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Q641K5

- NUAK1_MOUSE

UniProt

Q641K5 - NUAK1_MOUSE

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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

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

Mg2+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
Complete GO annotation...

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. microtubule cytoskeleton Source: Ensembl
  3. nucleolus Source: Ensembl
  4. nucleus Source: UniProtKB
Complete GO annotation...

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

MaxQBiQ641K5.
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 34-350.
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.
GeneTreeiENSGT00760000118892.
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.
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

        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
Length:658
Mass (Da):73,661
Last modified:October 25, 2004 - v1
Checksum:iE7176F13B75B899F
GO

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.
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:
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.
UniGenei Mm.25874.

3D structure databases

ProteinModelPortali Q641K5.
SMRi Q641K5. Positions 34-350.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 219063. 1 interaction.

PTM databases

PhosphoSitei Q641K5.

Proteomic databases

MaxQBi Q641K5.
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 ENSGT00760000118892.
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.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 98 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