ID NUAK2_RAT Reviewed; 630 AA.
AC Q66HE5;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 27-MAR-2024, entry version 138.
DE RecName: Full=NUAK family SNF1-like kinase 2;
DE EC=2.7.11.1;
DE AltName: Full=SNF1/AMP kinase-related kinase;
DE Short=SNARK;
GN Name=Nuak2 {ECO:0000312|EMBL:AAH81899.1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ALTERNATIVE SPLICING,
RP AUTOPHOSPHORYLATION, AND TISSUE SPECIFICITY.
RC TISSUE=Keratinocyte {ECO:0000269|PubMed:11284715},
RC Kidney {ECO:0000269|PubMed:11284715}, and
RC Lung {ECO:0000269|PubMed:11284715};
RX PubMed=11284715; DOI=10.1042/0264-6021:3550297;
RA Lefebvre D.L., Bai Y., Shahmolky N., Sharma M., Poon R., Drucker D.J.,
RA Rosen C.F.;
RT "Identification and characterization of a novel sucrose-non-fermenting
RT protein kinase/AMP-activated protein kinase-related protein kinase,
RT SNARK.";
RL Biochem. J. 355:297-305(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
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] {ECO:0000305}
RP FUNCTION, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=15893879; DOI=10.1016/j.bbagen.2005.03.015;
RA Lefebvre D.L., Rosen C.F.;
RT "Regulation of SNARK activity in response to cellular stresses.";
RL Biochim. Biophys. Acta 1724:71-85(2005).
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:0000269|PubMed:11284715, ECO:0000269|PubMed:15893879};
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:11284715,
CC ECO:0000269|PubMed:15893879};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11284715};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-212 by STK11
CC in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase
CC and CAB39. {ECO:0000250, ECO:0000269|PubMed:11284715,
CC ECO:0000269|PubMed:15893879}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=Additional isoforms seem to exist. At least one
CC kinase-inactive isoform is believed to be expressed.
CC {ECO:0000269|PubMed:11284715};
CC Name=1;
CC IsoId=Q66HE5-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Expressed in liver, skin, testis, uterus, ovary,
CC adrenal gland and brain (at protein level). Expressed in kidney, heart,
CC skin, spleen, lung, uterus, liver and the exocrine and endocrine
CC compartments of the human pancreas. A kinase-inactive isoform also
CC appears to be expressed in the skin, spleen, lung, uterus, liver and
CC testis. {ECO:0000269|PubMed:11284715, ECO:0000269|PubMed:15893879}.
CC -!- PTM: Phosphorylated at Thr-212 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39.
CC Autophosphorylation is also possible at Thr-212.
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; BC081899; AAH81899.1; -; mRNA.
DR RefSeq; NP_001007618.1; NM_001007617.1. [Q66HE5-1]
DR AlphaFoldDB; Q66HE5; -.
DR SMR; Q66HE5; -.
DR STRING; 10116.ENSRNOP00000000039; -.
DR PhosphoSitePlus; Q66HE5; -.
DR PaxDb; 10116-ENSRNOP00000000039; -.
DR Ensembl; ENSRNOT00000000039.4; ENSRNOP00000000039.2; ENSRNOG00000000034.7. [Q66HE5-1]
DR GeneID; 289419; -.
DR KEGG; rno:289419; -.
DR UCSC; RGD:1359167; rat. [Q66HE5-1]
DR AGR; RGD:1359167; -.
DR CTD; 81788; -.
DR RGD; 1359167; Nuak2.
DR eggNOG; KOG0611; Eukaryota.
DR GeneTree; ENSGT00940000158422; -.
DR HOGENOM; CLU_000288_63_42_1; -.
DR InParanoid; Q66HE5; -.
DR OrthoDB; 5475340at2759; -.
DR PRO; PR:Q66HE5; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000000034; Expressed in kidney and 19 other cell types or tissues.
DR Genevisible; Q66HE5; RN.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium 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: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; IDA: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:0032007; P:negative regulation of TOR signaling; IBA:GO_Central.
DR GO; GO:0034504; P:protein localization to nucleus; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0035330; P:regulation of hippo signaling; ISS:UniProtKB.
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.
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..630
FT /note="NUAK family SNF1-like kinase 2"
FT /id="PRO_0000247759"
FT DOMAIN 57..307
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 361..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 521..566
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 388..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 424..438
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 179
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:Q9H093,
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 212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 529
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 550
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 553
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H093"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BZN4"
SQ SEQUENCE 630 AA; 69953 MW; 1626427ABCD5F66E CRC64;
MESVALHRRG NLAPSASALA TESARPLADR LIKSPKPLMK KQAVKRHHHK HNLRHRYEFL
ETLGKGTYGK VKKARESSGR LVAIKSIRKD KIKDEQDLLH IRREIEIMSS LNHPHIIAIH
EVFENSSKIV IVMEYASRGD LYDYISERPR LNERDARHFF RQIVSALHYC HQNGIVHRDL
KLENILLDAS GNIKIADFGL SNLYHKGKFL QTFCGSPLYA SPEIVNGKPY VGPEVDSWSL
GVLLYILVHG TMPFDGQDHK TLVKQISSGA YREPCKPSDA CGLIRWLLMV NPIRRATLED
VASHWWVNWG YSTRIGEQEA LREGGHPSGD SGRASMADWL RRSSRPLLEN GAKVCSFFKQ
HVPGGGSTGP GLERQHSLKK SRKENDMAQT LQNDPAEDTS SRPGKNSLKL PKGILKKKAS
PSSGEVQEGP QELRPVSNTP GQPVPAIPLL PRKGILKKSR QRESGYYSSP EPSESGELLD
AGDVFVSGDP MEQKSPQASG RLHRKGILKL NGKFSRTALE GTAPSTFGSL DQLASPHPTA
RASRPSGAVS EDSILSSESF DQLDLPERLP ETPLRGCVSV DNLRRLEQPP SEGLKRWWQE
SLGDSCFSLT DCQEVTAAYR QALGICSKLS
//
