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Q9H093 (NUAK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NUAK family SNF1-like kinase 2

EC=2.7.11.1
Alternative name(s):
Omphalocele kinase 2
SNF1/AMP kinase-related kinase
Short name=SNARK
Gene names
Name:NUAK2
Synonyms:OMPHK2, SNARK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length628 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Able to phosphorylate 'Ser-464' of LATS1. Ref.1 Ref.5 Ref.6 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.5

Cofactor

Magnesium. Ref.1 Ref.5

Enzyme regulation

Activated by phosphorylation on Thr-208. Ref.1

Post-translational modification

Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Autophosphorylated in vitro. Ref.1 Ref.6

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 628628NUAK family SNF1-like kinase 2
PRO_0000247756

Regions

Domain53 – 303251Protein kinase
Nucleotide binding59 – 679ATP By similarity UniProtKB O60285

Sites

Active site1751Proton acceptor By similarity UniProtKB O60285
Binding site811ATP Ref.6

Amino acid modifications

Modified residue11N-acetylmethionine Ref.9
Modified residue2081Phosphothreonine; by LKB1 Ref.1
Modified residue4351Phosphoserine Ref.7
Modified residue5231Phosphoserine Ref.7
Modified residue5441Phosphoserine Ref.7
Modified residue5471Phosphoserine Ref.7
Modified residue5731Phosphoserine By similarity

Natural variations

Natural variant3091T → S. Ref.10
Corresponds to variant rs55745939 [ dbSNP | Ensembl ].
VAR_040964
Natural variant3411R → L. Ref.10
Corresponds to variant rs35208615 [ dbSNP | Ensembl ].
VAR_040965
Natural variant5031K → R in an ovarian Endometrioid carcinoma sample; somatic mutation. Ref.10
VAR_040966
Natural variant5161A → V. Ref.10
Corresponds to variant rs35070935 [ dbSNP | Ensembl ].
VAR_040967
Natural variant5411G → E in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.10
VAR_040968

Experimental info

Mutagenesis811K → R: Loss of autophosphorylation, kinase activity and of anti-apoptotic activity. Ref.6
Mutagenesis2081T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9H093 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: F76F8B1BF94F4C87

FASTA62869,612
        10         20         30         40         50         60 
MESLVFARRS GPTPSAAELA RPLAEGLIKS PKPLMKKQAV KRHHHKHNLR HRYEFLETLG 

        70         80         90        100        110        120 
KGTYGKVKKA RESSGRLVAI KSIRKDKIKD EQDLMHIRRE IEIMSSLNHP HIIAIHEVFE 

       130        140        150        160        170        180 
NSSKIVIVME YASRGDLYDY ISERQQLSER EARHFFRQIV SAVHYCHQNR VVHRDLKLEN 

       190        200        210        220        230        240 
ILLDANGNIK IADFGLSNLY HQGKFLQTFC GSPLYASPEI VNGKPYTGPE VDSWSLGVLL 

       250        260        270        280        290        300 
YILVHGTMPF DGHDHKILVK QISNGAYREP PKPSDACGLI RWLLMVNPTR RATLEDVASH 

       310        320        330        340        350        360 
WWVNWGYATR VGEQEAPHEG GHPGSDSARA SMADWLRRSS RPLLENGAKV CSFFKQHAPG 

       370        380        390        400        410        420 
GGSTTPGLER QHSLKKSRKE NDMAQSLHSD TADDTAHRPG KSNLKLPKGI LKKKVSASAE 

       430        440        450        460        470        480 
GVQEDPPELS PIPASPGQAA PLLPKKGILK KPRQRESGYY SSPEPSESGE LLDAGDVFVS 

       490        500        510        520        530        540 
GDPKEQKPPQ ASGLLLHRKG ILKLNGKFSQ TALELAAPTT FGSLDELAPP RPLARASRPS 

       550        560        570        580        590        600 
GAVSEDSILS SESFDQLDLP ERLPEPPLRG CVSVDNLTGL EEPPSEGPGS CLRRWRQDPL 

       610        620 
GDSCFSLTDC QEVTATYRQA LRVCSKLT 

« Hide

References

« Hide 'large scale' references
[1]"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1."
Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.
EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 205-224, FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-208, MUTAGENESIS OF THR-208.
[2]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Teratocarcinoma.
[4]"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].
Tissue: Lymph.
[5]"Induction of cell-cell detachment during glucose starvation through F-actin conversion by SNARK, the fourth member of the AMP-activated protein kinase catalytic subunit family."
Suzuki A., Kusakai G., Kishimoto A., Minegichi Y., Ogura T., Esumi H.
Biochem. Biophys. Res. Commun. 311:156-161(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Identification of SNF1/AMP kinase-related kinase as an NF-kappaB-regulated anti-apoptotic kinase involved in CD95-induced motility and invasiveness."
Legembre P., Schickel R., Barnhart B.C., Peter M.E.
J. Biol. Chem. 279:46742-46747(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, AUTOPHOSPHORYLATION, MUTAGENESIS OF LYS-81.
[7]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435; SER-523; SER-544 AND SER-547, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Regulation of ploidy and senescence by the AMPK-related kinase NUAK1."
Humbert N., Navaratnam N., Augert A., Da Costa M., Martien S., Wang J., Martinez D., Abbadie C., Carling D., de Launoit Y., Gil J., Bernard D.
EMBO J. 29:376-386(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-309; LEU-341; ARG-503; VAL-516 AND GLU-541.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL136891 mRNA. Translation: CAB66825.1.
AK074830 mRNA. Translation: BAC11234.1.
BC017306 mRNA. Translation: AAH17306.1.
RefSeqNP_112214.1. NM_030952.1.
UniGeneHs.497512.

3D structure databases

ProteinModelPortalQ9H093.
SMRQ9H093. Positions 10-335.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123581. 6 interactions.
IntActQ9H093. 3 interactions.
MINTMINT-4719062.
STRING9606.ENSP00000356125.

Chemistry

BindingDBQ9H093.
ChEMBLCHEMBL5698.
GuidetoPHARMACOLOGY2130.

PTM databases

PhosphoSiteQ9H093.

Polymorphism databases

DMDM74761376.

Proteomic databases

PaxDbQ9H093.
PRIDEQ9H093.

Protocols and materials databases

DNASU81788.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367157; ENSP00000356125; ENSG00000163545.
GeneID81788.
KEGGhsa:81788.
UCSCuc001hce.3. human.

Organism-specific databases

CTD81788.
GeneCardsGC01M205271.
HGNCHGNC:29558. NUAK2.
HPAHPA008958.
MIM608131. gene.
neXtProtNX_Q9H093.
PharmGKBPA142671243.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000004864.
HOVERGENHBG007160.
InParanoidQ9H093.
KOK08800.
OMATDCQEVT.
OrthoDBEOG7MD4PN.
PhylomeDBQ9H093.
TreeFamTF324572.

Enzyme and pathway databases

SignaLinkQ9H093.

Gene expression databases

ArrayExpressQ9H093.
BgeeQ9H093.
CleanExHS_NUAK2.
GenevestigatorQ9H093.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNUAK2.
GenomeRNAi81788.
NextBio72088.
PROQ9H093.
SOURCESearch...

Entry information

Entry nameNUAK2_HUMAN
AccessionPrimary (citable) accession number: Q9H093
Entry history
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM