NEK7_HUMAN
ID NEK7_HUMAN Reviewed; 302 AA.
AC Q8TDX7; A6NGT8;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Serine/threonine-protein kinase Nek7;
DE EC=2.7.11.1;
DE AltName: Full=Never in mitosis A-related kinase 7;
DE Short=NimA-related protein kinase 7;
GN Name=NEK7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=11701951; DOI=10.1159/000048779;
RA Kimura M., Okano Y.;
RT "Identification and assignment of the human NIMA-related protein kinase 7
RT gene (NEK7) to human chromosome 1q31.3.";
RL Cytogenet. Cell Genet. 94:33-38(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Pancreatic islet;
RA Melton D., Meadows A., Clifton S., Hillier L., Marra M., Pape D., Wylie T.,
RA Martin J., Blistain A., Schmitt A., Theising B., Ritter E., Ronko I.,
RA Bennett J., Cardenas M., Gibbons M., McCann R., Cole R., Tsagareishvili R.,
RA Williams T., Jackson Y., Bowers Y.;
RT "WashU-Harvard pancreas EST project.";
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION AT SER-195.
RX PubMed=12840024; DOI=10.1074/jbc.m303663200;
RA Belham C., Roig J., Caldwell J.A., Aoyama Y., Kemp B.E., Comb M.,
RA Avruch J.;
RT "A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6
RT and Nek7 kinases.";
RL J. Biol. Chem. 278:34897-34909(2003).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17101132; DOI=10.1016/j.febslet.2006.10.069;
RA Yissachar N., Salem H., Tennenbaum T., Motro B.;
RT "Nek7 kinase is enriched at the centrosome, and is required for proper
RT spindle assembly and mitotic progression.";
RL FEBS Lett. 580:6489-6495(2006).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17586473; DOI=10.1016/j.bbrc.2007.05.206;
RA Kim S., Lee K., Rhee K.;
RT "NEK7 is a centrosomal kinase critical for microtubule nucleation.";
RL Biochem. Biophys. Res. Commun. 360:56-62(2007).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NEK9.
RX PubMed=19414596; DOI=10.1128/mcb.01867-08;
RA O'Regan L., Fry A.M.;
RT "The Nek6 and Nek7 protein kinases are required for robust mitotic spindle
RT formation and cytokinesis.";
RL Mol. Cell. Biol. 29:3975-3990(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP SUBUNIT.
RX PubMed=21320329; DOI=10.1186/1472-6807-11-12;
RA Meirelles G.V., Silva J.C., Mendonca Yde A., Ramos C.H., Torriani I.L.,
RA Kobarg J.;
RT "Human Nek6 is a monomeric mostly globular kinase with an unfolded short N-
RT terminal domain.";
RL BMC Struct. Biol. 11:12-12(2011).
RN [12]
RP REVIEW.
RX PubMed=17727698; DOI=10.1186/1747-1028-2-25;
RA O'regan L., Blot J., Fry A.M.;
RT "Mitotic regulation by NIMA-related kinases.";
RL Cell Div. 2:25-25(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP INTERACTION WITH ANKS3.
RX PubMed=26188091; DOI=10.1016/j.bbrc.2015.07.063;
RA Ramachandran H., Engel C., Mueller B., Dengjel J., Walz G., Yakulov T.A.;
RT "Anks3 alters the sub-cellular localization of the Nek7 kinase.";
RL Biochem. Biophys. Res. Commun. 464:901-907(2015).
RN [16]
RP FUNCTION.
RX PubMed=26642356; DOI=10.1038/ni.3333;
RA Shi H., Wang Y., Li X., Zhan X., Tang M., Fina M., Su L., Pratt D.,
RA Bu C.H., Hildebrand S., Lyon S., Scott L., Quan J., Sun Q., Russell J.,
RA Arnett S., Jurek P., Chen D., Kravchenko V.V., Mathison J.C., Moresco E.M.,
RA Monson N.L., Ulevitch R.J., Beutler B.;
RT "NLRP3 activation and mitosis are mutually exclusive events coordinated by
RT NEK7, a new inflammasome component.";
RL Nat. Immunol. 17:250-258(2016).
RN [17]
RP FUNCTION.
RX PubMed=31409757; DOI=10.1126/scisignal.aaw2939;
RA Adib R., Montgomery J.M., Atherton J., O'Regan L., Richards M.W.,
RA Straatman K.R., Roth D., Straube A., Bayliss R., Moores C.A., Fry A.M.;
RT "Mitotic phosphorylation by NEK6 and NEK7 reduces the microtubule affinity
RT of EML4 to promote chromosome congression.";
RL Sci. Signal. 12:0-0(2019).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), DOMAIN, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF TYR-28; LEU-31; ASN-33 AND TYR-97.
RX PubMed=19941817; DOI=10.1016/j.molcel.2009.09.038;
RA Richards M.W., O'Regan L., Mas-Droux C., Blot J.M., Cheung J., Hoelder S.,
RA Fry A.M., Bayliss R.;
RT "An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase
RT is released through binding of Nek9.";
RL Mol. Cell 36:560-570(2009).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] GLY-35 AND MET-275.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Protein kinase which plays an important role in mitotic cell
CC cycle progression (PubMed:17101132). Required for microtubule
CC nucleation activity of the centrosome, robust mitotic spindle formation
CC and cytokinesis (PubMed:17586473, PubMed:19414596). Phosphorylates
CC RPS6KB1 (By similarity). Phosphorylates EML4 at 'Ser-146', promoting
CC its dissociation from microtubules during mitosis which is required for
CC efficient chromosome congression (PubMed:31409757). Essential protein
CC for NLRP3 inflammasome assembly and activation that acts downstream
CC stimuli such as K(+) efflux. Dispensable for the induction of core
CC inflammasome components, but necessary for subsequent formation of the
CC NLRP3:PYCARD complex, and activation of CASP1. Serves as a cellular
CC switch that enforces mutual exclusivity of the inflammasome response
CC and cell division. Exerts its effects on the NLRP3 inflammasome
CC independently of its kinase activity (PubMed:26642356).
CC {ECO:0000250|UniProtKB:D3ZBE5, ECO:0000269|PubMed:17101132,
CC ECO:0000269|PubMed:17586473, ECO:0000269|PubMed:19414596,
CC ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:31409757}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Binding to NEK9 stimulates its activity by
CC releasing the autoinhibitory function of Tyr-97.
CC {ECO:0000269|PubMed:19941817}.
CC -!- SUBUNIT: Monomer (PubMed:21320329). Interacts with NEK9
CC (PubMed:19414596). Interacts with ANKS3; this interaction alters the
CC subcellular distribution of NEK7 by preventing its nuclear
CC translocation (PubMed:26188091). Interacts (via N-terminus) with NLRP3
CC (via LRR repeat domain); the interaction is required for the formation
CC of the complex NLRP3:PYCARD, oligomerization of PYCARD and activation
CC of CASP1 (By similarity). {ECO:0000250|UniProtKB:Q9ES74,
CC ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:21320329,
CC ECO:0000269|PubMed:26188091}.
CC -!- INTERACTION:
CC Q8TDX7; Q8N1W1-4: ARHGEF28; NbExp=3; IntAct=EBI-1055945, EBI-13062134;
CC Q8TDX7; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-1055945, EBI-747505;
CC Q8TDX7; O94983-5: CAMTA2; NbExp=3; IntAct=EBI-1055945, EBI-10176008;
CC Q8TDX7; O75175: CNOT3; NbExp=3; IntAct=EBI-1055945, EBI-743073;
CC Q8TDX7; Q6UXH1-2: CRELD2; NbExp=3; IntAct=EBI-1055945, EBI-21670927;
