Q641K5 (NUAK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 85. History...
Names and origin
|Protein names||Recommended name:|
NUAK family SNF1-like kinase 1
AMPK-related protein kinase 5
Omphalocele kinase 1
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||658 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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 to 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 By similarity.
ATP + a protein = ADP + a phosphoprotein.
Magnesium By similarity.
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.
Interact (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A By similarity.
Expressed in the developing central nervous system, in epidermis, and some other tissues. Ref.3
At E7.5, 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 E8.5, 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 E9.5, 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 E12.5, 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 E14.5 and E18.5 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. Ref.3
The GILK motif mediates interaction with PPP1CB By similarity.
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.
Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X By similarity.
Lethal during development, no live-born. At E18.5, 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 E14.5 when the physiological hernia is almost rectified in wild-type embryos. Ref.3
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 658||658||NUAK family SNF1-like kinase 1||PRO_0000086454|
|Domain||56 – 307||252||Protein kinase|
|Nucleotide binding||62 – 70||9||ATP By similarity|
|Motif||400 – 403||4||GILK motif|
|Active site||179||1||Proton acceptor By similarity|
|Binding site||85||1||ATP By similarity|
Amino acid modifications
|Modified residue||1||1||N-acetylmethionine By similarity|
|Modified residue||22||1||Phosphoserine By similarity|
|Modified residue||212||1||Phosphothreonine; by LKB1 By similarity|
|Modified residue||456||1||Phosphoserine By similarity|
|Modified residue||601||1||Phosphoserine; by PKB/AKT1 By similarity|
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6 and FVB/N.
Tissue: Brain and Salivary gland.
|||"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."|
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 84-658.
Tissue: Fetal brain.
|||"A new serine/threonine protein kinase, Omphk1, essential to ventral body wall formation."|
Hirano M., Kiyonari H., Inoue A., Furushima K., Murata T., Suda Y., Aizawa S.
Dev. Dyn. 235:2229-2237(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
|+||Additional computationally mapped references.|
|BC040467 mRNA. Translation: AAH40467.1.|
BC082328 mRNA. Translation: AAH82328.1.
AB182364 mRNA. Translation: BAD23995.1.
|RefSeq||NP_001004363.1. NM_001004363.1. |
3D structure databases
|SMR||Q641K5. Positions 34-350. |
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000020220; ENSMUSP00000020220; ENSMUSG00000020032. |
|UCSC||uc007gko.1. mouse. |
|MGI||MGI:1925226. Nuak1. |
Gene expression databases
|GermOnline||ENSMUSG00000020032. Mus musculus. |
Family and domain databases
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF00069. Pkinase. 1 hit. |
|SMART||SM00220. S_TKc. 1 hit. |
|SUPFAM||SSF56112. Kinase_like. 1 hit. |
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
|Accession||Primary (citable) accession number: Q641K5|
Secondary accession number(s): Q6I6D6, Q8CGE1
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|