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Protein

NUAK family SNF1-like kinase 1

Gene

NUAK1

Organism
Homo sapiens (Human)
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 (PubMed:25329316).8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Activity regulationi

Activated by phosphorylation on Thr-211. Activated by phosphorylation at Ser-600 AKT1 during glucose starvation; the relevance of such activation in normal cells is however unsure.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei84ATPCurated1
Active sitei178Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi61 – 69ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • p53 binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
SignaLinkiO60285
SIGNORiO60285

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
Short name:
ARK5
Omphalocele kinase 1
Gene namesi
Name:NUAK1
Synonyms:ARK5, KIAA0537, OMPHK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000074590.13
HGNCiHGNC:14311 NUAK1
MIMi608130 gene
neXtProtiNX_O60285

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi84K → A: Abolishes kinase activity and ability to induce senescence. 2 Publications1
Mutagenesisi211T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Abolishes ability to induce senescence. 3 Publications1
Mutagenesisi400 – 401IL → KK: Abolishes interaction with PPP1CB and ability to regulate myosin PP1 activity. 1 Publication2
Mutagenesisi600S → A: Abrogates phosphorylation by PKB/AKT1. Does not affect ability to induce senescence. 2 Publications1

Organism-specific databases

DisGeNETi9891
OpenTargetsiENSG00000074590
PharmGKBiPA142671242

Chemistry databases

ChEMBLiCHEMBL5784
GuidetoPHARMACOLOGYi2129

Polymorphism and mutation databases

BioMutaiNUAK1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864531 – 661NUAK family SNF1-like kinase 1Add BLAST661

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei22PhosphoserineCombined sources1
Modified residuei211Phosphothreonine; by LKB1Combined sources2 Publications1
Modified residuei455PhosphoserineCombined sources1
Modified residuei600Phosphoserine; by PKB/AKT11 Publication1

Post-translational modificationi

Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X.1 Publication
Phosphorylated at Thr-211 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 IGF1.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO60285
PeptideAtlasiO60285
PRIDEiO60285
ProteomicsDBi49314
49315 [O60285-2]

PTM databases

iPTMnetiO60285
PhosphoSitePlusiO60285

Expressioni

Tissue specificityi

Expressed at high levels in heart and brain, and at lower levels in skeletal muscle, kidney, ovary, placenta, lung and liver. Highly up-regulated in colorectal cancer cell lines.1 Publication

Inductioni

Transcriptionally regulated by members of the MAF family.2 Publications

Gene expression databases

BgeeiENSG00000074590 Expressed in 238 organ(s), highest expression level in frontal cortex
CleanExiHS_NUAK1
ExpressionAtlasiO60285 baseline and differential
GenevisibleiO60285 HS

Organism-specific databases

HPAiHPA057143

Interactioni

Subunit structurei

Interact (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A. Interacts with CDKN1A.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115221, 24 interactors
IntActiO60285, 5 interactors
MINTiO60285
STRINGi9606.ENSP00000261402

Chemistry databases

BindingDBiO60285

Structurei

3D structure databases

ProteinModelPortaliO60285
SMRiO60285
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini55 – 306Protein kinasePROSITE-ProRule annotationAdd BLAST252

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi399 – 402GILK motif4

Domaini

The GILK motif mediates interaction with PPP1CB.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0611 Eukaryota
ENOG410XPDM LUCA
GeneTreeiENSGT00930000150880
HOGENOMiHOG000004864
HOVERGENiHBG007160
InParanoidiO60285
KOiK08800
OMAiVTQVYKQ
OrthoDBiEOG091G033W
PhylomeDBiO60285
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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O60285-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MEGAAAPVAG DRPDLGLGAP GSPREAVAGA TAALEPRKPH GVKRHHHKHN
60 70 80 90 100
LKHRYELQET LGKGTYGKVK RATERFSGRV VAIKSIRKDK IKDEQDMVHI
110 120 130 140 150
RREIEIMSSL NHPHIISIYE VFENKDKIVI IMEYASKGEL YDYISERRRL
160 170 180 190 200
SERETRHFFR QIVSAVHYCH KNGVVHRDLK LENILLDDNC NIKIADFGLS
210 220 230 240 250
NLYQKDKFLQ TFCGSPLYAS PEIVNGRPYR GPEVDSWALG VLLYTLVYGT
260 270 280 290 300
MPFDGFDHKN LIRQISSGEY REPTQPSDAR GLIRWMLMVN PDRRATIEDI
310 320 330 340 350
ANHWWVNWGY KSSVCDCDAL HDSESPLLAR IIDWHHRSTG LQADTEAKMK
360 370 380 390 400
GLAKPTTSEV MLERQRSLKK SKKENDFAQS GQDAVPESPS KLSSKRPKGI
410 420 430 440 450
LKKRSNSEHR SHSTGFIEGV VGPALPSTFK MEQDLCRTGV LLPSSPEAEV
460 470 480 490 500
PGKLSPKQSA TMPKKGILKK TQQRESGYYS SPERSESSEL LDSNDVMGSS
510 520 530 540 550
IPSPSPPDPA RVTSHSLSCR RKGILKHSSK YSAGTMDPAL VSPEMPTLES
560 570 580 590 600
LSEPGVPAEG LSRSYSRPSS VISDDSVLSS DSFDLLDLQE NRPARQRIRS
610 620 630 640 650
CVSAENFLQI QDFEGLQNRP RPQYLKRYRN RLADSSFSLL TDMDDVTQVY
660
KQALEICSKL N
Length:661
Mass (Da):74,305
Last modified:August 1, 1998 - v1
Checksum:i806F37D52CA4718F
GO
Isoform 2 (identifier: O60285-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     182-208: ENILLDDNCNIKIADFGLSNLYQKDKF → KKTSRENQVTTLPQSAVSLRSCWTVMM
     209-661: Missing.