CC Q8TDX7; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-1055945, EBI-742054;
CC Q8TDX7; P49184: DNASE1L1; NbExp=3; IntAct=EBI-1055945, EBI-20894690;
CC Q8TDX7; Q8IY82: DRC7; NbExp=3; IntAct=EBI-1055945, EBI-10262896;
CC Q8TDX7; Q99944: EGFL8; NbExp=3; IntAct=EBI-1055945, EBI-3924130;
CC Q8TDX7; P16422: EPCAM; NbExp=3; IntAct=EBI-1055945, EBI-1171184;
CC Q8TDX7; Q9NVM1: EVA1B; NbExp=3; IntAct=EBI-1055945, EBI-10314666;
CC Q8TDX7; Q96GK7: FAHD2A; NbExp=3; IntAct=EBI-1055945, EBI-21647872;
CC Q8TDX7; Q10981: FUT2; NbExp=3; IntAct=EBI-1055945, EBI-9090702;
CC Q8TDX7; P36382: GJA5; NbExp=3; IntAct=EBI-1055945, EBI-750433;
CC Q8TDX7; P09471: GNAO1; NbExp=3; IntAct=EBI-1055945, EBI-715087;
CC Q8TDX7; P79483: HLA-DRB3; NbExp=3; IntAct=EBI-1055945, EBI-3910269;
CC Q8TDX7; P14060: HSD3B1; NbExp=3; IntAct=EBI-1055945, EBI-17426018;
CC Q8TDX7; Q7Z6Z7-2: HUWE1; NbExp=3; IntAct=EBI-1055945, EBI-10975491;
CC Q8TDX7; O75874: IDH1; NbExp=3; IntAct=EBI-1055945, EBI-715695;
CC Q8TDX7; Q9ULR0: ISY1; NbExp=3; IntAct=EBI-1055945, EBI-2557660;
CC Q8TDX7; A0JP07: KIAA1683; NbExp=3; IntAct=EBI-1055945, EBI-10171456;
CC Q8TDX7; P26715: KLRC1; NbExp=3; IntAct=EBI-1055945, EBI-9018187;
CC Q8TDX7; Q6P5S2: LEG1; NbExp=3; IntAct=EBI-1055945, EBI-11750531;
CC Q8TDX7; P09382: LGALS1; NbExp=3; IntAct=EBI-1055945, EBI-1048875;
CC Q8TDX7; O00214-2: LGALS8; NbExp=3; IntAct=EBI-1055945, EBI-12069522;
CC Q8TDX7; P43356: MAGEA2B; NbExp=3; IntAct=EBI-1055945, EBI-5650739;
CC Q8TDX7; Q7Z434: MAVS; NbExp=3; IntAct=EBI-1055945, EBI-995373;
CC Q8TDX7; Q8NCR3: MFI; NbExp=3; IntAct=EBI-1055945, EBI-744790;
CC Q8TDX7; Q8TB02: MGC39372; NbExp=3; IntAct=EBI-1055945, EBI-25834188;
CC Q8TDX7; Q96EY8: MMAB; NbExp=3; IntAct=EBI-1055945, EBI-7825413;
CC Q8TDX7; A2RUH7: MYBPHL; NbExp=3; IntAct=EBI-1055945, EBI-9088235;
CC Q8TDX7; Q9NPC7: MYNN; NbExp=3; IntAct=EBI-1055945, EBI-3446748;
CC Q8TDX7; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-1055945, EBI-11750983;
CC Q8TDX7; Q8NCF5-2: NFATC2IP; NbExp=3; IntAct=EBI-1055945, EBI-12305293;
CC Q8TDX7; Q96P20: NLRP3; NbExp=4; IntAct=EBI-1055945, EBI-6253230;
CC Q8TDX7; Q8N323: NXPE1; NbExp=3; IntAct=EBI-1055945, EBI-25834085;
CC Q8TDX7; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-1055945, EBI-9091052;
CC Q8TDX7; P00558: PGK1; NbExp=2; IntAct=EBI-1055945, EBI-709599;
CC Q8TDX7; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-1055945, EBI-473160;
CC Q8TDX7; Q8NBT0: POC1A; NbExp=3; IntAct=EBI-1055945, EBI-2557132;
CC Q8TDX7; O14829: PPEF1; NbExp=3; IntAct=EBI-1055945, EBI-2931238;
CC Q8TDX7; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-1055945, EBI-2860740;
CC Q8TDX7; Q9Y617: PSAT1; NbExp=3; IntAct=EBI-1055945, EBI-709652;
CC Q8TDX7; P43686: PSMC4; NbExp=3; IntAct=EBI-1055945, EBI-743997;
CC Q8TDX7; Q13200: PSMD2; NbExp=3; IntAct=EBI-1055945, EBI-357648;
CC Q8TDX7; Q9Y3Y4: PYGO1; NbExp=3; IntAct=EBI-1055945, EBI-3397474;
CC Q8TDX7; Q13636: RAB31; NbExp=3; IntAct=EBI-1055945, EBI-725987;
CC Q8TDX7; Q96E17: RAB3C; NbExp=3; IntAct=EBI-1055945, EBI-4287022;
CC Q8TDX7; P61224: RAP1B; NbExp=3; IntAct=EBI-1055945, EBI-358143;
CC Q8TDX7; P50749: RASSF2; NbExp=3; IntAct=EBI-1055945, EBI-960081;
CC Q8TDX7; Q96I25: RBM17; NbExp=3; IntAct=EBI-1055945, EBI-740272;
CC Q8TDX7; P52756: RBM5; NbExp=3; IntAct=EBI-1055945, EBI-714003;
