UniProtKB - Q641K5 (NUAK1_MOUSE)
Protein
NUAK family SNF1-like kinase 1
Gene
Nuak1
Organism
Mus musculus (Mouse)
Status
Functioni
Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair.By similarity
Catalytic activityi
Cofactori
Mg2+By similarity
Activity regulationi
Activated by phosphorylation on Thr-212. Activated by phosphorylation at Ser-601 AKT1 during glucose starvation; the relevance of such activation in normal cells is however unsure (By similarity).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 85 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 179 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 62 – 70 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- p53 binding Source: MGI
- protein serine/threonine kinase activity Source: UniProtKB
GO - Biological processi
- cell adhesion Source: UniProtKB-KW
- cellular response to DNA damage stimulus Source: UniProtKB-KW
- cellular response to glucose starvation Source: GO_Central
- intracellular signal transduction Source: GO_Central
- protein phosphorylation Source: UniProtKB
- regulation of cell adhesion Source: UniProtKB
- regulation of cellular senescence Source: UniProtKB
- regulation of myosin-light-chain-phosphatase activity Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell adhesion, DNA damage |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-6804756, Regulation of TP53 Activity through Phosphorylation |
Names & Taxonomyi
Protein namesi | Recommended name: NUAK family SNF1-like kinase 1 (EC:2.7.11.1)Alternative name(s): AMPK-related protein kinase 5 Omphalocele kinase 1 |
Gene namesi | Name:Nuak1 Synonyms:Kiaa0537, Omphk1 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1925226, Nuak1 |
Subcellular locationi
Cytoskeleton
- microtubule cytoskeleton Source: MGI
Nucleus
- fibrillar center Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
Lethal during development, no live-born. At 18.5 dpc, homozygous mutants suffer from omphalocele with a failure in closure of the secondary body wall leading to organs outside of the abdomen. Omphalocele are apparent at 14.5 dpc when the physiological hernia is almost rectified in wild-type embryos.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086454 | 1 – 658 | NUAK family SNF1-like kinase 1Add BLAST | 658 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
Modified residuei | 22 | PhosphoserineBy similarity | 1 | |
Modified residuei | 212 | Phosphothreonine; by LKB1By similarity | 1 | |
Modified residuei | 456 | PhosphoserineBy similarity | 1 | |
Modified residuei | 601 | Phosphoserine; by PKB/AKT1By similarity | 1 |
Post-translational modificationi
Phosphorylated at Thr-212 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not dephosphorylated by the myosin PP1 complex when regulating its activity, due to the presence of PPP1R12A, which prevents myosin PP1 from dephosphorylating NUAK1. Phosphorylated by STK38L upon stimulation with IGF1 (By similarity).By similarity
Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X (By similarity).By similarity
Keywords - PTMi
Acetylation, Phosphoprotein, Ubl conjugationProteomic databases
MaxQBi | Q641K5 |
PaxDbi | Q641K5 |
PRIDEi | Q641K5 |
PTM databases
iPTMneti | Q641K5 |
PhosphoSitePlusi | Q641K5 |
Expressioni
Tissue specificityi
Expressed in the developing central nervous system, in epidermis, and some other tissues.1 Publication
Developmental stagei
At 7.5 dpc, expressed in allantois and anterior visceral endoderm. In the embryonic part, present in mesoderm migrating laterally but not in the primitive streak; the expression is not apparent in ectoderm or endoderm at this stage. At 8.5 dpc, no expression is found in mesodermal tissues, while it is expressed in midbrain and isthmic regions of the neuroectoderm; it is also found in the pharyngeal region of the foregut. At 9.5 dpc, the expression is found throughout the undifferentiated neuroectoderm, except the telencephalic region. The expression is also ubiquitous in the epidermis; it is especially apparent in the ventral body wall. Also expressed in dorsal root ganglia of neural crest origin. The expression persists in the anterior gut and is also found in bulb arteriosus, kidney, and several connective tissues. At 12.5 dpc, the expression is greatly reduced in most of the neuroectoderm, but some expression remains in pons, anterior tectum, tegmentum, pretectum, prethalamus, mammillary region and hypothalamus. In telencephalon, expression is present in the differentiating preplate of the cortex. The expression is sustained in the epidermis of the whole body. In 14.5 and 18.5 dpc brain, expressed in differentiated fields of the cortex; no significant expression is found in other parts of brain or in the spinal cord. The expression is also present in a variety of connective tissues and in the epidermis of the whole body.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000020032, Expressed in primary visual cortex and 271 other tissues |
Genevisiblei | Q641K5, MM |
Interactioni
Subunit structurei
Interacts (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A.
Interacts with CDKN1A.
