Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

NUAK family SNF1-like kinase 1

Gene

Nuak1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair.By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Activity 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)DescriptionActionsGraphical viewLength
Binding sitei85ATPPROSITE-ProRule annotation1
Active sitei179Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi62 – 70ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell adhesion, DNA damage
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-6804756 Regulation of TP53 Activity through Phosphorylation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1925226 Nuak1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
ChainiPRO_00000864541 – 658NUAK family SNF1-like kinase 1Add BLAST658

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei22PhosphoserineBy similarity1
Modified residuei212Phosphothreonine; by LKB1By similarity1
Modified residuei456PhosphoserineBy similarity1
Modified residuei601Phosphoserine; by PKB/AKT1By similarity1

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
PaxDbiQ641K5
PRIDEiQ641K5

PTM databases

iPTMnetiQ641K5
PhosphoSitePlusiQ641K5

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

BgeeiENSMUSG00000020032 Expressed in 252 organ(s), highest expression level in visual cortex
CleanExiMM_NUAK1
ExpressionAtlasiQ641K5 baseline and differential
GenevisibleiQ641K5 MM

Interactioni

Subunit structurei

Interact (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A. Interacts with CDKN1A.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi219063, 1 interactor
STRINGi10090.ENSMUSP00000020220

Structurei

3D structure databases

ProteinModelPortaliQ641K5
SMRiQ641K5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 307Protein kinasePROSITE-ProRule annotationAdd BLAST252

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi400 – 403GILK motif4

Domaini

The GILK motif mediates interaction with PPP1CB.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0611 Eukaryota
ENOG410XPDM LUCA
GeneTreeiENSGT00900000140868
HOGENOMiHOG000004864
HOVERGENiHBG007160
InParanoidiQ641K5
KOiK08800
OrthoDBiEOG091G033W
PhylomeDBiQ641K5
TreeFamiTF324572

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6XZX4F6XZX4_MOUSE
NUAK family SNF1-like kinase 1
Nuak1
160Annotation score:

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

Similar proteinsi

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
CCDSiCCDS24079.1
RefSeqiNP_001004363.1, NM_001004363.1
UniGeneiMm.25874

3D structure databases

ProteinModelPortaliQ641K5
SMRiQ641K5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi219063, 1 interactor
STRINGi10090.ENSMUSP00000020220

PTM databases

iPTMnetiQ641K5
PhosphoSitePlusiQ641K5

Proteomic databases

MaxQBiQ641K5
PaxDbiQ641K5
PRIDEiQ641K5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9891
MGIiMGI:1925226 Nuak1
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0611 Eukaryota
ENOG410XPDM LUCA
GeneTreeiENSGT00900000140868
HOGENOMiHOG000004864
HOVERGENiHBG007160
InParanoidiQ641K5
KOiK08800
OrthoDBiEOG091G033W
PhylomeDBiQ641K5
TreeFamiTF324572

Enzyme and pathway databases

ReactomeiR-MMU-6804756 Regulation of TP53 Activity through Phosphorylation

Miscellaneous databases

PROiPR:Q641K5
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020032 Expressed in 252 organ(s), highest expression level in visual cortex
CleanExiMM_NUAK1
ExpressionAtlasiQ641K5 baseline and differential
GenevisibleiQ641K5 MM

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNUAK1_MOUSE
AccessioniPrimary (citable) accession number: Q641K5
Secondary accession number(s): Q6I6D6, Q8CGE1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2006
Last sequence update: October 25, 2004
Last modified: September 12, 2018
This is version 127 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. SIMILARITY comments
    Index of protein domains and families
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again