NEK6_MOUSE
ID NEK6_MOUSE Reviewed; 313 AA.
AC Q9ES70; Q3TCE9; Q8C6E6; Q9D0E2; Q9DBI8;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Serine/threonine-protein kinase Nek6;
DE EC=2.7.11.1;
DE AltName: Full=Never in mitosis A-related kinase 6;
DE Short=NimA-related protein kinase 6;
GN Name=Nek6;
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], AND SUBCELLULAR LOCATION.
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=BALB/cJ, C57BL/6J, and NOD; TISSUE=Head, Liver, and Stomach;
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 TISSUE=Colon;
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 FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH
RP STAT3.
RX PubMed=20595392; DOI=10.1074/jbc.m110.137190;
RA Jeon Y.J., Lee K.Y., Cho Y.Y., Pugliese A., Kim H.G., Jeong C.H.,
RA Bode A.M., Dong Z.;
RT "Role of NEK6 in tumor promoter-induced transformation in JB6 C141 mouse
RT skin epidermal cells.";
RL J. Biol. Chem. 285:28126-28133(2010).
CC -!- FUNCTION: Protein kinase which plays an important role in mitotic cell
CC cycle progression. Required for chromosome segregation at metaphase-
CC anaphase transition, robust mitotic spindle formation and cytokinesis.
CC Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, TRIP4, RPS6KB1 and
CC histones H1 and H3. Phosphorylates KIF11 to promote mitotic spindle
CC formation. Involved in G2/M phase cell cycle arrest induced by DNA
CC damage. Inhibition of activity results in apoptosis. May contribute to
CC tumorigenesis by suppressing p53/TP53-induced cancer cell senescence
CC (By similarity). Phosphorylates STAT3 (PubMed:20595392). Phosphorylates
CC EML4 at 'Ser-144', promoting its dissociation from microtubules during
CC mitosis which is required for efficient chromosome congression (By
CC similarity). {ECO:0000250|UniProtKB:Q9HC98,
CC ECO:0000269|PubMed:20595392}.
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; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Binding to NEK9 stimulates its activity by
CC releasing the autoinhibitory function of Tyr-108. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with NEK9, predominantly in mitosis. Interacts with
CC KIF11 (via C-terminus). Interacts with APBB1 (via WW domain). Interacts
CC with ANKRA2, ATF4, ARHGAP33, CDC42, CIR1, PRAM1, PTN, PRDX3, PIN1,
CC RAD26L, RBBP6, RPS7, RPS6KB1 and TRIP4 (By similarity). Interacts with
CC STAT3. {ECO:0000250, ECO:0000269|PubMed:20595392}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus speckle
CC {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center,
CC centrosome {ECO:0000250}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000250}. Note=Co- localizes with APBB1 at the nuclear speckles.
CC Colocalizes with PIN1 in the nucleus. Colocalizes with ATF4, CIR1,
CC ARHGAP33, ANKRA2, CDC42, NEK9, RAD26L, RBBP6, RPS7, TRIP4, RELB and
CC PHF1 in the centrosome. Localizes to spindle microtubules in metaphase
CC and anaphase and to the midbody during cytokinesis (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: Displays an autoinhibited conformation: Tyr-108 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 (By similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylation at Ser-206 is required for its
CC activation. Phosphorylated upon IR or UV-induced DNA damage.
CC Phosphorylated by CHEK1 and CHEK2. Interaction with APBB1 down-
CC regulates phosphorylation at Thr-210 (By similarity). {ECO:0000250}.
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; AF218847; AAG16653.1; -; mRNA.
DR EMBL; AK004925; BAB23676.2; -; mRNA.
DR EMBL; AK011519; BAB27673.2; -; mRNA.
DR EMBL; AK075717; BAC35907.1; -; mRNA.
DR EMBL; AK075836; BAC35995.1; -; mRNA.
DR EMBL; AK086700; BAC39721.1; -; mRNA.
DR EMBL; AK089919; BAC40995.1; -; mRNA.
DR EMBL; AK170757; BAE42008.1; -; mRNA.
DR EMBL; BC019524; AAH19524.1; -; mRNA.
DR CCDS; CCDS16009.1; -.
DR RefSeq; NP_001153103.1; NM_001159631.1.
