Q9H093 (NUAK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	628 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Apoptosis
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Inferred from direct assay Ref.5. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cellular response to glucose starvation Inferred from direct assay Ref.5. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.1. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.1Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 628	628	NUAK family SNF1-like kinase 2		PRO_0000247756
Regions
	Domain	53 – 303	251	Protein kinase
	Nucleotide binding	59 – 67	9	ATP By similarity UniProtKB O60285
Sites
	Active site	175	1	Proton acceptor By similarity UniProtKB O60285
	Binding site	81	1	ATP Ref.6
Amino acid modifications
	Modified residue	208	1	Phosphothreonine; by LKB1 Ref.1
	Modified residue	435	1	Phosphoserine Ref.7
	Modified residue	523	1	Phosphoserine Ref.7
	Modified residue	544	1	Phosphoserine Ref.7
	Modified residue	547	1	Phosphoserine Ref.7
Natural variations
	Natural variant	309	1	T → S. Ref.9 Corresponds to variant rs55745939 [ dbSNP | Ensembl ].		VAR_040964
	Natural variant	341	1	R → L. Ref.9 Corresponds to variant rs35208615 [ dbSNP | Ensembl ].		VAR_040965
	Natural variant	503	1	K → R in an ovarian Endometrioid carcinoma sample; somatic mutation. Ref.9		VAR_040966
	Natural variant	516	1	A → V. Ref.9 Corresponds to variant rs35070935 [ dbSNP | Ensembl ].		VAR_040967
	Natural variant	541	1	G → E in a breast pleomorphic lobular carcinoma sample; somatic mutation. Ref.9		VAR_040968
Experimental info
	Mutagenesis	81	1	K → R: Loss of autophosphorylation, kinase activity and of anti-apoptotic activity. Ref.6
	Mutagenesis	208	1	T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9H093 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: F76F8B1BF94F4C87	FASTA	628	69,612
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY.
[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]	"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. , 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.
IPI	IPI00008883.
RefSeq	NP_112214.1. NM_030952.1.
UniGene	Hs.497512.
3D structure databases
ProteinModelPortal	Q9H093.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H093. 3 interactions.
STRING	9606.ENSP00000356125.
PTM databases
PhosphoSite	Q9H093.
Polymorphism databases
DMDM	74761376.
Proteomic databases
PaxDb	Q9H093.
PRIDE	Q9H093.
Protocols and materials databases
DNASU	81788.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367157; ENSP00000356125; ENSG00000163545.
GeneID	81788.
KEGG	hsa:81788.
UCSC	uc001hce.3. human.
Organism-specific databases
CTD	81788.
GeneCards	GC01M205271.
HGNC	HGNC:29558. NUAK2.
HPA	HPA008958.
MIM	608131. gene.
neXtProt	NX_Q9H093.
PharmGKB	PA142671243.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000004864.
HOVERGEN	HBG007160.
InParanoid	Q9H093.
KO	K08800.
OMA	TDCQEVT.
OrthoDB	EOG4MPHQ1.
Gene expression databases
ArrayExpress	Q9H093.
Bgee	Q9H093.
CleanEx	HS_NUAK2.
Genevestigator	Q9H093.
GermOnline	ENSG00000163545. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9H093.
ChEMBL	CHEMBL5698.
GenomeRNAi	81788.
NextBio	72088.
SOURCE	Search...

Entry information

Entry name

NUAK2_HUMAN

Accession

Primary (citable) accession number: Q9H093

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.