NUAK2_MOUSE
ID NUAK2_MOUSE Reviewed; 639 AA.
AC Q8BZN4; Q80ZW3; Q8CIC0; Q9DBV0;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=NUAK family SNF1-like kinase 2;
DE EC=2.7.11.1;
DE AltName: Full=Omphalocele kinase 2;
GN Name=Nuak2 {ECO:0000312|MGI:MGI:1921387}; Synonyms=Omphk2;
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] {ECO:0000305, ECO:0000312|EMBL:BAC28421.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC28421.1};
RC TISSUE=Cecum {ECO:0000312|EMBL:BAC28421.1},
RC Diencephalon {ECO:0000312|EMBL:BAC28575.1}, and
RC Lung {ECO:0000312|EMBL:BAB23518.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAH46833.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH46833.1}, and
RC Czech II {ECO:0000312|EMBL:AAH33302.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAH46833.1}, and
RC Mammary gland {ECO:0000312|EMBL:AAH33302.1};
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 [3]
RP 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
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: Stress-activated kinase involved in tolerance to glucose
CC starvation. Induces cell-cell detachment by increasing F-actin
CC conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via
CC NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required
CC for the increased motility and invasiveness of CD95-activated tumor
CC cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube
CC closure during embryonic development through LATS2 phosphorylation and
CC regulation of the nuclear localization of YAP1 a critical downstream
CC regulatory target in the Hippo signaling pathway.
CC {ECO:0000250|UniProtKB:Q9H093}.
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:0000250|UniProtKB:Q9H093};
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:0000250|UniProtKB:Q9H093};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9H093};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-220.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16141072};
CC IsoId=Q8BZN4-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16141072};
CC IsoId=Q8BZN4-2; Sequence=VSP_052095;
CC -!- DEVELOPMENTAL STAGE: First expressed in the anterior neuroectoderm at
CC 7.5 dpc. At 8.5 dpc, the expression is present in future forebrain and
CC midbrain regions. At 9.5 dpc, the expression is intense in the
CC forebrain and midbrain with a sharp caudal boundary at the isthmic
CC region; a low level of the expression is found throughout the
CC neuroectoderm. Not expressed in the ventral body wall.
CC {ECO:0000269|PubMed:16715502}.
CC -!- PTM: Phosphorylated at Thr-220 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39.
CC Autophosphorylation is also possible at Thr-220.
CC {ECO:0000250|UniProtKB:Q9H093}.
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; AK004737; BAB23518.1; -; mRNA.
DR EMBL; AK033672; BAC28421.1; -; mRNA.
DR EMBL; AK034082; BAC28575.1; -; mRNA.
DR EMBL; BC033302; AAH33302.1; -; mRNA.
DR EMBL; BC046833; AAH46833.1; -; mRNA.
DR CCDS; CCDS15283.1; -. [Q8BZN4-2]
DR CCDS; CCDS56642.1; -. [Q8BZN4-1]
DR RefSeq; NP_001181954.1; NM_001195025.1. [Q8BZN4-1]
DR RefSeq; NP_083054.1; NM_028778.4. [Q8BZN4-2]
DR AlphaFoldDB; Q8BZN4; -.
DR SMR; Q8BZN4; -.
DR BioGRID; 216519; 4.
DR STRING; 10090.ENSMUSP00000080769; -.
DR iPTMnet; Q8BZN4; -.
DR PhosphoSitePlus; Q8BZN4; -.
DR MaxQB; Q8BZN4; -.
DR PaxDb; Q8BZN4; -.
DR PRIDE; Q8BZN4; -.
DR ProteomicsDB; 293801; -. [Q8BZN4-1]
DR ProteomicsDB; 293802; -. [Q8BZN4-2]
DR Antibodypedia; 2090; 274 antibodies from 30 providers.
DR DNASU; 74137; -.
DR Ensembl; ENSMUST00000072177; ENSMUSP00000072039; ENSMUSG00000009772. [Q8BZN4-1]
DR Ensembl; ENSMUST00000082125; ENSMUSP00000080769; ENSMUSG00000009772. [Q8BZN4-2]
DR GeneID; 74137; -.
DR KEGG; mmu:74137; -.
DR UCSC; uc007coo.2; mouse. [Q8BZN4-2]
DR UCSC; uc007cop.2; mouse. [Q8BZN4-1]
DR CTD; 81788; -.
DR MGI; MGI:1921387; Nuak2.
DR VEuPathDB; HostDB:ENSMUSG00000009772; -.
DR eggNOG; KOG0611; Eukaryota.
DR GeneTree; ENSGT00940000158422; -.
DR HOGENOM; CLU_000288_63_42_1; -.
DR InParanoid; Q8BZN4; -.
DR OMA; NWGYKVP; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; Q8BZN4; -.
DR TreeFam; TF324572; -.
DR BioGRID-ORCS; 74137; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Nuak2; mouse.
DR PRO; PR:Q8BZN4; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8BZN4; protein.
DR Bgee; ENSMUSG00000009772; Expressed in right kidney and 157 other tissues.
DR Genevisible; Q8BZN4; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
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:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0035330; P:regulation of hippo signaling; 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; Alternative splicing; Apoptosis; ATP-binding; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..639
FT /note="NUAK family SNF1-like kinase 2"
FT /id="PRO_0000247757"
FT DOMAIN 57..315
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 529..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 400..414
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 187
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:O60285,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 63..71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O60285,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q9H093,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 220
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 559
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 122..129
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_052095"
FT CONFLICT 4
FT /note="V -> G (in Ref. 1; BAC28575)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="F -> S (in Ref. 2; AAH33302)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 639 AA; 70675 MW; FB9C40228F53872C CRC64;
MESVALLQRP SQAPSASALA SESARPLADG LIKSPKPLMK KQAVKRHHHK HNLRHRYEFL
ETLGKGTYGK VKKARESSGR LVAIKSIRKD KIKDEQDLLH IRREIEIMSS LNHPHIIAIH
EVGRSRLVTV FENSSKIVIV MEYASRGDLY DYISERPRLS ERDARHFFRQ IVSALHYCHQ
NGIVHRDLKL ENILLDANGN IKIADFGLSN LYHKGKFLQT FCGSPLYASP EIVNGKPYVG
PEVDSWSLGV LLYILVHGTM PFDGQDHKTL VKQISNGAYR EPPKPSDACG LIRWLLMVNP
TRRATLEDVA SHWWVNWGYT TGVGEQEALR EGGHPSGDFG RASMADWLRR SSRPLLENGA
KVCSFFKQHV PGGGSTVPGL ERQHSLKKSR KENDMAQNLQ GDPAEDTSSR PGKSSLKLPK
GILKKKSSTS SGEVQEDPQE LRPVPDTPGQ PVPAVSLLPR KGILKKSRQR ESGYYSSPEP
SESGELLDAS DVFVSGDPVE QKSPQASGLL LHRKGILKLN GKFSRTALEG TTPSTFGSLD
QLASSHPAAR PSRPSGAVSE DSILSSESFD QLDLPERLPE TPLRGCVSVD NLRGLEQPPS
EGLKRWWQES LGDSCFSLTD CQEVTAAYRQ ALGICSKLS
