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Q641K5 (NUAK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NUAK family SNF1-like kinase 1

EC=2.7.11.1
Alternative name(s):
AMPK-related protein kinase 5
Omphalocele kinase 1
Gene names
Name:Nuak1
Synonyms:Kiaa0537, Omphk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length658 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

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.

Subunit structure

Interact (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A By similarity.

Subcellular location

Nucleus By similarity. Cytoplasm By similarity.

Tissue specificity

Expressed in the developing central nervous system, in epidermis, and some other tissues. Ref.3

Developmental stage

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

Domain

The GILK motif mediates interaction with PPP1CB By similarity.

Post-translational modification

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.

Disruption phenotype

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

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 658658NUAK family SNF1-like kinase 1
PRO_0000086454

Regions

Domain56 – 307252Protein kinase
Nucleotide binding62 – 709ATP By similarity
Motif400 – 4034GILK motif

Sites

Active site1791Proton acceptor By similarity
Binding site851ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue221Phosphoserine By similarity
Modified residue2121Phosphothreonine; by LKB1 By similarity
Modified residue4561Phosphoserine By similarity
Modified residue6011Phosphoserine; by PKB/AKT1 By similarity

Sequences

Sequence LengthMass (Da)Tools
Q641K5 [UniParc].

Last modified October 25, 2004. Version 1.
Checksum: E7176F13B75B899F

FASTA65873,661
        10         20         30         40         50         60 
MEGAAVSAAG DGPAVETGLP GSPLEAVAGA TAAPVEPRKP HGVKRHHHKH NLKHRYELQE 

        70         80         90        100        110        120 
TLGKGTYGKV KRATERFSGR VVAIKSIRKD KIKDELDMVH IRREIEIMSS LNHPHIISIY 

       130        140        150        160        170        180 
EVFENKDKIV IIMEYASKGE LYDYISERRR LSERETRHFF RQIVSAVHYC HKNGVVHRDL 

       190        200        210        220        230        240 
KLENILLDDN CNIKIADFGL SNLYQKDKFL QTFCGSPLYA SPEIVNGRPY RGPEVDSWAL 

       250        260        270        280        290        300 
GVLLYTLIYG TMPFDGFDHK NLIRQISSGE YREPTQPSDA RGLIRWMLMV NPDRRATIED 

       310        320        330        340        350        360 
IANHWWVNWG YKSSVCDCDA LPDSESPLLA RIIDWHHRST GLQAEAEAKM KGLAKPGASE 

       370        380        390        400        410        420 
VVLERQRSLK KSKKENDFPQ SGQDSVPESP SKLSSKRPKG ILKKRSNSEH RSHSTGFIEG 

       430        440        450        460        470        480 
IVSPALPSPF KMEQDLCRTA IPLPSSPEAD MSGKLSLKQS ATMPKKGILK KTQQRESGYY 

       490        500        510        520        530        540 
SSPERSESSE LLDSNDVVIS GGLSSPPPDP ARGTSHSLSC RRKGILKHSS RYSDGGTDPA 

       550        560        570        580        590        600 
LTRPEMPTLE SLSPPGVPSD GISRSYSRPS SIISDDSVLS SDSFDLLELQ ENRPARQRIR 

       610        620        630        640        650 
SCVSAENFLQ LQDFETPHNR PRPQYLKRLA DSSFSLLTDM DDVTQVYKKA LEICSKLN 

« Hide

References

« Hide 'large scale' references
[1]"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.
[2]"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.
[3]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC040467 mRNA. Translation: AAH40467.1.
BC082328 mRNA. Translation: AAH82328.1.
AB182364 mRNA. Translation: BAD23995.1.
CCDSCCDS24079.1.
RefSeqNP_001004363.1. NM_001004363.1.
UniGeneMm.25874.

3D structure databases

ProteinModelPortalQ641K5.
SMRQ641K5. Positions 34-325.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid219063. 1 interaction.

PTM databases

PhosphoSiteQ641K5.

Proteomic databases

PRIDEQ641K5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000020220; ENSMUSP00000020220; ENSMUSG00000020032.
GeneID77976.
KEGGmmu:77976.
UCSCuc007gko.1. mouse.

Organism-specific databases

CTD9891.
MGIMGI:1925226. Nuak1.
RougeSearch...

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115114.
HOGENOMHOG000004864.
HOVERGENHBG007160.
InParanoidQ641K5.
KOK08800.
OMANRPRPQY.
OrthoDBEOG7MD4PN.
PhylomeDBQ641K5.
TreeFamTF324572.

Gene expression databases

BgeeQ641K5.
CleanExMM_NUAK1.
GenevestigatorQ641K5.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio347923.
PROQ641K5.
SOURCESearch...

Entry information

Entry nameNUAK1_MOUSE
AccessionPrimary (citable) accession number: Q641K5
Secondary accession number(s): Q6I6D6, Q8CGE1
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: October 25, 2004
Last modified: July 9, 2014
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot