NEK1_MOUSE
ID NEK1_MOUSE Reviewed; 1203 AA.
AC P51954;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Serine/threonine-protein kinase Nek1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:1382974};
DE AltName: Full=Never in mitosis A-related kinase 1;
DE Short=NimA-related protein kinase 1;
GN Name=Nek1;
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], TISSUE SPECIFICITY, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Blood;
RX PubMed=1382974; DOI=10.1002/j.1460-2075.1992.tb05435.x;
RA Letwin K., Mizzen L., Motro B., Ben-David Y., Bernstein A., Pawson T.;
RT "A mammalian dual specificity protein kinase, Nek1, is related to the NIMA
RT cell cycle regulator and highly expressed in meiotic germ cells.";
RL EMBO J. 11:3521-3531(1992).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Feige E., Motro B.;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH CBY2.
RC STRAIN=CD-1;
RX PubMed=12204287; DOI=10.1016/s0925-4773(02)00217-4;
RA Feige E., Chen A., Motro B.;
RT "Nurit, a novel leucine-zipper protein, expressed uniquely in the spermatid
RT flower-like structure.";
RL Mech. Dev. 117:369-377(2002).
RN [4]
RP IDENTIFICATION BY 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 SUBCELLULAR LOCATION.
RX PubMed=16267153; DOI=10.1681/asn.2005080824;
RA Mahjoub M.R., Trapp M.L., Quarmby L.M.;
RT "NIMA-related kinases defective in murine models of polycystic kidney
RT diseases localize to primary cilia and centrosomes.";
RL J. Am. Soc. Nephrol. 16:3485-3489(2005).
RN [6]
RP FUNCTION.
RX PubMed=18843199; DOI=10.4161/cc.7.20.6815;
RA Chen Y., Chen P.L., Chen C.F., Jiang X., Riley D.J.;
RT "Never-in-mitosis related kinase 1 functions in DNA damage response and
RT checkpoint control.";
RL Cell Cycle 7:3194-3201(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-437; SER-618 AND SER-1071,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Spleen, and
RC 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).
RN [8]
RP MUTAGENESIS OF SER-997, PHOSPHORYLATION AT SER-997, AND INTERACTION WITH
RP 14-3-3 PROTEINS.
RX PubMed=28235073; DOI=10.1371/journal.pone.0173013;
RA Sonntag T., Moresco J.J., Vaughan J.M., Matsumura S., Yates J.R. III,
RA Montminy M.;
RT "Analysis of a cAMP regulated coactivator family reveals an alternative
RT phosphorylation motif for AMPK family members.";
RL PLoS ONE 12:E0173013-E0173013(2017).
CC -!- FUNCTION: Phosphorylates serines and threonines, but also appears to
CC possess tyrosine kinase activity (PubMed:1382974). Involved in DNA
CC damage checkpoint control and for proper DNA damage repair
CC (PubMed:18843199). In response to injury that includes DNA damage, NEK1
CC phosphorylates VDAC1 to limit mitochondrial cell death (By similarity).
CC May be implicated in the control of meiosis (PubMed:1382974). Involved
CC in cilium assembly (By similarity). {ECO:0000250|UniProtKB:Q96PY6,
CC ECO:0000269|PubMed:1382974, ECO:0000269|PubMed:18843199}.
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:1382974};
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:1382974};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Binds to CBY2 (PubMed:12204287). Found in a complex with
CC CFAP410, NEK1 and SPATA7 (By similarity). Interacts with CFAP410 (By
CC similarity). Interacts (via Ser-997 phosphorylated form) with 14-3-3
CC proteins (PubMed:28235073). {ECO:0000250|UniProtKB:Q96PY6,
CC ECO:0000269|PubMed:12204287, ECO:0000269|PubMed:28235073}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:16267153}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:16267153}. Note=Associated with the pericentriolar
CC material (By similarity). Localizes to centrosome during interphase and
CC mitosis (PubMed:16267153). {ECO:0000250|UniProtKB:Q96PY6,
CC ECO:0000269|PubMed:16267153}.
CC -!- TISSUE SPECIFICITY: Predominantly in testes (germ cells and Sertoli
CC cells). Lower levels in ovary (oocytes and granulosa cells), thymus and
CC lung. {ECO:0000269|PubMed:1382974}.
CC -!- DEVELOPMENTAL STAGE: In female, expressed as follicles enter the
CC secondary stage until ovulation occurs. In the male reproductive
CC system, the expression is limited to spermatocytes and spermatids.
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; AY850065; AAB23529.2; -; mRNA.
DR CCDS; CCDS40347.1; -.
DR PIR; S25284; S25284.
DR RefSeq; NP_001280566.1; NM_001293637.1.
DR RefSeq; NP_001280567.1; NM_001293638.1.
DR RefSeq; NP_001280568.1; NM_001293639.1.
DR RefSeq; NP_780298.2; NM_175089.4.
DR AlphaFoldDB; P51954; -.
DR SMR; P51954; -.
DR BioGRID; 201727; 7.
DR IntAct; P51954; 4.
DR STRING; 10090.ENSMUSP00000034065; -.
DR iPTMnet; P51954; -.
DR PhosphoSitePlus; P51954; -.
DR EPD; P51954; -.
DR jPOST; P51954; -.
DR MaxQB; P51954; -.
DR PaxDb; P51954; -.
DR PRIDE; P51954; -.
DR ProteomicsDB; 252879; -.
DR Antibodypedia; 28454; 157 antibodies from 27 providers.
DR DNASU; 18004; -.
DR Ensembl; ENSMUST00000034065; ENSMUSP00000034065; ENSMUSG00000031644.
DR GeneID; 18004; -.
DR KEGG; mmu:18004; -.
DR UCSC; uc009ltt.2; mouse.
DR CTD; 4750; -.
DR MGI; MGI:97303; Nek1.
DR VEuPathDB; HostDB:ENSMUSG00000031644; -.
DR eggNOG; KOG0589; Eukaryota.
DR GeneTree; ENSGT00940000158460; -.
DR InParanoid; P51954; -.
DR OMA; EPKTHPP; -.
DR TreeFam; TF333575; -.
DR BioGRID-ORCS; 18004; 5 hits in 76 CRISPR screens.
DR ChiTaRS; Nek1; mouse.
DR PRO; PR:P51954; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P51954; protein.
DR Bgee; ENSMUSG00000031644; Expressed in sciatic nerve and 229 other tissues.
DR ExpressionAtlas; P51954; baseline and differential.
DR Genevisible; P51954; MM.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0000242; C:pericentriolar material; ISO:MGI.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine 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:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0060271; P:cilium assembly; ISO:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IMP:CACAO.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP: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 ATP-binding; Cell cycle; Cell division; Cilium biogenesis/degradation;
KW Cytoplasm; Cytoskeleton; Kinase; Magnesium; Metal-binding; Mitosis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..1203
FT /note="Serine/threonine-protein kinase Nek1"
FT /id="PRO_0000086419"
FT DOMAIN 4..258
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 329..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 643..662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 674..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 814..866
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 888..925
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1021..1045
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1063..1120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 646..662
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 814..836
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1022..1045
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 128
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 156
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96PY6"
FT MOD_RES 162
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 417
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PY6"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 615
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96PY6"
FT MOD_RES 618
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 750
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PY6"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PY6"
FT MOD_RES 820
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PY6"
FT MOD_RES 832
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96PY6"
FT MOD_RES 997
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:28235073"
FT MOD_RES 1071
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 997
FT /note="S->A: Loss of 14-3-3 protein-binding."
FT /evidence="ECO:0000269|PubMed:28235073"
SQ SEQUENCE 1203 AA; 136690 MW; 06393960F2E719DA CRC64;
MEKYVRLQKI GEGSFGKAVL VKSTEDGRHY VIKEINISRM SDKERQESRR EVAVLANMKH
PNIVQYKESF EENGSLYIVM DYCEGGDLFK RINAQKGALF QEDQILDWFV QICLALKHVH
DRKILHRDIK SQNIFLTKDG TVQLGDFGIA RVLNSTVELA RTCIGTPYYL SPEICENKPY
NNKSDIWALG CVLYELCTLK HAFEAGNMKN LVLKIISGSF PPVSPHYSYD LRSLLSQLFK
RNPRDRPSVN SILEKGFIAK RIEKFLSPQL IAEEFCLKTL SKFGPQPLPG KRPASGQGVS
SFVPAQKITK PAAKYGVPLT YKKYGDKKLL EKKPPPKHKQ AHQIPVKKMN SGEERKKMSE
EAAKKRRLEF IEKEKKQKDQ IRFLKAEQMK RQEKQRLERI NRAREQGWRN VLRAGGSGEV
KASFFGIGGA VSPSPCSPRG QYEHYHAIFD QMQRLRAEDN EARWKGGIYG RWLPERQKGH
LAVERANQVE EFLQRKREAM QNKARAEGHV VYLARLRQIR LQNFNERQQI KAKLRGENKE
ADGTKGQEAT EETDMRLKKM ESLKAQTNAR AAVLKEQLER KRKEAYEREK KVWEEHLVAR
VKSSDVPLPL ELLETGGSPS KQQVKPVISV TSALKEVGLD GSLTDTQEEE MEKSNSAISS
KREILRRLNE NLKAQEDEKE KQHHSGSCET VGHKDEREYE TENAISSDRK KWEMGGQLVI
PLDAVTLDTS FSATEKHTVG EVIKLDSNGS PRKVWGKNPT DSVLKILGEA ELQLQTELLE
NTSFKSEVYA EEENYKPLLT EEENLQCISK EINPSATVDS TETKSPKFTE VSPQMSEGNV
EEPDDLETEV LQEPSSTHTD GSLPPVLNDV WTREKEAAKE TELEDKVAVQ QSEVCEDRIP
GNVDQSCKDQ RDPAVDDSPQ SGCDVEKSVQ PESIFQKVVH SKDLNLVQAV HCSPEEPIPI
RSHSDSPPKT KSKNSLLIGL STGLFDANNP KMLRTCSLPD LSKLFRTLMD VPTVGDVHQD
SLEIDELEDE PIKEGPSDSE DTVFEETDTD LQELQASMEQ LLREQPGDEY SEEEESVLKS
SDVEQTARGT DAPDEEDNPS SESALNEEWH SDNSDAETTS ECEYDSVFNH LEELRLHLEQ
EMGFEKFFEV YEKVKAIHED EDENIEICST IVENILGNEH QHLYAKILHL VMADGAYQED
NDE
