ID   NUAK1_MOUSE             Reviewed;         658 AA.
AC   Q641K5; Q6I6D6; Q8CGE1;
DT   24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2004, sequence version 1.
DT   27-MAR-2024, entry version 156.
DE   RecName: Full=NUAK family SNF1-like kinase 1;
DE            EC=2.7.11.1;
DE   AltName: Full=AMPK-related protein kinase 5;
DE   AltName: Full=Omphalocele kinase 1;
GN   Name=Nuak1; Synonyms=Kiaa0537, Omphk1;
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 [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Salivary gland;
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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 84-658.
RC   TISSUE=Fetal brain;
RX   PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA   Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA   Saga Y., Nagase T., Ohara O., Koga H.;
RT   "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT   The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT   identified by screening of terminal sequences of cDNA clones randomly
RT   sampled from size-fractionated libraries.";
RL   DNA Res. 10:167-180(2003).
RN   [3]
RP   DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=16715502; DOI=10.1002/dvdy.20823;
RA   Hirano M., Kiyonari H., Inoue A., Furushima K., Murata T., Suda Y.,
RA   Aizawa S.;
RT   "A new serine/threonine protein kinase, Omphk1, essential to ventral body
RT   wall formation.";
RL   Dev. Dyn. 235:2229-2237(2006).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, and Brown adipose tissue;
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: Serine/threonine-protein kinase involved in various processes
CC       such as cell adhesion, regulation of cell ploidy and senescence, cell
CC       proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1,
CC       PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and
CC       cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1,
CC       thereby controlling its stability. Controls cell adhesion by regulating
CC       activity of the myosin protein phosphatase 1 (PP1) complex. Acts by
CC       mediating phosphorylation of PPP1R12A subunit of myosin PP1:
CC       phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced
CC       dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA
CC       damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and
CC       is recruited to the CDKN1A/WAF1 promoter to participate in
CC       transcription activation by p53/TP53. May also act as a tumor
CC       malignancy-associated factor by promoting tumor invasion and metastasis
CC       under regulation and phosphorylation by AKT1. Suppresses Fas-induced
CC       apoptosis by mediating phosphorylation of CASP6, thereby suppressing
CC       the activation of the caspase and the subsequent cleavage of CFLAR.
CC       Regulates UV radiation-induced DNA damage response mediated by CDKN1A.
CC       In association with STK11, phosphorylates CDKN1A in response to UV
CC       radiation and contributes to its degradation which is necessary for
CC       optimal DNA repair. {ECO:0000250|UniProtKB:O60285}.
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: Activated by phosphorylation on Thr-212. Activated
CC       by phosphorylation at Ser-601 AKT1 during glucose starvation; the
CC       relevance of such activation in normal cells is however unsure (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts (via GILK motif) with PPP1CB; the interaction is
CC       direct and bridges NUAK1 and PPP1R12A. Interacts with CDKN1A.
CC       {ECO:0000250|UniProtKB:O60285}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in the developing central nervous system,
CC       in epidermis, and some other tissues. {ECO:0000269|PubMed:16715502}.
CC   -!- DEVELOPMENTAL STAGE: At 7.5 dpc, expressed in allantois and anterior
CC       visceral endoderm. In the embryonic part, present in mesoderm migrating
CC       laterally but not in the primitive streak; the expression is not
CC       apparent in ectoderm or endoderm at this stage. At 8.5 dpc, no
CC       expression is found in mesodermal tissues, while it is expressed in
CC       midbrain and isthmic regions of the neuroectoderm; it is also found in
CC       the pharyngeal region of the foregut. At 9.5 dpc, the expression is
CC       found throughout the undifferentiated neuroectoderm, except the
CC       telencephalic region. The expression is also ubiquitous in the
CC       epidermis; it is especially apparent in the ventral body wall. Also
CC       expressed in dorsal root ganglia of neural crest origin. The expression
CC       persists in the anterior gut and is also found in bulb arteriosus,
CC       kidney, and several connective tissues. At 12.5 dpc, the expression is
CC       greatly reduced in most of the neuroectoderm, but some expression
CC       remains in pons, anterior tectum, tegmentum, pretectum, prethalamus,
CC       mammillary region and hypothalamus. In telencephalon, expression is
CC       present in the differentiating preplate of the cortex. The expression
CC       is sustained in the epidermis of the whole body. In 14.5 and 18.5 dpc
CC       brain, expressed in differentiated fields of the cortex; no significant
CC       expression is found in other parts of brain or in the spinal cord. The
CC       expression is also present in a variety of connective tissues and in
CC       the epidermis of the whole body. {ECO:0000269|PubMed:16715502}.
