NUAK1_MOUSE
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 03-AUG-2022, entry version 147.
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; Q641K5; -.
DR PRIDE; Q641K5; -.
DR ProteomicsDB; 252864; -.
DR Antibodypedia; 30646; 322 antibodies from 36 providers.
DR DNASU; 77976; -.
DR Ensembl; ENSMUST00000020220; ENSMUSP00000020220; ENSMUSG00000020032.
DR GeneID; 77976; -.
DR KEGG; mmu:77976; -.
DR UCSC; uc007gko.1; mouse.
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; PSPFKME; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q641K5; -.
DR TreeFam; TF324572; -.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR BioGRID-ORCS; 77976; 0 hits in 76 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 239 other tissues.
DR ExpressionAtlas; Q641K5; baseline and differential.
DR Genevisible; Q641K5; MM.
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: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:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW.
DR GO; GO:0042149; P:cellular response to glucose starvation; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; 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 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 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