Note: No experimental confirmation available.
Show »
Length:208
Mass (Da):23,824
Checksum:i36E0B4FB479B16EF
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VSH4F8VSH4_HUMAN
NUAK family SNF1-like kinase 1
NUAK1
152Annotation score:
F8VXF0F8VXF0_HUMAN
NUAK family SNF1-like kinase 1
NUAK1
74Annotation score:
F8VZ96F8VZ96_HUMAN
NUAK family SNF1-like kinase 1
NUAK1
118Annotation score:

Sequence cautioni

The sequence BAA25463 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti86I → V in BAB55026 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040963419G → D1 PublicationCorresponds to variant dbSNP:rs55774704Ensembl.1
Natural variantiVAR_017246543P → R1 PublicationCorresponds to variant dbSNP:rs3741883Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014236182 – 208ENILL…QKDKF → KKTSRENQVTTLPQSAVSLR SCWTVMM in isoform 2. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_014237209 – 661Missing in isoform 2. 1 PublicationAdd BLAST453

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011109 mRNA Translation: BAA25463.2 Different initiation.
AK027302 mRNA Translation: BAB55026.1
AK289992 mRNA Translation: BAF82681.1
AC010182 Genomic DNA No translation available.
AC011595 Genomic DNA No translation available.
CH471054 Genomic DNA Translation: EAW97768.1
BC152462 mRNA Translation: AAI52463.1
CCDSiCCDS31892.1 [O60285-1]
RefSeqiNP_055655.1, NM_014840.2 [O60285-1]
UniGeneiHs.524692

Genome annotation databases

EnsembliENST00000261402; ENSP00000261402; ENSG00000074590 [O60285-1]
GeneIDi9891
KEGGihsa:9891
UCSCiuc001tlj.2 human [O60285-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011109 mRNA Translation: BAA25463.2 Different initiation.
AK027302 mRNA Translation: BAB55026.1
AK289992 mRNA Translation: BAF82681.1
AC010182 Genomic DNA No translation available.
AC011595 Genomic DNA No translation available.
CH471054 Genomic DNA Translation: EAW97768.1
BC152462 mRNA Translation: AAI52463.1
CCDSiCCDS31892.1 [O60285-1]
RefSeqiNP_055655.1, NM_014840.2 [O60285-1]
UniGeneiHs.524692

3D structure databases

ProteinModelPortaliO60285
SMRiO60285
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115221, 24 interactors
IntActiO60285, 5 interactors
MINTiO60285
STRINGi9606.ENSP00000261402

Chemistry databases

BindingDBiO60285
ChEMBLiCHEMBL5784
GuidetoPHARMACOLOGYi2129

PTM databases

iPTMnetiO60285
PhosphoSitePlusiO60285

Polymorphism and mutation databases

BioMutaiNUAK1

Proteomic databases

PaxDbiO60285
PeptideAtlasiO60285
PRIDEiO60285
ProteomicsDBi49314
49315 [O60285-2]

Protocols and materials databases

DNASUi9891
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261402; ENSP00000261402; ENSG00000074590 [O60285-1]
GeneIDi9891
KEGGihsa:9891
UCSCiuc001tlj.2 human [O60285-1]

Organism-specific databases

CTDi9891
DisGeNETi9891
EuPathDBiHostDB:ENSG00000074590.13
GeneCardsiNUAK1
HGNCiHGNC:14311 NUAK1
HPAiHPA057143
MIMi608130 gene
neXtProtiNX_O60285
OpenTargetsiENSG00000074590
PharmGKBiPA142671242
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0611 Eukaryota
ENOG410XPDM LUCA
GeneTreeiENSGT00930000150880
HOGENOMiHOG000004864
HOVERGENiHBG007160
InParanoidiO60285
KOiK08800
OMAiVTQVYKQ
OrthoDBiEOG091G033W
PhylomeDBiO60285
TreeFamiTF324572

Enzyme and pathway databases

ReactomeiR-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
SignaLinkiO60285
SIGNORiO60285

Miscellaneous databases

ChiTaRSiNUAK1 human
GeneWikiiNUAK1
GenomeRNAii9891
PROiPR:O60285
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000074590 Expressed in 238 organ(s), highest expression level in frontal cortex
CleanExiHS_NUAK1
ExpressionAtlasiO60285 baseline and differential
GenevisibleiO60285 HS

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_HUMAN
AccessioniPrimary (citable) accession number: O60285
Secondary accession number(s): A7MD39, Q96KA8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: August 1, 1998
Last modified: November 7, 2018
This is version 172 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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