NEK4_MOUSE
ID NEK4_MOUSE Reviewed; 792 AA.
AC Q9Z1J2; O35673; Q9R1J1;
DT 25-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Serine/threonine-protein kinase Nek4;
DE EC=2.7.11.1 {ECO:0000269|PubMed:10529384};
DE AltName: Full=Never in mitosis A-related kinase 4;
DE Short=NimA-related protein kinase 4;
DE AltName: Full=Serine/threonine-protein kinase 2 {ECO:0000303|PubMed:10529384};
GN Name=Nek4; Synonyms=Stk2;
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] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP ACTIVITY, COFACTOR, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC STRAIN=BALB/cJ; TISSUE=Spleen;
RX PubMed=10529384; DOI=10.1006/bbrc.1999.1536;
RA Hayashi K., Igarashi H., Ogawa M., Sakaguchi N.;
RT "Activity and substrate specificity of the murine STK2 serine/threonine
RT kinase that is structurally related to the mitotic regulator protein NIMA
RT of Aspergillus nidulans.";
RL Biochem. Biophys. Res. Commun. 264:449-456(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-675, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, 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).
CC -!- FUNCTION: Required for normal entry into proliferative arrest after a
CC limited number of cell divisions, also called replicative senescence.
CC Required for normal cell cycle arrest in response to double-stranded
CC DNA damage (By similarity). Protein kinase that seems to act
CC exclusively upon threonine residues. {ECO:0000250|UniProtKB:P51957,
CC ECO:0000269|PubMed:10529384}.
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 Evidence={ECO:0000269|PubMed:10529384};
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; Evidence={ECO:0000269|PubMed:10529384};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:10529384};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10529384}. Cell
CC projection, cilium {ECO:0000250|UniProtKB:P51957}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=mSTK2L;
CC IsoId=Q9Z1J2-1; Sequence=Displayed;
CC Name=2; Synonyms=mSTK2S;
CC IsoId=Q9Z1J2-2; Sequence=VSP_007001;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously among various organs and is
CC up-regulated in the testis. {ECO:0000269|PubMed:10529384}.
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; AJ223071; CAA11072.1; -; mRNA.
DR EMBL; Y09234; CAA70436.1; -; mRNA.
DR EMBL; AF099067; AAD16287.1; -; mRNA.
DR CCDS; CCDS26902.1; -. [Q9Z1J2-1]
DR CCDS; CCDS88612.1; -. [Q9Z1J2-2]
DR PIR; JC7122; JC7122.
DR RefSeq; NP_001295257.1; NM_001308328.1. [Q9Z1J2-2]
DR RefSeq; NP_035979.1; NM_011849.3.
DR AlphaFoldDB; Q9Z1J2; -.
DR SMR; Q9Z1J2; -.
DR BioGRID; 204816; 3.
DR STRING; 10090.ENSMUSP00000057915; -.
DR iPTMnet; Q9Z1J2; -.
DR PhosphoSitePlus; Q9Z1J2; -.
DR MaxQB; Q9Z1J2; -.
DR PaxDb; Q9Z1J2; -.
DR PRIDE; Q9Z1J2; -.
DR ProteomicsDB; 287362; -. [Q9Z1J2-1]
DR ProteomicsDB; 287363; -. [Q9Z1J2-2]
DR Antibodypedia; 14725; 223 antibodies from 29 providers.
DR DNASU; 23955; -.
DR Ensembl; ENSMUST00000226551; ENSMUSP00000154678; ENSMUSG00000021918. [Q9Z1J2-2]
DR GeneID; 23955; -.
DR KEGG; mmu:23955; -.
DR CTD; 6787; -.
DR MGI; MGI:1344404; Nek4.
DR VEuPathDB; HostDB:ENSMUSG00000021918; -.
DR eggNOG; KOG0589; Eukaryota.
DR GeneTree; ENSGT00940000157448; -.
DR InParanoid; Q9Z1J2; -.
DR OrthoDB; 70360at2759; -.
DR PhylomeDB; Q9Z1J2; -.
DR BioGRID-ORCS; 23955; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Slk; mouse.
DR PRO; PR:Q9Z1J2; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9Z1J2; protein.
DR Bgee; ENSMUSG00000021918; Expressed in spermatocyte and 231 other tissues.
DR ExpressionAtlas; Q9Z1J2; baseline and differential.
DR GO; GO:0036064; C:ciliary basal body; ISO:MGI.
DR GO; GO:0097014; C:ciliary plasm; ISO:MGI.
DR GO; GO:0035253; C:ciliary rootlet; ISO:MGI.
DR GO; GO:0035869; C:ciliary transition zone; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0030145; F:manganese ion binding; IDA: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:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0000278; P:mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:2000772; P:regulation of cellular senescence; ISS:UniProtKB.
DR GO; GO:2001020; P:regulation of response to DNA damage stimulus; ISO:MGI.
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 Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Cell projection; Cytoplasm; Kinase; Magnesium; Metal-binding; Methylation;
KW Mitosis; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..792
FT /note="Serine/threonine-protein kinase Nek4"
FT /id="PRO_0000086426"
FT DOMAIN 6..261
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 329..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 379..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 527..611
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 628..657
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 399..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..483
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 527..554
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 555..569
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 642..656
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 131
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 12..20
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 35
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 165
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51957"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51957"
FT MOD_RES 566
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51957"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 456..503
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10529384"
FT /id="VSP_007001"
FT CONFLICT 499
FT /note="G -> R (in Ref. 2; AAD16287)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 792 AA; 88994 MW; CF9187311C807A1D CRC64;
MPQAAYCYMR VVGRGSYGEV TLVKHRRDGK QYVIKKLNLR NASSRERRAA EQEAQLLSQL
KHPNIVTYKE SWEGGDGLLY IVMGFCEGGD LYRKLKEQKG QLLPESQVVE WFVQIAMALQ
YLHEKHILHR DLKTQNVFLT RTNIIKVGDL GIARVLENHG DMASTLIGTP YYMSPELFSN
KPYNYKSDVW ALGCCVYEMA TLKHAFNAKD MNSLVYRIIE GKLPPMPKVY STELAELIRT
MLSRRPEERP SVRSILRQPY IKHHISLFLE ATKAKTSKNN VKNCDSRAKP VAAVVSRKEE
SNTDVIHYQP RSSEGSALHV MGEDKCLSQE KPVDIGPLRS PASLEGHTGK QDMNNTGESC
ATISRINIDI LPAERRDSAN AGVVQESQPQ HVDAADEVDS QCSISQEKER LQGNTKSSDQ
PGNLLPRRSS DGGDGEGSEL VKPLYPSNKD QKPDQDQVTG IIENQDSIHP RSQPHSSMSE
PSLSRQRRQK KREQTAHSGT KSQFQELPPR LLPSYPGIGK VDIIATQQND GNQGGPVAGC
VNSSRTSSTA SAKDRPLSAR ERRRLKQSQE EMLPSGPAVQ RTPSAVEPLK PQEEDQPIPA
QRFSSDCSIT QMNHTLPREK EKRLMHGLSE DELSSSTSST DKSDGDSREG KSHTNEMKDL
VQLMTQTLRL EAKESCEDLQ VLNPGSEFRL HRKYRDTLVL HGKVAEEVEP HCTELPTGII
PGSEKIRRIV EVLRADVIQG LGIQLLEQVF DLLGEEDELE REARLQEHMG DKYTTYCVKA
RQLKFFEENV SF