CC Q8TDX7; Q02978: SLC25A11; NbExp=3; IntAct=EBI-1055945, EBI-359174;
CC Q8TDX7; Q3SY56: SP6; NbExp=3; IntAct=EBI-1055945, EBI-11175533;
CC Q8TDX7; Q96L03: SPATA17; NbExp=3; IntAct=EBI-1055945, EBI-13322423;
CC Q8TDX7; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-1055945, EBI-7082156;
CC Q8TDX7; F6Y2X3: TAZ; NbExp=3; IntAct=EBI-1055945, EBI-25833693;
CC Q8TDX7; Q13428-5: TCOF1; NbExp=3; IntAct=EBI-1055945, EBI-25832010;
CC Q8TDX7; P48775: TDO2; NbExp=3; IntAct=EBI-1055945, EBI-743494;
CC Q8TDX7; Q9BQ29: THAP4; NbExp=3; IntAct=EBI-1055945, EBI-22013570;
CC Q8TDX7; Q9BT49: THAP7; NbExp=3; IntAct=EBI-1055945, EBI-741350;
CC Q8TDX7; P49746: THBS3; NbExp=3; IntAct=EBI-1055945, EBI-2530931;
CC Q8TDX7; P42166: TMPO; NbExp=2; IntAct=EBI-1055945, EBI-395393;
CC Q8TDX7; Q96JJ7-2: TMX3; NbExp=3; IntAct=EBI-1055945, EBI-25833898;
CC Q8TDX7; Q9H2S6-2: TNMD; NbExp=3; IntAct=EBI-1055945, EBI-12003398;
CC Q8TDX7; Q68CL5-3: TPGS2; NbExp=3; IntAct=EBI-1055945, EBI-9091010;
CC Q8TDX7; Q9ULW0: TPX2; NbExp=3; IntAct=EBI-1055945, EBI-1037322;
CC Q8TDX7; Q9NX07: TRNAU1AP; NbExp=3; IntAct=EBI-1055945, EBI-12581310;
CC Q8TDX7; P07437: TUBB; NbExp=3; IntAct=EBI-1055945, EBI-350864;
CC Q8TDX7; Q7Z780: U2AF1; NbExp=3; IntAct=EBI-1055945, EBI-25833730;
CC Q8TDX7; O75317: USP12; NbExp=3; IntAct=EBI-1055945, EBI-2511507;
CC Q8TDX7; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-1055945, EBI-25830993;
CC Q8TDX7-1; Q96P20-1: NLRP3; NbExp=6; IntAct=EBI-16193799, EBI-14029575;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9ES74}. Cytoplasm
CC {ECO:0000269|PubMed:17586473}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000269|PubMed:19414596}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:17101132,
CC ECO:0000269|PubMed:17586473}. Note=Present at centrosome throughout the
CC cell cycle (PubMed:17586473). Also detected at spindle midzone of the
CC anaphase cells and eventually concentrates at the midbody
CC (PubMed:17586473). Interaction with ANKS3 prevents its translocation to
CC the nucleus (By similarity). {ECO:0000250|UniProtKB:Q9ES74,
CC ECO:0000269|PubMed:17586473}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TDX7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TDX7-2; Sequence=VSP_041243, VSP_041244;
CC -!- TISSUE SPECIFICITY: Highly expressed in lung, muscle, testis, brain,
CC heart, liver, leukocyte and spleen. Lower expression in ovary, prostate
CC and kidney. No expression seen in small intestine.
CC {ECO:0000269|PubMed:11701951}.
CC -!- DOMAIN: Displays an autoinhibited conformation: Tyr-97 side chain
CC points into the active site, interacts with the activation loop, and
CC blocks the alphaC helix. The autoinhibitory conformation is released
CC upon binding with NEK9. {ECO:0000269|PubMed:19941817}.
CC -!- DOMAIN: The NTE (N-terminal extension) motif is a structural component
CC of the catalytic domain and thus contributes to activity.
CC {ECO:0000269|PubMed:19941817}.
CC -!- PTM: Phosphorylation at Ser-195 required for its activation.
CC {ECO:0000269|PubMed:12840024}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. NEK Ser/Thr
CC protein kinase family. NIMA subfamily. {ECO:0000305}.
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DR EMBL; AB062450; BAB85632.1; -; mRNA.