CC   -!- DOMAIN: The GILK motif mediates interaction with PPP1CB. {ECO:0000250}.
CC   -!- PTM: Phosphorylated at Thr-212 by STK11/LKB1 in complex with STE20-
CC       related adapter-alpha (STRADA) pseudo kinase and CAB39. Not
CC       dephosphorylated by the myosin PP1 complex when regulating its
CC       activity, due to the presence of PPP1R12A, which prevents myosin PP1
CC       from dephosphorylating NUAK1. Phosphorylated by STK38L upon stimulation
CC       with IGF1 (By similarity). {ECO:0000250}.
CC   -!- PTM: Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins
CC       which appear to impede LKB1-mediated phosphorylation. Deubiquitinated
CC       by USP9X (By similarity). {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Lethal during development, no live-born. At 18.5
CC       dpc, homozygous mutants suffer from omphalocele with a failure in
CC       closure of the secondary body wall leading to organs outside of the
CC       abdomen. Omphalocele are apparent at 14.5 dpc when the physiological
CC       hernia is almost rectified in wild-type embryos.
CC       {ECO:0000269|PubMed:16715502}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC       protein kinase family. SNF1 subfamily. {ECO:0000305}.
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DR   EMBL; BC040467; AAH40467.1; -; mRNA.
DR   EMBL; BC082328; AAH82328.1; -; mRNA.
DR   EMBL; AB182364; BAD23995.1; -; mRNA.
DR   CCDS; CCDS24079.1; -.
DR   RefSeq; NP_001004363.1; NM_001004363.1.
DR   AlphaFoldDB; Q641K5; -.
DR   SMR; Q641K5; -.
DR   BioGRID; 219063; 1.
DR   STRING; 10090.ENSMUSP00000020220; -.
DR   iPTMnet; Q641K5; -.
DR   PhosphoSitePlus; Q641K5; -.
DR   MaxQB; Q641K5; -.
DR   PaxDb; 10090-ENSMUSP00000020220; -.
DR   ProteomicsDB; 252864; -.
DR   Antibodypedia; 30646; 339 antibodies from 36 providers.
DR   DNASU; 77976; -.
DR   Ensembl; ENSMUST00000020220.15; ENSMUSP00000020220.9; ENSMUSG00000020032.15.
DR   GeneID; 77976; -.
DR   KEGG; mmu:77976; -.
DR   UCSC; uc007gko.1; mouse.
DR   AGR; MGI:1925226; -.
DR   CTD; 9891; -.
DR   MGI; MGI:1925226; Nuak1.
DR   VEuPathDB; HostDB:ENSMUSG00000020032; -.
DR   eggNOG; KOG0611; Eukaryota.
DR   GeneTree; ENSGT00940000157255; -.
DR   HOGENOM; CLU_000288_63_42_1; -.
DR   InParanoid; Q641K5; -.
DR   OMA; VCDCDTL; -.
DR   OrthoDB; 5475340at2759; -.
DR   PhylomeDB; Q641K5; -.
DR   TreeFam; TF324572; -.
DR   Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR   BioGRID-ORCS; 77976; 1 hit in 81 CRISPR screens.
DR   ChiTaRS; Nuak1; mouse.
DR   PRO; PR:Q641K5; -.
DR   Proteomes; UP000000589; Chromosome 10.
DR   RNAct; Q641K5; Protein.
DR   Bgee; ENSMUSG00000020032; Expressed in interventricular septum and 241 other cell types or tissues.
DR   ExpressionAtlas; Q641K5; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR   GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0031588; C:nucleotide-activated protein kinase complex; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0002039; F:p53 binding; ISO:MGI.
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:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR   GO; GO:0006974; P:DNA damage response; IEA:UniProtKB-KW.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0032007; P:negative regulation of TOR signaling; IBA:GO_Central.
DR   GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR   GO; GO:2000772; P:regulation of cellular senescence; ISS:UniProtKB.
DR   GO; GO:0035507; P:regulation of myosin-light-chain-phosphatase activity; ISS:UniProtKB.
DR   CDD; cd14073; STKc_NUAK; 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; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24346; MAP/MICROTUBULE AFFINITY-REGULATING KINASE; 1.
DR   PANTHER; PTHR24346:SF101; NUAK FAMILY SNF1-LIKE KINASE 1; 1.
DR   Pfam; PF00069; Pkinase; 1.
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.
DR   Genevisible; Q641K5; MM.
PE   1: Evidence at protein level;
KW   Acetylation; ATP-binding; Cell adhesion; Cytoplasm; DNA damage; Kinase;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT   CHAIN           1..658
FT                   /note="NUAK family SNF1-like kinase 1"
FT                   /id="PRO_0000086454"
FT   DOMAIN          56..307
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..53
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          353..422
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          441..568
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           400..403
FT                   /note="GILK motif"
FT   COMPBIAS        364..378
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        474..501
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        179
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         62..70
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         85
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:O60285"
FT   MOD_RES         22
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O60285"
FT   MOD_RES         212
FT                   /note="Phosphothreonine; by LKB1"
FT                   /evidence="ECO:0000250|UniProtKB:O60285"
FT   MOD_RES         456
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O60285"
FT   MOD_RES         601
FT                   /note="Phosphoserine; by PKB/AKT1"
FT                   /evidence="ECO:0000250|UniProtKB:O60285"
SQ   SEQUENCE   658 AA;  73661 MW;  E7176F13B75B899F CRC64;
     MEGAAVSAAG DGPAVETGLP GSPLEAVAGA TAAPVEPRKP HGVKRHHHKH NLKHRYELQE
     TLGKGTYGKV KRATERFSGR VVAIKSIRKD KIKDELDMVH IRREIEIMSS LNHPHIISIY
     EVFENKDKIV IIMEYASKGE LYDYISERRR LSERETRHFF RQIVSAVHYC HKNGVVHRDL
     KLENILLDDN CNIKIADFGL SNLYQKDKFL QTFCGSPLYA SPEIVNGRPY RGPEVDSWAL
     GVLLYTLIYG TMPFDGFDHK NLIRQISSGE YREPTQPSDA RGLIRWMLMV NPDRRATIED
     IANHWWVNWG YKSSVCDCDA LPDSESPLLA RIIDWHHRST GLQAEAEAKM KGLAKPGASE
     VVLERQRSLK KSKKENDFPQ SGQDSVPESP SKLSSKRPKG ILKKRSNSEH RSHSTGFIEG
     IVSPALPSPF KMEQDLCRTA IPLPSSPEAD MSGKLSLKQS ATMPKKGILK KTQQRESGYY
     SSPERSESSE LLDSNDVVIS GGLSSPPPDP ARGTSHSLSC RRKGILKHSS RYSDGGTDPA
     LTRPEMPTLE SLSPPGVPSD GISRSYSRPS SIISDDSVLS SDSFDLLELQ ENRPARQRIR
     SCVSAENFLQ LQDFETPHNR PRPQYLKRLA DSSFSLLTDM DDVTQVYKKA LEICSKLN
//