By similarityGO - Molecular functioni
- p53 binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 219063, 1 interactor |
STRINGi | 10090.ENSMUSP00000020220 |
Miscellaneous databases
RNActi | Q641K5, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 56 – 307 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 252 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 400 – 403 | GILK motif | 4 |
Domaini
The GILK motif mediates interaction with PPP1CB.By similarity
Sequence similaritiesi
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0611, Eukaryota |
GeneTreei | ENSGT00940000157255 |
HOGENOMi | CLU_000288_63_42_1 |
InParanoidi | Q641K5 |
OMAi | GAEWHPS |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q641K5 |
TreeFami | TF324572 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q641K5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEGAAVSAAG DGPAVETGLP GSPLEAVAGA TAAPVEPRKP HGVKRHHHKH
60 70 80 90 100
NLKHRYELQE TLGKGTYGKV KRATERFSGR VVAIKSIRKD KIKDELDMVH
110 120 130 140 150
IRREIEIMSS LNHPHIISIY EVFENKDKIV IIMEYASKGE LYDYISERRR
160 170 180 190 200
LSERETRHFF RQIVSAVHYC HKNGVVHRDL KLENILLDDN CNIKIADFGL
210 220 230 240 250
SNLYQKDKFL QTFCGSPLYA SPEIVNGRPY RGPEVDSWAL GVLLYTLIYG
260 270 280 290 300
TMPFDGFDHK NLIRQISSGE YREPTQPSDA RGLIRWMLMV NPDRRATIED
310 320 330 340 350
IANHWWVNWG YKSSVCDCDA LPDSESPLLA RIIDWHHRST GLQAEAEAKM
360 370 380 390 400
KGLAKPGASE VVLERQRSLK KSKKENDFPQ SGQDSVPESP SKLSSKRPKG
410 420 430 440 450
ILKKRSNSEH RSHSTGFIEG IVSPALPSPF KMEQDLCRTA IPLPSSPEAD
460 470 480 490 500
MSGKLSLKQS ATMPKKGILK KTQQRESGYY SSPERSESSE LLDSNDVVIS
510 520 530 540 550
GGLSSPPPDP ARGTSHSLSC RRKGILKHSS RYSDGGTDPA LTRPEMPTLE
560 570 580 590 600
SLSPPGVPSD GISRSYSRPS SIISDDSVLS SDSFDLLELQ ENRPARQRIR
610 620 630 640 650
SCVSAENFLQ LQDFETPHNR PRPQYLKRLA DSSFSLLTDM DDVTQVYKKA
LEICSKLN
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketF6XZX4 | F6XZX4_MOUSE | NUAK family SNF1-like kinase 1 | Nuak1 | 160 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC040467 mRNA Translation: AAH40467.1 BC082328 mRNA Translation: AAH82328.1 AB182364 mRNA Translation: BAD23995.1 |
CCDSi | CCDS24079.1 |
RefSeqi | NP_001004363.1, NM_001004363.1 |
Genome annotation databases
Ensembli | ENSMUST00000020220; ENSMUSP00000020220; ENSMUSG00000020032 |
GeneIDi | 77976 |
KEGGi | mmu:77976 |
UCSCi | uc007gko.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | BC040467 mRNA Translation: AAH40467.1 BC082328 mRNA Translation: AAH82328.1 AB182364 mRNA Translation: BAD23995.1 |
CCDSi | CCDS24079.1 |
RefSeqi | NP_001004363.1, NM_001004363.1 |
3D structure databases
SMRi | Q641K5 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 219063, 1 interactor |
STRINGi | 10090.ENSMUSP00000020220 |
PTM databases
iPTMneti | Q641K5 |
PhosphoSitePlusi | Q641K5 |
Proteomic databases
MaxQBi | Q641K5 |
PaxDbi | Q641K5 |
PRIDEi | Q641K5 |
Protocols and materials databases
Antibodypediai | 30646, 301 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000020220; ENSMUSP00000020220; ENSMUSG00000020032 |
GeneIDi | 77976 |
KEGGi | mmu:77976 |
UCSCi | uc007gko.1, mouse |
Organism-specific databases
CTDi | 9891 |
MGIi | MGI:1925226, Nuak1 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | KOG0611, Eukaryota |
GeneTreei | ENSGT00940000157255 |
HOGENOMi | CLU_000288_63_42_1 |
InParanoidi | Q641K5 |
OMAi | GAEWHPS |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q641K5 |
TreeFami | TF324572 |
Enzyme and pathway databases
Reactomei | R-MMU-6804756, Regulation of TP53 Activity through Phosphorylation |
Miscellaneous databases
BioGRID-ORCSi | 77976, 0 hits in 18 CRISPR screens |
ChiTaRSi | Nuak1, mouse |
PROi | PR:Q641K5 |
RNActi | Q641K5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000020032, Expressed in primary visual cortex and 271 other tissues |
Genevisiblei | Q641K5, MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NUAK1_MOUSE | |
Accessioni | Q641K5Primary (citable) accession number: Q641K5 Secondary accession number(s): Q6I6D6, Q8CGE1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 24, 2006 |
Last sequence update: | October 25, 2004 | |
Last modified: | December 2, 2020 | |
This is version 140 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human and mouse protein kinases
Human and mouse protein kinases: classification and index