NEK7_MOUSE
ID NEK7_MOUSE Reviewed; 302 AA.
AC Q9ES74; Q3UEV7;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Serine/threonine-protein kinase Nek7 {ECO:0000305};
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 {ECO:0000312|MGI:MGI:1890645};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10964517; DOI=10.1006/geno.2000.6293;
RA Kandli M., Feige E., Chen A., Kilfin G., Motro B.;
RT "Isolation and characterization of two evolutionarily conserved murine
RT kinases (Nek6 and Nek7) related to the fungal mitotic regulator, NIMA.";
RL Genomics 68:187-196(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Retina, Thymus, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
RX PubMed=20473324; DOI=10.1038/onc.2010.162;
RA Salem H., Rachmin I., Yissachar N., Cohen S., Amiel A., Haffner R.,
RA Lavi L., Motro B.;
RT "Nek7 kinase targeting leads to early mortality, cytokinesis disturbance
RT and polyploidy.";
RL Oncogene 29:4046-4057(2010).
RN [6]
RP INTERACTION WITH ANKS3, AND SUBCELLULAR LOCATION.
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 [7]
RP FUNCTION, INTERACTION WITH NLRP3, AND MUTAGENESIS OF 63-LYS-LYS-64; LYS-63
RP AND LYS-64.
RX PubMed=26814970; DOI=10.1038/nature16959;
RA He Y., Zeng M.Y., Yang D., Motro B., Nunez G.;
RT "NEK7 is an essential mediator of NLRP3 activation downstream of potassium
RT efflux.";
RL Nature 530:354-357(2016).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH NLRP3.
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).
CC -!- FUNCTION: Protein kinase which plays an important role in mitotic cell
CC cycle progression. Required for microtubule nucleation activity of the
CC centrosome, robust mitotic spindle formation and cytokinesis
CC (PubMed:20473324). Phosphorylates RPS6KB1 (By similarity).
CC Phosphorylates EML4 at 'Ser-146', promoting its dissociation from
CC microtubules during mitosis which is required for efficient chromosome
CC congression (By similarity). Essential protein for NLRP3 inflammasome
CC assembly and activation that acts downstream stimuli such as K(+)
CC efflux. Dispensable for the induction of core inflammasome components,
CC but necessary for subsequent formation of the NLRP3:PYCARD complex, and
CC activation of CASP1. Serves as a cellular switch that enforces mutual
CC exclusivity of the inflammasome response and cell division. Exerts its
CC effects on the NLRP3 inflammasome independently of its kinase activity
CC (PubMed:26814970, PubMed:26642356). {ECO:0000250|UniProtKB:D3ZBE5,
CC ECO:0000250|UniProtKB:Q8TDX7, ECO:0000269|PubMed:20473324,
CC ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:26814970}.
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:0000250|UniProtKB:Q8TDX7}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with NEK9 (By similarity).
CC Interacts with ANKS3; this interaction alters the subcellular
CC distribution of NEK7 by preventing its nuclear translocation
CC (PubMed:26188091). Interacts (via N-terminus) with NLRP3 (via LRR
CC repeat domain); the interaction is required for the formation of the
CC complex NLRP3:PYCARD, oligomerization of PYCARD and activation of CASP1
CC (PubMed:26814970, PubMed:26642356). {ECO:0000250|UniProtKB:Q8TDX7,
CC ECO:0000269|PubMed:26188091, ECO:0000269|PubMed:26642356,
CC ECO:0000269|PubMed:26814970}.
CC -!- INTERACTION:
CC Q9ES74; Q8R4B8: Nlrp3; NbExp=2; IntAct=EBI-16193749, EBI-6910832;
CC Q9ES74; Q96P20: NLRP3; Xeno; NbExp=2; IntAct=EBI-16193749, EBI-6253230;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26188091}. Cytoplasm
CC {ECO:0000269|PubMed:26188091}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000250|UniProtKB:Q8TDX7}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q8TDX7}.
CC Note=Present at centrosome throughout the cell cycle (By similarity).
CC Also detected at spindle midzone of the anaphase cells and eventually
CC concentrates at the midbody (By similarity). Interaction with ANKS3
CC prevents its translocation to the nucleus (PubMed:26188091).
CC {ECO:0000250|UniProtKB:Q8TDX7, ECO:0000269|PubMed:26188091}.
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:0000250|UniProtKB:Q8TDX7}.
CC -!- DOMAIN: The NTE (N-terminal extension) motif is a structural component
CC of the catalytic domain and thus contributes to activity.
CC {ECO:0000250|UniProtKB:Q8TDX7}.
CC -!- PTM: Phosphorylation at Ser-195 required for its activation.
