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Q641K5

- NUAK1_MOUSE

UniProt

Q641K5 - NUAK1_MOUSE

Protein

NUAK family SNF1-like kinase 1

Gene

Nuak1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 96 (01 Oct 2014)
      Sequence version 1 (25 Oct 2004)
      Previous versions | rss
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    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 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.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity

    Enzyme 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei85 – 851ATPPROSITE-ProRule annotation
    Active sitei179 – 1791Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi62 – 709ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. cell adhesion Source: UniProtKB-KW
    2. cellular response to DNA damage stimulus Source: UniProtKB-KW
    3. regulation of cell adhesion Source: UniProtKB
    4. regulation of cellular senescence Source: UniProtKB
    5. regulation of myosin-light-chain-phosphatase activity Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Cell adhesion, DNA damage

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    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
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:1925226. Nuak1.

    Subcellular locationi

    Nucleus By similarity. Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    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.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 658658NUAK family SNF1-like kinase 1PRO_0000086454Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionineBy similarity
    Modified residuei22 – 221PhosphoserineBy similarity
    Modified residuei212 – 2121Phosphothreonine; by LKB1By similarity
    Modified residuei456 – 4561PhosphoserineBy similarity
    Modified residuei601 – 6011Phosphoserine; by PKB/AKT1By similarity

    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 conjugation

    Proteomic databases

    PRIDEiQ641K5.

    PTM databases

    PhosphoSiteiQ641K5.

    Expressioni

    Tissue specificityi

    Expressed in the developing central nervous system, in epidermis, and some other tissues.1 Publication

    Developmental stagei

    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.1 Publication

    Gene expression databases

    BgeeiQ641K5.
    CleanExiMM_NUAK1.
    GenevestigatoriQ641K5.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    BioGridi219063. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliQ641K5.
    SMRiQ641K5. Positions 34-325.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini56 – 307252Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi400 – 4034GILK motif

    Domaini

    The GILK motif mediates interaction with PPP1CB.By similarity

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00740000115114.
    HOGENOMiHOG000004864.
    HOVERGENiHBG007160.
    InParanoidiQ641K5.
    KOiK08800.
    OMAiNRPRPQY.
    OrthoDBiEOG7MD4PN.
    PhylomeDBiQ641K5.
    TreeFamiTF324572.

    Family and domain databases

    InterProiIPR011009. 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]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q641K5-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEGAAVSAAG DGPAVETGLP GSPLEAVAGA TAAPVEPRKP HGVKRHHHKH    50
    NLKHRYELQE TLGKGTYGKV KRATERFSGR VVAIKSIRKD KIKDELDMVH 100
    IRREIEIMSS LNHPHIISIY EVFENKDKIV IIMEYASKGE LYDYISERRR 150
    LSERETRHFF RQIVSAVHYC HKNGVVHRDL KLENILLDDN CNIKIADFGL 200
    SNLYQKDKFL QTFCGSPLYA SPEIVNGRPY RGPEVDSWAL GVLLYTLIYG 250
    TMPFDGFDHK NLIRQISSGE YREPTQPSDA RGLIRWMLMV NPDRRATIED 300
    IANHWWVNWG YKSSVCDCDA LPDSESPLLA RIIDWHHRST GLQAEAEAKM 350
    KGLAKPGASE VVLERQRSLK KSKKENDFPQ SGQDSVPESP SKLSSKRPKG 400
    ILKKRSNSEH RSHSTGFIEG IVSPALPSPF KMEQDLCRTA IPLPSSPEAD 450
    MSGKLSLKQS ATMPKKGILK KTQQRESGYY SSPERSESSE LLDSNDVVIS 500
    GGLSSPPPDP ARGTSHSLSC RRKGILKHSS RYSDGGTDPA LTRPEMPTLE 550
    SLSPPGVPSD GISRSYSRPS SIISDDSVLS SDSFDLLELQ ENRPARQRIR 600
    SCVSAENFLQ LQDFETPHNR PRPQYLKRLA DSSFSLLTDM DDVTQVYKKA 650
    LEICSKLN 658
    Length:658
    Mass (Da):73,661
    Last modified:October 25, 2004 - v1
    Checksum:iE7176F13B75B899F
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC040467 mRNA. Translation: AAH40467.1.
    BC082328 mRNA. Translation: AAH82328.1.
    AB182364 mRNA. Translation: BAD23995.1.
    CCDSiCCDS24079.1.
    RefSeqiNP_001004363.1. NM_001004363.1.
    UniGeneiMm.25874.

    Genome annotation databases

    EnsembliENSMUST00000020220; ENSMUSP00000020220; ENSMUSG00000020032.
    GeneIDi77976.
    KEGGimmu:77976.
    UCSCiuc007gko.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    UniGenei Mm.25874.

    3D structure databases

    ProteinModelPortali Q641K5.
    SMRi Q641K5. Positions 34-325.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 219063. 1 interaction.

    PTM databases

    PhosphoSitei Q641K5.

    Proteomic databases

    PRIDEi Q641K5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    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 COG0515.
    GeneTreei ENSGT00740000115114.
    HOGENOMi HOG000004864.
    HOVERGENi HBG007160.
    InParanoidi Q641K5.
    KOi K08800.
    OMAi NRPRPQY.
    OrthoDBi EOG7MD4PN.
    PhylomeDBi Q641K5.
    TreeFami TF324572.

    Miscellaneous databases

    NextBioi 347923.
    PROi Q641K5.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q641K5.
    CleanExi MM_NUAK1.
    Genevestigatori Q641K5.

    Family and domain databases

    InterProi IPR011009. 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 ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.

    Entry informationi

    Entry nameiNUAK1_MOUSE
    AccessioniPrimary (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: October 1, 2014
    This is version 96 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3