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P51955

- NEK2_HUMAN

UniProt

P51955 - NEK2_HUMAN

Protein

Serine/threonine-protein kinase Nek2

Gene

NEK2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 162 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    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

    Magnesium.

    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 binding Source: UniProtKB
    4. protein kinase activity Source: UniProtKB
    5. protein phosphatase binding Source: UniProtKB
    6. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. blastocyst development Source: Ensembl
    2. centrosome separation Source: UniProtKB
    3. chromosome segregation Source: UniProtKB
    4. G2/M transition of mitotic cell cycle Source: Reactome
    5. meiotic nuclear division Source: UniProtKB-KW
    6. mitotic cell cycle Source: Reactome
    7. mitotic nuclear division Source: ProtInc
    8. mitotic sister chromatid segregation Source: Ensembl
    9. negative regulation of centriole-centriole cohesion Source: UniProtKB
    10. negative regulation of DNA binding Source: Ensembl
    11. protein autophosphorylation Source: UniProtKB
    12. protein phosphorylation Source: UniProtKB
    13. regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
    14. regulation of mitosis Source: ProtInc
    15. regulation of mitotic centrosome separation Source: UniProtKB
    16. spindle assembly Source: UniProtKB
    17. spindle assembly involved in mitosis Source: Ensembl

    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.
    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: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:7745. NEK2.

    Subcellular locationi

    Isoform 1 : Nucleus. Nucleusnucleolus. Cytoplasm. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmcytoskeletonspindle pole. Chromosomecentromerekinetochore. Chromosomecentromere By similarity
    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 : Cytoplasm
    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

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Involvement in diseasei

    Retinitis pigmentosa 67 (RP67) [MIM:615565]: A 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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    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.

    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.5 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

    ArrayExpressiP51955.
    BgeeiP51955.
    CleanExiHS_NEK2.
    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. 36 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 – 73
    Beta strandi8 – 169
    Beta strandi18 – 2710
    Turni28 – 303
    Beta strandi33 – 408
    Helixi41 – 433
    Helixi46 – 6116
    Beta strandi70 – 767
    Helixi77 – 793
    Beta strandi81 – 877
    Helixi94 – 10310
    Helixi110 – 13021
    Helixi144 – 1463
    Beta strandi147 – 1493
    Beta strandi151 – 1533
    Beta strandi155 – 1573
    Helixi162 – 1654
    Helixi171 – 1777
    Helixi185 – 1895
    Helixi195 – 21117
    Helixi221 – 23010
    Helixi242 – 25110
    Helixi256 – 2583
    Helixi262 – 2665

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    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_dom.
    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. Align

    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

    MPSRAEDYEV LYTIGTGSYG RCQKIRRKSD GKILVWKELD YGSMTEAEKQ    50
    MLVSEVNLLR ELKHPNIVRY YDRIIDRTNT TLYIVMEYCE GGDLASVITK 100
    GTKERQYLDE EFVLRVMTQL TLALKECHRR SDGGHTVLHR DLKPANVFLD 150
    GKQNVKLGDF GLARILNHDT SFAKTFVGTP YYMSPEQMNR MSYNEKSDIW 200
    SLGCLLYELC ALMPPFTAFS QKELAGKIRE GKFRRIPYRY SDELNEIITR 250
    MLNLKDYHRP SVEEILENPL IADLVADEQR RNLERRGRQL GEPEKSQDSS 300
    PVLSELKLKE IQLQERERAL KAREERLEQK EQELCVRERL AEDKLARAEN 350
    LLKNYSLLKE RKFLSLASNP ELLNLPSSVI KKKVHFSGES KENIMRSENS 400
    ESQLTSKSKC KDLKKRLHAA QLRAQALSDI EKNYQLKSRQ ILGMR 445
    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti84 – 852IV → LY in CAA80912. (PubMed:8274451)Curated
    Sequence conflicti325 – 3251E → K in BAD97073. 1 PublicationCurated

    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:
    EMBL
    GenBank
    DDBJ
    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 databases

    DMDMi1709252.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS1500.1. [P51955-1 ]
    CCDS55682.1. [P51955-2 ]
    PIRi G01452.
    I38215.
    RefSeqi NP_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 ]
    UniGenei Hs.153704.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    4A4X X-ray 2.40 A 1-271 [» ]
    4AFE X-ray 2.60 A 1-271 [» ]
    ProteinModelPortali P51955.
    SMRi P51955. Positions 3-363.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110826. 36 interactions.
    IntActi P51955. 31 interactions.
    MINTi MINT-3019433.
    STRINGi 9606.ENSP00000355966.

    Chemistry

    BindingDBi P51955.
    ChEMBLi CHEMBL3835.
    GuidetoPHARMACOLOGYi 2117.

    PTM databases

    PhosphoSitei P51955.

    Polymorphism databases

    DMDMi 1709252.

    Proteomic databases

    MaxQBi P51955.
    PaxDbi P51955.
    PRIDEi P51955.

    Protocols and materials databases

    DNASUi 4751.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000366998 ; ENSP00000355965 ; ENSG00000117650 . [P51955-2 ]
    ENST00000366999 ; ENSP00000355966 ; ENSG00000117650 . [P51955-1 ]
    GeneIDi 4751.
    KEGGi hsa:4751.
    UCSCi uc001hir.2. human. [P51955-1 ]
    uc001his.4. human. [P51955-2 ]

    Organism-specific databases

    CTDi 4751.
    GeneCardsi GC01M211836.
    HGNCi HGNC:7745. NEK2.
    HPAi CAB017530.
    HPA047522.
    MIMi 604043. gene.
    615565. phenotype.
    neXtProti NX_P51955.
    Orphaneti 791. Retinitis pigmentosa.
    PharmGKBi PA31546.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOVERGENi HBG006461.
    InParanoidi P51955.
    KOi K08857.
    OMAi SKCKDLK.
    OrthoDBi EOG715Q40.
    PhylomeDBi P51955.
    TreeFami TF101184.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 2681.
    Reactomei REACT_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.
    SignaLinki P51955.

    Miscellaneous databases

    EvolutionaryTracei P51955.
    GeneWikii NEK2.
    GenomeRNAii 4751.
    NextBioi 18310.
    PMAP-CutDB P51955.
    PROi P51955.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P51955.
    Bgeei P51955.
    CleanExi HS_NEK2.
    Genevestigatori P51955.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 162 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