DR EMBL; CK819069; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC093419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093561; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91294.1; -; Genomic_DNA.
DR CCDS; CCDS1394.1; -. [Q8TDX7-1]
DR RefSeq; NP_598001.1; NM_133494.2. [Q8TDX7-1]
DR PDB; 2WQM; X-ray; 2.10 A; A=1-302.
DR PDB; 2WQN; X-ray; 2.30 A; A=1-302.
DR PDB; 5DE2; X-ray; 2.78 A; A/B=1-302.
DR PDB; 6NPY; EM; 3.80 A; B=1-302.
DR PDB; 6S73; X-ray; 3.50 A; A/B/C/D=1-302.
DR PDB; 6S75; X-ray; 3.30 A; A/B/C/D=1-302.
DR PDB; 6S76; X-ray; 3.38 A; A/B/C/D=1-302.
DR PDBsum; 2WQM; -.
DR PDBsum; 2WQN; -.
DR PDBsum; 5DE2; -.
DR PDBsum; 6NPY; -.
DR PDBsum; 6S73; -.
DR PDBsum; 6S75; -.
DR PDBsum; 6S76; -.
DR AlphaFoldDB; Q8TDX7; -.
DR SMR; Q8TDX7; -.
DR BioGRID; 126636; 59.
DR DIP; DIP-50780N; -.
DR IntAct; Q8TDX7; 187.
DR MINT; Q8TDX7; -.
DR STRING; 9606.ENSP00000356355; -.
DR BindingDB; Q8TDX7; -.
DR ChEMBL; CHEMBL4849; -.
DR DrugCentral; Q8TDX7; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyGen; Q8TDX7; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q8TDX7; -.
DR MetOSite; Q8TDX7; -.
DR PhosphoSitePlus; Q8TDX7; -.
DR BioMuta; NEK7; -.
DR DMDM; 37537965; -.
DR CPTAC; CPTAC-1621; -.
DR EPD; Q8TDX7; -.
DR jPOST; Q8TDX7; -.
DR MassIVE; Q8TDX7; -.
DR MaxQB; Q8TDX7; -.
DR PaxDb; Q8TDX7; -.
DR PeptideAtlas; Q8TDX7; -.
DR PRIDE; Q8TDX7; -.
DR ProteomicsDB; 74364; -. [Q8TDX7-1]
DR ProteomicsDB; 74365; -. [Q8TDX7-2]
DR Antibodypedia; 20630; 372 antibodies from 37 providers.
DR DNASU; 140609; -.
DR Ensembl; ENST00000367383.5; ENSP00000356353.1; ENSG00000151414.15. [Q8TDX7-2]
DR Ensembl; ENST00000367385.9; ENSP00000356355.4; ENSG00000151414.15. [Q8TDX7-1]
DR Ensembl; ENST00000538004.5; ENSP00000444621.1; ENSG00000151414.15. [Q8TDX7-1]
DR GeneID; 140609; -.
DR KEGG; hsa:140609; -.
DR MANE-Select; ENST00000367385.9; ENSP00000356355.4; NM_133494.3; NP_598001.1.
DR UCSC; uc001gun.5; human. [Q8TDX7-1]
DR CTD; 140609; -.
DR DisGeNET; 140609; -.
DR GeneCards; NEK7; -.
DR HGNC; HGNC:13386; NEK7.
DR HPA; ENSG00000151414; Tissue enhanced (heart).
DR MIM; 606848; gene.
DR neXtProt; NX_Q8TDX7; -.
DR OpenTargets; ENSG00000151414; -.
DR PharmGKB; PA31551; -.
DR VEuPathDB; HostDB:ENSG00000151414; -.
DR eggNOG; KOG0591; Eukaryota.
DR GeneTree; ENSGT00940000156725; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q8TDX7; -.
DR OMA; MHSANIQ; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q8TDX7; -.
DR TreeFam; TF105135; -.
DR PathwayCommons; Q8TDX7; -.
DR Reactome; R-HSA-2980767; Activation of NIMA Kinases NEK9, NEK6, NEK7.
DR Reactome; R-HSA-3301854; Nuclear Pore Complex (NPC) Disassembly.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; Q8TDX7; -.
DR SIGNOR; Q8TDX7; -.
DR BioGRID-ORCS; 140609; 17 hits in 1116 CRISPR screens.
DR ChiTaRS; NEK7; human.
DR EvolutionaryTrace; Q8TDX7; -.
