NUAK family SNF1-like kinase 1 - Mus musculus (Mouse)

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Q641K5 (NUAK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 85. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:	Nuak1
Synonyms:	Kiaa0537, Omphk1

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

Protein attributes

Sequence length	658 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Cell adhesion DNA damage
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW regulation of cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB regulation of cellular senescence Inferred from sequence or structural similarity. Source: UniProtKB regulation of myosin-light-chain-phosphatase activity Inferred from sequence or structural similarity. Source: UniProtKB response to DNA damage stimulus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 658

658

NUAK family SNF1-like kinase 1

PRO_0000086454

Regions

Domain

56 – 307

252

Protein kinase

Nucleotide binding

62 – 70

ATP By similarity

Motif

400 – 403

GILK motif

Sites

Active site

179

Proton acceptor By similarity

Binding site

ATP By similarity

Amino acid modifications

Modified residue

N-acetylmethionine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

212

Phosphothreonine; by LKB1 By similarity

Modified residue

456

Phosphoserine By similarity

Modified residue

601

Phosphoserine; by PKB/AKT1 By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q641K5 [UniParc].

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

658

73,661

        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' referencesShow '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.
IPI	IPI00465504.
RefSeq	NP_001004363.1. NM_001004363.1.
UniGene	Mm.25874.
3D structure databases
ProteinModelPortal	Q641K5.
SMR	Q641K5. Positions 34-350.
ModBase	Search...
PTM databases
PhosphoSite	Q641K5.
Proteomic databases
PRIDE	Q641K5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000020220; ENSMUSP00000020220; ENSMUSG00000020032.
GeneID	77976.
KEGG	mmu:77976.
UCSC	uc007gko.1. mouse.
Organism-specific databases
CTD	9891.
MGI	MGI:1925226. Nuak1.
Rouge	Search...
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104353.
HOGENOM	HOG000004864.
HOVERGEN	HBG007160.
InParanoid	Q641K5.
KO	K08800.
OMA	NRPRPQY.
OrthoDB	EOG4KD6KP.
Gene expression databases
Bgee	Q641K5.
CleanEx	MM_NUAK1.
Genevestigator	Q641K5.
GermOnline	ENSMUSG00000020032. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
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. [Graphical view]
ProtoNet	Search...
Other
NextBio	347923.
SOURCE	Search...

Entry information

Entry name

NUAK1_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 85 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents