NEK3_MOUSE
ID NEK3_MOUSE Reviewed; 511 AA.
AC Q9R0A5; E9QLM2; Q9Z0X9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Serine/threonine-protein kinase Nek3;
DE EC=2.7.11.1;
DE AltName: Full=Never in mitosis A-related kinase 3;
DE Short=NimA-related protein kinase 3;
GN Name=Nek3;
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=10224116; DOI=10.1074/jbc.274.19.13491;
RA Tanaka K., Nigg E.A.;
RT "Cloning and characterization of the murine Nek3 protein kinase, a novel
RT member of the NIMA family of putative cell cycle regulators.";
RL J. Biol. Chem. 274:13491-13497(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10393247; DOI=10.1016/s0378-1119(99)00165-1;
RA Chen A., Yanai A., Arama E., Kilfin G., Motro B.;
RT "NIMA-related kinases: isolation and characterization of murine nek3 and
RT nek4 cDNAs, and chromosomal localization of nek1, nek2 and nek3.";
RL Gene 234:127-137(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY,
RP PHOSPHORYLATION AT THR-477, AND MUTAGENESIS OF THR-477.
RX PubMed=19509051; DOI=10.1242/jcs.048975;
RA Chang J., Baloh R.H., Milbrandt J.;
RT "The NIMA-family kinase Nek3 regulates microtubule acetylation in
RT neurons.";
RL J. Cell Sci. 122:2274-2282(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-477, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
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).
CC -!- FUNCTION: Protein kinase which influences neuronal morphogenesis and
CC polarity through effects on microtubules. Regulates microtubule
CC acetylation in neurons. Contributes to prolactin-mediated
CC phosphorylation of PXN and VAV2. {ECO:0000269|PubMed:19509051}.
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 -!- SUBUNIT: Interacts with PXN, PRLR, VAV1 and VAV2 and this interaction
CC is prolactin-dependent. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19509051}. Cell
CC projection, axon {ECO:0000269|PubMed:19509051}.
CC -!- TISSUE SPECIFICITY: Brain. {ECO:0000269|PubMed:19509051}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed during embryogenesis and early
CC postnatal life, but is expressed at lower levels in adults.
CC {ECO:0000269|PubMed:19509051}.
CC -!- PTM: Phosphorylation at Thr-477 regulates its catalytic activity.
CC {ECO:0000269|PubMed:19509051}.
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; AF093416; AAD20986.1; -; mRNA.
DR EMBL; AF099066; AAD16286.1; -; mRNA.
DR EMBL; AC117665; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS52519.1; -.
DR RefSeq; NP_001156419.1; NM_001162947.1.
DR RefSeq; XP_006509174.1; XM_006509111.3.
DR AlphaFoldDB; Q9R0A5; -.
DR SMR; Q9R0A5; -.
DR STRING; 10090.ENSMUSP00000033865; -.
DR iPTMnet; Q9R0A5; -.
DR PhosphoSitePlus; Q9R0A5; -.
DR MaxQB; Q9R0A5; -.
DR PaxDb; Q9R0A5; -.
DR PRIDE; Q9R0A5; -.
DR ProteomicsDB; 252946; -.
DR Antibodypedia; 24171; 244 antibodies from 29 providers.
DR DNASU; 23954; -.
DR Ensembl; ENSMUST00000110730; ENSMUSP00000106358; ENSMUSG00000031478.
DR Ensembl; ENSMUST00000178324; ENSMUSP00000136876; ENSMUSG00000031478.
DR GeneID; 23954; -.
DR KEGG; mmu:23954; -.
DR UCSC; uc012gbb.1; mouse.
DR CTD; 4752; -.
DR MGI; MGI:1344371; Nek3.
DR VEuPathDB; HostDB:ENSMUSG00000031478; -.
DR eggNOG; KOG0589; Eukaryota.
DR GeneTree; ENSGT00940000159738; -.
DR HOGENOM; CLU_000288_63_39_1; -.
DR InParanoid; Q9R0A5; -.
DR OMA; YSYELQY; -.
DR OrthoDB; 70360at2759; -.
DR PhylomeDB; Q9R0A5; -.
DR BioGRID-ORCS; 23954; 1 hit in 74 CRISPR screens.
DR PRO; PR:Q9R0A5; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q9R0A5; protein.
DR Bgee; ENSMUSG00000031478; Expressed in metanephric proximal tubule and 206 other tissues.
DR ExpressionAtlas; Q9R0A5; baseline and differential.
DR Genevisible; Q9R0A5; MM.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; 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; 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:0030010; P:establishment of cell polarity; IMP:CACAO.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:CACAO.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0090043; P:regulation of tubulin deacetylation; IMP:CACAO.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
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; Cell cycle; Cell division; Cell projection;
KW Cytoplasm; Kinase; Magnesium; Metal-binding; Mitosis; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..511
FT /note="Serine/threonine-protein kinase Nek3"
FT /id="PRO_0000086424"
FT DOMAIN 4..255
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..282
FT /note="Interaction with VAV2"
FT /evidence="ECO:0000250"
FT REGION 299..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 443..511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 125
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P51956"
FT MOD_RES 159
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 477
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19509051,
FT ECO:0007744|PubMed:15345747, ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MUTAGEN 477
FT /note="T->A: Distorted neuronal morphology with disturbed
FT polarity and deacetylation of microtubules."
FT /evidence="ECO:0000269|PubMed:19509051"
FT CONFLICT 95
FT /note="K -> N (in Ref. 1; AAD20986 and 2; AAD16286)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="N -> K (in Ref. 2; AAD16286)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="R -> G (in Ref. 1; AAD20986 and 2; AAD16286)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="S -> A (in Ref. 1; AAD20986 and 2; AAD16286)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="E -> G (in Ref. 1; AAD20986 and 2; AAD16286)"
FT /evidence="ECO:0000305"
FT CONFLICT 342..343
FT /note="Missing (in Ref. 2; AAD16286)"
FT /evidence="ECO:0000305"
FT CONFLICT 346
FT /note="P -> R (in Ref. 1; AAD20986 and 2; AAD16286)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="R -> S (in Ref. 1; AAD20986 and 2; AAD16286)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="W -> R (in Ref. 1; AAD20986 and 2; AAD16286)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 511 AA; 57464 MW; 31E777B3BFA31930 CRC64;
MDNYTVLRVI GQGSFGRALL VLQESSNQTF AMKEIRLLKS DTQTSRKEAV LLAKMKHPNI
VAFKESFEAE GYLYIVMEYC DGGDLMQRIK QQKGKLFPED TILNWFIQIC LGVNHIHKRR
VLHRDIKSKN VFLTHNGKVK LGDFGSARLL SSPMAFACTY VGTPYYVPPE IWENLPYNNK
SDIWSLGCIL YELCALKHPF QANSWKNLIL KICQGPIHPL PALYSCKLQG LVKQMLKRNP
SHRPSATTLL CRGSLAPLVP KCLPPQIIRE YGEQILDEIK ISTPKNMKKQ DSNRVRRALG
EANSASMQEE ERGRKCSHTE LESTGTTPAG NALERAARGN PESGNPQEHG RHTSPASPHR
PWWERHGPSS NVEALEKASI LTSSFTAEDD RGGSVIKYEE NARRQWVREP PEALLSMLKD
ADLSQAFQTY TIYRPGAEGF LKGPLSEDTA SDSVDGDLDS VMLDPERFEP RLDEEDTDFE
EDNENPDWVS ELKKHVGYGD GPGGQLLGER A
