 | |
Sequence conflicti | 253 | N → F in AAB67973 (PubMed:9187143).Curated | 1 | |
Sequence conflicti | 274 | L → M in AAB67973 (PubMed:9187143).Curated | 1 | |
Sequence conflicti | 274 | L → M in AAC35393 (PubMed:9583679).Curated | 1 | |
Sequence conflicti | 274 | L → M in AAB70470 (PubMed:9434622).Curated | 1 | |
Sequence conflicti | 311 | R → S in AAB67973 (PubMed:9187143).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U95610 mRNA Translation: AAB67973.1 AF013166 mRNA Translation: AAC35393.1 AF007247 mRNA Translation: AAB70470.1 AK147072 mRNA Translation: BAE27653.1 AK164467 mRNA Translation: BAE37799.1 |
CCDSi | CCDS15623.1 |
RefSeqi | NP_035022.2, NM_010892.3 |
UniGenei | Mm.33773 Mm.403999 |
Genome annotation databases
Ensembli | ENSMUST00000027931; ENSMUSP00000027931; ENSMUSG00000026622 ENSMUST00000213394; ENSMUSP00000149034; ENSMUSG00000110797 |
GeneIDi | 18005 |
KEGGi | mmu:18005 |
UCSCi | uc007ecx.2 mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U95610 mRNA Translation: AAB67973.1 AF013166 mRNA Translation: AAC35393.1 AF007247 mRNA Translation: AAB70470.1 AK147072 mRNA Translation: BAE27653.1 AK164467 mRNA Translation: BAE37799.1 |
CCDSi | CCDS15623.1 |
RefSeqi | NP_035022.2, NM_010892.3 |
UniGenei | Mm.33773 Mm.403999 |
3D structure databases
ProteinModelPortali | O35942 |
SMRi | O35942 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 201728, 38 interactors |
IntActi | O35942, 37 interactors |
STRINGi | 10090.ENSMUSP00000027931 |
PTM databases
iPTMneti | O35942 |
PhosphoSitePlusi | O35942 |
Proteomic databases
MaxQBi | O35942 |
PaxDbi | O35942 |
PRIDEi | O35942 |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENSMUST00000027931; ENSMUSP00000027931; ENSMUSG00000026622 ENSMUST00000213394; ENSMUSP00000149034; ENSMUSG00000110797 |
GeneIDi | 18005 |
KEGGi | mmu:18005 |
UCSCi | uc007ecx.2 mouse |
Organism-specific databases
CTDi | 4751 |
MGIi | MGI:109359 Nek2 |
Phylogenomic databases
eggNOGi | KOG0591 Eukaryota ENOG410XNQP LUCA |
GeneTreei | ENSGT00940000156989 |
HOGENOMi | HOG000233029 |
HOVERGENi | HBG006461 |
InParanoidi | O35942 |
KOi | K20872 |
OMAi | AYNQKEL |
OrthoDBi | 1290401at2759 |
TreeFami | TF101184 |
Enzyme and pathway databases
Reactomei | R-MMU-179409 APC-Cdc20 mediated degradation of Nek2A R-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition R-MMU-380259 Loss of Nlp from mitotic centrosomes R-MMU-380270 Recruitment of mitotic centrosome proteins and complexes R-MMU-380284 Loss of proteins required for interphase microtubule organization from the centrosome R-MMU-380320 Recruitment of NuMA to mitotic centrosomes R-MMU-5620912 Anchoring of the basal body to the plasma membrane R-MMU-8854518 AURKA Activation by TPX2 |
Miscellaneous databases
PROi | PR:O35942 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000026622 Expressed in 195 organ(s), highest expression level in testis |
Genevisiblei | O35942 MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR008271 Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069 Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220 S_TKc, 1 hit |
SUPFAMi | SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | NEK2_MOUSE | |
Accessioni | O35942Primary (citable) accession number: O35942 Secondary accession number(s): O35959, Q3TPD7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | July 27, 2011 | |
Last modified: | February 13, 2019 | |
This is version 164 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot