Reviewed, UniProtKB/Swiss-Prot O60285 (NUAK1_HUMAN)

Names and origin

Protein names

Recommended name:
    NUAK family SNF1-like kinase 1
    EC=2.7.11.1
Alternative name(s):
    AMPK-related protein kinase 5

Gene names

Name:	NUAK1
Synonyms:	ARK5, KIAA0537

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	661 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in tolerance to glucose starvation. Phosphorylates ATM. Suppresses Fas-induced apoptosis by phosphorylation of CASP6, thus suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Ref.1 Ref.4 Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by PKB/AKT1 during glucose starvation. Activated by phosphorylation on Thr-211 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39. Ref.1
Tissue specificity	Expressed at high levels in heart and brain, and at lower levels in skeletal muscle, kidney, ovary, placenta, lung and liver.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
IGHA2	P01877	1	EBI-1046789,EBI-1044357
PRKAR1A	P10644	1	EBI-1046789,EBI-476431
PRPSAP1	Q14558	1	EBI-1046789,EBI-724449
S100A8	P05109	1	EBI-1046789,EBI-355281
S100A9	P06702	1	EBI-1046789,EBI-1055001
USP9X	Q93008	1	EBI-1046789,EBI-302524

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60285-1)

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.

Isoform 2 (identifier: O60285-2)

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

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 661	661	NUAK family SNF1-like kinase 1		PRO_0000086453
Regions
	Domain	55 – 306	252	Protein kinase
	Nucleotide binding	61 – 69	9	ATP By similarity
Sites
	Active site	178	1	Proton acceptor By similarity
	Binding site	84	1	ATP By similarity
Amino acid modifications
	Modified residue	22	1	Phosphoserine
	Modified residue	211	1	Phosphothreonine Ref.1
	Modified residue	215	1	Phosphoserine By similarity
	Modified residue	371	1	Phosphoserine By similarity
	Modified residue	380	1	Phosphoserine By similarity
	Modified residue	388	1	Phosphoserine
	Modified residue	444	1	Phosphoserine
	Modified residue	445	1	Phosphoserine
	Modified residue	455	1	Phosphoserine
	Modified residue	600	1	Phosphoserine; by PKB/AKT1
Natural variations
	Alternative sequence	182 – 208	27	ENILL…QKDKF → KKTSRENQVTTLPQSAVSLR SCWTVMM in isoform 2.		VSP_014236
	Alternative sequence	209 – 661	453	Missing in isoform 2.		VSP_014237
	Natural variant	419	1	G → D: dbSNP rs55774704. Ref.7		VAR_040963
	Natural variant	543	1	P → R: dbSNP rs3741883. Ref.7		VAR_017246
Experimental info
	Mutagenesis	211	1	T → A: Prevents phosphorylation and activation by STK11 complex. Ref.1
	Mutagenesis	600	1	S → A: No phosphorylation. Ref.4
	Sequence conflict	86	1	I → V in BAB55026. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 806F37D52CA4718F	FASTA	661	74,305
	10 20 30 40 50 60 MEGAAAPVAG DRPDLGLGAP GSPREAVAGA TAALEPRKPH GVKRHHHKHN LKHRYELQET 70 80 90 100 110 120 LGKGTYGKVK RATERFSGRV VAIKSIRKDK IKDEQDMVHI RREIEIMSSL NHPHIISIYE 130 140 150 160 170 180 VFENKDKIVI IMEYASKGEL YDYISERRRL SERETRHFFR QIVSAVHYCH KNGVVHRDLK 190 200 210 220 230 240 LENILLDDNC NIKIADFGLS NLYQKDKFLQ TFCGSPLYAS PEIVNGRPYR GPEVDSWALG 250 260 270 280 290 300 VLLYTLVYGT MPFDGFDHKN LIRQISSGEY REPTQPSDAR GLIRWMLMVN PDRRATIEDI 310 320 330 340 350 360 ANHWWVNWGY KSSVCDCDAL HDSESPLLAR IIDWHHRSTG LQADTEAKMK GLAKPTTSEV 370 380 390 400 410 420 MLERQRSLKK SKKENDFAQS GQDAVPESPS KLSSKRPKGI LKKRSNSEHR SHSTGFIEGV 430 440 450 460 470 480 VGPALPSTFK MEQDLCRTGV LLPSSPEAEV PGKLSPKQSA TMPKKGILKK TQQRESGYYS 490 500 510 520 530 540 SPERSESSEL LDSNDVMGSS IPSPSPPDPA RVTSHSLSCR RKGILKHSSK YSAGTMDPAL 550 560 570 580 590 600 VSPEMPTLES LSEPGVPAEG LSRSYSRPSS VISDDSVLSS DSFDLLDLQE NRPARQRIRS 610 620 630 640 650 660 CVSAENFLQI QDFEGLQNRP RPQYLKRYRN RLADSSFSLL TDMDDVTQVY KQALEICSKL N
	Isoform 2. Checksum: 36E0B4FB479B16EF	FASTA	208	23,824
	10 20 30 40 50 60 MEGAAAPVAG DRPDLGLGAP GSPREAVAGA TAALEPRKPH GVKRHHHKHN LKHRYELQET 70 80 90 100 110 120 LGKGTYGKVK RATERFSGRV VAIKSIRKDK IKDEQDMVHI RREIEIMSSL NHPHIISIYE 130 140 150 160 170 180 VFENKDKIVI IMEYASKGEL YDYISERRRL SERETRHFFR QIVSAVHYCH KNGVVHRDLK 190 200 LKKTSRENQV TTLPQSAVSL RSCWTVMM

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: 14976552] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-211, MUTAGENESIS OF THR-211.
[2]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed: 9628581] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]	"Identification of a novel protein kinase mediating Akt survival signaling to the ATM protein." Suzuki A., Kusakai G., Kishimoto A., Lu J., Ogura T., Lavin M.F., Esumi H. J. Biol. Chem. 278:48-53(2003) [PubMed: 12409306] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-600.
[5]	"Regulation of caspase-6 and FLIP by the AMPK family member ARK5." Suzuki A., Kusakai G., Kishimoto A., Shimojo Y., Miyamoto S., Ogura T., Ochiai A., Esumi H. Oncogene 23:7067-7075(2004) [PubMed: 15273717] [Abstract] Cited for: FUNCTION.
[6]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; THR-211; SER-388; SER-444; SER-445 AND SER-455, MASS SPECTROMETRY.
[7]	"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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASP-419 AND ARG-543.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB011109 mRNA. Translation: BAA25463.2. Different initiation. AK027302 mRNA. Translation: BAB55026.1.
IPI	IPI00028566. IPI00386903.
RefSeq	NP_055655.1.
3D structure databases
SMR	O60285. Positions 18-306, 49-338.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60285. 7 interactions.
STRING	O60285.
PTM databases
PhosphoSite	O60285.
Proteomic databases
PRIDE	O60285.
Genome annotation databases
Ensembl	ENST00000261402; ENSP00000261402; ENSG00000074590; Homo sapiens. [Genome view]
GeneID	9891.
KEGG	hsa:9891.
UCSC	uc001tlj.1. human.
Organism-specific databases
CTD	9891.
GeneCards	GC12M104960.
H-InvDB	HIX0010951. HIX0021283.
HGNC	HGNC:14311. NUAK1.
MIM	608130. gene.
PharmGKB	PA142671242.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16403.
HOGENOM	HBG445847.
HOVERGEN	O60285.
InParanoid	O60285.
OMA	NRPRPQY.
OrthoDB	EOG9D55J2.
PhylomeDB	O60285.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	O60285.
Bgee	O60285.
CleanEx	HS_NUAK1.
Genevestigator	O60285.
GermOnline	ENSG00000074590. Homo sapiens.
Family and domain databases
InterPro	IPR020636. Ca/CaM-dep_prot_kinase-like. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. IPR020665. SNF1-like_kinase_NUAK-typ. [Graphical view]
PANTHER	PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit. PTHR22982:SF51. SNF1-like_kinase_NUAK-typ. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	37291.
SOURCE	Search...

Entry information

Entry name

NUAK1_HUMAN

Accession

Primary (citable) accession number: O60285
Secondary accession number(s): Q96KA8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	August 1, 1998
Last modified:	February 9, 2010
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.