ID   NEK7_RAT                Reviewed;         302 AA.
AC   D3ZBE5;
DT   21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
DT   20-APR-2010, sequence version 1.
DT   27-MAR-2024, entry version 86.
DE   RecName: Full=Serine/threonine-protein kinase Nek7 {ECO:0000305|PubMed:11516946};
DE            EC=2.7.11.34 {ECO:0000269|PubMed:11516946};
DE   AltName: Full=Never in mitosis A-related kinase 7 {ECO:0000303|PubMed:11516946};
DE            Short=NimA-related protein kinase 7 {ECO:0000303|PubMed:11516946};
GN   Name=Nek7 {ECO:0000303|PubMed:11516946};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=11516946; DOI=10.1016/s0960-9822(01)00369-4;
RA   Belham C., Comb M.J., Avruch J.;
RT   "Identification of the NIMA family kinases NEK6/7 as regulators of the p70
RT   ribosomal S6 kinase.";
RL   Curr. Biol. 11:1155-1167(2001).
CC   -!- FUNCTION: Protein kinase which plays an important role in mitotic cell
CC       cycle progression (PubMed:11516946). Required for microtubule
CC       nucleation activity of the centrosome, robust mitotic spindle formation
CC       and cytokinesis (By similarity). Phosphorylates EML4 at 'Ser-146',
CC       promoting its dissociation from microtubules during mitosis which is
CC       required for efficient chromosome congression (By similarity).
CC       Phosphorylates RPS6KB1 (PubMed:11516946). Acts as an essential
CC       activator of the NLRP3 inflammasome assembly independently of its
CC       kinase activity (By similarity). Acts by unlocking NLRP3 following
CC       NLRP3 tranlocation into the microtubule organizing center (MTOC),
CC       relieving NLRP3 autoinhibition and promoting formation of the
CC       NLRP3:PYCARD complex, and activation of CASP1 (By similarity). Serves
CC       as a cellular switch that enforces mutual exclusivity of the
CC       inflammasome response and cell division: interaction with NEK9 prevents
CC       interaction with NLRP3 and activation of the inflammasome during
CC       mitosis (By similarity). {ECO:0000250|UniProtKB:Q8TDX7,
CC       ECO:0000269|PubMed:11516946}.
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=2.7.11.34;
CC         Evidence={ECO:0000269|PubMed:11516946};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC         Evidence={ECO:0000250|UniProtKB:Q8TDX7};
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=2.7.11.34; Evidence={ECO:0000269|PubMed:11516946};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC         Evidence={ECO:0000250|UniProtKB:Q8TDX7};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:Q8TD19};
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; interaction
CC       takes place during mitosis; it relieves NEK7 autoinhibition and
CC       prevents interaction with NLRP3 (By similarity). Interacts with ANKS3;
CC       this interaction alters the subcellular distribution of NEK7 by
CC       preventing its nuclear translocation (By similarity). Interacts (via N-
CC       terminus) with NLRP3 (via LRR repeat domain); the interaction is
CC       required for the formation of the complex NLRP3:PYCARD, oligomerization
CC       of PYCARD and activation of CASP1 (By similarity).
CC       {ECO:0000250|UniProtKB:Q8TDX7, ECO:0000250|UniProtKB:Q9ES74}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8TDX7}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q8TDX7}. 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. Also detected at
CC       spindle midzone of the anaphase cells and eventually concentrates at
CC       the midbody (By similarity). Interaction with ANKS3 prevents its
CC       translocation to the nucleus (By similarity).
CC       {ECO:0000250|UniProtKB:Q8TDX7}.
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   -!- SIMILARITY: Belongs to the protein kinase superfamily. NEK Ser/Thr
CC       protein kinase family. NIMA subfamily. {ECO:0000305}.
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DR   EMBL; CH473958; EDM09639.1; -; Genomic_DNA.
DR   RefSeq; NP_001101816.1; NM_001108346.2.
DR   RefSeq; XP_006249988.1; XM_006249926.3.
DR   AlphaFoldDB; D3ZBE5; -.
DR   SMR; D3ZBE5; -.
DR   BioGRID; 262254; 1.
DR   IntAct; D3ZBE5; 4.
DR   STRING; 10116.ENSRNOP00000069169; -.
DR   iPTMnet; D3ZBE5; -.
DR   PhosphoSitePlus; D3ZBE5; -.
DR   jPOST; D3ZBE5; -.
DR   PaxDb; 10116-ENSRNOP00000000817; -.
DR   PeptideAtlas; D3ZBE5; -.
DR   Ensembl; ENSRNOT00000000817.7; ENSRNOP00000000817.4; ENSRNOG00000000657.8.
DR   Ensembl; ENSRNOT00055001534; ENSRNOP00055001230; ENSRNOG00055000899.
DR   Ensembl; ENSRNOT00060007788; ENSRNOP00060005851; ENSRNOG00060004647.
DR   Ensembl; ENSRNOT00065035755; ENSRNOP00065028816; ENSRNOG00065021005.
DR   GeneID; 360850; -.
DR   KEGG; rno:360850; -.
DR   UCSC; RGD:1311160; rat.
DR   AGR; RGD:1311160; -.
DR   CTD; 140609; -.
DR   RGD; 1311160; Nek7.
DR   eggNOG; KOG0591; Eukaryota.
DR   GeneTree; ENSGT00940000156725; -.
DR   HOGENOM; CLU_000288_63_23_1; -.
DR   InParanoid; D3ZBE5; -.
DR   OrthoDB; 198307at2759; -.
DR   PhylomeDB; D3ZBE5; -.
DR   TreeFam; TF105135; -.
DR   PRO; PR:D3ZBE5; -.
DR   Proteomes; UP000002494; Chromosome 13.
DR   Proteomes; UP000234681; Chromosome 13.
DR   Bgee; ENSRNOG00000000657; Expressed in quadriceps femoris and 18 other cell types or tissues.
DR   ExpressionAtlas; D3ZBE5; baseline and differential.
DR   GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005815; C:microtubule organizing center; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; ISS: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:0140677; F:molecular function activator activity; ISS:UniProtKB.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0035865; P:cellular response to potassium ion; ISS:UniProtKB.
DR   GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR   GO; GO:1904355; P:positive regulation of telomere capping; ISO:RGD.
DR   GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:RGD.
DR   GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0007346; P:regulation of mitotic cell cycle; ISS:UniProtKB.
DR   CDD; cd08224; STKc_Nek6_7; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR43289; MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 20-RELATED; 1.
DR   PANTHER; PTHR43289:SF2; SERINE_THREONINE-PROTEIN KINASE NEK7; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   PIRSF; PIRSF000654; Integrin-linked_kinase; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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_0000412823"
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|UniProtKB:Q8TDX7"
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|UniProtKB:Q8TDX7"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TDX7"
FT   MOD_RES         195
FT                   /note="Phosphoserine; by NEK9"
FT                   /evidence="ECO:0000250|UniProtKB:Q8TDX7"
SQ   SEQUENCE   302 AA;  34529 MW;  1773BB6E19DFBEDA CRC64;
     MDEQPQGMQG PPVPQFQPQK 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
     SS
//