DR GenomeRNAi; 140609; -.
DR Pharos; Q8TDX7; Tchem.
DR PRO; PR:Q8TDX7; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8TDX7; protein.
DR Bgee; ENSG00000151414; Expressed in heart right ventricle and 206 other tissues.
DR ExpressionAtlas; Q8TDX7; baseline and differential.
DR Genevisible; Q8TDX7; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0035865; P:cellular response to potassium ion; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:BHF-UCL.
DR GO; GO:1904355; P:positive regulation of telomere capping; IMP:BHF-UCL.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; TAS:UniProtKB.
DR GO; GO:0051225; P:spindle assembly; TAS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Cytoskeleton; Kinase; Magnesium; Metal-binding; Microtubule;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..302
FT /note="Serine/threonine-protein kinase Nek7"
FT /id="PRO_0000086430"
FT DOMAIN 34..299
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 20..33
FT /note="NTE motif"
FT ACT_SITE 161
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 40..48
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT SITE 97
FT /note="Autoinhibitory"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 195
FT /note="Phosphoserine; by NEK9"
FT /evidence="ECO:0000269|PubMed:12840024"
FT VAR_SEQ 67..119
FT /note="IFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELADAGD
FT L -> VCLLPVWERRVCALNACYFLEIIKGSESLQYMATLTNLFENLPVSHHGSFAKK
FT (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_041243"
FT VAR_SEQ 120..302
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_041244"
FT VARIANT 35
FT /note="R -> G (in dbSNP:rs55833332)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040924"
FT VARIANT 275
FT /note="I -> M (in an ovarian serous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040925"
FT MUTAGEN 28
FT /note="Y->A: Significant decrease in catalytic activity;
FT when associated with A-31."
FT /evidence="ECO:0000269|PubMed:19941817"
FT MUTAGEN 31
FT /note="L->A: Significant decrease in catalytic activity;
FT when associated with A-28."
FT /evidence="ECO:0000269|PubMed:19941817"
FT MUTAGEN 33
FT /note="N->D: Significant decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:19941817"
FT MUTAGEN 97
FT /note="Y->A: 5-fold increase in catalytic activity."
FT /evidence="ECO:0000269|PubMed:19941817"
FT MUTAGEN 97
FT /note="Y->F,L: Moderate increase in catalytic activity."
FT /evidence="ECO:0000269|PubMed:19941817"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:2WQM"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:2WQM"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:2WQM"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:6S76"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:2WQM"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:2WQM"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:2WQM"
FT TURN 67..70
FT /evidence="ECO:0007829|PDB:2WQN"
FT HELIX 73..87
FT /evidence="ECO:0007829|PDB:2WQM"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:2WQM"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:2WQM"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:6S75"
FT HELIX 119..128
FT /evidence="ECO:0007829|PDB:2WQM"
FT HELIX 135..154
FT /evidence="ECO:0007829|PDB:2WQM"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:2WQM"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:2WQM"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:6S75"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:2WQM"
FT HELIX 205..208
FT /evidence="ECO:0007829|PDB:2WQM"
FT TURN 209..211
FT /evidence="ECO:0007829|PDB:6S73"
FT HELIX 215..231
FT /evidence="ECO:0007829|PDB:2WQM"
FT HELIX 243..251
FT /evidence="ECO:0007829|PDB:2WQM"
FT TURN 260..262
FT /evidence="ECO:0007829|PDB:2WQM"
FT HELIX 265..274
FT /evidence="ECO:0007829|PDB:2WQM"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:2WQM"
FT HELIX 285..299
FT /evidence="ECO:0007829|PDB:2WQM"
SQ SEQUENCE 302 AA; 34551 MW; C1FC990B34D94D4C CRC64;
MDEQSQGMQG PPVPQFQPQK ALRPDMGYNT LANFRIEKKI GRGQFSEVYR AACLLDGVPV
ALKKVQIFDL MDAKARADCI KEIDLLKQLN HPNVIKYYAS FIEDNELNIV LELADAGDLS
RMIKHFKKQK RLIPERTVWK YFVQLCSALE HMHSRRVMHR DIKPANVFIT ATGVVKLGDL
GLGRFFSSKT TAAHSLVGTP YYMSPERIHE NGYNFKSDIW SLGCLLYEMA ALQSPFYGDK
MNLYSLCKKI EQCDYPPLPS DHYSEELRQL VNMCINPDPE KRPDVTYVYD VAKRMHACTA
SS