CC {ECO:0000250|UniProtKB:Q8TDX7}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are viable but are born at sub-
CC Mendelian ratios. They further suffer from severe growth retardation,
CC infertility, abnormal gait and slight paralysis of the limbs. In an
CC experimental autoimmune encephalitis (EAE) model, mutant mice exhibited
CC reduced disease severity relative to wild-type mice, as well as reduced
CC recruitment of lymphocytes, monocytes/microglia, and NK cells to the
CC spinal cord. {ECO:0000269|PubMed:26642356}.
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; AF217650; AAG16652.1; -; mRNA.
DR EMBL; BC037697; AAH37697.1; -; mRNA.
DR EMBL; AK035502; BAC29080.1; -; mRNA.
DR EMBL; AK088173; BAC40190.1; -; mRNA.
DR EMBL; AK149308; BAE28804.1; -; mRNA.
DR CCDS; CCDS15332.1; -.
DR RefSeq; NP_001298077.1; NM_001311148.1.
DR RefSeq; NP_067618.1; NM_021605.4.
DR AlphaFoldDB; Q9ES74; -.
DR SMR; Q9ES74; -.
DR BioGRID; 208541; 3.
DR DIP; DIP-61936N; -.
DR IntAct; Q9ES74; 4.
DR MINT; Q9ES74; -.
DR STRING; 10090.ENSMUSP00000027642; -.
DR iPTMnet; Q9ES74; -.
DR PhosphoSitePlus; Q9ES74; -.
DR EPD; Q9ES74; -.
DR MaxQB; Q9ES74; -.
DR PaxDb; Q9ES74; -.
DR PeptideAtlas; Q9ES74; -.
DR PRIDE; Q9ES74; -.
DR ProteomicsDB; 287367; -.
DR Antibodypedia; 20630; 372 antibodies from 37 providers.
DR DNASU; 59125; -.
DR Ensembl; ENSMUST00000186017; ENSMUSP00000140903; ENSMUSG00000026393.
DR Ensembl; ENSMUST00000187407; ENSMUSP00000140635; ENSMUSG00000026393.
DR GeneID; 59125; -.
DR KEGG; mmu:59125; -.
DR UCSC; uc007cvn.1; mouse.
DR CTD; 140609; -.
DR MGI; MGI:1890645; Nek7.
DR VEuPathDB; HostDB:ENSMUSG00000026393; -.
DR eggNOG; KOG0591; Eukaryota.
DR GeneTree; ENSGT00940000156725; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q9ES74; -.
DR OMA; MHAHTAT; -.
DR OrthoDB; 1290401at2759; -.
DR PhylomeDB; Q9ES74; -.
DR TreeFam; TF105135; -.
DR BioGRID-ORCS; 59125; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Nek7; mouse.
DR PRO; PR:Q9ES74; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9ES74; protein.
DR Bgee; ENSMUSG00000026393; Expressed in extensor digitorum longus and 283 other tissues.
DR ExpressionAtlas; Q9ES74; baseline and differential.
DR Genevisible; Q9ES74; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IDA:UniProtKB.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:1904355; P:positive regulation of telomere capping; ISO:MGI.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS: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 Acetylation; ATP-binding; Cytoplasm; Cytoskeleton; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..302
FT /note="Serine/threonine-protein kinase Nek7"
FT /id="PRO_0000086431"
FT DOMAIN 34..299
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 20..33
FT /note="NTE motif"
FT /evidence="ECO:0000250"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 63
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 97
FT /note="Autoinhibitory"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDX7"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDX7"
FT MOD_RES 195
FT /note="Phosphoserine; by NEK9"
FT /evidence="ECO:0000250|UniProtKB:Q8TDX7"
FT MUTAGEN 63..64
FT /note="KK->MM: No effect on interaction with NLRP3."
FT /evidence="ECO:0000269|PubMed:26814970"
FT MUTAGEN 63
FT /note="K->M: No effect on interaction with NLRP3."
FT /evidence="ECO:0000269|PubMed:26814970"
FT MUTAGEN 64
FT /note="K->M: No effect on interaction with NLRP3."
FT /evidence="ECO:0000269|PubMed:26814970"
SQ SEQUENCE 302 AA; 34537 MW; C5474CD0E63478EC CRC64;
MDEQSQGMQG PPVTQFQPQK ALRPDMGYNT LANFRIEKKI GRGQFSEVYR ASCLLDGVPV
ALKKVQIFDL MDAKARADCI KEIDLLKQLN HPNVIKYYAS FIEDNELNIV LELADAGDLS
RMIKHFKKQK RLIPERTVWK YFVQLCSALD HMHSRRVMHR DIKPANVFIT ATGVVKLGDL
GLGRFFSSKT TAAHSLVGTP YYMSPERIHE NGYNFKSDIW SLGCLLYEMA ALQSPFYGDK
MNLYSLCKKI EQCDYPPLPS DHYSEELRQL VNICINPDPE KRPDIAYVYD VAKRMHACTA
ST
