O35942 · NEK2_MOUSE
- ProteinSerine/threonine-protein kinase Nek2
- GeneNek2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids443 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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; 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).
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).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Activity regulation
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.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase Nek2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionO35942
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000086422 | 1-443 | Serine/threonine-protein kinase Nek2 | |||
Sequence: MPSRVEDYEVLHSIGTGSYGRCQKIRRKSDGKILVWKELDYGSMTEVEKQMLVSEVNLLRELKHPNIVSYYDRIIDRTNTTLYIVMEYCEGGDLASVISKGTKDRQYLEEEFVLRVMTQLTLALKECHRRSDGGHTVLHRDLKPANVFLDSKHNVKLGDFGLARILNHDTSFAKTFVGTPYYMSPEQMSCLSYNEKSDIWSLGCLLYELCALMPPFTAFNQKELAGKIREGRFRRIPYRYSDGLNDLITRMLNLKDYHRPSVEEILESPLIADLVAEEQRRNLERRGRRSGEPSKLPDSSPVLSELKLKERQLQDREQALRAREDILEQKERELCIRERLAEDKLARAESLMKNYSLLKEHRLLCLAGGPELDLPSSAMKKKVHFHGESKENTARSENSESYLAKSKCRDLKKRLHAAQLRAQALADIEKNYQLKSRQILGMR | ||||||
Modified residue | 170 | Phosphothreonine; by autocatalysis | ||||
Sequence: T | ||||||
Modified residue | 171 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 175 | Phosphothreonine; by autocatalysis | ||||
Sequence: T | ||||||
Modified residue | 179 | Phosphothreonine; by autocatalysis | ||||
Sequence: T | ||||||
Modified residue | 184 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 241 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 300 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 356 | Phosphoserine; by STK3/MST2 | ||||
Sequence: S | ||||||
Modified residue | 389 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 396 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 401 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 436 | Phosphoserine; by STK3/MST2 | ||||
Sequence: S |
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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.
Gene expression databases
Interaction
Subunit
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:14668482, PubMed:14697346).
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).
Interacts with NECAB3 and HMGA2 (PubMed:14668482, PubMed:14697346).
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).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 8-271 | Protein kinase | ||||
Sequence: YEVLHSIGTGSYGRCQKIRRKSDGKILVWKELDYGSMTEVEKQMLVSEVNLLRELKHPNIVSYYDRIIDRTNTTLYIVMEYCEGGDLASVISKGTKDRQYLEEEFVLRVMTQLTLALKECHRRSDGGHTVLHRDLKPANVFLDSKHNVKLGDFGLARILNHDTSFAKTFVGTPYYMSPEQMSCLSYNEKSDIWSLGCLLYELCALMPPFTAFNQKELAGKIREGRFRRIPYRYSDGLNDLITRMLNLKDYHRPSVEEILESPLI | ||||||
Region | 264-443 | Interaction with PCNT | ||||
Sequence: EILESPLIADLVAEEQRRNLERRGRRSGEPSKLPDSSPVLSELKLKERQLQDREQALRAREDILEQKERELCIRERLAEDKLARAESLMKNYSLLKEHRLLCLAGGPELDLPSSAMKKKVHFHGESKENTARSENSESYLAKSKCRDLKKRLHAAQLRAQALADIEKNYQLKSRQILGMR | ||||||
Region | 282-303 | Disordered | ||||
Sequence: NLERRGRRSGEPSKLPDSSPVL | ||||||
Region | 301-443 | Interaction with CEP85 | ||||
Sequence: PVLSELKLKERQLQDREQALRAREDILEQKERELCIRERLAEDKLARAESLMKNYSLLKEHRLLCLAGGPELDLPSSAMKKKVHFHGESKENTARSENSESYLAKSKCRDLKKRLHAAQLRAQALADIEKNYQLKSRQILGMR | ||||||
Coiled coil | 303-361 | |||||
Sequence: LSELKLKERQLQDREQALRAREDILEQKERELCIRERLAEDKLARAESLMKNYSLLKEH | ||||||
Region | 306-334 | Leucine-zipper | ||||
Sequence: LKLKERQLQDREQALRAREDILEQKEREL | ||||||
Region | 329-443 | Necessary for interaction with MAD1L1 | ||||
Sequence: QKERELCIRERLAEDKLARAESLMKNYSLLKEHRLLCLAGGPELDLPSSAMKKKVHFHGESKENTARSENSESYLAKSKCRDLKKRLHAAQLRAQALADIEKNYQLKSRQILGMR | ||||||
Region | 333-370 | Required for microtubule binding and for localization to the centrosomes | ||||
Sequence: ELCIRERLAEDKLARAESLMKNYSLLKEHRLLCLAGGP | ||||||
Region | 383-402 | Disordered | ||||
Sequence: VHFHGESKENTARSENSESY | ||||||
Region | 402-437 | Interaction with SAV1 and STK3/MST2 | ||||
Sequence: YLAKSKCRDLKKRLHAAQLRAQALADIEKNYQLKSR | ||||||
Coiled coil | 403-427 | |||||
Sequence: LAKSKCRDLKKRLHAAQLRAQALAD |
Domain
The leucine-zipper domain is required for its dimerization and activation.
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length443
- Mass (Da)51,243
- Last updated2011-07-27 v2
- Checksum1EF2CA320F60FB5C
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 69 | in Ref. 1; AAB67973, 2; AAC35393 and 3; AAB70470 | ||||
Sequence: S → R | ||||||
Sequence conflict | 203 | in Ref. 1; AAB67973 | ||||
Sequence: G → A | ||||||
Sequence conflict | 253 | in Ref. 1; AAB67973 | ||||
Sequence: N → F | ||||||
Sequence conflict | 274 | in Ref. 1; AAB67973, 2; AAC35393 and 3; AAB70470 | ||||
Sequence: L → M | ||||||
Sequence conflict | 311 | in Ref. 1; AAB67973 | ||||
Sequence: R → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U95610 EMBL· GenBank· DDBJ | AAB67973.1 EMBL· GenBank· DDBJ | mRNA | ||
AF013166 EMBL· GenBank· DDBJ | AAC35393.1 EMBL· GenBank· DDBJ | mRNA | ||
AF007247 EMBL· GenBank· DDBJ | AAB70470.1 EMBL· GenBank· DDBJ | mRNA | ||
AK147072 EMBL· GenBank· DDBJ | BAE27653.1 EMBL· GenBank· DDBJ | mRNA | ||
AK164467 EMBL· GenBank· DDBJ | BAE37799.1 EMBL· GenBank· DDBJ | mRNA |