DR RefSeq; NP_067619.1; NM_021606.3.
DR RefSeq; XP_006498273.1; XM_006498210.3.
DR AlphaFoldDB; Q9ES70; -.
DR SMR; Q9ES70; -.
DR BioGRID; 208542; 5.
DR STRING; 10090.ENSMUSP00000049723; -.
DR iPTMnet; Q9ES70; -.
DR PhosphoSitePlus; Q9ES70; -.
DR EPD; Q9ES70; -.
DR MaxQB; Q9ES70; -.
DR PaxDb; Q9ES70; -.
DR PeptideAtlas; Q9ES70; -.
DR PRIDE; Q9ES70; -.
DR ProteomicsDB; 287475; -.
DR Antibodypedia; 30447; 311 antibodies from 32 providers.
DR DNASU; 59126; -.
DR Ensembl; ENSMUST00000054234; ENSMUSP00000049723; ENSMUSG00000026749.
DR Ensembl; ENSMUST00000112895; ENSMUSP00000108516; ENSMUSG00000026749.
DR GeneID; 59126; -.
DR KEGG; mmu:59126; -.
DR UCSC; uc008jnn.2; mouse.
DR CTD; 10783; -.
DR MGI; MGI:1891638; Nek6.
DR VEuPathDB; HostDB:ENSMUSG00000026749; -.
DR eggNOG; KOG0591; Eukaryota.
DR GeneTree; ENSGT00940000159990; -.
DR InParanoid; Q9ES70; -.
DR OMA; MHAWTSS; -.
DR OrthoDB; 1290401at2759; -.
DR PhylomeDB; Q9ES70; -.
DR TreeFam; TF101021; -.
DR BioGRID-ORCS; 59126; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Nek6; mouse.
DR PRO; PR:Q9ES70; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9ES70; protein.
DR Bgee; ENSMUSG00000026749; Expressed in ventricular zone and 247 other tissues.
DR ExpressionAtlas; Q9ES70; baseline and differential.
DR Genevisible; Q9ES70; MM.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0019894; F:kinesin binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
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:0001222; F:transcription corepressor binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0030071; P:regulation of mitotic metaphase/anaphase transition; 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 Apoptosis; ATP-binding; Cell cycle; Cell division; Chromosome partition;
KW Cytoplasm; Cytoskeleton; Kinase; Magnesium; Metal-binding; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..313
FT /note="Serine/threonine-protein kinase Nek6"
FT /id="PRO_0000086428"
FT DOMAIN 45..310
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..44
FT /note="Interaction with ARHGAP33, ANKRA2, CDC42, PRDX3,
FT RAD26L, RBBP6, RPS7 and TRIP4"
FT /evidence="ECO:0000250"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 267..270
FT /note="Interaction with APBB1"
FT /evidence="ECO:0000250"
FT ACT_SITE 172
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 51..59
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 108
FT /note="Autoinhibitory"
FT /evidence="ECO:0000250"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HC98"
FT MOD_RES 202
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9HC98"
FT MOD_RES 206
FT /note="Phosphoserine; by NEK9"
FT /evidence="ECO:0000250|UniProtKB:Q9HC98"
FT MOD_RES 210
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9HC98"
FT CONFLICT 210
FT /note="T -> A (in Ref. 2; BAC35995)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="Q -> R (in Ref. 2; BAB23676)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="P -> R (in Ref. 2; BAC35995)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 313 AA; 35742 MW; 14A8BC9F2C34397C CRC64;
MAGQPSHMPH GGSPNHLCHA LGPAPPPDPQ RLPNTLSFRC SLADFQIEKK IGRGQFSEVY
KATCLLDRKT VALKKVQIFE MMDAKARQDC VKEIGLLKQL NHPNIIKYLD SFIEDNELNI
VLELADAGDL SQMIKYFKKQ KRLIPERTVW KYFVQLCSAV EHMHSRRVMH RDIKPANVFI
TATGIVKLGD LGLGRFFSSE TTAAHSLVGT PYYMSPERIH ENGYNFKSDI WSLGCLLYEM
AALQSPFYGD KMNLFSLCQK IEQCDYPPLP GEHYSEKLRE LVSMCIYPDP DHRPDIVYVH
QVARQMHVWT SST
